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NCT01947153	Two-way Crossover Study in Healthy Male and Female Subjects to Evaluate the Bioequivalence of Jentadueto®.	The objective of the current study is to demonstrate bioequivalence of two 2.5 mg linagliptin/500 mg metformin fixed dose combination tablets compared to the free combination of the linagliptin 5 mg and metformin 1000 mg in healthy male and female volunteers.		Two-way Crossover Study in Healthy Male and Female Subjects to Evaluate the Bioequivalence of Jentadueto® (Two Fixed Dose Combination Tablets of Linagliptin 2.5 mg and Metformin 500 mg) Compared With the Free Combination of Linagliptin 5 mg and Metformin 1000 mg Tablets Under Fasting Conditions.	Healthy	* Drug: Metformin * Drug: Linagliptin * Drug: Metformin * Drug: Linagliptin	Inclusion criteria:~Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation~Healthy males and females according to the following criteria:~Based upon a complete medical history, including physical examination, vital signs (BP, PR), 12-lead ECG and clinical laboratory tests (haematology, clinical chemistry and urinalysis).~Age 18 to 45 years (incl.)~Body mass index by Quetelet between 18.50 to 24.99 kg/m2 (incl.)~Female subjects of childbearing potential who agree on using double-barrier contraception during the study. If a female is postmenopausal (no menses for at least 2 years) or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) she will be exempt from the requirement. In case of using oral contraceptives, these should be withdrawn at least 2 months before the first drug dosing.~Male subjects who agree on using effective contraception during the study (barrier contraceptive methods)~Exclusion criteria:~Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance~Any laboratory value outside the reference range that is of clinical relevance~Any evidence of a clinically relevant concomitant disease~Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders~Positive results of blood tests for infections (HIV, syphilis, hepatitis B or C)~A positive urine drug screening test at screening and on admission to the trial site in each treatment period.~A positive alcohol breath test at screening and on admission to the trial site in each treatment period.~Surgery of the gastrointestinal tract (except appendectomy)	18 Years	45 Years	All	Accepts Healthy Volunteers	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Linagliptin: AUC 0-72 (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to 72 Hours) \| Linagliptin:~AUC 0-72 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 72 hours) \| 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration \| \| Metformin: AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) \| Metformin:~AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point) \| 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration \| \| Linagliptin: Cmax (Maximum Measured Concentration of the Analyte in Plasma) \| Linagliptin:~Cmax (maximum measured concentration of the analyte in plasma) \| 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration \| \| Metformin: Cmax (Maximum Measured Concentration of the Analyte in Plasma) \| Metformin:~Cmax (maximum measured concentration of the analyte in plasma) \| 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Linagliptin: AUC 0-inf (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity) \| Linagliptin:~AUC 0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) \| 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration \| \| Metformin: AUC 0-inf (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity) \| Metformin:~AUC 0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) \| 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration \| \| Linagliptin: AUC 0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) \| Linagliptin:~AUC 0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point) \| 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration \|		Metformin, Linagliptin, Hypoglycemic Agents, Physiological Effects of Drugs, Incretins, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Dipeptidyl-Peptidase IV Inhibitors, Protease Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Fixed dose combination<br>Linagliptin/Metformin \| Drug: Linagliptin<br>* Fixed dose combination<br>Drug: Metformin<br>* Combination<br>\| \| Experimental: Free combination<br>Linagliptin and Metformin \| Drug: Metformin<br>* Free combination<br>Drug: Linagliptin<br>* Free combination<br>\|	Two-way Crossover Study in Healthy Male and Female Subjects to Evaluate the Bioequivalence of Jentadueto®. Study Overview ================= Brief Summary ----------------- The objective of the current study is to demonstrate bioequivalence of two 2.5 mg linagliptin/500 mg metformin fixed dose combination tablets compared to the free combination of the linagliptin 5 mg and metformin 1000 mg in healthy male and female volunteers. Official Title ----------------- Two-way Crossover Study in Healthy Male and Female Subjects to Evaluate the Bioequivalence of Jentadueto® (Two Fixed Dose Combination Tablets of Linagliptin 2.5 mg and Metformin 500 mg) Compared With the Free Combination of Linagliptin 5 mg and Metformin 1000 mg Tablets Under Fasting Conditions. Conditions ----------------- Healthy Intervention / Treatment ----------------- * Drug: Metformin * Drug: Linagliptin * Drug: Metformin * Drug: Linagliptin Participation Criteria ================= Eligibility Criteria ----------------- Inclusion criteria: Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation Healthy males and females according to the following criteria: Based upon a complete medical history, including physical examination, vital signs (BP, PR), 12-lead ECG and clinical laboratory tests (haematology, clinical chemistry and urinalysis). Age 18 to 45 years (incl.) Body mass index by Quetelet between 18.50 to 24.99 kg/m2 (incl.) Female subjects of childbearing potential who agree on using double-barrier contraception during the study. If a female is postmenopausal (no menses for at least 2 years) or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) she will be exempt from the requirement. In case of using oral contraceptives, these should be withdrawn at least 2 months before the first drug dosing. Male subjects who agree on using effective contraception during the study (barrier contraceptive methods) Exclusion criteria: Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance Any laboratory value outside the reference range that is of clinical relevance Any evidence of a clinically relevant concomitant disease Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Positive results of blood tests for infections (HIV, syphilis, hepatitis B or C) A positive urine drug screening test at screening and on admission to the trial site in each treatment period. A positive alcohol breath test at screening and on admission to the trial site in each treatment period. Surgery of the gastrointestinal tract (except appendectomy) Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 45 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Fixed dose combination<br>Linagliptin/Metformin \| Drug: Linagliptin<br>* Fixed dose combination<br>Drug: Metformin<br>* Combination<br>\| \| Experimental: Free combination<br>Linagliptin and Metformin \| Drug: Metformin<br>* Free combination<br>Drug: Linagliptin<br>* Free combination<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Linagliptin: AUC 0-72 (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to 72 Hours) \| Linagliptin: AUC 0-72 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 72 hours) \| 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration \| \| Metformin: AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) \| Metformin: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point) \| 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration \| \| Linagliptin: Cmax (Maximum Measured Concentration of the Analyte in Plasma) \| Linagliptin: Cmax (maximum measured concentration of the analyte in plasma) \| 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration \| \| Metformin: Cmax (Maximum Measured Concentration of the Analyte in Plasma) \| Metformin: Cmax (maximum measured concentration of the analyte in plasma) \| 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Linagliptin: AUC 0-inf (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity) \| Linagliptin: AUC 0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) \| 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration \| \| Metformin: AUC 0-inf (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity) \| Metformin: AUC 0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) \| 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration \| \| Linagliptin: AUC 0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) \| Linagliptin: AUC 0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point) \| 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration \|
NCT00533429	Study of Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin Versus Pemetrexed + Carboplatin + Bevacizumab + Placebo in Participants With Non-Small Cell Lung Cancer Who Have Not Been Previously Treated With Chemotherapy	The purpose of this study is to determine if Pemetrexed plus Carboplatin plus Bevacizumab plus Enzastaurin, followed by maintenance Bevacizumab plus Enzastaurin can extend survival time without disease progression in the first-line treatment of participants with advanced stage non-small cell lung cancer.		Protocol H6Q-MC-S034(a) Randomized, Double-Blind, Phase 2 Study of Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin Versus Pemetrexed + Carboplatin + Bevacizumab + Placebo in Chemonaive Patients With Stage IIIB or IV Non-Small Cell Lung Cancer	Non-small Cell Lung Cancer	* Drug: enzastaurin * Drug: pemetrexed * Drug: carboplatin * Drug: bevacizumab * Drug: Placebo	Inclusion Criteria:~participants or their legal representative must have signed an informed consent document for clinical research~have laboratory confirmed diagnosis of advanced, nonsquamous cell non-small cell lung cancer (NSCLC) (Stage IIIB or IV disease) which is not curable~have not received any prior systemic chemotherapy, immunotherapy, targeted therapy, or biological therapy for advanced NSCLC, prior radiation therapy is allowed to less than 25% of the bone marrow~have measurable disease~have adequate organ function and estimated life expectancy of 12 weeks~Exclusion Criteria:~have known central nervous system (CNS) disease; major surgery within 28 days; minor surgery within 7 days; serious concomitant systemic disorder; serious cardiac condition; have a serious, nonhealing wound, ulcer, or bone fracture~have received treatment within the last 30 days with any drug that has not received regulatory approval for any indication at the time of study entry~have previously received treatment with enzastaurin, pemetrexed, or bevacizumab~are pregnant or breast-feeding~are unable to swallow tablets	18 Years	null	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Progression-Free Survival (PFS) \| PFS was defined as the time from date of randomization to the first observation of progressive disease (PD) or death due to any cause. For participants not known to have died as of the data cutoff date and who did not have objective PD, PFS was censored at the date of the last objective progression-free assessment. For participants who received subsequent anticancer therapy (after discontinuation from all study treatment) prior to objective disease progression or death, PFS was censored at the date of the last objective progression-free assessment prior to the initiation of post-discontinuation anticancer therapy. \| Randomization to measured PD or death from any cause up to 12.2 months \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Response Rate) \| Tumor response rate was defined as number of participants with overall best response of CR or PR over number of protocol qualified participants using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria. CR was defined as the disappearance of all tumor lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum of LDs or complete disappearance of target lesions, with persistence (but not worsening) of 1 or more non-target lesions. In either case, no new lesions may have appeared.~Percentage of participants was calculated as: (number of participants with CR or PR/ number of participants qualified for tumor response analysis) × 100. \| Randomization to measured progressive disease or death from any cause up to 12.2 months \| \| Overall Survival (OS) \| OS was defined as the time from the date of randomization to the date of death from any cause. For participants who were not known to have died as of the data cutoff, OS was censored at the last contact date. \| Randomization to date of death up to 14.3 months \| \| Time to Progressive Disease (TTPD) \| TTPD was defined as the time from the date of randomization until the first date of objectively determined progressive disease (PD). For participants who died without objective PD (including death from study disease), TTPD was censored at the date of the last objective progression-free disease assessment. For participants not known to have died as of the data cutoff and did not have PD, TTPD was censored at the date of the last objective progression-free disease assessment. \| Randomization to measured PD or death from any cause up to 12.2 months \| \| Duration of Response (DoR) \| The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death from any cause. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.0) criteria. CR was defined as the disappearance of all target lesions and PR was defined as having at least a 30% decrease in sum of longest diameter (LD) of target lesions taking as reference the baseline sum of LDs. For participants who died without progressive disease or who were alive, DoR was censored at the last contact of progression free assessment. For participants who received subsequent anticancer therapy (after discontinuation from all study treatment) prior to PD, DoR was censored at the date of last progression-free assessment prior to the initiation of post-discontinuation anticancer therapy. Due to early study closure, DoR was not analyzed. \| Time of response to disease progression or death from any cause up to 12.2 months \| \| Pharmacology Toxicity and Adverse Events (AEs) \| Clinically significant events were defined as serious AEs (SAEs) and other non-serious AEs. Participants who died due to progressive disease (PD) or an AE while on treatment and or died during the 30 day post-treatment follow-up are included. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. \| Randomization up to 14.3 months and 30-day follow-up \|		Bevacizumab, Carboplatin, Pemetrexed, Antineoplastic Agents, Immunological, Antineoplastic Agents, Angiogenesis Inhibitors, Angiogenesis Modulating Agents, Growth Substances, Physiological Effects of Drugs, Growth Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Folic Acid Antagonists, Nucleic Acid Synthesis Inhibitors	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: A<br>Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin \| Drug: enzastaurin<br>* 1125 milligram (mg) loading dose then 500 mg, oral, daily until disease progression<br>* Other names: LY317615;Drug: pemetrexed<br>* 500 milligrams per square meter (mg/m^2), intravenously ( IV), Day 8 of cycle 1 - 28 days, Day 1 of subsequent cycles every (q) 21 days x 3 cycles<br>* Other names: Alimta;Drug: carboplatin<br>* Area under the curve (AUC) 6, IV, Day 8 cycle 1 - 28 days, Day 1 of subsequent cycles q 21 days x 3 cycles<br>Drug: bevacizumab<br>* 15 milligrams/kilogram (mg/kg), IV, Day 8 of cycle 1 - 28 days, Day 1 of subsequent cycles q 21 days x 3 cycles<br>\| \| Placebo Comparator: B<br>Pemetrexed + Carboplatin + Bevacizumab + Placebo \| Drug: pemetrexed<br>* 500 milligrams per square meter (mg/m^2), intravenously ( IV), Day 8 of cycle 1 - 28 days, Day 1 of subsequent cycles every (q) 21 days x 3 cycles<br>* Other names: Alimta;Drug: carboplatin<br>* Area under the curve (AUC) 6, IV, Day 8 cycle 1 - 28 days, Day 1 of subsequent cycles q 21 days x 3 cycles<br>Drug: bevacizumab<br>* 15 milligrams/kilogram (mg/kg), IV, Day 8 of cycle 1 - 28 days, Day 1 of subsequent cycles q 21 days x 3 cycles<br>Drug: Placebo<br>* oral, daily<br>\|	Study of Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin Versus Pemetrexed + Carboplatin + Bevacizumab + Placebo in Participants With Non-Small Cell Lung Cancer Who Have Not Been Previously Treated With Chemotherapy Study Overview ================= Brief Summary ----------------- The purpose of this study is to determine if Pemetrexed plus Carboplatin plus Bevacizumab plus Enzastaurin, followed by maintenance Bevacizumab plus Enzastaurin can extend survival time without disease progression in the first-line treatment of participants with advanced stage non-small cell lung cancer. Official Title ----------------- Protocol H6Q-MC-S034(a) Randomized, Double-Blind, Phase 2 Study of Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin Versus Pemetrexed + Carboplatin + Bevacizumab + Placebo in Chemonaive Patients With Stage IIIB or IV Non-Small Cell Lung Cancer Conditions ----------------- Non-small Cell Lung Cancer Intervention / Treatment ----------------- * Drug: enzastaurin * Drug: pemetrexed * Drug: carboplatin * Drug: bevacizumab * Drug: Placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: participants or their legal representative must have signed an informed consent document for clinical research have laboratory confirmed diagnosis of advanced, nonsquamous cell non-small cell lung cancer (NSCLC) (Stage IIIB or IV disease) which is not curable have not received any prior systemic chemotherapy, immunotherapy, targeted therapy, or biological therapy for advanced NSCLC, prior radiation therapy is allowed to less than 25% of the bone marrow have measurable disease have adequate organ function and estimated life expectancy of 12 weeks Exclusion Criteria: have known central nervous system (CNS) disease; major surgery within 28 days; minor surgery within 7 days; serious concomitant systemic disorder; serious cardiac condition; have a serious, nonhealing wound, ulcer, or bone fracture have received treatment within the last 30 days with any drug that has not received regulatory approval for any indication at the time of study entry have previously received treatment with enzastaurin, pemetrexed, or bevacizumab are pregnant or breast-feeding are unable to swallow tablets Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: A<br>Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin \| Drug: enzastaurin<br>* 1125 milligram (mg) loading dose then 500 mg, oral, daily until disease progression<br>* Other names: LY317615;Drug: pemetrexed<br>* 500 milligrams per square meter (mg/m^2), intravenously ( IV), Day 8 of cycle 1 - 28 days, Day 1 of subsequent cycles every (q) 21 days x 3 cycles<br>* Other names: Alimta;Drug: carboplatin<br>* Area under the curve (AUC) 6, IV, Day 8 cycle 1 - 28 days, Day 1 of subsequent cycles q 21 days x 3 cycles<br>Drug: bevacizumab<br>* 15 milligrams/kilogram (mg/kg), IV, Day 8 of cycle 1 - 28 days, Day 1 of subsequent cycles q 21 days x 3 cycles<br>\| \| Placebo Comparator: B<br>Pemetrexed + Carboplatin + Bevacizumab + Placebo \| Drug: pemetrexed<br>* 500 milligrams per square meter (mg/m^2), intravenously ( IV), Day 8 of cycle 1 - 28 days, Day 1 of subsequent cycles every (q) 21 days x 3 cycles<br>* Other names: Alimta;Drug: carboplatin<br>* Area under the curve (AUC) 6, IV, Day 8 cycle 1 - 28 days, Day 1 of subsequent cycles q 21 days x 3 cycles<br>Drug: bevacizumab<br>* 15 milligrams/kilogram (mg/kg), IV, Day 8 of cycle 1 - 28 days, Day 1 of subsequent cycles q 21 days x 3 cycles<br>Drug: Placebo<br>* oral, daily<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Progression-Free Survival (PFS) \| PFS was defined as the time from date of randomization to the first observation of progressive disease (PD) or death due to any cause. For participants not known to have died as of the data cutoff date and who did not have objective PD, PFS was censored at the date of the last objective progression-free assessment. For participants who received subsequent anticancer therapy (after discontinuation from all study treatment) prior to objective disease progression or death, PFS was censored at the date of the last objective progression-free assessment prior to the initiation of post-discontinuation anticancer therapy. \| Randomization to measured PD or death from any cause up to 12.2 months \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Response Rate) \| Tumor response rate was defined as number of participants with overall best response of CR or PR over number of protocol qualified participants using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria. CR was defined as the disappearance of all tumor lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum of LDs or complete disappearance of target lesions, with persistence (but not worsening) of 1 or more non-target lesions. In either case, no new lesions may have appeared. Percentage of participants was calculated as: (number of participants with CR or PR/ number of participants qualified for tumor response analysis) × 100. \| Randomization to measured progressive disease or death from any cause up to 12.2 months \| \| Overall Survival (OS) \| OS was defined as the time from the date of randomization to the date of death from any cause. For participants who were not known to have died as of the data cutoff, OS was censored at the last contact date. \| Randomization to date of death up to 14.3 months \| \| Time to Progressive Disease (TTPD) \| TTPD was defined as the time from the date of randomization until the first date of objectively determined progressive disease (PD). For participants who died without objective PD (including death from study disease), TTPD was censored at the date of the last objective progression-free disease assessment. For participants not known to have died as of the data cutoff and did not have PD, TTPD was censored at the date of the last objective progression-free disease assessment. \| Randomization to measured PD or death from any cause up to 12.2 months \| \| Duration of Response (DoR) \| The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death from any cause. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.0) criteria. CR was defined as the disappearance of all target lesions and PR was defined as having at least a 30% decrease in sum of longest diameter (LD) of target lesions taking as reference the baseline sum of LDs. For participants who died without progressive disease or who were alive, DoR was censored at the last contact of progression free assessment. For participants who received subsequent anticancer therapy (after discontinuation from all study treatment) prior to PD, DoR was censored at the date of last progression-free assessment prior to the initiation of post-discontinuation anticancer therapy. Due to early study closure, DoR was not analyzed. \| Time of response to disease progression or death from any cause up to 12.2 months \| \| Pharmacology Toxicity and Adverse Events (AEs) \| Clinically significant events were defined as serious AEs (SAEs) and other non-serious AEs. Participants who died due to progressive disease (PD) or an AE while on treatment and or died during the 30 day post-treatment follow-up are included. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. \| Randomization up to 14.3 months and 30-day follow-up \|
NCT02696928	Methylene Blue Against Vivax Malaria in Ethiopia	Feasibility of methylene blue-based combination therapy in the radical treatment of adult patients with Plasmodium vivax malaria in Ethiopia: a randomised controlled pilot trial~Study rationale:~Elimination has become the goal of malaria programmes in an increasing number of endemic countries and regions. Primaquine (PQ) is the only registered drug for radical cure of Plasmodium vivax malaria. Prolonged PQ-based combination therapy carries safety concerns and resistance to chloroquine (CQ) and PQ is emerging. Methylene blue (MB) has recently been shown to be safe and effective in the treatment of Plasmodium falciparum malaria in West Africa. As there is evidence for MB probably being effective against the hypnozoites of Plasmodium vivax, MB-based drug regimens could be an alternative to PQ-based combination therapy in Plasmodium vivax malaria.~Study objectives:~The main objective of this trial is to study the feasibility of MB-based combination therapy in patients with uncomplicated P. vivax malaria in an endemic area of Ethiopia.	The specific aims are (1) to test the feasibility and costs of methods and procedures for later use of MB-based combination therapy on a large scale, (2) to assess the safety of MB-based combination therapy, (3) to estimate the efficacy of MB-based combination therapy against malaria relapse, (4) to study the community acceptance of MB-based combination therapy, and (5) to strengthen the local capacity for malaria research and control in Jimma/Ethiopia.~Study design:~The study is designed as a pilot trial in adult patients with uncomplicated P. vivax malaria in Jimma, Ethiopia. Patients will be randomised to three treatment groups:~Arthemeter/Lumefantrine (AL)~AL-PQ, and~AL-MB. Follow-up will be over a period of 6 months.~Study population:~Adult patients with uncomplicated P. vivax malaria (age ≥18 years) in Jimma/Ethiopia (G6PD deficient subjects are excluded) will become enrolled in the outpatient departments of the study centres. The sample size will be 33 per study arm, a total of 99 patients.~Study treatments:~AL standard treatments twice daily (total of 80 mg/dose A plus 480 mg/dose L) over first three study days~PQ 15 mg once daily for 14 days~MB 780 mg once daily for 14 days Treatments will be 100% directly observed.~Study outcomes:~Outcome parameters will be on feasibility and costs (e.g. recruitment rates, retention rates, costs per patient), on safety parameters (e.g. haemoglobin development during follow-up, incidence of adverse events), on efficacy parameters (e.g. incidence of P. vivax relapse during follow-up, malaria recurrence-free efficacy until day 180), and on community acceptance (e.g. perceptions on blue urine) during follow-up.	Feasibility of Methylene Blue-based Combination Therapy in the Radical Treatment of Adult Patients With Plasmodium Vivax Malaria in Ethiopia: a Randomised Controlled Pilot Trial	Vivax Malaria	* Drug: Artemeter-Lumefantrine and MB (combination therapy) * Drug: Artemeter-Lumefantrine (combination therapy) * Drug: Artemeter-Lumefantrine and Primaquine (combination therapy)	Inclusion Criteria:~Age ≥18 years~Uncomplicated P. vivax monoinfection (asexual parasite count >250/µl)~Axillary temperature ≥ 37.5°C or history of fever during last 48 hours~Ability to tolerate oral drug therapy~Written informed consent of patient~Permanent residence in the study area~Exclusion Criteria:~Therapy with an antimalarial (e.g. CQ, amodiaquine, pyrimethamine-sulfadoxine, quinine, any ACT) or an antibiotic which is effective against malaria parasites (e.g. doxycyclin, clindamycin, CoTrim) during last three weeks~Mixed malaria infection~Clinical danger signals (e.g. unable to stand or to sit, unable to drink, repeated vomiting, convulsions) or signs and symptoms of severe malaria (according to WHO definition)~Known other serious illnesses (e.g. cardiac, renal, hepatic, pulmonary disease, severe malnutrition, severe infectious diseases)~G6PD deficiency (<60% activity, WHO classification 1-3)~Patients with known allergy to one or more of the study drugs~Hemoglobin value <7 g/dL~Pregnancy or breastfeeding	18 Years	null	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Study feasibility \| Patient recruitment rates \| 180 days \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Incidence of P. vivax \| Passive and active surveillance \| 180 days \| \| Adverse events (AE) during total follow-up period \| Passive and active surveillance \| 180 days \| \| Study costs \| Costs per patient \| 180 days \|		Lumefantrine, Primaquine, Antimalarials, Antiprotozoal Agents, Antiparasitic Agents, Anti-Infective Agents	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Other: Artemeter-Lumefantrine (combination therapy)<br>33 patients~(standard of care) \| Drug: Artemeter-Lumefantrine (combination therapy)<br>* AL first 3 days<br>* Other names: AL;\| \| Active Comparator: Artemeter-Lumefantrine and Primaquine (combination therapy)<br>33 patients \| Drug: Artemeter-Lumefantrine and Primaquine (combination therapy)<br>* AL first 3 days PQ next 14 days<br>* Other names: AL and PQ;\| \| Experimental: Artemeter-Lumefantrine and MB (combination therapy)<br>33 patients \| Drug: Artemeter-Lumefantrine and MB (combination therapy)<br>* AL first 3 days MB next 14 days<br>* Other names: CID 6099;\|	Methylene Blue Against Vivax Malaria in Ethiopia Study Overview ================= Brief Summary ----------------- Feasibility of methylene blue-based combination therapy in the radical treatment of adult patients with Plasmodium vivax malaria in Ethiopia: a randomised controlled pilot trial Study rationale: Elimination has become the goal of malaria programmes in an increasing number of endemic countries and regions. Primaquine (PQ) is the only registered drug for radical cure of Plasmodium vivax malaria. Prolonged PQ-based combination therapy carries safety concerns and resistance to chloroquine (CQ) and PQ is emerging. Methylene blue (MB) has recently been shown to be safe and effective in the treatment of Plasmodium falciparum malaria in West Africa. As there is evidence for MB probably being effective against the hypnozoites of Plasmodium vivax, MB-based drug regimens could be an alternative to PQ-based combination therapy in Plasmodium vivax malaria. Study objectives: The main objective of this trial is to study the feasibility of MB-based combination therapy in patients with uncomplicated P. vivax malaria in an endemic area of Ethiopia. Detailed Description ----------------- The specific aims are (1) to test the feasibility and costs of methods and procedures for later use of MB-based combination therapy on a large scale, (2) to assess the safety of MB-based combination therapy, (3) to estimate the efficacy of MB-based combination therapy against malaria relapse, (4) to study the community acceptance of MB-based combination therapy, and (5) to strengthen the local capacity for malaria research and control in Jimma/Ethiopia. Study design: The study is designed as a pilot trial in adult patients with uncomplicated P. vivax malaria in Jimma, Ethiopia. Patients will be randomised to three treatment groups: Arthemeter/Lumefantrine (AL) AL-PQ, and AL-MB. Follow-up will be over a period of 6 months. Study population: Adult patients with uncomplicated P. vivax malaria (age ≥18 years) in Jimma/Ethiopia (G6PD deficient subjects are excluded) will become enrolled in the outpatient departments of the study centres. The sample size will be 33 per study arm, a total of 99 patients. Study treatments: AL standard treatments twice daily (total of 80 mg/dose A plus 480 mg/dose L) over first three study days PQ 15 mg once daily for 14 days MB 780 mg once daily for 14 days Treatments will be 100% directly observed. Study outcomes: Outcome parameters will be on feasibility and costs (e.g. recruitment rates, retention rates, costs per patient), on safety parameters (e.g. haemoglobin development during follow-up, incidence of adverse events), on efficacy parameters (e.g. incidence of P. vivax relapse during follow-up, malaria recurrence-free efficacy until day 180), and on community acceptance (e.g. perceptions on blue urine) during follow-up. Official Title ----------------- Feasibility of Methylene Blue-based Combination Therapy in the Radical Treatment of Adult Patients With Plasmodium Vivax Malaria in Ethiopia: a Randomised Controlled Pilot Trial Conditions ----------------- Vivax Malaria Intervention / Treatment ----------------- * Drug: Artemeter-Lumefantrine and MB (combination therapy) * Drug: Artemeter-Lumefantrine (combination therapy) * Drug: Artemeter-Lumefantrine and Primaquine (combination therapy) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age ≥18 years Uncomplicated P. vivax monoinfection (asexual parasite count >250/µl) Axillary temperature ≥ 37.5°C or history of fever during last 48 hours Ability to tolerate oral drug therapy Written informed consent of patient Permanent residence in the study area Exclusion Criteria: Therapy with an antimalarial (e.g. CQ, amodiaquine, pyrimethamine-sulfadoxine, quinine, any ACT) or an antibiotic which is effective against malaria parasites (e.g. doxycyclin, clindamycin, CoTrim) during last three weeks Mixed malaria infection Clinical danger signals (e.g. unable to stand or to sit, unable to drink, repeated vomiting, convulsions) or signs and symptoms of severe malaria (according to WHO definition) Known other serious illnesses (e.g. cardiac, renal, hepatic, pulmonary disease, severe malnutrition, severe infectious diseases) G6PD deficiency (<60% activity, WHO classification 1-3) Patients with known allergy to one or more of the study drugs Hemoglobin value <7 g/dL Pregnancy or breastfeeding Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Other: Artemeter-Lumefantrine (combination therapy)<br>33 patients (standard of care) \| Drug: Artemeter-Lumefantrine (combination therapy)<br>* AL first 3 days<br>* Other names: AL;\| \| Active Comparator: Artemeter-Lumefantrine and Primaquine (combination therapy)<br>33 patients \| Drug: Artemeter-Lumefantrine and Primaquine (combination therapy)<br>* AL first 3 days PQ next 14 days<br>* Other names: AL and PQ;\| \| Experimental: Artemeter-Lumefantrine and MB (combination therapy)<br>33 patients \| Drug: Artemeter-Lumefantrine and MB (combination therapy)<br>* AL first 3 days MB next 14 days<br>* Other names: CID 6099;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Study feasibility \| Patient recruitment rates \| 180 days \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Incidence of P. vivax \| Passive and active surveillance \| 180 days \| \| Adverse events (AE) during total follow-up period \| Passive and active surveillance \| 180 days \| \| Study costs \| Costs per patient \| 180 days \|
NCT03166696	Acute Myocardial Infarction and Acute Cerebral Infarction (AMIAC) Registry and Follow-up	A registry of consecutive patients who were admitted and diagnosed with acute myocardial infarction or acute cerebral infarction were conducted at the Guangdong General Hospital or the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Yue Bei People's Hospital, China, between January 2000 and December 2016. The adverse clinical outcomes, including all-cause mortality, were followed from the date of admission for acute myocardial infarction or acute cerebral infarction until study end (December 31, 2016). All-cause mortality, including the date of death, was identified from the electronic hospitalization data, phone follow-up, and confirmed by the household registration (HUKOU) system, a record of registration required by law in China. Baseline characteristics, including major treatment of acute myocardial infarction or acute cerebral infarction, estimated glomerular filtration rate (eGFR) and proteinuria, were collected. Demographic data were determined from the electronic hospitalization data and electronic hospital discharge records. All comorbid conditions were identified using International Statistical Classification of Diseases, Tenth Revision (ICD-10), coding algorithms applied to electronic physician claims and electronic hospital discharge records. Life style (smoking), treatment regimen at discharge, including angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor blocker (ARB), were determined from the electronic hospitalization data.		The Registry and Follow-up of Patients With Acute Myocardial Infarction or Acute Cerebral Infarction	Myocardial Infarction, Cerebral Infarction, Chronic Kidney Diseases, Mortality		Inclusion Criteria:~consecutive patients who were admitted and diagnosed with acute myocardial infarction or acute cerebral infarction~Exclusion Criteria:~lacunar infarction	null	null	All	No		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| all-cause mortality \| all-cause mortality \| follow up until the study end (May 2018,Anticipated) \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| kidney outcome \| ESRD or 50%eGFR decline \| follow up until the study end (May 2018,Anticipated) \|		Cerebral Infarction, Kidney Diseases, Renal Insufficiency, Chronic, Myocardial Infarction, Infarction, Urologic Diseases, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Male Urogenital Diseases, Ischemia, Pathologic Processes, Necrosis, Myocardial Ischemia, Heart Diseases, Cardiovascular Diseases, Vascular Diseases, Renal Insufficiency, Chronic Disease, Disease Attributes, Brain Infarction, Brain Ischemia, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Stroke	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| acute cerebral infarction<br>the registry and follow up of consecutive patients who were admitted and diagnosed with acute cerebral infarction \| \| \| acute myocardial infarction<br>the registry and follow up of consecutive patients who were admitted and diagnosed with acute myocardial infarction \| \|	Acute Myocardial Infarction and Acute Cerebral Infarction (AMIAC) Registry and Follow-up Study Overview ================= Brief Summary ----------------- A registry of consecutive patients who were admitted and diagnosed with acute myocardial infarction or acute cerebral infarction were conducted at the Guangdong General Hospital or the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Yue Bei People's Hospital, China, between January 2000 and December 2016. The adverse clinical outcomes, including all-cause mortality, were followed from the date of admission for acute myocardial infarction or acute cerebral infarction until study end (December 31, 2016). All-cause mortality, including the date of death, was identified from the electronic hospitalization data, phone follow-up, and confirmed by the household registration (HUKOU) system, a record of registration required by law in China. Baseline characteristics, including major treatment of acute myocardial infarction or acute cerebral infarction, estimated glomerular filtration rate (eGFR) and proteinuria, were collected. Demographic data were determined from the electronic hospitalization data and electronic hospital discharge records. All comorbid conditions were identified using International Statistical Classification of Diseases, Tenth Revision (ICD-10), coding algorithms applied to electronic physician claims and electronic hospital discharge records. Life style (smoking), treatment regimen at discharge, including angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor blocker (ARB), were determined from the electronic hospitalization data. Official Title ----------------- The Registry and Follow-up of Patients With Acute Myocardial Infarction or Acute Cerebral Infarction Conditions ----------------- Myocardial Infarction, Cerebral Infarction, Chronic Kidney Diseases, Mortality Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: consecutive patients who were admitted and diagnosed with acute myocardial infarction or acute cerebral infarction Exclusion Criteria: lacunar infarction Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| acute cerebral infarction<br>the registry and follow up of consecutive patients who were admitted and diagnosed with acute cerebral infarction \| \| \| acute myocardial infarction<br>the registry and follow up of consecutive patients who were admitted and diagnosed with acute myocardial infarction \| \| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| all-cause mortality \| all-cause mortality \| follow up until the study end (May 2018,Anticipated) \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| kidney outcome \| ESRD or 50%eGFR decline \| follow up until the study end (May 2018,Anticipated) \|
NCT03003533	A Gene Transfer Study for Hemophilia A	This clinical research study is being conducted by Spark Therapeutics, Inc. to determine the safety and efficacy of the factor VIII gene transfer treatment with SPK-8011 in individuals with hemophilia A.	Hemophilia A is a condition in which blood is unable to clot effectively. It is caused by a mutation or deletion in the gene that is responsible for producing blood-clotting factor VIII protein. Individuals with hemophilia A suffer from repeated bleeding episodes, often into the joints, which can cause chronic joint disease and sometime results in death due to the inability of the blood to clot efficiently. This chronic joint disease can have significant physical, psychosocial, and quality-of-life effects, including financial burden. The current treatment is intravenous (i.v.) injections of factor VIII protein products, either 2-3 times weekly or in response to bleeding.~Recent preliminary clinical data of a hemophilia B gene transfer study (which is also being conducted by Spark Therapeutics) shows all study participants achieving therapeutic factor IX activity levels (average of maintaining factor IX activity levels around 30% of normal with no confirmed bleeds, after receiving Spark gene transfer, with the approach of using the novel bio-engineered recombinant adeno-associated viral (rAAV) vector carrying a high specific activity of a factor IX gene. The approach being tested in this clinical research study uses a further modified novel AAV vector (with a stronger attraction to the human liver) to deliver the human factor VIII (hFVIII) gene into liver cells so that they can produce factor VIII protein.	Gene-transfer, Open-label, Dose-escalation Study of SPK-8011 [Adeno-associated Viral Vector With B-domain Deleted Human Factor VIII Gene] in Individuals With Hemophilia A	Hemophilia A	* Genetic: SPK-8011	Inclusion Criteria:~Males age18 years or older~Confirmed diagnosis of hemophilia A as evidenced by their medical history with plasma FVIII activity levels ≤ 2% of normal~Have received >150 exposure days (EDs) to FVIII concentrates or cryoprecipitate~Have experienced >10 bleeding events over the previous 12 months only if receiving on-demand therapy and having FVIII baseline level 1-2% of normal~Have no prior history of allergic reaction to any FVIII product~Have no measurable inhibitor against Factor VIII as assessed by the central laboratory and have no prior history of inhibitors to FVIII protein~Agree to use reliable barrier contraception~Exclusion Criteria:~Evidence of active hepatitis B or C~Currently on antiviral therapy for hepatitis B or C~Have significant underlying liver disease~Have serological evidence* of HIV-1 or HIV-2 with CD4 counts ≤200/mm3 (* participants who are HIV+ and stable with CD4 count >200/mm3 and undetectable viral load are eligible to enroll)~Have detectable antibodies reactive with AAV-Spark200 capsid~Participated in a gene transfer trial within the last 52 weeks or in a clinical trial with an investigational product within the last 12 weeks	18 Years	null	Male	No	Primary Purpose: Treatment Intervention Model: Sequential Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of study-related adverse events, including clinically significant abnormal laboratory values \| adverse events \| 52 weeks \| \| Changes from baseline in FVIII activity levels after a single outpatient administration of SPK-8011 \| changes in FVIII activity levels \| 52 weeks \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Kinetic assessment of SPK-8011 including shedding of vector DNA in bodily fluids \| vector shedding \| 52 weeks \| \| Number of participants requiring a course of steroid therapy for the elevations in liver enzymes \| number of participants requiring steroids \| 52 weeks \|	Adeno-Associated Virus (AAV), Blood Coagulation Disorders, Blood Coagulation Disorders, Inherited, Coagulation Protein Disorders, Factor VIII (FVIII), Factor VIII (FVIII) Deficiency, Factor VIII (FVIII) Gene, Factor VIII (FVIII) Protein, Genetic Diseases, Inborn, Genetic Diseases, X-Linked, Gene Therapy, Gene Transfer, Hematologic Diseases, Hemorrhagic Disorders, Recombinant, Vector	Hemophilia A, Blood Coagulation Disorders, Inherited, Blood Coagulation Disorders, Hematologic Diseases, Coagulation Protein Disorders, Hemorrhagic Disorders, Genetic Diseases, Inborn	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: SPK-8011<br>All participants who meet the eligibility criteria will receive an outpatient single intravenous (i.v.) administration of SPK-8011. \| Genetic: SPK-8011<br>* A novel, bio-engineered, recombinant adeno-associated viral vector carrying human factor VIII gene<br>\|	A Gene Transfer Study for Hemophilia A Study Overview ================= Brief Summary ----------------- This clinical research study is being conducted by Spark Therapeutics, Inc. to determine the safety and efficacy of the factor VIII gene transfer treatment with SPK-8011 in individuals with hemophilia A. Detailed Description ----------------- Hemophilia A is a condition in which blood is unable to clot effectively. It is caused by a mutation or deletion in the gene that is responsible for producing blood-clotting factor VIII protein. Individuals with hemophilia A suffer from repeated bleeding episodes, often into the joints, which can cause chronic joint disease and sometime results in death due to the inability of the blood to clot efficiently. This chronic joint disease can have significant physical, psychosocial, and quality-of-life effects, including financial burden. The current treatment is intravenous (i.v.) injections of factor VIII protein products, either 2-3 times weekly or in response to bleeding. Recent preliminary clinical data of a hemophilia B gene transfer study (which is also being conducted by Spark Therapeutics) shows all study participants achieving therapeutic factor IX activity levels (average of maintaining factor IX activity levels around 30% of normal with no confirmed bleeds, after receiving Spark gene transfer, with the approach of using the novel bio-engineered recombinant adeno-associated viral (rAAV) vector carrying a high specific activity of a factor IX gene. The approach being tested in this clinical research study uses a further modified novel AAV vector (with a stronger attraction to the human liver) to deliver the human factor VIII (hFVIII) gene into liver cells so that they can produce factor VIII protein. Official Title ----------------- Gene-transfer, Open-label, Dose-escalation Study of SPK-8011 [Adeno-associated Viral Vector With B-domain Deleted Human Factor VIII Gene] in Individuals With Hemophilia A Conditions ----------------- Hemophilia A Intervention / Treatment ----------------- * Genetic: SPK-8011 Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Males age18 years or older Confirmed diagnosis of hemophilia A as evidenced by their medical history with plasma FVIII activity levels ≤ 2% of normal Have received >150 exposure days (EDs) to FVIII concentrates or cryoprecipitate Have experienced >10 bleeding events over the previous 12 months only if receiving on-demand therapy and having FVIII baseline level 1-2% of normal Have no prior history of allergic reaction to any FVIII product Have no measurable inhibitor against Factor VIII as assessed by the central laboratory and have no prior history of inhibitors to FVIII protein Agree to use reliable barrier contraception Exclusion Criteria: Evidence of active hepatitis B or C Currently on antiviral therapy for hepatitis B or C Have significant underlying liver disease Have serological evidence* of HIV-1 or HIV-2 with CD4 counts ≤200/mm3 (* participants who are HIV+ and stable with CD4 count >200/mm3 and undetectable viral load are eligible to enroll) Have detectable antibodies reactive with AAV-Spark200 capsid Participated in a gene transfer trial within the last 52 weeks or in a clinical trial with an investigational product within the last 12 weeks Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- Male Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Sequential Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: SPK-8011<br>All participants who meet the eligibility criteria will receive an outpatient single intravenous (i.v.) administration of SPK-8011. \| Genetic: SPK-8011<br>* A novel, bio-engineered, recombinant adeno-associated viral vector carrying human factor VIII gene<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of study-related adverse events, including clinically significant abnormal laboratory values \| adverse events \| 52 weeks \| \| Changes from baseline in FVIII activity levels after a single outpatient administration of SPK-8011 \| changes in FVIII activity levels \| 52 weeks \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Kinetic assessment of SPK-8011 including shedding of vector DNA in bodily fluids \| vector shedding \| 52 weeks \| \| Number of participants requiring a course of steroid therapy for the elevations in liver enzymes \| number of participants requiring steroids \| 52 weeks \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Adeno-Associated Virus (AAV), Blood Coagulation Disorders, Blood Coagulation Disorders, Inherited, Coagulation Protein Disorders, Factor VIII (FVIII), Factor VIII (FVIII) Deficiency, Factor VIII (FVIII) Gene, Factor VIII (FVIII) Protein, Genetic Diseases, Inborn, Genetic Diseases, X-Linked, Gene Therapy, Gene Transfer, Hematologic Diseases, Hemorrhagic Disorders, Recombinant, Vector
NCT02353169	The Effects of Dexmedetomidine on the Heart Beat During Elective Surgery in Children	Dexmedetomidine is a sedative drug that is commonly used to improve calmness and reduce pain in children waking up after surgery. Some of the side effects of dexmedetomidine, such as a potential change in how the heart muscles contract and changes in blood sugar and potassium levels, are poorly understood. The current study aims to examine these changes directly in healthy children undergoing elective surgery by measuring the heart beats (with an electrocardiogram) and blood sugar and potassium at specific times before and after dexmedetomidine is given. The investigators aim to establish a better understanding of this drug's safety profile.	Purpose:~This study is being conducted to evaluate the effect of three different doses of dexmedetomidine (Precedex® , Hospira Healthcare) on myocardial repolarization, and blood glucose and potassium levels in children undergoing elective surgery.~Hypotheses:~The investigators hypothesize that administering a dexmedetomidine bolus will have some effect on myocardial repolarization, blood glucose, and potassium concentrations in a dose-dependent manner, whereas a saline bolus will not.~Justification:~Dexmedetomidine is a potent, centrally acting α-2 adrenoreceptor agonist with sympatholytic, sedative, amnestic, anxiolytic and analgesic effects, which properties make it popular for use in both pediatric anesthesia and intensive care. In 2013, dexmedetomidine was added to the possible risk factor for torsades de pointes (TdP) drug list on crediblemeds.org. Clinicians are currently advised to be vigilant about potential QT prolongation with dexmedetomidine, especially in patients with congenital long QT syndrome (LQTS). However, current evidence for dexmedetomidine-induced prolonged QT is sparse and somewhat contradictory, and the effect of dexmedetomidine on the Tp-e interval has yet to be reported in detail in adults or children. Another poorly defined pharmacodynamic effect of dexmedetomidine is its effect on blood glucose concentration. Theoretically, dexmedetomidine would be expected to cause hypoinsulinaemia and a resultant increase in blood glucose levels (hyperglycemia). Previous studies are in contrast to this however; with reports of hypoglycemia after large doses of the drug. Considering the use of dexmedetomidine in pediatric anesthesia, pediatric intensive care and its increasing use in the neonatal population, increased knowledge of the effect of dexmedetomidine on blood glucose would be valuable.~Finally, hypokalemia is listed as a treatment-emergent adverse event occurring in >2% of adult patients receiving dexmedetomidine in long-term intensive care unit sedation studies. The effect of dexmedetomidine on serum potassium levels in healthy children has yet to be elucidated. Given that hypokalemia increases the risk of TdP, and that there is a possibility that dexmedetomidine may be torsadogenic, this effect is also worthy of investigation.~In sum, the use of dexmedetomidine is associated with many clinical benefits, but its effects on indices of myocardial repolarization, as well as its effects on glucose and potassium metabolism, remain poorly understood and need to be better defined in order to use this drug safely and effectively.~Objectives:~The primary objective of this study is to investigate the effects of three different doses of dexmedetomidine (0.25/0.5/0.75 mcg/kg) on indices of myocardial repolarization (QTc and Tp-e intervals). As a secondary objective, this study will also sample blood glucose and potassium levels before and after dexmedetomidine administration to ascertain if there is any significant effect of a single bolus dose on blood glucose concentrations.~Research Method:~The investigators propose a randomized, single-blinded, 4-group comparative study to characterize the effects of different doses of dexmedetomidine on myocardial repolarization and blood glucose levels in healthy children undergoing elective surgery. The study-specific interventions will include giving a bolus of dexmedetomidine (0.25/0.5/0.75 mcg/kg; or 10mL saline) after induction of general anesthesia, recording two 12-lead ECGs (one before and one after dexmedetomidine administration), and taking three venous blood samples (one before and two after dexmedetomidine administration) to measure glucose and potassium. If the anesthetist would like to administer dexmedetomidine to a participant in the control (saline) group as part of their normal practice, they can do so after the study period is over (after the last blood sample).	The Effects of Dexmedetomidine on Myocardial Repolarization in Children	Myocardial Repolarization, Healthy	* Drug: Dexmedetomidine * Drug: Saline	Inclusion Criteria:~ASA Physical Status I-II~Age 3 to 10yrs~Elective surgical procedure requiring general anesthesia~Use of dexmedetomidine acceptable to the staff anesthesiologist~Un-premedicated~Ability to read and understand English (parent/legal guardian(s) and child)~Exclusion Criteria:~Long QT syndrome (LQTS)~Cardiac disease or rhythm abnormalities~Family history of LQTS or abnormal cardiac conduction~Currently taking medications known to prolong QT~Currently taking medications known to predispose to hypokalemia~Known hypersensitivity to dexmedetomidine or other study medication~Weight < 5th centile or > 95th centile for age~Previously diagnosed hypokalemia~Impaired renal or liver function~Pre-operative anxiety requiring sedatives or opioids~Refusal to participate	3 Years	10 Years	All	No	Primary Purpose: Basic Science Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Myocardial Repolarization (QTc and TP-e Intervals) 1min After Intervention \| Absolute QTc and TP-e values 1min after a bolus of dexmedetomidine or saline. Measured with 12-lead ECG. \| 60 seconds post-intervention \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Blood Glucose Levels at 15min and 30min Post-intervention \| Blood glucose levels at 15 min and 30 min after a bolus of dexmedetomidine or saline. Measured from 1 mL venous blood sample with blood gas analyzer. \| over 30 minutes post-intervention \| \| Blood Potassium Levels at 15min and 30min Post-intervention \| Blood potassium levels at 15 min and 30 min after a bolus of dexmedetomidine or saline. Measured from 1mL venous blood sample with blood gas analyzer \| over 30 minutes post-intervention \|	changes in myocardial repolarization in healthy children	Dexmedetomidine, Hypnotics and Sedatives, Central Nervous System Depressants, Physiological Effects of Drugs, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Adrenergic alpha-2 Receptor Agonists, Adrenergic alpha-Agonists, Adrenergic Agonists, Adrenergic Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Dexmedetomidine 0.25mcg/kg<br>0.25mcg/kg dexmedetomidine diluted with normal saline in a 10mL syringe, administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia. \| Drug: Dexmedetomidine<br> <br> * Other names: Precedex;\| \| Experimental: Dexmedetomidine 0.5mcg/kg<br>0.5mcg/kg dexmedetomidine diluted with normal saline in a 10mL syringe, administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia. \| Drug: Dexmedetomidine<br> <br> * Other names: Precedex;\| \| Experimental: Dexmedetomidine 0.75mcg/kg<br>0.75mcg/kg dexmedetomidine diluted with normal saline in a 10mL syringe, administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia. \| Drug: Dexmedetomidine<br> <br> * Other names: Precedex;\| \| Sham Comparator: Saline bolus<br>10mL normal saline solution administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia. \| Drug: Saline<br> <br> * Other names: 9% NaCl;\|	The Effects of Dexmedetomidine on the Heart Beat During Elective Surgery in Children Study Overview ================= Brief Summary ----------------- Dexmedetomidine is a sedative drug that is commonly used to improve calmness and reduce pain in children waking up after surgery. Some of the side effects of dexmedetomidine, such as a potential change in how the heart muscles contract and changes in blood sugar and potassium levels, are poorly understood. The current study aims to examine these changes directly in healthy children undergoing elective surgery by measuring the heart beats (with an electrocardiogram) and blood sugar and potassium at specific times before and after dexmedetomidine is given. The investigators aim to establish a better understanding of this drug's safety profile. Detailed Description ----------------- Purpose: This study is being conducted to evaluate the effect of three different doses of dexmedetomidine (Precedex® , Hospira Healthcare) on myocardial repolarization, and blood glucose and potassium levels in children undergoing elective surgery. Hypotheses: The investigators hypothesize that administering a dexmedetomidine bolus will have some effect on myocardial repolarization, blood glucose, and potassium concentrations in a dose-dependent manner, whereas a saline bolus will not. Justification: Dexmedetomidine is a potent, centrally acting α-2 adrenoreceptor agonist with sympatholytic, sedative, amnestic, anxiolytic and analgesic effects, which properties make it popular for use in both pediatric anesthesia and intensive care. In 2013, dexmedetomidine was added to the possible risk factor for torsades de pointes (TdP) drug list on crediblemeds.org. Clinicians are currently advised to be vigilant about potential QT prolongation with dexmedetomidine, especially in patients with congenital long QT syndrome (LQTS). However, current evidence for dexmedetomidine-induced prolonged QT is sparse and somewhat contradictory, and the effect of dexmedetomidine on the Tp-e interval has yet to be reported in detail in adults or children. Another poorly defined pharmacodynamic effect of dexmedetomidine is its effect on blood glucose concentration. Theoretically, dexmedetomidine would be expected to cause hypoinsulinaemia and a resultant increase in blood glucose levels (hyperglycemia). Previous studies are in contrast to this however; with reports of hypoglycemia after large doses of the drug. Considering the use of dexmedetomidine in pediatric anesthesia, pediatric intensive care and its increasing use in the neonatal population, increased knowledge of the effect of dexmedetomidine on blood glucose would be valuable. Finally, hypokalemia is listed as a treatment-emergent adverse event occurring in >2% of adult patients receiving dexmedetomidine in long-term intensive care unit sedation studies. The effect of dexmedetomidine on serum potassium levels in healthy children has yet to be elucidated. Given that hypokalemia increases the risk of TdP, and that there is a possibility that dexmedetomidine may be torsadogenic, this effect is also worthy of investigation. In sum, the use of dexmedetomidine is associated with many clinical benefits, but its effects on indices of myocardial repolarization, as well as its effects on glucose and potassium metabolism, remain poorly understood and need to be better defined in order to use this drug safely and effectively. Objectives: The primary objective of this study is to investigate the effects of three different doses of dexmedetomidine (0.25/0.5/0.75 mcg/kg) on indices of myocardial repolarization (QTc and Tp-e intervals). As a secondary objective, this study will also sample blood glucose and potassium levels before and after dexmedetomidine administration to ascertain if there is any significant effect of a single bolus dose on blood glucose concentrations. Research Method: The investigators propose a randomized, single-blinded, 4-group comparative study to characterize the effects of different doses of dexmedetomidine on myocardial repolarization and blood glucose levels in healthy children undergoing elective surgery. The study-specific interventions will include giving a bolus of dexmedetomidine (0.25/0.5/0.75 mcg/kg; or 10mL saline) after induction of general anesthesia, recording two 12-lead ECGs (one before and one after dexmedetomidine administration), and taking three venous blood samples (one before and two after dexmedetomidine administration) to measure glucose and potassium. If the anesthetist would like to administer dexmedetomidine to a participant in the control (saline) group as part of their normal practice, they can do so after the study period is over (after the last blood sample). Official Title ----------------- The Effects of Dexmedetomidine on Myocardial Repolarization in Children Conditions ----------------- Myocardial Repolarization, Healthy Intervention / Treatment ----------------- * Drug: Dexmedetomidine * Drug: Saline Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: ASA Physical Status I-II Age 3 to 10yrs Elective surgical procedure requiring general anesthesia Use of dexmedetomidine acceptable to the staff anesthesiologist Un-premedicated Ability to read and understand English (parent/legal guardian(s) and child) Exclusion Criteria: Long QT syndrome (LQTS) Cardiac disease or rhythm abnormalities Family history of LQTS or abnormal cardiac conduction Currently taking medications known to prolong QT Currently taking medications known to predispose to hypokalemia Known hypersensitivity to dexmedetomidine or other study medication Weight < 5th centile or > 95th centile for age Previously diagnosed hypokalemia Impaired renal or liver function Pre-operative anxiety requiring sedatives or opioids Refusal to participate Ages Eligible for Study ----------------- Minimum Age: 3 Years Maximum Age: 10 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Basic Science Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Dexmedetomidine 0.25mcg/kg<br>0.25mcg/kg dexmedetomidine diluted with normal saline in a 10mL syringe, administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia. \| Drug: Dexmedetomidine<br> <br> * Other names: Precedex;\| \| Experimental: Dexmedetomidine 0.5mcg/kg<br>0.5mcg/kg dexmedetomidine diluted with normal saline in a 10mL syringe, administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia. \| Drug: Dexmedetomidine<br> <br> * Other names: Precedex;\| \| Experimental: Dexmedetomidine 0.75mcg/kg<br>0.75mcg/kg dexmedetomidine diluted with normal saline in a 10mL syringe, administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia. \| Drug: Dexmedetomidine<br> <br> * Other names: Precedex;\| \| Sham Comparator: Saline bolus<br>10mL normal saline solution administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia. \| Drug: Saline<br> <br> * Other names: 9% NaCl;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Myocardial Repolarization (QTc and TP-e Intervals) 1min After Intervention \| Absolute QTc and TP-e values 1min after a bolus of dexmedetomidine or saline. Measured with 12-lead ECG. \| 60 seconds post-intervention \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Blood Glucose Levels at 15min and 30min Post-intervention \| Blood glucose levels at 15 min and 30 min after a bolus of dexmedetomidine or saline. Measured from 1 mL venous blood sample with blood gas analyzer. \| over 30 minutes post-intervention \| \| Blood Potassium Levels at 15min and 30min Post-intervention \| Blood potassium levels at 15 min and 30 min after a bolus of dexmedetomidine or saline. Measured from 1mL venous blood sample with blood gas analyzer \| over 30 minutes post-intervention \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- changes in myocardial repolarization in healthy children
NCT01230918	Study to Develop a Non-invasive Marker for Monitoring Myocardial Fibrosis	The objective is to determine whether 99Technetium-NC100692 uptake in patients with ACS (MI) can serve as a marker for scar formation as detected by contrast-enhanced MRI during the process of myocardial remodelling after the ischemic insult.~Comparison of ACS and HCM Populations:~The primary objective is to determine whether TcNC100692 imaging is able to quantify the extent to which myocardial fibrogenesis occurring early post myocardial infarction differs from that in patients with hypertrophic cardiomyopathy.~The primary hypothesis is that since fibrogenesis is known to occur most intensely in the first days to weeks post myocardial infarction, while it is a more protracted, less predictable process in HCM, there will be significantly more TcNC100692 uptake in the early post-ACS population than in the HCM population.~Control Population:~Normal control images will allow for differentiation of uptake in the myocardium.	HCM Population:~The primary objective is to determine whether fibrosis detected by MRI and 99mTc-NC100692 uptake in patients with HCM are associated. The secondary objective is to determine whether 99mTc-NC100692 uptake correlates on a segmental basis with fibrosis visualised by late Gd-enhancement MRI. The tertiary objective is to evaluate the relationship between the extent of fibrosis assessed by 99mTc-NC100692 uptake and mean longitudinal strain as determined by speckle tracking echocardiography.~The primary hypothesis is that there is an increased uptake of 99mTc-NC100692 in patients with HCM fibrosis detected by MRI. The secondary hypothesis is that the location and extent of increased 99mTc-NC100692 uptake will correlate with localization and extent measurements of fibrosis by Gd-enhanced magnetic resonance imaging. The tertiary hypothesis is that the extent of fibrosis assessed by the number of segments with and the magnitude of 99mTc NC100692 uptake will correlate with mean longitudinal strain as determined by speckle tracking echocardiography.~ACS Population:~The objective is to determine whether 99Technetium-NC100692 uptake in patients with ACS (MI) can serve as a marker for scar formation as detected by contrast-enhanced MRI during the process of myocardial remodelling after the ischemic insult.~The primary hypothesis is that there is an increased uptake of 99Technetium-NC100692 in patients following an ACS event (MI) and that the location and extent of increased 99Technetium-NC100692 uptake will correlate with the presence and extent of scar as detected by contrast-enhanced magnetic resonance imaging.~Normal Control Population:~Preliminary analysis of images from HCM population showed a diffuse, low grade uptake of 99Technetium-NC100692 in non-hypertrophied myocardial segments. Although not entirely unexpected, comparison with control images will allow for quantification of low grade fibrosis and low grade uptake.	Technetium-NC100692 SCintigraphy to Detect avB3 Integrin Expression as a mARker of Fibrosis in Hypertrophic Cardiomyopathy and Acute Coronary Syndrome: the SCAR Study	Hypertrophic Cardiomyopathy, Acute Coronary Syndrome	* Radiation: 99mTc-NC100692	HCM Population:~Inclusion Criteria:~Diagnosis of HCM as defined as: Interventricular septal thickness greater than 12 mm on a 2D echocardiogram, or septal: posterior wall thickness as measured on parasternal long axis view of >1.3 in the absence of secondary causes of cardiac hypertrophy such as aortic stenosis and systemic hypertension.~Exclusion Criteria:~Concomitant diseases that can lead to myocardial hypertrophy including valvular heart disease and uncontrolled hypertension. If HCM is proven by either the presence of a family history of HCM or through genotyping, patients with controlled hypertension will not be excluded.~Documented coronary artery disease including a history of previous myocardial infarction or coronary intervention or revascularization.~Known diabetic cardiomyopathy.~ACS Population:~Inclusion Criteria:~Diagnosis of ACS, either NSTEMI as determined by positive myocardial markers or STEMI patients who have an onset of symptoms 12 hours or less before presentation and an ST-segment elevation of at least 1 mm in two or more contiguous limb leads or of at least 2 mm in two or more contiguous precordial leads during prehospital 12-lead ECGs. Patients will undergo 99mTc-NC100692 imaging within 1 week of acute myocardial infarction.~Exclusion Criteria:~Patients presenting with an acute STEMI secondary to an occlusive thrombus who were revascularized with coronary artery bypass surgery.~Patients with a known prior history of cardiomyopathy of any cause (ex. ischemic, hypertrophic, infiltrative, idiopathic dilated), preceding the index referral for primary PCI.~Hemodynamic instability or cardiogenic shock.~Normal Control:~Inclusion Criteria:~No clinically significant chronic or acute illness as determined by history, echocardiogram and/or available reports.~Exclusion Criteria:~Subjects with pre-existing confounding factors, such as hypertension, diabetes mellitus, hyperlipidemia, CAD, known structural heart disease, left ventricular dysfunction, previous cerebrovascular event, malignancy, connective tissue or inflammatory disease, chronic infection, and hepatic or renal impairment will be excluded.~Possess abnormal cardiac structure and function after examination with ECHO~All populations:~Inclusion Criteria:~The subject is greater than or equal to 18 years of age at study entry.~Before any study procedure is carried out, the subject is able and willing to comply with study procedures and has provided signed and dated informed consent, including permission to access medical records.~The subject is male, or a female who is either surgically sterile (has had a documented bilateral oophorectomy and/or documented hysterectomy), postmenopausal (cessation of menses for more than 1 year), non-lactating, or of childbearing potential for whom the result of a urine pregnancy test performed before administration of IMP is negative.~Exclusion Criteria:~Hypersensitivity to any component of 99mTc-NC100692 injection (e.g. p- aminobenzoate).~Pregnancy.~Unwillingness to provide and sign for informed consent.~Creatinine clearance <30 ml/min.	18 Years	null	All	Accepts Healthy Volunteers	Primary Purpose: Diagnostic Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| TcNC100692 uptake \| The primary objective is to determine whether TcNC100692 imaging is able to quantify the extent to which myocardial fibrogenesis occurring early post myocardial infarction differs from that in patients with hypertrophic cardiomyopathy. \| 3 hours \|		Hypertrophic Cardiomyopathy, Acute Coronary Syndrome, Myocardial Fibrosis, Fibrogenesis, Intimal Hyperplasia, Sudden Death, avB3 Integrin Expression	Acute Coronary Syndrome, Cardiomyopathies, Cardiomyopathy, Hypertrophic, Syndrome, Fibrosis, Hypertrophy, Disease, Pathologic Processes, Myocardial Ischemia, Heart Diseases, Cardiovascular Diseases, Vascular Diseases, Pathological Conditions, Anatomical, Aortic Stenosis, Subvalvular, Aortic Valve Stenosis, Aortic Valve Disease, Heart Valve Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Diagnostic Imaging<br>A single dose of 800 to 1100 mBq of 99mTc-NC100692 radiopharmaceutical will be injected. Serial cardiac nuclear imaging will be done over a 3 hour period. \| Radiation: 99mTc-NC100692<br>* HCM and ACS subjects: 99mTc-NC100692 SPECT scan, CMR and echocardiography images will be obtained and compared.~Normal control: 99mTc-NC100692 SPECT scan, CMR and echocardiography imaging obtained for comparison with HCM and ACS images.<br>\|	Study to Develop a Non-invasive Marker for Monitoring Myocardial Fibrosis Study Overview ================= Brief Summary ----------------- The objective is to determine whether 99Technetium-NC100692 uptake in patients with ACS (MI) can serve as a marker for scar formation as detected by contrast-enhanced MRI during the process of myocardial remodelling after the ischemic insult. Comparison of ACS and HCM Populations: The primary objective is to determine whether TcNC100692 imaging is able to quantify the extent to which myocardial fibrogenesis occurring early post myocardial infarction differs from that in patients with hypertrophic cardiomyopathy. The primary hypothesis is that since fibrogenesis is known to occur most intensely in the first days to weeks post myocardial infarction, while it is a more protracted, less predictable process in HCM, there will be significantly more TcNC100692 uptake in the early post-ACS population than in the HCM population. Control Population: Normal control images will allow for differentiation of uptake in the myocardium. Detailed Description ----------------- HCM Population: The primary objective is to determine whether fibrosis detected by MRI and 99mTc-NC100692 uptake in patients with HCM are associated. The secondary objective is to determine whether 99mTc-NC100692 uptake correlates on a segmental basis with fibrosis visualised by late Gd-enhancement MRI. The tertiary objective is to evaluate the relationship between the extent of fibrosis assessed by 99mTc-NC100692 uptake and mean longitudinal strain as determined by speckle tracking echocardiography. The primary hypothesis is that there is an increased uptake of 99mTc-NC100692 in patients with HCM fibrosis detected by MRI. The secondary hypothesis is that the location and extent of increased 99mTc-NC100692 uptake will correlate with localization and extent measurements of fibrosis by Gd-enhanced magnetic resonance imaging. The tertiary hypothesis is that the extent of fibrosis assessed by the number of segments with and the magnitude of 99mTc NC100692 uptake will correlate with mean longitudinal strain as determined by speckle tracking echocardiography. ACS Population: The objective is to determine whether 99Technetium-NC100692 uptake in patients with ACS (MI) can serve as a marker for scar formation as detected by contrast-enhanced MRI during the process of myocardial remodelling after the ischemic insult. The primary hypothesis is that there is an increased uptake of 99Technetium-NC100692 in patients following an ACS event (MI) and that the location and extent of increased 99Technetium-NC100692 uptake will correlate with the presence and extent of scar as detected by contrast-enhanced magnetic resonance imaging. Normal Control Population: Preliminary analysis of images from HCM population showed a diffuse, low grade uptake of 99Technetium-NC100692 in non-hypertrophied myocardial segments. Although not entirely unexpected, comparison with control images will allow for quantification of low grade fibrosis and low grade uptake. Official Title ----------------- Technetium-NC100692 SCintigraphy to Detect avB3 Integrin Expression as a mARker of Fibrosis in Hypertrophic Cardiomyopathy and Acute Coronary Syndrome: the SCAR Study Conditions ----------------- Hypertrophic Cardiomyopathy, Acute Coronary Syndrome Intervention / Treatment ----------------- * Radiation: 99mTc-NC100692 Participation Criteria ================= Eligibility Criteria ----------------- HCM Population: Inclusion Criteria: Diagnosis of HCM as defined as: Interventricular septal thickness greater than 12 mm on a 2D echocardiogram, or septal: posterior wall thickness as measured on parasternal long axis view of >1.3 in the absence of secondary causes of cardiac hypertrophy such as aortic stenosis and systemic hypertension. Exclusion Criteria: Concomitant diseases that can lead to myocardial hypertrophy including valvular heart disease and uncontrolled hypertension. If HCM is proven by either the presence of a family history of HCM or through genotyping, patients with controlled hypertension will not be excluded. Documented coronary artery disease including a history of previous myocardial infarction or coronary intervention or revascularization. Known diabetic cardiomyopathy. ACS Population: Inclusion Criteria: Diagnosis of ACS, either NSTEMI as determined by positive myocardial markers or STEMI patients who have an onset of symptoms 12 hours or less before presentation and an ST-segment elevation of at least 1 mm in two or more contiguous limb leads or of at least 2 mm in two or more contiguous precordial leads during prehospital 12-lead ECGs. Patients will undergo 99mTc-NC100692 imaging within 1 week of acute myocardial infarction. Exclusion Criteria: Patients presenting with an acute STEMI secondary to an occlusive thrombus who were revascularized with coronary artery bypass surgery. Patients with a known prior history of cardiomyopathy of any cause (ex. ischemic, hypertrophic, infiltrative, idiopathic dilated), preceding the index referral for primary PCI. Hemodynamic instability or cardiogenic shock. Normal Control: Inclusion Criteria: No clinically significant chronic or acute illness as determined by history, echocardiogram and/or available reports. Exclusion Criteria: Subjects with pre-existing confounding factors, such as hypertension, diabetes mellitus, hyperlipidemia, CAD, known structural heart disease, left ventricular dysfunction, previous cerebrovascular event, malignancy, connective tissue or inflammatory disease, chronic infection, and hepatic or renal impairment will be excluded. Possess abnormal cardiac structure and function after examination with ECHO All populations: Inclusion Criteria: The subject is greater than or equal to 18 years of age at study entry. Before any study procedure is carried out, the subject is able and willing to comply with study procedures and has provided signed and dated informed consent, including permission to access medical records. The subject is male, or a female who is either surgically sterile (has had a documented bilateral oophorectomy and/or documented hysterectomy), postmenopausal (cessation of menses for more than 1 year), non-lactating, or of childbearing potential for whom the result of a urine pregnancy test performed before administration of IMP is negative. Exclusion Criteria: Hypersensitivity to any component of 99mTc-NC100692 injection (e.g. p- aminobenzoate). Pregnancy. Unwillingness to provide and sign for informed consent. Creatinine clearance <30 ml/min. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Diagnostic Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Diagnostic Imaging<br>A single dose of 800 to 1100 mBq of 99mTc-NC100692 radiopharmaceutical will be injected. Serial cardiac nuclear imaging will be done over a 3 hour period. \| Radiation: 99mTc-NC100692<br>* HCM and ACS subjects: 99mTc-NC100692 SPECT scan, CMR and echocardiography images will be obtained and compared. Normal control: 99mTc-NC100692 SPECT scan, CMR and echocardiography imaging obtained for comparison with HCM and ACS images.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| TcNC100692 uptake \| The primary objective is to determine whether TcNC100692 imaging is able to quantify the extent to which myocardial fibrogenesis occurring early post myocardial infarction differs from that in patients with hypertrophic cardiomyopathy. \| 3 hours \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Hypertrophic Cardiomyopathy, Acute Coronary Syndrome, Myocardial Fibrosis, Fibrogenesis, Intimal Hyperplasia, Sudden Death, avB3 Integrin Expression
NCT02718014	Evaluation of Periodontal Response to Non Surgical Therapy in Pre and Post Menopausal Women With Periodontitis	The present study was evaluated periodontal status in pre and post-menopausal women with periodontitis following non-surgical therapy.	AIM: The aim of the present study was to evaluate periodontal status in pre and post-menopausal women with periodontitis following non-surgical therapy.~MATERIALS AND METHODS: Periodontal status was measured by Periodontal index (PRI), and oral hygiene status was measured by plaque index (PI). Both the parameters were measured at baseline i.e before Scaling and Root Planing (SRP) and after 3 months intervals post treatment. SRP was done in both pre&post menopause groups.	Evaluation of Periodontal Response to Non Surgical Therapy in Pre and Post Menopausal Women With Periodontitis	Periodontitis, Menopause, Plaque, Inflammation	* Other: scaling and root planing (srp)	Inclusion Criteria:Patients should have at least 15 natural teeth remaining~Non smokers~Systemically healthy from past 6 months~Exclusion Criteria:Present or past smokers~Below 40 years of age~With gross oral pathology or tumors~Patients on long term steroid medication~Undergoing Hormone replacement therapy (HRT)~Pregnant women or planning for pregnancy~Those who have received periodontal therapy in the preceding 6 months~Those that are under medication in the preceding 6 months~Any systemic disorders or any medication that affects the periodontal status was excluded from this study.	40 Years	60 Years	Female	Accepts Healthy Volunteers	Primary Purpose: Supportive Care Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Evaluation of periodontal response to non surgical therapy in pre and post menopausal women with periodontitis \| pocket depth reduction calculated with PRI index \| 3 months \| \| Evaluation of periodontal response to non surgical therapy in pre and post menopausal \| plaque scores was calculated with Silness and Loe index \| 3 months \|		Non Surgical Therapy	Periodontitis, Inflammation, Pathologic Processes, Periodontal Diseases, Mouth Diseases, Stomatognathic Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Other: pre menopause with periodontitis<br>non surgical periodontal therapy (SCALING & ROOT PLANING) (SRP) \| Other: scaling and root planing (srp)<br> <br> \| \| Other: post menopause with periodontitis<br>non surgical periodontal therapy (SCALING & ROOT PLANING) (SRP) \| Other: scaling and root planing (srp)<br> <br> \|	Evaluation of Periodontal Response to Non Surgical Therapy in Pre and Post Menopausal Women With Periodontitis Study Overview ================= Brief Summary ----------------- The present study was evaluated periodontal status in pre and post-menopausal women with periodontitis following non-surgical therapy. Detailed Description ----------------- AIM: The aim of the present study was to evaluate periodontal status in pre and post-menopausal women with periodontitis following non-surgical therapy. MATERIALS AND METHODS: Periodontal status was measured by Periodontal index (PRI), and oral hygiene status was measured by plaque index (PI). Both the parameters were measured at baseline i.e before Scaling and Root Planing (SRP) and after 3 months intervals post treatment. SRP was done in both pre&post menopause groups. Official Title ----------------- Evaluation of Periodontal Response to Non Surgical Therapy in Pre and Post Menopausal Women With Periodontitis Conditions ----------------- Periodontitis, Menopause, Plaque, Inflammation Intervention / Treatment ----------------- * Other: scaling and root planing (srp) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria:Patients should have at least 15 natural teeth remaining Non smokers Systemically healthy from past 6 months Exclusion Criteria:Present or past smokers Below 40 years of age With gross oral pathology or tumors Patients on long term steroid medication Undergoing Hormone replacement therapy (HRT) Pregnant women or planning for pregnancy Those who have received periodontal therapy in the preceding 6 months Those that are under medication in the preceding 6 months Any systemic disorders or any medication that affects the periodontal status was excluded from this study. Ages Eligible for Study ----------------- Minimum Age: 40 Years Maximum Age: 60 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Supportive Care Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Other: pre menopause with periodontitis<br>non surgical periodontal therapy (SCALING & ROOT PLANING) (SRP) \| Other: scaling and root planing (srp)<br> <br> \| \| Other: post menopause with periodontitis<br>non surgical periodontal therapy (SCALING & ROOT PLANING) (SRP) \| Other: scaling and root planing (srp)<br> <br> \| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Evaluation of periodontal response to non surgical therapy in pre and post menopausal women with periodontitis \| pocket depth reduction calculated with PRI index \| 3 months \| \| Evaluation of periodontal response to non surgical therapy in pre and post menopausal \| plaque scores was calculated with Silness and Loe index \| 3 months \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Non Surgical Therapy
NCT05376514	Central Blood Pressure and Variability Evaluation	Background: A sub-study of the AARDVARK (Aortic Aneurysmal Regression of Dilation: Value of ACE-Inhibition on RisK) trial indicated a statistically significant association between central blood pressure (BP) variability and abdominal aortic aneurysm (AAA) growth. The role of anti-hypertensive adherence has not been explored in the context of AAA growth.~Objective: To confirm whether higher central BP variability is associated with higher AAA growth rates and to examine the effect of medication adherence on AAA growth rates in a prospective longitudinal cohort study.~Methods: Up to 175 patients will be recruited over ten months from two sites with standardised quality control of AAA, BP and antihypertensive non-adherence measurement. Patients (>55 years), with AAAs ≥3cm in diameter (including AAA ≥5.5cm, not proceeding to surgery) will be recruited and undergo AAA ultrasound (US), BP (peripheral and central) and antihypertensive non-adherence measurements every four months (+/- one month) for 24 months. Ambulatory BP variability data will be collected. Data on medication adherence and beliefs around medications will be collected with validated questionnaires.~Analysis: Primarily, the relationship between central diastolic BP visit-to-visit variability and AAA growth (estimated by multilevel modelling) based on US measurements and secondarily the relationship between central diastolic BP variability and time taken to reach the threshold for AAA repair (5.5 cm) or rupture.	The AARDVARK (Aortic Aneurysmal Regression of Dilation: Value of ACE-Inhibition on RisK) trial was designed to investigate the hypothesis that an ACE-inhibitor (perindopril) would reduce growth rate of small AAAs in a three-arm randomised placebo-controlled trial. While this didn't show a significant effect, results from an in-trial sub-study (CAVE study) demonstrated a significant relationship between central BP variability and aneurysm growth rates. This requires confirmation, in a dedicated study.~Design:~This is a multicentre prospective longitudinal observational cohort study. Each patient will have a study visit every 4 months with a minimum of 6 clinical visits where the study team will collect demographic data; psychological data (short form questionnaires that can be independently filled in); and physical data. The study team will also access routinely collected NHS cross-sectional imaging for comparison throughout the study, as quality control. No additional procedures involving ionising radiation will take place.~Study timeline:~There will be a 10-month recruitment period; all subjects will attend visits for a period of 18-24 months. The data collection will continue for 24 months in total. There will be a 6-month period of data analysis and write up.~Recruitment:~A cohort of up to 175 patients will be recruited from two trusts in London comprising four hospitals - Imperial College Healthcare NHS Trust (ICH) at St Mary's and Charing Cross hospitals, and London North West University Healthcare Trust (LNWH) at Northwick Park and Hillingdon hospitals. All visits and measurements will take place at central sites (St Mary's and Northwick Park hospitals).~Data Collection:~Demographic data - e.g. current prescribed anti-hypertensive medication and other cardiovascular medications, height and weight, medical history, smoking status~Psychological data - three short-form questionnaires that can be independently filled in by participants. Questionnaires will constitute measures of anxiety and depression (Hospital Anxiety and Depression Score [HADS]), current medication adherence (modified Voils Adherence Score), and beliefs around medication and adherence (Beliefs about Medicines Questionnaire [BMQ]).~Physical data - sitting mean peripheral and central systolic and diastolic BP, visit-to-visit central systolic and diastolic BP variability measured as standard deviation, coefficient of variation and variation independent of the mean will be measured using a validated arm cuff-based method. Ambulatory BP parameters will be measured using a validated monitor. USS AAA measurement will take place at bedside in supine position with outer-to-outer (OTO) calliper placement.~Primary Endpoint Analysis:~The association between central BP variability measured as standard deviation and AAA growth will be analysed using regression models where BP variability is the exposure and AAA growth is the outcome.~Random effects multilevel models where level-1 units are AAA repeated measurements nested within patients (level-2 units) will be used to estimate AAA growth. To explore non-linearity in AAA growth appropriate modelling will be used eg. linear splines.~Secondary Endpoints Analyses:~Survival analysis techniques such as Cox proportional hazards models will be used to assess the relationship between central BP variability and time taken for the AAA to reach the threshold for intervention (5.5 cm) or rupture.~Associations between haemodynamic parameters and aneurysm growth rate will be investigated. For each of the other measurements of systolic and diastolic central BP variability (coefficient of variation (SD ÷ mean) and variation independent of the mean calculated as SD÷(mean x) where x is determined empirically by curve fitting) and for other BP and haemodynamic parameters studied, the same multilevel model or generalised linear models will be used to estimate AAA growth. All analyses will be adjusted for an a-priori list of confounding variables.	Investigation Into the Effects of Central Blood Pressure Variability and Antihypertensive Adherence on the Size and Growth Rate of Abdominal Aortic Aneurysms	AAA, Abdominal Aortic Aneurysm, Blood Pressure		Inclusion Criteria:~Willing and able to give written informed consent~infrarenal aneurysms of ≥3cm in size (to include AAA ≥5.5cm in those not proceeding to surgery)~Exclusion Criteria:~Patient's with a known genetic aetiology of their AAA~age<55~known bilateral proximal upper extremity obstructive lesions~persistent cardiac arrhythmia~those unable to give informed consent~those too frail to travel for four monthly surveillance~any clinically significant medical condition which, in the opinion of the investigator, may interfere with the study results and/or reduce life expectancy to < 2 years~participation in another trial of an investigational product or device within the previous 30 days~unable or unwilling to comply with the requirements of the study, in the opinion of the investigator	55 Years	null	All	No		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Growth \| AAA growth as measured by multilevel modelling \| 24 months \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Time to rupture or repair \| Time taken for patient's AAA to rupture or to reach threshold for repair \| 24 months \|	AAA, Central blood pressure, Growth, Medication adherence, Blood pressure variability	Aortic Diseases, Aneurysm, Aortic Aneurysm, Aortic Aneurysm, Abdominal, Vascular Diseases, Cardiovascular Diseases		Central Blood Pressure and Variability Evaluation Study Overview ================= Brief Summary ----------------- Background: A sub-study of the AARDVARK (Aortic Aneurysmal Regression of Dilation: Value of ACE-Inhibition on RisK) trial indicated a statistically significant association between central blood pressure (BP) variability and abdominal aortic aneurysm (AAA) growth. The role of anti-hypertensive adherence has not been explored in the context of AAA growth. Objective: To confirm whether higher central BP variability is associated with higher AAA growth rates and to examine the effect of medication adherence on AAA growth rates in a prospective longitudinal cohort study. Methods: Up to 175 patients will be recruited over ten months from two sites with standardised quality control of AAA, BP and antihypertensive non-adherence measurement. Patients (>55 years), with AAAs ≥3cm in diameter (including AAA ≥5.5cm, not proceeding to surgery) will be recruited and undergo AAA ultrasound (US), BP (peripheral and central) and antihypertensive non-adherence measurements every four months (+/- one month) for 24 months. Ambulatory BP variability data will be collected. Data on medication adherence and beliefs around medications will be collected with validated questionnaires. Analysis: Primarily, the relationship between central diastolic BP visit-to-visit variability and AAA growth (estimated by multilevel modelling) based on US measurements and secondarily the relationship between central diastolic BP variability and time taken to reach the threshold for AAA repair (5.5 cm) or rupture. Detailed Description ----------------- The AARDVARK (Aortic Aneurysmal Regression of Dilation: Value of ACE-Inhibition on RisK) trial was designed to investigate the hypothesis that an ACE-inhibitor (perindopril) would reduce growth rate of small AAAs in a three-arm randomised placebo-controlled trial. While this didn't show a significant effect, results from an in-trial sub-study (CAVE study) demonstrated a significant relationship between central BP variability and aneurysm growth rates. This requires confirmation, in a dedicated study. Design: This is a multicentre prospective longitudinal observational cohort study. Each patient will have a study visit every 4 months with a minimum of 6 clinical visits where the study team will collect demographic data; psychological data (short form questionnaires that can be independently filled in); and physical data. The study team will also access routinely collected NHS cross-sectional imaging for comparison throughout the study, as quality control. No additional procedures involving ionising radiation will take place. Study timeline: There will be a 10-month recruitment period; all subjects will attend visits for a period of 18-24 months. The data collection will continue for 24 months in total. There will be a 6-month period of data analysis and write up. Recruitment: A cohort of up to 175 patients will be recruited from two trusts in London comprising four hospitals - Imperial College Healthcare NHS Trust (ICH) at St Mary's and Charing Cross hospitals, and London North West University Healthcare Trust (LNWH) at Northwick Park and Hillingdon hospitals. All visits and measurements will take place at central sites (St Mary's and Northwick Park hospitals). Data Collection: Demographic data - e.g. current prescribed anti-hypertensive medication and other cardiovascular medications, height and weight, medical history, smoking status Psychological data - three short-form questionnaires that can be independently filled in by participants. Questionnaires will constitute measures of anxiety and depression (Hospital Anxiety and Depression Score [HADS]), current medication adherence (modified Voils Adherence Score), and beliefs around medication and adherence (Beliefs about Medicines Questionnaire [BMQ]). Physical data - sitting mean peripheral and central systolic and diastolic BP, visit-to-visit central systolic and diastolic BP variability measured as standard deviation, coefficient of variation and variation independent of the mean will be measured using a validated arm cuff-based method. Ambulatory BP parameters will be measured using a validated monitor. USS AAA measurement will take place at bedside in supine position with outer-to-outer (OTO) calliper placement. Primary Endpoint Analysis: The association between central BP variability measured as standard deviation and AAA growth will be analysed using regression models where BP variability is the exposure and AAA growth is the outcome. Random effects multilevel models where level-1 units are AAA repeated measurements nested within patients (level-2 units) will be used to estimate AAA growth. To explore non-linearity in AAA growth appropriate modelling will be used eg. linear splines. Secondary Endpoints Analyses: Survival analysis techniques such as Cox proportional hazards models will be used to assess the relationship between central BP variability and time taken for the AAA to reach the threshold for intervention (5.5 cm) or rupture. Associations between haemodynamic parameters and aneurysm growth rate will be investigated. For each of the other measurements of systolic and diastolic central BP variability (coefficient of variation (SD ÷ mean) and variation independent of the mean calculated as SD÷(mean x) where x is determined empirically by curve fitting) and for other BP and haemodynamic parameters studied, the same multilevel model or generalised linear models will be used to estimate AAA growth. All analyses will be adjusted for an a-priori list of confounding variables. Official Title ----------------- Investigation Into the Effects of Central Blood Pressure Variability and Antihypertensive Adherence on the Size and Growth Rate of Abdominal Aortic Aneurysms Conditions ----------------- AAA, Abdominal Aortic Aneurysm, Blood Pressure Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Willing and able to give written informed consent infrarenal aneurysms of ≥3cm in size (to include AAA ≥5.5cm in those not proceeding to surgery) Exclusion Criteria: Patient's with a known genetic aetiology of their AAA age<55 known bilateral proximal upper extremity obstructive lesions persistent cardiac arrhythmia those unable to give informed consent those too frail to travel for four monthly surveillance any clinically significant medical condition which, in the opinion of the investigator, may interfere with the study results and/or reduce life expectancy to < 2 years participation in another trial of an investigational product or device within the previous 30 days unable or unwilling to comply with the requirements of the study, in the opinion of the investigator Ages Eligible for Study ----------------- Minimum Age: 55 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Growth \| AAA growth as measured by multilevel modelling \| 24 months \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Time to rupture or repair \| Time taken for patient's AAA to rupture or to reach threshold for repair \| 24 months \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- AAA, Central blood pressure, Growth, Medication adherence, Blood pressure variability
NCT02743871	Study Of PF-06817024 In Healthy Subjects, In Patients With Chronic Rhinosinusitis With Nasal Polyps And in Patients With Atopic Dermatitis	The purpose of this study is to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06817024 in healthy volunteers, in participants with chronic rhinosinusitis, with nasal polyps and in participants with moderate-to-severe Atopic Dermatitis	The purpose of the study for Part 1 is to evaluate the safety and tolerability of PF-06817024 in healthy subjects.~The purpose of the study for Part 2 is to evaluate the safety and tolerability of PF-06817024 in patients with chronic rhinosinusitis with nasal polyps.~The purpose of the study for Part 3 is to evaluate the safety and tolerability of PF-06817024 in patients with moderate-to-severe Atopic Dermatitis	A PHASE 1, RANDOMIZED, DOUBLE-BLIND, THIRD-PARTY OPEN, PLACEBO-CONTROLLED, DOSE ESCALATING STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF SINGLE AND/OR MULTIPLE INTRAVENOUS AND/OR SUBCUTANEOUS DOSES OF PF-06817024 IN HEALTHY SUBJECTS WHO MAY BE MILDLY ATOPIC, SUBJECTS WITH CHRONIC RHINOSINUSITIS WITH NASAL POLYPS, AND SUBJECTS WITH MODERATE-SEVERE ATOPIC DERMATITIS	Healthy, Chronic Rhinosinusitis With Nasal Polyps, Atopic Dermatitis	* Biological: PF-06817024 * Other: Placebo for PF-06817024 * Biological: PF-06817024 * Other: Placebo for PF-06817024 * Biological: PF-06817024 * Other: Placebo for PF-06817024 * Biological: PF-06817024 * Other: Placebo for PF-06817024 * Biological: PF-06817024 * Other: Placebo for PF-06817024	Inclusion Criteria~Healthy male subjects, healthy female subjects of non-childbearing potential, 18-55 years of age (Part 1)~Male subjects, female subjects of non-childbearing potential, female subjects of childbearing potential with documented bilateral tubal ligation (tubes tied) or bilateral salpingectomy (tubes removed), 18-65 years of age, and 2 of the following symptoms: nasal congestion/obstruction, nasal discharge, face pain/pressure,or reduction/loss of smell (Part 2)~Male or female subjects between the ages of 18 and 75 years, inclusive with moderate-to-severe Atopic Dermatitis, agree to avoid prolonged exposure to the sun and not to use tanning booths, sun lamps, or other ultraviolet light sources during the study (Part 3)~Exclusion Criteria:~Clinically significant diseases (cardiac, psychiatric, autoimmune, renal, etc.), positive urine drug test, fever within 7 days of dosing, active infections within 28 days of dosing (Part 1 and 2 and 3)~History of allergic reaction to topical lidocaine, nasal surgery within 6 months (Part 2)~Exposure to live or attenuated vaccines, have skin conditions other than Atopic Dermatitis, use of JAK inhibitors and biologics (Part 3)	18 Years	75 Years	All	Accepts Healthy Volunteers	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Sequential Assignment Masking: Quadruple	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 \| An adverse event (AE) was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence at any dose that: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect. \| From Study Day 1 (baseline) up to Day 421 (Cohort 1 and 2), Day 601 (Cohort 3), Day 691 (Cohort 4), Day 781 (Cohort 5), and Day 511 (Cohort 7). \| \| Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 \| An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence at any dose that: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect. The causality of TEAEs and SAEs was determined by the investigator. \| From Study Day 1 (baseline) up to Day 421 (Cohort 1 and 2), Day 601 (Cohort 3), Day 691 (Cohort 4), Day 781 (Cohort 5), and Day 511 (Cohort 7). \| \| Number of All-Causality TEAEs According to Severity in Part 1 \| An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. TEAE was assessed by the investigator according to severity; Mild: did not interfere with participant's usual function; moderate: interfered to some extent with participant's usual function; severe: interfered significantly with participant's usual function. \| From Study Day 1 (baseline) up to Day 421 (Cohort 1 and 2), Day 601 (Cohort 3), Day 691 (Cohort 4), Day 781 (Cohort 5), and Day 511 (Cohort 7). \| \| Number of Participants With Permanent Discontinuation Due to TEAEs in Part 1 \| An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. \| From Study Day 1 (baseline) up to Day 421 (Cohort 1 and 2), Day 601 (Cohort 3), Day 691 (Cohort 4), Day 781 (Cohort 5), and Day 511 (Cohort 7). \| \| Number of Participants With All-Causality TEAEs and SAEs in Part 2 \| An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence at any dose that: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect. \| From Study Day 1 (baseline) up to Day 691. \| \| Number of Participants With Treatment-Related TEAEs and SAEs in Part 2 \| An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence at any dose that: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect. The causality of TEAEs and SAEs was determined by the investigator. \| From Study Day 1 (baseline) up to Day 691. \| \| Number of All-Causality TEAEs According to Severity in Part 2 \| An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. TEAE was assessed by the investigator according to severity; Mild: did not interfere with participant's usual function; moderate: interfered to some extent with participant's usual function; severe: interfered significantly with participant's usual function. \| From Study Day 1 (baseline) up to Day 691. \| \| Number of Participants With Permanent Discontinuation Due to TEAEs in Part 2 \| An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. \| From Study Day 1 (baseline) up to Day 691. \| \| Number of Participants With All-Causality TEAEs and SAEs in Part 3 \| An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence at any dose that: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect. \| From Study Day 1 (baseline) up to Day 1105. \| \| Number of Participants With Treatment-Related TEAEs and SAEs in Part 3 \| An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence at any dose that: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect. The causality of TEAEs and SAEs was determined by the investigator. \| From Study Day 1 (baseline) up to Day 1105. \| \| Number of All-Causality TEAEs According to Severity in Part 3 \| An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. TEAE was assessed by the investigator according to severity; Mild: did not interfere with participant's usual function; moderate: interfered to some extent with participant's usual function; severe: interfered significantly with participant's usual function. \| From Study Day 1 (baseline) up to Day 1105. \| \| Number of Participants With Permanent Discontinuation Due to TEAEs in Part 3 \| An AE was any untoward medical occurrence in a clinical investigation participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. \| From Study Day 1 (baseline) up to Day 1105. \| \| Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 \| Hematology parameters included hemoglobin, hematocrit, red blood cell, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet and white blood cell count, total neutrophils, eosinophils, monocytes, basophils and lymphocytes. Chemistry parameters included blood urea nitrogen, glucose (fasting), calcium, sodium, potassium, chloride, bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein. Urine parameters included pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy. Clinical significance was judged by the investigator and those met the criteria of AE are listed here. Clinically significant laboratory abnormalities reported for at least 1 participant in the whole study are presented here. \| Part 1 single-dose cohorts: from Study Day 1 (baseline) up to Day 211. Part 1 multiple-dose cohorts: from Study Day 1 (baseline) up to Day 241. \| \| Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 2 \| Hematology parameters included hemoglobin, hematocrit, red blood cell, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet and white blood cell count, total neutrophils, eosinophils, monocytes, basophils and lymphocytes. Chemistry parameters included blood urea nitrogen, glucose (fasting), calcium, sodium, potassium, chloride, bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein. Urine parameters included pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy. Clinical significance was judged by the investigator and those met the criteria of AE are listed here. Clinically significant laboratory abnormalities reported for at least 1 participant in the whole study are presented here. \| Part 2: from Study Day 1 (baseline) up to Day 211. \| \| Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 3 \| Hematology parameters included hemoglobin, hematocrit, red blood cell, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet and white blood cell count, total neutrophils, eosinophils, monocytes, basophils and lymphocytes. Chemistry parameters included blood urea nitrogen, glucose (fasting), calcium, sodium, potassium, chloride, bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein. Urine parameters included pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy. Clinical significance was judged by the investigator and those met the criteria of AE are listed here. Clinically significant laboratory abnormalities reported for at least 1 participant in the whole study are presented here. \| Part 3: from Study Day 1 (baseline) up to Day 966. \| \| Number of Participants With Vital Sign Abnormalities in Part 1 \| Criteria for abnormality in vital signs: supine pulse rate <40 beats per minute (bpm) or >120 bpm; supine diastolic blood pressure (DBP) <50 mmHg, maximum increase or decrease from baseline of >=20 mmHg; supine systolic blood pressure (SBP) <90 mmHg, maximum increase or decrease from baseline of >=30 mmHg. Baseline was defined as the last measurement prior to the first dosing. Vital sign abnormalities reported for at least 1 participant are presented here. \| Study Day 1 (baseline) up to end of study (Study Day 211 for Part 1 SD cohorts, and Study Day 241 for Part 1 MD cohorts). \| \| Number of Participants With Vital Sign Abnormalities in Part 2 \| Criteria for abnormality in vital signs: supine pulse rate <40 bpm or >120 bpm; supine DBP <50 mmHg, maximum increase or decrease from baseline of >=20 mmHg; supine SBP <90 mmHg, maximum increase or decrease from baseline of >=30 mmHg. Baseline was defined as the last measurement prior to the first dosing. Vital sign abnormalities reported for at least 1 participant are presented here. \| Study Day 1 (baseline) up to end of study (Study Day 211). \| \| Number of Participants With Vital Sign Abnormalities in Part 3 \| Criteria for abnormality in vital signs: supine pulse rate <40 bpm or >120 bpm; supine DBP <50 mmHg, maximum increase or decrease from baseline of >=20 mmHg; supine SBP <90 mmHg, maximum increase or decrease from baseline of >=30 mmHg. Baseline was defined as the last measurement prior to the first dosing. Vital sign abnormalities reported for at least 1 participant are presented here. \| Study Day 1 (baseline) up to end of study (Study Day 337). \| \| Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 \| ECG abnormalities criteria included: 1) maximum QTc interval adjusted according Fridericia formula (QTcF) (msec): 450<= QTcF <480, 480<= QTcF <500, and QTcF >=500; QTcF maximum increase from baseline(msec): 30<= change <60, and change >=60; 2) maximum PR interval (msec): >=300; PR increase from baseline (msec): baseline >200 with 25% increase at maximum, baseline <=200 with 50% increase at maximum; 3) maximum QRS (msec): >=140; QRS increase from baseline (msec) >=50%. Baseline was defined as the average of the last triplicate measurement prior to the first dosing. ECG abnormalities reported for at least 1 participant are presented here. \| Study Day 1 (baseline) up to end of study (Study Day 211 for Part 1 SD cohorts, and Study Day 241 for Part 1 MD cohorts). \| \| Number of Participants With ECG Abnormalities in Part 2 \| ECG abnormalities criteria included: 1) maximum QTc interval adjusted according Fridericia formula (QTcF) (msec): 450<= QTcF <480, 480<= QTcF <500, and QTcF >=500; QTcF maximum increase from baseline(msec): 30<= change <60, and change >=60; 2) maximum PR interval (msec): >=300; PR increase from baseline (msec): baseline >200 with 25% increase at maximum, baseline <=200 with 50% increase at maximum; 3) maximum QRS (msec): >=140; QRS increase from baseline (msec) >=50%. Baseline was defined as the average of the last triplicate measurement prior to the first dosing. ECG abnormalities reported for at least 1 participant are presented here. \| Study Day 1 (baseline) up to end of study (Study Day 211). \| \| Number of Participants With ECG Abnormalities in Part 3 \| ECG abnormalities criteria included: 1) maximum QTc interval adjusted according Fridericia formula (QTcF) (msec): 450<= QTcF <480, 480<= QTcF <500, and QTcF >=500; QTcF maximum increase from baseline(msec): 30<= change <60, and change >=60; 2) maximum PR interval (msec): >=300; PR increase from baseline (msec): baseline >200 with 25% increase at maximum, baseline <=200 with 50% increase at maximum; 3) maximum QRS (msec): >=140; QRS increase from baseline (msec) >=50%. Baseline was defined as the average of the last triplicate measurement prior to the first dosing. ECG abnormalities reported for at least 1 participant are presented here. \| Study Day 1 (baseline) up to end of study (Study Day 337). \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Maximum Observed Serum Concentration (Cmax) of PF-06817024 Following Single Dose in Part 1 \| Maximum observed serum concentration (Cmax) of PF-06817024 following single dose in Part 1; Cmax was defined as the maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose). \| \| Cmax of PF-06817024 Following Multiple Doses in Part 1 \| Cmax was defined as the maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose). \| \| Cmax of PF-06817024 in Part 2 \| Cmax was defined as the maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to a maximum of 690 days/16560 hours post dose). \| \| Cmax of PF-06817024 in Part 3 \| Cmax was defined as the maximum observed serum concentration. \| On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85). \| \| Dose Normalized Maximum Observed Serum Concentration (Cmax[dn]) of PF-06817024 Following Single Dose in Part 1 \| Cmax(dn) was defined as the dose normalized maximum observed serum concentration, and calculated by Cmax/Dose. Cmax was defined as the maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose). \| \| Cmax(dn) of PF-06817024 Following Multiple Doses in Part 1 \| Cmax(dn) was defined as dose normalized maximum observed serum concentration, and calculated by Cmax/Dose. Cmax was defined as the maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose). \| \| Cmax(dn) of PF-06817024 in Part 2 \| Cmax(dn) was defined as the dose normalized maximum observed serum concentration, and calculated by Cmax/Dose. Cmax was defined as the maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to a maximum of 690 days/16560 hours post dose). \| \| Cmax(dn) of PF-06817024 in Part 3 \| Cmax(dn) was defined as the dose normalized maximum observed serum concentration, and calculated by Cmax/Dose. Cmax was defined as the maximum observed serum concentration. \| On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85). \| \| Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06817024 Following Single Dose in Part 1 \| Time to reach maximum observed serum concentration (Tmax) of PF-06817024 in Part 1; Tmax was defined as time to reach maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose). \| \| Tmax of PF-06817024 Following Multiple Doses in Part 1 \| Tmax was defined as time to reach maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose). \| \| Tmax of PF-06817024 in Part 2 \| Tmax was defined as time to reach maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to a maximum of 690 days/16560 hours post dose). \| \| Tmax of PF-06817024 in Part 3 \| Tmax was defined as time to reach maximum observed serum concentration. \| On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85). \| \| Area Under the Curve From Time Zero to Infinity Concentration (AUCinf) of PF-06817024 Following Single Dose in Part 1 and 2 \| Area under the curve from time zero to infinity concentration (AUCinf) of PF-06817024 following single dose in Part 1 and 2; AUCinf was defined as area under the curve from time zero to infinity concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to 780 days for Part 1 and 690 days for Part 2). For Part 1 only: at post-dose 48 and 72 hour, Days 46 and 151. \| \| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06817024 Following Single Dose in Part 1 and 2 \| Area under the curve from time zero to last quantifiable concentration (AUClast) of PF-06817024 following single dose in Part 1 and 2; AUClast was defined as area under the curve from time zero to last quantifiable concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to 780 days for Part 1 and 690 days for Part 2). For Part 1 only: at post-dose 48 and 72 hour, Days 46 and 151. \| \| Area Under the Curve Within Dosing Interval (AUCtau) of PF-06817024 Following Multiple Doses in Part 1 \| Area under the curve within dosing interval (AUCtau) of PF-06817024 following multiple doses in Part 1; AUCtau was defined as area under the curve within dosing interval. The dosing interval was 720 hours. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose). \| \| AUCtau of PF-06817024 in Part 3 \| AUCtau was defined as area under the curve within dosing interval. The dosing interval was 672 hours. \| On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85). \| \| Dose Normalized Area Under the Curve Within Dosing Interval (AUCtau[dn]) of PF-06817024 Following Multiple Doses in Part 1 \| Dose normalized area under the curve within dosing interval (AUCtau[dn]) of PF-06817024 following multiple doses in Part 1; AUCtau(dn) was defined as dose normalized area under the curve within dosing interval. The dosing interval was 720 hours. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose). \| \| AUCtau(dn) of PF-06817024 Following Multiple Doses in Part 3 \| AUCtau(dn) was defined as dose normalized area under the curve within dosing interval. The dosing interval was 672 hours. \| On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85). \| \| Average Concentration Over Dosing Interval (Cav) of PF-06817024 Following Multiple Doses in Part 1 \| Average concentration over dosing interval (Cav) of PF-06817024 following multiple doses in Part 1; Cav was defined as average concentration over dosing interval. The dosing interval was 720 hours. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose). \| \| Cav of PF-06817024 Following Multiple Doses in Part 3 \| Cav was defined as average concentration over dosing interval. The dosing interval was 672 hours. \| On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85). \| \| Terminal Elimination Half Life (t1/2) of PF-06817024 Following Single Dose in Part 1 \| t1/2 was defined as terminal elimination half life, and was calculated by Loge(2)/kel, where kel was the terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose). \| \| t1/2 of PF-06817024 Following Multiple Doses in Part 1 \| T1/2 of PF-06817024 following multiple doses in Part 1; t1/2 was defined as terminal elimination half life. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose). \| \| t1/2 of PF-06817024 in Part 2 \| t1/2 was defined as terminal elimination half life, and was calculated by Loge(2)/kel, where kel was the terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. \| Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to a maximum of 690 days/16560 hours post dose). \| \| t1/2 of PF-06817024 in Part 3 \| t1/2 was defined as terminal elimination half life, and was calculated by Loge(2)/kel, where kel was the terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. For Part 3 Cohort 13: PF-06817024 600 mg + 300 mg IV AD, t1/2 of the last dose on Day 85 was reported in the table. \| On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85). \| \| Apparent Volume of Distribution (Vz/F) of PF-06817024 for the Subcutaneous Cohort in Part 1 \| Apparent volume of distribution (Vz/F) of PF-06817024 for the subcutaneous cohort in Part 1; Vz/F was defined as apparent volume of distribution. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose). \| \| Apparent Clearance (CL/F) of PF-06817024 for the Subcutaneous Cohort in Part 1 \| Apparent clearance (CL/F) of PF-06817024 for the subcutaneous cohort in Part 1; CL/F was defined as apparent clearance. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose). \| \| Volume of Distribution at Steady State (Vss) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2 \| Volume of distribution at steady state (Vss) of PF-06817024 following a single dose in Part 1 and Part 2; Vss was defined as volume of distribution at steady state. \| Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to 780 days for Part 1 and 690 days for Part 2). For Part 1 only: at post-dose 48 and 72 hour, Days 46 and 151. \| \| Clearance (CL) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2 \| CL was defined as Clearance, calculated by Dose/AUCinf. AUCinf was defined as area under the curve from time zero to infinity concentration. \| On Day 1 at pre-dose, post-dose 1, 2, 4, 8, 12, 24, 96 hour, Day 8, 15, 32, 61, 91, 121,181, 211, 241, 331, and 421. For Part 1 only: at post-dose 48 and 72 hour, Day 46 and 151. For Part 2 only: on Day 511, 601, and 691. \| \| Trough Serum Concentration (Cmin) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1 \| Trough serum concentration (Cmin) of PF-06817024 post second dose following multiple doses in Part 1; Cmin was defined as the trough serum concentration. \| At pre-dose on Day 31 or Day 46. \| \| Cmin of PF-06817024 Post Last Dose Following Multiple Doses in Part 3 \| Cmin of PF-06817024 post last dose following multiple doses in Part 3; Cmin was defined as the trough serum concentration. \| At pre dose (0 hour) on Day 85. \| \| Accumulation Ratio for Cmax (Rac, Cmax) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1 \| Rac, Cmax was defined as accumulation ratio for Cmax, and was calculated by (Cmax on Day 31 or Day 46) / Cmax on Day 1. Cmax was defined as the maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose). \| \| Rac, Cmax of PF-06817024 Post Last Dose Following Multiple Doses in Part 3 \| Rac, Cmax was defined as accumulation ratio for Cmax, and was calculated by (Cmax on Day 85) / (Cmax on Day 1). Cmax was defined as the maximum observed serum concentration. \| On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85). \| \| Accumulation Ratio for AUCtau (Rac) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1 \| Rac was defined as accumulation ratio for AUCtau. AUCtau was defined as area under the curve within dosing interval. The dosing interval was 720 hours. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose). \| \| Rac of PF-06817024 Post Last Dose Following Multiple Doses in Part 3 \| Rac was defined as accumulation ratio for AUCtau. AUCtau was defined as area under the curve within dosing interval. The dosing interval was 672 hours. \| On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85). \| \| Number of Participants With Treatment-Induced Anti-Drug Antibody (ADA) Against PF-06817024 in Part 1, 2, and 3 \| ADA was an immunogenicity endpoint. A participant had treatment-induced ADA when baseline titer was missing or negative and the participant had >=1 post-treatment positive titer. \| Part 1 SD cohorts: baseline up to Day 780; Part 1 MD cohort: baseline up to Day 693; Part 2: baseline up to Day 692, Part 3: baseline up to Day 964. \| \| Number of Participants With Treatment-Induced Neutralizing Antibodies (NAbs) Against PF-06817024 in Part 1, 2, and 3 \| NAb was an immunogenicity endpoint. A participant had treatment-induced NAb when baseline titer was missing or negative and the participant had >=1 post-treatment positive titer. \| Part 1 SD cohorts: baseline up to Day 780; Part 1 MD cohort: baseline up to Day 693; Part 2: baseline up to Day 692, Part 3: baseline up to Day 964. \|	FIH, Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, Atopic Dermatitis, Chronic Rhinosinusitis, Nasal Polyps	Eczema, Hypersensitivity, Sinusitis, Dermatitis, Nasal Polyps, Dermatitis, Atopic, Polyps, Skin Diseases, Skin Diseases, Genetic, Genetic Diseases, Inborn, Skin Diseases, Eczematous, Hypersensitivity, Immediate, Immune System Diseases, Pathological Conditions, Anatomical, Respiratory Tract Infections, Infections, Paranasal Sinus Diseases, Nose Diseases, Respiratory Tract Diseases, Otorhinolaryngologic Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Cohort 1<br>10 mg of PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given one dose of PF-06817024 intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given one dose of placebo for PF-06817024 intravenously<br>\| \| Experimental: Cohort 2<br>30 mg of PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given one dose of PF-06817024 intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given one dose of placebo for PF-06817024 intravenously<br>\| \| Experimental: Cohort 3<br>100 mg of PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given two doses of PF-06817024 intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given two doses of PF-06817024 intravenously<br>\| \| Experimental: Cohort 4<br>300 mg of PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given one dose of PF-06817024 intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given one dose of placebo for PF-06817024 intravenously<br>\| \| Experimental: Cohort 5<br>1000 mg of PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given one dose of PF-06817024 intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given one dose of placebo for PF-06817024 intravenously<br>\| \| Experimental: Cohort 6<br>2000 mg of PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given one dose of PF-06817024 intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given one dose of placebo for PF-06817024 intravenously<br>\| \| Experimental: Cohort 7<br>30 mg subcutaneous dose of PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given one dose of PF-06817024 subcutaneously<br>Other: Placebo for PF-06817024<br>* Subjects will be given one dose of placebo for PF-06817024 subcutaneously<br>\| \| Experimental: Cohort 8<br>300 mg of PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given one dose of PF-06817024 intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given one dose of placebo for PF-06817024 intravenously<br>\| \| Experimental: Cohort 9<br>IV dose to be determined of PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given one dose of PF-06817024 intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given one dose of placebo for PF-06817024 intravenously<br>\| \| Experimental: Cohort 10<br>PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given 2 doses intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given 2 doses intravenously<br>\| \| Experimental: Cohort 11<br>PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given 2 doses intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given 2 doses intravenously<br>\| \| Experimental: Cohort 12<br>PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given 2 doses intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given 2 doses intravenously<br>\| \| Experimental: Cohort 13<br>PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given doses of PF-06817024 intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given doses of Placebo intravenously<br>\|	Study Of PF-06817024 In Healthy Subjects, In Patients With Chronic Rhinosinusitis With Nasal Polyps And in Patients With Atopic Dermatitis Study Overview ================= Brief Summary ----------------- The purpose of this study is to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06817024 in healthy volunteers, in participants with chronic rhinosinusitis, with nasal polyps and in participants with moderate-to-severe Atopic Dermatitis Detailed Description ----------------- The purpose of the study for Part 1 is to evaluate the safety and tolerability of PF-06817024 in healthy subjects. The purpose of the study for Part 2 is to evaluate the safety and tolerability of PF-06817024 in patients with chronic rhinosinusitis with nasal polyps. The purpose of the study for Part 3 is to evaluate the safety and tolerability of PF-06817024 in patients with moderate-to-severe Atopic Dermatitis Official Title ----------------- A PHASE 1, RANDOMIZED, DOUBLE-BLIND, THIRD-PARTY OPEN, PLACEBO-CONTROLLED, DOSE ESCALATING STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF SINGLE AND/OR MULTIPLE INTRAVENOUS AND/OR SUBCUTANEOUS DOSES OF PF-06817024 IN HEALTHY SUBJECTS WHO MAY BE MILDLY ATOPIC, SUBJECTS WITH CHRONIC RHINOSINUSITIS WITH NASAL POLYPS, AND SUBJECTS WITH MODERATE-SEVERE ATOPIC DERMATITIS Conditions ----------------- Healthy, Chronic Rhinosinusitis With Nasal Polyps, Atopic Dermatitis Intervention / Treatment ----------------- * Biological: PF-06817024 * Other: Placebo for PF-06817024 * Biological: PF-06817024 * Other: Placebo for PF-06817024 * Biological: PF-06817024 * Other: Placebo for PF-06817024 * Biological: PF-06817024 * Other: Placebo for PF-06817024 * Biological: PF-06817024 * Other: Placebo for PF-06817024 Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria Healthy male subjects, healthy female subjects of non-childbearing potential, 18-55 years of age (Part 1) Male subjects, female subjects of non-childbearing potential, female subjects of childbearing potential with documented bilateral tubal ligation (tubes tied) or bilateral salpingectomy (tubes removed), 18-65 years of age, and 2 of the following symptoms: nasal congestion/obstruction, nasal discharge, face pain/pressure,or reduction/loss of smell (Part 2) Male or female subjects between the ages of 18 and 75 years, inclusive with moderate-to-severe Atopic Dermatitis, agree to avoid prolonged exposure to the sun and not to use tanning booths, sun lamps, or other ultraviolet light sources during the study (Part 3) Exclusion Criteria: Clinically significant diseases (cardiac, psychiatric, autoimmune, renal, etc.), positive urine drug test, fever within 7 days of dosing, active infections within 28 days of dosing (Part 1 and 2 and 3) History of allergic reaction to topical lidocaine, nasal surgery within 6 months (Part 2) Exposure to live or attenuated vaccines, have skin conditions other than Atopic Dermatitis, use of JAK inhibitors and biologics (Part 3) Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 75 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Sequential Assignment Masking: Quadruple Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Cohort 1<br>10 mg of PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given one dose of PF-06817024 intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given one dose of placebo for PF-06817024 intravenously<br>\| \| Experimental: Cohort 2<br>30 mg of PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given one dose of PF-06817024 intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given one dose of placebo for PF-06817024 intravenously<br>\| \| Experimental: Cohort 3<br>100 mg of PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given two doses of PF-06817024 intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given two doses of PF-06817024 intravenously<br>\| \| Experimental: Cohort 4<br>300 mg of PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given one dose of PF-06817024 intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given one dose of placebo for PF-06817024 intravenously<br>\| \| Experimental: Cohort 5<br>1000 mg of PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given one dose of PF-06817024 intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given one dose of placebo for PF-06817024 intravenously<br>\| \| Experimental: Cohort 6<br>2000 mg of PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given one dose of PF-06817024 intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given one dose of placebo for PF-06817024 intravenously<br>\| \| Experimental: Cohort 7<br>30 mg subcutaneous dose of PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given one dose of PF-06817024 subcutaneously<br>Other: Placebo for PF-06817024<br>* Subjects will be given one dose of placebo for PF-06817024 subcutaneously<br>\| \| Experimental: Cohort 8<br>300 mg of PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given one dose of PF-06817024 intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given one dose of placebo for PF-06817024 intravenously<br>\| \| Experimental: Cohort 9<br>IV dose to be determined of PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given one dose of PF-06817024 intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given one dose of placebo for PF-06817024 intravenously<br>\| \| Experimental: Cohort 10<br>PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given 2 doses intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given 2 doses intravenously<br>\| \| Experimental: Cohort 11<br>PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given 2 doses intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given 2 doses intravenously<br>\| \| Experimental: Cohort 12<br>PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given 2 doses intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given 2 doses intravenously<br>\| \| Experimental: Cohort 13<br>PF-06817024 or placebo \| Biological: PF-06817024<br>* Subjects will be given doses of PF-06817024 intravenously<br>Other: Placebo for PF-06817024<br>* Subjects will be given doses of Placebo intravenously<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 \| An adverse event (AE) was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence at any dose that: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect. \| From Study Day 1 (baseline) up to Day 421 (Cohort 1 and 2), Day 601 (Cohort 3), Day 691 (Cohort 4), Day 781 (Cohort 5), and Day 511 (Cohort 7). \| \| Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 \| An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence at any dose that: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect. The causality of TEAEs and SAEs was determined by the investigator. \| From Study Day 1 (baseline) up to Day 421 (Cohort 1 and 2), Day 601 (Cohort 3), Day 691 (Cohort 4), Day 781 (Cohort 5), and Day 511 (Cohort 7). \| \| Number of All-Causality TEAEs According to Severity in Part 1 \| An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. TEAE was assessed by the investigator according to severity; Mild: did not interfere with participant's usual function; moderate: interfered to some extent with participant's usual function; severe: interfered significantly with participant's usual function. \| From Study Day 1 (baseline) up to Day 421 (Cohort 1 and 2), Day 601 (Cohort 3), Day 691 (Cohort 4), Day 781 (Cohort 5), and Day 511 (Cohort 7). \| \| Number of Participants With Permanent Discontinuation Due to TEAEs in Part 1 \| An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. \| From Study Day 1 (baseline) up to Day 421 (Cohort 1 and 2), Day 601 (Cohort 3), Day 691 (Cohort 4), Day 781 (Cohort 5), and Day 511 (Cohort 7). \| \| Number of Participants With All-Causality TEAEs and SAEs in Part 2 \| An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence at any dose that: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect. \| From Study Day 1 (baseline) up to Day 691. \| \| Number of Participants With Treatment-Related TEAEs and SAEs in Part 2 \| An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence at any dose that: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect. The causality of TEAEs and SAEs was determined by the investigator. \| From Study Day 1 (baseline) up to Day 691. \| \| Number of All-Causality TEAEs According to Severity in Part 2 \| An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. TEAE was assessed by the investigator according to severity; Mild: did not interfere with participant's usual function; moderate: interfered to some extent with participant's usual function; severe: interfered significantly with participant's usual function. \| From Study Day 1 (baseline) up to Day 691. \| \| Number of Participants With Permanent Discontinuation Due to TEAEs in Part 2 \| An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. \| From Study Day 1 (baseline) up to Day 691. \| \| Number of Participants With All-Causality TEAEs and SAEs in Part 3 \| An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence at any dose that: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect. \| From Study Day 1 (baseline) up to Day 1105. \| \| Number of Participants With Treatment-Related TEAEs and SAEs in Part 3 \| An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence at any dose that: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect. The causality of TEAEs and SAEs was determined by the investigator. \| From Study Day 1 (baseline) up to Day 1105. \| \| Number of All-Causality TEAEs According to Severity in Part 3 \| An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. TEAE was assessed by the investigator according to severity; Mild: did not interfere with participant's usual function; moderate: interfered to some extent with participant's usual function; severe: interfered significantly with participant's usual function. \| From Study Day 1 (baseline) up to Day 1105. \| \| Number of Participants With Permanent Discontinuation Due to TEAEs in Part 3 \| An AE was any untoward medical occurrence in a clinical investigation participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. \| From Study Day 1 (baseline) up to Day 1105. \| \| Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 \| Hematology parameters included hemoglobin, hematocrit, red blood cell, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet and white blood cell count, total neutrophils, eosinophils, monocytes, basophils and lymphocytes. Chemistry parameters included blood urea nitrogen, glucose (fasting), calcium, sodium, potassium, chloride, bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein. Urine parameters included pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy. Clinical significance was judged by the investigator and those met the criteria of AE are listed here. Clinically significant laboratory abnormalities reported for at least 1 participant in the whole study are presented here. \| Part 1 single-dose cohorts: from Study Day 1 (baseline) up to Day 211. Part 1 multiple-dose cohorts: from Study Day 1 (baseline) up to Day 241. \| \| Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 2 \| Hematology parameters included hemoglobin, hematocrit, red blood cell, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet and white blood cell count, total neutrophils, eosinophils, monocytes, basophils and lymphocytes. Chemistry parameters included blood urea nitrogen, glucose (fasting), calcium, sodium, potassium, chloride, bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein. Urine parameters included pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy. Clinical significance was judged by the investigator and those met the criteria of AE are listed here. Clinically significant laboratory abnormalities reported for at least 1 participant in the whole study are presented here. \| Part 2: from Study Day 1 (baseline) up to Day 211. \| \| Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 3 \| Hematology parameters included hemoglobin, hematocrit, red blood cell, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet and white blood cell count, total neutrophils, eosinophils, monocytes, basophils and lymphocytes. Chemistry parameters included blood urea nitrogen, glucose (fasting), calcium, sodium, potassium, chloride, bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein. Urine parameters included pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy. Clinical significance was judged by the investigator and those met the criteria of AE are listed here. Clinically significant laboratory abnormalities reported for at least 1 participant in the whole study are presented here. \| Part 3: from Study Day 1 (baseline) up to Day 966. \| \| Number of Participants With Vital Sign Abnormalities in Part 1 \| Criteria for abnormality in vital signs: supine pulse rate <40 beats per minute (bpm) or >120 bpm; supine diastolic blood pressure (DBP) <50 mmHg, maximum increase or decrease from baseline of >=20 mmHg; supine systolic blood pressure (SBP) <90 mmHg, maximum increase or decrease from baseline of >=30 mmHg. Baseline was defined as the last measurement prior to the first dosing. Vital sign abnormalities reported for at least 1 participant are presented here. \| Study Day 1 (baseline) up to end of study (Study Day 211 for Part 1 SD cohorts, and Study Day 241 for Part 1 MD cohorts). \| \| Number of Participants With Vital Sign Abnormalities in Part 2 \| Criteria for abnormality in vital signs: supine pulse rate <40 bpm or >120 bpm; supine DBP <50 mmHg, maximum increase or decrease from baseline of >=20 mmHg; supine SBP <90 mmHg, maximum increase or decrease from baseline of >=30 mmHg. Baseline was defined as the last measurement prior to the first dosing. Vital sign abnormalities reported for at least 1 participant are presented here. \| Study Day 1 (baseline) up to end of study (Study Day 211). \| \| Number of Participants With Vital Sign Abnormalities in Part 3 \| Criteria for abnormality in vital signs: supine pulse rate <40 bpm or >120 bpm; supine DBP <50 mmHg, maximum increase or decrease from baseline of >=20 mmHg; supine SBP <90 mmHg, maximum increase or decrease from baseline of >=30 mmHg. Baseline was defined as the last measurement prior to the first dosing. Vital sign abnormalities reported for at least 1 participant are presented here. \| Study Day 1 (baseline) up to end of study (Study Day 337). \| \| Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 \| ECG abnormalities criteria included: 1) maximum QTc interval adjusted according Fridericia formula (QTcF) (msec): 450<= QTcF <480, 480<= QTcF <500, and QTcF >=500; QTcF maximum increase from baseline(msec): 30<= change <60, and change >=60; 2) maximum PR interval (msec): >=300; PR increase from baseline (msec): baseline >200 with 25% increase at maximum, baseline <=200 with 50% increase at maximum; 3) maximum QRS (msec): >=140; QRS increase from baseline (msec) >=50%. Baseline was defined as the average of the last triplicate measurement prior to the first dosing. ECG abnormalities reported for at least 1 participant are presented here. \| Study Day 1 (baseline) up to end of study (Study Day 211 for Part 1 SD cohorts, and Study Day 241 for Part 1 MD cohorts). \| \| Number of Participants With ECG Abnormalities in Part 2 \| ECG abnormalities criteria included: 1) maximum QTc interval adjusted according Fridericia formula (QTcF) (msec): 450<= QTcF <480, 480<= QTcF <500, and QTcF >=500; QTcF maximum increase from baseline(msec): 30<= change <60, and change >=60; 2) maximum PR interval (msec): >=300; PR increase from baseline (msec): baseline >200 with 25% increase at maximum, baseline <=200 with 50% increase at maximum; 3) maximum QRS (msec): >=140; QRS increase from baseline (msec) >=50%. Baseline was defined as the average of the last triplicate measurement prior to the first dosing. ECG abnormalities reported for at least 1 participant are presented here. \| Study Day 1 (baseline) up to end of study (Study Day 211). \| \| Number of Participants With ECG Abnormalities in Part 3 \| ECG abnormalities criteria included: 1) maximum QTc interval adjusted according Fridericia formula (QTcF) (msec): 450<= QTcF <480, 480<= QTcF <500, and QTcF >=500; QTcF maximum increase from baseline(msec): 30<= change <60, and change >=60; 2) maximum PR interval (msec): >=300; PR increase from baseline (msec): baseline >200 with 25% increase at maximum, baseline <=200 with 50% increase at maximum; 3) maximum QRS (msec): >=140; QRS increase from baseline (msec) >=50%. Baseline was defined as the average of the last triplicate measurement prior to the first dosing. ECG abnormalities reported for at least 1 participant are presented here. \| Study Day 1 (baseline) up to end of study (Study Day 337). \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Maximum Observed Serum Concentration (Cmax) of PF-06817024 Following Single Dose in Part 1 \| Maximum observed serum concentration (Cmax) of PF-06817024 following single dose in Part 1; Cmax was defined as the maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose). \| \| Cmax of PF-06817024 Following Multiple Doses in Part 1 \| Cmax was defined as the maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose). \| \| Cmax of PF-06817024 in Part 2 \| Cmax was defined as the maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to a maximum of 690 days/16560 hours post dose). \| \| Cmax of PF-06817024 in Part 3 \| Cmax was defined as the maximum observed serum concentration. \| On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85). \| \| Dose Normalized Maximum Observed Serum Concentration (Cmax[dn]) of PF-06817024 Following Single Dose in Part 1 \| Cmax(dn) was defined as the dose normalized maximum observed serum concentration, and calculated by Cmax/Dose. Cmax was defined as the maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose). \| \| Cmax(dn) of PF-06817024 Following Multiple Doses in Part 1 \| Cmax(dn) was defined as dose normalized maximum observed serum concentration, and calculated by Cmax/Dose. Cmax was defined as the maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose). \| \| Cmax(dn) of PF-06817024 in Part 2 \| Cmax(dn) was defined as the dose normalized maximum observed serum concentration, and calculated by Cmax/Dose. Cmax was defined as the maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to a maximum of 690 days/16560 hours post dose). \| \| Cmax(dn) of PF-06817024 in Part 3 \| Cmax(dn) was defined as the dose normalized maximum observed serum concentration, and calculated by Cmax/Dose. Cmax was defined as the maximum observed serum concentration. \| On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85). \| \| Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06817024 Following Single Dose in Part 1 \| Time to reach maximum observed serum concentration (Tmax) of PF-06817024 in Part 1; Tmax was defined as time to reach maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose). \| \| Tmax of PF-06817024 Following Multiple Doses in Part 1 \| Tmax was defined as time to reach maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose). \| \| Tmax of PF-06817024 in Part 2 \| Tmax was defined as time to reach maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to a maximum of 690 days/16560 hours post dose). \| \| Tmax of PF-06817024 in Part 3 \| Tmax was defined as time to reach maximum observed serum concentration. \| On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85). \| \| Area Under the Curve From Time Zero to Infinity Concentration (AUCinf) of PF-06817024 Following Single Dose in Part 1 and 2 \| Area under the curve from time zero to infinity concentration (AUCinf) of PF-06817024 following single dose in Part 1 and 2; AUCinf was defined as area under the curve from time zero to infinity concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to 780 days for Part 1 and 690 days for Part 2). For Part 1 only: at post-dose 48 and 72 hour, Days 46 and 151. \| \| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06817024 Following Single Dose in Part 1 and 2 \| Area under the curve from time zero to last quantifiable concentration (AUClast) of PF-06817024 following single dose in Part 1 and 2; AUClast was defined as area under the curve from time zero to last quantifiable concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to 780 days for Part 1 and 690 days for Part 2). For Part 1 only: at post-dose 48 and 72 hour, Days 46 and 151. \| \| Area Under the Curve Within Dosing Interval (AUCtau) of PF-06817024 Following Multiple Doses in Part 1 \| Area under the curve within dosing interval (AUCtau) of PF-06817024 following multiple doses in Part 1; AUCtau was defined as area under the curve within dosing interval. The dosing interval was 720 hours. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose). \| \| AUCtau of PF-06817024 in Part 3 \| AUCtau was defined as area under the curve within dosing interval. The dosing interval was 672 hours. \| On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85). \| \| Dose Normalized Area Under the Curve Within Dosing Interval (AUCtau[dn]) of PF-06817024 Following Multiple Doses in Part 1 \| Dose normalized area under the curve within dosing interval (AUCtau[dn]) of PF-06817024 following multiple doses in Part 1; AUCtau(dn) was defined as dose normalized area under the curve within dosing interval. The dosing interval was 720 hours. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose). \| \| AUCtau(dn) of PF-06817024 Following Multiple Doses in Part 3 \| AUCtau(dn) was defined as dose normalized area under the curve within dosing interval. The dosing interval was 672 hours. \| On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85). \| \| Average Concentration Over Dosing Interval (Cav) of PF-06817024 Following Multiple Doses in Part 1 \| Average concentration over dosing interval (Cav) of PF-06817024 following multiple doses in Part 1; Cav was defined as average concentration over dosing interval. The dosing interval was 720 hours. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose). \| \| Cav of PF-06817024 Following Multiple Doses in Part 3 \| Cav was defined as average concentration over dosing interval. The dosing interval was 672 hours. \| On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85). \| \| Terminal Elimination Half Life (t1/2) of PF-06817024 Following Single Dose in Part 1 \| t1/2 was defined as terminal elimination half life, and was calculated by Loge(2)/kel, where kel was the terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose). \| \| t1/2 of PF-06817024 Following Multiple Doses in Part 1 \| T1/2 of PF-06817024 following multiple doses in Part 1; t1/2 was defined as terminal elimination half life. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose). \| \| t1/2 of PF-06817024 in Part 2 \| t1/2 was defined as terminal elimination half life, and was calculated by Loge(2)/kel, where kel was the terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. \| Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to a maximum of 690 days/16560 hours post dose). \| \| t1/2 of PF-06817024 in Part 3 \| t1/2 was defined as terminal elimination half life, and was calculated by Loge(2)/kel, where kel was the terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. For Part 3 Cohort 13: PF-06817024 600 mg + 300 mg IV AD, t1/2 of the last dose on Day 85 was reported in the table. \| On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85). \| \| Apparent Volume of Distribution (Vz/F) of PF-06817024 for the Subcutaneous Cohort in Part 1 \| Apparent volume of distribution (Vz/F) of PF-06817024 for the subcutaneous cohort in Part 1; Vz/F was defined as apparent volume of distribution. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose). \| \| Apparent Clearance (CL/F) of PF-06817024 for the Subcutaneous Cohort in Part 1 \| Apparent clearance (CL/F) of PF-06817024 for the subcutaneous cohort in Part 1; CL/F was defined as apparent clearance. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose). \| \| Volume of Distribution at Steady State (Vss) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2 \| Volume of distribution at steady state (Vss) of PF-06817024 following a single dose in Part 1 and Part 2; Vss was defined as volume of distribution at steady state. \| Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to 780 days for Part 1 and 690 days for Part 2). For Part 1 only: at post-dose 48 and 72 hour, Days 46 and 151. \| \| Clearance (CL) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2 \| CL was defined as Clearance, calculated by Dose/AUCinf. AUCinf was defined as area under the curve from time zero to infinity concentration. \| On Day 1 at pre-dose, post-dose 1, 2, 4, 8, 12, 24, 96 hour, Day 8, 15, 32, 61, 91, 121,181, 211, 241, 331, and 421. For Part 1 only: at post-dose 48 and 72 hour, Day 46 and 151. For Part 2 only: on Day 511, 601, and 691. \| \| Trough Serum Concentration (Cmin) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1 \| Trough serum concentration (Cmin) of PF-06817024 post second dose following multiple doses in Part 1; Cmin was defined as the trough serum concentration. \| At pre-dose on Day 31 or Day 46. \| \| Cmin of PF-06817024 Post Last Dose Following Multiple Doses in Part 3 \| Cmin of PF-06817024 post last dose following multiple doses in Part 3; Cmin was defined as the trough serum concentration. \| At pre dose (0 hour) on Day 85. \| \| Accumulation Ratio for Cmax (Rac, Cmax) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1 \| Rac, Cmax was defined as accumulation ratio for Cmax, and was calculated by (Cmax on Day 31 or Day 46) / Cmax on Day 1. Cmax was defined as the maximum observed serum concentration. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose). \| \| Rac, Cmax of PF-06817024 Post Last Dose Following Multiple Doses in Part 3 \| Rac, Cmax was defined as accumulation ratio for Cmax, and was calculated by (Cmax on Day 85) / (Cmax on Day 1). Cmax was defined as the maximum observed serum concentration. \| On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85). \| \| Accumulation Ratio for AUCtau (Rac) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1 \| Rac was defined as accumulation ratio for AUCtau. AUCtau was defined as area under the curve within dosing interval. The dosing interval was 720 hours. \| Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose). \| \| Rac of PF-06817024 Post Last Dose Following Multiple Doses in Part 3 \| Rac was defined as accumulation ratio for AUCtau. AUCtau was defined as area under the curve within dosing interval. The dosing interval was 672 hours. \| On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85). \| \| Number of Participants With Treatment-Induced Anti-Drug Antibody (ADA) Against PF-06817024 in Part 1, 2, and 3 \| ADA was an immunogenicity endpoint. A participant had treatment-induced ADA when baseline titer was missing or negative and the participant had >=1 post-treatment positive titer. \| Part 1 SD cohorts: baseline up to Day 780; Part 1 MD cohort: baseline up to Day 693; Part 2: baseline up to Day 692, Part 3: baseline up to Day 964. \| \| Number of Participants With Treatment-Induced Neutralizing Antibodies (NAbs) Against PF-06817024 in Part 1, 2, and 3 \| NAb was an immunogenicity endpoint. A participant had treatment-induced NAb when baseline titer was missing or negative and the participant had >=1 post-treatment positive titer. \| Part 1 SD cohorts: baseline up to Day 780; Part 1 MD cohort: baseline up to Day 693; Part 2: baseline up to Day 692, Part 3: baseline up to Day 964. \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- FIH, Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, Atopic Dermatitis, Chronic Rhinosinusitis, Nasal Polyps
NCT04021550	Improving 24-hour Blood Pressure in Obstructive Sleep Apnea	This study examines the combined effects of an angiotensin receptor blocker (ARB), antioxidant supplementation, and continuous positive airway pressure (CPAP) therapy on the lowering of 24-hour blood pressure in persons with moderate to severe Obstructive Sleep Apnea (OSA). All participants will undergo CPAP therapy as prescribed by their doctor; however, half of the participants will receive the combined ARB and antioxidant treatment while the other half of the participants will receive a placebo.	OSA is a sleep disorder characterized by repetitive collapses (apneas) or partial collapses (hypopneas) of the upper airway. These airway obstructions result in intermittent reductions in arterial oxygen saturation (hypoxia), which causes a reflexive increase in sympathetic activation and systemic vasoconstriction. Resumption of breathing results in transient surges in blood pressure (BP) that can reach as high as 240/130 mm/Hg.~OSA effects up to 24% of the adult population and evidence suggests a causal relationship between OSA and cardiovascular disease (CVD) development. While the exact mechanisms are unknown, data from animal and human models suggest that exposure to chronic intermittent hypoxia (IH) plays a significant role in the pathogenesis of cardiovascular comorbidity. Persons with OSA exhibit increased daytime sympathetic activity, markers of oxidative stress, and vasoactive hormones, particularly angiotensin II, that contribute to systemic vasoconstriction. These factors contribute to early endothelial dysfunction and contribute to sustained elevations in BP.~While CPAP is the gold standard OSA treatment, adherence rates are low and evidence suggests that treatment does not reduce the rates of CVD in large population-based studies.~Telmisartan is a receptor blocker for angiotensin II and not only has BP lowering effects, but also has unique anti-inflammatory properties and beneficial influences on endothelial function. The addition of an antioxidant supplement may increase the reactive oxygen species scavenging capacity and, in combination with ARB treatment, may provide more robust effects on BP in persons with OSA.	Combined Treatment of Angiotensin Receptor Blocker and Antioxidant Supplementation as a Novel Adjunctive Therapy for 24-hour Blood Pressure Improvement in Obstructive Sleep Apnea	Obstructive Sleep Apnea	* Device: Continuous Positive Airway Pressure CPAP * Drug: Telmisartan 80mg * Dietary Supplement: Alpha-Lipoic Acid 600mg * Other: Microcrystalline Cellulose	Inclusion Criteria:~Apnea/Hypopnea Index (AHI) greater than/equal to 15 events per hour of sleep~No prior use of CPAP~Body mass index less than 30kg/m2~Does not take ARBs or angiotensin converting enzyme inhibitors for blood pressure control~Females of childbearing potential on an effective or highly effective means of contraception~Exclusion Criteria:~Prescribed and/or taking the following medications: diuretics (including potassium-sparing diuretics), Digoxin, lithium salts, and/or nonsteroidal anti-inflammatory drugs~Over the counter supplements that affect the cardiovascular system, such as fish oils, vitamins, or other antioxidants~History of heart failure~History of myocardial infarction~History of coronary artery disease~History of stroke~History of diabetes mellitus~History of impaired renal function~History of chronic obstructive pulmonary disease~History of asthma~History of central sleep apnea~Smoked within the past year~Hypotensive (Systolic blood pressure (SBP) <90 mmHg and diastolic blood pressure (DBP) <60 mmHg)~Females who do not have a means of contraception, are pregnant, planning to become pregnant, and/or are breast-feeding	18 Years	65 Years	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change in 24-hour blood pressure \| Systolic, diastolic, and mean arterial blood pressure (mmHg) \| Change from baseline of 24-hour systolic, diastolic, and mean arterial blood pressure at 6 weeks \|		Continuous Positive Airway Pressure, 24-hour blood pressure, Telmisartan, Alpha-Lipoic Acid	Thioctic Acid, Telmisartan, Antihypertensive Agents, Angiotensin II Type 1 Receptor Blockers, Angiotensin Receptor Antagonists, Micronutrients, Molecular Mechanisms of Pharmacological Action, Antioxidants, Protective Agents, Physiological Effects of Drugs, Vitamin B Complex, Vitamins	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Combined Treatment<br>Subjects will be given 80 mg/day Telmisartan + 600 mg/day Alpha-Lipoic Acid. Subjects will also be prescribed CPAP therapy by their physician. Subjects will be instructed to use their CPAP device according to their physician's guidelines. \| Device: Continuous Positive Airway Pressure CPAP<br>* All subjects will be advised to use their continuous positive airway pressure (CPAP) in accordance to their physician's guidelines.<br>Drug: Telmisartan 80mg<br>* Subjects in this group will receive 80mg/day of Telmisartan (an angiotensin receptor blocker). Treatments will be administered in pre-packaged blister packages. Subjects will take Telmisartan once per day for 6 weeks.<br>Dietary Supplement: Alpha-Lipoic Acid 600mg<br>* Subjects in this group will receive 600mg/day of Alpha-Lipoic Acid (an antioxidant). Treatments will be administered in pre-packaged blister packages. Subjects will take Alpha-Lipoic Acid once per day for 6 weeks.<br>\| \| Placebo Comparator: Placebo Control<br>Subjects will be given placebo capsules. Subjects will also be prescribed CPAP therapy by their physician. Subjects will be instructed to use their CPAP device according to their physician's guidelines. \| Device: Continuous Positive Airway Pressure CPAP<br>* All subjects will be advised to use their continuous positive airway pressure (CPAP) in accordance to their physician's guidelines.<br>Other: Microcrystalline Cellulose<br>* Subjects in this group will receive two capsules of Microcrystalline Cellulose (placebo). Treatments will be administered in pre-packaged blister packages. Subjects will take placebo pills once per day for 6 weeks.<br>\|	Improving 24-hour Blood Pressure in Obstructive Sleep Apnea Study Overview ================= Brief Summary ----------------- This study examines the combined effects of an angiotensin receptor blocker (ARB), antioxidant supplementation, and continuous positive airway pressure (CPAP) therapy on the lowering of 24-hour blood pressure in persons with moderate to severe Obstructive Sleep Apnea (OSA). All participants will undergo CPAP therapy as prescribed by their doctor; however, half of the participants will receive the combined ARB and antioxidant treatment while the other half of the participants will receive a placebo. Detailed Description ----------------- OSA is a sleep disorder characterized by repetitive collapses (apneas) or partial collapses (hypopneas) of the upper airway. These airway obstructions result in intermittent reductions in arterial oxygen saturation (hypoxia), which causes a reflexive increase in sympathetic activation and systemic vasoconstriction. Resumption of breathing results in transient surges in blood pressure (BP) that can reach as high as 240/130 mm/Hg. OSA effects up to 24% of the adult population and evidence suggests a causal relationship between OSA and cardiovascular disease (CVD) development. While the exact mechanisms are unknown, data from animal and human models suggest that exposure to chronic intermittent hypoxia (IH) plays a significant role in the pathogenesis of cardiovascular comorbidity. Persons with OSA exhibit increased daytime sympathetic activity, markers of oxidative stress, and vasoactive hormones, particularly angiotensin II, that contribute to systemic vasoconstriction. These factors contribute to early endothelial dysfunction and contribute to sustained elevations in BP. While CPAP is the gold standard OSA treatment, adherence rates are low and evidence suggests that treatment does not reduce the rates of CVD in large population-based studies. Telmisartan is a receptor blocker for angiotensin II and not only has BP lowering effects, but also has unique anti-inflammatory properties and beneficial influences on endothelial function. The addition of an antioxidant supplement may increase the reactive oxygen species scavenging capacity and, in combination with ARB treatment, may provide more robust effects on BP in persons with OSA. Official Title ----------------- Combined Treatment of Angiotensin Receptor Blocker and Antioxidant Supplementation as a Novel Adjunctive Therapy for 24-hour Blood Pressure Improvement in Obstructive Sleep Apnea Conditions ----------------- Obstructive Sleep Apnea Intervention / Treatment ----------------- * Device: Continuous Positive Airway Pressure CPAP * Drug: Telmisartan 80mg * Dietary Supplement: Alpha-Lipoic Acid 600mg * Other: Microcrystalline Cellulose Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Apnea/Hypopnea Index (AHI) greater than/equal to 15 events per hour of sleep No prior use of CPAP Body mass index less than 30kg/m2 Does not take ARBs or angiotensin converting enzyme inhibitors for blood pressure control Females of childbearing potential on an effective or highly effective means of contraception Exclusion Criteria: Prescribed and/or taking the following medications: diuretics (including potassium-sparing diuretics), Digoxin, lithium salts, and/or nonsteroidal anti-inflammatory drugs Over the counter supplements that affect the cardiovascular system, such as fish oils, vitamins, or other antioxidants History of heart failure History of myocardial infarction History of coronary artery disease History of stroke History of diabetes mellitus History of impaired renal function History of chronic obstructive pulmonary disease History of asthma History of central sleep apnea Smoked within the past year Hypotensive (Systolic blood pressure (SBP) <90 mmHg and diastolic blood pressure (DBP) <60 mmHg) Females who do not have a means of contraception, are pregnant, planning to become pregnant, and/or are breast-feeding Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Combined Treatment<br>Subjects will be given 80 mg/day Telmisartan + 600 mg/day Alpha-Lipoic Acid. Subjects will also be prescribed CPAP therapy by their physician. Subjects will be instructed to use their CPAP device according to their physician's guidelines. \| Device: Continuous Positive Airway Pressure CPAP<br>* All subjects will be advised to use their continuous positive airway pressure (CPAP) in accordance to their physician's guidelines.<br>Drug: Telmisartan 80mg<br>* Subjects in this group will receive 80mg/day of Telmisartan (an angiotensin receptor blocker). Treatments will be administered in pre-packaged blister packages. Subjects will take Telmisartan once per day for 6 weeks.<br>Dietary Supplement: Alpha-Lipoic Acid 600mg<br>* Subjects in this group will receive 600mg/day of Alpha-Lipoic Acid (an antioxidant). Treatments will be administered in pre-packaged blister packages. Subjects will take Alpha-Lipoic Acid once per day for 6 weeks.<br>\| \| Placebo Comparator: Placebo Control<br>Subjects will be given placebo capsules. Subjects will also be prescribed CPAP therapy by their physician. Subjects will be instructed to use their CPAP device according to their physician's guidelines. \| Device: Continuous Positive Airway Pressure CPAP<br>* All subjects will be advised to use their continuous positive airway pressure (CPAP) in accordance to their physician's guidelines.<br>Other: Microcrystalline Cellulose<br>* Subjects in this group will receive two capsules of Microcrystalline Cellulose (placebo). Treatments will be administered in pre-packaged blister packages. Subjects will take placebo pills once per day for 6 weeks.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change in 24-hour blood pressure \| Systolic, diastolic, and mean arterial blood pressure (mmHg) \| Change from baseline of 24-hour systolic, diastolic, and mean arterial blood pressure at 6 weeks \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Continuous Positive Airway Pressure, 24-hour blood pressure, Telmisartan, Alpha-Lipoic Acid
NCT01813838	GFM-Acadesine: A Phase I-II Trial of Acadesine	A phase I-II trial of Acadesine in IPSS high and int 2 myelodysplastic syndromes, acute myeloid leukemia with 20-30% marrow blasts and chronic myelomonocytic leukemia type 2 not responding to Azacitidine or Decitabine for at least 6 courses or relapsing after a response:~Patients will receive 6 treatment cycles unless disease progression, transformation, or unacceptable toxicity occurs, or the patient refuses to continue participating in the study.~Efficacy will be assessed at the end of the 2nd, 4th and 6th cycles. After 6 cycles, patients demonstrating a response (CR, PR, marrow CR, or HI) will be able to continue with cycles of Acadesine (at the same dose as in the preceding cycles, depending on their cohort) until progression.	Primary objectives~Phase I:~To determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLTs) of increasing doses of IV Acadesine administered on D1, D3, D5, D8, D10 and D12 of 28 to 56 day-courses~Phase II:~To confirm safety and hematological toxicity in 18 additional patients~Secondary objectives:~Phase I:~To determine response rates, as defined by the 2006 modified IWG criteria,~To evaluate response duration, time to IPSS progression, and loss of RBC transfusion independence in these patients.~To evaluate hospitalization duration, rates of rehospitalization for non-hematological toxicities, severe bleeding or febrile neutropenia.~Phase II:~To determine~response rate as defined by the 2006 modified IWG criteria~toxicity profile and safety~response duration~rate of progression to AML~overall survival	A Phase I-II Trial of Acadesine in IPSS High and Int-2 SMD, LAM With 20-30% Marrow Blasts and CMML Type 2 Not Responding to Azacitidine or Decitabine for at Least 6 Courses or Relapsing After a Response	SMD	* Drug: ACADESINE 140mg/kg/d * Drug: ACADESINE 210mg/kg/d * Drug: ACADESINE 315mg/kg/d	Inclusion Criteria:~Myelodysplastic syndrome including the following WHO categories: refractory anemia with excess blasts (RAEB), non-proliferative chronic myelomonocytic leukemia (CMML) (leukocytes < 13 G/L but > 10% marrow blasts), WHO- AML with 20-30% marrow blasts (RAEB-T according to the FAB classification)~Prior treatment with Azacitidine or Decitabine for at least 6 courses without response (including CR, PR, marrow CR and stable disease with hematological improvement) or relapse after a response~IPSS score >1 (IPSS: Int-2 or High);~Age ≥ 18 years;~Normal liver function tests, defined by total bilirubin and transaminases less than 1.5 time the upper limit of normal;~Normal renal function, defined by creatinine less than 1.5 time the upper limit of normal, creatinine clearance ≥ 50 mL/min.~Patient ineligible for allogeneic hematopoietic stem cell transplantation;~Written informed consent;~Patient must understand and voluntarily sign consent form;~Patient must be able to adhere to the visit schedule as outlined in the study and follow protocol requirements;~ECOG performance status between 0-2 at the time of screening;~Women of childbearing potential must:~Agree to use effective contraception without interruption throughout the study and for a further 1 month after the end of treatment;~Men must:~Agree to not conceive during the treatment and to use effective contraception during the treatment period (including periods of dose reduction or temporary suspension) and for a further 1 month after the end of treatment if their partner is of childbearing potential.~Exclusion Criteria:~Severe infection or any other uncontrolled severe condition~Significant cardiac disease - NYHA Class III or IV or having suffered a myocardial infarction in the last 6 months~Less than 30 days since prior treatment with growth factors (EPO, G-CSF)~Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicities from any previous therapy.~Active cancer, or cancer during the year prior to trial entry other than basal cell carcinoma or carcinoma in situ of the cervix or breast;~Patient already enrolled in another therapeutic trial of an investigational drug;~HIV infection or active hepatitis B or C;~Women who are or could become pregnant or who are currently breastfeeding;~Any medical or psychiatric contraindication that would prevent the patient from understanding and signing the informed consent form;~Patient eligible for allotransplantation.~Known allergy to acadesine or any of its excipients~No affiliation to an insurance system	18 Years	null	All	No	Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Determine the maximal tolerated dose (MTD) \| Phase I: Evaluation after 6 month of treatment. Responders will be treated until progression \| 6 month of treatment \|				\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: ACADESINE 140mg/kg/d<br>3 patients will be included at the initial dose of Acadesine 140mg/kg/d \| Drug: ACADESINE 140mg/kg/d<br>* 3 patients will be included at the initial dose of 140mg/kg/d. In absence of toxicity, 3 additional patients will be included at the higher dosage.~In case of 1/3 toxicity, 3 additionnal patients will be included at the same dose level, currently 140mg/kg/d.~In case of toxicity in 2 or more patients, the dose of acadesine will be reduced at the the dose of 85mg/kg/d<br>* Other names: ACADESINE;\| \| Experimental: ACADESINE 210mg/kg/d<br>In absence of toxicity at the dose of 140mg/kg/d. There is a dose escalation of acadesine at the dose of 210mg/kg/d for 3 additionnal patients \| Drug: ACADESINE 210mg/kg/d<br>* 3 patients will be included at the dose of 210mg/kg/d. In absence of toxicity, 3 additional patients will be included at the higher dosage.~In case of 1/3 toxicity, 3 additionnal patients will be included at the same dose level, currently 210mg/kg/d.~In case of toxicity in 2 or more patients, the dose of acadesine will be reduced at the the dose of 140mg/kg/d<br>* Other names: ACADESINE;\| \| Experimental: ACADESINE 315mg/kg/d<br>In absence of toxicity at the dose of 210mg/kg/d. There is a dose escalation of acadesine at the dose of 315mg/kg/d for 3 additionnal patients \| Drug: ACADESINE 315mg/kg/d<br>* 3 patients will be included at the dose of 315mg/kg/d.~In case of 1/3 toxicity, 3 additionnal patients will be included at the same dose level, currently 315mg/kg/d.~In case of toxicity in 2 or more patients, the dose of acadesine will be reduced at the the dose of 210mg/kg/d<br>* Other names: ACADESINE;\|	GFM-Acadesine: A Phase I-II Trial of Acadesine Study Overview ================= Brief Summary ----------------- A phase I-II trial of Acadesine in IPSS high and int 2 myelodysplastic syndromes, acute myeloid leukemia with 20-30% marrow blasts and chronic myelomonocytic leukemia type 2 not responding to Azacitidine or Decitabine for at least 6 courses or relapsing after a response: Patients will receive 6 treatment cycles unless disease progression, transformation, or unacceptable toxicity occurs, or the patient refuses to continue participating in the study. Efficacy will be assessed at the end of the 2nd, 4th and 6th cycles. After 6 cycles, patients demonstrating a response (CR, PR, marrow CR, or HI) will be able to continue with cycles of Acadesine (at the same dose as in the preceding cycles, depending on their cohort) until progression. Detailed Description ----------------- Primary objectives Phase I: To determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLTs) of increasing doses of IV Acadesine administered on D1, D3, D5, D8, D10 and D12 of 28 to 56 day-courses Phase II: To confirm safety and hematological toxicity in 18 additional patients Secondary objectives: Phase I: To determine response rates, as defined by the 2006 modified IWG criteria, To evaluate response duration, time to IPSS progression, and loss of RBC transfusion independence in these patients. To evaluate hospitalization duration, rates of rehospitalization for non-hematological toxicities, severe bleeding or febrile neutropenia. Phase II: To determine response rate as defined by the 2006 modified IWG criteria toxicity profile and safety response duration rate of progression to AML overall survival Official Title ----------------- A Phase I-II Trial of Acadesine in IPSS High and Int-2 SMD, LAM With 20-30% Marrow Blasts and CMML Type 2 Not Responding to Azacitidine or Decitabine for at Least 6 Courses or Relapsing After a Response Conditions ----------------- SMD Intervention / Treatment ----------------- * Drug: ACADESINE 140mg/kg/d * Drug: ACADESINE 210mg/kg/d * Drug: ACADESINE 315mg/kg/d Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Myelodysplastic syndrome including the following WHO categories: refractory anemia with excess blasts (RAEB), non-proliferative chronic myelomonocytic leukemia (CMML) (leukocytes < 13 G/L but > 10% marrow blasts), WHO- AML with 20-30% marrow blasts (RAEB-T according to the FAB classification) Prior treatment with Azacitidine or Decitabine for at least 6 courses without response (including CR, PR, marrow CR and stable disease with hematological improvement) or relapse after a response IPSS score >1 (IPSS: Int-2 or High); Age ≥ 18 years; Normal liver function tests, defined by total bilirubin and transaminases less than 1.5 time the upper limit of normal; Normal renal function, defined by creatinine less than 1.5 time the upper limit of normal, creatinine clearance ≥ 50 mL/min. Patient ineligible for allogeneic hematopoietic stem cell transplantation; Written informed consent; Patient must understand and voluntarily sign consent form; Patient must be able to adhere to the visit schedule as outlined in the study and follow protocol requirements; ECOG performance status between 0-2 at the time of screening; Women of childbearing potential must: Agree to use effective contraception without interruption throughout the study and for a further 1 month after the end of treatment; Men must: Agree to not conceive during the treatment and to use effective contraception during the treatment period (including periods of dose reduction or temporary suspension) and for a further 1 month after the end of treatment if their partner is of childbearing potential. Exclusion Criteria: Severe infection or any other uncontrolled severe condition Significant cardiac disease - NYHA Class III or IV or having suffered a myocardial infarction in the last 6 months Less than 30 days since prior treatment with growth factors (EPO, G-CSF) Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicities from any previous therapy. Active cancer, or cancer during the year prior to trial entry other than basal cell carcinoma or carcinoma in situ of the cervix or breast; Patient already enrolled in another therapeutic trial of an investigational drug; HIV infection or active hepatitis B or C; Women who are or could become pregnant or who are currently breastfeeding; Any medical or psychiatric contraindication that would prevent the patient from understanding and signing the informed consent form; Patient eligible for allotransplantation. Known allergy to acadesine or any of its excipients No affiliation to an insurance system Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: ACADESINE 140mg/kg/d<br>3 patients will be included at the initial dose of Acadesine 140mg/kg/d \| Drug: ACADESINE 140mg/kg/d<br>* 3 patients will be included at the initial dose of 140mg/kg/d. In absence of toxicity, 3 additional patients will be included at the higher dosage. In case of 1/3 toxicity, 3 additionnal patients will be included at the same dose level, currently 140mg/kg/d. In case of toxicity in 2 or more patients, the dose of acadesine will be reduced at the the dose of 85mg/kg/d<br>* Other names: ACADESINE;\| \| Experimental: ACADESINE 210mg/kg/d<br>In absence of toxicity at the dose of 140mg/kg/d. There is a dose escalation of acadesine at the dose of 210mg/kg/d for 3 additionnal patients \| Drug: ACADESINE 210mg/kg/d<br>* 3 patients will be included at the dose of 210mg/kg/d. In absence of toxicity, 3 additional patients will be included at the higher dosage. In case of 1/3 toxicity, 3 additionnal patients will be included at the same dose level, currently 210mg/kg/d. In case of toxicity in 2 or more patients, the dose of acadesine will be reduced at the the dose of 140mg/kg/d<br>* Other names: ACADESINE;\| \| Experimental: ACADESINE 315mg/kg/d<br>In absence of toxicity at the dose of 210mg/kg/d. There is a dose escalation of acadesine at the dose of 315mg/kg/d for 3 additionnal patients \| Drug: ACADESINE 315mg/kg/d<br>* 3 patients will be included at the dose of 315mg/kg/d. In case of 1/3 toxicity, 3 additionnal patients will be included at the same dose level, currently 315mg/kg/d. In case of toxicity in 2 or more patients, the dose of acadesine will be reduced at the the dose of 210mg/kg/d<br>* Other names: ACADESINE;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Determine the maximal tolerated dose (MTD) \| Phase I: Evaluation after 6 month of treatment. Responders will be treated until progression \| 6 month of treatment \|
NCT02875899	Surfacer System to Facilitate Access in Venous Occlusions	Prospective, single-arm, multicentre, international Registry of the Surfacer System for the treatment of patients with limited or diminishing upper body venous access or pathology impeding standard access methods.The purpose of this post-market Registry is to assess the standard of care and clinical outcomes of the Surfacer System used in clinical routine according to the approved commercial indications.	This is a prospective, single-arm, multicenter registry of the Surfacer System for patients with limited or diminishing upper body venous access or pathology impeding standard access methods. The need for long term access and lack of availability of veins has led to the development of the Surfacer System, which facilitates reliable and repeatable placement of central venous catheters and restores central venous access. Based on European legislation, this Registry is considered to be an observational study. No additional diagnostic or monitoring procedures as a result of the inclusion are applied to the patients. Available data will be collected in a protected database. Up to 30 patients will be enrolled in 5 sites in Europe. Patients requiring central venous access will be enrolled who meet inclusion and exclusion criteria and for whom the device is indicated.	Surfacer System to Facilitate Access in Venous Occlusions	Chronic Venous Thrombosis, Venous Thrombosis Upper Extremity, Venous Thrombosis Upper Extremity Superficial Veins		Inclusion Criteria: patients referred for placement of a central venous catheter~patients with limited or diminishing upper body venous access~pathology impeding standard access methods~signed informed consent~Exclusion Criteria:~vulnerable subjects or incapable of giving consent~contraindications to central venous access based on treating physicians opinion or standard of care~occlusion of the right femoral vein~occlusion of the iliac vein~occlusion of the inferior vena~acute thrombosis within a vessel (IVC, brachiocephalic and subclavian)	18 Years	80 Years	All	No		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Absence of all acute safety and device related serious adverse event recorded on case report forms \| overall complication rate compared to safety data \| Procedure through discharge at 24 hours post procedure. Data will be presented through study completion, 1 year. \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Ability to place central venous access catheter using Surfacer system \| performance evaluated by procedure time measured by time to create access \| Procedure \| \| Surfacer system advancement of the exit wire outside the vein \| Ability to advance system from femoral vein to supraclavicular exit as measured by time \| procedure \| \| Insertion of a standard central venous access catheter to deliver fluid or pharmacological agents \| introducing a standard central venous access catheter over the needle wire \| procedure \|		Thrombosis, Venous Thrombosis, Embolism and Thrombosis, Vascular Diseases, Cardiovascular Diseases		Surfacer System to Facilitate Access in Venous Occlusions Study Overview ================= Brief Summary ----------------- Prospective, single-arm, multicentre, international Registry of the Surfacer System for the treatment of patients with limited or diminishing upper body venous access or pathology impeding standard access methods.The purpose of this post-market Registry is to assess the standard of care and clinical outcomes of the Surfacer System used in clinical routine according to the approved commercial indications. Detailed Description ----------------- This is a prospective, single-arm, multicenter registry of the Surfacer System for patients with limited or diminishing upper body venous access or pathology impeding standard access methods. The need for long term access and lack of availability of veins has led to the development of the Surfacer System, which facilitates reliable and repeatable placement of central venous catheters and restores central venous access. Based on European legislation, this Registry is considered to be an observational study. No additional diagnostic or monitoring procedures as a result of the inclusion are applied to the patients. Available data will be collected in a protected database. Up to 30 patients will be enrolled in 5 sites in Europe. Patients requiring central venous access will be enrolled who meet inclusion and exclusion criteria and for whom the device is indicated. Official Title ----------------- Surfacer System to Facilitate Access in Venous Occlusions Conditions ----------------- Chronic Venous Thrombosis, Venous Thrombosis Upper Extremity, Venous Thrombosis Upper Extremity Superficial Veins Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: patients referred for placement of a central venous catheter patients with limited or diminishing upper body venous access pathology impeding standard access methods signed informed consent Exclusion Criteria: vulnerable subjects or incapable of giving consent contraindications to central venous access based on treating physicians opinion or standard of care occlusion of the right femoral vein occlusion of the iliac vein occlusion of the inferior vena acute thrombosis within a vessel (IVC, brachiocephalic and subclavian) Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Absence of all acute safety and device related serious adverse event recorded on case report forms \| overall complication rate compared to safety data \| Procedure through discharge at 24 hours post procedure. Data will be presented through study completion, 1 year. \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Ability to place central venous access catheter using Surfacer system \| performance evaluated by procedure time measured by time to create access \| Procedure \| \| Surfacer system advancement of the exit wire outside the vein \| Ability to advance system from femoral vein to supraclavicular exit as measured by time \| procedure \| \| Insertion of a standard central venous access catheter to deliver fluid or pharmacological agents \| introducing a standard central venous access catheter over the needle wire \| procedure \|
NCT01361620	Genotypic and Phenotypic Correlates of Resistance to Aspirin	The study seeks to identify genomic markers associated with aspirin resistance.	Not desired	Genotypic and Phenotypic Correlates of Resistance to Anti-platelet Actions of Aspirin in an At-risk Patient Population and in the General Population	Platelet Dysfunction Due to Aspirin	* Drug: aspirin	Inclusion Criteria:~Volunteers 40 to 80 years old willing to sign consent and take 81 mg of aspirin for 7 - 10 days and return for laboratory testing.~Exclusion Criteria:~Patient requiring more than 81 mg aspirin daily~Known GI bleeding attributed to ASA~Active peptic ulcer disease or history within the last year~Known aspirin allergy~Current use of:~warfarin,~heparin,~NSAIDs (except aspirin),~clopidogrel,~dipyridamole,~fish-oil/omega 3 supplements,~Women of childbearing potential who are pregnant, planning to become pregnant or nursing.	40 Years	80 Years	All	Accepts Healthy Volunteers	Primary Purpose: Basic Science Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Whole Blood Coagulation \| Whole blood coagulation after stimulation with arachidonic acid, as measured in the VerifyNow Aspirin system (Accumetrics). Aspirin response units (ARU) are the residual coagulation present in patients taking aspirin. The higher the ARU, the greater residual coagulation (resistance) to the aspirin effect. \| Single measurement at 7-10 days after beginning aspirin \|		genomic markers, aspirin resistance	Anti-Inflammatory Agents, Non-Steroidal, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anti-Inflammatory Agents, Antirheumatic Agents, Fibrinolytic Agents, Fibrin Modulating Agents, Molecular Mechanisms of Pharmacological Action, Platelet Aggregation Inhibitors, Cyclooxygenase Inhibitors, Enzyme Inhibitors, Antipyretics, Aspirin	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Other: Aspirin<br>All subjects took 7-10 days of 81 mg aspirin \| Drug: aspirin<br>* aspirin 81mg, 7-10 days<br>\|	Genotypic and Phenotypic Correlates of Resistance to Aspirin Study Overview ================= Brief Summary ----------------- The study seeks to identify genomic markers associated with aspirin resistance. Detailed Description ----------------- Not desired Official Title ----------------- Genotypic and Phenotypic Correlates of Resistance to Anti-platelet Actions of Aspirin in an At-risk Patient Population and in the General Population Conditions ----------------- Platelet Dysfunction Due to Aspirin Intervention / Treatment ----------------- * Drug: aspirin Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Volunteers 40 to 80 years old willing to sign consent and take 81 mg of aspirin for 7 - 10 days and return for laboratory testing. Exclusion Criteria: Patient requiring more than 81 mg aspirin daily Known GI bleeding attributed to ASA Active peptic ulcer disease or history within the last year Known aspirin allergy Current use of: warfarin, heparin, NSAIDs (except aspirin), clopidogrel, dipyridamole, fish-oil/omega 3 supplements, Women of childbearing potential who are pregnant, planning to become pregnant or nursing. Ages Eligible for Study ----------------- Minimum Age: 40 Years Maximum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Basic Science Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Other: Aspirin<br>All subjects took 7-10 days of 81 mg aspirin \| Drug: aspirin<br>* aspirin 81mg, 7-10 days<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Whole Blood Coagulation \| Whole blood coagulation after stimulation with arachidonic acid, as measured in the VerifyNow Aspirin system (Accumetrics). Aspirin response units (ARU) are the residual coagulation present in patients taking aspirin. The higher the ARU, the greater residual coagulation (resistance) to the aspirin effect. \| Single measurement at 7-10 days after beginning aspirin \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- genomic markers, aspirin resistance
NCT02976129	A Six Week Efficacy, Safety and Tolerability Study of V565 in Crohn's Disease	The purpose of this study is to evaluate the efficacy and safety of V565 in participants with active Crohn's Disease (CD).	This study will be a multiple-site, double-blind, placebo-controlled, parallel-group study in approximately 126 subjects with a confirmed diagnosis of CD for at least three months and have CD involving the ileum and/or colon. Following a screening period of up to 28 days, subjects will be randomly allocated into one of two treatment arms: either V565 or placebo using a 2:1 active:placebo ratio for a treatment period of 6 weeks.~Subjects will be treated with study drug as an add-on to any permitted stable medications already being taken for CD.	Phase 2 Study to Investigate the Efficacy, Safety, and Tolerability of Six Weeks Treatment With V565 in Subjects With Active Crohn's Disease	Crohn's Disease	* Drug: V565 * Drug: Placebo	Inclusion Criteria:~History of Crohn's Disease of at least 3 months duration prior to screening~Crohn's Disease Activity Index (CDAI) score of ≥220 to ≤450 during screening~C-reactive protein (CRP) ≥5 mg/L (or, if CRP is normal, faecal calprotectin (FCP) ≥250 µg/g) at screening~Permitted CD medication regimen expected to remain stable during the period of the study~Exclusion Criteria:~Previous lack of response or current contra-indication to an anti-tumour necrosis factor α (anti-TNFα) agent~Certain complications of Crohn's Disease that would make it hard to assess response to study drug~Known history or suspicion of inflammatory bowel disease other than Crohn's disease~History of tuberculosis (TB) or latent TB infection that has not been treated~Any significant illness or condition which would preclude effective participation in the study~GI infection as demonstrated by presence of enteric pathogens~Pregnant or lactating women~Abdominal surgery in the previous 6 months~Unsuitable for inclusion in the study in the opinion of the investigator or sponsor for any reason that may compromise the subject's safety or confound data interpretation	18 Years	80 Years	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Subjects Achieving Response to Therapy, Defined as Reduction in the CDAI Score and in Inflammatory Markers CRP or FCP at Day 42. \| Number of responders at Day 42, defined as subjects achieving both CDAI ≥ 70-point reduction from baseline or CDAI score < 150, and a reduction of ≥ 40% from the baseline value of CRP or FCP.~Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. \| Day 42 \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Subjects Achieving Response to Therapy, Defined as Reduction in the CDAI Score and in Inflammatory Markers CRP or FCP at Day 42. \| Number of subjects achieving a ≥ 100-point reduction in CDAI score and a concomitant reduction of at least 50% in CRP or FCP at Day 42~Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. \| Day 42 \|		Digestive System Diseases, Crohn Disease, Inflammatory Bowel Diseases, Gastroenteritis, Gastrointestinal Diseases, Intestinal Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: V565<br>V565 three times a day (TID) PO for 6 weeks \| Drug: V565<br>* Daily dosing of V565 three times a day orally for 6 weeks<br>\| \| Placebo Comparator: Placebo<br>Placebo TID PO for 6 weeks \| Drug: Placebo<br>* Daily dosing of placebo three times a day orally for 6 weeks<br>\|	A Six Week Efficacy, Safety and Tolerability Study of V565 in Crohn's Disease Study Overview ================= Brief Summary ----------------- The purpose of this study is to evaluate the efficacy and safety of V565 in participants with active Crohn's Disease (CD). Detailed Description ----------------- This study will be a multiple-site, double-blind, placebo-controlled, parallel-group study in approximately 126 subjects with a confirmed diagnosis of CD for at least three months and have CD involving the ileum and/or colon. Following a screening period of up to 28 days, subjects will be randomly allocated into one of two treatment arms: either V565 or placebo using a 2:1 active:placebo ratio for a treatment period of 6 weeks. Subjects will be treated with study drug as an add-on to any permitted stable medications already being taken for CD. Official Title ----------------- Phase 2 Study to Investigate the Efficacy, Safety, and Tolerability of Six Weeks Treatment With V565 in Subjects With Active Crohn's Disease Conditions ----------------- Crohn's Disease Intervention / Treatment ----------------- * Drug: V565 * Drug: Placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: History of Crohn's Disease of at least 3 months duration prior to screening Crohn's Disease Activity Index (CDAI) score of ≥220 to ≤450 during screening C-reactive protein (CRP) ≥5 mg/L (or, if CRP is normal, faecal calprotectin (FCP) ≥250 µg/g) at screening Permitted CD medication regimen expected to remain stable during the period of the study Exclusion Criteria: Previous lack of response or current contra-indication to an anti-tumour necrosis factor α (anti-TNFα) agent Certain complications of Crohn's Disease that would make it hard to assess response to study drug Known history or suspicion of inflammatory bowel disease other than Crohn's disease History of tuberculosis (TB) or latent TB infection that has not been treated Any significant illness or condition which would preclude effective participation in the study GI infection as demonstrated by presence of enteric pathogens Pregnant or lactating women Abdominal surgery in the previous 6 months Unsuitable for inclusion in the study in the opinion of the investigator or sponsor for any reason that may compromise the subject's safety or confound data interpretation Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: V565<br>V565 three times a day (TID) PO for 6 weeks \| Drug: V565<br>* Daily dosing of V565 three times a day orally for 6 weeks<br>\| \| Placebo Comparator: Placebo<br>Placebo TID PO for 6 weeks \| Drug: Placebo<br>* Daily dosing of placebo three times a day orally for 6 weeks<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Subjects Achieving Response to Therapy, Defined as Reduction in the CDAI Score and in Inflammatory Markers CRP or FCP at Day 42. \| Number of responders at Day 42, defined as subjects achieving both CDAI ≥ 70-point reduction from baseline or CDAI score < 150, and a reduction of ≥ 40% from the baseline value of CRP or FCP. Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. \| Day 42 \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Subjects Achieving Response to Therapy, Defined as Reduction in the CDAI Score and in Inflammatory Markers CRP or FCP at Day 42. \| Number of subjects achieving a ≥ 100-point reduction in CDAI score and a concomitant reduction of at least 50% in CRP or FCP at Day 42 Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. \| Day 42 \|
NCT03986931	A Pharmacist Intervention for Monitoring and Treating Hypertension Using Bidirectional Texting	Bidirectional texting is an effective way to collect home blood pressure (BP) measurements from subjects, but collecting BP measurements and sending them to physicians does not necessarily lead to decreased BP. Pharmacist interventions have been successful in decreasing subject BP. However, pharmacists are expensive, and in successful interventions, spent a substantial amount of time collecting home BP measurements. In this study, a proven pharmacist intervention will be added to a bidirectional texting program to determine if a combined pharmacist-bidirectional texting intervention is successful at decreasing subject BP and increasing subject BP treatment intensification in a cost-effective manner. This study will be a cluster-randomized, controlled trial of a new intervention.	HTN is associated with the greatest attributable risk for mortality among all modifiable risk factors for cardiovascular disease.[1] In 2014, there were approximately 72 million adults (29%) with HTN in the US.[2] Several clinical trials have demonstrated that antihypertensive medications reduce cardiovascular events.[3] For example, even a 5 mm Hg difference in systolic BP (SBP) over 3-5 years can reduce the risk of cardiovascular complications and strokes by 25-30%.[4] Yet, approximately 20% of U.S. adults are unaware of their HTN,[5] and among patients diagnosed with HTN, 47% are uncontrolled.[2] Thus, there is a critical need to effectively treat patients with HTN.~Clinical inertia has been identified as the primary cause for delays in achieving BP control for over 20 years.[6-8] Providers often discount office BP readings that may be falsely elevated due to observer or measurement error and/or the clinical surroundings (e.g., white coat HTN).[9-11] Patients are often seen only once or twice a year which further delays BP control. Furthermore,[8, 12] BP goals are achieved in only 49% of the patients who take anti-hypertensive medications.[5] New approaches for acquiring more BP readings are also needed to better monitor and titrate treatment because a significant proportion of patients on therapy are not adequately controlled despite frequent physician visits.~Home BP measurements, (i.e., having patients take their BP at home), can facilitate the more timely diagnosis of HTN by reducing diagnostic uncertainty. In fact, home measurements are better prognostic indicators of stroke and cardiovascular mortality than clinic measurements,[13-15] are more closely correlated with end-organ damage from HTN than clinic measurements,[16, 17] are cost effective and well-tolerated by patients,[18] and generate BP readings that are at least as reproducible as clinic readings.[19] Home BP measurements, if available, may help physicians overcome barriers related to clinical inertia.[20] However, the data must be followed by action. The researchers have pioneered physician-pharmacist collaborative management (PPCM) that has been shown to decrease clinical inertia and improve BP control.[21, 22] Pharmacists have been embedded within the medical office to perform BP management. The pharmacists are able to assess patients' needs and provide recommendations to physicians regarding treatment changes, providing patients with timely therapy adjustments.[23] However, many medical office leaders are unable to hire clinical pharmacists due to limited resources. Therefore, a virtual, remote clinical pharmacy service has been developed.[24] Pharmacists were able to obtain electronic medical record (EMR) access at all intervention offices for private physician offices throughout Iowa. While the physicians accepted 95% of the pharmacists' recommendations, the effect on improving BP was modest (manuscript under review). Adding the proposed texting platform with home BP monitoring should markedly improve the potency of our remote, telepharmacy intervention.~This trial exhibits clinical equipoise because, although it is known that texting is an efficient method for obtaining home BP measurements, and that pharmacist interventions to improve BP are cost-effective, it is not known if combining these two interventions will also be cost effective. There are four reasons why this study might not be successful. First, while meta-analyses have found significantly improved BP with pharmacist interventions some studies were not successful.[25] Second, more data does not necessarily mean better data: patients could report false values, BP could be abnormally low or high during the measurement period, or the data could be ignored. Third, even better data might not lead to better outcomes: data could be ignored by pharmacists, physicians or patients; pharmacists' recommendations could be ignored by physicians or patients. Fourth, even if the study is effective at improving subject outcomes, it might not be cost effective. Texting might not save as much time as hypothesized. Thus, further research is needed to address these gaps in knowledge.~There is a critical need for an easy-to-use, cost-effective, mobile health (m-health) approach to assist patients and healthcare providers with screening, diagnosis, and monitoring of HTN. Small medical offices and those located in poor or rural areas are unable to operationalize team-based care with pharmacists. The researchers have overcome this barrier with the use of a remote clinical pharmacy services. Coronary heart disease deaths could be reduced by 15-20% and stroke deaths by 20-30% if this intervention effectively improves BP and is implemented more widely in primary care offices.~The goal of this proposal is to evaluate whether a scalable, short messaging service (SMS) approach combined with a pharmacist-based intervention improves BP management cost effectively. To achieve this objective, the following specific aims are proposed:~Determine if mean BP 12 months after the intervention decreases more for the intervention group than the control group. The working hypothesis is that those in the pharmacist-intervention group will achieve larger BP decreases than those in the control group.~Determine if the intervention leads to more intensification of therapy than in the control group. The working hypothesis is that subjects in the pharmacist-intervention group will have more treatment changes than those in the control group.~Determine the cost effectiveness of the intervention. The working hypothesis is that the intervention will be cost effective when compared to the control group.	A Pharmacist Intervention for Monitoring and Treating Hypertension Using Bidirectional Texting	Hypertension	* Other: Experimental: Pharmacist-Bidirectional Texting Group * Other: Active Comparator: Control Group	Inclusion Criteria:~Fluent in English or Spanish~Have a clinic measured blood pressure of > or = 145 mmHg and/or > or = 95 mmHg at two previous clinic visits or one previous clinic visit and on the day of enrollment~Must be a patient at Family Medicine, River Crossings, Scott Blvd, or Muscatine University of Iowa Clinics~Live in a zip code that is scored as a 4-10 on the Rural-Urban Commuting Area codes~Exclusion Criteria:~Currently pregnant or planning to become pregnant in the next year~Upper arm circumference greater than 50 cm (20 in)~Prisoner status~Unable to provide own informed consent	21 Years	100 Years	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change in Systolic Blood Pressure- 12 Months \| Change from baseline in systolic blood pressure in mm Hg at 12 months. \| 12 months \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change in Diastolic Blood Pressure- 12 Months \| Change from baseline in diastolic blood pressure in mm Hg at 12 months. \| 12 months \| \| Number of Medication Changes in 12 Months \| Total number of medication changes (i.e., dose, discontinuation, initiation, etc.) from baseline as documented in the medical record. \| 12 months \| \| Dollars Spent per Patient for 12 Month Bidirectional Texting/Pharmacist Intervention \| Total cost of medications, time spent by research staff, and clinics visits per patient from baseline. \| 12 months \|		Hypertension, Vascular Diseases, Cardiovascular Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Pharmacist-Bidirectional Texting Group<br>Patients enrolled in the Pharmacist-Bidirectional Texting Group will return 7 morning and 7 evening blood pressure measurements via text message. The report will be shared with a pharmacist who will monitor them for 12 months. The pharmacist will have access to their entire medical record and will provide support and education via text messaging, email, or phone calls, whichever is preferred by the patient. The pharmacist will develop a care plan and make recommendations to the physician through the electronic medical record to quickly adjust therapy to improve control. They will also recommend laboratory testing if indicated. They will have contact with the patient every 2-3 weeks while blood pressure is uncontrolled, and at least every 2 months when it is controlled. The pharmacist will track all recommendations made to physicians and whether or not they were implemented, modified, or rejected. \| Other: Experimental: Pharmacist-Bidirectional Texting Group<br>* The goal of this intervention is to determine if bidirectional texting and pharmacist monitoring will improve blood pressure control.<br>\| \| Active Comparator: Control Group<br>Patients randomized to the control group will also return 7 morning and 7 evening blood pressure measurements. The report will be shared with a pharmacist who will call the patient to discuss the measurements and possibly recommend follow up with a physician, but no other pharmacist intervention or monitoring will occur during the 12 months. \| Other: Active Comparator: Control Group<br>* This group will receive bidirectional texting, but no pharmacist monitoring.<br>\|	A Pharmacist Intervention for Monitoring and Treating Hypertension Using Bidirectional Texting Study Overview ================= Brief Summary ----------------- Bidirectional texting is an effective way to collect home blood pressure (BP) measurements from subjects, but collecting BP measurements and sending them to physicians does not necessarily lead to decreased BP. Pharmacist interventions have been successful in decreasing subject BP. However, pharmacists are expensive, and in successful interventions, spent a substantial amount of time collecting home BP measurements. In this study, a proven pharmacist intervention will be added to a bidirectional texting program to determine if a combined pharmacist-bidirectional texting intervention is successful at decreasing subject BP and increasing subject BP treatment intensification in a cost-effective manner. This study will be a cluster-randomized, controlled trial of a new intervention. Detailed Description ----------------- HTN is associated with the greatest attributable risk for mortality among all modifiable risk factors for cardiovascular disease.[1] In 2014, there were approximately 72 million adults (29%) with HTN in the US.[2] Several clinical trials have demonstrated that antihypertensive medications reduce cardiovascular events.[3] For example, even a 5 mm Hg difference in systolic BP (SBP) over 3-5 years can reduce the risk of cardiovascular complications and strokes by 25-30%.[4] Yet, approximately 20% of U.S. adults are unaware of their HTN,[5] and among patients diagnosed with HTN, 47% are uncontrolled.[2] Thus, there is a critical need to effectively treat patients with HTN. Clinical inertia has been identified as the primary cause for delays in achieving BP control for over 20 years.[6-8] Providers often discount office BP readings that may be falsely elevated due to observer or measurement error and/or the clinical surroundings (e.g., white coat HTN).[9-11] Patients are often seen only once or twice a year which further delays BP control. Furthermore,[8, 12] BP goals are achieved in only 49% of the patients who take anti-hypertensive medications.[5] New approaches for acquiring more BP readings are also needed to better monitor and titrate treatment because a significant proportion of patients on therapy are not adequately controlled despite frequent physician visits. Home BP measurements, (i.e., having patients take their BP at home), can facilitate the more timely diagnosis of HTN by reducing diagnostic uncertainty. In fact, home measurements are better prognostic indicators of stroke and cardiovascular mortality than clinic measurements,[13-15] are more closely correlated with end-organ damage from HTN than clinic measurements,[16, 17] are cost effective and well-tolerated by patients,[18] and generate BP readings that are at least as reproducible as clinic readings.[19] Home BP measurements, if available, may help physicians overcome barriers related to clinical inertia.[20] However, the data must be followed by action. The researchers have pioneered physician-pharmacist collaborative management (PPCM) that has been shown to decrease clinical inertia and improve BP control.[21, 22] Pharmacists have been embedded within the medical office to perform BP management. The pharmacists are able to assess patients' needs and provide recommendations to physicians regarding treatment changes, providing patients with timely therapy adjustments.[23] However, many medical office leaders are unable to hire clinical pharmacists due to limited resources. Therefore, a virtual, remote clinical pharmacy service has been developed.[24] Pharmacists were able to obtain electronic medical record (EMR) access at all intervention offices for private physician offices throughout Iowa. While the physicians accepted 95% of the pharmacists' recommendations, the effect on improving BP was modest (manuscript under review). Adding the proposed texting platform with home BP monitoring should markedly improve the potency of our remote, telepharmacy intervention. This trial exhibits clinical equipoise because, although it is known that texting is an efficient method for obtaining home BP measurements, and that pharmacist interventions to improve BP are cost-effective, it is not known if combining these two interventions will also be cost effective. There are four reasons why this study might not be successful. First, while meta-analyses have found significantly improved BP with pharmacist interventions some studies were not successful.[25] Second, more data does not necessarily mean better data: patients could report false values, BP could be abnormally low or high during the measurement period, or the data could be ignored. Third, even better data might not lead to better outcomes: data could be ignored by pharmacists, physicians or patients; pharmacists' recommendations could be ignored by physicians or patients. Fourth, even if the study is effective at improving subject outcomes, it might not be cost effective. Texting might not save as much time as hypothesized. Thus, further research is needed to address these gaps in knowledge. There is a critical need for an easy-to-use, cost-effective, mobile health (m-health) approach to assist patients and healthcare providers with screening, diagnosis, and monitoring of HTN. Small medical offices and those located in poor or rural areas are unable to operationalize team-based care with pharmacists. The researchers have overcome this barrier with the use of a remote clinical pharmacy services. Coronary heart disease deaths could be reduced by 15-20% and stroke deaths by 20-30% if this intervention effectively improves BP and is implemented more widely in primary care offices. The goal of this proposal is to evaluate whether a scalable, short messaging service (SMS) approach combined with a pharmacist-based intervention improves BP management cost effectively. To achieve this objective, the following specific aims are proposed: Determine if mean BP 12 months after the intervention decreases more for the intervention group than the control group. The working hypothesis is that those in the pharmacist-intervention group will achieve larger BP decreases than those in the control group. Determine if the intervention leads to more intensification of therapy than in the control group. The working hypothesis is that subjects in the pharmacist-intervention group will have more treatment changes than those in the control group. Determine the cost effectiveness of the intervention. The working hypothesis is that the intervention will be cost effective when compared to the control group. Official Title ----------------- A Pharmacist Intervention for Monitoring and Treating Hypertension Using Bidirectional Texting Conditions ----------------- Hypertension Intervention / Treatment ----------------- * Other: Experimental: Pharmacist-Bidirectional Texting Group * Other: Active Comparator: Control Group Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Fluent in English or Spanish Have a clinic measured blood pressure of > or = 145 mmHg and/or > or = 95 mmHg at two previous clinic visits or one previous clinic visit and on the day of enrollment Must be a patient at Family Medicine, River Crossings, Scott Blvd, or Muscatine University of Iowa Clinics Live in a zip code that is scored as a 4-10 on the Rural-Urban Commuting Area codes Exclusion Criteria: Currently pregnant or planning to become pregnant in the next year Upper arm circumference greater than 50 cm (20 in) Prisoner status Unable to provide own informed consent Ages Eligible for Study ----------------- Minimum Age: 21 Years Maximum Age: 100 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Pharmacist-Bidirectional Texting Group<br>Patients enrolled in the Pharmacist-Bidirectional Texting Group will return 7 morning and 7 evening blood pressure measurements via text message. The report will be shared with a pharmacist who will monitor them for 12 months. The pharmacist will have access to their entire medical record and will provide support and education via text messaging, email, or phone calls, whichever is preferred by the patient. The pharmacist will develop a care plan and make recommendations to the physician through the electronic medical record to quickly adjust therapy to improve control. They will also recommend laboratory testing if indicated. They will have contact with the patient every 2-3 weeks while blood pressure is uncontrolled, and at least every 2 months when it is controlled. The pharmacist will track all recommendations made to physicians and whether or not they were implemented, modified, or rejected. \| Other: Experimental: Pharmacist-Bidirectional Texting Group<br>* The goal of this intervention is to determine if bidirectional texting and pharmacist monitoring will improve blood pressure control.<br>\| \| Active Comparator: Control Group<br>Patients randomized to the control group will also return 7 morning and 7 evening blood pressure measurements. The report will be shared with a pharmacist who will call the patient to discuss the measurements and possibly recommend follow up with a physician, but no other pharmacist intervention or monitoring will occur during the 12 months. \| Other: Active Comparator: Control Group<br>* This group will receive bidirectional texting, but no pharmacist monitoring.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change in Systolic Blood Pressure- 12 Months \| Change from baseline in systolic blood pressure in mm Hg at 12 months. \| 12 months \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change in Diastolic Blood Pressure- 12 Months \| Change from baseline in diastolic blood pressure in mm Hg at 12 months. \| 12 months \| \| Number of Medication Changes in 12 Months \| Total number of medication changes (i.e., dose, discontinuation, initiation, etc.) from baseline as documented in the medical record. \| 12 months \| \| Dollars Spent per Patient for 12 Month Bidirectional Texting/Pharmacist Intervention \| Total cost of medications, time spent by research staff, and clinics visits per patient from baseline. \| 12 months \|
NCT03197402	Leucine-enriched Nutraceutical and Attenuating Muscle Loss	This leucine-enriched protein gummy (as a gummy bar/slab) will be studied to address age-related loss of muscle mass and strength/function in older persons. The product is small volume (approximately 35 g per serve) and low energy (approximately 100 kcal per serve). It is easy to chew and swallow with the consistency of a firm Jello. In addition, it contains an effective dose of leucine in a high-quality protein matrix consisting of milk proteins. Understanding the efficacy of this product on changes in levels of blood amino acids and the molecular signaling required to enhance muscle growth will provide helpful insight for the suggestion of supplemental use.	General experimental design:~Pre-testing will require participants to become familiarized with performing maximal voluntary isometric contractions, as well as touring the laboratory facilities. Participants will be asked to complete dietary records for three days to determine habitual caloric intake. The experimental trial will be conducted in three phases. A baseline run-in phase (Phase 1) during which participants will consume a diet matching their estimated energy requirement to put them in a weight-stable phase. Energy requirements will be estimated using the Harris Benedict equation using an appropriate physical activity factor based on interview responses to a standard activity questionnaire. Participants will then be assigned to either the comparator group (n=10) or leucine-enriched protein food group (n=10). For the subsequent 10d (Phase 2), participants will undergo a period of step reduction (< 1000 steps.d-1) whilst in a 500 kcal.d-1 deficit that will be adjusted for the reduced physical activity due to the step reduction. The reason for inducing an energy deficit is to mimic a situation where older individuals will be both physically inactive and 'undernourished', such as during home-bound periods of sickness or while in hospital. After completing Phase 2, participants will then return to their normal step count (from measured habitual steps pre-intervention) under energy balanced conditions for 10d that will serve as a recovery phase, Phase 3. We will complete assessments of body composition, leg lean mass, maximal voluntary isometric strength, measures of physical performance, and rate of force development will be made. Skeletal muscle biopsies will be obtained for biochemical analysis. At these time points, maximal voluntary isometric force, maximal leg press strength, a battery of physical performance measures and body composition will once again be obtained.	Efficacy of a High Quality Protein Leucine-enriched Nutraceutical in Attenuating Inactivity- and Hypo-energetic Diet-induced Muscle Loss in Older Women	Muscle Loss	* Dietary Supplement: Leucine-enriched protein gel delivery system * Dietary Supplement: Milk protein gel delivery system	Inclusion Criteria:~Females between 70 and 75 years of age (a narrow age range improved homogeneity of the sample for this proof-of-concept trial) with a body mass index (BMI) between 27 and 35, and muscle mass 1 standard deviation below that of sex- and ethnicity-matched 30 year olds (note: this has been called 'stage 1 sarcopenia' or 'pre-sarcopenia') will be recruited. In addition, participants will be non-smokers and generally healthy per responses to a standard health screening questionnaire.~Exclusion Criteria:~Participants who have any one of the following conditions will be excluded:~diabetes mellitus~cardiovascular disease~renal disease~gastrointestinal disease~musculoskeletal injuries~hormone replacement therapy~significant weight loss in the 3-month period prior to the study~vegan diet~dairy protein allergy~use of medications known to interfere with muscle metabolism. For example, chronically taking any analgesic or anti-inflammatory drugs(s), prescription or non-prescription~a history of neuromuscular problems or muscle and/or bone wasting diseases~any acute or chronic illness, cardiac, pulmonary, liver, or kidney abnormalities, uncontrolled hypertension, insulin- or non-insulin dependent diabetes or other metabolic disorders-all ascertained through medical history screening questionnaires~use medications known to affect protein metabolism (i.e. corticosteroids, non-steroidal anti-inflammatories, or prescription strength acne medications)	70 Years	75 Years	Female	Accepts Healthy Volunteers	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: parallel group design (with repeated measurements within each group) Masking: Double	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change from baseline molecular signalling \| protein synthetic pathway \| Through study completion, an average of 1 year \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change from baseline lean body mass \| body composition \| Through study completion, an average of 1 year \|	Leucine, Protein, Supplementation	Caseins, Chelating Agents, Sequestering Agents, Molecular Mechanisms of Pharmacological Action	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Comparator group<br>Milk protein gel delivery system supplementation \| Dietary Supplement: Milk protein gel delivery system<br>* Non-leucine enriched<br>\| \| Experimental: Leucine-enriched protein group<br>Leucine-enriched protein gel delivery system supplementation \| Dietary Supplement: Leucine-enriched protein gel delivery system<br>* Leucine enriched<br>\|	Leucine-enriched Nutraceutical and Attenuating Muscle Loss Study Overview ================= Brief Summary ----------------- This leucine-enriched protein gummy (as a gummy bar/slab) will be studied to address age-related loss of muscle mass and strength/function in older persons. The product is small volume (approximately 35 g per serve) and low energy (approximately 100 kcal per serve). It is easy to chew and swallow with the consistency of a firm Jello. In addition, it contains an effective dose of leucine in a high-quality protein matrix consisting of milk proteins. Understanding the efficacy of this product on changes in levels of blood amino acids and the molecular signaling required to enhance muscle growth will provide helpful insight for the suggestion of supplemental use. Detailed Description ----------------- General experimental design: Pre-testing will require participants to become familiarized with performing maximal voluntary isometric contractions, as well as touring the laboratory facilities. Participants will be asked to complete dietary records for three days to determine habitual caloric intake. The experimental trial will be conducted in three phases. A baseline run-in phase (Phase 1) during which participants will consume a diet matching their estimated energy requirement to put them in a weight-stable phase. Energy requirements will be estimated using the Harris Benedict equation using an appropriate physical activity factor based on interview responses to a standard activity questionnaire. Participants will then be assigned to either the comparator group (n=10) or leucine-enriched protein food group (n=10). For the subsequent 10d (Phase 2), participants will undergo a period of step reduction (< 1000 steps.d-1) whilst in a 500 kcal.d-1 deficit that will be adjusted for the reduced physical activity due to the step reduction. The reason for inducing an energy deficit is to mimic a situation where older individuals will be both physically inactive and 'undernourished', such as during home-bound periods of sickness or while in hospital. After completing Phase 2, participants will then return to their normal step count (from measured habitual steps pre-intervention) under energy balanced conditions for 10d that will serve as a recovery phase, Phase 3. We will complete assessments of body composition, leg lean mass, maximal voluntary isometric strength, measures of physical performance, and rate of force development will be made. Skeletal muscle biopsies will be obtained for biochemical analysis. At these time points, maximal voluntary isometric force, maximal leg press strength, a battery of physical performance measures and body composition will once again be obtained. Official Title ----------------- Efficacy of a High Quality Protein Leucine-enriched Nutraceutical in Attenuating Inactivity- and Hypo-energetic Diet-induced Muscle Loss in Older Women Conditions ----------------- Muscle Loss Intervention / Treatment ----------------- * Dietary Supplement: Leucine-enriched protein gel delivery system * Dietary Supplement: Milk protein gel delivery system Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Females between 70 and 75 years of age (a narrow age range improved homogeneity of the sample for this proof-of-concept trial) with a body mass index (BMI) between 27 and 35, and muscle mass 1 standard deviation below that of sex- and ethnicity-matched 30 year olds (note: this has been called 'stage 1 sarcopenia' or 'pre-sarcopenia') will be recruited. In addition, participants will be non-smokers and generally healthy per responses to a standard health screening questionnaire. Exclusion Criteria: Participants who have any one of the following conditions will be excluded: diabetes mellitus cardiovascular disease renal disease gastrointestinal disease musculoskeletal injuries hormone replacement therapy significant weight loss in the 3-month period prior to the study vegan diet dairy protein allergy use of medications known to interfere with muscle metabolism. For example, chronically taking any analgesic or anti-inflammatory drugs(s), prescription or non-prescription a history of neuromuscular problems or muscle and/or bone wasting diseases any acute or chronic illness, cardiac, pulmonary, liver, or kidney abnormalities, uncontrolled hypertension, insulin- or non-insulin dependent diabetes or other metabolic disorders-all ascertained through medical history screening questionnaires use medications known to affect protein metabolism (i.e. corticosteroids, non-steroidal anti-inflammatories, or prescription strength acne medications) Ages Eligible for Study ----------------- Minimum Age: 70 Years Maximum Age: 75 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: parallel group design (with repeated measurements within each group) Masking: Double Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Comparator group<br>Milk protein gel delivery system supplementation \| Dietary Supplement: Milk protein gel delivery system<br>* Non-leucine enriched<br>\| \| Experimental: Leucine-enriched protein group<br>Leucine-enriched protein gel delivery system supplementation \| Dietary Supplement: Leucine-enriched protein gel delivery system<br>* Leucine enriched<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change from baseline molecular signalling \| protein synthetic pathway \| Through study completion, an average of 1 year \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change from baseline lean body mass \| body composition \| Through study completion, an average of 1 year \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Leucine, Protein, Supplementation
NCT03273114	Cognitive Functional Therapy (CFT) Compared With Core Training Exercise and Manual Therapy (CORE-MT) in Patients With Chronic Low Back Pain	There is evidence, of a single randomized controlled trial, that CFT is better than combined manual therapy and motor control exercise for chronic low back pain. However, this study had significant methodological shortcomings regarding the failure to carry out the intention to treat analysis and a considerable loss of follow-up of patients. As it is, it is important to carry out more studies involving CFT compared to other interventions already used in clinical practice and to correct these methodological shortcomings. Therefore, the aim of the study is to assess the efficacy of Cognitive Functional Therapy in patients with chronic non specific low back pain.	Randomized controlled trial with concealed allocation, blinded assessor, blinded participants and intention to treat analysis. Patients will be evaluated at baseline, 8 weeks, 6 and 12 months after randomization, to assess the maintenance of any effect of treatment. The patients in the CFT group will be treated by a physical therapists that attended twice the CFT workshops with two of the tutors of the method. She completed 106 hours of training including workshops, patient examinations and a pilot study with the supervision of a physical therapist with more than three years of clinical experience in CFT. Patients in CORE-MT group will be treated by a physical therapist with clinical experience in manual therapy and core training exercises.	Cognitive Functional Therapy (CFT) Compared With a Combined Core Training Exercise and Manual Therapy (CORE-MT) in Patients With Non-specific Chronic Low Back Pain: a Randomized Controlled Trial	Low Back Pain, Back Pain, Pain, Signs and Symptoms, Neuromuscular Manifestations	* Behavioral: Cognitive Functional Therapy * Other: Core Training Exercise and Manual Therapy	Inclusion Criteria:~Aged between 18 and 65 years~Low back pain for more than 3 months~Disability score of 14% or more on the Oswestry Disability Index (ODI)~Being able to walk independently with or without support~Understand Portuguese well enough to be able to fill in the questionnaires~Exclusion Criteria:~Main pain area is not the lumbar spine (from T12 to buttocks)~Main pain as leg pain (eg: nerve root compression or herniated disc with radicular pain / radiculopathy, lateral and central stenosis)~Less than 6 months after lumbar spine, lower limb or abdomen surgery~Invasive procedures for pain relief (ex: epidural injection, rhizotomy) in the last 3 months~Pregnancy~Inflammatory/rheumatological diseases (e.g., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, systemic lupus erythematosus, Scheuermann's disease)	18 Years	65 Years	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Randomized controlled trial with concealed allocation, blinded assessor, blinded participants and intention to treat analysis. Patients will be evaluated at baseline, 8 weeks, 6 and 12 months after randomization, to assess the maintenance of any effect of treatment. The patients in the CFT group will be treated by a physical therapists that attended twice the CFT workshops with two of the tutors of the method. She completed 106 hours of training including workshops, patient examinations and a pilot study with the supervision of a physical therapist with more than three years of clinical experience in CFT. Patients in CORE group will be treated by a physical therapist with clinical experience in manual therapy and core training exercises. Masking: Double	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Pain intensity \| It will be measured by the Brazilian version of the Numerical Scale of Pain 11 points (END). The END scale goes from 0 to 10, where 0 is no pain and 10 is the worst pain imaginable. Participants will be asked to answer about their pain levels based on the last seven days \| 8 weeks \| \| Disability associated to low back pain \| It will be assessed by the Brazilian version of the Oswestry Disability Index (ODI). It is a tool widely used in research and clinical practice to assess the disability low back pain. This questionnaire has 10 items (0-5 points each) related to activities of daily living that patients with low back pain have more difficulties to do. The sum of the scores of items is multiplied by two and the percentage of disability varies from 0 to 100 %. \| 8 weeks \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Global impression of recovery \| It will be evaluated based on the Global Perceived Effect Scale (GPES) which is an 11-point scale ranging from -5 ('vastly worse'), through 0 (no change) to +5 (completely recovered). \| 8 weeks, 6 and 12 months after randomization \| \| Pain intensity \| It will be measured by the Brazilian version of the Numerical Scale of Pain 11 points (END) 13. The END scale goes from 0 to 10, where 0 is no pain and 10 is the worst pain imaginable. Participants will be asked to answer about their pain levels based on the last seven days. \| 6 and 12 months after randomization \| \| Disability associated to low back pain \| It will be assessed by the Brazilian version of the Oswestry Disability Index (ODI). It is a tool widely used in research and clinical practice to assess the disability low back pain. This questionnaire has 10 items (0-5 points each) related to activities of daily living that patients with low back pain have more difficulties to do. The sum of the scores of items is multiplied by two and the percentage of disability varies from 0 to 100 %. \| 6 and 12 months after randomization \| \| Patient Satisfaction (mediator of outcome) \| This is a simple questionnaire from 1 to 5 asking the patients how satisfied they were with their treatment: 1 = satisfied, 2 = just a little satisfied, 3 = neither satisfied nor dissatisfied, 4 = just a little dissatisfied, 5 = dissatisfied \| 8 weeks, 6 and 12 months after randomization \| \| Catastrophization (mediator of outcome) \| It will be evaluated by the question When I feel pain, it's terrible and I feel it's never going to get any better.with the response options ranging from Never do that = 0 to Always do that = 10. \| 8 weeks, 6 and 12 months after randomization \| \| Depression (mediator of outcome) \| It will be evaluated by the question During the past month have you often been bothered by feeling down, depressed or hopeless? with the response options ranging from Never = 0 to All the time = 10. \| 8 weeks, 6 and 12 months months after randomization \| \| Fear of movement (mediator of outcome) \| It will be assessed by the question Physical activity might harm my back and the response options will range from 0 (completely disagree) to 10 (completely agree). \| 8 weeks, 6 and 12 months months after randomization \| \| Stress (mediator of outcome) \| It will be evaluated by the question Do you feel stressed? and the response options will range from 0 (completely disagree) to 10 (completely agree) \| 8 weeks, 6 and 12 months months after randomization \| \| Sleep (mediator of outcome) \| It will be evaluated by the question Did you have sleep problems last month? based on Subjective Health Complaints Inventory19. The response options will be Not at all=0, A little=1, Some=2, and Serious=3 \| 8 weeks, 6 and 12 months months after randomization \|	back pain, physiotherapy, exercise therapy, cognitive functional therapy, low back pain, backache, lower back pain, lumbago, multidimensional, biopsychosocial	Neuromuscular Manifestations, Back Pain, Low Back Pain, Pain, Neurologic Manifestations, Nervous System Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Cognitive Functional Therapy (CFT)<br>Cognitive Functional Therapy (CFT) is a behavioral intervention that addresses multiple aspects of low back pain. This approach focuses on changing the patient's beliefs, confronting their fears, educating them about pain mechanisms, increasing mental strength, and control of their body. This is done with functional tasks performed by individuals training them to reduce excessive muscle activity in the trunk and generate behavioral changes related to pain, from postures and provocative movements. \| Behavioral: Cognitive Functional Therapy<br>* There will be four main components in the intervention, following the protocol used by O'Keefe et al. (2015):~The cognitive component will focus on on the multidimensional nature of persistent pain about individual beliefs, and how emotions and behaviors (movement and lifestyle) can reinforce a vicious cycle of pain and disability.~Specific Functional training is designed to normalize maladaptive or provocative movement and posture.~Functional integration directed to activities of daily life that are avoided by the patient (rolling in bed, sitting, sitting to standing, walking, bending and lifting)~Patients will be advised to gradually increase physical activity based on their preference, also focusing on sleep hygiene, stress, and management strategies<br>\| \| Active Comparator: Core Training Exercise and Manual Therapy (CORE-MT)<br>The active comparator will be the combination of Core Training Exercise and Manual Therapy (CORE-MT). \| Other: Core Training Exercise and Manual Therapy<br>* According to the pragmatic clinical decision of the physiotherapist responsible for this intervention arm, participants allocated to the comparison group will be treated with active exercises will involve contractions of abdominal and back muscles in different functional positions, as well as joint mobilization or manipulation techniques applied to the lower back or pélvis, when necessary. Most patients in this group will receive exercises to perform at home, but not related to CFT.<br>\|	Cognitive Functional Therapy (CFT) Compared With Core Training Exercise and Manual Therapy (CORE-MT) in Patients With Chronic Low Back Pain Study Overview ================= Brief Summary ----------------- There is evidence, of a single randomized controlled trial, that CFT is better than combined manual therapy and motor control exercise for chronic low back pain. However, this study had significant methodological shortcomings regarding the failure to carry out the intention to treat analysis and a considerable loss of follow-up of patients. As it is, it is important to carry out more studies involving CFT compared to other interventions already used in clinical practice and to correct these methodological shortcomings. Therefore, the aim of the study is to assess the efficacy of Cognitive Functional Therapy in patients with chronic non specific low back pain. Detailed Description ----------------- Randomized controlled trial with concealed allocation, blinded assessor, blinded participants and intention to treat analysis. Patients will be evaluated at baseline, 8 weeks, 6 and 12 months after randomization, to assess the maintenance of any effect of treatment. The patients in the CFT group will be treated by a physical therapists that attended twice the CFT workshops with two of the tutors of the method. She completed 106 hours of training including workshops, patient examinations and a pilot study with the supervision of a physical therapist with more than three years of clinical experience in CFT. Patients in CORE-MT group will be treated by a physical therapist with clinical experience in manual therapy and core training exercises. Official Title ----------------- Cognitive Functional Therapy (CFT) Compared With a Combined Core Training Exercise and Manual Therapy (CORE-MT) in Patients With Non-specific Chronic Low Back Pain: a Randomized Controlled Trial Conditions ----------------- Low Back Pain, Back Pain, Pain, Signs and Symptoms, Neuromuscular Manifestations Intervention / Treatment ----------------- * Behavioral: Cognitive Functional Therapy * Other: Core Training Exercise and Manual Therapy Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Aged between 18 and 65 years Low back pain for more than 3 months Disability score of 14% or more on the Oswestry Disability Index (ODI) Being able to walk independently with or without support Understand Portuguese well enough to be able to fill in the questionnaires Exclusion Criteria: Main pain area is not the lumbar spine (from T12 to buttocks) Main pain as leg pain (eg: nerve root compression or herniated disc with radicular pain / radiculopathy, lateral and central stenosis) Less than 6 months after lumbar spine, lower limb or abdomen surgery Invasive procedures for pain relief (ex: epidural injection, rhizotomy) in the last 3 months Pregnancy Inflammatory/rheumatological diseases (e.g., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, systemic lupus erythematosus, Scheuermann's disease) Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Randomized controlled trial with concealed allocation, blinded assessor, blinded participants and intention to treat analysis. Patients will be evaluated at baseline, 8 weeks, 6 and 12 months after randomization, to assess the maintenance of any effect of treatment. The patients in the CFT group will be treated by a physical therapists that attended twice the CFT workshops with two of the tutors of the method. She completed 106 hours of training including workshops, patient examinations and a pilot study with the supervision of a physical therapist with more than three years of clinical experience in CFT. Patients in CORE group will be treated by a physical therapist with clinical experience in manual therapy and core training exercises. Masking: Double Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Cognitive Functional Therapy (CFT)<br>Cognitive Functional Therapy (CFT) is a behavioral intervention that addresses multiple aspects of low back pain. This approach focuses on changing the patient's beliefs, confronting their fears, educating them about pain mechanisms, increasing mental strength, and control of their body. This is done with functional tasks performed by individuals training them to reduce excessive muscle activity in the trunk and generate behavioral changes related to pain, from postures and provocative movements. \| Behavioral: Cognitive Functional Therapy<br>* There will be four main components in the intervention, following the protocol used by O'Keefe et al. (2015): The cognitive component will focus on on the multidimensional nature of persistent pain about individual beliefs, and how emotions and behaviors (movement and lifestyle) can reinforce a vicious cycle of pain and disability. Specific Functional training is designed to normalize maladaptive or provocative movement and posture. Functional integration directed to activities of daily life that are avoided by the patient (rolling in bed, sitting, sitting to standing, walking, bending and lifting) Patients will be advised to gradually increase physical activity based on their preference, also focusing on sleep hygiene, stress, and management strategies<br>\| \| Active Comparator: Core Training Exercise and Manual Therapy (CORE-MT)<br>The active comparator will be the combination of Core Training Exercise and Manual Therapy (CORE-MT). \| Other: Core Training Exercise and Manual Therapy<br>* According to the pragmatic clinical decision of the physiotherapist responsible for this intervention arm, participants allocated to the comparison group will be treated with active exercises will involve contractions of abdominal and back muscles in different functional positions, as well as joint mobilization or manipulation techniques applied to the lower back or pélvis, when necessary. Most patients in this group will receive exercises to perform at home, but not related to CFT.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Pain intensity \| It will be measured by the Brazilian version of the Numerical Scale of Pain 11 points (END). The END scale goes from 0 to 10, where 0 is no pain and 10 is the worst pain imaginable. Participants will be asked to answer about their pain levels based on the last seven days \| 8 weeks \| \| Disability associated to low back pain \| It will be assessed by the Brazilian version of the Oswestry Disability Index (ODI). It is a tool widely used in research and clinical practice to assess the disability low back pain. This questionnaire has 10 items (0-5 points each) related to activities of daily living that patients with low back pain have more difficulties to do. The sum of the scores of items is multiplied by two and the percentage of disability varies from 0 to 100 %. \| 8 weeks \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Global impression of recovery \| It will be evaluated based on the Global Perceived Effect Scale (GPES) which is an 11-point scale ranging from -5 ('vastly worse'), through 0 (no change) to +5 (completely recovered). \| 8 weeks, 6 and 12 months after randomization \| \| Pain intensity \| It will be measured by the Brazilian version of the Numerical Scale of Pain 11 points (END) 13. The END scale goes from 0 to 10, where 0 is no pain and 10 is the worst pain imaginable. Participants will be asked to answer about their pain levels based on the last seven days. \| 6 and 12 months after randomization \| \| Disability associated to low back pain \| It will be assessed by the Brazilian version of the Oswestry Disability Index (ODI). It is a tool widely used in research and clinical practice to assess the disability low back pain. This questionnaire has 10 items (0-5 points each) related to activities of daily living that patients with low back pain have more difficulties to do. The sum of the scores of items is multiplied by two and the percentage of disability varies from 0 to 100 %. \| 6 and 12 months after randomization \| \| Patient Satisfaction (mediator of outcome) \| This is a simple questionnaire from 1 to 5 asking the patients how satisfied they were with their treatment: 1 = satisfied, 2 = just a little satisfied, 3 = neither satisfied nor dissatisfied, 4 = just a little dissatisfied, 5 = dissatisfied \| 8 weeks, 6 and 12 months after randomization \| \| Catastrophization (mediator of outcome) \| It will be evaluated by the question When I feel pain, it's terrible and I feel it's never going to get any better.with the response options ranging from Never do that = 0 to Always do that = 10. \| 8 weeks, 6 and 12 months after randomization \| \| Depression (mediator of outcome) \| It will be evaluated by the question During the past month have you often been bothered by feeling down, depressed or hopeless? with the response options ranging from Never = 0 to All the time = 10. \| 8 weeks, 6 and 12 months months after randomization \| \| Fear of movement (mediator of outcome) \| It will be assessed by the question Physical activity might harm my back and the response options will range from 0 (completely disagree) to 10 (completely agree). \| 8 weeks, 6 and 12 months months after randomization \| \| Stress (mediator of outcome) \| It will be evaluated by the question Do you feel stressed? and the response options will range from 0 (completely disagree) to 10 (completely agree) \| 8 weeks, 6 and 12 months months after randomization \| \| Sleep (mediator of outcome) \| It will be evaluated by the question Did you have sleep problems last month? based on Subjective Health Complaints Inventory19. The response options will be Not at all=0, A little=1, Some=2, and Serious=3 \| 8 weeks, 6 and 12 months months after randomization \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- back pain, physiotherapy, exercise therapy, cognitive functional therapy, low back pain, backache, lower back pain, lumbago, multidimensional, biopsychosocial
NCT00416546	Safety of AEB071 in Healthy Volunteers and to Compare the Ethnicity, Metabolic, and Safety Effects Between Caucasian and Japanese Healthy Subjects	This is a study to assess the safety effects after multiple doses of AEB071 in healthy volunteers and to compare the ethnicity, metabolic, and safety effects between Caucasian and Japanese healthy subjects receiving single and multiple doses of AEB071.		A Double Blind, Randomized, Placebo-Controlled Study of AEB071 in Healthy Volunteers to Evaluate the Safety/Tolerability of 14 Day Multiple-Dose AEB071 and Measure the Effect of Ethnicity on Pharmacokinetics, Pharmacodynamics and Safety/Tolerability in Caucasian and Japanese Subjects Receiving Single and Multiple Doses of AEB071	Healthy	* Drug: AEB071	Inclusion Criteria:~Healthy, male or female subjects having provided written, informed, consent before entering the study. Light smokers (≤10 cigarettes/day) will be eligible for inclusion in this study. Smokers will be defined as any subject who reports cigarette use or has a urine cotinine greater than 500 ng/mL.~Female subjects must be either surgically sterilized at least 6 months or practicing an acceptable form of birth control (i.e. double barrier method - intrauterine device plus condom, spermicidal gel plus condom).~Subjects must have a body weight between 45 and 90 kg and a body mass index (BMI) between 18-28 kg/m2.~Japanese subjects of 1st, 2nd, or 3rd generation ethnic origin or Caucasian.~Japanese subjects will be defined as being of Japanese ethnicity with all 4 grandparents of Japanese descent. Generations will be defined as follows:~'First generation' Japanese are subjects who were born in Japan to parents of Japanese ethnicity.~'Second generation' will be defined as subjects who were born outside of Japan to 1st generation Japanese parents.~'Third generation' will be defined as subjects born outside of Japan to 2nd generation Japanese parents, i.e. 4 grandparents from Japan but both parents and subject born elsewhere.~Caucasians are defined as subjects with all four grandparents of European descent.~Exclusion Criteria:~Presence and/or history of a clinically significant illness within two weeks prior to dosing, history of drug or alcohol abuse within the 12 months prior to dosing, use of any prescription drug or over-the-counter (OTC) medication (acetaminophen is acceptable) within 14 days prior to dosing.~Presence of a clinically significant systemic illness, active infectious process (viral or bacterial), e.g., cold sore, or documented drug allergies that may deteriorate or affect the subject's safety or ability to cooperate during the study.~Laboratory or clinical evidence suggestive of liver or renal disease, history of heart disease, history of autonomic dysfunction (e.g. history of fainting, orthostatic hypotension, sinus arrhythmia), history of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated), history of major gastrointestinal disease, history or clinical evidence of pancreatic injury or pancreatitis~Subjects with a resting heart rate < 50 beats per minute (bpm)~Subjects with systolic blood pressure < 90 or diastolic blood pressure < 50.~Subjects with lymphocyte counts less than 1200/mm3 or total white blood cell (WBC) greater than 10000/mm3 at baseline~A past medical history of clinically significant electrocardiogram (ECG) abnormalities or a family history of a prolonged QT-interval syndrome.~Subjects who intend to or have received any live attenuated vaccines 4 weeks prior to or during the study period.~Other protocol-defined inclusion/exclusion criteria may apply.	18 Years	50 Years	All	Accepts Healthy Volunteers	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| To compare the pharmacokinetics between healthy Caucasian and Japanese subjects after a single oral dose of AEB071 \| \| \| \| To compare the pharmacokinetics between healthy Caucasian and Japanese subjects after 7 days of oral, daily doses of AEB071 \| \| \| \| To compare the safety and tolerability of single and multiple oral doses of AEB071 in healthy Japanese and Caucasian subjects \| \| \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| To compare the dose response, temporal course and effect of AEB071 on lymphocyte proliferation after single oral doses of AEB071 in healthy Caucasian and Japanese subjects \| \| \|	Healthy Caucasians, Healthy Japanese subjects, Immunosuppressant, early T-cell activation blockers, inhibition of protein kinase C		\| Intervention/Treatment \| \| --- \| \|Drug: AEB071\|nan\|	Safety of AEB071 in Healthy Volunteers and to Compare the Ethnicity, Metabolic, and Safety Effects Between Caucasian and Japanese Healthy Subjects Study Overview ================= Brief Summary ----------------- This is a study to assess the safety effects after multiple doses of AEB071 in healthy volunteers and to compare the ethnicity, metabolic, and safety effects between Caucasian and Japanese healthy subjects receiving single and multiple doses of AEB071. Official Title ----------------- A Double Blind, Randomized, Placebo-Controlled Study of AEB071 in Healthy Volunteers to Evaluate the Safety/Tolerability of 14 Day Multiple-Dose AEB071 and Measure the Effect of Ethnicity on Pharmacokinetics, Pharmacodynamics and Safety/Tolerability in Caucasian and Japanese Subjects Receiving Single and Multiple Doses of AEB071 Conditions ----------------- Healthy Intervention / Treatment ----------------- * Drug: AEB071 Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Healthy, male or female subjects having provided written, informed, consent before entering the study. Light smokers (≤10 cigarettes/day) will be eligible for inclusion in this study. Smokers will be defined as any subject who reports cigarette use or has a urine cotinine greater than 500 ng/mL. Female subjects must be either surgically sterilized at least 6 months or practicing an acceptable form of birth control (i.e. double barrier method - intrauterine device plus condom, spermicidal gel plus condom). Subjects must have a body weight between 45 and 90 kg and a body mass index (BMI) between 18-28 kg/m2. Japanese subjects of 1st, 2nd, or 3rd generation ethnic origin or Caucasian. Japanese subjects will be defined as being of Japanese ethnicity with all 4 grandparents of Japanese descent. Generations will be defined as follows: 'First generation' Japanese are subjects who were born in Japan to parents of Japanese ethnicity. 'Second generation' will be defined as subjects who were born outside of Japan to 1st generation Japanese parents. 'Third generation' will be defined as subjects born outside of Japan to 2nd generation Japanese parents, i.e. 4 grandparents from Japan but both parents and subject born elsewhere. Caucasians are defined as subjects with all four grandparents of European descent. Exclusion Criteria: Presence and/or history of a clinically significant illness within two weeks prior to dosing, history of drug or alcohol abuse within the 12 months prior to dosing, use of any prescription drug or over-the-counter (OTC) medication (acetaminophen is acceptable) within 14 days prior to dosing. Presence of a clinically significant systemic illness, active infectious process (viral or bacterial), e.g., cold sore, or documented drug allergies that may deteriorate or affect the subject's safety or ability to cooperate during the study. Laboratory or clinical evidence suggestive of liver or renal disease, history of heart disease, history of autonomic dysfunction (e.g. history of fainting, orthostatic hypotension, sinus arrhythmia), history of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated), history of major gastrointestinal disease, history or clinical evidence of pancreatic injury or pancreatitis Subjects with a resting heart rate < 50 beats per minute (bpm) Subjects with systolic blood pressure < 90 or diastolic blood pressure < 50. Subjects with lymphocyte counts less than 1200/mm3 or total white blood cell (WBC) greater than 10000/mm3 at baseline A past medical history of clinically significant electrocardiogram (ECG) abnormalities or a family history of a prolonged QT-interval syndrome. Subjects who intend to or have received any live attenuated vaccines 4 weeks prior to or during the study period. Other protocol-defined inclusion/exclusion criteria may apply. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 50 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions \| Intervention/Treatment \| \| --- \| \|Drug: AEB071\|nan\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| To compare the pharmacokinetics between healthy Caucasian and Japanese subjects after a single oral dose of AEB071 \| \| \| \| To compare the pharmacokinetics between healthy Caucasian and Japanese subjects after 7 days of oral, daily doses of AEB071 \| \| \| \| To compare the safety and tolerability of single and multiple oral doses of AEB071 in healthy Japanese and Caucasian subjects \| \| \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| To compare the dose response, temporal course and effect of AEB071 on lymphocyte proliferation after single oral doses of AEB071 in healthy Caucasian and Japanese subjects \| \| \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Healthy Caucasians, Healthy Japanese subjects, Immunosuppressant, early T-cell activation blockers, inhibition of protein kinase C
NCT01659268	Performance of Baccalaureate Nursing Students in Insertion of Laryngeal Mask: a Trial in Mannequins	The purpose of this study is to compare if there difference in acquisition of knowledge and skills in airway management to baccalaureate nursing students submitted to different learning strategies: exhibition-dialogued class and practical activity in skill lab with low-fidelity mannequin or simulation class with low-fidelity mannequin.	The airway control is priority in patient resuscitation. The Laryngeal Mask Airway (LMA) can minimize complications, establishing a safe airway. Is fundamental to nurse acquired skills to act in emergency situations; the simulation is a important learning tool for this, because allows a realistic environment and allows to student the possibility of training skills.~Hypothesis: There difference in acquisition of knowledge and skills in airway management to baccalaureate nursing students submitted to different learning strategies: classroom lecture-dialogued follow of laboratory activity practice with low-fidelity mannequin or simulation in laboratory with low-fidelity mannequin?~The aim of this study is compare the effect of teaching-learning strategies: classroom lecture-dialogued follow of laboratory activity practice with low-fidelity mannequin or simulation in laboratory with low-fidelity mannequin, in the acquisition of knowledge and skills to baccalaureate nursing. This is a randomized controlled trial, the population is all students of baccalaureate nursing of EERP-USP, eighth period, 69 students in total; the sample will be voluntary and composed for students that accept participate of study. The intervention group (IG) will be submitted to simulation class and the control group (CG)to exhibition-dialogued class, and practical activity in skill lab. The study will have 3 steps:~The participants will be recruited with letters and posters, randomized to IG or CG and follow submitted to write pre-test.~The GI will submitted to simulation in laboratory and de CG classroom lecture-dialogued follow of laboratory activity practice. The focus will be the airway management with emphasis in LMA.~All participants will be submitted to write post test and follow to practice test in simulation scenario, with medium-fidelity mannequin, which simulates human physiologic conditions.~The scenario will have a appraiser with a checklist which performance scores of skills and interventions observed. The activities will be filmed and recorded. To data analysis will be used the SPSS software: descriptive statistics, chi-square test, t-test of Student.	Performance of Nursing Students in the Insertion of Supraglottic Device (Laryngeal Mask): Randomized Controlled Trial on Mannequins.	Respiratory Failure	* Other: Simulation class * Other: Exhibition-dialogued class	Inclusion Criteria:~student must be in the eighth period of course;~must be registered regular in the baccalaureate nursing course.~Exclusion Criteria:~absence in any step of study.	18 Years	null	All	Accepts Healthy Volunteers	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Scores in Pre and Post-test, Number of Participants Successfully Completing the Overall Performance Simulated Scenario(OSCE). \| Score obtained in pre and post-test written, time to obtain the first effective ventilation (chest expansion through adequate ventilation on the mannequin), number of attempts to insert the LMA in the simulation scenario (OSCE).~Pre-test: 20 questions with score of 0.5 points each - minimum score=0 points and maximum score=10 points. Score 5-7 points was considered satisfactory; scores between 7-8 points was considered good performance; above 8 points excellent.~Post-test: 20 questions with score of 0.5 points each - minimum score=0 points and maximum score=10 points. Score 5-7 points was considered satisfactory; scores between 7-8 points was considered good performance; above 8 points excellent.~OSCE: instrument with total of 10 skills - each skill was subdivided in 4-5 activities (0.2-0.25 points each) - poor performance was score < 5.0; satisfactory performance 5.0-7.0; good 7.0-8.5 and excellent above 8.5 points. \| Pretest: 40 minutes; Post-test: 40 minutes; OSCE: 10 minutes \| \| Time to Conclusion of Simulation Scenario (OSCE) \| This result present the total time for execution of simulation scenario (OSCE) by the students. \| 10 minutes \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Time for Acquisition of First Effective Ventilation, Adequate Tidal Volume and Stabilization of Patient. \| Time of achievement to first effective ventilation and tidal volume (adequate chest expansion).~Stabilization of mannequin parameters (spO2 e HR). \| 10 minutes (600 sec) \| \| Number of Attempts to Insertion of LMA \| Number of attempts for insertion of LMA and obtainment of effective ventilation. \| 10 minutes (total time of scenario) \|	teaching, patient simulation, laryngeal masks, baccalaureate nursing education, teaching strategies, simulation	Respiratory Insufficiency, Respiration Disorders, Respiratory Tract Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Simulation class<br>The students will be submitted a simulation scenario in laboratory with low-fidelity mannequin for 60 minutes, in subgroups of 4-5 students. The simulated condition is a patient in respiratory failure which need of emergency interventions.~The approach concepts of anatomic, physiology and clinical interventions using LMA will be discussed during simulation. \| Other: Simulation class<br>* The students will be submitted a simulation scenario in laboratory with low-fidelity mannequin for 60 minutes, in subgroups of 4-5 students. The simulated condition is a patient in respiratory failure which need of emergency interventions.~The approach concepts of anatomic, physiology and clinical interventions using LMA will be discussed during simulation.<br>\| \| Other: Exhibition-dialogued class<br>Students will be submitted to exhibition-dialogued class with duration of 60 minutes; after this, each subgroup composed of 4-5 students will go to the and practical activity in skill lab using the low-fidelity mannequin for 35 minutes. \| Other: Exhibition-dialogued class<br>* The students randomized to CG will be submitted to exhibition-dialogued class with duration of 60 minutes; after this, will go to practical activity in skill lab using the low-fidelity mannequin with duration of 35 minutes.~Each subgroup will be composed of 5-6 students for the practice activity which will last 45 minutes.<br>\|	Performance of Baccalaureate Nursing Students in Insertion of Laryngeal Mask: a Trial in Mannequins Study Overview ================= Brief Summary ----------------- The purpose of this study is to compare if there difference in acquisition of knowledge and skills in airway management to baccalaureate nursing students submitted to different learning strategies: exhibition-dialogued class and practical activity in skill lab with low-fidelity mannequin or simulation class with low-fidelity mannequin. Detailed Description ----------------- The airway control is priority in patient resuscitation. The Laryngeal Mask Airway (LMA) can minimize complications, establishing a safe airway. Is fundamental to nurse acquired skills to act in emergency situations; the simulation is a important learning tool for this, because allows a realistic environment and allows to student the possibility of training skills. Hypothesis: There difference in acquisition of knowledge and skills in airway management to baccalaureate nursing students submitted to different learning strategies: classroom lecture-dialogued follow of laboratory activity practice with low-fidelity mannequin or simulation in laboratory with low-fidelity mannequin? The aim of this study is compare the effect of teaching-learning strategies: classroom lecture-dialogued follow of laboratory activity practice with low-fidelity mannequin or simulation in laboratory with low-fidelity mannequin, in the acquisition of knowledge and skills to baccalaureate nursing. This is a randomized controlled trial, the population is all students of baccalaureate nursing of EERP-USP, eighth period, 69 students in total; the sample will be voluntary and composed for students that accept participate of study. The intervention group (IG) will be submitted to simulation class and the control group (CG)to exhibition-dialogued class, and practical activity in skill lab. The study will have 3 steps: The participants will be recruited with letters and posters, randomized to IG or CG and follow submitted to write pre-test. The GI will submitted to simulation in laboratory and de CG classroom lecture-dialogued follow of laboratory activity practice. The focus will be the airway management with emphasis in LMA. All participants will be submitted to write post test and follow to practice test in simulation scenario, with medium-fidelity mannequin, which simulates human physiologic conditions. The scenario will have a appraiser with a checklist which performance scores of skills and interventions observed. The activities will be filmed and recorded. To data analysis will be used the SPSS software: descriptive statistics, chi-square test, t-test of Student. Official Title ----------------- Performance of Nursing Students in the Insertion of Supraglottic Device (Laryngeal Mask): Randomized Controlled Trial on Mannequins. Conditions ----------------- Respiratory Failure Intervention / Treatment ----------------- * Other: Simulation class * Other: Exhibition-dialogued class Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: student must be in the eighth period of course; must be registered regular in the baccalaureate nursing course. Exclusion Criteria: absence in any step of study. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Simulation class<br>The students will be submitted a simulation scenario in laboratory with low-fidelity mannequin for 60 minutes, in subgroups of 4-5 students. The simulated condition is a patient in respiratory failure which need of emergency interventions. The approach concepts of anatomic, physiology and clinical interventions using LMA will be discussed during simulation. \| Other: Simulation class<br>* The students will be submitted a simulation scenario in laboratory with low-fidelity mannequin for 60 minutes, in subgroups of 4-5 students. The simulated condition is a patient in respiratory failure which need of emergency interventions. The approach concepts of anatomic, physiology and clinical interventions using LMA will be discussed during simulation.<br>\| \| Other: Exhibition-dialogued class<br>Students will be submitted to exhibition-dialogued class with duration of 60 minutes; after this, each subgroup composed of 4-5 students will go to the and practical activity in skill lab using the low-fidelity mannequin for 35 minutes. \| Other: Exhibition-dialogued class<br>* The students randomized to CG will be submitted to exhibition-dialogued class with duration of 60 minutes; after this, will go to practical activity in skill lab using the low-fidelity mannequin with duration of 35 minutes. Each subgroup will be composed of 5-6 students for the practice activity which will last 45 minutes.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Scores in Pre and Post-test, Number of Participants Successfully Completing the Overall Performance Simulated Scenario(OSCE). \| Score obtained in pre and post-test written, time to obtain the first effective ventilation (chest expansion through adequate ventilation on the mannequin), number of attempts to insert the LMA in the simulation scenario (OSCE). Pre-test: 20 questions with score of 0.5 points each - minimum score=0 points and maximum score=10 points. Score 5-7 points was considered satisfactory; scores between 7-8 points was considered good performance; above 8 points excellent. Post-test: 20 questions with score of 0.5 points each - minimum score=0 points and maximum score=10 points. Score 5-7 points was considered satisfactory; scores between 7-8 points was considered good performance; above 8 points excellent. OSCE: instrument with total of 10 skills - each skill was subdivided in 4-5 activities (0.2-0.25 points each) - poor performance was score < 5.0; satisfactory performance 5.0-7.0; good 7.0-8.5 and excellent above 8.5 points. \| Pretest: 40 minutes; Post-test: 40 minutes; OSCE: 10 minutes \| \| Time to Conclusion of Simulation Scenario (OSCE) \| This result present the total time for execution of simulation scenario (OSCE) by the students. \| 10 minutes \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Time for Acquisition of First Effective Ventilation, Adequate Tidal Volume and Stabilization of Patient. \| Time of achievement to first effective ventilation and tidal volume (adequate chest expansion). Stabilization of mannequin parameters (spO2 e HR). \| 10 minutes (600 sec) \| \| Number of Attempts to Insertion of LMA \| Number of attempts for insertion of LMA and obtainment of effective ventilation. \| 10 minutes (total time of scenario) \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- teaching, patient simulation, laryngeal masks, baccalaureate nursing education, teaching strategies, simulation
NCT03869060	Expansion of a Dengue-1 Live Virus Human Challenge	To evaluate the effectiveness of candidate dengue vaccine formulations, it is prudent to develop an appropriate challenge model. This study supports the expansion of the data set of the current Dengue 1 Live Virus Human Challenge (DENV-1-LVHC) model to produce uncomplicated dengue-like illness.	This is an expansion of a previous study conducted under NCT02372175. In this study up to nine healthy subjects between 18 and 45 years old will be inoculated with Dengue 1 Live Virus Human Challenge (DENV-1-LVHC) at a dose used in the previous study. Subjects will be closely monitored for the first 28 days with continued follow up through 6 months. Clinical and laboratory parameters, viremia and antibody levels will be assess. The goal is to expand the data set of symptoms produced by uncomplicated dengue-like illness.	Phase One, Open Label Expansion of a Dengue-1-Virus-Live Virus Human Challenge - (DENV-1-LVHC) Virus Strain.	Dengue	* Biological: Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC)	Inclusion Criteria:~Age 18-45 at the time of consent~Ability and willingness to sign informed consent~Passing score on comprehension test of at least 75%, with up to 3 attempts~Available for the study period~Willing to use contraception for the duration of the study~Provide consent for release of medical history records from primary care physician, college or university, urgent care or emergency room visit~Exclusion Criteria:~Female: pregnant or lactating~Heavy menstrual bleeding within the last 6 months- menstrual periods lasting longer than 6 days, or requiring 5 or more pads or tampons per day.~Female subjects using an intrauterine device (IUD) or Mirena®~Female subjects with fibroids or uterine polyps, endometriosis, adenomyosis, and uterine scarring (e.g., after D&C)~Blood tests confirming infection with human immunodeficiency virus- 1 (HIV-1), hepatitis C, hepatitis B (assessed by HbsAg) virus, or positive antibodies to the flaviviruses (FV) dengue, West Nile, Yellow Fever, Japanese encephalitis, or Zika.~Active Diabetes or active peptic ulcer disease (PUD)~Chronic obstructive pulmonary disease (COPD) or coronary artery disease (CAD)~Known or suspected congenital or acquired immunodeficiency; or receipt of immunomodulation therapy such as anti-cancer chemotherapy or radiation therapy; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)~Current, or a history of, auto-immune disease~History of Guillain-Barré syndrome (GBS)~Any history of FV infection or FV vaccination; or planned FV vaccination, outside the study protocol, during the study period~Diagnosis with Bipolar Disorder or Schizophrenia, hospitalization in the past year for a mental health disorder, or any other psychiatric condition, which in the opinion of the investigator prevents the subject from participating in the study.~Planned travel during the study period (180 days) which would interfere with the ability to complete all study visits~Recent (in the past 4 weeks) travel to any dengue endemic area. These potential subjects may be eligible for enrollment a minimum of 4 weeks later~Any grade 2 laboratory abnormalities prior to inoculation for the tests specified in Table 18 and Table 19 of the protocol, except those listed in exclusion criteria 16~Subjects with the following grade 1 or greater lab abnormalities: Creatinine; Liver Function Tests - ALT, AST; Hemoglobin (females and males); White Blood Cell (WBC) decrease; Platelets decreased; Prothrombin Time (PT); Partial Thromboplastin Time (PTT); Fibrinogen decrease~Significant screening physical examination abnormalities at the discretion of the investigator~Women who intend to become pregnant or men who intend to father a child during the study period (approximately 180 days)~Hives, shortness of breath, swelling of the lips or throat, or hospitalization related to a previous vaccination or an allergy to specific medications/animals for which antigens may be in the virus preparations to include: shellfish allergy, fetal bovine serum, L-glutamine, neomycin and streptomycin~Planning to donate blood in the 1 year following inoculation with dengue~Recent blood donation within prior 56 days of inoculation~Receipt of blood products or antibodies within 56 days of inoculation or during the study period~Participation (active or follow-up phase) or planned participation in another vaccine, drug, medical device, or medical procedure clinical trial in the 4 weeks prior to this trial, during the trial, or 6 months following inoculation in this clinical trial~Recent or scheduled receipt of any vaccine 4 weeks prior to or after virus inoculation~Beliefs that bar the administration of blood products or transfusions~Positive urine screen for cocaine, amphetamines, or opiates~Currently taking Methadone or Suboxone~Currently taking anti-coagulant medication, aspirin or non-steroidal anti-inflammatory drugs (NSAIDs)~Chronic migraine headaches, defined as more than 15 headache days per month over a 3 month period of which more than 8 are migraines, in the absence of medication over use~Chronic medical condition that, in the opinion of the investigator, impacts subject safety.	18 Years	45 Years	All	Accepts Healthy Volunteers	Primary Purpose: Other Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Abnormal Laboratory Parameters \| Total number of all abnormal labs \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Intensity of Abnormal Laboratory Parameters \| Graded according clinical laboratory normals and FDA toxicity scale \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Duration of Abnormal Laboratory Parameters \| Number of days of abnormal lab \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Occurrence of Solicited Injection site symptoms \| Number of solicited symptoms \| 7 days post virus inoculation \| \| Intensity of Solicited Injection site symptoms \| Symptoms graded according to FDA toxicity scale \| 7 days post virus inoculation \| \| Duration of Solicited Injection site symptoms \| Number of days per symptom \| 7 days post virus inoculation \| \| Occurrence of Unsolicited Injection site symptoms \| Number of unsolicited site symptoms \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Intensity of Unsolicited Injection site symptoms \| Symptoms graded according to FDA toxicity scale \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Duration of Unsolicited Injection site symptoms \| Number of days per symptom \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Occurrence of Solicited systemic symptoms \| Number of systemic symptoms \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Intensity of Solicited systemic symptoms \| Symptoms graded according to FDA toxicity scale \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Duration of Solicited systemic symptoms \| Number of days per symptom \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Occurrence of Unsolicited systemic symptoms \| Number of symptoms \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Intensity of Unsolicited systemic symptoms \| Symptoms graded according to FDA toxicity scale \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Duration of Unsolicited systemic symptoms \| Number of days per symptom \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Number of Serious Adverse Events \| Total number \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Number of Serious Adverse Events \| Total number \| 6 months post virus inoculation \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Incubation period before onset of fever \| Number of days prior to fever \| Up to 28 days post virus inoculation \| \| Viremia by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) \| Levels of viremia \| Up to 28 days post virus inoculation \| \| Viremia by plaque assay \| Quantitation of infectious virus \| Up to 28 days post virus inoculation \| \| Occurrence of fever without other identifiable cause, such as strep infection or influenza \| The occurrence of fever defined as greater than or equal to 38°C (100.4°F) measured at least 2 times in 24 hours but not lasting more than 72 hours \| Up to 28 days post virus inoculation \| \| Occurrence of Headache \| Number of headaches \| Up to 28 days post virus inoculation \| \| Grade of Headache \| Graded according to FDA toxicity scale \| Up to 28 days post virus inoculation \| \| Occurrence of Myalgia \| Number of reported myalgias \| Up to 28 days post virus inoculation \| \| Grade of Myalgia \| Graded according to FDA toxicity scale \| Up to 28 days post virus inoculation \| \| Occurrence of Rash \| Number of rashes \| Up to 28 days post virus inoculation \| \| Grade of Rash \| Graded according to FDA toxicity scale \| Up to 28 days post virus inoculation \| \| Occurrence of Abnormal Liver Function Test [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] \| Number of abnormal liver function tests \| Up to 28 days post virus inoculation \| \| Grade of Abnormal Liver Function Test [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] \| Graded according clinical laboratory normals and FDA toxicity scale \| Up to 28 days post virus inoculation \| \| Occurrence of Leukopenia \| Number of occurrences \| Up to 28 days post virus inoculation \| \| Grade of Leukopenia \| Graded according clinical laboratory normals and FDA toxicity scale \| Up to 28 days post virus inoculation \| \| Occurrence of Thrombocytopenia \| Number of occurrences \| Up to 28 days post virus inoculation \| \| Grade of Thrombocytopenia \| Graded according clinical laboratory normals and FDA toxicity scale \| Up to 28 days post virus inoculation \|	Dengue, Flavivirus Infections, Virus Diseases	Dengue, Arbovirus Infections, Vector Borne Diseases, Infections, Virus Diseases, Flavivirus Infections, Flaviviridae Infections, RNA Virus Infections, Hemorrhagic Fevers, Viral	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Inoculated Group<br>Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC) given as a single dose [0.5 mL of 6.5 x 10^3 plaque forming units/milliliter (PFU/mL)] inoculated subcutaneously. \| Biological: Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC)<br>* Dengue subtype 1 Challenge Virus (DENV-1) strain 45AZ5<br>\|	Expansion of a Dengue-1 Live Virus Human Challenge Study Overview ================= Brief Summary ----------------- To evaluate the effectiveness of candidate dengue vaccine formulations, it is prudent to develop an appropriate challenge model. This study supports the expansion of the data set of the current Dengue 1 Live Virus Human Challenge (DENV-1-LVHC) model to produce uncomplicated dengue-like illness. Detailed Description ----------------- This is an expansion of a previous study conducted under NCT02372175. In this study up to nine healthy subjects between 18 and 45 years old will be inoculated with Dengue 1 Live Virus Human Challenge (DENV-1-LVHC) at a dose used in the previous study. Subjects will be closely monitored for the first 28 days with continued follow up through 6 months. Clinical and laboratory parameters, viremia and antibody levels will be assess. The goal is to expand the data set of symptoms produced by uncomplicated dengue-like illness. Official Title ----------------- Phase One, Open Label Expansion of a Dengue-1-Virus-Live Virus Human Challenge - (DENV-1-LVHC) Virus Strain. Conditions ----------------- Dengue Intervention / Treatment ----------------- * Biological: Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age 18-45 at the time of consent Ability and willingness to sign informed consent Passing score on comprehension test of at least 75%, with up to 3 attempts Available for the study period Willing to use contraception for the duration of the study Provide consent for release of medical history records from primary care physician, college or university, urgent care or emergency room visit Exclusion Criteria: Female: pregnant or lactating Heavy menstrual bleeding within the last 6 months- menstrual periods lasting longer than 6 days, or requiring 5 or more pads or tampons per day. Female subjects using an intrauterine device (IUD) or Mirena® Female subjects with fibroids or uterine polyps, endometriosis, adenomyosis, and uterine scarring (e.g., after D&C) Blood tests confirming infection with human immunodeficiency virus- 1 (HIV-1), hepatitis C, hepatitis B (assessed by HbsAg) virus, or positive antibodies to the flaviviruses (FV) dengue, West Nile, Yellow Fever, Japanese encephalitis, or Zika. Active Diabetes or active peptic ulcer disease (PUD) Chronic obstructive pulmonary disease (COPD) or coronary artery disease (CAD) Known or suspected congenital or acquired immunodeficiency; or receipt of immunomodulation therapy such as anti-cancer chemotherapy or radiation therapy; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months) Current, or a history of, auto-immune disease History of Guillain-Barré syndrome (GBS) Any history of FV infection or FV vaccination; or planned FV vaccination, outside the study protocol, during the study period Diagnosis with Bipolar Disorder or Schizophrenia, hospitalization in the past year for a mental health disorder, or any other psychiatric condition, which in the opinion of the investigator prevents the subject from participating in the study. Planned travel during the study period (180 days) which would interfere with the ability to complete all study visits Recent (in the past 4 weeks) travel to any dengue endemic area. These potential subjects may be eligible for enrollment a minimum of 4 weeks later Any grade 2 laboratory abnormalities prior to inoculation for the tests specified in Table 18 and Table 19 of the protocol, except those listed in exclusion criteria 16 Subjects with the following grade 1 or greater lab abnormalities: Creatinine; Liver Function Tests - ALT, AST; Hemoglobin (females and males); White Blood Cell (WBC) decrease; Platelets decreased; Prothrombin Time (PT); Partial Thromboplastin Time (PTT); Fibrinogen decrease Significant screening physical examination abnormalities at the discretion of the investigator Women who intend to become pregnant or men who intend to father a child during the study period (approximately 180 days) Hives, shortness of breath, swelling of the lips or throat, or hospitalization related to a previous vaccination or an allergy to specific medications/animals for which antigens may be in the virus preparations to include: shellfish allergy, fetal bovine serum, L-glutamine, neomycin and streptomycin Planning to donate blood in the 1 year following inoculation with dengue Recent blood donation within prior 56 days of inoculation Receipt of blood products or antibodies within 56 days of inoculation or during the study period Participation (active or follow-up phase) or planned participation in another vaccine, drug, medical device, or medical procedure clinical trial in the 4 weeks prior to this trial, during the trial, or 6 months following inoculation in this clinical trial Recent or scheduled receipt of any vaccine 4 weeks prior to or after virus inoculation Beliefs that bar the administration of blood products or transfusions Positive urine screen for cocaine, amphetamines, or opiates Currently taking Methadone or Suboxone Currently taking anti-coagulant medication, aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) Chronic migraine headaches, defined as more than 15 headache days per month over a 3 month period of which more than 8 are migraines, in the absence of medication over use Chronic medical condition that, in the opinion of the investigator, impacts subject safety. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 45 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Other Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Inoculated Group<br>Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC) given as a single dose [0.5 mL of 6.5 x 10^3 plaque forming units/milliliter (PFU/mL)] inoculated subcutaneously. \| Biological: Dengue-1 Virus-Live Virus Human Challenge (DENV-1-LVHC)<br>* Dengue subtype 1 Challenge Virus (DENV-1) strain 45AZ5<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Abnormal Laboratory Parameters \| Total number of all abnormal labs \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Intensity of Abnormal Laboratory Parameters \| Graded according clinical laboratory normals and FDA toxicity scale \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Duration of Abnormal Laboratory Parameters \| Number of days of abnormal lab \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Occurrence of Solicited Injection site symptoms \| Number of solicited symptoms \| 7 days post virus inoculation \| \| Intensity of Solicited Injection site symptoms \| Symptoms graded according to FDA toxicity scale \| 7 days post virus inoculation \| \| Duration of Solicited Injection site symptoms \| Number of days per symptom \| 7 days post virus inoculation \| \| Occurrence of Unsolicited Injection site symptoms \| Number of unsolicited site symptoms \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Intensity of Unsolicited Injection site symptoms \| Symptoms graded according to FDA toxicity scale \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Duration of Unsolicited Injection site symptoms \| Number of days per symptom \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Occurrence of Solicited systemic symptoms \| Number of systemic symptoms \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Intensity of Solicited systemic symptoms \| Symptoms graded according to FDA toxicity scale \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Duration of Solicited systemic symptoms \| Number of days per symptom \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Occurrence of Unsolicited systemic symptoms \| Number of symptoms \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Intensity of Unsolicited systemic symptoms \| Symptoms graded according to FDA toxicity scale \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Duration of Unsolicited systemic symptoms \| Number of days per symptom \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Number of Serious Adverse Events \| Total number \| 28 days post virus inoculation or 7 days post hospitalization, whichever is later \| \| Number of Serious Adverse Events \| Total number \| 6 months post virus inoculation \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Incubation period before onset of fever \| Number of days prior to fever \| Up to 28 days post virus inoculation \| \| Viremia by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) \| Levels of viremia \| Up to 28 days post virus inoculation \| \| Viremia by plaque assay \| Quantitation of infectious virus \| Up to 28 days post virus inoculation \| \| Occurrence of fever without other identifiable cause, such as strep infection or influenza \| The occurrence of fever defined as greater than or equal to 38°C (100.4°F) measured at least 2 times in 24 hours but not lasting more than 72 hours \| Up to 28 days post virus inoculation \| \| Occurrence of Headache \| Number of headaches \| Up to 28 days post virus inoculation \| \| Grade of Headache \| Graded according to FDA toxicity scale \| Up to 28 days post virus inoculation \| \| Occurrence of Myalgia \| Number of reported myalgias \| Up to 28 days post virus inoculation \| \| Grade of Myalgia \| Graded according to FDA toxicity scale \| Up to 28 days post virus inoculation \| \| Occurrence of Rash \| Number of rashes \| Up to 28 days post virus inoculation \| \| Grade of Rash \| Graded according to FDA toxicity scale \| Up to 28 days post virus inoculation \| \| Occurrence of Abnormal Liver Function Test [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] \| Number of abnormal liver function tests \| Up to 28 days post virus inoculation \| \| Grade of Abnormal Liver Function Test [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] \| Graded according clinical laboratory normals and FDA toxicity scale \| Up to 28 days post virus inoculation \| \| Occurrence of Leukopenia \| Number of occurrences \| Up to 28 days post virus inoculation \| \| Grade of Leukopenia \| Graded according clinical laboratory normals and FDA toxicity scale \| Up to 28 days post virus inoculation \| \| Occurrence of Thrombocytopenia \| Number of occurrences \| Up to 28 days post virus inoculation \| \| Grade of Thrombocytopenia \| Graded according clinical laboratory normals and FDA toxicity scale \| Up to 28 days post virus inoculation \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Dengue, Flavivirus Infections, Virus Diseases
NCT03620253	Modafinil's Effects on Cognition in Remitted MDD	Cognitive difficulties such as indecisiveness or inability to concentrate are core symptoms of depression with up to 90% of untreated depressed individuals experiencing these symptoms. As many as half of those who remit from a major depressive episode continue to experience residual cognitive deficits, but these symptoms are frequently overlooked in clinical practice. This leads to persistent cognitive deficits which can cause reduced level of functioning and loss of productivity. As standard antidepressants have an inadequate impact on these residual cognitive symptoms, further treatment options are required. Modafinil is a wakefulness agent with evidence that it improves some domains in cognition such as memory in those whose non-cognitive depressive symptoms have been treated over a short term period. This medication may have favourable lasting effects on cognition, such as the ability to plan and execute tasks in those who receive modafinil for a longer time period. The aim of this study is to investigate whether modafinil can enhance cognition and have additional effects on functioning and work productivity in a sample of participants who were treated for depression but who continue to experience cognitive deficits.	Background:~Major Depressive Disorder (MDD) is a chronic mental disorder with a lifetime prevalence of 5-20% (Kessler et al., 2003; Woo et al., 2016). While depressed mood and loss of interest in activities are core features of MDD, cognitive deficits such as indecisiveness and inattention are present and interfere with work and social functioning (McIntyre et al., 2013). These cognitive deficits frequently persist beyond remission from a Major Depressive Episode (MDE), with up to 94% of those impaired during an episode continuing to experience deficits after the episode (Bhalla et al., 2006), including deficits in attention, executive functioning, and psychomotor speed (Salagre et al., 2017). These residual cognitive symptoms often persist and are associated with poor functioning and loss of productivity (Lam et al., 2014).~In a systematic review examining MDD patients in remission, multiple regression analyses found that MDD predicted lower performance on measures of attention, processing speed, and cognitive flexibility relative to healthy controls (HCs; Hasselbalch et al., 2011). Further evidence for the presence of neuropsychological deficits in remitted MDD patients comes from a systematic review and meta-analysis that found the remitted MDD patient group had executive function and attentional deficits, while symptomatic patients exhibited executive function, attentional, and memory deficits (Roc et al., 2013).~Importantly, there are no medications with evidence to modify cognition in remitted depression. This suggests that in order to assist in the recovery of cognitive and functional abilities, additional novel treatment options are required.~There is considerable evidence that subjective and objective measures of cognition are not well correlated in MDD. This has informed the investigators' choice of separate subjective and objective measures for this study. In addition, cognitive disturbances affect psychosocial function and quality of life across several areas, and this necessitated measurement of quality of life. In this study, the investigators will use a computerized version of the Central Nervous System (CNS) Vital Signs Cognitive Battery, which will provide a Neurocognitive Index score (NCI). The NCI is a global measure of cognitive functioning, averaging the scores from 7 tests over 5 domains: composite memory, psychomotor speed, reaction time, complex attention, and cognitive flexibility.~Pilot results from the The Canadian Biomarker Integration Network in Depression (CAN-BIND)-1 study, involving treatment with escitalopram, have clearly documented the nature of deficits, and are in line with expectations in remitted depression. In this pilot sample of 208 participants, 15% of participants had global cognitive impairment despite 8 weeks of antidepressant treatment and achievement of clinical remission (McInerney, personal communication).~In an 8-week antidepressant study, those who significantly improved in global cognitive functioning (assessed using NCI) had superior functioning and work productivity relative to those who did not significantly improve (Hasselbalch et al., 2011). Vortioxetine is the only antidepressant with modest evidence for improving cognitive parameters during a depressive episode (Rock et al., 2013). Research into the use of psychostimulants as a treatment for cognitive deficits in depressed patients has led to the consideration of modafinil and methylphenidate as potential novel pharmacological treatments (Minzenberg et al., 2008). Modafinil is a well-tolerated wakefulness agent where only two clinical studies have previously examined its role on cognition in depression; one where currently depressed patients had improvements in one measure of executive function after 4 weeks of treatment as an adjuvant (DeBattista et al., 2004), and the other where there were improvements in memory after a single dose in depressed participants who achieved remission (Kaser et al., 2016). Unlike methylphenidate, modafinil appears to impact both hot (emotion-laden) and cold (independent of emotion) cognitive deficits, which are commonly seen in remitted depression.~Immediate effects of modafinil on cognition have been shown (Kaser et al., 2016) and the investigators will be the first to examine the pro-cognitive effects in a remitted depressed sample over 8 weeks. The dose of modafinil (200mg) used in the study, sample size, and randomized control trial (RCT) study design parallels those described in the immediate effect study, and this maintains continuity. However, the study does not examine whether the immediate effects are maintained. More importantly, it is unclear whether the cognitive improvements translate into improvement in functioning.~The added focus on functional outcomes fits with patient-centered models of healthcare, as functional outcomes are of greatest importance to most patients. Thus, the RCT study and choice of outcome variables have been carefully designed with specific endpoints to delineate these aspects. Cognitive flexibility, memory, and attention will be domains of importance in this study, since these domains have been shown in previous literature to be improved by modafinil (Minzenberg et al., 2008; DeBattista et al., 2004; Kaser et al., 2016).~Objectives, Hypotheses, and Impact:~The primary objective of this study is to delineate the cognitive effects of modafinil in patients with remitted depression at baseline and 4 weeks, and monitor whether these effects are maintained with continual dosage over an 8-week period. The secondary objective of this study is to understand the effect of modafinil in patients with remitted depression on measures of functioning at baseline, 4 weeks, and 8 weeks, and whether these effects parallel the cognitive changes.~The investigators' overarching hypothesis is that specific aspects of cognitive functioning, including the domains of memory, attention, and cognitive flexibility, will improve through treatment with modafinil. The investigators hypothesize that participants with remitted depression who continue to experience cognitive deficits and are taking modafinil will have improvements in aspects of cognitive domains at 4 weeks, and these improvements will be sustained at 8 weeks. It is also hypothesized that functional improvements will parallel the improvements in cognitive domains.~The study ensures a closer examination of modafinil's effect on individual facets of cognition in patients with remitted MDD. This enhanced understanding will enable the development of new treatment plans for residual cognitive symptoms, where none currently exist. Moreover, it could spur interest in new drug development programs to address an unmet need of targeting cognition across disorders where depression is a central feature (e.g. Bipolar Disorder, Generalized Anxiety Disorder). Finally, the study would delineate the specific endophenotypes within cognition (e.g. working memory) and functional improvement (e.g. social functioning), which would lead to personalized treatment options based on the endophenotype profile.~Methods In this randomized control trial, remitted MDD patients with residual cognitive deficits (n=50) will have cognitive symptoms and functioning evaluated before and after an 8-week trial of modafinil 200mg or placebo. Participants will be recruited through the ongoing CAN-BIND 1 Wellness Study; the Depression Program at St. Michael's Hospital; the shared care network at St. Michael's Hospital; and referrals from residents, family doctors, and other St. Michael's psychiatrists. All participants who meet inclusion criteria will be asked to enrol in this study and provide written informed consent.~Participants will be on a stable dose of an antidepressant for at least 6 months prior to enrolment. They will be required to remain on this stable dose for the duration (8 weeks) of the trial. They will be prescribed modafinil or placebo at a dose of 100 mg for the first week then 200mg for 7 weeks. After week 8, participants will be informed of which group they were in and if they were taking modafinil, they can choose to continue on modafinil or to discontinue.~Participants will undergo an 8-week randomized, placebo controlled treatment trial of modafinil 200mg with a total of 3 study visits. Participants may require more clinical visits as needed. Screening will be done to confirm study eligibility. At the screening visit all participants will provide demographic data (age, gender, education, ethnicity, occupation, family history of mental illness), undergo a structured diagnostic assessment (Mini-International Neuropsychiatric Interview), complete the CNS Vital Signs cognitive battery, and have the Montgomery-Asberg Depression Rating Scale administered. At the baseline visit, participants will initiate the study drug trial, complete clinician rated and self-report scales, and complete the cognitive battery in CNS Vital Signs. Participants will start with a 100 mg dose at baseline, and increase to the 200 mg dose at week 1 if the drug is well tolerated. Participants will repeat all measures at week 4 and 8. Adverse events will be recorded at each study visit. For participants who wish to discontinue the study drug at week 8, they will first have their dose decreased to 100 mg for one week and attend an additional week 9 safety visit to evaluate adverse events before full discontinuation of the study drug.	Does Modafinil Have Pro-cognitive Effects in Those With Residual Cognitive Impairment Despite Remitted Depression?	Major Depressive Disorder, Cognitive Impairment	* Drug: Modafinil * Drug: Placebo	Inclusion Criteria:~Diagnostic and Statistical Manual (DSM)-5 criteria for past Major Depressive Episode within MDD, confirmed through Mini-International Neuropsychiatric Interview (MINI) diagnosis~Age between 18 and 55 years~Montgomery-Åsberg Depression Rating Scale < 7 (in remission)~Ability to read and understand English~Participant has been treated with an antidepressant for ≥ 6 months prior to enrolment~Participant agrees to remain on a stable antidepressant regimen for the duration of the trial (8 weeks)~Participant is currently experiencing cognitive deficits, as confirmed by an NCI >1 standard deviation below the mean on CNS Vital Signs cognitive battery~Women of child bearing potential must agree to use birth control for the duration of the study and 1 month following discontinuation of the study drug~Exclusion Criteria:~Pregnancy/lactation~Lifetime history of Bipolar I, II or psychosis; other comorbidities (e.g. Generalized Anxiety, Panic Disorder) may be allowed by clinician judgement~Subject has current clinical diagnosis of autism, dementia, intellectual disability, or mild cognitive impairment~Meets DSM-5 criteria for active Post-Traumatic Stress Disorder, confirmed through MINI diagnosis~Subject meets criteria for current personality disorder~Concomitant use of monoamine oxidase inhibitors and/or other psychotropic drugs including lithium, clomipramine, and triazolam~Recent (< 6 months) stimulant use, such as medications used for attention deficit hyperactivity disorder~Subject is taking antipsychotics~Subject is taking herbaceuticals (i.e. natural products that have psychoactive properties, such as St. John's wort)~Concomitant use of medications that may interact with modafinil, including warfarin and cyclosporine~Medical condition requiring immediate investigation or treatment~Recent (< 6 months)/current history of drug abuse/dependence (other than caffeine or nicotine)~Previous intolerance or failure to respond to an adequate trial of modafinil~Any past history of head injury or concussion, as confirmed by the Ohio State University Traumatic brain injury (TBI) Identification Short Form~Current suicidal ideation (MADRS Item 10 ≤2 or by clinician judgement)~History of coronary artery disease, recent (<1 year) myocardial infarction, or unstable angina~History of left ventricular hypertrophy, ischemic ECG changes, chest pain, arrhythmia, or clinically significant manifestations of mitral valve prolapse in association with use of CNS stimulants~Involvement in another treatment study during the time of the study	18 Years	55 Years	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: 50 Participants (aged 18-55) who are experiencing cognitive deficits (measured as Neurocognitive Index >1 standard deviation below the mean) despite remission from depression (Montgomery-Asberg Rating Scale for Depression (MADRAS) score <7) will be eligible to receive modafinil (100-200mg daily) or two identical placebo capsules each morning for a period of 8 weeks. Masking: Quadruple	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Cognition \| Cognition will be measured using a Neurocognitive Index, which will be calculated using the CNS Vital Signs Neurocognitive Battery (a computer program). The domains tested within the cognitive battery include composite memory, psychomotor speed, reaction time, complex attention, cognitive flexibility, and processing speed. The Neurocognitive Index is based on a composite, average score of the scores on these 6 domains. From the Neurocognitive Index score, the CNS Vital Signs program classifies the participant as above, average, low average, low, or very low based on their deviation from a standard score of 85. \| 8 weeks \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Composite Memory \| This is a measure of how well participants can recognize, remember, and retrieve words and images. Composite memory will be measured based on performance on a series of tests in the CNS Vital Signs Neurocognitive Battery (a computer program). Based on performance, the CNS Vital Signs program classifies the participant as above, average, low average, low, or very low based on their deviation from a standard score of 103. \| 8 weeks \| \| Psychomotor Speed \| This is a measure of how well a participant is able to perceive, attend, and respond to complex visual-perceptual information and perform simple, fine motor coordination. Psychomotor speed will be measured based on performance on a series of tests in the CNS Vital Signs Neurocognitive Battery (a computer program). Based on performance, the CNS Vital Signs program classifies the participant as above, average, low average, low, or very low based on their deviation from a standard score of 93. \| 8 weeks \| \| Reaction Time \| This is a measure of how quickly a participant can react to simple and complex direction sets. Reaction time will be measured based on performance on a series of tests in the CNS Vital Signs Neurocognitive Battery (a computer program). Based on performance, the CNS Vital Signs program classifies the participant as above, average, low average, low, or very low based on their deviation from a standard score of 107. \| 8 weeks \| \| Complex Attention \| This is a measure of a participant's ability to track and respond to multiple stimuli over long periods of time, and perform complex mental tasks quickly and accurately. Complex attention will be measured based on performance on a series of tests in the CNS Vital Signs Neurocognitive Battery (a computer program). Based on performance, the CNS Vital Signs program classifies the participant as above, average, low average, low, or very low based on their deviation from a standard score of 56. \| 8 weeks \| \| Cognitive Flexibility \| This is a measure of how well a participant can adapt to rapidly changing and complex directions, and manipulate information. Cognitive flexibility will be measured based on performance on a series of tests in the CNS Vital Signs Neurocognitive Battery (a computer program). Based on performance, the CNS Vital Signs program classifies the participant as above, average, low average, low, or very low based on their deviation from a standard score of 63. \| 8 weeks \| \| Processing Speed \| This is a measure of a participant's ability to recognize and process information. Processing speed will be measured based on performance on a series of tests in the CNS Vital Signs Neurocognitive Battery (a computer program). Based on performance, the CNS Vital Signs program classifies the participant as above, average, low average, low, or very low based on their deviation from a standard score of 79. \| 8 weeks \| \| Subjective Cognitive Improvement \| This is a measure of how well the participant feels their cognition has improved after using the study drug. This will be measured using the British Columbia Cognitive Complaints Inventory, a 6-item screening tool that assesses perceived cognitive difficulties in patients with MDD over the past 7 days. A total score between 0 and 18 is calculated based on participant self-report, where a higher score represents greater cognitive impairment. \| 8 weeks \| \| Functional Disability \| This will be assessed using the Sheehan Disability Scale, which assesses functional impairment in work/school, social life, and family life. This is scored based on a self-report scale of 0-10 in 3 domains: work/school, social life, and family life/home responsibilities. A total score between 0 and 30 is calculated based on the sum of these 3 domains. Higher values represent greater disability. \| 8 weeks \| \| Work Productivity \| This will be assessed using the Lam Employment and Productivity Scale, a brief questionnaire designed to assess occupational productivity.This is scored based on a self-report scale from 0-4 in 7 domains: low energy or motivation, poor concentration or memory, anxiety or irritability, getting less work done, doing poor quality work, making more mistakes, and having trouble getting along with people or avoiding them. A total score between 0 and 28 is calculated as a sum of all sub scores. Higher values represent greater impairment. \| 8 weeks \| \| Motivation and Energy \| This is be assessed using the Motivation and Energy Inventory, an 18-item inventory to measure changes in lassitude and energy with antidepressant treatment. Based on self-report measurements, a total score between 0-108 is determined, where a lower score corresponds to lower levels of motivation and energy. \| 8 weeks \|	modafinil, remitted depression, cognition	Modafinil, Central Nervous System Stimulants, Physiological Effects of Drugs, Wakefulness-Promoting Agents, Cytochrome P-450 CYP3A Inducers, Cytochrome P-450 Enzyme Inducers, Molecular Mechanisms of Pharmacological Action	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Modafinil<br>Participants will be administered 100 mg modafinil tablets, that will be over-encapsulated, for one week. If the drug is well tolerated, the dosage will be increased to 200 mg for the remaining 7 weeks of the study. Capsules are taken daily in the morning. \| Drug: Modafinil<br>* Participants randomized to the modafinil group will receive 100 mg of modafinil capsules for 1 week, followed by 200 mg for 7 weeks (as long as the drug is well tolerated), which they will take daily in the morning. During this time, participants will complete questionnaires and neurocognitive tests, and report adverse events at study visits.<br>* Other names: 2-benzhydrylsulfinylacetamide;\| \| Placebo Comparator: Placebo<br>Participants will be administered 100 mg placebo capsule. This capsule will have all the same ingredients as the modafinil tablets, minus the active ingredient. After 1 week, participants' dosage will be increased to 200 mg for the remaining 7 weeks of the study. Capsules are taken daily in the morning. \| Drug: Placebo<br>* Participants randomized to the placebo group will receive 100 mg placebo capsules for 1 week, followed by 200 mg for 7 weeks, which they will take daily in the morning. During this time, participants will complete questionnaires and neurocognitive tests, and report adverse events at study visits.<br>\|	Modafinil's Effects on Cognition in Remitted MDD Study Overview ================= Brief Summary ----------------- Cognitive difficulties such as indecisiveness or inability to concentrate are core symptoms of depression with up to 90% of untreated depressed individuals experiencing these symptoms. As many as half of those who remit from a major depressive episode continue to experience residual cognitive deficits, but these symptoms are frequently overlooked in clinical practice. This leads to persistent cognitive deficits which can cause reduced level of functioning and loss of productivity. As standard antidepressants have an inadequate impact on these residual cognitive symptoms, further treatment options are required. Modafinil is a wakefulness agent with evidence that it improves some domains in cognition such as memory in those whose non-cognitive depressive symptoms have been treated over a short term period. This medication may have favourable lasting effects on cognition, such as the ability to plan and execute tasks in those who receive modafinil for a longer time period. The aim of this study is to investigate whether modafinil can enhance cognition and have additional effects on functioning and work productivity in a sample of participants who were treated for depression but who continue to experience cognitive deficits. Detailed Description ----------------- Background: Major Depressive Disorder (MDD) is a chronic mental disorder with a lifetime prevalence of 5-20% (Kessler et al., 2003; Woo et al., 2016). While depressed mood and loss of interest in activities are core features of MDD, cognitive deficits such as indecisiveness and inattention are present and interfere with work and social functioning (McIntyre et al., 2013). These cognitive deficits frequently persist beyond remission from a Major Depressive Episode (MDE), with up to 94% of those impaired during an episode continuing to experience deficits after the episode (Bhalla et al., 2006), including deficits in attention, executive functioning, and psychomotor speed (Salagre et al., 2017). These residual cognitive symptoms often persist and are associated with poor functioning and loss of productivity (Lam et al., 2014). In a systematic review examining MDD patients in remission, multiple regression analyses found that MDD predicted lower performance on measures of attention, processing speed, and cognitive flexibility relative to healthy controls (HCs; Hasselbalch et al., 2011). Further evidence for the presence of neuropsychological deficits in remitted MDD patients comes from a systematic review and meta-analysis that found the remitted MDD patient group had executive function and attentional deficits, while symptomatic patients exhibited executive function, attentional, and memory deficits (Roc et al., 2013). Importantly, there are no medications with evidence to modify cognition in remitted depression. This suggests that in order to assist in the recovery of cognitive and functional abilities, additional novel treatment options are required. There is considerable evidence that subjective and objective measures of cognition are not well correlated in MDD. This has informed the investigators' choice of separate subjective and objective measures for this study. In addition, cognitive disturbances affect psychosocial function and quality of life across several areas, and this necessitated measurement of quality of life. In this study, the investigators will use a computerized version of the Central Nervous System (CNS) Vital Signs Cognitive Battery, which will provide a Neurocognitive Index score (NCI). The NCI is a global measure of cognitive functioning, averaging the scores from 7 tests over 5 domains: composite memory, psychomotor speed, reaction time, complex attention, and cognitive flexibility. Pilot results from the The Canadian Biomarker Integration Network in Depression (CAN-BIND)-1 study, involving treatment with escitalopram, have clearly documented the nature of deficits, and are in line with expectations in remitted depression. In this pilot sample of 208 participants, 15% of participants had global cognitive impairment despite 8 weeks of antidepressant treatment and achievement of clinical remission (McInerney, personal communication). In an 8-week antidepressant study, those who significantly improved in global cognitive functioning (assessed using NCI) had superior functioning and work productivity relative to those who did not significantly improve (Hasselbalch et al., 2011). Vortioxetine is the only antidepressant with modest evidence for improving cognitive parameters during a depressive episode (Rock et al., 2013). Research into the use of psychostimulants as a treatment for cognitive deficits in depressed patients has led to the consideration of modafinil and methylphenidate as potential novel pharmacological treatments (Minzenberg et al., 2008). Modafinil is a well-tolerated wakefulness agent where only two clinical studies have previously examined its role on cognition in depression; one where currently depressed patients had improvements in one measure of executive function after 4 weeks of treatment as an adjuvant (DeBattista et al., 2004), and the other where there were improvements in memory after a single dose in depressed participants who achieved remission (Kaser et al., 2016). Unlike methylphenidate, modafinil appears to impact both hot (emotion-laden) and cold (independent of emotion) cognitive deficits, which are commonly seen in remitted depression. Immediate effects of modafinil on cognition have been shown (Kaser et al., 2016) and the investigators will be the first to examine the pro-cognitive effects in a remitted depressed sample over 8 weeks. The dose of modafinil (200mg) used in the study, sample size, and randomized control trial (RCT) study design parallels those described in the immediate effect study, and this maintains continuity. However, the study does not examine whether the immediate effects are maintained. More importantly, it is unclear whether the cognitive improvements translate into improvement in functioning. The added focus on functional outcomes fits with patient-centered models of healthcare, as functional outcomes are of greatest importance to most patients. Thus, the RCT study and choice of outcome variables have been carefully designed with specific endpoints to delineate these aspects. Cognitive flexibility, memory, and attention will be domains of importance in this study, since these domains have been shown in previous literature to be improved by modafinil (Minzenberg et al., 2008; DeBattista et al., 2004; Kaser et al., 2016). Objectives, Hypotheses, and Impact: The primary objective of this study is to delineate the cognitive effects of modafinil in patients with remitted depression at baseline and 4 weeks, and monitor whether these effects are maintained with continual dosage over an 8-week period. The secondary objective of this study is to understand the effect of modafinil in patients with remitted depression on measures of functioning at baseline, 4 weeks, and 8 weeks, and whether these effects parallel the cognitive changes. The investigators' overarching hypothesis is that specific aspects of cognitive functioning, including the domains of memory, attention, and cognitive flexibility, will improve through treatment with modafinil. The investigators hypothesize that participants with remitted depression who continue to experience cognitive deficits and are taking modafinil will have improvements in aspects of cognitive domains at 4 weeks, and these improvements will be sustained at 8 weeks. It is also hypothesized that functional improvements will parallel the improvements in cognitive domains. The study ensures a closer examination of modafinil's effect on individual facets of cognition in patients with remitted MDD. This enhanced understanding will enable the development of new treatment plans for residual cognitive symptoms, where none currently exist. Moreover, it could spur interest in new drug development programs to address an unmet need of targeting cognition across disorders where depression is a central feature (e.g. Bipolar Disorder, Generalized Anxiety Disorder). Finally, the study would delineate the specific endophenotypes within cognition (e.g. working memory) and functional improvement (e.g. social functioning), which would lead to personalized treatment options based on the endophenotype profile. Methods In this randomized control trial, remitted MDD patients with residual cognitive deficits (n=50) will have cognitive symptoms and functioning evaluated before and after an 8-week trial of modafinil 200mg or placebo. Participants will be recruited through the ongoing CAN-BIND 1 Wellness Study; the Depression Program at St. Michael's Hospital; the shared care network at St. Michael's Hospital; and referrals from residents, family doctors, and other St. Michael's psychiatrists. All participants who meet inclusion criteria will be asked to enrol in this study and provide written informed consent. Participants will be on a stable dose of an antidepressant for at least 6 months prior to enrolment. They will be required to remain on this stable dose for the duration (8 weeks) of the trial. They will be prescribed modafinil or placebo at a dose of 100 mg for the first week then 200mg for 7 weeks. After week 8, participants will be informed of which group they were in and if they were taking modafinil, they can choose to continue on modafinil or to discontinue. Participants will undergo an 8-week randomized, placebo controlled treatment trial of modafinil 200mg with a total of 3 study visits. Participants may require more clinical visits as needed. Screening will be done to confirm study eligibility. At the screening visit all participants will provide demographic data (age, gender, education, ethnicity, occupation, family history of mental illness), undergo a structured diagnostic assessment (Mini-International Neuropsychiatric Interview), complete the CNS Vital Signs cognitive battery, and have the Montgomery-Asberg Depression Rating Scale administered. At the baseline visit, participants will initiate the study drug trial, complete clinician rated and self-report scales, and complete the cognitive battery in CNS Vital Signs. Participants will start with a 100 mg dose at baseline, and increase to the 200 mg dose at week 1 if the drug is well tolerated. Participants will repeat all measures at week 4 and 8. Adverse events will be recorded at each study visit. For participants who wish to discontinue the study drug at week 8, they will first have their dose decreased to 100 mg for one week and attend an additional week 9 safety visit to evaluate adverse events before full discontinuation of the study drug. Official Title ----------------- Does Modafinil Have Pro-cognitive Effects in Those With Residual Cognitive Impairment Despite Remitted Depression? Conditions ----------------- Major Depressive Disorder, Cognitive Impairment Intervention / Treatment ----------------- * Drug: Modafinil * Drug: Placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Diagnostic and Statistical Manual (DSM)-5 criteria for past Major Depressive Episode within MDD, confirmed through Mini-International Neuropsychiatric Interview (MINI) diagnosis Age between 18 and 55 years Montgomery-Åsberg Depression Rating Scale < 7 (in remission) Ability to read and understand English Participant has been treated with an antidepressant for ≥ 6 months prior to enrolment Participant agrees to remain on a stable antidepressant regimen for the duration of the trial (8 weeks) Participant is currently experiencing cognitive deficits, as confirmed by an NCI >1 standard deviation below the mean on CNS Vital Signs cognitive battery Women of child bearing potential must agree to use birth control for the duration of the study and 1 month following discontinuation of the study drug Exclusion Criteria: Pregnancy/lactation Lifetime history of Bipolar I, II or psychosis; other comorbidities (e.g. Generalized Anxiety, Panic Disorder) may be allowed by clinician judgement Subject has current clinical diagnosis of autism, dementia, intellectual disability, or mild cognitive impairment Meets DSM-5 criteria for active Post-Traumatic Stress Disorder, confirmed through MINI diagnosis Subject meets criteria for current personality disorder Concomitant use of monoamine oxidase inhibitors and/or other psychotropic drugs including lithium, clomipramine, and triazolam Recent (< 6 months) stimulant use, such as medications used for attention deficit hyperactivity disorder Subject is taking antipsychotics Subject is taking herbaceuticals (i.e. natural products that have psychoactive properties, such as St. John's wort) Concomitant use of medications that may interact with modafinil, including warfarin and cyclosporine Medical condition requiring immediate investigation or treatment Recent (< 6 months)/current history of drug abuse/dependence (other than caffeine or nicotine) Previous intolerance or failure to respond to an adequate trial of modafinil Any past history of head injury or concussion, as confirmed by the Ohio State University Traumatic brain injury (TBI) Identification Short Form Current suicidal ideation (MADRS Item 10 ≤2 or by clinician judgement) History of coronary artery disease, recent (<1 year) myocardial infarction, or unstable angina History of left ventricular hypertrophy, ischemic ECG changes, chest pain, arrhythmia, or clinically significant manifestations of mitral valve prolapse in association with use of CNS stimulants Involvement in another treatment study during the time of the study Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 55 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: 50 Participants (aged 18-55) who are experiencing cognitive deficits (measured as Neurocognitive Index >1 standard deviation below the mean) despite remission from depression (Montgomery-Asberg Rating Scale for Depression (MADRAS) score <7) will be eligible to receive modafinil (100-200mg daily) or two identical placebo capsules each morning for a period of 8 weeks. Masking: Quadruple Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Modafinil<br>Participants will be administered 100 mg modafinil tablets, that will be over-encapsulated, for one week. If the drug is well tolerated, the dosage will be increased to 200 mg for the remaining 7 weeks of the study. Capsules are taken daily in the morning. \| Drug: Modafinil<br>* Participants randomized to the modafinil group will receive 100 mg of modafinil capsules for 1 week, followed by 200 mg for 7 weeks (as long as the drug is well tolerated), which they will take daily in the morning. During this time, participants will complete questionnaires and neurocognitive tests, and report adverse events at study visits.<br>* Other names: 2-benzhydrylsulfinylacetamide;\| \| Placebo Comparator: Placebo<br>Participants will be administered 100 mg placebo capsule. This capsule will have all the same ingredients as the modafinil tablets, minus the active ingredient. After 1 week, participants' dosage will be increased to 200 mg for the remaining 7 weeks of the study. Capsules are taken daily in the morning. \| Drug: Placebo<br>* Participants randomized to the placebo group will receive 100 mg placebo capsules for 1 week, followed by 200 mg for 7 weeks, which they will take daily in the morning. During this time, participants will complete questionnaires and neurocognitive tests, and report adverse events at study visits.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Cognition \| Cognition will be measured using a Neurocognitive Index, which will be calculated using the CNS Vital Signs Neurocognitive Battery (a computer program). The domains tested within the cognitive battery include composite memory, psychomotor speed, reaction time, complex attention, cognitive flexibility, and processing speed. The Neurocognitive Index is based on a composite, average score of the scores on these 6 domains. From the Neurocognitive Index score, the CNS Vital Signs program classifies the participant as above, average, low average, low, or very low based on their deviation from a standard score of 85. \| 8 weeks \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Composite Memory \| This is a measure of how well participants can recognize, remember, and retrieve words and images. Composite memory will be measured based on performance on a series of tests in the CNS Vital Signs Neurocognitive Battery (a computer program). Based on performance, the CNS Vital Signs program classifies the participant as above, average, low average, low, or very low based on their deviation from a standard score of 103. \| 8 weeks \| \| Psychomotor Speed \| This is a measure of how well a participant is able to perceive, attend, and respond to complex visual-perceptual information and perform simple, fine motor coordination. Psychomotor speed will be measured based on performance on a series of tests in the CNS Vital Signs Neurocognitive Battery (a computer program). Based on performance, the CNS Vital Signs program classifies the participant as above, average, low average, low, or very low based on their deviation from a standard score of 93. \| 8 weeks \| \| Reaction Time \| This is a measure of how quickly a participant can react to simple and complex direction sets. Reaction time will be measured based on performance on a series of tests in the CNS Vital Signs Neurocognitive Battery (a computer program). Based on performance, the CNS Vital Signs program classifies the participant as above, average, low average, low, or very low based on their deviation from a standard score of 107. \| 8 weeks \| \| Complex Attention \| This is a measure of a participant's ability to track and respond to multiple stimuli over long periods of time, and perform complex mental tasks quickly and accurately. Complex attention will be measured based on performance on a series of tests in the CNS Vital Signs Neurocognitive Battery (a computer program). Based on performance, the CNS Vital Signs program classifies the participant as above, average, low average, low, or very low based on their deviation from a standard score of 56. \| 8 weeks \| \| Cognitive Flexibility \| This is a measure of how well a participant can adapt to rapidly changing and complex directions, and manipulate information. Cognitive flexibility will be measured based on performance on a series of tests in the CNS Vital Signs Neurocognitive Battery (a computer program). Based on performance, the CNS Vital Signs program classifies the participant as above, average, low average, low, or very low based on their deviation from a standard score of 63. \| 8 weeks \| \| Processing Speed \| This is a measure of a participant's ability to recognize and process information. Processing speed will be measured based on performance on a series of tests in the CNS Vital Signs Neurocognitive Battery (a computer program). Based on performance, the CNS Vital Signs program classifies the participant as above, average, low average, low, or very low based on their deviation from a standard score of 79. \| 8 weeks \| \| Subjective Cognitive Improvement \| This is a measure of how well the participant feels their cognition has improved after using the study drug. This will be measured using the British Columbia Cognitive Complaints Inventory, a 6-item screening tool that assesses perceived cognitive difficulties in patients with MDD over the past 7 days. A total score between 0 and 18 is calculated based on participant self-report, where a higher score represents greater cognitive impairment. \| 8 weeks \| \| Functional Disability \| This will be assessed using the Sheehan Disability Scale, which assesses functional impairment in work/school, social life, and family life. This is scored based on a self-report scale of 0-10 in 3 domains: work/school, social life, and family life/home responsibilities. A total score between 0 and 30 is calculated based on the sum of these 3 domains. Higher values represent greater disability. \| 8 weeks \| \| Work Productivity \| This will be assessed using the Lam Employment and Productivity Scale, a brief questionnaire designed to assess occupational productivity.This is scored based on a self-report scale from 0-4 in 7 domains: low energy or motivation, poor concentration or memory, anxiety or irritability, getting less work done, doing poor quality work, making more mistakes, and having trouble getting along with people or avoiding them. A total score between 0 and 28 is calculated as a sum of all sub scores. Higher values represent greater impairment. \| 8 weeks \| \| Motivation and Energy \| This is be assessed using the Motivation and Energy Inventory, an 18-item inventory to measure changes in lassitude and energy with antidepressant treatment. Based on self-report measurements, a total score between 0-108 is determined, where a lower score corresponds to lower levels of motivation and energy. \| 8 weeks \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- modafinil, remitted depression, cognition
NCT02850627	The Effect of Tongguan Capsule for MicroRNA Profiles in Coronary Heart Disease Patients	The purpose of this study is to test the expression of microRNAs related to the syndromes after the intervention of Tongguan capsule,preliminarily to investigate the mechanism of the effects of Tongguan capsule, and provide the biological foundation of curative effect of Tongguan capsule.	The primary end points is the core of the whole experiment scheme. miRNAs regulate gene expression posttranscriptionally by degrading messenger RNA (mRNA) targets and by blocking their translation Secondary endpoints will include The adverse cardiac clinical events (MACE) in terms of cardiac death,periprocedural myocardial infarction (MI),spontaneous MI and target vessel revascularization(TVR). Related parameters of qi and blood are the material basis of blood conversion and objective performance is used to evaluate the effect on Tongguan capsule on patients with blood stagnation, which can be either interpretation theory of qi deficiency and blood stagnation and mutual transformation between qi and blood can find targets through Tongguan capsule on blood . Routine laboratory tests are used for screening patients basic situation and ensure the safety of the experiment The traditional Chinese medicine syndrome scale Including the the score of deficiency of qi and score of blood stasis syndrome mainly used to identify patients with the traditional Chinese medicine syndrome type Approximately 100 patients in Coronary Heart Disease Patients with Blood Stasis Syndrome undergoing percutaneous coronary intervention will be enrolled and randomized to divided into Qi -stagnation and blood stasis, Qi- deficiency and blood stasis, after the PCI surgery, Qi deficiency and blood stasis group were randomly divided into Tongguan capsule group and the control group, and qi stagnation and blood stasis group, too ,giving patients through Tongguan capsule 3 pills three times a day(1.5g/day), once every three months follow-up, after have been followed up to six months	The Effect of Tongguan Capsule for MicroRNA Profiles Between Qi-Stagnation and Qi-Deficiency in Coronary Heart Disease Patients With Blood Stasis Syndrome Undergoing Percutaneous Coronary Intervention	Coronary Heart Disease, Acute Myocardial Infarction	* Drug: Tongguan capsule * Drug: placebo capsule	Inclusion Criteria:~In line with the diagnostic criteria for acute coronary syndrome (ACS), coronary angiography confirmed for coronary heart disease (CHD), parallel Percutaneous transluminal coronary angioplasty( PTCA) and/or coronary stent implantation was successful~Postoperative routine drug treatment~Traditional Chinese Medicine syndrome differentiation of qi -deficiency and qi -stagnation blood stasis or blood stasis license~Aged 35 to 75 years old~Must sign a consent form.~Exclusion Criteria:~Renal insufficiency, the male serum creatinine > 2.5 mg/dl (> 220 umo/l), women > 2.0 mg/dl (> 175 umo/l)~With obvious liver disease or Alanine aminotransferase ( ALT)， Aspartate aminotransferase ( AST), 3 times higher than normal ceiling~Serious cardiac insufficiency (EF < 35%)~Uncontrolled patients with high blood pressure~Merger or severe valvular heart disease in acute cerebrovascular disease~Random blood glucose or greater tendency for 13.7 / L diabetes or glycosylated hemoglobin 9.5% or more~Patients with severe mental illness~Patients with malignant tumor or life expectancy in less than three years~Patients with severe hematopoietic system disease~Refused to sign a consent form, or estimated compliance is poorer, follow-up possibilities claim;~Pregnancy or ready to pregnant women, nursing mothers;~Participated in nearly three months, or is in other clinical subjects . -	35 Years	75 Years	All	No	Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| miRNAs spectrum \| Test the expression of microRNAs related to the syndromes after the intervention of Tongguan capsule,preliminarily to investigate the mechanism of the effects of Tongguan capsule, and provide the biological foundation of curative effect of Tongguan capsule. \| six months \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| major adverse cardiac event \| frequency of the reported cardiovascular events (defined as cardiogenic death, stroke, recurrent myocardial infarction, readmission on account of deterioration of congestive heart failure or unstable angina, target vessel revascularization) \| six months \| \| Renin predicts cardiovascular homeostasis and ventricular remodeling \| renin（ng/ml） predicts cardiovascular homeostasis and blood pressure maintenance and plays an important role in ventricular remodeling \| 6 months \| \| Ang II predicts cardiovascular homeostasis and ventricular remodeling \| Ang II（pg/ml） predicts cardiovascular homeostasis and blood pressure maintenance and plays an important role in ventricular remodeling \| 6 months \| \| Serum E \| Acute coronary syndrome is caused by atherosclerotic plaque instability and rupture. The stability of plaque is closely related to inflammation.Serum E (pmol / L) is an important pathway of various immune and inflammatory regulation, which promotes the development of atherosclerosis and is a risk factor for atherosclerosis. \| 6 months \| \| Inflammatory mediators \| Tumor Necrosis factor alpha (ng/L)and Interleukin-6，IL-6 (ng/L) measure of the general situation of patients \| 6 months \| \| Brain Natriuretic Peptide \| B-type natriuretic peptide（pg/ml） is a neurohormone synthesized in the cardiac ventricles upon ventricular pressure overload and ventricular dilatation \| 6 months \| \| Echocardiography measure of left ventricular systolic function \| Evaluation of left ventricular systolic function by left ventricular ejection fraction( LVEF) (%) \| 6 months \| \| Echocardiography measure of left ventricular diastolic function \| Left ventricular end diastolic diameter (LVEDD) (mm )measure of left ventricular diastolic function in patients \| 6 months \| \| New York Heart Association functional classification \| I Cardiac disease, but no symptoms and no limitation in ordinary physical activity, e.g. no shortness of breath when walking, climbing stairs etc. II Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. III Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m).Comfortable only at rest. IV Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients. \| 6 months \| \| Coronary angiography \| Quantitative coronary angiography in the stenosis degree, 25%, 50%, 75%, 90%, 99%, 100%, 1, 2, 4, 6, 8,, 16, 32, and, respectively.~Scoring multiplication will segment coefficients corresponding to the degree of stenosis and the stenosis of total score that is the sum of Gensini score of coronary artery stenosis in the patients. \| 6 months \| \| Seattle Angina Questionnaire score \| The Seattle Angina Questionnaire is a valid and reliable instrument that measures five clinically important dimensions of health in patients with coronary artery disease (physical limitation, anginal stability, anginal frequency, treatment satisfaction, and disease perception). (in Units on a Scale). \| 6 months \| \| The traditional Chinese medicine syndrome scale \| The traditional Chinese medicine syndrome scale Including the the score of deficiency of qi and score of blood stasis syndrome mainly used to identify patients with traditional Chinese medicine syndrome type \| 6 months \|	acute coronary syndrome, Tongguan capsule, miRNAs	Heart Diseases, Myocardial Infarction, Coronary Disease, Coronary Artery Disease, Myocardial Ischemia, Infarction, Ischemia, Pathologic Processes, Necrosis, Cardiovascular Diseases, Vascular Diseases, Arteriosclerosis, Arterial Occlusive Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Tongguan capsule<br>Tongguan capsule (0.5 g tid. for 6 months) \| Drug: Tongguan capsule<br>* eligible participants were randomized to receive Tongguan capsule ( 1.5 g/day for six months immediately after PCI)<br>\| \| Placebo Comparator: placebo capsule<br>same volume/day of placebo capsule (0.5 g tid. for 6 months) \| Drug: placebo capsule<br>* eligible participants were randomized to receive placebo capsule ( 1.5 g/day for six months immediately after PCI)<br>\|	The Effect of Tongguan Capsule for MicroRNA Profiles in Coronary Heart Disease Patients Study Overview ================= Brief Summary ----------------- The purpose of this study is to test the expression of microRNAs related to the syndromes after the intervention of Tongguan capsule,preliminarily to investigate the mechanism of the effects of Tongguan capsule, and provide the biological foundation of curative effect of Tongguan capsule. Detailed Description ----------------- The primary end points is the core of the whole experiment scheme. miRNAs regulate gene expression posttranscriptionally by degrading messenger RNA (mRNA) targets and by blocking their translation Secondary endpoints will include The adverse cardiac clinical events (MACE) in terms of cardiac death,periprocedural myocardial infarction (MI),spontaneous MI and target vessel revascularization(TVR). Related parameters of qi and blood are the material basis of blood conversion and objective performance is used to evaluate the effect on Tongguan capsule on patients with blood stagnation, which can be either interpretation theory of qi deficiency and blood stagnation and mutual transformation between qi and blood can find targets through Tongguan capsule on blood . Routine laboratory tests are used for screening patients basic situation and ensure the safety of the experiment The traditional Chinese medicine syndrome scale Including the the score of deficiency of qi and score of blood stasis syndrome mainly used to identify patients with the traditional Chinese medicine syndrome type Approximately 100 patients in Coronary Heart Disease Patients with Blood Stasis Syndrome undergoing percutaneous coronary intervention will be enrolled and randomized to divided into Qi -stagnation and blood stasis, Qi- deficiency and blood stasis, after the PCI surgery, Qi deficiency and blood stasis group were randomly divided into Tongguan capsule group and the control group, and qi stagnation and blood stasis group, too ,giving patients through Tongguan capsule 3 pills three times a day(1.5g/day), once every three months follow-up, after have been followed up to six months Official Title ----------------- The Effect of Tongguan Capsule for MicroRNA Profiles Between Qi-Stagnation and Qi-Deficiency in Coronary Heart Disease Patients With Blood Stasis Syndrome Undergoing Percutaneous Coronary Intervention Conditions ----------------- Coronary Heart Disease, Acute Myocardial Infarction Intervention / Treatment ----------------- * Drug: Tongguan capsule * Drug: placebo capsule Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: In line with the diagnostic criteria for acute coronary syndrome (ACS), coronary angiography confirmed for coronary heart disease (CHD), parallel Percutaneous transluminal coronary angioplasty( PTCA) and/or coronary stent implantation was successful Postoperative routine drug treatment Traditional Chinese Medicine syndrome differentiation of qi -deficiency and qi -stagnation blood stasis or blood stasis license Aged 35 to 75 years old Must sign a consent form. Exclusion Criteria: Renal insufficiency, the male serum creatinine > 2.5 mg/dl (> 220 umo/l), women > 2.0 mg/dl (> 175 umo/l) With obvious liver disease or Alanine aminotransferase ( ALT)， Aspartate aminotransferase ( AST), 3 times higher than normal ceiling Serious cardiac insufficiency (EF < 35%) Uncontrolled patients with high blood pressure Merger or severe valvular heart disease in acute cerebrovascular disease Random blood glucose or greater tendency for 13.7 / L diabetes or glycosylated hemoglobin 9.5% or more Patients with severe mental illness Patients with malignant tumor or life expectancy in less than three years Patients with severe hematopoietic system disease Refused to sign a consent form, or estimated compliance is poorer, follow-up possibilities claim; Pregnancy or ready to pregnant women, nursing mothers; Participated in nearly three months, or is in other clinical subjects . - Ages Eligible for Study ----------------- Minimum Age: 35 Years Maximum Age: 75 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Tongguan capsule<br>Tongguan capsule (0.5 g tid. for 6 months) \| Drug: Tongguan capsule<br>* eligible participants were randomized to receive Tongguan capsule ( 1.5 g/day for six months immediately after PCI)<br>\| \| Placebo Comparator: placebo capsule<br>same volume/day of placebo capsule (0.5 g tid. for 6 months) \| Drug: placebo capsule<br>* eligible participants were randomized to receive placebo capsule ( 1.5 g/day for six months immediately after PCI)<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| miRNAs spectrum \| Test the expression of microRNAs related to the syndromes after the intervention of Tongguan capsule,preliminarily to investigate the mechanism of the effects of Tongguan capsule, and provide the biological foundation of curative effect of Tongguan capsule. \| six months \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| major adverse cardiac event \| frequency of the reported cardiovascular events (defined as cardiogenic death, stroke, recurrent myocardial infarction, readmission on account of deterioration of congestive heart failure or unstable angina, target vessel revascularization) \| six months \| \| Renin predicts cardiovascular homeostasis and ventricular remodeling \| renin（ng/ml） predicts cardiovascular homeostasis and blood pressure maintenance and plays an important role in ventricular remodeling \| 6 months \| \| Ang II predicts cardiovascular homeostasis and ventricular remodeling \| Ang II（pg/ml） predicts cardiovascular homeostasis and blood pressure maintenance and plays an important role in ventricular remodeling \| 6 months \| \| Serum E \| Acute coronary syndrome is caused by atherosclerotic plaque instability and rupture. The stability of plaque is closely related to inflammation.Serum E (pmol / L) is an important pathway of various immune and inflammatory regulation, which promotes the development of atherosclerosis and is a risk factor for atherosclerosis. \| 6 months \| \| Inflammatory mediators \| Tumor Necrosis factor alpha (ng/L)and Interleukin-6，IL-6 (ng/L) measure of the general situation of patients \| 6 months \| \| Brain Natriuretic Peptide \| B-type natriuretic peptide（pg/ml） is a neurohormone synthesized in the cardiac ventricles upon ventricular pressure overload and ventricular dilatation \| 6 months \| \| Echocardiography measure of left ventricular systolic function \| Evaluation of left ventricular systolic function by left ventricular ejection fraction( LVEF) (%) \| 6 months \| \| Echocardiography measure of left ventricular diastolic function \| Left ventricular end diastolic diameter (LVEDD) (mm )measure of left ventricular diastolic function in patients \| 6 months \| \| New York Heart Association functional classification \| I Cardiac disease, but no symptoms and no limitation in ordinary physical activity, e.g. no shortness of breath when walking, climbing stairs etc. II Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. III Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m).Comfortable only at rest. IV Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients. \| 6 months \| \| Coronary angiography \| Quantitative coronary angiography in the stenosis degree, 25%, 50%, 75%, 90%, 99%, 100%, 1, 2, 4, 6, 8,, 16, 32, and, respectively. Scoring multiplication will segment coefficients corresponding to the degree of stenosis and the stenosis of total score that is the sum of Gensini score of coronary artery stenosis in the patients. \| 6 months \| \| Seattle Angina Questionnaire score \| The Seattle Angina Questionnaire is a valid and reliable instrument that measures five clinically important dimensions of health in patients with coronary artery disease (physical limitation, anginal stability, anginal frequency, treatment satisfaction, and disease perception). (in Units on a Scale). \| 6 months \| \| The traditional Chinese medicine syndrome scale \| The traditional Chinese medicine syndrome scale Including the the score of deficiency of qi and score of blood stasis syndrome mainly used to identify patients with traditional Chinese medicine syndrome type \| 6 months \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- acute coronary syndrome, Tongguan capsule, miRNAs
NCT04006262	Pre-operative Nivolumab and Ipilimumab, Followed by Post-operative Nivolumab, for MSI/dMMR Oeso-gastric Adenocarcinoma.	This is a non-randomized study, open label phase II study. The purpose of this study is to evaluate the complete pathologic response rate (cPRR) with neoadjuvant nivolumab and ipilimumab combination in patients with MSI and/or dMMR localized oeso-gastric cancer.	In patients with resectable oeso-gastric adenocarcinoma, radical surgery is the only curative option. Despite the evolution in treatment with multimodality treatment strategies, oeso-gastric cancer remains one of the most lethal malignancies with 5-year survival rates reaching only 22%. When the disease is localized, perioperative chemotherapy with cytotoxic agents is the preferred strategy since it increases the overall survival (OS) rate. However, in oeso-gastric cancers with microsatellite instability (MSI), is a favorable prognostic factor, the recommended cytotoxic chemotherapy combination seems inefficient and even deleterious.~It is now well established that dMMR and or the MSI phenotype are the surrogate markers of response to immunotherapy.~The combination of nivolumab and ipilimumab had shown promising efficacy in multiple tumor types (dMMR/MSI).~Based on the data above, we have designed this phase II study to evaluate the complete pathological response rate (cPRR) in patients with non-metastatic MSI/dMMR oeso-gastric adenocarcinoma treated with neoadjuvant nivolumab and ipilimumab treatment.	Peri-operative Association of Immunotherapy (Pre-operative Association of Nivolumab and Ipilimumab, Post-operative Nivolumab Alone) in Localized Microsatellite Instability (MSI) and/or Deficient Mismatch Repair (dMMR) Oeso-gastric Adenocarcinoma: An Open-label GERCOR Phase II Study	MSI and or dMMR, Localized Oesogastric Adenocarcimona	* Drug: Nivolumab 10 MG/ML * Drug: Ipilimumab 200 MG in 40 ML Injection	Inclusion Criteria:~Signed and dated informed consent,~Age ≥18 years to ≤75 years of age,~Histologically proven non-metastatic gastric adenocarcinoma or of the oeso-gastric junction T2 to T4, Nx, M0 after thoraco-abdominopelvic computed tomography (CT) and echo-endoscopy,~Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study,~dMMR (protein expression by immunohistochemistry [ICH] and/or MSI by polymerase chain reaction [PCR]), MMR and/or MSI tumors should be assessed per local guidelines: ICH with two (anti-MLH1 and anti-MSH2 or anti-MSH6, and antiPMS2) or four antibodies (anti-MLH1, anti-MSH2, anti-MSH6, and anti-PMS2) and/or PCR (with PROMEGA: BAT- 25, BAT-26, NR-21, NR-24, and NR-27) by the investigators prior to screening, Extinct MLH1 (+/- PMS2), MSH2 (+/- MSH6), MSH6, or PMS2 alone protein expression by IHC (dMMR), and/or tumor with ≥ 2 instable MSI-H markers on PCR: BAT25, BAT26, NR21, NR24, and NR27 (pentaplex panel is recommended),~The Eastern Cooperative Oncology Group Performance status (ECOG PS) 0-1, for patients over 70 years ECOG PS of 0;~Hematological status: absolute neutrophil count (ANC) ≥1.5 x 109/L; platelets ≥100 x 109/L; hemoglobin ≥9 g/dL,~Adequate renal function: serum creatinine level <120 µM, clearance > 50ml/min (Modification of the Diet in Renal Disease [MDRD] or Cockcroft and Gault),~Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alkaline phosphatase <5 x ULN, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3.0 x ULN,~No prior therapy for localized oeso-gastric cancer,~Radiological tumor assessment within 21 days before the start of treatment according to RECIST version 1.1 by Chest Abdomen and Pelvis CT,~For female patients of childbearing potential, negative pregnancy test within 7 days before starting the study drug,~Men and women are required to use adequate birth control during the study (when applicable), Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use a highly effective method of birth control (i.e., pregnancy rate of less than 1% per year) during the period of treatment and during 5 and 7 months, woman and men, respectively, from the last treatment administration. Men must refrain from donating sperm during this same period, Contraceptive methods that result in a low failure rate when used consistently and correctly include methods such as combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), some intrauterine devices, intrauterine hormone- releasing stem, true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant), bilateral tubal occlusion, or a female partner who is not of childbearing potential or a male partner who has had a vasectomy. Women and female partners using hormonal contraceptive must also use a barrier method i.e. condom or occlusive cap (diaphragm or cervical/vault caps), A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (>12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus),~Subject willing to comply to provide primary tumor tissue (archival or fresh biopsy specimen), including possible pre-treatment biopsy for PD-L1 expression analysis and other biomarker correlative studies~Registration in a National Health Care System (PUMa - Protection Universelle Maladie included)~Exclusion Criteria:~Non-eligible to clinical trial if one of following parameter is reported:~Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),~Treatment with any investigational medicinal product within 28 days prior to study entry,~Major surgical procedure within 4 weeks prior to initiation of study treatment,~Other serious and uncontrolled non-malignant disease (including active infection),~Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years,~Metastases (M stage disease) whatever the location,~Pregnant or breastfeeding women,~Human immunodeficiency virus (HIV),~Active hepatitis B virus (HBV, defined as having a positive hepatitis B surface antigen [HBsAg] test prior to inclusion) or hepatitis C virus (HCV). Note: Patients with past HBV infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen antibody test) are eligible. Note: Patients positive for HCV antibody are eligible only if PCR testing is negative for HCV RNA~Patient on tutelage or guardianship or under the protection of justice.~Impossibility of submitting to the medical follow-up of the study for geographical, social or psychiatric reasons.~Non-eligible to immunotherapy:~History of autoimmune disease including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis, Note: History of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. Note: Controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible.~History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest imaging,~Administration of a live, attenuated vaccine within 4 weeks prior to start of treatment or anticipation that such a live attenuated vaccine will be required during the remainder of the study,~Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or antiPD-L1 therapeutic antibody or pathway-targeting agents,~Prior allogeneic bone marrow transplantation or prior solid organ transplantation,~Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including, but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to start of adjuvant treatment, or requirement for systemic immunosuppressive medications during the remainder of the study. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.~Note: Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled into the study after approval of the Medical Contact. Subjects are permitted the use of topical, ocular, intra- articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption).~Adrenal replacement steroid doses including doses >10 mg daily prednisone is permitted. A brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g. contrast dye allergy) or for treatment of non-autoimmune conditions (e.g. delayed-type hypersensitivity reaction caused by a contact allergen) is permitted	18 Years	75 Years	All	No	Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Complete pathological response (cPRR) rate \| Each center will assess the pathologic response with a centralized center review in case of cPRR and the analysis will be in intention-to-treat (ITT).~cPRR will be defined as complete tumor disappearance of tumor in the low esophagus or the stomach (from 1/3 inferior of the esophagus to pylorus) after surgery anatomopathologic examination according to mandard scale.~Surgery will be performed within 5 weeks +\- 1 week after the last cycle (cycle 6) of neoadjuvant therapy \| time point when the tumor is examined after the surgery (up to 30 months) \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Disease-free survival (DFS) \| DFS is defined as the time from the date of starting treatment to local recurrence and/or metastases or death irrespective of cause and censored at the date of last contact. \| Up to 36 months \| \| Overall Survival (OS) \| OS is defined as the time between the date of the first dose of study treatment and the death date. Patients alive at last report will be considered censored at the endpoint. Alive patients will be censored at the last date known to be alive, either during study treatment period or during follow-up period. \| Up to 36 months \| \| Number of participants with treatment-related adverse events \| Number of participants with treatment-related adverse events as assessed by National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] v5.0 \| Patients will be assessed for AEs throughout the study at every visit during treatment and at 3-month follow-up visit (3 months after treatment ends). Investigators using the NCI-CTCAE version 5.0 will grade the severity of AEs. \| \| Analyze MSI status \| Confirmation of MSI and/or dMMR has to be confirmed retrospectively on archival or fresh tumor FFPET block from the primary tumor obtained at the time of the initial diagnosis \| up to 36 months \| \| Quantification of antigen-specific CD4+ T cells as biomarker of anti-PD1/PDL1 immunotherapy in dMMR tumors \| Quantification of antigen-specific CD4+ T cells as biomarker of anti-PD1/PDL1 immunotherapy in blood of dMMR tumors. \| Blood samples at baseline, C3D1 and C6D1 of neoadjuvant therapy - cycle every 2 weeks, after surgery at C1 D1(first cycle of adjuvant treatment) and at the end of treatment visit (28 days after the last dose of treatment (up to 36 months) \| \| Number of Species of bacteria and yeast composition \| To investigate the microbiota composition changes during neoadjuvant therapy with nivolumab and ipilimumab and its relation to response and/or chemotoxicity.~Number of Species of bacteria and yeast will be quantitfy and identify. Number of Change of composition will be investigate based on baseline samples compared to 12 weeks sample.~DNA will be extracted from fecal samples taken prior to therapy and on-treatment (week 12). A gene sequencing approach will be utilized to survey microbial species in the gut in order to define microbiota as a function of the efficacy and safety. \| Baseline and at week 12 \|		Nivolumab, Ipilimumab, Antineoplastic Agents, Immunological, Antineoplastic Agents, Immune Checkpoint Inhibitors, Molecular Mechanisms of Pharmacological Action	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Experimental arm<br>Neo-adjuvant treatment (6 cycles - 12 weeks)~Surgery~Adjuvant treatment (9 cycles - 9 months) \| Drug: Nivolumab 10 MG/ML<br>* Neo-adjuvant treatment : 240 mg intravenous (I.V.) in 30 minutes - every 2 weeks - 6 cycles~- Adjuvant treatment : 480mg I.V. in 30 minutes - every 4 weeks - 9 cycles<br>* Other names: Opdivo;Drug: Ipilimumab 200 MG in 40 ML Injection<br>* Neo-adjuvant treatment : 1mg/kg over 30 minutes every 6 cycles - 2 cycles<br>* Other names: Yervoy;\|	Pre-operative Nivolumab and Ipilimumab, Followed by Post-operative Nivolumab, for MSI/dMMR Oeso-gastric Adenocarcinoma. Study Overview ================= Brief Summary ----------------- This is a non-randomized study, open label phase II study. The purpose of this study is to evaluate the complete pathologic response rate (cPRR) with neoadjuvant nivolumab and ipilimumab combination in patients with MSI and/or dMMR localized oeso-gastric cancer. Detailed Description ----------------- In patients with resectable oeso-gastric adenocarcinoma, radical surgery is the only curative option. Despite the evolution in treatment with multimodality treatment strategies, oeso-gastric cancer remains one of the most lethal malignancies with 5-year survival rates reaching only 22%. When the disease is localized, perioperative chemotherapy with cytotoxic agents is the preferred strategy since it increases the overall survival (OS) rate. However, in oeso-gastric cancers with microsatellite instability (MSI), is a favorable prognostic factor, the recommended cytotoxic chemotherapy combination seems inefficient and even deleterious. It is now well established that dMMR and or the MSI phenotype are the surrogate markers of response to immunotherapy. The combination of nivolumab and ipilimumab had shown promising efficacy in multiple tumor types (dMMR/MSI). Based on the data above, we have designed this phase II study to evaluate the complete pathological response rate (cPRR) in patients with non-metastatic MSI/dMMR oeso-gastric adenocarcinoma treated with neoadjuvant nivolumab and ipilimumab treatment. Official Title ----------------- Peri-operative Association of Immunotherapy (Pre-operative Association of Nivolumab and Ipilimumab, Post-operative Nivolumab Alone) in Localized Microsatellite Instability (MSI) and/or Deficient Mismatch Repair (dMMR) Oeso-gastric Adenocarcinoma: An Open-label GERCOR Phase II Study Conditions ----------------- MSI and or dMMR, Localized Oesogastric Adenocarcimona Intervention / Treatment ----------------- * Drug: Nivolumab 10 MG/ML * Drug: Ipilimumab 200 MG in 40 ML Injection Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Signed and dated informed consent, Age ≥18 years to ≤75 years of age, Histologically proven non-metastatic gastric adenocarcinoma or of the oeso-gastric junction T2 to T4, Nx, M0 after thoraco-abdominopelvic computed tomography (CT) and echo-endoscopy, Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study, dMMR (protein expression by immunohistochemistry [ICH] and/or MSI by polymerase chain reaction [PCR]), MMR and/or MSI tumors should be assessed per local guidelines: ICH with two (anti-MLH1 and anti-MSH2 or anti-MSH6, and antiPMS2) or four antibodies (anti-MLH1, anti-MSH2, anti-MSH6, and anti-PMS2) and/or PCR (with PROMEGA: BAT- 25, BAT-26, NR-21, NR-24, and NR-27) by the investigators prior to screening, Extinct MLH1 (+/- PMS2), MSH2 (+/- MSH6), MSH6, or PMS2 alone protein expression by IHC (dMMR), and/or tumor with ≥ 2 instable MSI-H markers on PCR: BAT25, BAT26, NR21, NR24, and NR27 (pentaplex panel is recommended), The Eastern Cooperative Oncology Group Performance status (ECOG PS) 0-1, for patients over 70 years ECOG PS of 0; Hematological status: absolute neutrophil count (ANC) ≥1.5 x 109/L; platelets ≥100 x 109/L; hemoglobin ≥9 g/dL, Adequate renal function: serum creatinine level <120 µM, clearance > 50ml/min (Modification of the Diet in Renal Disease [MDRD] or Cockcroft and Gault), Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alkaline phosphatase <5 x ULN, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3.0 x ULN, No prior therapy for localized oeso-gastric cancer, Radiological tumor assessment within 21 days before the start of treatment according to RECIST version 1.1 by Chest Abdomen and Pelvis CT, For female patients of childbearing potential, negative pregnancy test within 7 days before starting the study drug, Men and women are required to use adequate birth control during the study (when applicable), Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use a highly effective method of birth control (i.e., pregnancy rate of less than 1% per year) during the period of treatment and during 5 and 7 months, woman and men, respectively, from the last treatment administration. Men must refrain from donating sperm during this same period, Contraceptive methods that result in a low failure rate when used consistently and correctly include methods such as combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), some intrauterine devices, intrauterine hormone- releasing stem, true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant), bilateral tubal occlusion, or a female partner who is not of childbearing potential or a male partner who has had a vasectomy. Women and female partners using hormonal contraceptive must also use a barrier method i.e. condom or occlusive cap (diaphragm or cervical/vault caps), A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (>12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus), Subject willing to comply to provide primary tumor tissue (archival or fresh biopsy specimen), including possible pre-treatment biopsy for PD-L1 expression analysis and other biomarker correlative studies Registration in a National Health Care System (PUMa - Protection Universelle Maladie included) Exclusion Criteria: Non-eligible to clinical trial if one of following parameter is reported: Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy), Treatment with any investigational medicinal product within 28 days prior to study entry, Major surgical procedure within 4 weeks prior to initiation of study treatment, Other serious and uncontrolled non-malignant disease (including active infection), Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years, Metastases (M stage disease) whatever the location, Pregnant or breastfeeding women, Human immunodeficiency virus (HIV), Active hepatitis B virus (HBV, defined as having a positive hepatitis B surface antigen [HBsAg] test prior to inclusion) or hepatitis C virus (HCV). Note: Patients with past HBV infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen antibody test) are eligible. Note: Patients positive for HCV antibody are eligible only if PCR testing is negative for HCV RNA Patient on tutelage or guardianship or under the protection of justice. Impossibility of submitting to the medical follow-up of the study for geographical, social or psychiatric reasons. Non-eligible to immunotherapy: History of autoimmune disease including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis, Note: History of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. Note: Controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest imaging, Administration of a live, attenuated vaccine within 4 weeks prior to start of treatment or anticipation that such a live attenuated vaccine will be required during the remainder of the study, Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or antiPD-L1 therapeutic antibody or pathway-targeting agents, Prior allogeneic bone marrow transplantation or prior solid organ transplantation, Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including, but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to start of adjuvant treatment, or requirement for systemic immunosuppressive medications during the remainder of the study. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Note: Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled into the study after approval of the Medical Contact. Subjects are permitted the use of topical, ocular, intra- articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Adrenal replacement steroid doses including doses >10 mg daily prednisone is permitted. A brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g. contrast dye allergy) or for treatment of non-autoimmune conditions (e.g. delayed-type hypersensitivity reaction caused by a contact allergen) is permitted Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 75 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Experimental arm<br>Neo-adjuvant treatment (6 cycles - 12 weeks) Surgery Adjuvant treatment (9 cycles - 9 months) \| Drug: Nivolumab 10 MG/ML<br>* Neo-adjuvant treatment : 240 mg intravenous (I.V.) in 30 minutes - every 2 weeks - 6 cycles - Adjuvant treatment : 480mg I.V. in 30 minutes - every 4 weeks - 9 cycles<br>* Other names: Opdivo;Drug: Ipilimumab 200 MG in 40 ML Injection<br>* Neo-adjuvant treatment : 1mg/kg over 30 minutes every 6 cycles - 2 cycles<br>* Other names: Yervoy;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Complete pathological response (cPRR) rate \| Each center will assess the pathologic response with a centralized center review in case of cPRR and the analysis will be in intention-to-treat (ITT). cPRR will be defined as complete tumor disappearance of tumor in the low esophagus or the stomach (from 1/3 inferior of the esophagus to pylorus) after surgery anatomopathologic examination according to mandard scale. Surgery will be performed within 5 weeks +\- 1 week after the last cycle (cycle 6) of neoadjuvant therapy \| time point when the tumor is examined after the surgery (up to 30 months) \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Disease-free survival (DFS) \| DFS is defined as the time from the date of starting treatment to local recurrence and/or metastases or death irrespective of cause and censored at the date of last contact. \| Up to 36 months \| \| Overall Survival (OS) \| OS is defined as the time between the date of the first dose of study treatment and the death date. Patients alive at last report will be considered censored at the endpoint. Alive patients will be censored at the last date known to be alive, either during study treatment period or during follow-up period. \| Up to 36 months \| \| Number of participants with treatment-related adverse events \| Number of participants with treatment-related adverse events as assessed by National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] v5.0 \| Patients will be assessed for AEs throughout the study at every visit during treatment and at 3-month follow-up visit (3 months after treatment ends). Investigators using the NCI-CTCAE version 5.0 will grade the severity of AEs. \| \| Analyze MSI status \| Confirmation of MSI and/or dMMR has to be confirmed retrospectively on archival or fresh tumor FFPET block from the primary tumor obtained at the time of the initial diagnosis \| up to 36 months \| \| Quantification of antigen-specific CD4+ T cells as biomarker of anti-PD1/PDL1 immunotherapy in dMMR tumors \| Quantification of antigen-specific CD4+ T cells as biomarker of anti-PD1/PDL1 immunotherapy in blood of dMMR tumors. \| Blood samples at baseline, C3D1 and C6D1 of neoadjuvant therapy - cycle every 2 weeks, after surgery at C1 D1(first cycle of adjuvant treatment) and at the end of treatment visit (28 days after the last dose of treatment (up to 36 months) \| \| Number of Species of bacteria and yeast composition \| To investigate the microbiota composition changes during neoadjuvant therapy with nivolumab and ipilimumab and its relation to response and/or chemotoxicity. Number of Species of bacteria and yeast will be quantitfy and identify. Number of Change of composition will be investigate based on baseline samples compared to 12 weeks sample. DNA will be extracted from fecal samples taken prior to therapy and on-treatment (week 12). A gene sequencing approach will be utilized to survey microbial species in the gut in order to define microbiota as a function of the efficacy and safety. \| Baseline and at week 12 \|
NCT05296031	Drug Eluting Stent Zilver PTX vs Bare Metal Stent Zilver Flex	Randomized study comparing the results between drug-eluting stents and standard bare metal stents, when treating femoropopliteal lesions in patients with critical limb ischemia.		Randomized Trial Comparing Drug Eluting Stent Zilver PTX vs Bare Metal Stent Zilver Flex in Critical Limb Ischemia and Treatment of Lesions in Femoral and Popliteal Arteries	Vascular Diseases	* Device: Treatment with Zilver PTX Drug Eluting Stent (DES) in femoropopliteal lesions * Device: Treatment with Zilver Flex Bare Metal Stent (BMS) in femoropopliteal lesions	Inclusion Criteria:~Critical limb ischemia RC 4-6~Lesions in superficial femoral artery and popliteal artery (p1 -p2)~Target vessel 4-8mm~At least I 1 vessel runoff to the foot~Age >18 years~Exclusion Criteria:~Pregnancy~Patient disapproval~Age <18 years	18 Years	100 Years	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Randomized trial comparing drug eluting stent Zilver PTX vs Bare metal stent Zilver Flex in critical limb ischemia and treatment of lesions in femoral and popliteal arteries Masking: Single	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Freedom from TLR (Target Lesion Revascularization) \| Fraction of study subjects without need for retreatment at treatment location \| 6 months \| \| Freedom from TLR (Target Lesion Revascularization) \| Fraction of study subjects without need for retreatment at treatment location \| 12 months \| \| Freedom from TLR (Target Lesion Revascularization) \| Fraction of study subjects without need for retreatment at treatment location \| 24 months \| \| Open (functioning and not stenosed) vascular reconstruction (Primary Patency) \| Functioning revascularization without adjunctive measures \| 12months \| \| Open (functioning and not stenosed) vascular reconstruction (Primary Patency) \| Functioning revascularization without adjunctive measures \| 24 months \| \| Event Free Survival \| Alive without vascular events \| 24 months \|			Vascular Diseases, Cardiovascular Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Drug Eluting Stent (DES)<br>Drug Eluting Stent (DES). Zilver PTX. \| Device: Treatment with Zilver PTX Drug Eluting Stent (DES) in femoropopliteal lesions<br>* Randomized trial comparing drug eluting stent Zilver PTX vs Bare metal stent Zilver Flex in critical limb ischemia and treatment of lesions in femoral and popliteal arteries<br>\| \| Placebo Comparator: Bare Metal Stent (BMS)<br>Bare Metal Stent (BMS). Zilver Flex \| Device: Treatment with Zilver Flex Bare Metal Stent (BMS) in femoropopliteal lesions<br>* Randomized trial comparing drug eluting stent Zilver PTX vs Bare metal stent Zilver Flex in critical limb ischemia and treatment of lesions in femoral and popliteal arteries<br>\|	Drug Eluting Stent Zilver PTX vs Bare Metal Stent Zilver Flex Study Overview ================= Brief Summary ----------------- Randomized study comparing the results between drug-eluting stents and standard bare metal stents, when treating femoropopliteal lesions in patients with critical limb ischemia. Official Title ----------------- Randomized Trial Comparing Drug Eluting Stent Zilver PTX vs Bare Metal Stent Zilver Flex in Critical Limb Ischemia and Treatment of Lesions in Femoral and Popliteal Arteries Conditions ----------------- Vascular Diseases Intervention / Treatment ----------------- * Device: Treatment with Zilver PTX Drug Eluting Stent (DES) in femoropopliteal lesions * Device: Treatment with Zilver Flex Bare Metal Stent (BMS) in femoropopliteal lesions Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Critical limb ischemia RC 4-6 Lesions in superficial femoral artery and popliteal artery (p1 -p2) Target vessel 4-8mm At least I 1 vessel runoff to the foot Age >18 years Exclusion Criteria: Pregnancy Patient disapproval Age <18 years Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 100 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Randomized trial comparing drug eluting stent Zilver PTX vs Bare metal stent Zilver Flex in critical limb ischemia and treatment of lesions in femoral and popliteal arteries Masking: Single Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Drug Eluting Stent (DES)<br>Drug Eluting Stent (DES). Zilver PTX. \| Device: Treatment with Zilver PTX Drug Eluting Stent (DES) in femoropopliteal lesions<br>* Randomized trial comparing drug eluting stent Zilver PTX vs Bare metal stent Zilver Flex in critical limb ischemia and treatment of lesions in femoral and popliteal arteries<br>\| \| Placebo Comparator: Bare Metal Stent (BMS)<br>Bare Metal Stent (BMS). Zilver Flex \| Device: Treatment with Zilver Flex Bare Metal Stent (BMS) in femoropopliteal lesions<br>* Randomized trial comparing drug eluting stent Zilver PTX vs Bare metal stent Zilver Flex in critical limb ischemia and treatment of lesions in femoral and popliteal arteries<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Freedom from TLR (Target Lesion Revascularization) \| Fraction of study subjects without need for retreatment at treatment location \| 6 months \| \| Freedom from TLR (Target Lesion Revascularization) \| Fraction of study subjects without need for retreatment at treatment location \| 12 months \| \| Freedom from TLR (Target Lesion Revascularization) \| Fraction of study subjects without need for retreatment at treatment location \| 24 months \| \| Open (functioning and not stenosed) vascular reconstruction (Primary Patency) \| Functioning revascularization without adjunctive measures \| 12months \| \| Open (functioning and not stenosed) vascular reconstruction (Primary Patency) \| Functioning revascularization without adjunctive measures \| 24 months \| \| Event Free Survival \| Alive without vascular events \| 24 months \|
NCT01605487	Study to Assess Efficacy, Safety and Mechanism of Rupatadine in Cold Urticaria	Main objective of this study is to evaluate the efficacy of rupatadine in 20 mg and 40 mg doses in the development of symptoms of cold contact urticaria. For this purpose, a Peltier element-based electronic provocation device (TempTest®, emo systems GmbH, Berlin, Germany) will be used. This allows skin exposure to 12 different temperatures from 4 to 42 °C simultaneously in a standardized and reproducible way and thus the determination of individual temperature and/or stimulation time thresholds.~In addition mediators related from activated must cells such as histamine, PAF, PGD2 should be identified in the period between the application of stimulus and the appearance of symptoms of cold urticaria and should be characterized qualitatively and quantitatively.		Double-blind, Three-way Cross-over, Placebo-controlled Study to Assess the Efficacy, Safety and Mechanisms of Treatment With Rupatadine 20 mg and 40 mg in Cold Contact Urticaria (CCU)	Cold Contact Urticaria	* Drug: Rupatadine * Drug: Rupatadine * Drug: Rupatadine * Drug: Rupatadine * Drug: Rupatadine * Drug: Rupatadine	Inclusion Criteria:~Informed consent signed and dated~Reliable method of contraception for both women of childbearing potential as well as man during the study and 3 months thereafter. A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner~Outpatients with CCU for more than 6 weeks. Urticaria symptoms must comprise wheal and itch after contact cooling of the skin. Provocation should be performed by application of Temptest®3.0 which allows for reproducible and standardized cold provocation tests and the identification of temperature and stimulation time thresholds.~Age 18 and above 18 years.~No participation in other clinical trials 1 months before and after participation in this study~Exclusion Criteria:~Subjects who are inmates of psychiatric wards, prisons, or other state institutions. Existing or planned placement in an institution after ruling according to § 40 passage 1, number 4 AMG (Arzneimittelgesetz).~The presence of permanent severe diseases, especially those affecting the immune system, except urticaria and cold urticaria~The presence of permanent gastrointestinal condition which may influence the oral therapy (chronic diarrhoea diseases, congenital malformations or surgical mutilations of gastrointestinal tract)~History or presence of epilepsy, significant neurological disorders, cerebrovascular attacks or ischemia~History or presence of myocardial infarction or cardiac arrhythmia which requires drug therapy~ECG alterations of repolarisation (QTc prolongations > 450ms)~Blood pressure >180/100 mmHg and/or heart rate >100/min.~Evidence of significant hepatic or renal disease (GOT and/or GPT 3 times above the upper reference value, serum creatinine 1.5 times above the upper reference value)~History of hypersensitivity or allergic reaction to rupatadine or its ingredients or any other antihistamine compounds.~Presence of active cancer which requires chemotherapy or radiation therapy~Presence of lactose and galactose intolerance or with glucose-galactose malabsorption~Simultaneous chronic spontaneous or physical urticaria that could interfere CCU clinical assessment~Intake of antihistamines or antileukotrienes within 7 days before beginning of the study~Intake of oral or depot corticosteroids within 14 days prior to screening visit~Use of systemic immunosupressants/immunomodulators like cyclosporine A, dapsone, methotrexate, mycophenolate, chloroquine, and comparable drugs within 28 days prior to screening visit.~Use of ketoconazole, erythromycin or potential inhibitors of the isoenzyme CYP3A4 of the cytochrome P450.~Currently abusing drugs or alcohol~Unwilling or unable to comply with the protocol~Pregnancy or breast-feeding	18 Years	null	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Masking: Triple	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Critical stimulation time threshold(CSTT) after challenge with cold \| Critical stimulation time threshold (CSTT) determines the shortest stimulation time sufficient for inducing a wheal-and-flare reaction \| Visit 1(day -14 Screening), Visit 2 (Randomization; day 0), Visit 3(Last day of treatment period 1; day 7), Visit 4(Last day of treatment period 2; day 28), Visit 5(Last day of treatment period 3; day 49) \| \| Critical temperature threshold (CTT)after challenge with cold \| Critical temperature threshold (CTT) determines the highest temperature sufficient for inducing a wheal-and-flare reaction \| Visit 1(day -14 Screening), Visit 2 (Randomization; day 0), Visit 3(Last day of treatment period 1; day 7), Visit 4(Last day of treatment period 2; day 28), Visit 5(Last day of treatment period 3; day 49) \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Mast cell mediator release \| \| Visit 3(Last day of treatment period 1; day 7), Visit 4(Last day of treatment period 2; day 28), Visit 5(Last day of treatment period 3; day 49) \| \| Safety and tolerability following administration of Rupatadine to patients with cold contact urticaria \| Safety and tolerability: This includes physical examination, routine safety laboratory assessments, clinical observation, vital sings and adverse event reporting \| up to 9 weeks \|		Cyproheptadine, Antipruritics, Dermatologic Agents, Gastrointestinal Agents, Histamine H1 Antagonists, Histamine Antagonists, Histamine Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Physiological Effects of Drugs, Serotonin Antagonists, Serotonin Agents, Anti-Allergic Agents	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Other: Rupatadine 20mg - Placebo - Rupatadine 40mg<br> \| Drug: Rupatadine<br>* Rupatadine in Tab 10mg: 4 Tab.(2 Tab. of Rupatadine + 2 Tab. of Placebo) once daily during 7 days, then 14 days washout period; Placebo 4 Tab once daily during 7 days, then 14 days washout period; Rupatadine in Tab. 10mg, 4 Tab. once daily during 7 days<br>\| \| Other: Rupatadine 20mg - Rupatadine 40mg - Placebo<br> \| Drug: Rupatadine<br>* Rupatadine in Tab 10mg: 4 Tab.(2 Tab. of Rupatadine + 2 Tab. of Placebo) once daily during 7 days, then 14 days washout period; Rupatadine in Tab. 10mg, 4 Tab. once daily during 7 days,then 14 days washout period; Placebo 4 Tab once daily during 7 days<br>\| \| Other: Placebo - Rupatadine 20mg - Rupatadine 40mg<br> \| Drug: Rupatadine<br>* Placebo 4 Tab once daily during 7 days, then 14 days washout period; Rupatadine in Tab 10mg: 4 Tab.(2 Tab. of Rupatadine + 2 Tab. of Placebo) once daily during 7 days, then 14 days washout period; Rupatadine in Tab. 10mg, 4 Tab. once daily during 7 days<br>\| \| Other: Rupatadine 40mg - Placebo - Rupatadine 20mg<br> \| Drug: Rupatadine<br>* Rupatadine in Tab. 10mg, 4 Tab. once daily during 7 days,then 14 days washout period; Placebo 4 Tab once daily during 7 days, then 14 days washout period; Rupatadine in Tab 10mg: 4 Tab.(2 Tab. of Rupatadine + 2 Tab. of Placebo) once daily during 7 days<br>\| \| Other: Placebo - Rupatadine 40mg - Rupatadine 20mg<br> \| Drug: Rupatadine<br>* Placebo 4 Tab once daily during 7 days, then 14 days washout period; Rupatadine in Tab. 10mg, 4 Tab. once daily during 7 days, then 14 days washout period; Rupatadine in Tab 10mg: 4 Tab.(2 Tab. of Rupatadine + 2 Tab. of Placebo) once daily during 7 days<br>\| \| Other: Rupatadine 40mg - Rupatadine 20mg - Placebo<br> \| Drug: Rupatadine<br>* Rupatadine in Tab. 10mg: 4 Tab. once daily during 7 days, then 14 days washout period; Rupatadine in Tab 10mg: 4 Tab.(2 Tab. of Rupatadine + 2 Tab. of Placebo) once daily during 7 days, then 14 days washout period; Placebo 4 Tab once daily during 7 days<br>\|	Study to Assess Efficacy, Safety and Mechanism of Rupatadine in Cold Urticaria Study Overview ================= Brief Summary ----------------- Main objective of this study is to evaluate the efficacy of rupatadine in 20 mg and 40 mg doses in the development of symptoms of cold contact urticaria. For this purpose, a Peltier element-based electronic provocation device (TempTest®, emo systems GmbH, Berlin, Germany) will be used. This allows skin exposure to 12 different temperatures from 4 to 42 °C simultaneously in a standardized and reproducible way and thus the determination of individual temperature and/or stimulation time thresholds. In addition mediators related from activated must cells such as histamine, PAF, PGD2 should be identified in the period between the application of stimulus and the appearance of symptoms of cold urticaria and should be characterized qualitatively and quantitatively. Official Title ----------------- Double-blind, Three-way Cross-over, Placebo-controlled Study to Assess the Efficacy, Safety and Mechanisms of Treatment With Rupatadine 20 mg and 40 mg in Cold Contact Urticaria (CCU) Conditions ----------------- Cold Contact Urticaria Intervention / Treatment ----------------- * Drug: Rupatadine * Drug: Rupatadine * Drug: Rupatadine * Drug: Rupatadine * Drug: Rupatadine * Drug: Rupatadine Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Informed consent signed and dated Reliable method of contraception for both women of childbearing potential as well as man during the study and 3 months thereafter. A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner Outpatients with CCU for more than 6 weeks. Urticaria symptoms must comprise wheal and itch after contact cooling of the skin. Provocation should be performed by application of Temptest®3.0 which allows for reproducible and standardized cold provocation tests and the identification of temperature and stimulation time thresholds. Age 18 and above 18 years. No participation in other clinical trials 1 months before and after participation in this study Exclusion Criteria: Subjects who are inmates of psychiatric wards, prisons, or other state institutions. Existing or planned placement in an institution after ruling according to § 40 passage 1, number 4 AMG (Arzneimittelgesetz). The presence of permanent severe diseases, especially those affecting the immune system, except urticaria and cold urticaria The presence of permanent gastrointestinal condition which may influence the oral therapy (chronic diarrhoea diseases, congenital malformations or surgical mutilations of gastrointestinal tract) History or presence of epilepsy, significant neurological disorders, cerebrovascular attacks or ischemia History or presence of myocardial infarction or cardiac arrhythmia which requires drug therapy ECG alterations of repolarisation (QTc prolongations > 450ms) Blood pressure >180/100 mmHg and/or heart rate >100/min. Evidence of significant hepatic or renal disease (GOT and/or GPT 3 times above the upper reference value, serum creatinine 1.5 times above the upper reference value) History of hypersensitivity or allergic reaction to rupatadine or its ingredients or any other antihistamine compounds. Presence of active cancer which requires chemotherapy or radiation therapy Presence of lactose and galactose intolerance or with glucose-galactose malabsorption Simultaneous chronic spontaneous or physical urticaria that could interfere CCU clinical assessment Intake of antihistamines or antileukotrienes within 7 days before beginning of the study Intake of oral or depot corticosteroids within 14 days prior to screening visit Use of systemic immunosupressants/immunomodulators like cyclosporine A, dapsone, methotrexate, mycophenolate, chloroquine, and comparable drugs within 28 days prior to screening visit. Use of ketoconazole, erythromycin or potential inhibitors of the isoenzyme CYP3A4 of the cytochrome P450. Currently abusing drugs or alcohol Unwilling or unable to comply with the protocol Pregnancy or breast-feeding Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Masking: Triple Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Other: Rupatadine 20mg - Placebo - Rupatadine 40mg<br> \| Drug: Rupatadine<br>* Rupatadine in Tab 10mg: 4 Tab.(2 Tab. of Rupatadine + 2 Tab. of Placebo) once daily during 7 days, then 14 days washout period; Placebo 4 Tab once daily during 7 days, then 14 days washout period; Rupatadine in Tab. 10mg, 4 Tab. once daily during 7 days<br>\| \| Other: Rupatadine 20mg - Rupatadine 40mg - Placebo<br> \| Drug: Rupatadine<br>* Rupatadine in Tab 10mg: 4 Tab.(2 Tab. of Rupatadine + 2 Tab. of Placebo) once daily during 7 days, then 14 days washout period; Rupatadine in Tab. 10mg, 4 Tab. once daily during 7 days,then 14 days washout period; Placebo 4 Tab once daily during 7 days<br>\| \| Other: Placebo - Rupatadine 20mg - Rupatadine 40mg<br> \| Drug: Rupatadine<br>* Placebo 4 Tab once daily during 7 days, then 14 days washout period; Rupatadine in Tab 10mg: 4 Tab.(2 Tab. of Rupatadine + 2 Tab. of Placebo) once daily during 7 days, then 14 days washout period; Rupatadine in Tab. 10mg, 4 Tab. once daily during 7 days<br>\| \| Other: Rupatadine 40mg - Placebo - Rupatadine 20mg<br> \| Drug: Rupatadine<br>* Rupatadine in Tab. 10mg, 4 Tab. once daily during 7 days,then 14 days washout period; Placebo 4 Tab once daily during 7 days, then 14 days washout period; Rupatadine in Tab 10mg: 4 Tab.(2 Tab. of Rupatadine + 2 Tab. of Placebo) once daily during 7 days<br>\| \| Other: Placebo - Rupatadine 40mg - Rupatadine 20mg<br> \| Drug: Rupatadine<br>* Placebo 4 Tab once daily during 7 days, then 14 days washout period; Rupatadine in Tab. 10mg, 4 Tab. once daily during 7 days, then 14 days washout period; Rupatadine in Tab 10mg: 4 Tab.(2 Tab. of Rupatadine + 2 Tab. of Placebo) once daily during 7 days<br>\| \| Other: Rupatadine 40mg - Rupatadine 20mg - Placebo<br> \| Drug: Rupatadine<br>* Rupatadine in Tab. 10mg: 4 Tab. once daily during 7 days, then 14 days washout period; Rupatadine in Tab 10mg: 4 Tab.(2 Tab. of Rupatadine + 2 Tab. of Placebo) once daily during 7 days, then 14 days washout period; Placebo 4 Tab once daily during 7 days<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Critical stimulation time threshold(CSTT) after challenge with cold \| Critical stimulation time threshold (CSTT) determines the shortest stimulation time sufficient for inducing a wheal-and-flare reaction \| Visit 1(day -14 Screening), Visit 2 (Randomization; day 0), Visit 3(Last day of treatment period 1; day 7), Visit 4(Last day of treatment period 2; day 28), Visit 5(Last day of treatment period 3; day 49) \| \| Critical temperature threshold (CTT)after challenge with cold \| Critical temperature threshold (CTT) determines the highest temperature sufficient for inducing a wheal-and-flare reaction \| Visit 1(day -14 Screening), Visit 2 (Randomization; day 0), Visit 3(Last day of treatment period 1; day 7), Visit 4(Last day of treatment period 2; day 28), Visit 5(Last day of treatment period 3; day 49) \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Mast cell mediator release \| \| Visit 3(Last day of treatment period 1; day 7), Visit 4(Last day of treatment period 2; day 28), Visit 5(Last day of treatment period 3; day 49) \| \| Safety and tolerability following administration of Rupatadine to patients with cold contact urticaria \| Safety and tolerability: This includes physical examination, routine safety laboratory assessments, clinical observation, vital sings and adverse event reporting \| up to 9 weeks \|
NCT02287545	Biomechanical Changes After Trabeculectomy	Corneal biomechanics are studied in glaucoma patients prior and at least 6 month after trabeculectomy.	Prior to trabeculectomy corneal biomechanics are measured with the Ocular Response Analyzer (ORA, Reichert) and the Corvis st (Oculus). Both instruments work with an air-puff which deforms the cornea. Intraocular pressure is measured like in non-contact air-puff tonometry. The ORA also measures corneal hysteresis (CH) and the corneal resistance factor (CRF) which are qualitative measures of corneal biomechanics. The Corvis is a high-speed Scheimpflug-camera (4330 frames/sec) that records the quantitative movements of the cornea. At least 6 month after uncomplicated trabeculectomy the measurements are repeated.	Corneal Biomechanical Changes Following Trabeculectomy	Glaucoma, Primary	* Procedure: trabeculectomy	Inclusion Criteria:~Glaucoma patients in need of further IOP-reduction despite maximally tolerated therapy and assigned for trabeculectomy. Minimum of 18 years.~Exclusion Criteria:~Corneal pathologies.	18 Years	null	All	No		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Corneal biomechanical changes following trabeculectomy \| Evaluation of biomechanical properties of the cornea before and after trabeculectomy to evaluate whether intraocular pressure is accurately measured after trabeculectomy. Corneal hysteresis and corneal resistance factor as measured with the Ocular Response Analyzer and the corneal deformation response to an air-puff as measured with an ultra-high-speed Scheimpflug camera are assessed. \| 2-3 years \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Intraocular pressure after trabeculectomy \| Intraocular pressure is measured with 3 different devices (Goldmann applanation tonometry, Ocular Response Analyzer, Corvis st) prior and at least 6 month after trabeculectomy. \| 2-3 years \|	trabeculectomy, open angle glaucoma, corneal biomechanics	Glaucoma, Ocular Hypertension, Eye Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Glaucoma, primary<br>Glaucoma patients undergoing trabeculectomy \| Procedure: trabeculectomy<br>* Standard trabeculectomy with the use of antimetabolites (mitomycin C) for glaucoma patients with insufficient intraocular pressure (IOP) control taking maximally tolerated IOP-reducing medication, visual field progression despite maximally tolerated IOP-reducing medication, adverse events because of maximally tolerated IOP-reducing medication or nono.compliance.<br>* Other names: filtering glaucoma surgery;\|	Biomechanical Changes After Trabeculectomy Study Overview ================= Brief Summary ----------------- Corneal biomechanics are studied in glaucoma patients prior and at least 6 month after trabeculectomy. Detailed Description ----------------- Prior to trabeculectomy corneal biomechanics are measured with the Ocular Response Analyzer (ORA, Reichert) and the Corvis st (Oculus). Both instruments work with an air-puff which deforms the cornea. Intraocular pressure is measured like in non-contact air-puff tonometry. The ORA also measures corneal hysteresis (CH) and the corneal resistance factor (CRF) which are qualitative measures of corneal biomechanics. The Corvis is a high-speed Scheimpflug-camera (4330 frames/sec) that records the quantitative movements of the cornea. At least 6 month after uncomplicated trabeculectomy the measurements are repeated. Official Title ----------------- Corneal Biomechanical Changes Following Trabeculectomy Conditions ----------------- Glaucoma, Primary Intervention / Treatment ----------------- * Procedure: trabeculectomy Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Glaucoma patients in need of further IOP-reduction despite maximally tolerated therapy and assigned for trabeculectomy. Minimum of 18 years. Exclusion Criteria: Corneal pathologies. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Glaucoma, primary<br>Glaucoma patients undergoing trabeculectomy \| Procedure: trabeculectomy<br>* Standard trabeculectomy with the use of antimetabolites (mitomycin C) for glaucoma patients with insufficient intraocular pressure (IOP) control taking maximally tolerated IOP-reducing medication, visual field progression despite maximally tolerated IOP-reducing medication, adverse events because of maximally tolerated IOP-reducing medication or nono.compliance.<br>* Other names: filtering glaucoma surgery;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Corneal biomechanical changes following trabeculectomy \| Evaluation of biomechanical properties of the cornea before and after trabeculectomy to evaluate whether intraocular pressure is accurately measured after trabeculectomy. Corneal hysteresis and corneal resistance factor as measured with the Ocular Response Analyzer and the corneal deformation response to an air-puff as measured with an ultra-high-speed Scheimpflug camera are assessed. \| 2-3 years \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Intraocular pressure after trabeculectomy \| Intraocular pressure is measured with 3 different devices (Goldmann applanation tonometry, Ocular Response Analyzer, Corvis st) prior and at least 6 month after trabeculectomy. \| 2-3 years \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- trabeculectomy, open angle glaucoma, corneal biomechanics
NCT01651702	Comparison of Carto Versus Ensite 3D Electroanatomical Mapping Systems for Arrhythmias Ablations	Three dimensional anatomical mapping is an established method facilitating ablation of cardiac arrhythmias. The most commonly used systems are CARTO® System (Biosense Webster, Inc., Diamond Bar, CA, USA) and EnSite NavX™ (St. Jude Medical, Inc., St. Paul, MN, USA). These two systems has been compared in only a few studies. Recent technical advances resulted in the development of new versions of both systems. To the best of the investigators knowledge no studies have been performed for direct comparison of the newer versions of these two systems. The aim of the study to compare two systems for the use in the ablation of complex arrhythmias.	Background:~Three dimensional anatomical mapping is an established method facilitating ablation of cardiac arrhythmias. It is nowadays an excepted method especially for complex arrhythmias such as atrial fibrillation and ventricular tachycardia.~The most commonly used systems are CARTO® System (Biosense Webster, Inc., Diamond Bar, CA, USA) and EnSite NavX™ (St. Jude Medical, Inc., St. Paul, MN, USA). These mapping systems have helped to decrease procedural complexity, procedure time, and improve safety. The EnSite NavX system uses impedance measurements between the individual catheter electrodes and the patches placed on the patient's chest and abdomen. The CARTO system utilizes magnetic location technology to provide accurate visualization of the magnet sensor-equipped catheter tip.~These two systems has been compared in only a few studies. Different results have been found in simple ablations versus more complex ablation of atrial fibrillation. Recent technical advances resulted in the development of new versions of both systems. Carto Express version allows quicker mapping and reconstruction of heart cavities and great vessels geometry as compared to previous versions of Carto XP. EnSite Velocity system incorporates more precise catheter visualization, and allows quicker mapping as compared to previous version of EnSite.~To the best of the investigators knowledge no studies have been performed for direct comparison of the newer versions of these two systems.~Study design Prospective single-center non-randomized open label comparison study. Primary objective Comparison of Carto Express system vs. EnSite Velocity system for ablation of complex arrhythmias.~End points:~Procedure duration.~Fluoroscopy time~Procedure success -will be measured in terms of the 1-year recurrent arrhythmia rate Study population Patients planned for ablation of complex arrhythmia.	Comparative Study of Two 3D Electroanatomical Mapping Systems for Ablations of Different Complex Arrhythmias	Arrhythmias	* Device: Carto * Device: Ensite	Inclusion Criteria:~Age 18- 80.~Ability to sign informed consent.~History of one of the following arrhythmias requiring the use of 3D electroanatomical mapping:~Symptomatic paroxysmal or persistent atrial fibrillation with failed treatment of at least two anti-arrhythmic drugs.~Ischemic ventricular tachycardia necessitating ablation as per decision of electrophysiologist.~Symptomatic atrial tachycardia after failed medical treatment.~Symptomatic idiopathic ventricular tachycardia.~Exclusion Criteria:~Unstable patients not allowing performing procedure more than 2 hours~Patients planned for one of the two systems compared for whatever reason Ex. procedure planned with NAVX system Array Balloon).	18 Years	80 Years	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Procedure duration \| Average procedure duration (needle to catheters withdrawal) \| Procedure duration - average expected 2.5 hours \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Fluoroscopy time \| Average fluro time in each of groups. \| Procedures will be evaluated for the fluoro time, expected average 30 min \| \| Procedure success \| Recurrency of the arrhythmia assessed by blinded electrophysiologist \| Patients will be followed for one year for recurrency of arrhythmia \|	Arrhythmia, Electroanatomical mapping	Arrhythmias, Cardiac, Heart Diseases, Cardiovascular Diseases, Pathologic Processes	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Carto<br>Patients in whom Carto system will be used \| Device: Carto<br>* Group of patients where Carto Express system will be used for electroanatomical mapping.<br>\| \| Active Comparator: Ensite<br>Patients in whom Ensite system will be used \| Device: Ensite<br>* Group of patients where Ensite Velocity system will be used for electroanatomical mapping.<br>\|	Comparison of Carto Versus Ensite 3D Electroanatomical Mapping Systems for Arrhythmias Ablations Study Overview ================= Brief Summary ----------------- Three dimensional anatomical mapping is an established method facilitating ablation of cardiac arrhythmias. The most commonly used systems are CARTO® System (Biosense Webster, Inc., Diamond Bar, CA, USA) and EnSite NavX™ (St. Jude Medical, Inc., St. Paul, MN, USA). These two systems has been compared in only a few studies. Recent technical advances resulted in the development of new versions of both systems. To the best of the investigators knowledge no studies have been performed for direct comparison of the newer versions of these two systems. The aim of the study to compare two systems for the use in the ablation of complex arrhythmias. Detailed Description ----------------- Background: Three dimensional anatomical mapping is an established method facilitating ablation of cardiac arrhythmias. It is nowadays an excepted method especially for complex arrhythmias such as atrial fibrillation and ventricular tachycardia. The most commonly used systems are CARTO® System (Biosense Webster, Inc., Diamond Bar, CA, USA) and EnSite NavX™ (St. Jude Medical, Inc., St. Paul, MN, USA). These mapping systems have helped to decrease procedural complexity, procedure time, and improve safety. The EnSite NavX system uses impedance measurements between the individual catheter electrodes and the patches placed on the patient's chest and abdomen. The CARTO system utilizes magnetic location technology to provide accurate visualization of the magnet sensor-equipped catheter tip. These two systems has been compared in only a few studies. Different results have been found in simple ablations versus more complex ablation of atrial fibrillation. Recent technical advances resulted in the development of new versions of both systems. Carto Express version allows quicker mapping and reconstruction of heart cavities and great vessels geometry as compared to previous versions of Carto XP. EnSite Velocity system incorporates more precise catheter visualization, and allows quicker mapping as compared to previous version of EnSite. To the best of the investigators knowledge no studies have been performed for direct comparison of the newer versions of these two systems. Study design Prospective single-center non-randomized open label comparison study. Primary objective Comparison of Carto Express system vs. EnSite Velocity system for ablation of complex arrhythmias. End points: Procedure duration. Fluoroscopy time Procedure success -will be measured in terms of the 1-year recurrent arrhythmia rate Study population Patients planned for ablation of complex arrhythmia. Official Title ----------------- Comparative Study of Two 3D Electroanatomical Mapping Systems for Ablations of Different Complex Arrhythmias Conditions ----------------- Arrhythmias Intervention / Treatment ----------------- * Device: Carto * Device: Ensite Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age 18- 80. Ability to sign informed consent. History of one of the following arrhythmias requiring the use of 3D electroanatomical mapping: Symptomatic paroxysmal or persistent atrial fibrillation with failed treatment of at least two anti-arrhythmic drugs. Ischemic ventricular tachycardia necessitating ablation as per decision of electrophysiologist. Symptomatic atrial tachycardia after failed medical treatment. Symptomatic idiopathic ventricular tachycardia. Exclusion Criteria: Unstable patients not allowing performing procedure more than 2 hours Patients planned for one of the two systems compared for whatever reason Ex. procedure planned with NAVX system Array Balloon). Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Carto<br>Patients in whom Carto system will be used \| Device: Carto<br>* Group of patients where Carto Express system will be used for electroanatomical mapping.<br>\| \| Active Comparator: Ensite<br>Patients in whom Ensite system will be used \| Device: Ensite<br>* Group of patients where Ensite Velocity system will be used for electroanatomical mapping.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Procedure duration \| Average procedure duration (needle to catheters withdrawal) \| Procedure duration - average expected 2.5 hours \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Fluoroscopy time \| Average fluro time in each of groups. \| Procedures will be evaluated for the fluoro time, expected average 30 min \| \| Procedure success \| Recurrency of the arrhythmia assessed by blinded electrophysiologist \| Patients will be followed for one year for recurrency of arrhythmia \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Arrhythmia, Electroanatomical mapping
NCT04176549	Assessment of Biomarkers in Ectopic Pregnancy	To further develop a patient care pathway (incorporating a statistical model which uses the values of biomarkers) in routine clinical practice that will aid the diagnosis and management of women with an ectopic pregnancy.	Purpose and design-There is a need for the patient care pathway to evolve in order to aid and improve the diagnosis and management of women with a pregnancy of unknown location (PUL) and ectopic pregnancy (EP). There is potential for this to be achieved by the incorporation of a statistical model that uses one or more novel markers identified by this study. These markers may replace or add to the effectiveness of markers used in the current statistical model.~Recruitment-200 patients. Inclusion: Patients attending the Early Pregnancy Unit (EPU) in the first trimester with a PUL or ectopic pregnancy on trans-vaginal ultrasound scan between the ages of 18-50 years. Exclusion: Patients diagnosed with cancer, presence of acute medical condition, patients aged less than 18 years, patients who cannot give fully informed study consent.~Consent - Posters will advertise the study. Patients in EPU will be invited to the study by a member of the clinical care team. Written consent will be required for all aspects of the study other than for 3-dimensional scanning of PUL and EP patients, where verbal consent will be obtained. Patients will be given at least 24 hours to consider whether they wish to participate.~Confidentiality - The Chief Investigator will preserve the confidentiality of participants taking part in the study and is registered under the Data Protection Act. Patient consent forms will be stored securely within the study file. All patient identifiable information, where required, will be stored electronically on National Health Service (NHS) approved computers, accessible only by personnel involved in the study via password.~Conflict of interest - None involved in the study have a conflict of interest.~Dissemination of results - No patient identifiable information will be included in the research report or publication. Anonymised results will be disseminated to scientific community by means of publication in peer-reviewed literature and presented at national and international meetings.	The Assessment of Biomarkers in Ectopic Pregnancy	Ectopic Pregnancy	* Other: Management of Ectopic Pregnancy * Other: Management of termination of pregnancy * Other: Elective management of gynaecology patients	Inclusion Criteria:~Patients attending the Early Pregnancy Unit (EPU) in the first trimester (up to 14 weeks gestation) with a PUL or ectopic pregnancy on trans-vaginal ultrasound scan between the ages of 18 and 50 years.~Patients attending the gynaecology unit for a surgical termination of pregnancy or for a salpingo-oophorectomy.~Exclusion Criteria:~Patients diagnosed with cancer, presence of an acute medical condition, patients aged less than 18 years, patients who cannot give fully informed study consent (language or learning impairment), presence of a viable intrauterine pregnancy and presence of miscarriage.~Exclusion to fallopian tube samples - presence of any ectopic pregnancy that does not require operative salpingectomy.~Exclusion to peritoneal washings - presence of any ectopic pregnancy that does not require access to the peritoneal cavity as part of management.~Exclusion to trophoblast tissue sampling - presence of an ectopic pregnancy that does not require surgical removal.	18 Years	50 Years	Female	Accepts Healthy Volunteers		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Novel biomarkers for Ectopic Pregnancy prediction and diagnosis \| Identification of microRNA and microbiome markers identified in blood, urine, swabs, fallopian tubes, peritoneal washings and trophoblastic tissue that have predictive value in identifying ectopic pregnancies as well as high and low risk pregnancy of unknown location. microRNA will be assessed using blood and trophoblast using cell free profiling assays and quantitative reverse transcription polymerase chain reaction and microbiome will be assessed using Illumina microbiome genomic sequencing. \| 3 years \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| microRNA as a biomarker \| Identification of novel microRNA markers from blood and trophoblast tissue samples associated with ectopic pregnancy and high-risk pregnancy of unknown location. MicroRNA will be assessed using blood and trophoblast using cell free profiling assays and quantitative reverse transcription polymerase chain reaction. \| 3 years \| \| Microbiome as a biomarker \| Identification of novel microbiome markers from blood and trophoblast tissue samples associated with ectopic pregnancy and high-risk pregnancy of unknown location. Microbiome will be assessed using Illumina microbiome genomic sequencing. \| 3 years \|	Ectopic Pregnancy, Biomarker	Pregnancy, Ectopic, Cardiac Complexes, Premature, Arrhythmias, Cardiac, Heart Diseases, Cardiovascular Diseases, Cardiac Conduction System Disease, Pathologic Processes, Pregnancy Complications, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Ectopic Pregnancy<br>Patients diagnosed with ectopic pregnancy Samples collected: Plasma, Serum, Urine, Oral swab, Vaginal Swab If surgery required for tubal ectopic: Fallopian tube, peritoneal washing, trophoblast \| Other: Management of Ectopic Pregnancy<br>* Expectant, Medical or Surgical management of Ectopic Pregnancy<br>\| \| Surgical termination of pregnancy<br>Patients undergoing elective surgical termination of pregnancy Samples collected: Plasma, Serum, Urine, Oral swab Vaginal swab, Trophoblast \| Other: Management of termination of pregnancy<br>* Surgical termination of pregnancy<br>\| \| Elective hysterectomy and salpingo-oophorectomy<br>Patients undergoing elective hysterectomy and salpingo-oophorectomy Samples collected: Fallopian tube, peritoneal washing \| Other: Elective management of gynaecology patients<br>* Elective hysterectomy and salpingo-oophorectomy<br>\|	Assessment of Biomarkers in Ectopic Pregnancy Study Overview ================= Brief Summary ----------------- To further develop a patient care pathway (incorporating a statistical model which uses the values of biomarkers) in routine clinical practice that will aid the diagnosis and management of women with an ectopic pregnancy. Detailed Description ----------------- Purpose and design-There is a need for the patient care pathway to evolve in order to aid and improve the diagnosis and management of women with a pregnancy of unknown location (PUL) and ectopic pregnancy (EP). There is potential for this to be achieved by the incorporation of a statistical model that uses one or more novel markers identified by this study. These markers may replace or add to the effectiveness of markers used in the current statistical model. Recruitment-200 patients. Inclusion: Patients attending the Early Pregnancy Unit (EPU) in the first trimester with a PUL or ectopic pregnancy on trans-vaginal ultrasound scan between the ages of 18-50 years. Exclusion: Patients diagnosed with cancer, presence of acute medical condition, patients aged less than 18 years, patients who cannot give fully informed study consent. Consent - Posters will advertise the study. Patients in EPU will be invited to the study by a member of the clinical care team. Written consent will be required for all aspects of the study other than for 3-dimensional scanning of PUL and EP patients, where verbal consent will be obtained. Patients will be given at least 24 hours to consider whether they wish to participate. Confidentiality - The Chief Investigator will preserve the confidentiality of participants taking part in the study and is registered under the Data Protection Act. Patient consent forms will be stored securely within the study file. All patient identifiable information, where required, will be stored electronically on National Health Service (NHS) approved computers, accessible only by personnel involved in the study via password. Conflict of interest - None involved in the study have a conflict of interest. Dissemination of results - No patient identifiable information will be included in the research report or publication. Anonymised results will be disseminated to scientific community by means of publication in peer-reviewed literature and presented at national and international meetings. Official Title ----------------- The Assessment of Biomarkers in Ectopic Pregnancy Conditions ----------------- Ectopic Pregnancy Intervention / Treatment ----------------- * Other: Management of Ectopic Pregnancy * Other: Management of termination of pregnancy * Other: Elective management of gynaecology patients Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients attending the Early Pregnancy Unit (EPU) in the first trimester (up to 14 weeks gestation) with a PUL or ectopic pregnancy on trans-vaginal ultrasound scan between the ages of 18 and 50 years. Patients attending the gynaecology unit for a surgical termination of pregnancy or for a salpingo-oophorectomy. Exclusion Criteria: Patients diagnosed with cancer, presence of an acute medical condition, patients aged less than 18 years, patients who cannot give fully informed study consent (language or learning impairment), presence of a viable intrauterine pregnancy and presence of miscarriage. Exclusion to fallopian tube samples - presence of any ectopic pregnancy that does not require operative salpingectomy. Exclusion to peritoneal washings - presence of any ectopic pregnancy that does not require access to the peritoneal cavity as part of management. Exclusion to trophoblast tissue sampling - presence of an ectopic pregnancy that does not require surgical removal. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 50 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Ectopic Pregnancy<br>Patients diagnosed with ectopic pregnancy Samples collected: Plasma, Serum, Urine, Oral swab, Vaginal Swab If surgery required for tubal ectopic: Fallopian tube, peritoneal washing, trophoblast \| Other: Management of Ectopic Pregnancy<br>* Expectant, Medical or Surgical management of Ectopic Pregnancy<br>\| \| Surgical termination of pregnancy<br>Patients undergoing elective surgical termination of pregnancy Samples collected: Plasma, Serum, Urine, Oral swab Vaginal swab, Trophoblast \| Other: Management of termination of pregnancy<br>* Surgical termination of pregnancy<br>\| \| Elective hysterectomy and salpingo-oophorectomy<br>Patients undergoing elective hysterectomy and salpingo-oophorectomy Samples collected: Fallopian tube, peritoneal washing \| Other: Elective management of gynaecology patients<br>* Elective hysterectomy and salpingo-oophorectomy<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Novel biomarkers for Ectopic Pregnancy prediction and diagnosis \| Identification of microRNA and microbiome markers identified in blood, urine, swabs, fallopian tubes, peritoneal washings and trophoblastic tissue that have predictive value in identifying ectopic pregnancies as well as high and low risk pregnancy of unknown location. microRNA will be assessed using blood and trophoblast using cell free profiling assays and quantitative reverse transcription polymerase chain reaction and microbiome will be assessed using Illumina microbiome genomic sequencing. \| 3 years \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| microRNA as a biomarker \| Identification of novel microRNA markers from blood and trophoblast tissue samples associated with ectopic pregnancy and high-risk pregnancy of unknown location. MicroRNA will be assessed using blood and trophoblast using cell free profiling assays and quantitative reverse transcription polymerase chain reaction. \| 3 years \| \| Microbiome as a biomarker \| Identification of novel microbiome markers from blood and trophoblast tissue samples associated with ectopic pregnancy and high-risk pregnancy of unknown location. Microbiome will be assessed using Illumina microbiome genomic sequencing. \| 3 years \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Ectopic Pregnancy, Biomarker
NCT00001161	Abnormalities of the Eye's Anterior Chamber, Iris, Cornea and Lens	This study will investigate congenital or developmental eye abnormalities that affect the iris, cornea and lens, and are usually accompanied by elevated pressure within the eye. These disorders can cause vision loss, and the increased eye pressure can lead to glaucoma, a condition that may also cause loss of eyesight.~Patients with eye anterior chamber eye disease, such as Axenfeld's syndrome, Rieger's anomaly, Peter's anomaly, iridocorneal endothelial syndrome, megalocornea, ocular hypertension, and others, are eligible for this study. Participants will have a medical examination, family history, and comprehensive eye examination. Tests and procedures may include photographs of the cornea, iris, and the structure through which fluid that normally circulates behind the cornea drains out of the eye. Some patients may undergo indentation tonography to measure how easily this fluid drains. In this procedure, the patient lies on an examination table and both eyes are numbed with eye drops. A small instrument (tonometer) is placed on the surface of one eye, and with the other eye, the patient looks at an overhead light. Other tests may include photographs of the back of the eye and ultrasound imaging of the structures of the eye. A blood sample may be drawn to study the genetic disorder responsible for the disease. Patients will have follow-up examinations every 6 months for the duration of the study.~Medical or surgical therapy will be recommended, as appropriate, for patients who develop elevated eye pressure or vision loss.	This study will concentrate on abnormalities of the anterior chamber with or without elevated intraocular pressure. The purpose of the study will be to determine if there is a common pathogenesis shared by these conditions. A natural history study of 40 individuals with these diseases will utilize clinical measurements and photographs for documentation of this hypothesis. In addition, surgical specimens, when available, will be studied.	Anomalies of the Anterior Chamber, Angle, Iris, Cornea and Lens With or Without Glaucoma or Ocular Hypertension	Aniridia, Eye Abnormality, Ocular Hypertension, Open Angle Glaucoma		The eye conditions to be studied include Axenfeld's syndrome, Rieger's anomaly, Peter's anomaly, (all with or without glaucoma), Iridocorneal Endothelial syndrome, Aniridia, Pigment Dispersion syndrome, Megalocornea and other conditions with clinical abnormalities of the anterior chamber.~Patients will not be included in the study if they do not fit the morphologic characteristics of the disease in question or if the patient's general medical condition or other related factors make it impossible for him or her to continue participation in the study.	null	null	All	No		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \|		Mesothelium, Glaucoma, Irido Corneal Angle, Congenital Anomalies, Neural Crest, Increased Intraocular Pressure, Axenfeld's Syndrome, Rieger's Anomaly, Peter's Anomaly, Iridocorneal Endothelial Syndrome, Aniridia, Pigment Dispersion Syndrome, Megalocornea	Glaucoma, Glaucoma, Open-Angle, Ocular Hypertension, Aniridia, Eye Abnormalities, Hypertension, Congenital Abnormalities, Vascular Diseases, Cardiovascular Diseases, Eye Diseases, Eye Diseases, Hereditary, Iris Diseases, Uveal Diseases, Genetic Diseases, Inborn		Abnormalities of the Eye's Anterior Chamber, Iris, Cornea and Lens Study Overview ================= Brief Summary ----------------- This study will investigate congenital or developmental eye abnormalities that affect the iris, cornea and lens, and are usually accompanied by elevated pressure within the eye. These disorders can cause vision loss, and the increased eye pressure can lead to glaucoma, a condition that may also cause loss of eyesight. Patients with eye anterior chamber eye disease, such as Axenfeld's syndrome, Rieger's anomaly, Peter's anomaly, iridocorneal endothelial syndrome, megalocornea, ocular hypertension, and others, are eligible for this study. Participants will have a medical examination, family history, and comprehensive eye examination. Tests and procedures may include photographs of the cornea, iris, and the structure through which fluid that normally circulates behind the cornea drains out of the eye. Some patients may undergo indentation tonography to measure how easily this fluid drains. In this procedure, the patient lies on an examination table and both eyes are numbed with eye drops. A small instrument (tonometer) is placed on the surface of one eye, and with the other eye, the patient looks at an overhead light. Other tests may include photographs of the back of the eye and ultrasound imaging of the structures of the eye. A blood sample may be drawn to study the genetic disorder responsible for the disease. Patients will have follow-up examinations every 6 months for the duration of the study. Medical or surgical therapy will be recommended, as appropriate, for patients who develop elevated eye pressure or vision loss. Detailed Description ----------------- This study will concentrate on abnormalities of the anterior chamber with or without elevated intraocular pressure. The purpose of the study will be to determine if there is a common pathogenesis shared by these conditions. A natural history study of 40 individuals with these diseases will utilize clinical measurements and photographs for documentation of this hypothesis. In addition, surgical specimens, when available, will be studied. Official Title ----------------- Anomalies of the Anterior Chamber, Angle, Iris, Cornea and Lens With or Without Glaucoma or Ocular Hypertension Conditions ----------------- Aniridia, Eye Abnormality, Ocular Hypertension, Open Angle Glaucoma Participation Criteria ================= Eligibility Criteria ----------------- The eye conditions to be studied include Axenfeld's syndrome, Rieger's anomaly, Peter's anomaly, (all with or without glaucoma), Iridocorneal Endothelial syndrome, Aniridia, Pigment Dispersion syndrome, Megalocornea and other conditions with clinical abnormalities of the anterior chamber. Patients will not be included in the study if they do not fit the morphologic characteristics of the disease in question or if the patient's general medical condition or other related factors make it impossible for him or her to continue participation in the study. Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Mesothelium, Glaucoma, Irido Corneal Angle, Congenital Anomalies, Neural Crest, Increased Intraocular Pressure, Axenfeld's Syndrome, Rieger's Anomaly, Peter's Anomaly, Iridocorneal Endothelial Syndrome, Aniridia, Pigment Dispersion Syndrome, Megalocornea
NCT05442814	Anterior and Posterior Approaches of Suprascapular Nerve Block	Suprascapular nerve is a mixed motor and sensory peripheral nerve arising from the superior trunk of brachial plexus.The suprascapular nerve runs through the posterior triangle of the neck, anterior of the trapezius muscle and dorsal of the omohyoid muscle, in direction of the scapula. Suprascapular nerve block is performed by anterior and posterior approach. Posterior approach of the suprascapular nerve block has been shown for many years to provide effective analgesia in the shoulder region for the chronic and acute pain. There are studies showing that suprascapular block with anterior approach provides effective analgesia in shoulder arthroscopy.~The aim of our study was to compare anterior and posterior approaches of suprascapular nerve block in terms of analgesic efficacy and patient safety.	This study is a prospective randomized clinical trial will be conducted between March 2022 and March 2023.Participant will divide into two groups as participant who underwent suprascapular nerve block with the anterior approach and participant who underwent suprascapular nerve block with the posterior approach. Bupivacaine 5 ml %0.5 will be injected both group. Diaphragmatic thickness fraction will be evaluated with ultrasound left and right 7.-8. subcostal anterior axillary border with the participant with the semi-sitting position. Diaphragmatic thickness fraction will measure before the block and after 30 minutes the surgery. Participants will administered intravenous morphine patient controlled analgesia for 24 hours stay. The amount of opioid analgesics given in both groups will be determined (in mg). Postoperative 4th, 6th, 12th, 24th hour Visual Analogue Scale scores of the participants and opioid consumptions until that hours will be evaluated. An addition participant will be determined according to the surgery.	Comparison of Anterior and Posterior Approaches of Suprascapular Nerve Block in Arthroscopic Shoulder Surgery	Shoulder Pain, Postoperative Pain, Diaphragmatic Paralysis, Subomohyoid Suprascapular Nerve Block, Anterior Suprascapular Nerve Block, Suprascapular Nerve Block	* Procedure: Posterior suprascapular block * Procedure: Anterior suprascapular block	Inclusion Criteria:~Patient who accepts to study protocol~Scheduled for shoulder surgery~Between the ages of 18 and 80~Exclusion Criteria:~Patients with coagulopathy~Patients with a history of local anesthetic drug allergy and toxicity~Patients with advanced organ failure~Patients with mental retardation~Patients with infection present at the injection site~Patients with diaphragm paralysis~Pregnant patients	18 Years	80 Years	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: participant with anterior suprascapular block ,group 1 participant with posterior suprascapular block, group 2 Masking: Single	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Postoperative pain \| Visual analog scale (1-10): 1= no pain, 10= the worst pain ever feel. \| The first postoperative 30 minutes \| \| Pain rating \| Measured by VAS ( Visual analog scale). \| Postoperative 4 hours \| \| Pain Rating \| Measured by VAS ( Visual analog scale). \| Postoperative 6 hours \| \| Pain Rating \| Measured by VAS ( Visual analog scale). \| Postoperative 12 hours \| \| Pain Rating \| Measured by VAS ( Visual analog scale). \| Postoperative 24 hours \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Diaphragmatic movements \| Ratio of diaphragm thickness in end-inspiration and end-expiration measured by ultrasonography \| Baseline (Before the block performed) and 30 minutes after the end of surgery \| \| Postoperative opioid analgesic consumption (morphine) \| milligram \| postoperative 4 hours \| \| Postoperative opioid analgesic consumption (morphine) \| milligram \| postoperative 6 hours \| \| Postoperative opioid analgesic consumption (morphine) \| milligram \| postoperative 12 hours \| \| Postoperative opioid analgesic consumption (morphine) \| milligram \| postoperative 24 hours \|	Shoulder pain, Nerve Block, Diaphragmatic paralysis, Postoperative pain, Suprascapular block, Subomohyoid suprascapular block, Posterior Suprascapular block, Anterior Suprascapular block	Pain, Shoulder Pain, Respiratory Paralysis, Paralysis, Pain, Postoperative, Postoperative Complications, Pathologic Processes, Neurologic Manifestations, Arthralgia, Joint Diseases, Musculoskeletal Diseases, Nervous System Diseases, Respiratory Insufficiency, Respiration Disorders, Respiratory Tract Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Posterior suprascapular block<br>Suprascapular block performed by posterior approach \| Procedure: Posterior suprascapular block<br>* Diaphragmatic thickness fraction will be evaluated in the participant underwent suprascapular block performed by posterior approach<br>\| \| Active Comparator: Anterior suprascapular block<br>Suprascapular block performed by anterior approach \| Procedure: Anterior suprascapular block<br>* Diaphragmatic thickness fraction will be evaluated in the participant underwent suprascapular block performed by anterior approach<br>\|	Anterior and Posterior Approaches of Suprascapular Nerve Block Study Overview ================= Brief Summary ----------------- Suprascapular nerve is a mixed motor and sensory peripheral nerve arising from the superior trunk of brachial plexus.The suprascapular nerve runs through the posterior triangle of the neck, anterior of the trapezius muscle and dorsal of the omohyoid muscle, in direction of the scapula. Suprascapular nerve block is performed by anterior and posterior approach. Posterior approach of the suprascapular nerve block has been shown for many years to provide effective analgesia in the shoulder region for the chronic and acute pain. There are studies showing that suprascapular block with anterior approach provides effective analgesia in shoulder arthroscopy. The aim of our study was to compare anterior and posterior approaches of suprascapular nerve block in terms of analgesic efficacy and patient safety. Detailed Description ----------------- This study is a prospective randomized clinical trial will be conducted between March 2022 and March 2023.Participant will divide into two groups as participant who underwent suprascapular nerve block with the anterior approach and participant who underwent suprascapular nerve block with the posterior approach. Bupivacaine 5 ml %0.5 will be injected both group. Diaphragmatic thickness fraction will be evaluated with ultrasound left and right 7.-8. subcostal anterior axillary border with the participant with the semi-sitting position. Diaphragmatic thickness fraction will measure before the block and after 30 minutes the surgery. Participants will administered intravenous morphine patient controlled analgesia for 24 hours stay. The amount of opioid analgesics given in both groups will be determined (in mg). Postoperative 4th, 6th, 12th, 24th hour Visual Analogue Scale scores of the participants and opioid consumptions until that hours will be evaluated. An addition participant will be determined according to the surgery. Official Title ----------------- Comparison of Anterior and Posterior Approaches of Suprascapular Nerve Block in Arthroscopic Shoulder Surgery Conditions ----------------- Shoulder Pain, Postoperative Pain, Diaphragmatic Paralysis, Subomohyoid Suprascapular Nerve Block, Anterior Suprascapular Nerve Block, Suprascapular Nerve Block Intervention / Treatment ----------------- * Procedure: Posterior suprascapular block * Procedure: Anterior suprascapular block Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patient who accepts to study protocol Scheduled for shoulder surgery Between the ages of 18 and 80 Exclusion Criteria: Patients with coagulopathy Patients with a history of local anesthetic drug allergy and toxicity Patients with advanced organ failure Patients with mental retardation Patients with infection present at the injection site Patients with diaphragm paralysis Pregnant patients Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: participant with anterior suprascapular block ,group 1 participant with posterior suprascapular block, group 2 Masking: Single Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Posterior suprascapular block<br>Suprascapular block performed by posterior approach \| Procedure: Posterior suprascapular block<br>* Diaphragmatic thickness fraction will be evaluated in the participant underwent suprascapular block performed by posterior approach<br>\| \| Active Comparator: Anterior suprascapular block<br>Suprascapular block performed by anterior approach \| Procedure: Anterior suprascapular block<br>* Diaphragmatic thickness fraction will be evaluated in the participant underwent suprascapular block performed by anterior approach<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Postoperative pain \| Visual analog scale (1-10): 1= no pain, 10= the worst pain ever feel. \| The first postoperative 30 minutes \| \| Pain rating \| Measured by VAS ( Visual analog scale). \| Postoperative 4 hours \| \| Pain Rating \| Measured by VAS ( Visual analog scale). \| Postoperative 6 hours \| \| Pain Rating \| Measured by VAS ( Visual analog scale). \| Postoperative 12 hours \| \| Pain Rating \| Measured by VAS ( Visual analog scale). \| Postoperative 24 hours \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Diaphragmatic movements \| Ratio of diaphragm thickness in end-inspiration and end-expiration measured by ultrasonography \| Baseline (Before the block performed) and 30 minutes after the end of surgery \| \| Postoperative opioid analgesic consumption (morphine) \| milligram \| postoperative 4 hours \| \| Postoperative opioid analgesic consumption (morphine) \| milligram \| postoperative 6 hours \| \| Postoperative opioid analgesic consumption (morphine) \| milligram \| postoperative 12 hours \| \| Postoperative opioid analgesic consumption (morphine) \| milligram \| postoperative 24 hours \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Shoulder pain, Nerve Block, Diaphragmatic paralysis, Postoperative pain, Suprascapular block, Subomohyoid suprascapular block, Posterior Suprascapular block, Anterior Suprascapular block
NCT00163150	Vasomotor Reactivity In Cerebral Small Vessel Disease And New Approach To Treat Lacunar Stroke	The main purpose of this study is to evaluate the efficacy of atorvastatin treatment during 3 months (80mg/day) on cerebral vasoreactivity (CVR) in lacunar patients.		Lacunar-Brain Infarction Cerebral Hyperactivity And Atorvastatin Trial. A Placebo-Controlled Trial Of High-Dose Atorvastatin In Patients With Cerebral Small Vessel Disease.	Cerebrovascular Accident, Hypercholesterolemia	* Drug: Atorvastatin	Inclusion Criteria:~clinically defined lacunar syndrome 3 months before inclusion~small deep infarct on diffusion MRI (Diffusion Weighted Imaging)~no atherothrombotic, cardio-embolic, or other rarer cause.~Exclusion Criteria:~patients with past coronary event~contra-indication for assessment of vasomotor reactivity~patients being on statin therapy at the time of brain infarction~contra-indication for statin therapy~patient still under statin therapy	18 Years	null	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Evaluate the efficacy of atorvastatin treatment during 3 months (80mg/day) on cerebral vasoreactivity (CVR) in lacunar patients. CVR, humeral and carotid vasoreactivity will be measured in all patients at M0 and M3. \| \| \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Evaluate the efficacy of atorvastatin treatment during 3 months (80mg/day) on endothelium dependant and independent vasomotoricity of humeral and / or common carotid artery (according to validation study) in lacunar patients. \| \| \|		Atorvastatin, Anticholesteremic Agents, Hypolipidemic Agents, Antimetabolites, Molecular Mechanisms of Pharmacological Action, Lipid Regulating Agents, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Enzyme Inhibitors	\| Intervention/Treatment \| \| --- \| \|Drug: Atorvastatin\|nan\|	Vasomotor Reactivity In Cerebral Small Vessel Disease And New Approach To Treat Lacunar Stroke Study Overview ================= Brief Summary ----------------- The main purpose of this study is to evaluate the efficacy of atorvastatin treatment during 3 months (80mg/day) on cerebral vasoreactivity (CVR) in lacunar patients. Official Title ----------------- Lacunar-Brain Infarction Cerebral Hyperactivity And Atorvastatin Trial. A Placebo-Controlled Trial Of High-Dose Atorvastatin In Patients With Cerebral Small Vessel Disease. Conditions ----------------- Cerebrovascular Accident, Hypercholesterolemia Intervention / Treatment ----------------- * Drug: Atorvastatin Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: clinically defined lacunar syndrome 3 months before inclusion small deep infarct on diffusion MRI (Diffusion Weighted Imaging) no atherothrombotic, cardio-embolic, or other rarer cause. Exclusion Criteria: patients with past coronary event contra-indication for assessment of vasomotor reactivity patients being on statin therapy at the time of brain infarction contra-indication for statin therapy patient still under statin therapy Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions \| Intervention/Treatment \| \| --- \| \|Drug: Atorvastatin\|nan\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Evaluate the efficacy of atorvastatin treatment during 3 months (80mg/day) on cerebral vasoreactivity (CVR) in lacunar patients. CVR, humeral and carotid vasoreactivity will be measured in all patients at M0 and M3. \| \| \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Evaluate the efficacy of atorvastatin treatment during 3 months (80mg/day) on endothelium dependant and independent vasomotoricity of humeral and / or common carotid artery (according to validation study) in lacunar patients. \| \| \|
NCT02839590	Aqueous Dynamics and Glaucoma Surgeries	There are currently many surgical options for patients with glaucoma and ocular hypertension (OHT), including the Hydrus Microstent implant, HiFU (High intensity Focused ultrasound), STAR flo, Kahook Dual Blade, Diode laser, trabeculectomy and the Baerveldt implant, but little is known about how these different surgical techniques used to treat glaucoma affect the flow of fluid through and out of the eye (aqueous dynamics).	Trial objectives~Main outcome measures: The following aqueous dynamics parameters will be measured: IOP, aqueous flow rate, trabecular outflow facility and uveoscleral outflow. These parameters will be measured pre-treatment (up to 2 months before glaucoma surgery) and repeated 3 months and 12 months post-surgery. Measures will be taken from the operated eye and the contra lateral non-operated eye which will be used as the control.~Trial design~This is a prospective observational study with the contra lateral untreated eye being used as control. Baseline measures will be conducted at a routine clinic visit up to 2 months before glaucoma surgery after 4 weeks of treatment washout.~Post-treatment follow-up measurements of the main outcomes will be conducted 3 months and 12 months after surgery, again, after 4 weeks wash out. A number of additional eye tests will also be performed to collect data for the study at the pre-operative appointment when the baseline measurements are taken and at the post-operative follow-up appointments 3 months and 12 months after the surgery. Other data will be collected from eye tests that are routinely performed pre-operatively and at the post-operative follow-up appointments 1 day, 1 week, 1 month, 3 months, 6 months, and 12 months after their surgery.~Study participants will be recruited from patients attending the Ophthalmology Department Outpatients Clinic at St Thomas' Hospital, London, United Kingdom who have a diagnosis of glaucoma or OHT (ocular hypertension) requiring glaucoma drainage surgery. One hundred patients with glaucoma or OHT and where a clinical decision has been made that they need glaucoma surgery will be included in the study such that 100 eyes undergoing surgery will be included together with the contra-lateral untreated eyes that will be used as controls for comparison with the treated eyes.~Data will be collected for the study at the following routine appointments that patients undergoing glaucoma surgery are asked to attend: a pre-operative appointment, surgery, and follow-up assessments 1 day, 1 week, 1 month, 3 months, 6 months, and 12 months after surgery. Baseline measurements will be taken up to 2 months before glaucoma surgery.~At the baseline assessment demographic information will be collected~Details of participants' relevant past medical history will be collected at the baseline pre-operative assessment and at 12 months post-surgery.~All tests will be performed on both eyes as the contra-lateral non-operated eye will be used as control.~Aqueous parameters~• Aqueous flow rate: Participants will be asked to self-administer 3 to 6 drops (depending on their age) of fluorescein sodium 2% topically into both eyes at 5 minute intervals on the night before the fluorophotometric scans. Fluorophotometry will be performed using a scanning ocular fluorophotometer from 9:00 am -12:00 midday. Four sets of triplicate scans will be collected at 1 hour intervals to determine the aqueous flow rate (Ft). The 3 scans are done in quick succession, taking approximately 2 seconds in total to complete the set. Following each set of scans, IOP will be measured using pneumatonometry. and rebound tonometry. IOP will be recorded as the mean of a total of 12 measurements per eye: 3 measurements every hour alternating between eyes.~Patients who have had previous cataract surgeries or iridotomy/iridectomy will be excluded from this aspect of the measurements as fluorophotometry is inaccurate in these eyes.~Outflow facility: Tonographic outflow facility (C) measurement will be performed using an electronic Schiøtz tonographer (Model 720, Berkeley Bioengineering Inc, USA) between 9:00 am -12:00 midday. The facility of outflow will be measured from the rate of decay of IOP in the supine position during application of a recording Schiøtz tonometer over a period of 4 minutes with a standard 5.5 gram weight. The R values of the curve at every 30-second time point will be manually entered into the McLaren tonography computer program. The program fits a second-degree polynomial by least squares to the nine data points and determines the best-fit values for time 0 and time 4 minutes by extrapolation.~Intraocular pressure (IOP): Pneumatonometry and rebound tonometry will be used to measure IOP for patients undergoing fluorophotometry. The IOP measurements will be recorded at 1 hour intervals between the hours of 9:00 am -12:00 midday following each set of fluorophotometric scans.~Uveoscleral outflow: There are currently no reliable clinical methods of measuring uveoscleral outflow (Fu) and episcleral venous pressure (Pv). Fu will be therefore calculated using the Goldmann equation (see below) with an assumed episcleral venous pressure of 8-11 mmHg:~Ft = C(IOP - Pv) +Fu Where:~Ft = Measured aqueous flow rate Fu = Ft - C(IOP - Pv) Fu = Calculated uveoscleral outflow C = Tonographic outflow facility (value computed by the measurement device) IOP = Mean morning intraocular pressure as measured by pneumatonometry Pv = Episcleral venous pressure (8-11 mmHg, exact value calculated based on patient parameters)~Routine tests~At the pre-operative visit when baseline measurements are taken and at each routine post-operative follow-up visit (1 day, 1 week, 1 month, 3 months, 6 months, and 12 months after surgery) patients will undergo a clinical ophthalmological examination including the following tests and examinations:~Visual acuity measurement (Snellen and ETDRS charts will be used. Best Corrected Distance Visual Acuity (BCVA) and Non Corrected Distance Visual Acuity (NCVA) will be measured using ETDRS (early treatment diabetic retinopathy study) charts. Best Corrected Near Visual Acuity (BCVA) will be measured using a standard near vision chart).~Slit lamp examination~Visual fields~IOP (intraocular pressure) measurement (Goldmann applanation tonometry will be used to measure IOP, except when there is irregular corneal astigmatism or other corneal problems which may preclude accurate reading. The IOP measurement will be done after application of topical anesthetic (eye drop) with fluorescein)~Gonioscopy~Dilated fundoscopy~Anterior chamber depth and axial length~Central corneal thickness~Refraction (routine at baseline only)~Description of the surgical interventions~There are potentially four types of operation that patients may have as part of their glaucoma care in the department:~Trans-trabecular meshwork implants (Hydrus implant or iStent implant)~Ciliary Ablation Treatment (Diode laser or HiFu ultrasound treatment)~External (sub-conjunctival) Drainage Surgery (Trabeculectomy, Baerveldt implant or Ahmed Implant)~Suprachoroidal Shunt Surgery (STARflo)	The Effect of Glaucoma Surgery on Aqueous Dynamics in Patients With Glaucoma or Ocular Hypertension: An Observational Study	Glaucoma, Ocular Hypertension	* Device: HiFU * Device: Baerveldt implant * Device: Ahmed implant * Device: STARflo * Device: Hydrus Microstent implant * Device: iStent implant * Device: Kahook Dual Blade	Inclusion Criteria:~Males or females between the ages of 18 and 90 (inclusive).~Able to understand the study and give informed consent.~Willing, able and available to participate in all aspects of the study.~Diagnosis of glaucoma or OHT which requires glaucoma surgery. (Defined as primary or secondary glaucoma; all types of secondary glaucoma may be included. Glaucoma will be diagnosed based on abnormal visual field testing and corresponding disc changes once seen by a glaucoma specialist.)~Able to undergo accurate fluorophotometry and tonography.~Exclusion Criteria:~Mental impairment conflicting with informed consent or follow-up.~Allergy to fluorescein.~Current use of any investigational drug or device or current participation in an interventional clinical trial.~Patients who might not adequately understand written information given in English or verbal explanations in English will not be included as participants in the study must be able to understand English to complete some of the tests.~Any inclusion criteria not met	18 Years	90 Years	All	No		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change from baseline of Intraocular pressure at 12 months \| It would be measured by Goldmann tonometer, iCare and pneumatonometer. The unit of measurement for all of these devices is the same. It is mmHg \| baseline and 12 months \| \| Change from baseline of aqueous flow at 12 months \| This parameter is measured by fluorophotometry \| baseline and12 months \| \| Change from baseline of uveoscleral outflow at 12 months \| It would be calculated by Goldmann's equation \| baseline and 12 months \| \| Change from baseline of trabecular outflow facility at 12 months \| It will be measured by Electronic Schiotz tonography \| baseline and 12 months \|		Glaucoma, Ocular hypertension, Aqueous dynamics	Glaucoma, Ocular Hypertension, Hypertension, Vascular Diseases, Cardiovascular Diseases, Eye Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| HiFu (ultrasound)<br>Manufacturer Name Eyehope Principle intended use Surgical treatment of uncontrolled glaucoma and OHT The device is currently routinely used in the department for the treatment of uncontrolled glaucoma and OHT, and will be used in accordance with usual clinical practice. It is not anticipated that there will be any changes to the device or its usage during the course of the study. \| Device: HiFU<br>* Ciliary Ablation Treatment ( HiFu ultrasound treatment)<br>\| \| Baerveldt implant<br>Manufacturer Name Abbott Medical Optics Inc., Abbott Laboratories Inc., Abbott Park, Illinois, USA.~Principle intended use Surgical treatment of uncontrolled glaucoma and OHT~The device is currently routinely used in the department for the treatment of uncontrolled glaucoma and OHT, and will be used in accordance with usual clinical practice. It is not anticipated that there will be any changes to the device or its usage during the course of the study. \| Device: Baerveldt implant<br>* External (sub-conjunctival) Drainage Surgery (Baerveldt implant)<br>\| \| Ahmed Implant<br>Manufacturer Name New World Medical, Inc., 10763 Edison Court, Rancho Cucamonga, CA 91730, USA.~Principle intended use Surgical treatment of uncontrolled glaucoma and OHT~The device is currently routinely used in the department for the treatment of uncontrolled glaucoma and OHT, and will be used in accordance with usual clinical practice. It is not anticipated that there will be any changes to the device or its usage during the course of the study. \| Device: Ahmed implant<br>* External (sub-conjunctival) Drainage Surgery (Ahmed Implant)<br>\| \| STARflo<br>Manufacturer Name iSTAR Medical SA, Parc Créalys, Rue Phocas Lejeune, Bâtiment Regain 25/3, 5032 Isnes, Belgium.~Principle intended use Surgical treatment of uncontrolled glaucoma and OHT~The device is currently routinely used in the department for the treatment of uncontrolled glaucoma and OHT, and will be used in accordance with usual clinical practice. It is not anticipated that there will be any changes to the device or its usage during the course of the study. \| Device: STARflo<br>* Suprachoroidal Shunt Surgery (STARflo)<br>\| \| Hydrus Microstent implant<br>Manufacturer Name Ivantis, Inc., 38 Discovery, Suite 150, Irvine, CA 92618, USA.~Principle intended use Surgical treatment of uncontrolled glaucoma and OHT~The device is currently routinely used in the department for the treatment of uncontrolled glaucoma and OHT, and will be used in accordance with usual clinical practice. It is not anticipated that there will be any changes to the device or its usage during the course of the study. \| Device: Hydrus Microstent implant<br>* Trans-trabecular meshwork implants (Hydrus Microstent implant).<br>\| \| iStent implant<br>Manufacturer Name Glaukos Corporation, 26051 Merit Circle, Suite 103, Laguna Hills, CA 92653, USA.~Principle intended use Surgical treatment of uncontrolled glaucoma and OHT~The device is currently routinely used in the department for the treatment of uncontrolled glaucoma and OHT, and will be used in accordance with usual clinical practice. It is not anticipated that there will be any changes to the device or its usage during the course of the study. \| Device: iStent implant<br>* Trans-trabecular meshwork implants (iStent implant).<br>\| \| Kahook Dual Blade<br>Manufacturer: New World Medical. Inc. Single use, ophthalmic blade Utilizes ab interno approach through a clear cornea micro incision Dual blades positioned for precise parallel incisions of the trabecular meshwork with minimal residual leaflets Maintains natural physiologic outflow pathways \| Device: Kahook Dual Blade<br>* It removes part of the trabecular meshwork<br>\|	Aqueous Dynamics and Glaucoma Surgeries Study Overview ================= Brief Summary ----------------- There are currently many surgical options for patients with glaucoma and ocular hypertension (OHT), including the Hydrus Microstent implant, HiFU (High intensity Focused ultrasound), STAR flo, Kahook Dual Blade, Diode laser, trabeculectomy and the Baerveldt implant, but little is known about how these different surgical techniques used to treat glaucoma affect the flow of fluid through and out of the eye (aqueous dynamics). Detailed Description ----------------- Trial objectives Main outcome measures: The following aqueous dynamics parameters will be measured: IOP, aqueous flow rate, trabecular outflow facility and uveoscleral outflow. These parameters will be measured pre-treatment (up to 2 months before glaucoma surgery) and repeated 3 months and 12 months post-surgery. Measures will be taken from the operated eye and the contra lateral non-operated eye which will be used as the control. Trial design This is a prospective observational study with the contra lateral untreated eye being used as control. Baseline measures will be conducted at a routine clinic visit up to 2 months before glaucoma surgery after 4 weeks of treatment washout. Post-treatment follow-up measurements of the main outcomes will be conducted 3 months and 12 months after surgery, again, after 4 weeks wash out. A number of additional eye tests will also be performed to collect data for the study at the pre-operative appointment when the baseline measurements are taken and at the post-operative follow-up appointments 3 months and 12 months after the surgery. Other data will be collected from eye tests that are routinely performed pre-operatively and at the post-operative follow-up appointments 1 day, 1 week, 1 month, 3 months, 6 months, and 12 months after their surgery. Study participants will be recruited from patients attending the Ophthalmology Department Outpatients Clinic at St Thomas' Hospital, London, United Kingdom who have a diagnosis of glaucoma or OHT (ocular hypertension) requiring glaucoma drainage surgery. One hundred patients with glaucoma or OHT and where a clinical decision has been made that they need glaucoma surgery will be included in the study such that 100 eyes undergoing surgery will be included together with the contra-lateral untreated eyes that will be used as controls for comparison with the treated eyes. Data will be collected for the study at the following routine appointments that patients undergoing glaucoma surgery are asked to attend: a pre-operative appointment, surgery, and follow-up assessments 1 day, 1 week, 1 month, 3 months, 6 months, and 12 months after surgery. Baseline measurements will be taken up to 2 months before glaucoma surgery. At the baseline assessment demographic information will be collected Details of participants' relevant past medical history will be collected at the baseline pre-operative assessment and at 12 months post-surgery. All tests will be performed on both eyes as the contra-lateral non-operated eye will be used as control. Aqueous parameters • Aqueous flow rate: Participants will be asked to self-administer 3 to 6 drops (depending on their age) of fluorescein sodium 2% topically into both eyes at 5 minute intervals on the night before the fluorophotometric scans. Fluorophotometry will be performed using a scanning ocular fluorophotometer from 9:00 am -12:00 midday. Four sets of triplicate scans will be collected at 1 hour intervals to determine the aqueous flow rate (Ft). The 3 scans are done in quick succession, taking approximately 2 seconds in total to complete the set. Following each set of scans, IOP will be measured using pneumatonometry. and rebound tonometry. IOP will be recorded as the mean of a total of 12 measurements per eye: 3 measurements every hour alternating between eyes. Patients who have had previous cataract surgeries or iridotomy/iridectomy will be excluded from this aspect of the measurements as fluorophotometry is inaccurate in these eyes. Outflow facility: Tonographic outflow facility (C) measurement will be performed using an electronic Schiøtz tonographer (Model 720, Berkeley Bioengineering Inc, USA) between 9:00 am -12:00 midday. The facility of outflow will be measured from the rate of decay of IOP in the supine position during application of a recording Schiøtz tonometer over a period of 4 minutes with a standard 5.5 gram weight. The R values of the curve at every 30-second time point will be manually entered into the McLaren tonography computer program. The program fits a second-degree polynomial by least squares to the nine data points and determines the best-fit values for time 0 and time 4 minutes by extrapolation. Intraocular pressure (IOP): Pneumatonometry and rebound tonometry will be used to measure IOP for patients undergoing fluorophotometry. The IOP measurements will be recorded at 1 hour intervals between the hours of 9:00 am -12:00 midday following each set of fluorophotometric scans. Uveoscleral outflow: There are currently no reliable clinical methods of measuring uveoscleral outflow (Fu) and episcleral venous pressure (Pv). Fu will be therefore calculated using the Goldmann equation (see below) with an assumed episcleral venous pressure of 8-11 mmHg: Ft = C(IOP - Pv) +Fu Where: Ft = Measured aqueous flow rate Fu = Ft - C(IOP - Pv) Fu = Calculated uveoscleral outflow C = Tonographic outflow facility (value computed by the measurement device) IOP = Mean morning intraocular pressure as measured by pneumatonometry Pv = Episcleral venous pressure (8-11 mmHg, exact value calculated based on patient parameters) Routine tests At the pre-operative visit when baseline measurements are taken and at each routine post-operative follow-up visit (1 day, 1 week, 1 month, 3 months, 6 months, and 12 months after surgery) patients will undergo a clinical ophthalmological examination including the following tests and examinations: Visual acuity measurement (Snellen and ETDRS charts will be used. Best Corrected Distance Visual Acuity (BCVA) and Non Corrected Distance Visual Acuity (NCVA) will be measured using ETDRS (early treatment diabetic retinopathy study) charts. Best Corrected Near Visual Acuity (BCVA) will be measured using a standard near vision chart). Slit lamp examination Visual fields IOP (intraocular pressure) measurement (Goldmann applanation tonometry will be used to measure IOP, except when there is irregular corneal astigmatism or other corneal problems which may preclude accurate reading. The IOP measurement will be done after application of topical anesthetic (eye drop) with fluorescein) Gonioscopy Dilated fundoscopy Anterior chamber depth and axial length Central corneal thickness Refraction (routine at baseline only) Description of the surgical interventions There are potentially four types of operation that patients may have as part of their glaucoma care in the department: Trans-trabecular meshwork implants (Hydrus implant or iStent implant) Ciliary Ablation Treatment (Diode laser or HiFu ultrasound treatment) External (sub-conjunctival) Drainage Surgery (Trabeculectomy, Baerveldt implant or Ahmed Implant) Suprachoroidal Shunt Surgery (STARflo) Official Title ----------------- The Effect of Glaucoma Surgery on Aqueous Dynamics in Patients With Glaucoma or Ocular Hypertension: An Observational Study Conditions ----------------- Glaucoma, Ocular Hypertension Intervention / Treatment ----------------- * Device: HiFU * Device: Baerveldt implant * Device: Ahmed implant * Device: STARflo * Device: Hydrus Microstent implant * Device: iStent implant * Device: Kahook Dual Blade Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Males or females between the ages of 18 and 90 (inclusive). Able to understand the study and give informed consent. Willing, able and available to participate in all aspects of the study. Diagnosis of glaucoma or OHT which requires glaucoma surgery. (Defined as primary or secondary glaucoma; all types of secondary glaucoma may be included. Glaucoma will be diagnosed based on abnormal visual field testing and corresponding disc changes once seen by a glaucoma specialist.) Able to undergo accurate fluorophotometry and tonography. Exclusion Criteria: Mental impairment conflicting with informed consent or follow-up. Allergy to fluorescein. Current use of any investigational drug or device or current participation in an interventional clinical trial. Patients who might not adequately understand written information given in English or verbal explanations in English will not be included as participants in the study must be able to understand English to complete some of the tests. Any inclusion criteria not met Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 90 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| HiFu (ultrasound)<br>Manufacturer Name Eyehope Principle intended use Surgical treatment of uncontrolled glaucoma and OHT The device is currently routinely used in the department for the treatment of uncontrolled glaucoma and OHT, and will be used in accordance with usual clinical practice. It is not anticipated that there will be any changes to the device or its usage during the course of the study. \| Device: HiFU<br>* Ciliary Ablation Treatment ( HiFu ultrasound treatment)<br>\| \| Baerveldt implant<br>Manufacturer Name Abbott Medical Optics Inc., Abbott Laboratories Inc., Abbott Park, Illinois, USA. Principle intended use Surgical treatment of uncontrolled glaucoma and OHT The device is currently routinely used in the department for the treatment of uncontrolled glaucoma and OHT, and will be used in accordance with usual clinical practice. It is not anticipated that there will be any changes to the device or its usage during the course of the study. \| Device: Baerveldt implant<br>* External (sub-conjunctival) Drainage Surgery (Baerveldt implant)<br>\| \| Ahmed Implant<br>Manufacturer Name New World Medical, Inc., 10763 Edison Court, Rancho Cucamonga, CA 91730, USA. Principle intended use Surgical treatment of uncontrolled glaucoma and OHT The device is currently routinely used in the department for the treatment of uncontrolled glaucoma and OHT, and will be used in accordance with usual clinical practice. It is not anticipated that there will be any changes to the device or its usage during the course of the study. \| Device: Ahmed implant<br>* External (sub-conjunctival) Drainage Surgery (Ahmed Implant)<br>\| \| STARflo<br>Manufacturer Name iSTAR Medical SA, Parc Créalys, Rue Phocas Lejeune, Bâtiment Regain 25/3, 5032 Isnes, Belgium. Principle intended use Surgical treatment of uncontrolled glaucoma and OHT The device is currently routinely used in the department for the treatment of uncontrolled glaucoma and OHT, and will be used in accordance with usual clinical practice. It is not anticipated that there will be any changes to the device or its usage during the course of the study. \| Device: STARflo<br>* Suprachoroidal Shunt Surgery (STARflo)<br>\| \| Hydrus Microstent implant<br>Manufacturer Name Ivantis, Inc., 38 Discovery, Suite 150, Irvine, CA 92618, USA. Principle intended use Surgical treatment of uncontrolled glaucoma and OHT The device is currently routinely used in the department for the treatment of uncontrolled glaucoma and OHT, and will be used in accordance with usual clinical practice. It is not anticipated that there will be any changes to the device or its usage during the course of the study. \| Device: Hydrus Microstent implant<br>* Trans-trabecular meshwork implants (Hydrus Microstent implant).<br>\| \| iStent implant<br>Manufacturer Name Glaukos Corporation, 26051 Merit Circle, Suite 103, Laguna Hills, CA 92653, USA. Principle intended use Surgical treatment of uncontrolled glaucoma and OHT The device is currently routinely used in the department for the treatment of uncontrolled glaucoma and OHT, and will be used in accordance with usual clinical practice. It is not anticipated that there will be any changes to the device or its usage during the course of the study. \| Device: iStent implant<br>* Trans-trabecular meshwork implants (iStent implant).<br>\| \| Kahook Dual Blade<br>Manufacturer: New World Medical. Inc. Single use, ophthalmic blade Utilizes ab interno approach through a clear cornea micro incision Dual blades positioned for precise parallel incisions of the trabecular meshwork with minimal residual leaflets Maintains natural physiologic outflow pathways \| Device: Kahook Dual Blade<br>* It removes part of the trabecular meshwork<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change from baseline of Intraocular pressure at 12 months \| It would be measured by Goldmann tonometer, iCare and pneumatonometer. The unit of measurement for all of these devices is the same. It is mmHg \| baseline and 12 months \| \| Change from baseline of aqueous flow at 12 months \| This parameter is measured by fluorophotometry \| baseline and12 months \| \| Change from baseline of uveoscleral outflow at 12 months \| It would be calculated by Goldmann's equation \| baseline and 12 months \| \| Change from baseline of trabecular outflow facility at 12 months \| It will be measured by Electronic Schiotz tonography \| baseline and 12 months \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Glaucoma, Ocular hypertension, Aqueous dynamics
NCT00040508	Sirolimus for Focal Segmental Glomerulosclerosis	This study will determine the safety and effectiveness of sirolimus (Rapamune® (Registered Trademark)) in treating focal segmental glomerulosclerosis (FSGS), a disease involving kidney scarring and increased protein in the urine. About one-half of patients with FSGS go on to develop end-stage kidney disease within 6 years, requiring dialysis or kidney transplant. Therapies to reduce urine protein are likely to stop the progression of renal scarring and reduce the chance of developing kidney failure. However, current treatments for FSGS, such as prednisone, cyclophosphamide, and cyclosporine, are not effective in many patients and can cause serious side effects. This study will see if sirolimus, a drug with both anti-scarring and immune suppressing properties, can lower the amount of protein in the urine and slow or stop the kidney disease.~Patients 13 years of age and older with FSGS who have had at least one standard treatment for FSGS may be eligible for this 24-month study. Pregnant and nursing women may not participate. Candidates will be screened with a medical history and physical examination, review of medical records and kidney biopsy, 24-hour urine collection, and blood tests.~Participants will take sirolimus tablets once a day for 1 year. Three 24-hour urine collections will be done before starting treatment. Blood will be drawn to measure drug levels every week for the first month after starting treatment, then every other week for 1 month, and then every 2 months until treatment stops. Patients who do not have a complete response to the drug at low levels will have their dose increased. Patients will be seen at the NIH clinic in Bethesda, Md., for the screening visit and then at 1, 4, 8, 12, and 15 months for blood and urine tests. Additional urine collections and blood tests will be done periodically throughout the 24-month study period by the patient's local physician.~Patients whose urine protein decreases on therapy will be asked to wait 3 months before starting another treatment and will monitored during that time to determine if the response is sustained. Patients whose urine protein levels do not decrease with sirolimus will not be asked to wait 3 months before starting another therapy. Follow-up with the local physician will continue at 18 and 24 months after starting the study.~Patients whose urine protein levels increase with sirolimus treatment will be taken off the study and may seek other treatment at any time.	Sirolimus is an immunosuppressive agent that was recently approved for use in organ transplantation. We propose to carry out a pilot study whose objectives are to determine the safety and efficacy profile of sirolimus in focal segmental glomerulosclerosis (FSGS). Current therapy for FSGS has limited efficacy. Sirolimus was selected for the following reasons: 1) sirolimus reduces proliferation of mesangial cells and endothelial cells, 2) sirolimus reduces fibrosis in experimental models of liver and kidney disease, 3) sirolimus is a potent immunosuppressive, and other immunosuppressives including glucocorticoids and cyclosporine have shown some efficacy in FSGS, and 4) sirolimus may have a direct anti-proteinuric effect, as suggested by in vitro studies. We will recruit up to 30 patients, including adults and children greater than or equal to 13.0 years of age. The study design is open label, with therapy for one year using doses adjusted to achieve trough levels of 5-15 ng/mL during the first 4 months and if a complete remission is not achieved and sustained, 10-20 ng/mL during the remainder of the study. The primary outcome will be reduction in proteinuria, categorized as complete remission and partial remission, comparing baseline values and 12 month values. The study will recruit patients in two groups: 1) a drug washout group, for patients who can tolerate receiving no immunosuppressive therapy for 4 weeks prior to initiating sirolimus therapy, and 2) a drug overlap group, for patients who cannot tolerate cessation of immunosuppressive therapy due to severe edema or other complications of nephrotic syndrome; these patients will receive prednisone for up to 6 months while taking sirolimus (with a target of prednisone less than 20 mg QOD by month 3) or will receive cyclosporine, tacrolimus, or mycophenolate mofetil for up to 4 weeks while initiating sirolimus therapy.	Sirolimus for Focal Segmental Glomerulosclerosis	Focal Glomerulosclerosis	* Drug: Sirolimus	INCLUSION CRITERIA~Renal biopsy showing FSGS, including all variants with the exception of HIV-associated FSGS.~Nephrotic range proteinuria, defined as 24 hour urine protein excretion greater than or equal to 3.5 g/d in adults and children weighing greater than or equal to 70 kg and greater than or equal to 50 mg/kg in adults or children weighing less than 70 kg. Proteinuria will be assessed with at least three 24 hour urine collections obtained during the baseline period (for these collections, there is no minimum period, the maximum period is 3 months prior to study entry, and the most recent must be within 1 month of entry). These measurements will be obtained while on angiotensin antagonist therapy (if tolerant of this medication) and will exclude urine collections judged inadequate based on creatinine appearance. For patients in the drug overlap group, baseline proteinuria will be determined from patient's records demonstrating on at least one urine collection, proteinuria greater than 3.5 g/d while off immunosuppressive therapy.~Ability and willingness to provide informed consent (adults greater than or equal to 18.0 years) or assent (children greater than or equal to 13.0 years).~Completion of a therapeutic trial of at least one of the following, without sustained CR:~Steroid therapy for greater than or equal to 8 weeks, either daily or alternate day or intermittent (oral or parenteral)~Cyclosporine or tacrolimus or mycophenolate mofetil for greater than or equal to 3 months~Cyclophosphamide (either oral or intravenous) or chlorambucil for greater than or equal to three months~EXCLUSION CRITERIA~Intolerance to sirolimus or prior use of sirolimus for FSGS.~Estimated GFR less than 30 mL/min/1.73m(2). The rational is that 1) sirolimus therapy is most likely to be beneficial during the early phase of FSGS, before progressive fibrosis in the glomeruli and interstitium has become the dominant abnormality and may be irreversible, and 2) we wish to enroll patients who are unlikely to progress to ESRD within the one year treatment period.~Patients following renal transplant. We wish to rest sirolimus with a minimum of other immunosuppressive therapy.~Children less than 13.0 years.~Uncontrolled hypertension, defined as BP greater than 140/90 on greater than 25% of measurements.~Pregnancy, lactation, or unwillingness or inability to practice effective contraception. The rationale is that the safety of sirolimus in pregnancy has not been determined and excretion via breast milk may alter pharmacokinetics.~Chronic active infections requiring treatment, including untreated reactive PPD, or any infection sufficiently severe require parenteral antibiotics during the preceding 30 days. The rationale is that immunosuppression may exacerbate infection.~HIV-1 infection or hepatitis B infection or hepatitis C infection (defined as detectable RNA off anti-viral therapy). The rationale is that immunosuppression may exacerbate infection.~Chronic liver disease sufficiently severe to impair sirolimus metabolism; this would include prolonged pro-thrombin time.~Basal thrombocytopenia less than 100,000 cells/microliter or absolute neutrophil count less than 2000 cells/microliter or hematocrit less than 30. The rationale is that sirolimus may further lower cell counts.~Cancer diagnosis or cancer recurrence within the preceding 5 years, excluding basal cell carcinoma of the skin. The rationale is that cancer progression may be accelerated by immunosuppression.	null	null	All	No	Primary Purpose: Treatment	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \|		Proteinuria, Renal Failure, Fibrosis, Rapamycin, Immunosuppression, Focal Segmental Glomerulosclerosis, FSGS	Sirolimus, Anti-Bacterial Agents, Anti-Infective Agents, Antibiotics, Antineoplastic, Antineoplastic Agents, Antifungal Agents, Immunosuppressive Agents, Immunologic Factors, Physiological Effects of Drugs	\| Intervention/Treatment \| \| --- \| \|Drug: Sirolimus\|nan\|	Sirolimus for Focal Segmental Glomerulosclerosis Study Overview ================= Brief Summary ----------------- This study will determine the safety and effectiveness of sirolimus (Rapamune® (Registered Trademark)) in treating focal segmental glomerulosclerosis (FSGS), a disease involving kidney scarring and increased protein in the urine. About one-half of patients with FSGS go on to develop end-stage kidney disease within 6 years, requiring dialysis or kidney transplant. Therapies to reduce urine protein are likely to stop the progression of renal scarring and reduce the chance of developing kidney failure. However, current treatments for FSGS, such as prednisone, cyclophosphamide, and cyclosporine, are not effective in many patients and can cause serious side effects. This study will see if sirolimus, a drug with both anti-scarring and immune suppressing properties, can lower the amount of protein in the urine and slow or stop the kidney disease. Patients 13 years of age and older with FSGS who have had at least one standard treatment for FSGS may be eligible for this 24-month study. Pregnant and nursing women may not participate. Candidates will be screened with a medical history and physical examination, review of medical records and kidney biopsy, 24-hour urine collection, and blood tests. Participants will take sirolimus tablets once a day for 1 year. Three 24-hour urine collections will be done before starting treatment. Blood will be drawn to measure drug levels every week for the first month after starting treatment, then every other week for 1 month, and then every 2 months until treatment stops. Patients who do not have a complete response to the drug at low levels will have their dose increased. Patients will be seen at the NIH clinic in Bethesda, Md., for the screening visit and then at 1, 4, 8, 12, and 15 months for blood and urine tests. Additional urine collections and blood tests will be done periodically throughout the 24-month study period by the patient's local physician. Patients whose urine protein decreases on therapy will be asked to wait 3 months before starting another treatment and will monitored during that time to determine if the response is sustained. Patients whose urine protein levels do not decrease with sirolimus will not be asked to wait 3 months before starting another therapy. Follow-up with the local physician will continue at 18 and 24 months after starting the study. Patients whose urine protein levels increase with sirolimus treatment will be taken off the study and may seek other treatment at any time. Detailed Description ----------------- Sirolimus is an immunosuppressive agent that was recently approved for use in organ transplantation. We propose to carry out a pilot study whose objectives are to determine the safety and efficacy profile of sirolimus in focal segmental glomerulosclerosis (FSGS). Current therapy for FSGS has limited efficacy. Sirolimus was selected for the following reasons: 1) sirolimus reduces proliferation of mesangial cells and endothelial cells, 2) sirolimus reduces fibrosis in experimental models of liver and kidney disease, 3) sirolimus is a potent immunosuppressive, and other immunosuppressives including glucocorticoids and cyclosporine have shown some efficacy in FSGS, and 4) sirolimus may have a direct anti-proteinuric effect, as suggested by in vitro studies. We will recruit up to 30 patients, including adults and children greater than or equal to 13.0 years of age. The study design is open label, with therapy for one year using doses adjusted to achieve trough levels of 5-15 ng/mL during the first 4 months and if a complete remission is not achieved and sustained, 10-20 ng/mL during the remainder of the study. The primary outcome will be reduction in proteinuria, categorized as complete remission and partial remission, comparing baseline values and 12 month values. The study will recruit patients in two groups: 1) a drug washout group, for patients who can tolerate receiving no immunosuppressive therapy for 4 weeks prior to initiating sirolimus therapy, and 2) a drug overlap group, for patients who cannot tolerate cessation of immunosuppressive therapy due to severe edema or other complications of nephrotic syndrome; these patients will receive prednisone for up to 6 months while taking sirolimus (with a target of prednisone less than 20 mg QOD by month 3) or will receive cyclosporine, tacrolimus, or mycophenolate mofetil for up to 4 weeks while initiating sirolimus therapy. Official Title ----------------- Sirolimus for Focal Segmental Glomerulosclerosis Conditions ----------------- Focal Glomerulosclerosis Intervention / Treatment ----------------- * Drug: Sirolimus Participation Criteria ================= Eligibility Criteria ----------------- INCLUSION CRITERIA Renal biopsy showing FSGS, including all variants with the exception of HIV-associated FSGS. Nephrotic range proteinuria, defined as 24 hour urine protein excretion greater than or equal to 3.5 g/d in adults and children weighing greater than or equal to 70 kg and greater than or equal to 50 mg/kg in adults or children weighing less than 70 kg. Proteinuria will be assessed with at least three 24 hour urine collections obtained during the baseline period (for these collections, there is no minimum period, the maximum period is 3 months prior to study entry, and the most recent must be within 1 month of entry). These measurements will be obtained while on angiotensin antagonist therapy (if tolerant of this medication) and will exclude urine collections judged inadequate based on creatinine appearance. For patients in the drug overlap group, baseline proteinuria will be determined from patient's records demonstrating on at least one urine collection, proteinuria greater than 3.5 g/d while off immunosuppressive therapy. Ability and willingness to provide informed consent (adults greater than or equal to 18.0 years) or assent (children greater than or equal to 13.0 years). Completion of a therapeutic trial of at least one of the following, without sustained CR: Steroid therapy for greater than or equal to 8 weeks, either daily or alternate day or intermittent (oral or parenteral) Cyclosporine or tacrolimus or mycophenolate mofetil for greater than or equal to 3 months Cyclophosphamide (either oral or intravenous) or chlorambucil for greater than or equal to three months EXCLUSION CRITERIA Intolerance to sirolimus or prior use of sirolimus for FSGS. Estimated GFR less than 30 mL/min/1.73m(2). The rational is that 1) sirolimus therapy is most likely to be beneficial during the early phase of FSGS, before progressive fibrosis in the glomeruli and interstitium has become the dominant abnormality and may be irreversible, and 2) we wish to enroll patients who are unlikely to progress to ESRD within the one year treatment period. Patients following renal transplant. We wish to rest sirolimus with a minimum of other immunosuppressive therapy. Children less than 13.0 years. Uncontrolled hypertension, defined as BP greater than 140/90 on greater than 25% of measurements. Pregnancy, lactation, or unwillingness or inability to practice effective contraception. The rationale is that the safety of sirolimus in pregnancy has not been determined and excretion via breast milk may alter pharmacokinetics. Chronic active infections requiring treatment, including untreated reactive PPD, or any infection sufficiently severe require parenteral antibiotics during the preceding 30 days. The rationale is that immunosuppression may exacerbate infection. HIV-1 infection or hepatitis B infection or hepatitis C infection (defined as detectable RNA off anti-viral therapy). The rationale is that immunosuppression may exacerbate infection. Chronic liver disease sufficiently severe to impair sirolimus metabolism; this would include prolonged pro-thrombin time. Basal thrombocytopenia less than 100,000 cells/microliter or absolute neutrophil count less than 2000 cells/microliter or hematocrit less than 30. The rationale is that sirolimus may further lower cell counts. Cancer diagnosis or cancer recurrence within the preceding 5 years, excluding basal cell carcinoma of the skin. The rationale is that cancer progression may be accelerated by immunosuppression. Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Arms and Interventions \| Intervention/Treatment \| \| --- \| \|Drug: Sirolimus\|nan\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Proteinuria, Renal Failure, Fibrosis, Rapamycin, Immunosuppression, Focal Segmental Glomerulosclerosis, FSGS
NCT02989415	Assessment of Ventilatory Management During General Anesthesia for Robotic Surgery	The aim of this study is to assess the incidence of postoperative pulmonary complications in patients undergoing mechanical ventilation during general anesthesia for robotic surgery, to characterize current practices of mechanical ventilation and to evaluate a possible association between ventilatory parameters and postoperative pulmonary complications.	Research questions:~What is the incidence of PPC in patients undergoing mechanical ventilation during general anesthesia for robotic surgery?~Are the outcomes in patients undergoing robotic surgery dependent on ventilation practice and surgical positioning?~What is the incidence of patients at high risk for PPC undergoing robotic surgery~Methods:~In this international observational study, consecutive patients undergoing mechanical ventilation for robotic surgery are eligible for participation. Patients in participating centers will be screened on a daily basis. Patients undergoing mechanical ventilation for robotic surgery will be included during a 30-day period. The inclusion period will be flexible for participating centers and determined at a later stage together with the study-coordinator.~Time points of data collection:~Demographic data and baseline data, including severity scores (e.g. ASA) and ARISCAT, are collected from the clinical files on the day of surgery~Ventilation settings, gas exchange variables, positioning and vital parameters are collected hourly during surgery~Chest radiography data from available chest X-rays (i.e., no extra chest X-rays are obtained)~Predefined complications are recorded from medical chart until the first five postoperative days, discharge from hospital or death, whatever comes first~Length of hospital stay, and hospital mortality~Centres: The investigators aim to recruit 20 - 50 centers worldwide.~Ethics Approval: National coordinators will be responsible for clarifying the need for ethics approval and applying for this where appropriate according to local policy. Centres will not be permitted to record data unless ethics approval or an equivalent waiver is in place. The investigators expect that in most, if not every participating country, a patient informed consent is not be required.~Monitoring: Due to the observational nature of the study, a DSMB is not be necessary.~Study Population: Adult patients undergoing mechanical ventilation for robotic surgery.~Data Collection: Data will be collected at inclusion, during surgery and every day during five days, and day of hospital discharge. Data will be coded by a patient identification number (PIN) of which the code will be kept safe at the local sites. The data will be transcribed by local investigators onto an internet based electronic CRF.~Sample Size Calculation: A formal sample size will not be calculated, seen the largely descriptive character of this investigation. Data from 500 patients is expected to be collected, which will be sufficient to test the hypotheses.~Statistical Analysis: Patient characteristics will be compared and described by appropriate statistics. Student's t-test or Mann-Whitney U-tests are used to compare continuous variables and chi-squared tests are used for categorical variables. Data are expressed as means (SD), medians (interquartile range) and proportions as appropriate. Comparisons between and within groups are performed using one-way ANOVA and post-hoc analyses for continuous variables.~The primary analysis concerns the determination of the incidence of postoperative pulmonary complications in patients undergoing mechanical ventilation for robotic surgery.~To identify potential factors associated with outcome like development of postoperative pulmonary complications, or death, univariable analyses will be performed. A multi-level multivariable logistic regression model will be used to identify independent risk factors. A gradual approach will be used to enter new terms into the model, with a limit of p < 0.2 to enter the terms. Time to event variables will be analyzed using Cox regression and visualized by Kaplan-Meier.~Organization: The study is conducted by the PROtective VEntilation Network (PROVENet). National co-ordinators will lead the project within individual nations and identify participating hospitals, translate study paperwork, distribute study paperwork and ensure necessary regulatory approvals are in place. They provide assistance to the participating clinical sites in trial management, record keeping and data management. Local coordinators in each site will supervise data collection and ensure adherence to Good Clinical Practice during the trial.	Assessment of Ventilatory Management During General Anesthesia for Robotic Surgery and Its Effects on Postoperative Pulmonary Complications: A Prospective Observational Multicenter Study	Robotic Surgery, Mechanical Ventilation	* Other: Mechanical Ventilation	Inclusion Criteria:~Age ≥ 18 years~All surgical procedures performed under general anesthesia for robotic surgery, including head and neck operations, chest, cardiac, and abdominal surgeries~Exclusion Criteria:~Any procedure during pregnancy~Procedures outside of the operating room	18 Years	null	All	No		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Incidence of postoperative pulmonary complications \| Composite of five postoperative pulmonary complications \| Five days or until hospital discharge, whichever occurs first \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Mechanical ventilation practice \| Mechanical ventilation practice in patients submitted to general anesthesia for robotic surgery \| Intraoperatively \| \| Mechanical ventilation practice and postoperative pulmonary complications \| Association between mechanical ventilation practice and development of postoperative pulmonary complications \| Five days or until hospital discharge, whichever occurs first \| \| Surgical positioning and ventilation \| Association between surgical positioning and ventilatory parameters \| Intraoperatively \| \| Patients at high risk for postoperative pulmonary complications \| Incidence of patients at high risk for postoperative pulmonary complications according to the ARISCAT score \| Pre-operatively \| \| Mechanical ventilation practice and intraoperative complications \| Association between mechanical ventilation practice and development of intraoperative complications \| Intraoperatively \|	Anesthesia, Mechanical Ventilation, Robotic Surgery, Postoperative Pulmonary Complications		\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Mechanical Ventilation<br>Patients undergoing mechanical ventilation during robotic surgery \| Other: Mechanical Ventilation<br>* Mechanical ventilation during robotic surgery<br>\|	Assessment of Ventilatory Management During General Anesthesia for Robotic Surgery Study Overview ================= Brief Summary ----------------- The aim of this study is to assess the incidence of postoperative pulmonary complications in patients undergoing mechanical ventilation during general anesthesia for robotic surgery, to characterize current practices of mechanical ventilation and to evaluate a possible association between ventilatory parameters and postoperative pulmonary complications. Detailed Description ----------------- Research questions: What is the incidence of PPC in patients undergoing mechanical ventilation during general anesthesia for robotic surgery? Are the outcomes in patients undergoing robotic surgery dependent on ventilation practice and surgical positioning? What is the incidence of patients at high risk for PPC undergoing robotic surgery Methods: In this international observational study, consecutive patients undergoing mechanical ventilation for robotic surgery are eligible for participation. Patients in participating centers will be screened on a daily basis. Patients undergoing mechanical ventilation for robotic surgery will be included during a 30-day period. The inclusion period will be flexible for participating centers and determined at a later stage together with the study-coordinator. Time points of data collection: Demographic data and baseline data, including severity scores (e.g. ASA) and ARISCAT, are collected from the clinical files on the day of surgery Ventilation settings, gas exchange variables, positioning and vital parameters are collected hourly during surgery Chest radiography data from available chest X-rays (i.e., no extra chest X-rays are obtained) Predefined complications are recorded from medical chart until the first five postoperative days, discharge from hospital or death, whatever comes first Length of hospital stay, and hospital mortality Centres: The investigators aim to recruit 20 - 50 centers worldwide. Ethics Approval: National coordinators will be responsible for clarifying the need for ethics approval and applying for this where appropriate according to local policy. Centres will not be permitted to record data unless ethics approval or an equivalent waiver is in place. The investigators expect that in most, if not every participating country, a patient informed consent is not be required. Monitoring: Due to the observational nature of the study, a DSMB is not be necessary. Study Population: Adult patients undergoing mechanical ventilation for robotic surgery. Data Collection: Data will be collected at inclusion, during surgery and every day during five days, and day of hospital discharge. Data will be coded by a patient identification number (PIN) of which the code will be kept safe at the local sites. The data will be transcribed by local investigators onto an internet based electronic CRF. Sample Size Calculation: A formal sample size will not be calculated, seen the largely descriptive character of this investigation. Data from 500 patients is expected to be collected, which will be sufficient to test the hypotheses. Statistical Analysis: Patient characteristics will be compared and described by appropriate statistics. Student's t-test or Mann-Whitney U-tests are used to compare continuous variables and chi-squared tests are used for categorical variables. Data are expressed as means (SD), medians (interquartile range) and proportions as appropriate. Comparisons between and within groups are performed using one-way ANOVA and post-hoc analyses for continuous variables. The primary analysis concerns the determination of the incidence of postoperative pulmonary complications in patients undergoing mechanical ventilation for robotic surgery. To identify potential factors associated with outcome like development of postoperative pulmonary complications, or death, univariable analyses will be performed. A multi-level multivariable logistic regression model will be used to identify independent risk factors. A gradual approach will be used to enter new terms into the model, with a limit of p < 0.2 to enter the terms. Time to event variables will be analyzed using Cox regression and visualized by Kaplan-Meier. Organization: The study is conducted by the PROtective VEntilation Network (PROVENet). National co-ordinators will lead the project within individual nations and identify participating hospitals, translate study paperwork, distribute study paperwork and ensure necessary regulatory approvals are in place. They provide assistance to the participating clinical sites in trial management, record keeping and data management. Local coordinators in each site will supervise data collection and ensure adherence to Good Clinical Practice during the trial. Official Title ----------------- Assessment of Ventilatory Management During General Anesthesia for Robotic Surgery and Its Effects on Postoperative Pulmonary Complications: A Prospective Observational Multicenter Study Conditions ----------------- Robotic Surgery, Mechanical Ventilation Intervention / Treatment ----------------- * Other: Mechanical Ventilation Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age ≥ 18 years All surgical procedures performed under general anesthesia for robotic surgery, including head and neck operations, chest, cardiac, and abdominal surgeries Exclusion Criteria: Any procedure during pregnancy Procedures outside of the operating room Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Mechanical Ventilation<br>Patients undergoing mechanical ventilation during robotic surgery \| Other: Mechanical Ventilation<br>* Mechanical ventilation during robotic surgery<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Incidence of postoperative pulmonary complications \| Composite of five postoperative pulmonary complications \| Five days or until hospital discharge, whichever occurs first \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Mechanical ventilation practice \| Mechanical ventilation practice in patients submitted to general anesthesia for robotic surgery \| Intraoperatively \| \| Mechanical ventilation practice and postoperative pulmonary complications \| Association between mechanical ventilation practice and development of postoperative pulmonary complications \| Five days or until hospital discharge, whichever occurs first \| \| Surgical positioning and ventilation \| Association between surgical positioning and ventilatory parameters \| Intraoperatively \| \| Patients at high risk for postoperative pulmonary complications \| Incidence of patients at high risk for postoperative pulmonary complications according to the ARISCAT score \| Pre-operatively \| \| Mechanical ventilation practice and intraoperative complications \| Association between mechanical ventilation practice and development of intraoperative complications \| Intraoperatively \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Anesthesia, Mechanical Ventilation, Robotic Surgery, Postoperative Pulmonary Complications
NCT04086641	Comparison of Prosthetic Feet for People With Syme's Amputation (XF Symes Study)	The purpose of this study is to compare the functional differences between two types of foot prostheses for people with ankle disarticulation (Syme's) amputations. The two feet being tested are low- and high-profile feet, with the difference being the latter has an extended keel and attaches to the posterior of the prosthetic socket, rather than the distal end. The hypothesis is that the high-profile foot (i.e., the crossover foot) will lead to functional and biomechanical improvements compared to low-profile feet.	Syme's prostheses are typically limited to low-profile prosthetic feet due to clearance restrictions below the prosthetic socket. As a result, the functional benefits provided by the long residual limb are mitigated by prosthetic design limitations. Recently, high-profile, posteriorly-attaching crossover feet have been modified for use with people who have Syme's amputation. Crossover feet theoretically improve motion and energy storage-and-return compared to traditional foot options for the Syme's level. Crossover feet also have the potential to broaden the range of high-impact activities that can be performed with a single prosthesis. However, to date there is no empirical evidence that compares functional differences when walking with high-profile crossover feet compared to low-profile feet for people with Syme's amputation. This mixed-method pilot research will use a randomized, controlled within-participants design. Investigators will assess gait biomechanics, self-reported health outcomes, and qualitative interviews to compare relative advantages and disadvantages of traditional low-profile Syme's feet and high-profile crossover feet. This proposed work will create a foundation for future research that examines the potential benefits of crossover feet in people with Syme's amputation. In addition, results from this research will be used clinically to inform prosthetic options for people with limited clearance for distally-attached prosthetic feet.	Functional Assessment of High-profile Crossover Feet in People With Syme's Amputation	Amputation, Artificial Limb	* Device: Crossover foot * Device: Energy Storing Foot	Inclusion Criteria:~18 years of age or older~Have a unilateral Syme's amputation that occurred >1 year prior~Owns a crossover foot modified for Syme's use~Able to walk in the community without assistance~Able to read and write in English~Exclusion Criteria:~Have other amputations~Have a health condition that would limit completion of the study protocol (e.g., skin breakdown, heart disease)	18 Years	null	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Ratio Between Sound and Prosthetic Side Step Lengths \| The symmetry between prosthetic and sound side step lengths. Step lengths were calculated as the distance between heels from heel strike of the contralateral foot to heel strike of the ipsilateral foot. \| Sessions 3 (after 2 weeks of prosthesis 1 wear) and 4 (after 2 weeks of prosthesis 2 wear) \| \| Total Prosthetic Ankle Range of Motion \| The change in total angular motion of the ankle in the sagittal plane (e.g., dorsiflexion & plantarflexion) during stance phase between prosthetic feet, in degrees \| Sessions 3 (after 2 weeks of prosthesis 1 wear) and 4 (after 2 weeks of prosthesis 2 wear) \| \| Prosthetic-side Energy Return \| Intersegmental flow of power out of the prosthesis \| Sessions 3 (after 2 weeks of prosthesis 1 wear) and 4 (after 2 weeks of prosthesis 2 wear) \| \| Peak Sound-side Limb Loading \| Maximum vertical ground reaction force in early stance \| Sessions 3 (after 2 weeks of prosthesis 1 wear) and 4 (after 2 weeks of prosthesis 2 wear) \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Preference Questionnaire \| At the end of the study, participants will engage in a preference questionnaire with open-ended follow-up questions to elicit preferences and experiences with both feet. Questions will ask about overall preference, and preference for a range of mobility activities (e.g., Which foot did you prefer overall, and why? and Which foot did you prefer for walking up stairs, and why?). \| Session 4 (after 4 weeks of prosthesis wear, 2 weeks of prosthesis 1 and 2 weeks of prosthesis 2) \| \| Change in Prosthetic Limb Users Survey of Mobility (PLUS-M) 12-item Short Form Version 1.2 \| Self-reported measure of mobility, the PLUS-M 12-item Short Form is a single measure, scores range from 17.5-76.6, higher scores represent better mobility. \| Sessions 3 (after 2 weeks of prosthesis 1 wear) and 4 (after 2 weeks of prosthesis 2 wear) \| \| Change in Activities-Specific Balance Confidence Scale (ABC) \| Self-reported measure of balance confidence, the ABC is a single measure, scores range from 0-4, higher scores represent better balance confidence. \| Sessions 3 (after 2 weeks of prosthesis 1 wear) and 4 (after 2 weeks of prosthesis 2 wear) \| \| Change in Trinity Amputation and Prosthesis Experience Scales- Revised Aesthetic Satisfaction \| Self-reported measures of aesthetic prosthetic satisfaction, scores on items are averaged and range from 0-2, higher values represent more satisfaction (better outcome) \| Sessions 3 (after 2 weeks of prosthesis 1 wear) and 4 (after 2 weeks of prosthesis 2 wear) \|	Ankle disarticulation, Syme, Amputation, Prosthesis, Prosthetic foot, Crossover foot, Biomechanics		\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Foot 1: Crossover Foot, Foot 2: Energy Storing Foot<br>Participant randomized to crossover foot as first condition, energy storing foot as second condition \| Device: Crossover foot<br>* A prosthetic foot that features an extended strut (keel) that attaches to the posterior proximal aspect of the prosthetic socket.<br>Device: Energy Storing Foot<br>* A prosthetic foot that features a short strut (keel) that attaches to the distal aspect of the prosthetic socket.<br>\| \| Experimental: Foot 1: Energy Storing Foot, Foot 2: Crossover Foot<br>Participant randomized to energy storing foot as first condition, crossover foot as second condition \| Device: Crossover foot<br>* A prosthetic foot that features an extended strut (keel) that attaches to the posterior proximal aspect of the prosthetic socket.<br>Device: Energy Storing Foot<br>* A prosthetic foot that features a short strut (keel) that attaches to the distal aspect of the prosthetic socket.<br>\|	Comparison of Prosthetic Feet for People With Syme's Amputation (XF Symes Study) Study Overview ================= Brief Summary ----------------- The purpose of this study is to compare the functional differences between two types of foot prostheses for people with ankle disarticulation (Syme's) amputations. The two feet being tested are low- and high-profile feet, with the difference being the latter has an extended keel and attaches to the posterior of the prosthetic socket, rather than the distal end. The hypothesis is that the high-profile foot (i.e., the crossover foot) will lead to functional and biomechanical improvements compared to low-profile feet. Detailed Description ----------------- Syme's prostheses are typically limited to low-profile prosthetic feet due to clearance restrictions below the prosthetic socket. As a result, the functional benefits provided by the long residual limb are mitigated by prosthetic design limitations. Recently, high-profile, posteriorly-attaching crossover feet have been modified for use with people who have Syme's amputation. Crossover feet theoretically improve motion and energy storage-and-return compared to traditional foot options for the Syme's level. Crossover feet also have the potential to broaden the range of high-impact activities that can be performed with a single prosthesis. However, to date there is no empirical evidence that compares functional differences when walking with high-profile crossover feet compared to low-profile feet for people with Syme's amputation. This mixed-method pilot research will use a randomized, controlled within-participants design. Investigators will assess gait biomechanics, self-reported health outcomes, and qualitative interviews to compare relative advantages and disadvantages of traditional low-profile Syme's feet and high-profile crossover feet. This proposed work will create a foundation for future research that examines the potential benefits of crossover feet in people with Syme's amputation. In addition, results from this research will be used clinically to inform prosthetic options for people with limited clearance for distally-attached prosthetic feet. Official Title ----------------- Functional Assessment of High-profile Crossover Feet in People With Syme's Amputation Conditions ----------------- Amputation, Artificial Limb Intervention / Treatment ----------------- * Device: Crossover foot * Device: Energy Storing Foot Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: 18 years of age or older Have a unilateral Syme's amputation that occurred >1 year prior Owns a crossover foot modified for Syme's use Able to walk in the community without assistance Able to read and write in English Exclusion Criteria: Have other amputations Have a health condition that would limit completion of the study protocol (e.g., skin breakdown, heart disease) Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Foot 1: Crossover Foot, Foot 2: Energy Storing Foot<br>Participant randomized to crossover foot as first condition, energy storing foot as second condition \| Device: Crossover foot<br>* A prosthetic foot that features an extended strut (keel) that attaches to the posterior proximal aspect of the prosthetic socket.<br>Device: Energy Storing Foot<br>* A prosthetic foot that features a short strut (keel) that attaches to the distal aspect of the prosthetic socket.<br>\| \| Experimental: Foot 1: Energy Storing Foot, Foot 2: Crossover Foot<br>Participant randomized to energy storing foot as first condition, crossover foot as second condition \| Device: Crossover foot<br>* A prosthetic foot that features an extended strut (keel) that attaches to the posterior proximal aspect of the prosthetic socket.<br>Device: Energy Storing Foot<br>* A prosthetic foot that features a short strut (keel) that attaches to the distal aspect of the prosthetic socket.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Ratio Between Sound and Prosthetic Side Step Lengths \| The symmetry between prosthetic and sound side step lengths. Step lengths were calculated as the distance between heels from heel strike of the contralateral foot to heel strike of the ipsilateral foot. \| Sessions 3 (after 2 weeks of prosthesis 1 wear) and 4 (after 2 weeks of prosthesis 2 wear) \| \| Total Prosthetic Ankle Range of Motion \| The change in total angular motion of the ankle in the sagittal plane (e.g., dorsiflexion & plantarflexion) during stance phase between prosthetic feet, in degrees \| Sessions 3 (after 2 weeks of prosthesis 1 wear) and 4 (after 2 weeks of prosthesis 2 wear) \| \| Prosthetic-side Energy Return \| Intersegmental flow of power out of the prosthesis \| Sessions 3 (after 2 weeks of prosthesis 1 wear) and 4 (after 2 weeks of prosthesis 2 wear) \| \| Peak Sound-side Limb Loading \| Maximum vertical ground reaction force in early stance \| Sessions 3 (after 2 weeks of prosthesis 1 wear) and 4 (after 2 weeks of prosthesis 2 wear) \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Preference Questionnaire \| At the end of the study, participants will engage in a preference questionnaire with open-ended follow-up questions to elicit preferences and experiences with both feet. Questions will ask about overall preference, and preference for a range of mobility activities (e.g., Which foot did you prefer overall, and why? and Which foot did you prefer for walking up stairs, and why?). \| Session 4 (after 4 weeks of prosthesis wear, 2 weeks of prosthesis 1 and 2 weeks of prosthesis 2) \| \| Change in Prosthetic Limb Users Survey of Mobility (PLUS-M) 12-item Short Form Version 1.2 \| Self-reported measure of mobility, the PLUS-M 12-item Short Form is a single measure, scores range from 17.5-76.6, higher scores represent better mobility. \| Sessions 3 (after 2 weeks of prosthesis 1 wear) and 4 (after 2 weeks of prosthesis 2 wear) \| \| Change in Activities-Specific Balance Confidence Scale (ABC) \| Self-reported measure of balance confidence, the ABC is a single measure, scores range from 0-4, higher scores represent better balance confidence. \| Sessions 3 (after 2 weeks of prosthesis 1 wear) and 4 (after 2 weeks of prosthesis 2 wear) \| \| Change in Trinity Amputation and Prosthesis Experience Scales- Revised Aesthetic Satisfaction \| Self-reported measures of aesthetic prosthetic satisfaction, scores on items are averaged and range from 0-2, higher values represent more satisfaction (better outcome) \| Sessions 3 (after 2 weeks of prosthesis 1 wear) and 4 (after 2 weeks of prosthesis 2 wear) \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Ankle disarticulation, Syme, Amputation, Prosthesis, Prosthetic foot, Crossover foot, Biomechanics
NCT00005806	Combination Chemotherapy in Treating Patients With Advanced Non-Small Cell Lung Cancer	RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.~PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy in treating patients who have advanced non-small cell lung cancer.	OBJECTIVES: I. Determine the maximum tolerated dose of ZD 1839 given intermittently or continuously and concurrently with standard doses of carboplatin and paclitaxel in patients with advanced non-small cell lung cancer. II. Determine the safety of ZD 1839 in these regimens in these patients. III. Determine whether the exposure of either free carboplatin or paclitaxel in an established treatment regimen is significantly altered by the addition of oral ZD 1839 in this patient population. IV. Determine the exposure of ZD 1839 before and after standard doses of carboplatin and paclitaxel to assess whether ZD 1839 steady state is significantly altered by coadministration of chemotherapy.~OUTLINE: This is an open label, 2 part, multicenter study. Part 1 is a randomized, dose escalation, 2 period, 2 sequence, crossover design. Part 2 is a nonrandomized, single dose evaluation design. Part 1: Patients are randomized to receive ZD 1839 beginning 1 week before either the first (arm I) or second (arm II) course of carboplatin and paclitaxel. Arm I: Patients receive oral ZD 1839 daily on days 1-14. On day 1 only, ZD 1839 is given twice at 12 hour intervals. Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on days 8 and 36. Subsequent courses consist of ZD 1839 for 14 days and paclitaxel and carboplatin every 28 days. Arm II: Patients receive paclitaxel and carboplatin as in arm I on days 1 and 29. Patients receive oral ZD 1839 daily on days 22-35. On day 22 only, ZD 1839 is given twice at 12 hour intervals. Subsequent courses are administered as in arm I. Part 2: Patients receive oral ZD 1839 daily on days 1-56. On day 1 only, ZD 1839 is given twice at 12 hour intervals. Patients receive paclitaxel and carboplatin as in part 1 on days 8 and 36. Subsequent courses consist of ZD 1839 continuously and paclitaxel and carboplatin every 28 days. Treatment continues in both parts for a maximum of 6 months in the absence of unacceptable toxicity or disease progression. In both parts 1 and 2, cohorts of 6-12 patients receive escalating doses of ZD 1839 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 4 of 6 or 4 of 12 patients experience dose limiting toxicities.~PROJECTED ACCRUAL: A maximum of 48 patients will be accrued for this study.	A Pilot Trial of Daily Oral ZD1839 (Iressa) With Standard Doses of Carboplatin and Paclitaxel in Patients With Advanced Non-Small Cell Lung Cancer	Lung Cancer	* Drug: carboplatin * Drug: gefitinib * Drug: paclitaxel	DISEASE CHARACTERISTICS: Histologically and/or cytologically confirmed advanced or metastatic non-small cell lung cancer considered incurable with standard surgery or irradiation No active brain metastases as indicated by clinical symptoms, cerebral edema, and/or progressive growth~PATIENT CHARACTERISTICS: Age: 18 and over Performance status: WHO 0-1 that has not worsened within the past 7 days Life expectancy: At least 12 weeks Hematopoietic: Neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.25 times upper limit of normal (ULN) ALT/AST no greater than 2.5 times ULN (5 times ULN if liver metastases) Renal: Creatinine no greater than 1.25 times ULN No greater than a trace of blood or protein on urine labstix test Cardiovascular: No prior history of clinically significant cardiac dysrhythmia, first degree heart block, or other severe cardiac disease Opthalmologic: No potentially visually threatening epithelial abnormality of the cornea other than scars, congenital abnormality, or corneal tear film (e.g., neurotrophic keratitis, corneal edema, or recurrent erosions) No signs and symptoms of keratoconjunctivitis sicca No concurrent use of contact lenses Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancies within the past 5 years except basal cell carcinoma or carcinoma in situ of the cervix No evidence of severe or uncontrolled systemic diseases (e.g., hepatitis B, hepatitis C, or HIV) No known chronic conditions No active dermatoses involving the face No evidence of any other significant clinical disorder or laboratory finding that would preclude study participation~PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy for non-small cell lung cancer No concurrent biologic response modifiers Concurrent filgrastim (G-CSF) allowed only for persistent neutropenia despite dose reductions in prior course Chemotherapy: No prior chemotherapy for non-small cell lung cancer Endocrine therapy: No concurrent hormonal therapy No concurrent tamoxifen Radiotherapy: See Disease Characteristics At least 2 weeks since prior radiotherapy No concurrent radiotherapy Surgery: See Disease Characteristics Recovered from prior oncologic or other major surgery Other: No other concurrent anticancer therapy No other concurrent investigational agents No concurrent drugs with known significant 3A4 inhibitory effects (i.e., ketoconazole, itraconazole, troleandomycin, erythromycin, diltiazem, verapamil) No concurrent hydroxychloroquine, amiodarone, or chlorpromazine No concurrent topical eye medication	18 Years	null	All	No	Primary Purpose: Treatment	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \|		recurrent non-small cell lung cancer, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer	Gefitinib, Paclitaxel, Carboplatin, Antineoplastic Agents, Phytogenic, Antineoplastic Agents, Tubulin Modulators, Antimitotic Agents, Mitosis Modulators, Molecular Mechanisms of Pharmacological Action, Protein Kinase Inhibitors, Enzyme Inhibitors	\| Intervention/Treatment \| \| --- \| \|Drug: carboplatin\|nan\| \|Drug: gefitinib\|nan\| \|Drug: paclitaxel\|nan\|	Combination Chemotherapy in Treating Patients With Advanced Non-Small Cell Lung Cancer Study Overview ================= Brief Summary ----------------- RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy in treating patients who have advanced non-small cell lung cancer. Detailed Description ----------------- OBJECTIVES: I. Determine the maximum tolerated dose of ZD 1839 given intermittently or continuously and concurrently with standard doses of carboplatin and paclitaxel in patients with advanced non-small cell lung cancer. II. Determine the safety of ZD 1839 in these regimens in these patients. III. Determine whether the exposure of either free carboplatin or paclitaxel in an established treatment regimen is significantly altered by the addition of oral ZD 1839 in this patient population. IV. Determine the exposure of ZD 1839 before and after standard doses of carboplatin and paclitaxel to assess whether ZD 1839 steady state is significantly altered by coadministration of chemotherapy. OUTLINE: This is an open label, 2 part, multicenter study. Part 1 is a randomized, dose escalation, 2 period, 2 sequence, crossover design. Part 2 is a nonrandomized, single dose evaluation design. Part 1: Patients are randomized to receive ZD 1839 beginning 1 week before either the first (arm I) or second (arm II) course of carboplatin and paclitaxel. Arm I: Patients receive oral ZD 1839 daily on days 1-14. On day 1 only, ZD 1839 is given twice at 12 hour intervals. Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on days 8 and 36. Subsequent courses consist of ZD 1839 for 14 days and paclitaxel and carboplatin every 28 days. Arm II: Patients receive paclitaxel and carboplatin as in arm I on days 1 and 29. Patients receive oral ZD 1839 daily on days 22-35. On day 22 only, ZD 1839 is given twice at 12 hour intervals. Subsequent courses are administered as in arm I. Part 2: Patients receive oral ZD 1839 daily on days 1-56. On day 1 only, ZD 1839 is given twice at 12 hour intervals. Patients receive paclitaxel and carboplatin as in part 1 on days 8 and 36. Subsequent courses consist of ZD 1839 continuously and paclitaxel and carboplatin every 28 days. Treatment continues in both parts for a maximum of 6 months in the absence of unacceptable toxicity or disease progression. In both parts 1 and 2, cohorts of 6-12 patients receive escalating doses of ZD 1839 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 4 of 6 or 4 of 12 patients experience dose limiting toxicities. PROJECTED ACCRUAL: A maximum of 48 patients will be accrued for this study. Official Title ----------------- A Pilot Trial of Daily Oral ZD1839 (Iressa) With Standard Doses of Carboplatin and Paclitaxel in Patients With Advanced Non-Small Cell Lung Cancer Conditions ----------------- Lung Cancer Intervention / Treatment ----------------- * Drug: carboplatin * Drug: gefitinib * Drug: paclitaxel Participation Criteria ================= Eligibility Criteria ----------------- DISEASE CHARACTERISTICS: Histologically and/or cytologically confirmed advanced or metastatic non-small cell lung cancer considered incurable with standard surgery or irradiation No active brain metastases as indicated by clinical symptoms, cerebral edema, and/or progressive growth PATIENT CHARACTERISTICS: Age: 18 and over Performance status: WHO 0-1 that has not worsened within the past 7 days Life expectancy: At least 12 weeks Hematopoietic: Neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.25 times upper limit of normal (ULN) ALT/AST no greater than 2.5 times ULN (5 times ULN if liver metastases) Renal: Creatinine no greater than 1.25 times ULN No greater than a trace of blood or protein on urine labstix test Cardiovascular: No prior history of clinically significant cardiac dysrhythmia, first degree heart block, or other severe cardiac disease Opthalmologic: No potentially visually threatening epithelial abnormality of the cornea other than scars, congenital abnormality, or corneal tear film (e.g., neurotrophic keratitis, corneal edema, or recurrent erosions) No signs and symptoms of keratoconjunctivitis sicca No concurrent use of contact lenses Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancies within the past 5 years except basal cell carcinoma or carcinoma in situ of the cervix No evidence of severe or uncontrolled systemic diseases (e.g., hepatitis B, hepatitis C, or HIV) No known chronic conditions No active dermatoses involving the face No evidence of any other significant clinical disorder or laboratory finding that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy for non-small cell lung cancer No concurrent biologic response modifiers Concurrent filgrastim (G-CSF) allowed only for persistent neutropenia despite dose reductions in prior course Chemotherapy: No prior chemotherapy for non-small cell lung cancer Endocrine therapy: No concurrent hormonal therapy No concurrent tamoxifen Radiotherapy: See Disease Characteristics At least 2 weeks since prior radiotherapy No concurrent radiotherapy Surgery: See Disease Characteristics Recovered from prior oncologic or other major surgery Other: No other concurrent anticancer therapy No other concurrent investigational agents No concurrent drugs with known significant 3A4 inhibitory effects (i.e., ketoconazole, itraconazole, troleandomycin, erythromycin, diltiazem, verapamil) No concurrent hydroxychloroquine, amiodarone, or chlorpromazine No concurrent topical eye medication Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Arms and Interventions \| Intervention/Treatment \| \| --- \| \|Drug: carboplatin\|nan\| \|Drug: gefitinib\|nan\| \|Drug: paclitaxel\|nan\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- recurrent non-small cell lung cancer, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer
NCT03044600	Gene Expression in Hyperparathyroidism	Objectives:~To better define the differences in molecular genetics of parathyroid tumors in patients with MEN1, single gland parathyroid disease in patients less than 50 years old and single gland disease in patients greater than 50 years old.~To better define the incidence of HRPT2 mutation in young patients with primary hyperparathyroidism and determine whether routine testing in these patients is indicated.	Patient charts will be reviewed to collect demographic data, pre-operative and post-operative clinical and laboratory data, operative reports, and pathology reports. Archived formalin-fixed paraffin-embedded (FFPE) tissue blocks from surgical specimens of patients will be stained for parafibromin to evaluate for HRPT2 mutations.	Gene Expression in Hyperparathyroidism: Identifying Molecular Differences in MEN1 Patients Versus Young MEN1 Negative Patients	Parathyroid Disease, Hyperparathyroidism	* Other: Chart Review * Other: HRPT2 Mutation Evaluation	Inclusion Criteria:~All patients previously enrolled in parathyroid tissue banking under protocol Lab08-0034.~For the subgroup designated for HRPT2 mutation testing:~Patients with primary hyperparathyroidism who are younger than 50 years of age and have tested negative for MEN1, between January 1, 1980 and the present.~Exclusion Criteria:~N/A	18 Years	null	All	No		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Molecular Genetics of Parathyroid Tumors \| RNA isolated from banked frozen tissues. cDNA microarray prepared using an Illumina array chip. Results analyzed using Ingenuity analysis software to detect 2-fold changes in gene expression. T-statistics used to determine significantly discriminating genes. \| 10 years \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| HRPT2 Mutations \| Archived formalin-fixed paraffin-embedded (FFPE) tissue blocks from surgical specimens of patients stained for parafibromin to evaluate for HRPT2 mutations. \| 10 years \|	Parathyroid disease, Hyperparathyroidism, Chart review, MEN1-negative, HRPT2 mutations	Hyperparathyroidism, Parathyroid Diseases, Endocrine System Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Young MEN1 Negative Group<br>Participants under 50 years of age who have been diagnosed with MEN1-negative primary hyperparathyroidism. \| Other: Chart Review<br>* Patient charts will be reviewed to collect demographic data, pre-operative and post-operative clinical and laboratory data, operative reports, and pathology reports.<br>Other: HRPT2 Mutation Evaluation<br>* Archived formalin-fixed paraffin-embedded (FFPE) tissue blocks from surgical specimens of patients stained for parafibromin to evaluate for HRPT2 mutations.<br>\|	Gene Expression in Hyperparathyroidism Study Overview ================= Brief Summary ----------------- Objectives: To better define the differences in molecular genetics of parathyroid tumors in patients with MEN1, single gland parathyroid disease in patients less than 50 years old and single gland disease in patients greater than 50 years old. To better define the incidence of HRPT2 mutation in young patients with primary hyperparathyroidism and determine whether routine testing in these patients is indicated. Detailed Description ----------------- Patient charts will be reviewed to collect demographic data, pre-operative and post-operative clinical and laboratory data, operative reports, and pathology reports. Archived formalin-fixed paraffin-embedded (FFPE) tissue blocks from surgical specimens of patients will be stained for parafibromin to evaluate for HRPT2 mutations. Official Title ----------------- Gene Expression in Hyperparathyroidism: Identifying Molecular Differences in MEN1 Patients Versus Young MEN1 Negative Patients Conditions ----------------- Parathyroid Disease, Hyperparathyroidism Intervention / Treatment ----------------- * Other: Chart Review * Other: HRPT2 Mutation Evaluation Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: All patients previously enrolled in parathyroid tissue banking under protocol Lab08-0034. For the subgroup designated for HRPT2 mutation testing: Patients with primary hyperparathyroidism who are younger than 50 years of age and have tested negative for MEN1, between January 1, 1980 and the present. Exclusion Criteria: N/A Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Young MEN1 Negative Group<br>Participants under 50 years of age who have been diagnosed with MEN1-negative primary hyperparathyroidism. \| Other: Chart Review<br>* Patient charts will be reviewed to collect demographic data, pre-operative and post-operative clinical and laboratory data, operative reports, and pathology reports.<br>Other: HRPT2 Mutation Evaluation<br>* Archived formalin-fixed paraffin-embedded (FFPE) tissue blocks from surgical specimens of patients stained for parafibromin to evaluate for HRPT2 mutations.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Molecular Genetics of Parathyroid Tumors \| RNA isolated from banked frozen tissues. cDNA microarray prepared using an Illumina array chip. Results analyzed using Ingenuity analysis software to detect 2-fold changes in gene expression. T-statistics used to determine significantly discriminating genes. \| 10 years \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| HRPT2 Mutations \| Archived formalin-fixed paraffin-embedded (FFPE) tissue blocks from surgical specimens of patients stained for parafibromin to evaluate for HRPT2 mutations. \| 10 years \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Parathyroid disease, Hyperparathyroidism, Chart review, MEN1-negative, HRPT2 mutations
NCT02977936	Management of Joint Pain Associated With Osteoarthritis of the Knee With Association of Plant Extracts.	The aim of the study is to evaluate at 3 months the effect of a supplementation with extracts of Curcuma longa, Boswellia serrata and Porphyra umbilicalis on the acceptability of pain for patients suffering from gonarthritic pain.	For this study, 126 patients are going to be included. They will have a supplementation of Cartimotil Fort®, from 1 to 4 capsules per day during 90 days.~on the one hand, during the two visits (inclusion and follow-up), the investigator completes the questionnaire about neuropathic pain (DN4).~on the other hand, patients complete the Osteoarthritis Symptom Inventory Scale (OASIS) 4 times : just after the inclusion visit, at day 30, at day 60 and just before the follow-up visit (day 90). He completes the Patient Global Impression of Improvement (PGII), the Minimal Clinically Important Improvement (MCII) and the Acceptable Symptomatic Statement (PASS) 6 times : just after the inclusion visit, at day 10, at day 20, at day 30, at day 60 and just before the follow-up visit (day 90).	Descriptive Study for the Management of Joint Pain Associated With Osteoarthritis of the Knee: Association of Extracts of Curcuma Longa, Boswellia Serrata and Porphyra Umbilicalis.	Gonarthrosis	* Dietary Supplement: Cartimotil Fort	Inclusion Criteria:~VAS of pain : minimum 5/10 on walking or 4/10 at rest~Patients with a negative PASS (patient considering that the symptomatic state is not acceptable)~Suffering from mono or bilateral femoro-tibial knee osteoarthrosis with painful seizures (confirmed by a radio of less than two years: stage 2 or 3 on the Kellgreen scale - clinical examination)~Having agreed to participate in the investigation after receiving information from the investigator~Exclusion Criteria:~Patients with rheumatological disorders other than osteoarthritis~Patients for whom knee surgery is planned within 3 months~Patients who started treatment with chondroitin sulphate (or all treatments of osteoarthritis other than anti-inflammatories and analgesics) for less than one month~Patients with a BMI greater than 35~Patients with chronic pain that can interfere with knee osteoarthritis pain~Patients with reduced mobility or bedridden~Patients with cognitive impairments not able to participate in the study~Patients with known allergies to any of the ingredients of Cartimotil Fort®~Pregnant or breastfeeding patients~Patients who do not wish to participate in the study.	18 Years	null	All	No		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Percentage of patients reaching the acceptability threshold of their state \| Percentage of patients reaching the acceptability threshold of their state between D0 and D30 measured by the binary response of the PASS (yes = acceptable). \| day 30 \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| OASIS Score \| \| Day 30 \| \| OASIS Score \| \| Day 60 \| \| OASIS Score \| \| Day 90 \| \| Yes answer for the PASS \| \| Day 60 \| \| Yes answer for the PASS \| \| Day 90 \|		Pain, Osteoarthritis, Osteoarthritis, Knee, Arthralgia, Arthritis, Joint Diseases, Musculoskeletal Diseases, Rheumatic Diseases, Neurologic Manifestations	\| Intervention/Treatment \| \| --- \| \|Dietary Supplement: Cartimotil Fort\|1 to 4 capsules per day during 90 days\|	Management of Joint Pain Associated With Osteoarthritis of the Knee With Association of Plant Extracts. Study Overview ================= Brief Summary ----------------- The aim of the study is to evaluate at 3 months the effect of a supplementation with extracts of Curcuma longa, Boswellia serrata and Porphyra umbilicalis on the acceptability of pain for patients suffering from gonarthritic pain. Detailed Description ----------------- For this study, 126 patients are going to be included. They will have a supplementation of Cartimotil Fort®, from 1 to 4 capsules per day during 90 days. on the one hand, during the two visits (inclusion and follow-up), the investigator completes the questionnaire about neuropathic pain (DN4). on the other hand, patients complete the Osteoarthritis Symptom Inventory Scale (OASIS) 4 times : just after the inclusion visit, at day 30, at day 60 and just before the follow-up visit (day 90). He completes the Patient Global Impression of Improvement (PGII), the Minimal Clinically Important Improvement (MCII) and the Acceptable Symptomatic Statement (PASS) 6 times : just after the inclusion visit, at day 10, at day 20, at day 30, at day 60 and just before the follow-up visit (day 90). Official Title ----------------- Descriptive Study for the Management of Joint Pain Associated With Osteoarthritis of the Knee: Association of Extracts of Curcuma Longa, Boswellia Serrata and Porphyra Umbilicalis. Conditions ----------------- Gonarthrosis Intervention / Treatment ----------------- * Dietary Supplement: Cartimotil Fort Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: VAS of pain : minimum 5/10 on walking or 4/10 at rest Patients with a negative PASS (patient considering that the symptomatic state is not acceptable) Suffering from mono or bilateral femoro-tibial knee osteoarthrosis with painful seizures (confirmed by a radio of less than two years: stage 2 or 3 on the Kellgreen scale - clinical examination) Having agreed to participate in the investigation after receiving information from the investigator Exclusion Criteria: Patients with rheumatological disorders other than osteoarthritis Patients for whom knee surgery is planned within 3 months Patients who started treatment with chondroitin sulphate (or all treatments of osteoarthritis other than anti-inflammatories and analgesics) for less than one month Patients with a BMI greater than 35 Patients with chronic pain that can interfere with knee osteoarthritis pain Patients with reduced mobility or bedridden Patients with cognitive impairments not able to participate in the study Patients with known allergies to any of the ingredients of Cartimotil Fort® Pregnant or breastfeeding patients Patients who do not wish to participate in the study. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions \| Intervention/Treatment \| \| --- \| \|Dietary Supplement: Cartimotil Fort\|1 to 4 capsules per day during 90 days\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Percentage of patients reaching the acceptability threshold of their state \| Percentage of patients reaching the acceptability threshold of their state between D0 and D30 measured by the binary response of the PASS (yes = acceptable). \| day 30 \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| OASIS Score \| \| Day 30 \| \| OASIS Score \| \| Day 60 \| \| OASIS Score \| \| Day 90 \| \| Yes answer for the PASS \| \| Day 60 \| \| Yes answer for the PASS \| \| Day 90 \|
NCT00289419	Intraarticular Analgesia After Total Hip Arthroplasty, a Randomised Study	The purpose of this study is to determine whether wound infiltration with following single-shot bolus injection with local anesthetic and NASIDs are effective in the treatment of postoperative pain after total hip replacement compared to continuous epidural infusion.	Sufficient postoperative pain relief after total hip replacement is necessary to achieve normal mobilisation and a reduction of the surgical stress response. After total hip replacement epidural treatment has proven superior, with regards to pain relief, than treatment with parenteral infusions and periphery nerve blocks. Even though epidural treatment gives excellent pain relief adverse effect as motor block, urine retention, hypotension and itching occurs regularly which delays rehabilitation.~Treatment with the administration of local anesthetic in the operating field has shown its efficiency in reducing postoperative pain with a low incidence of adverse effects after various surgical procedures.~This study compares continuous epidural infusion of ropivacaine added morphine to a new technique, where ropivacaine, ketorolac and adrenaline is used to infiltrate the tissue around the hip joint during surgery, and is injected by an intraarticular catheter 8 hours postoperative.~Data of pain scores, analgesia consumption, adverse effects and mobilisation is collected for the first 4 postoperative days.	Postoperative Analgesia After Total Hip Arthroplasty. A Comparison of Continuous Epidural Infusion and Wound Infiltration With Intraarticular Bolus Injection.	Arthroplasty, Replacement, Hip	* Drug: Epidural Ropivacaine, morphine * Drug: Ropivacaine, Ketorolac and Adrenaline	Inclusion Criteria:~Patients admitted consecutively to primary total hip arthroplasty due to arthrosis~Exclusion Criteria:~Patients unable to provide informed consent~Patients with contraindications for spinal anesthesia~Patients with known hypersensitivity towards the used drugs~Patients with severe chronic neurogenic pain~Patients with Rheumatoid arthritis~Patients with a daily opioid consumption	18 Years	null	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Consumption af analgesics \| \| 96 h \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Side effects \| \| 96 h \| \| Mobilization level \| \| 8 h \| \| Pain scores VAS \| \| 96 h \|	Arthroplasty, Replacement, Hip, Anesthetics, Local, Pain, Postoperative	Ketorolac, Epinephrine, Racepinephrine, Morphine, Ropivacaine, Epinephryl borate, Analgesics, Opioid, Narcotics, Central Nervous System Depressants, Physiological Effects of Drugs, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Anesthetics, Local, Anesthetics, Anti-Inflammatory Agents, Non-Steroidal, Analgesics, Non-Narcotic, Anti-Inflammatory Agents, Antirheumatic Agents, Cyclooxygenase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Adrenergic alpha-Agonists, Adrenergic Agonists, Adrenergic Agents, Neurotransmitter Agents, Adrenergic beta-Agonists, Bronchodilator Agents, Autonomic Agents, Anti-Asthmatic Agents, Respiratory System Agents, Mydriatics, Sympathomimetics, Vasoconstrictor Agents	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: A<br> \| Drug: Epidural Ropivacaine, morphine<br>* Infusion rate 4 ml/h in 48 h Solution 200 ml Ropivacaine 2mg/ml added 1 ml morphine 10 mg/ml<br>\| \| Experimental: B<br> \| Drug: Ropivacaine, Ketorolac and Adrenaline<br>* Wound infiltration: 100 ml Ropivacaine 2 mg/ml added 1 ml Ketorolac 30 mg/ml and 0,5 ml adrenaline 1 mg/ml Bolus injection: 20 ml Ropivacaine 7,5mg/ml added 1 ml Ketorolac 30 mg/ml and 0,5 ml adrenaline 1 mg/ml<br>\|	Intraarticular Analgesia After Total Hip Arthroplasty, a Randomised Study Study Overview ================= Brief Summary ----------------- The purpose of this study is to determine whether wound infiltration with following single-shot bolus injection with local anesthetic and NASIDs are effective in the treatment of postoperative pain after total hip replacement compared to continuous epidural infusion. Detailed Description ----------------- Sufficient postoperative pain relief after total hip replacement is necessary to achieve normal mobilisation and a reduction of the surgical stress response. After total hip replacement epidural treatment has proven superior, with regards to pain relief, than treatment with parenteral infusions and periphery nerve blocks. Even though epidural treatment gives excellent pain relief adverse effect as motor block, urine retention, hypotension and itching occurs regularly which delays rehabilitation. Treatment with the administration of local anesthetic in the operating field has shown its efficiency in reducing postoperative pain with a low incidence of adverse effects after various surgical procedures. This study compares continuous epidural infusion of ropivacaine added morphine to a new technique, where ropivacaine, ketorolac and adrenaline is used to infiltrate the tissue around the hip joint during surgery, and is injected by an intraarticular catheter 8 hours postoperative. Data of pain scores, analgesia consumption, adverse effects and mobilisation is collected for the first 4 postoperative days. Official Title ----------------- Postoperative Analgesia After Total Hip Arthroplasty. A Comparison of Continuous Epidural Infusion and Wound Infiltration With Intraarticular Bolus Injection. Conditions ----------------- Arthroplasty, Replacement, Hip Intervention / Treatment ----------------- * Drug: Epidural Ropivacaine, morphine * Drug: Ropivacaine, Ketorolac and Adrenaline Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients admitted consecutively to primary total hip arthroplasty due to arthrosis Exclusion Criteria: Patients unable to provide informed consent Patients with contraindications for spinal anesthesia Patients with known hypersensitivity towards the used drugs Patients with severe chronic neurogenic pain Patients with Rheumatoid arthritis Patients with a daily opioid consumption Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: A<br> \| Drug: Epidural Ropivacaine, morphine<br>* Infusion rate 4 ml/h in 48 h Solution 200 ml Ropivacaine 2mg/ml added 1 ml morphine 10 mg/ml<br>\| \| Experimental: B<br> \| Drug: Ropivacaine, Ketorolac and Adrenaline<br>* Wound infiltration: 100 ml Ropivacaine 2 mg/ml added 1 ml Ketorolac 30 mg/ml and 0,5 ml adrenaline 1 mg/ml Bolus injection: 20 ml Ropivacaine 7,5mg/ml added 1 ml Ketorolac 30 mg/ml and 0,5 ml adrenaline 1 mg/ml<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Consumption af analgesics \| \| 96 h \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Side effects \| \| 96 h \| \| Mobilization level \| \| 8 h \| \| Pain scores VAS \| \| 96 h \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Arthroplasty, Replacement, Hip, Anesthetics, Local, Pain, Postoperative
NCT03745248	Aerobic Exercise, Balance Training, and Ataxia	The first aim is to show aerobic training improves degenerative cerebellar patients functionally~The second aim is to compare the effects of balance and aerobic training on degenerative cerebellar disease.	Individuals with degenerative cerebellar disease (DCD) exhibit gradual loss of coordination resulting in impaired balance, gait deviations, and severe, progressive disability. With no available disease-modifying medications, balance training is the primary treatment option to improve motor skills and functional performance.~Aerobic training, on the other hand, may modify DCD progression as evident from animal data. Compared to sedentary controls, aerobically trained DCD rats have enhanced lifespan, motor function, and cerebellar Purkinje cell survival. Numerous animal studies also document that aerobic training has a direct, favorable effect on the brain that includes production of neurotrophic hormones, enhancement of neuroplasticity mechanisms, and protection from neurotoxins.~The effects of aerobic training in humans with DCD are relatively unknown, despite these encouraging animal data. A single study to date has evaluated the benefits of aerobic exercise on DCD in humans, and this was a secondary outcome of the study. Although participants performed limited aerobic training during the study, modest functional benefits were still detected.~The main objective of this project will be to compare the benefits of aerobic versus balance training in DCD. The investigators hypothesize that both aerobic and balance training will improve function in DCD subjects, but that the mechanisms in which these improvements occur differ.	Effects of Aerobic Exercise on Degenerative Cerebellar Disease	Ataxia, Spino Cerebellar Degeneration, Spinocerebellar Ataxias	* Behavioral: Aerobic training * Behavioral: Balance Training	Inclusion Criteria:~Diagnosed with spinocerebellar ataxia~Cerebellar atrophy on MRI~Prevalence of ataxia on clinical exam~Ability to safely ride a stationary exercise bike~Exclusion Criteria:~Other neurologic conditions~Heart disease~Cognitive impairment~Medical instability	18 Years	null	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Single blind randomized control trial Masking: Single	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change in SARA score \| Ataxia severity will be measured using the Scale for the Assessment and Rating of Ataxia (SARA).SARA evaluates the degree of ataxia by measuring gait, stance, sitting balance, speech, finger-chase test, nose-finger test, fast alternating movements, and heel-shin test. \| 1 month \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change in gait speed \| For the walking assessment, participants will walk as fast as possible on a 10-meter runway six times, and the investigators will average the times of trials 3-6 to determine gait speed expressed in meters/second. \| 1 month \| \| Change in static balance \| Static standing balance will be assessed by measuring postural sway during two, one-minute trials. Participants will stand with arms crossed over their chest and feet shoulder-width apart under two conditions: eyes open and eyes closed. Data will be collected using Bertec's dual split-belt treadmill (Bertec, Columbus, OH) embedded with force plates. Balance deficits will be calculated as the magnitude of postural sway (sway amplitude) using custom Nexus and Bodybuilder software (Vicon, Denver, CO). \| 1 month \|	Degenerative cerebellar disease, Ataxia, Aerobic Exercise	Ataxia, Cerebellar Ataxia, Spinocerebellar Ataxias, Spinocerebellar Degenerations, Cerebellar Diseases, Dyskinesias, Neurologic Manifestations, Nervous System Diseases, Brain Diseases, Central Nervous System Diseases, Spinal Cord Diseases, Heredodegenerative Disorders, Nervous System, Neurodegenerative Diseases, Genetic Diseases, Inborn	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Aerobic Training<br>Participants will be given a stationary exercise bike for home use. They will be instructed to use the exercise bike five times a week for thirty-minute sessions. The exercise intensity prescription will be based on the subject's VO2max determined on pre-test day. The exercise program will start at 60% of intensity per session, and then will be increased by steps of 5% intensity every 2 sessions until participants reach 30 minutes of training at 80% intensity. Participants will be contacted weekly by e-mail or phone to answer any questions about the exercise protocol and will be instructed to log each training session. Subjects will record duration of exercise, perceived exertion, average heart rate, maximum heart rate, and distance. \| Behavioral: Aerobic training<br>* Aerobic training on stationary bicycle for 30 minutes a day, 5 days a week for 1 month<br>\| \| Active Comparator: Balance Training<br>A physical therapist will tailor a home balance training program for each participant based on pre-training capabilities. Subjects will be asked to perform exercises five times a week for thirty-minute sessions. Both dynamic and static exercises will be performed in sitting and standing positions. Exercises will start with stabilizing in a challenging static position and progress to dynamic arm and leg movements in the same or modified position. Participants will be contacted weekly by e-mail or phone to answer any questions about the exercise protocol and will be required to log their exercise effort in terms of frequency and level of balance challenge. Individuals will be instructed to perform more difficult exercises if balance challenge scores are low. \| Behavioral: Balance Training<br>* Standard of care<br>\|	Aerobic Exercise, Balance Training, and Ataxia Study Overview ================= Brief Summary ----------------- The first aim is to show aerobic training improves degenerative cerebellar patients functionally The second aim is to compare the effects of balance and aerobic training on degenerative cerebellar disease. Detailed Description ----------------- Individuals with degenerative cerebellar disease (DCD) exhibit gradual loss of coordination resulting in impaired balance, gait deviations, and severe, progressive disability. With no available disease-modifying medications, balance training is the primary treatment option to improve motor skills and functional performance. Aerobic training, on the other hand, may modify DCD progression as evident from animal data. Compared to sedentary controls, aerobically trained DCD rats have enhanced lifespan, motor function, and cerebellar Purkinje cell survival. Numerous animal studies also document that aerobic training has a direct, favorable effect on the brain that includes production of neurotrophic hormones, enhancement of neuroplasticity mechanisms, and protection from neurotoxins. The effects of aerobic training in humans with DCD are relatively unknown, despite these encouraging animal data. A single study to date has evaluated the benefits of aerobic exercise on DCD in humans, and this was a secondary outcome of the study. Although participants performed limited aerobic training during the study, modest functional benefits were still detected. The main objective of this project will be to compare the benefits of aerobic versus balance training in DCD. The investigators hypothesize that both aerobic and balance training will improve function in DCD subjects, but that the mechanisms in which these improvements occur differ. Official Title ----------------- Effects of Aerobic Exercise on Degenerative Cerebellar Disease Conditions ----------------- Ataxia, Spino Cerebellar Degeneration, Spinocerebellar Ataxias Intervention / Treatment ----------------- * Behavioral: Aerobic training * Behavioral: Balance Training Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Diagnosed with spinocerebellar ataxia Cerebellar atrophy on MRI Prevalence of ataxia on clinical exam Ability to safely ride a stationary exercise bike Exclusion Criteria: Other neurologic conditions Heart disease Cognitive impairment Medical instability Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Single blind randomized control trial Masking: Single Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Aerobic Training<br>Participants will be given a stationary exercise bike for home use. They will be instructed to use the exercise bike five times a week for thirty-minute sessions. The exercise intensity prescription will be based on the subject's VO2max determined on pre-test day. The exercise program will start at 60% of intensity per session, and then will be increased by steps of 5% intensity every 2 sessions until participants reach 30 minutes of training at 80% intensity. Participants will be contacted weekly by e-mail or phone to answer any questions about the exercise protocol and will be instructed to log each training session. Subjects will record duration of exercise, perceived exertion, average heart rate, maximum heart rate, and distance. \| Behavioral: Aerobic training<br>* Aerobic training on stationary bicycle for 30 minutes a day, 5 days a week for 1 month<br>\| \| Active Comparator: Balance Training<br>A physical therapist will tailor a home balance training program for each participant based on pre-training capabilities. Subjects will be asked to perform exercises five times a week for thirty-minute sessions. Both dynamic and static exercises will be performed in sitting and standing positions. Exercises will start with stabilizing in a challenging static position and progress to dynamic arm and leg movements in the same or modified position. Participants will be contacted weekly by e-mail or phone to answer any questions about the exercise protocol and will be required to log their exercise effort in terms of frequency and level of balance challenge. Individuals will be instructed to perform more difficult exercises if balance challenge scores are low. \| Behavioral: Balance Training<br>* Standard of care<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change in SARA score \| Ataxia severity will be measured using the Scale for the Assessment and Rating of Ataxia (SARA).SARA evaluates the degree of ataxia by measuring gait, stance, sitting balance, speech, finger-chase test, nose-finger test, fast alternating movements, and heel-shin test. \| 1 month \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change in gait speed \| For the walking assessment, participants will walk as fast as possible on a 10-meter runway six times, and the investigators will average the times of trials 3-6 to determine gait speed expressed in meters/second. \| 1 month \| \| Change in static balance \| Static standing balance will be assessed by measuring postural sway during two, one-minute trials. Participants will stand with arms crossed over their chest and feet shoulder-width apart under two conditions: eyes open and eyes closed. Data will be collected using Bertec's dual split-belt treadmill (Bertec, Columbus, OH) embedded with force plates. Balance deficits will be calculated as the magnitude of postural sway (sway amplitude) using custom Nexus and Bodybuilder software (Vicon, Denver, CO). \| 1 month \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Degenerative cerebellar disease, Ataxia, Aerobic Exercise
NCT04942275	Lung Perfusion PET / CT Using Ga68-MAA for Preservation of Lung Function During Stereotactic Pulmonary Radiation Therapy	This is a prospective study evaluating the feasibility of treatment planning integrating lung perfusion PET/CT using Ga68-MAA to preserve functional lung areas during stereotactic body radiation therapy (SBRT).	Lung perfusion PET / CT is a new imaging modality based on the use of the same cold molecules as those used for a conventional perfusion lung scan. Similartly, perfusion images are obtained after intravenous administration of human albumin macroaggregates, which are embolized in pulmonary capillaries according to pulmonary blood flow. However, these cold molecules are radiolabeled, not with Technetium99m, but with Gallium68, a ß + isotope, allowing image acquisition with PET technology. The same physiological processes are therefore observed with conventional scintigraphy PET imaging, but PET is an intrinsically superior technique for image acquisition, with greater sensitivity, better spatial and temporal resolutions and the possibility to perform respiratory-gated acquisition, allowing a better definition of the pulmonary functional volumes.~The aim is to evaluate the feasability of functional lung avoidance planification using lung perfusion PET/CT imaging during SBRT.~Patients will benefit from a pre-treatment functional assessment including PET/CT imaging.~The treatment planning will be carried out in 2 stages:~First, an anatomical planning will be carried out, blinded to the PET results.~Then, a functional planning, respecting the standard constraints applied during anatomical planning, but also incorporating a new functional lung volume constraint defined by PET/CT images, will be carried out.~A follow-up will be carried out for 12 months, including repeated perfusion PET/CT imaging at 3 and 12 months.	Lung Perfusion PET / CT Using Gallium68-MMA for Preservation of Lung Function During Stereotactic Pulmonary Radiation Therapy	SBRT, Non-small Cell Lung Cancer, Lung Metastasis	* Drug: Pre-therapeutic imaging test	Inclusion Criteria:~Age >18 years~Insured patient~Patient treated at the Brest CHRU for SBRT of a primary or secondary pulmonary lesion~Exclusion Criteria:~Unable/unwilling to give informed consent~Pregnancy / breast-feeding patient~Patient under guardianship or curatorship~Patient with contraindication to the administration of macroaggregates of human albumin	18 Years	null	All	No	Primary Purpose: Other Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Patients with a dose reduction to the functional lung (estimated during functional planning). \| Percentage of patients for whom it is possible to reduce the dose to the functional lung (estimated during the functional planning).~A reduction in the dose to the functional lung will be defined by:~A decrease of at least 5% in functional lung volume included in V20Gy. or~A decrease of at least 5% in total relative lung function included in the V20G. \| Baseline, one week after lung perfusion PET / CT scan using Ga68-MAA \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Impact of lung perfusion PET / CT scan on lung activity during SBRT (stereotactic body radiation therapy) planning \| Percentage of activity included in the V20Gy with the anatomical planning and the functional planning. \| Baseline, one week after lung perfusion PET / CT scan using Ga68-MAA \| \| Impact of lung perfusion PET / CT scan on lung activity during SBRT (stereotactic body radiation therapy) planning \| Percentage of functional lung volume included in the V20Gy with anatomical planning and during functional planning \| Baseline, one week after lung perfusion PET / CT scan using Ga68-MAA \| \| Pulmonary toxicity at 3 months \| Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-C30 : European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire - Cancer module 30) at 3 months \| At 3 months after SBRT (stereotactic body radiation therapy) \| \| Pulmonary toxicity at 3 months \| Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-LC13 :European Organisation for Research and Treatment of Cancer- Quality of Life Questionnaire - Lung Cancer module 13) at 3 months \| At 3 months after SBRT( stereotactic body radiation therapy) \| \| Pulmonary toxicity at 6 months \| Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-C30 : European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire -Cancer module 30) at 6 months \| At 6 months after SBRT (stereotactic body radiation therapy) \| \| Pulmonary toxicity at 6 months \| Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-LC13 : European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire - Lung Cancer module 13) at 6 months \| At 6 months after SBRT (stereotactic body radiation therapy) \| \| Pulmonary toxicity at 9 months \| Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-C30 : European Organisation for Research and Treatment of Cancer -Quality of Life Questionnaire - Cancer module 30) at 9 months \| At 9 months after SBRT (stereotactic body radiation therapy) \| \| Pulmonary toxicity at 9 months \| Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-LC13 : European Organisation for Research and Treatment of Cancer -Quality of Life Questionnaire - Lung Cancer module 13) at 9 months \| At 9 months after SBRT (stereotactic body radiation therapy) \| \| Pulmonary toxicity at 12 months \| Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-C30 : European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire - Cancer module 30) at 12 months \| At 12 months after SBRT (stereotactic body radiation therapy) \| \| Pulmonary toxicity at 12 months \| Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-LC13 : European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire - Lung Cancer module 13) at 12 months \| At 12 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at Day 0 (inclusion) \| Results of EuroQol (EQ-5D-5L) questionnaire \| Baseline, Day 0 \| \| Dyspnea at Day 0 (inclusion) \| Results of Pulmonary Function testing (PFT) : FEV1 \| Baseline, Day 0 \| \| Dyspnea at Day 0 (inclusion) \| Results of Pulmonary Function testing (PFT) : FEV1/FVC \| Baseline, Day 0 \| \| Dyspnea at Day 0 (inclusion) \| Results of 6 minutes Walk Test (6MWT) \| Baseline, Day 0 \| \| Dyspnea at 3 months \| Results of EuroQol (EQ-5D-5L) questionnaire \| At 3 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 3 months \| Results of Pulmonary Function testing (PFT) : FEV1 \| At 3 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 3 months \| Results of Pulmonary Function testing (PFT) : FEV1/FVC \| At 3 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 3 months \| Results of 6 minutes Walk Test (6MWT) \| At 3 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 6 months \| Results of EuroQol (EQ-5D-5L) questionnaire \| At 6 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 6 months \| Results of Pulmonary Function testing (PFT) : FEV1 \| At 6 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 6 months \| Results of Pulmonary Function testing (PFT) : FEV1/FVC \| At 6 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 6 months \| Results of 6 minutes Walk Test (6MWT) \| At 6 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 9 months \| Results of EuroQol (EQ-5D-5L) questionnaire \| At 9 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 9 months \| Results of Pulmonary Function testing (PFT) : FEV1 \| At 9 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 9 months \| Results of Pulmonary Function testing (PFT) : FEV1/FVC \| At 9 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 9 months \| Results of 6 minutes Walk Test (6MWT) \| At 9 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 12 months \| Results of EuroQol (EQ-5D-5L) questionnaire \| At 12 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 12 months \| Results of Pulmonary Function testing (PFT) : FEV1 \| At 12 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 12 months \| Results of Pulmonary Function testing (PFT) : FEV1/FVC \| At 12 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 12 months \| Results of 6 minutes Walk Test (6MWT) \| At 12 months after SBRT (stereotactic body radiation therapy) \|	SBRT, Radiation induced lung injury, Perfusion imaging, Positron EmissionTomography, Lung cancer	Neoplasms, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Intervention : Lung perfusion PET/CT using Ga68-MAA and SBRT planification<br>All patients included for treatment with stereotactic radiotherapy for non-small cell lung cancer or lung metastasis will benefit from a pre-therapeutic functional assessment including:~The standard functional assessment recommended before performing an SBRT.~A perfusion PET/CT scan~The treatment planning will be carried out in 2 stages:~First, an anatomical planning will be carried out, blinded to the PET results.~Then, a functional planning, respecting the standard constraints applied during anatomical planning, but also incorporating a new functional lung volume constraint defined by pulmonary PET, will then be carried out.~A follow-up will be carried out for 12 months, including repeated perfusion PET/CT imaging at 3 and 12 months \| Drug: Pre-therapeutic imaging test<br>* The radiopharmaceutical used for lung perfusion PET consists in human albumin macroaggregates labeled with Ga-68 (68Ga-MAA). 68Ga- MAA are administrated intravenously.<br>\|	Lung Perfusion PET / CT Using Ga68-MAA for Preservation of Lung Function During Stereotactic Pulmonary Radiation Therapy Study Overview ================= Brief Summary ----------------- This is a prospective study evaluating the feasibility of treatment planning integrating lung perfusion PET/CT using Ga68-MAA to preserve functional lung areas during stereotactic body radiation therapy (SBRT). Detailed Description ----------------- Lung perfusion PET / CT is a new imaging modality based on the use of the same cold molecules as those used for a conventional perfusion lung scan. Similartly, perfusion images are obtained after intravenous administration of human albumin macroaggregates, which are embolized in pulmonary capillaries according to pulmonary blood flow. However, these cold molecules are radiolabeled, not with Technetium99m, but with Gallium68, a ß + isotope, allowing image acquisition with PET technology. The same physiological processes are therefore observed with conventional scintigraphy PET imaging, but PET is an intrinsically superior technique for image acquisition, with greater sensitivity, better spatial and temporal resolutions and the possibility to perform respiratory-gated acquisition, allowing a better definition of the pulmonary functional volumes. The aim is to evaluate the feasability of functional lung avoidance planification using lung perfusion PET/CT imaging during SBRT. Patients will benefit from a pre-treatment functional assessment including PET/CT imaging. The treatment planning will be carried out in 2 stages: First, an anatomical planning will be carried out, blinded to the PET results. Then, a functional planning, respecting the standard constraints applied during anatomical planning, but also incorporating a new functional lung volume constraint defined by PET/CT images, will be carried out. A follow-up will be carried out for 12 months, including repeated perfusion PET/CT imaging at 3 and 12 months. Official Title ----------------- Lung Perfusion PET / CT Using Gallium68-MMA for Preservation of Lung Function During Stereotactic Pulmonary Radiation Therapy Conditions ----------------- SBRT, Non-small Cell Lung Cancer, Lung Metastasis Intervention / Treatment ----------------- * Drug: Pre-therapeutic imaging test Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age >18 years Insured patient Patient treated at the Brest CHRU for SBRT of a primary or secondary pulmonary lesion Exclusion Criteria: Unable/unwilling to give informed consent Pregnancy / breast-feeding patient Patient under guardianship or curatorship Patient with contraindication to the administration of macroaggregates of human albumin Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Other Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Intervention : Lung perfusion PET/CT using Ga68-MAA and SBRT planification<br>All patients included for treatment with stereotactic radiotherapy for non-small cell lung cancer or lung metastasis will benefit from a pre-therapeutic functional assessment including: The standard functional assessment recommended before performing an SBRT. A perfusion PET/CT scan The treatment planning will be carried out in 2 stages: First, an anatomical planning will be carried out, blinded to the PET results. Then, a functional planning, respecting the standard constraints applied during anatomical planning, but also incorporating a new functional lung volume constraint defined by pulmonary PET, will then be carried out. A follow-up will be carried out for 12 months, including repeated perfusion PET/CT imaging at 3 and 12 months \| Drug: Pre-therapeutic imaging test<br>* The radiopharmaceutical used for lung perfusion PET consists in human albumin macroaggregates labeled with Ga-68 (68Ga-MAA). 68Ga- MAA are administrated intravenously.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Patients with a dose reduction to the functional lung (estimated during functional planning). \| Percentage of patients for whom it is possible to reduce the dose to the functional lung (estimated during the functional planning). A reduction in the dose to the functional lung will be defined by: A decrease of at least 5% in functional lung volume included in V20Gy. or A decrease of at least 5% in total relative lung function included in the V20G. \| Baseline, one week after lung perfusion PET / CT scan using Ga68-MAA \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Impact of lung perfusion PET / CT scan on lung activity during SBRT (stereotactic body radiation therapy) planning \| Percentage of activity included in the V20Gy with the anatomical planning and the functional planning. \| Baseline, one week after lung perfusion PET / CT scan using Ga68-MAA \| \| Impact of lung perfusion PET / CT scan on lung activity during SBRT (stereotactic body radiation therapy) planning \| Percentage of functional lung volume included in the V20Gy with anatomical planning and during functional planning \| Baseline, one week after lung perfusion PET / CT scan using Ga68-MAA \| \| Pulmonary toxicity at 3 months \| Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-C30 : European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire - Cancer module 30) at 3 months \| At 3 months after SBRT (stereotactic body radiation therapy) \| \| Pulmonary toxicity at 3 months \| Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-LC13 :European Organisation for Research and Treatment of Cancer- Quality of Life Questionnaire - Lung Cancer module 13) at 3 months \| At 3 months after SBRT( stereotactic body radiation therapy) \| \| Pulmonary toxicity at 6 months \| Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-C30 : European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire -Cancer module 30) at 6 months \| At 6 months after SBRT (stereotactic body radiation therapy) \| \| Pulmonary toxicity at 6 months \| Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-LC13 : European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire - Lung Cancer module 13) at 6 months \| At 6 months after SBRT (stereotactic body radiation therapy) \| \| Pulmonary toxicity at 9 months \| Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-C30 : European Organisation for Research and Treatment of Cancer -Quality of Life Questionnaire - Cancer module 30) at 9 months \| At 9 months after SBRT (stereotactic body radiation therapy) \| \| Pulmonary toxicity at 9 months \| Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-LC13 : European Organisation for Research and Treatment of Cancer -Quality of Life Questionnaire - Lung Cancer module 13) at 9 months \| At 9 months after SBRT (stereotactic body radiation therapy) \| \| Pulmonary toxicity at 12 months \| Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-C30 : European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire - Cancer module 30) at 12 months \| At 12 months after SBRT (stereotactic body radiation therapy) \| \| Pulmonary toxicity at 12 months \| Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-LC13 : European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire - Lung Cancer module 13) at 12 months \| At 12 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at Day 0 (inclusion) \| Results of EuroQol (EQ-5D-5L) questionnaire \| Baseline, Day 0 \| \| Dyspnea at Day 0 (inclusion) \| Results of Pulmonary Function testing (PFT) : FEV1 \| Baseline, Day 0 \| \| Dyspnea at Day 0 (inclusion) \| Results of Pulmonary Function testing (PFT) : FEV1/FVC \| Baseline, Day 0 \| \| Dyspnea at Day 0 (inclusion) \| Results of 6 minutes Walk Test (6MWT) \| Baseline, Day 0 \| \| Dyspnea at 3 months \| Results of EuroQol (EQ-5D-5L) questionnaire \| At 3 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 3 months \| Results of Pulmonary Function testing (PFT) : FEV1 \| At 3 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 3 months \| Results of Pulmonary Function testing (PFT) : FEV1/FVC \| At 3 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 3 months \| Results of 6 minutes Walk Test (6MWT) \| At 3 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 6 months \| Results of EuroQol (EQ-5D-5L) questionnaire \| At 6 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 6 months \| Results of Pulmonary Function testing (PFT) : FEV1 \| At 6 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 6 months \| Results of Pulmonary Function testing (PFT) : FEV1/FVC \| At 6 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 6 months \| Results of 6 minutes Walk Test (6MWT) \| At 6 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 9 months \| Results of EuroQol (EQ-5D-5L) questionnaire \| At 9 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 9 months \| Results of Pulmonary Function testing (PFT) : FEV1 \| At 9 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 9 months \| Results of Pulmonary Function testing (PFT) : FEV1/FVC \| At 9 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 9 months \| Results of 6 minutes Walk Test (6MWT) \| At 9 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 12 months \| Results of EuroQol (EQ-5D-5L) questionnaire \| At 12 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 12 months \| Results of Pulmonary Function testing (PFT) : FEV1 \| At 12 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 12 months \| Results of Pulmonary Function testing (PFT) : FEV1/FVC \| At 12 months after SBRT (stereotactic body radiation therapy) \| \| Dyspnea at 12 months \| Results of 6 minutes Walk Test (6MWT) \| At 12 months after SBRT (stereotactic body radiation therapy) \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- SBRT, Radiation induced lung injury, Perfusion imaging, Positron EmissionTomography, Lung cancer
NCT04419597	Hemopatch Safety and Efficacy Evaluation Versus Standard Practice for Sealing the Dura in Cerebrospinal Fluid Leaks	Posterior fossa surgeries are generally complicated by difficulties in creating a watertight dural closure, which often requires the use of dural substitutes. In particular, surgical procedures at this location are associated with an increased rate of fluid leakage (cerebrospinal fluid (CSF)) or inflow (blood, air, etc.) creating hydrodynamic complications. Effective sealing of the dura is required to prevent such complications and infections by minimizing the introduction of irritating blood products into the CSF. Since true hermetic dural seals are often impossible to achieve, dural sealants have been developed that can be applied to the sutured dural perimeter to help prevent complications related to CSF. Adjuvant use of such sealants may be prudent, particularly in posterior fossa surgeries, as the incidence of CSF leakage has been reported to be as high as approximately 15-28% with such surgeries, with an increased risk of leakage. 5.84 times greater than supratentorial procedures.	Various techniques have been developed to overcome this problem and achieve a tight dural closure. Although there is published evidence showing the efficacy and safety of some of these sealants in posterior fossa surgery, the different types of pathologies and various population risk factors included in these trials make it difficult to interpret the results. Having selective inclusion criteria and including patients with a selected pathology could be essential to obtain clearer results.~Postoperative CSF leak has two aspects: one is pseudomeningocele (a subcutaneous collection of CSF); the other is a CSF fistula in which CSF reaches the skin. This second one is much more dangerous and constitutes one of the most important complications of this surgery, but the pseudomeningocele is a clinical demonstration of failure of the dural closure.~HEMOPATCH is a soft, thin, foldable and flexible collagen patch, coated with NHS-PEG. HEMOPATCH is indicated as a hemostatic device and surgical seal for procedures in which control of bleeding or leakage of other body fluids or air by conventional surgical techniques is ineffective or impractical.~Preliminary clinical evidence collects a prospective case series of 200 patients, in which the authors reviewed the use of HEMOPATCH for dural augmentation in high-risk patients from 2014 to this year. After 2 years of refining the technique, a decrease in CSF leaks from 27% to 7% was achieved, and no adverse events related to the application of the product were observed. A retrospective cohort study has recently been published comparing the use of HEMOPATCH versus routine clinical practice in 290 patients, in which 147 used standard dural reinforcement techniques, and 143 used HEMOPATCH. The CSF fistula appearance rates were 7.69% in the HEMOPATCH group, compared to 32.65% in the control group.~These recent results, along with the characteristics and properties of the patch, could make this sealant a safe and plausible option to achieve sealing after posterior fossa surgery.	Randomized Multicenter Controlled Study to Evaluate the Safety and Efficacy of HEMOPATCH® Compared to Routine Care for Dural Closure as Reinforcement for the Prevention of Postoperative Cerebrospinal Fluid Leakage (CSF) in Patients Undergoing Posterior Fossa Surgery	Surgery	* Device: HEMOPATCH * Device: Standard of care	Inclusion Criteria:~Patients who are planned for non-traumatic posterior fossa surgery~Surgery that requires opening and closing of the dura mater.~Patients who have a clean surgical wound (class I surgical wound classification)~Patients undergoing one of the following surgical procedures:~Space occupant injuries (LOEs) rese dried through the following approaches:~Approaching the rear pit of the middle line~Approach to the posterior paramedian fossa~Approach to the cerebellar pontine angle (PC) and the back of the petrous vertex~Clinical diagnosis of primary Chiari 1 (CM1) malformation and scheduled decompression surgery, with evidence of NM of tonsil herniation down by an independent official radiology report.~Subjects who are able to provide written informed consent prior to participating in the clinical trial.~Be over 18 years of age.~Understand the purpose of the study and be available for frequent hospital visits.~Women of childbearing potential and males with partners of childbearing potential should commit to using a highly effective method of contraception (such as surgical sterilization, double barrier method, oral contraceptives or contraceptive hormonal implants) and to continue to use them for up to 6 months after surgery.~Exclusion Criteria:~Patients undergoing a supratentorial surgical procedure/approach.~Patients undergoing any other approach/surgical procedure at the base of the skull that is not in the posterior pit:~Side boarding of the foramen magno: far side, extreme side, anterolateral, posterolateral,~Approaching the jugular foramen: infratemporal, condylar juxta, transjugular~Approach to the middle pit: subtemporal (+/-petrous apex perforation), pterional approach (any temporary fronto approach +/- orbitozygomatic replacement)~Approach to the previous pit: subfrontal (uni or bilateral)~Presence of hydrocephalus not resolved prior to surgery~Previous surgery in the posterior pit.~Pre-radiation therapy treatment.~Previous (within the last 6 months) or anticipated neurosurgical procedure involving the opening of the dura mater that may affect the safety assessment~> 1 dural opening~Inability to understand informed consent or unwillingness to participate in the study.~Inability, at the time of consent, to return for follow-up evaluations after surgery~Evidence of spinal dysraphism.~Allergy, hypersensitivity or history of allergic reaction to Hemopatch or its components (to bovine proteins or bright blue dye: FD&C blue No. 1 [blue 1]).~Evidence of an infection within 5 days prior to the start of the study.~Pregnancy or planning to become pregnant during the course of the study. Breast feeding	18 Years	null	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| proportion of participants with clinically evident CSF leak after the operation up to 4 weeks. \| Clinically evident CSF leak, observed from the operation to 4 weeks later. It will be measured every 24 hours until the patient is discharged. The following measurement will be made at the visit of the 4 weeks (+/- 7 days) from the operation \| 4 weeks \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Proportion of participants with clinical pseudomeningocele or evident MRI \| Clinical evidence of Pseudomeningocele or by imaging techniques, evaluated by CT or MRI during the 4 postoperative weeks, by MRI at 6 postoperative months, or at any visit of patients within 6 postoperative months according to the criteria of the investigator \| 6 months \| \| Proportion of participants with ascent of the cerebellar tonsils \| The elevation of the cerebellar tonsils will be measured, according to the baseline preoperative CT / MRI, in the MRI test performed 6 months after the operation. \| 6 months \| \| Proportion of participants with readmissions related to CSF leaks \| The need for readmission / reoperation related to CSF leak will be collected up to 4 weeks after the operation. \| 4 weeks \| \| Number of Participants with Surgical site infections (SSI) \| Bacterial or chemical meningitis (SSI) \| 4 weeks \| \| Assessment of quality of life (QoL): SF12 questionnaire (Short Form 12 questionnaire) \| The SF-12 measures overall quality of life and includes items that assess participation. The SF-12 is a frequently used measure and has shown to have good internal consistency, reliability, construct validity and responsiveness in patients with chronic (low) back pain (Luo et al., 2003). The measure is a subset of 12 items from the SF-36 including 6 items from the physical summary measure (PCS) and 6 items from the mental summary measure (MCS). \| 6 months \|	Posterior fossa, HEMOPATCH, cerebrospinal fluid (CSF), CSF leak		\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: HEMOPATCH Collagen Patch and PEG Haemostatic Sealant<br>Two units of the large patch are applied as reinforcement of the primary dural seal (HEMOPATCH 4,5x9cm, 1506253). \| Device: HEMOPATCH<br>* The treatment will be performed with the HEMOPATCH collagen patch and hemostatic PEG sealant (Baxter), applying two units of the large patch to reinforce the primary dural closure (HEMOPATCH 4.5x9cm, 1506253).<br>\| \| Active Comparator: Standard of care treatment<br>Usual clinical practice techniques for reinforcing primary dural closure. \| Device: Standard of care<br>* Usual clinical practice techniques for reinforcing primary dural closure.<br>\|	Hemopatch Safety and Efficacy Evaluation Versus Standard Practice for Sealing the Dura in Cerebrospinal Fluid Leaks Study Overview ================= Brief Summary ----------------- Posterior fossa surgeries are generally complicated by difficulties in creating a watertight dural closure, which often requires the use of dural substitutes. In particular, surgical procedures at this location are associated with an increased rate of fluid leakage (cerebrospinal fluid (CSF)) or inflow (blood, air, etc.) creating hydrodynamic complications. Effective sealing of the dura is required to prevent such complications and infections by minimizing the introduction of irritating blood products into the CSF. Since true hermetic dural seals are often impossible to achieve, dural sealants have been developed that can be applied to the sutured dural perimeter to help prevent complications related to CSF. Adjuvant use of such sealants may be prudent, particularly in posterior fossa surgeries, as the incidence of CSF leakage has been reported to be as high as approximately 15-28% with such surgeries, with an increased risk of leakage. 5.84 times greater than supratentorial procedures. Detailed Description ----------------- Various techniques have been developed to overcome this problem and achieve a tight dural closure. Although there is published evidence showing the efficacy and safety of some of these sealants in posterior fossa surgery, the different types of pathologies and various population risk factors included in these trials make it difficult to interpret the results. Having selective inclusion criteria and including patients with a selected pathology could be essential to obtain clearer results. Postoperative CSF leak has two aspects: one is pseudomeningocele (a subcutaneous collection of CSF); the other is a CSF fistula in which CSF reaches the skin. This second one is much more dangerous and constitutes one of the most important complications of this surgery, but the pseudomeningocele is a clinical demonstration of failure of the dural closure. HEMOPATCH is a soft, thin, foldable and flexible collagen patch, coated with NHS-PEG. HEMOPATCH is indicated as a hemostatic device and surgical seal for procedures in which control of bleeding or leakage of other body fluids or air by conventional surgical techniques is ineffective or impractical. Preliminary clinical evidence collects a prospective case series of 200 patients, in which the authors reviewed the use of HEMOPATCH for dural augmentation in high-risk patients from 2014 to this year. After 2 years of refining the technique, a decrease in CSF leaks from 27% to 7% was achieved, and no adverse events related to the application of the product were observed. A retrospective cohort study has recently been published comparing the use of HEMOPATCH versus routine clinical practice in 290 patients, in which 147 used standard dural reinforcement techniques, and 143 used HEMOPATCH. The CSF fistula appearance rates were 7.69% in the HEMOPATCH group, compared to 32.65% in the control group. These recent results, along with the characteristics and properties of the patch, could make this sealant a safe and plausible option to achieve sealing after posterior fossa surgery. Official Title ----------------- Randomized Multicenter Controlled Study to Evaluate the Safety and Efficacy of HEMOPATCH® Compared to Routine Care for Dural Closure as Reinforcement for the Prevention of Postoperative Cerebrospinal Fluid Leakage (CSF) in Patients Undergoing Posterior Fossa Surgery Conditions ----------------- Surgery Intervention / Treatment ----------------- * Device: HEMOPATCH * Device: Standard of care Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients who are planned for non-traumatic posterior fossa surgery Surgery that requires opening and closing of the dura mater. Patients who have a clean surgical wound (class I surgical wound classification) Patients undergoing one of the following surgical procedures: Space occupant injuries (LOEs) rese dried through the following approaches: Approaching the rear pit of the middle line Approach to the posterior paramedian fossa Approach to the cerebellar pontine angle (PC) and the back of the petrous vertex Clinical diagnosis of primary Chiari 1 (CM1) malformation and scheduled decompression surgery, with evidence of NM of tonsil herniation down by an independent official radiology report. Subjects who are able to provide written informed consent prior to participating in the clinical trial. Be over 18 years of age. Understand the purpose of the study and be available for frequent hospital visits. Women of childbearing potential and males with partners of childbearing potential should commit to using a highly effective method of contraception (such as surgical sterilization, double barrier method, oral contraceptives or contraceptive hormonal implants) and to continue to use them for up to 6 months after surgery. Exclusion Criteria: Patients undergoing a supratentorial surgical procedure/approach. Patients undergoing any other approach/surgical procedure at the base of the skull that is not in the posterior pit: Side boarding of the foramen magno: far side, extreme side, anterolateral, posterolateral, Approaching the jugular foramen: infratemporal, condylar juxta, transjugular Approach to the middle pit: subtemporal (+/-petrous apex perforation), pterional approach (any temporary fronto approach +/- orbitozygomatic replacement) Approach to the previous pit: subfrontal (uni or bilateral) Presence of hydrocephalus not resolved prior to surgery Previous surgery in the posterior pit. Pre-radiation therapy treatment. Previous (within the last 6 months) or anticipated neurosurgical procedure involving the opening of the dura mater that may affect the safety assessment > 1 dural opening Inability to understand informed consent or unwillingness to participate in the study. Inability, at the time of consent, to return for follow-up evaluations after surgery Evidence of spinal dysraphism. Allergy, hypersensitivity or history of allergic reaction to Hemopatch or its components (to bovine proteins or bright blue dye: FD&C blue No. 1 [blue 1]). Evidence of an infection within 5 days prior to the start of the study. Pregnancy or planning to become pregnant during the course of the study. Breast feeding Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: HEMOPATCH Collagen Patch and PEG Haemostatic Sealant<br>Two units of the large patch are applied as reinforcement of the primary dural seal (HEMOPATCH 4,5x9cm, 1506253). \| Device: HEMOPATCH<br>* The treatment will be performed with the HEMOPATCH collagen patch and hemostatic PEG sealant (Baxter), applying two units of the large patch to reinforce the primary dural closure (HEMOPATCH 4.5x9cm, 1506253).<br>\| \| Active Comparator: Standard of care treatment<br>Usual clinical practice techniques for reinforcing primary dural closure. \| Device: Standard of care<br>* Usual clinical practice techniques for reinforcing primary dural closure.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| proportion of participants with clinically evident CSF leak after the operation up to 4 weeks. \| Clinically evident CSF leak, observed from the operation to 4 weeks later. It will be measured every 24 hours until the patient is discharged. The following measurement will be made at the visit of the 4 weeks (+/- 7 days) from the operation \| 4 weeks \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Proportion of participants with clinical pseudomeningocele or evident MRI \| Clinical evidence of Pseudomeningocele or by imaging techniques, evaluated by CT or MRI during the 4 postoperative weeks, by MRI at 6 postoperative months, or at any visit of patients within 6 postoperative months according to the criteria of the investigator \| 6 months \| \| Proportion of participants with ascent of the cerebellar tonsils \| The elevation of the cerebellar tonsils will be measured, according to the baseline preoperative CT / MRI, in the MRI test performed 6 months after the operation. \| 6 months \| \| Proportion of participants with readmissions related to CSF leaks \| The need for readmission / reoperation related to CSF leak will be collected up to 4 weeks after the operation. \| 4 weeks \| \| Number of Participants with Surgical site infections (SSI) \| Bacterial or chemical meningitis (SSI) \| 4 weeks \| \| Assessment of quality of life (QoL): SF12 questionnaire (Short Form 12 questionnaire) \| The SF-12 measures overall quality of life and includes items that assess participation. The SF-12 is a frequently used measure and has shown to have good internal consistency, reliability, construct validity and responsiveness in patients with chronic (low) back pain (Luo et al., 2003). The measure is a subset of 12 items from the SF-36 including 6 items from the physical summary measure (PCS) and 6 items from the mental summary measure (MCS). \| 6 months \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Posterior fossa, HEMOPATCH, cerebrospinal fluid (CSF), CSF leak
NCT03808428	CUHK Jockey Club HOPE 4 Care Programme - Ankle Robot	The Hong Kong Jockey Club Charities Trust has supported CUHK to launch a three-year project 'CUHK Jockey Club HOPE4Care Programme' to implement four evidence-based advanced rehabilitation technologies in 40 local elderly day care centres and rehabilitation centres, to benefit the community. The Exoskeleton Ankle Robot is a robot-assisted Ankle-Foot-Orthosis to facilitate gait training of person after stroke with drop foot.		CUHK Jockey Club Tech-Based Stroke Rehabilitation Programme for Elderly Centre - Interactive Exoskeleton Ankle Robot	Stroke	* Device: Ankle Group	Inclusion Criteria:~have the ability to walk on the ground independently or with one personal assistance with or without walking aids~able to understand simple commends~Exclusion Criteria:~have other neurological, neuromuscular, and orthopedic diseases~uncontrolled cardiovascular or respiratory disorders~moderate to severe contractures in the lower extremities	18 Years	null	All	Accepts Healthy Volunteers	Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Fugl-Meyer Assessment Lower Extremity (FMA-LE) \| \| 3-month follow-up \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Functional Ambulation Classification (FAC) \| \| 3-month follow-up \| \| Modified Ashworth Scale (MAS) \| \| 3-month follow-up \| \| Berg Balance Scale (BBS) \| \| 3-month follow-up \| \| Timed 10-Meter Walk Test (10MWT) \| \| 3-month follow-up \| \| 6 Minute Walk Test (6MWT) \| \| 3-month follow-up \|		Stroke, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Vascular Diseases, Cardiovascular Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Ankle Group<br>Integrated with force and motion sensors to identify gait phase and classify user walking intention using machine learning control algorithm. \| Device: Ankle Group<br>* Provide sensory feedback to help subjects relearn how to walk in correct gait pattern.<br>\|	CUHK Jockey Club HOPE 4 Care Programme - Ankle Robot Study Overview ================= Brief Summary ----------------- The Hong Kong Jockey Club Charities Trust has supported CUHK to launch a three-year project 'CUHK Jockey Club HOPE4Care Programme' to implement four evidence-based advanced rehabilitation technologies in 40 local elderly day care centres and rehabilitation centres, to benefit the community. The Exoskeleton Ankle Robot is a robot-assisted Ankle-Foot-Orthosis to facilitate gait training of person after stroke with drop foot. Official Title ----------------- CUHK Jockey Club Tech-Based Stroke Rehabilitation Programme for Elderly Centre - Interactive Exoskeleton Ankle Robot Conditions ----------------- Stroke Intervention / Treatment ----------------- * Device: Ankle Group Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: have the ability to walk on the ground independently or with one personal assistance with or without walking aids able to understand simple commends Exclusion Criteria: have other neurological, neuromuscular, and orthopedic diseases uncontrolled cardiovascular or respiratory disorders moderate to severe contractures in the lower extremities Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Ankle Group<br>Integrated with force and motion sensors to identify gait phase and classify user walking intention using machine learning control algorithm. \| Device: Ankle Group<br>* Provide sensory feedback to help subjects relearn how to walk in correct gait pattern.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Fugl-Meyer Assessment Lower Extremity (FMA-LE) \| \| 3-month follow-up \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Functional Ambulation Classification (FAC) \| \| 3-month follow-up \| \| Modified Ashworth Scale (MAS) \| \| 3-month follow-up \| \| Berg Balance Scale (BBS) \| \| 3-month follow-up \| \| Timed 10-Meter Walk Test (10MWT) \| \| 3-month follow-up \| \| 6 Minute Walk Test (6MWT) \| \| 3-month follow-up \|
NCT03848078	(Cost)-Effectiveness of Optical Coherence Tomography (OCT) in Basal Cell Carcinoma (BCC)	A multi-centre randomized non-inferiority trial investigating the (cost-)effectiveness of Optical Coherence Tomography (OCT) versus regular punch biopsy in the diagnosis and subtyping of Basal Cell Carcinoma (BCC).	Skin cancer incidence rises worldwide due to high sun exposure and ageing. Basal cell carcinoma (BCC) is the most prevalent form, with a lifetime risk of 16-20% in the Netherlands. Currently, the gold standard for diagnosing and subtyping BCC is a punch biopsy. Since this technique is invasive, new non-invasive diagnostic methods have been developed, including optical coherence tomography (OCT). In patients with clinical and dermoscopic suspicion of BCC, OCT makes it possible to confirm and subtype BCC with high confidence, thereby obviating the need for a punch biopsy in a substantial part of patients. Hence, BCC diagnosis and treatment can be accomplished in one day. As a result, patients experience less distress and costs can be saved. By discussing diagnosis and treatment with the patient directly, care can be provided more efficiently, preventing treatment delay and saving extra hospital visits. The investigators hypothesize that the use of OCT is a cost-effective strategy when compared to regular care (always punch biopsy). However, it is important to evaluate whether an alternative OCT guided diagnostic approach does not lead to an unacceptable increase in risk of recurrent BCC.	(Cost)-Effectiveness of Optical Coherence Tomography Versus Regular Punch Biopsy in the Diagnosis and Subtyping of Basal Cell Carcinoma: a Multi Center Randomized Non-inferiority Trial	Basal Cell Carcinoma, Optical Coherence Tomography	* Device: Optical Coherence Tomography	Inclusion Criteria:~Adult patient (>18 years)~Clinical and dermoscopic suspicion of BCC~BCC is in the differential diagnosis and a biopsy would normally be obtained to confirm the diagnosis and subtype or exclude other skin lesions.~Exclusion Criteria:~Patients with BCC in the high-risk zone of the face (ear, nose, eye region)~Patients with a large BCC referred to our (tertiary care) head and neck tumour working group.	18 Years	null	All	No	Primary Purpose: Diagnostic Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Multi-centre randomised controlled non-inferiority trial Masking: Single	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Proportion of patients with treatment failure \| The main endpoint for the non-inferiority trial is the proportion of patients with treatment failure after 12 months follow-up, where treatment failure is defined as inadequate treatment or recurrence of malignant or premalignant lesions. \| 12 months \| \| Cost-effectiveness of OCT \| The main endpoint for the cost-effectiveness analysis is the Incremental Cost-Effectiveness Ratio (ICER) defined as extra cost per gained Quality-Adjusted Life Year (QALY). \| 12 months \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| The proportion of patients with avoided biopsies \| What percentage of biopsies can be avoided in patients when using optical coherence tomography compared to regular care. \| 12 months \| \| Diagnostic performance of OCT \| The design of the study also enables evaluation of the ability of OCT to discriminate between BCC and non-BCC and between BCC subtypes (superficial, nodular and infiltrative BCC) using punch biopsy as reference standard. Diagnostic performance will be expressed as sensitivity, specificity, positive and negative predictive value. A receiver operating characteristic (ROC) curve with area under the curve (AUC) will also be calculated. \| 12 months \| \| Discrete Choice Experiment to determine patient preferences \| Patient preferences will be assessed by designing and conducting a discrete choice experiment. \| 2 months \| \| Quality of life measured with EQ-5D-5L \| Quality of life will be evaluated using the 5-level EQ-5D version (EQ-5D-5L) questionnaire. \| Baseline, 12 months \|	Basal Cell Carcinoma, Optical Coherence Tomography, Punch biopsy	Carcinoma, Carcinoma, Basal Cell, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Neoplasms, Neoplasms, Basal Cell	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Other: Optical Coherence Tomography arm<br>In the intervention arm, OCT imaging is performed which will take about 3 minutes. The decision on the most adequate treatment strategy will be based directly on the OCT diagnosis, but only when there is certainty about the presence of BCC and BCC subtype according to the OCT diagnosis. A 'safety' biopsy will be performed after the OCT scan. In patients where the OCT diagnosis leaves doubt or it is certain that there is no BCC, a biopsy will be taken anyway and the treatment decision will be based on the result of this punch biopsy. \| Device: Optical Coherence Tomography<br>* OCT is an imaging technique, which is able to produce real-time, in vivo, cross-sectional images of lesions with a depth of 1,5-2 mm. OCT imaging is based on light-interferometry, calculating the interference of an optical beam reflected by the tissue with a reference. In such ways, microscopic details of lesions and tissues can be visualized. This information can be used to identify a lesion as BCC, and to specify the subtype. Therefore, we assume that the use of the OCT might reduce the number of biopsies and the accompanying morbidity.~The investigator scans 6mm of skin with the OCT (30 seconds) and decides whether the lesion is a BCC or not.<br>* Other names: Vivosight, Michelson diagnostics;\| \| No Intervention: Regular care arm<br>In patients assigned to regular care, the result of punch biopsy will always be used to decide which treatment is most adequate. Therefore, a next consultation will be planned to discuss the outcome of the biopsy and the intended treatment strategy. \| \|	(Cost)-Effectiveness of Optical Coherence Tomography (OCT) in Basal Cell Carcinoma (BCC) Study Overview ================= Brief Summary ----------------- A multi-centre randomized non-inferiority trial investigating the (cost-)effectiveness of Optical Coherence Tomography (OCT) versus regular punch biopsy in the diagnosis and subtyping of Basal Cell Carcinoma (BCC). Detailed Description ----------------- Skin cancer incidence rises worldwide due to high sun exposure and ageing. Basal cell carcinoma (BCC) is the most prevalent form, with a lifetime risk of 16-20% in the Netherlands. Currently, the gold standard for diagnosing and subtyping BCC is a punch biopsy. Since this technique is invasive, new non-invasive diagnostic methods have been developed, including optical coherence tomography (OCT). In patients with clinical and dermoscopic suspicion of BCC, OCT makes it possible to confirm and subtype BCC with high confidence, thereby obviating the need for a punch biopsy in a substantial part of patients. Hence, BCC diagnosis and treatment can be accomplished in one day. As a result, patients experience less distress and costs can be saved. By discussing diagnosis and treatment with the patient directly, care can be provided more efficiently, preventing treatment delay and saving extra hospital visits. The investigators hypothesize that the use of OCT is a cost-effective strategy when compared to regular care (always punch biopsy). However, it is important to evaluate whether an alternative OCT guided diagnostic approach does not lead to an unacceptable increase in risk of recurrent BCC. Official Title ----------------- (Cost)-Effectiveness of Optical Coherence Tomography Versus Regular Punch Biopsy in the Diagnosis and Subtyping of Basal Cell Carcinoma: a Multi Center Randomized Non-inferiority Trial Conditions ----------------- Basal Cell Carcinoma, Optical Coherence Tomography Intervention / Treatment ----------------- * Device: Optical Coherence Tomography Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Adult patient (>18 years) Clinical and dermoscopic suspicion of BCC BCC is in the differential diagnosis and a biopsy would normally be obtained to confirm the diagnosis and subtype or exclude other skin lesions. Exclusion Criteria: Patients with BCC in the high-risk zone of the face (ear, nose, eye region) Patients with a large BCC referred to our (tertiary care) head and neck tumour working group. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Diagnostic Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Multi-centre randomised controlled non-inferiority trial Masking: Single Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Other: Optical Coherence Tomography arm<br>In the intervention arm, OCT imaging is performed which will take about 3 minutes. The decision on the most adequate treatment strategy will be based directly on the OCT diagnosis, but only when there is certainty about the presence of BCC and BCC subtype according to the OCT diagnosis. A 'safety' biopsy will be performed after the OCT scan. In patients where the OCT diagnosis leaves doubt or it is certain that there is no BCC, a biopsy will be taken anyway and the treatment decision will be based on the result of this punch biopsy. \| Device: Optical Coherence Tomography<br>* OCT is an imaging technique, which is able to produce real-time, in vivo, cross-sectional images of lesions with a depth of 1,5-2 mm. OCT imaging is based on light-interferometry, calculating the interference of an optical beam reflected by the tissue with a reference. In such ways, microscopic details of lesions and tissues can be visualized. This information can be used to identify a lesion as BCC, and to specify the subtype. Therefore, we assume that the use of the OCT might reduce the number of biopsies and the accompanying morbidity. The investigator scans 6mm of skin with the OCT (30 seconds) and decides whether the lesion is a BCC or not.<br>* Other names: Vivosight, Michelson diagnostics;\| \| No Intervention: Regular care arm<br>In patients assigned to regular care, the result of punch biopsy will always be used to decide which treatment is most adequate. Therefore, a next consultation will be planned to discuss the outcome of the biopsy and the intended treatment strategy. \| \| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Proportion of patients with treatment failure \| The main endpoint for the non-inferiority trial is the proportion of patients with treatment failure after 12 months follow-up, where treatment failure is defined as inadequate treatment or recurrence of malignant or premalignant lesions. \| 12 months \| \| Cost-effectiveness of OCT \| The main endpoint for the cost-effectiveness analysis is the Incremental Cost-Effectiveness Ratio (ICER) defined as extra cost per gained Quality-Adjusted Life Year (QALY). \| 12 months \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| The proportion of patients with avoided biopsies \| What percentage of biopsies can be avoided in patients when using optical coherence tomography compared to regular care. \| 12 months \| \| Diagnostic performance of OCT \| The design of the study also enables evaluation of the ability of OCT to discriminate between BCC and non-BCC and between BCC subtypes (superficial, nodular and infiltrative BCC) using punch biopsy as reference standard. Diagnostic performance will be expressed as sensitivity, specificity, positive and negative predictive value. A receiver operating characteristic (ROC) curve with area under the curve (AUC) will also be calculated. \| 12 months \| \| Discrete Choice Experiment to determine patient preferences \| Patient preferences will be assessed by designing and conducting a discrete choice experiment. \| 2 months \| \| Quality of life measured with EQ-5D-5L \| Quality of life will be evaluated using the 5-level EQ-5D version (EQ-5D-5L) questionnaire. \| Baseline, 12 months \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Basal Cell Carcinoma, Optical Coherence Tomography, Punch biopsy
NCT01923038	Evaluation of Ventilatory Strategies During Laparoscopic Surgery	Atelectasis involving declive areas often occurs during general anesthesia and may persist postoperatively. This phenomenon could be amplified by pneumoperitoneum and Trendelenburg position. Hypothesis: To evaluate whether the shape of the airway pressure-time curve, Stress Index (SI), during constant flow inflation can lead ventilator setting during general anesthesia.		Re-expansion of Atelectasis During Laparoscopic Surgery. Recruitment Maneuver vs Positive End-expiratory Pressure: a Randomized Study	Pneumonia	* Procedure: First arm: patients ventilated with zero end expiratory pressure * Procedure: Patients ventilated with Positive End Expiratory Pressure * Procedure: Patients ventilated with Positive End Expiratory Pressure plus Recruitment maneuver	Inclusion Criteria:~American Society Anesthesiology (ASA) I, II;~age > 18 years;~elective surgery~Exclusion Criteria:~ASA III, IV;~Age < 18 years;~emergency surgery	18 Years	70 Years	Female	Accepts Healthy Volunteers	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Pulmonary Stress Index \| \| Continuous evaluation during time of surgery. Partecipants will be followed for the duration of hospital stay, an expected average of 1 weeks \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Cardiac Index \| \| Continuous evaluation during the time of surgery \|	atelectasis, laparoscopic surgery, anesthesia, mechanical ventilation, Prevent, shape of the airway, pressure-time curve	Pneumonia, Respiratory Tract Infections, Infections, Lung Diseases, Respiratory Tract Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Patients ventilated with zero end expiratory pressure (ZEEP)<br>patients undergoing gynecologic laparoscopic surgery ventilated at zero end expiratory pressure \| Procedure: First arm: patients ventilated with zero end expiratory pressure<br> <br> \| \| Active Comparator: Patients ventilated with positive end expiratory pressure<br>patients undergoing gynecologic laparoscopic surgery ventilated at PEEP \| Procedure: Patients ventilated with Positive End Expiratory Pressure<br> <br> \| \| Active Comparator: recruitment plus PEEP<br>patients undergoing gynecologic laparoscopic surgery undergoing recruitment plus PEEP \| Procedure: Patients ventilated with Positive End Expiratory Pressure plus Recruitment maneuver<br> <br> \|	Evaluation of Ventilatory Strategies During Laparoscopic Surgery Study Overview ================= Brief Summary ----------------- Atelectasis involving declive areas often occurs during general anesthesia and may persist postoperatively. This phenomenon could be amplified by pneumoperitoneum and Trendelenburg position. Hypothesis: To evaluate whether the shape of the airway pressure-time curve, Stress Index (SI), during constant flow inflation can lead ventilator setting during general anesthesia. Official Title ----------------- Re-expansion of Atelectasis During Laparoscopic Surgery. Recruitment Maneuver vs Positive End-expiratory Pressure: a Randomized Study Conditions ----------------- Pneumonia Intervention / Treatment ----------------- * Procedure: First arm: patients ventilated with zero end expiratory pressure * Procedure: Patients ventilated with Positive End Expiratory Pressure * Procedure: Patients ventilated with Positive End Expiratory Pressure plus Recruitment maneuver Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: American Society Anesthesiology (ASA) I, II; age > 18 years; elective surgery Exclusion Criteria: ASA III, IV; Age < 18 years; emergency surgery Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 70 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Patients ventilated with zero end expiratory pressure (ZEEP)<br>patients undergoing gynecologic laparoscopic surgery ventilated at zero end expiratory pressure \| Procedure: First arm: patients ventilated with zero end expiratory pressure<br> <br> \| \| Active Comparator: Patients ventilated with positive end expiratory pressure<br>patients undergoing gynecologic laparoscopic surgery ventilated at PEEP \| Procedure: Patients ventilated with Positive End Expiratory Pressure<br> <br> \| \| Active Comparator: recruitment plus PEEP<br>patients undergoing gynecologic laparoscopic surgery undergoing recruitment plus PEEP \| Procedure: Patients ventilated with Positive End Expiratory Pressure plus Recruitment maneuver<br> <br> \| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Pulmonary Stress Index \| \| Continuous evaluation during time of surgery. Partecipants will be followed for the duration of hospital stay, an expected average of 1 weeks \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Cardiac Index \| \| Continuous evaluation during the time of surgery \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- atelectasis, laparoscopic surgery, anesthesia, mechanical ventilation, Prevent, shape of the airway, pressure-time curve
NCT00080743	Gefitinib With or Without Tamoxifen in Treating Patients With Tamoxifen-Resistant Metastatic Breast Cancer	RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Hormone therapy using tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells. Combining gefitinib with tamoxifen may be effective in killing tumor cells that have become resistant (stopped responding) to tamoxifen.~PURPOSE: This randomized phase II trial is studying how well giving gefitinib together with tamoxifen works compared to gefitinib alone in treating patients with metastatic breast cancer that has stopped responding to tamoxifen.	OBJECTIVES:~Primary~Compare the rate of clinical benefit in patients with tamoxifen-resistant breast cancer treated with gefitinib with or without tamoxifen.~Secondary~Determine the toxic effects of these regimens in these patients.~Determine whether changes in fludeoxyglucose F 18 uptake by positron emission tomography scan and changes in plasma DNA levels are indicators of an early response to gefitinib in these patients.~Determine the pharmacokinetics of these regimens in these patients.~OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to population (intent-to-treat population comprising all patients who receive 1 dose of treatment vs a subset of the intent-to-treat population, excluding patients with nonmeasurable/evaluable only disease). Patients are randomized to 1 of 2 treatment arms.~Arm I: Patients receive oral tamoxifen once daily. Beginning 14 days after the start of tamoxifen, patients receive oral gefitinib once daily.~Arm II: Patients receive oral placebo once daily. Beginning 14 days after the start of placebo, patients receive oral gefitinib as in arm I.~In both arms, treatment continues for 26 weeks in the absence of disease progression or unacceptable toxicity.~Patients are followed for 6 months.~PROJECTED ACCRUAL: A total of 46 patients (23 per treatment arm) will be accrued for this study within 23 months.	ZD1839 (IRESSA) In Tamoxifen-Resistant Metastatic Breast Cancer	Breast Cancer	* Drug: gefitinib * Drug: tamoxifen citrate * Drug: Placebo	DISEASE CHARACTERISTICS:~Histologically confirmed breast cancer~Metastatic disease~Initial clinical benefit from tamoxifen for metastatic disease, defined by 1 of the following:~Stable disease for 24 weeks or longer~Objective tumor response~Documentation of clinical progression on tamoxifen within the past 6 weeks~Hormone receptor status:~Estrogen or progesterone receptor positive on most recently analyzed biopsy~PATIENT CHARACTERISTICS:~Age~18 and over~Sex~Not specified~Menopausal status~Not specified~Performance status~ECOG 0-2~Life expectancy~At least 6 months~Hematopoietic~Absolute neutrophil count ≥ 1,500/mm^3~Platelet count ≥ 100,000/mm^3~Hepatic~AST ≤ 1.5 times upper limit of normal (ULN)~Bilirubin ≤ 1.5 times ULN~Renal~Creatinine ≤ 1.5 times ULN OR~Creatinine clearance ≥ 50 mL/min~Pulmonary~No clinically active interstitial lung disease~Patients with asymptomatic chronic stable radiographic changes are eligible~Other~Not pregnant or nursing~Fertile patients must use effective contraception~No known hypersensitivity to gefitinib~No other malignancy within the past 5 years except basal cell carcinoma or carcinoma in situ of the cervix~PRIOR CONCURRENT THERAPY:~Biologic therapy~No concurrent trastuzumab (Herceptin®)~Chemotherapy~No concurrent cytotoxic chemotherapy~Endocrine therapy~See Disease Characteristics~At least 2 weeks since other prior tamoxifen~No concurrent hormone replacement therapy~No other concurrent antiestrogens, including raloxifene~No concurrent aromatase inhibitors~No concurrent megestrol~Concurrent systemic steroids for reasons other than skin toxicity allowed provided the steroids were initiated before study entry AND dose remains stable~Radiotherapy~Concurrent palliative radiotherapy as short-term treatment for symptomatic bone metastases allowed provided other evaluable sites of disease are present AND treatment lasts no more than 14 days~Surgery~Recovered from prior oncologic or other major surgery~No concurrent surgery during and for 7 days after study treatment~No concurrent ophthalmic surgery~Other~Recovered from all prior therapy (except alopecia)~More than 30 days since prior investigational drugs~No other concurrent investigational agents~No concurrent administration of any of the following:~Phenytoin~Carbamazepine~Barbiturates~Rifampin~Phenobarbital~Hypericum perforatum (St. John's wort)~Systemic retinoids~CYP3A4 inhibitors (e.g., itraconazole)~Drugs that cause significant sustained elevation in gastric pH ≥ 5	18 Years	null	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Clinical benefit rate (complete response, partial response, and stable disease) for 26 weeks \| \| 26 weeks \|		recurrent breast cancer, stage IV breast cancer	Tamoxifen, Gefitinib, Molecular Mechanisms of Pharmacological Action, Estrogen Antagonists, Hormone Antagonists, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs, Antineoplastic Agents, Hormonal, Antineoplastic Agents, Selective Estrogen Receptor Modulators, Estrogen Receptor Modulators, Bone Density Conservation Agents, Protein Kinase Inhibitors, Enzyme Inhibitors	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Tamoxifen<br>Tamoxifen 20 mg po once daily \| Drug: gefitinib<br>* 250 mg po once daily<br>* Other names: ZD1839, Iressa;Drug: tamoxifen citrate<br>* 20 mg po once daily<br>* Other names: Nolvadex;\| \| Placebo Comparator: Placebo<br>Placebo comparator one tablet po once daily \| Drug: gefitinib<br>* 250 mg po once daily<br>* Other names: ZD1839, Iressa;Drug: Placebo<br>* One pill po once daily<br>* Other names: Sugar pill;\|	Gefitinib With or Without Tamoxifen in Treating Patients With Tamoxifen-Resistant Metastatic Breast Cancer Study Overview ================= Brief Summary ----------------- RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Hormone therapy using tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells. Combining gefitinib with tamoxifen may be effective in killing tumor cells that have become resistant (stopped responding) to tamoxifen. PURPOSE: This randomized phase II trial is studying how well giving gefitinib together with tamoxifen works compared to gefitinib alone in treating patients with metastatic breast cancer that has stopped responding to tamoxifen. Detailed Description ----------------- OBJECTIVES: Primary Compare the rate of clinical benefit in patients with tamoxifen-resistant breast cancer treated with gefitinib with or without tamoxifen. Secondary Determine the toxic effects of these regimens in these patients. Determine whether changes in fludeoxyglucose F 18 uptake by positron emission tomography scan and changes in plasma DNA levels are indicators of an early response to gefitinib in these patients. Determine the pharmacokinetics of these regimens in these patients. OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to population (intent-to-treat population comprising all patients who receive 1 dose of treatment vs a subset of the intent-to-treat population, excluding patients with nonmeasurable/evaluable only disease). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral tamoxifen once daily. Beginning 14 days after the start of tamoxifen, patients receive oral gefitinib once daily. Arm II: Patients receive oral placebo once daily. Beginning 14 days after the start of placebo, patients receive oral gefitinib as in arm I. In both arms, treatment continues for 26 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed for 6 months. PROJECTED ACCRUAL: A total of 46 patients (23 per treatment arm) will be accrued for this study within 23 months. Official Title ----------------- ZD1839 (IRESSA) In Tamoxifen-Resistant Metastatic Breast Cancer Conditions ----------------- Breast Cancer Intervention / Treatment ----------------- * Drug: gefitinib * Drug: tamoxifen citrate * Drug: Placebo Participation Criteria ================= Eligibility Criteria ----------------- DISEASE CHARACTERISTICS: Histologically confirmed breast cancer Metastatic disease Initial clinical benefit from tamoxifen for metastatic disease, defined by 1 of the following: Stable disease for 24 weeks or longer Objective tumor response Documentation of clinical progression on tamoxifen within the past 6 weeks Hormone receptor status: Estrogen or progesterone receptor positive on most recently analyzed biopsy PATIENT CHARACTERISTICS: Age 18 and over Sex Not specified Menopausal status Not specified Performance status ECOG 0-2 Life expectancy At least 6 months Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic AST ≤ 1.5 times upper limit of normal (ULN) Bilirubin ≤ 1.5 times ULN Renal Creatinine ≤ 1.5 times ULN OR Creatinine clearance ≥ 50 mL/min Pulmonary No clinically active interstitial lung disease Patients with asymptomatic chronic stable radiographic changes are eligible Other Not pregnant or nursing Fertile patients must use effective contraception No known hypersensitivity to gefitinib No other malignancy within the past 5 years except basal cell carcinoma or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent trastuzumab (Herceptin®) Chemotherapy No concurrent cytotoxic chemotherapy Endocrine therapy See Disease Characteristics At least 2 weeks since other prior tamoxifen No concurrent hormone replacement therapy No other concurrent antiestrogens, including raloxifene No concurrent aromatase inhibitors No concurrent megestrol Concurrent systemic steroids for reasons other than skin toxicity allowed provided the steroids were initiated before study entry AND dose remains stable Radiotherapy Concurrent palliative radiotherapy as short-term treatment for symptomatic bone metastases allowed provided other evaluable sites of disease are present AND treatment lasts no more than 14 days Surgery Recovered from prior oncologic or other major surgery No concurrent surgery during and for 7 days after study treatment No concurrent ophthalmic surgery Other Recovered from all prior therapy (except alopecia) More than 30 days since prior investigational drugs No other concurrent investigational agents No concurrent administration of any of the following: Phenytoin Carbamazepine Barbiturates Rifampin Phenobarbital Hypericum perforatum (St. John's wort) Systemic retinoids CYP3A4 inhibitors (e.g., itraconazole) Drugs that cause significant sustained elevation in gastric pH ≥ 5 Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Tamoxifen<br>Tamoxifen 20 mg po once daily \| Drug: gefitinib<br>* 250 mg po once daily<br>* Other names: ZD1839, Iressa;Drug: tamoxifen citrate<br>* 20 mg po once daily<br>* Other names: Nolvadex;\| \| Placebo Comparator: Placebo<br>Placebo comparator one tablet po once daily \| Drug: gefitinib<br>* 250 mg po once daily<br>* Other names: ZD1839, Iressa;Drug: Placebo<br>* One pill po once daily<br>* Other names: Sugar pill;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Clinical benefit rate (complete response, partial response, and stable disease) for 26 weeks \| \| 26 weeks \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- recurrent breast cancer, stage IV breast cancer
NCT03750383	Drug-Drug Interaction Study Between EDP-938, Cyclosporine and Prednisone in Healthy Adult Subjects	A Non-Randomized, Open-Label, Two-Part, Drug-Drug Interaction Study to Evaluate the Effects of Cyclosporine and Prednisone on the Pharmacokinetics and Safety of EDP-938 in Healthy Adult Subjects		A Non-Randomized, Open-Label, Two-Part, Drug-Drug Interaction Study to Evaluate the Effects of Cyclosporine and Prednisone on the Pharmacokinetics and Safety of EDP-938 in Healthy Adult Subjects	RSV Infection	* Drug: EDP-938 * Drug: EDP-938 * Drug: Cyclosporine * Drug: Prednisone	Inclusion Criteria:~An informed consent document signed and dated by the subject.~Healthy male and female subjects of any ethnic origin between the ages of 18 and 55 years, inclusive.~Screening body mass index (BMI) of 18 to 30 kg/m2 with a minimum body weight of 50 kg~Female subjects of childbearing potential must agree to use two effective methods of contraception from the date of Screening until 90 days after the last dose of EDP 938.~Exclusion Criteria:~Clinically relevant evidence or history of illness or disease.~Pregnant or nursing females.~History of febrile illness within 7 days prior to the first dose of study drug or subjects with evidence of active infection.~A positive urine drug screen at screening or Day -1.~Current tobacco smokers or use of tobacco within 3 months prior to screening.~Any condition possibly affecting drug absorption (e.g., gastrectomy, cholecystectomy).~History of regular alcohol consumption.~Participation in a clinical trial within 30 days prior to the first dose of study drug.	18 Years	55 Years	All	Accepts Healthy Volunteers	Primary Purpose: Basic Science Allocation: Non-Randomized Intervention Model: Single Group Assignment Interventional Model Description: 2-Part Single Group study Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Cmax of EDP-938 with and without coadministration with cyclosporine \| \| Up to 12 days \| \| AUC of EDP-938 with and without coadministration with cyclosporine \| \| Up to 12 days \| \| Cmax of EDP-938 with and without coadministration with prednisone \| \| Up to 21 days \| \| AUC of EDP-938 with and without coadministration with prednisone \| \| Up to 21 days \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Safety measured by adverse events \| \| Up to 21 days \|	drug drug interaction study	Hormones, Antineoplastic Agents, Prednisone, Anti-Infective Agents, Cyclosporine, Cyclosporins, Anti-Inflammatory Agents, Glucocorticoids, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs, Antineoplastic Agents, Hormonal, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Immunosuppressive Agents, Immunologic Factors, Antifungal Agents, Dermatologic Agents, Antirheumatic Agents, Calcineurin Inhibitors	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: EDP-938 and cyclosporine interaction (Part 1)<br> \| Drug: EDP-938<br>* Subjects will receive EDP-938 once daily on Day 1 and Day 5 (Part 1)<br>Drug: Cyclosporine<br>* Subjects will receive one dose of cyclosporine on Day 5<br>\| \| Experimental: EDP-938 and prednisone interaction (Part 2)<br> \| Drug: EDP-938<br>* Subjects will receive one dose of EDP-938 on Day 1 and Day 8 (Part 2)<br>Drug: Prednisone<br>* Subjects will receive prednisone once daily from Day 5 to Day 14<br>\|	Drug-Drug Interaction Study Between EDP-938, Cyclosporine and Prednisone in Healthy Adult Subjects Study Overview ================= Brief Summary ----------------- A Non-Randomized, Open-Label, Two-Part, Drug-Drug Interaction Study to Evaluate the Effects of Cyclosporine and Prednisone on the Pharmacokinetics and Safety of EDP-938 in Healthy Adult Subjects Official Title ----------------- A Non-Randomized, Open-Label, Two-Part, Drug-Drug Interaction Study to Evaluate the Effects of Cyclosporine and Prednisone on the Pharmacokinetics and Safety of EDP-938 in Healthy Adult Subjects Conditions ----------------- RSV Infection Intervention / Treatment ----------------- * Drug: EDP-938 * Drug: EDP-938 * Drug: Cyclosporine * Drug: Prednisone Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: An informed consent document signed and dated by the subject. Healthy male and female subjects of any ethnic origin between the ages of 18 and 55 years, inclusive. Screening body mass index (BMI) of 18 to 30 kg/m2 with a minimum body weight of 50 kg Female subjects of childbearing potential must agree to use two effective methods of contraception from the date of Screening until 90 days after the last dose of EDP 938. Exclusion Criteria: Clinically relevant evidence or history of illness or disease. Pregnant or nursing females. History of febrile illness within 7 days prior to the first dose of study drug or subjects with evidence of active infection. A positive urine drug screen at screening or Day -1. Current tobacco smokers or use of tobacco within 3 months prior to screening. Any condition possibly affecting drug absorption (e.g., gastrectomy, cholecystectomy). History of regular alcohol consumption. Participation in a clinical trial within 30 days prior to the first dose of study drug. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 55 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Basic Science Allocation: Non-Randomized Intervention Model: Single Group Assignment Interventional Model Description: 2-Part Single Group study Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: EDP-938 and cyclosporine interaction (Part 1)<br> \| Drug: EDP-938<br>* Subjects will receive EDP-938 once daily on Day 1 and Day 5 (Part 1)<br>Drug: Cyclosporine<br>* Subjects will receive one dose of cyclosporine on Day 5<br>\| \| Experimental: EDP-938 and prednisone interaction (Part 2)<br> \| Drug: EDP-938<br>* Subjects will receive one dose of EDP-938 on Day 1 and Day 8 (Part 2)<br>Drug: Prednisone<br>* Subjects will receive prednisone once daily from Day 5 to Day 14<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Cmax of EDP-938 with and without coadministration with cyclosporine \| \| Up to 12 days \| \| AUC of EDP-938 with and without coadministration with cyclosporine \| \| Up to 12 days \| \| Cmax of EDP-938 with and without coadministration with prednisone \| \| Up to 21 days \| \| AUC of EDP-938 with and without coadministration with prednisone \| \| Up to 21 days \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Safety measured by adverse events \| \| Up to 21 days \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- drug drug interaction study
NCT04291040	Use of an Educational Multimedia Tool Versus Routine Care for the Uptake of Postpartum LARC in High-Risk Pregnancies	The purpose of the study is to evaluate if the implementation of a multimedia based educational tool and regular reminders with shared decision-making will increase the rate of LARC uptake and retention in high risk pregnancy patients within 12 weeks of delivery and to study the rates of retention of LARC at 12 and 24 months and short-interval pregnancy rates.	This study will include 380 women aged 18-50 enrolled between 28 weeks gestation and postpartum day #1 who have a pregnancy that is considered high-risk. After consent, participants will be randomized to either routine care or multimedia based intervention. The intervention will include an investigator created decision aid presented at the time of randomization and reminder texts until 12 weeks postpartum.~The primary objective is to evaluate the rate of LARC uptake and retention within 12 weeks of delivery. Secondary objectives include i) the retention of LARC at 12 and 24 months and ii) short-interval pregnancy rates.	Use of an Educational Multimedia Tool Versus Routine Care for the Uptake of Postpartum LARC in High-Risk Pregnancies (SUSTAIN): A Randomized Clinical Trial	Pregnancy, High Risk, Contraception	* Behavioral: Decision Aid * Behavioral: Routine Care	Inclusion Criteria:~Aged 13-50 years old~High risk pregnancy due to either maternal medical conditions or obstetric/neonatal complications~Exclusion Criteria:~Planned cesarean hysterectomy~Unable to provide informed consent in either English or Spanish~Unable to provide reliable cell phone access for the study duration~Not willing to provide follow-up for two years	13 Years	50 Years	Female	No	Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Rate of initial LARC utilization \| Number of subjects who elect to have LARC procedure between the 2 arms \| 12 weeks postpartum (12 weeks) \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of patients who keep the LARC after placement \| \| 12 months \| \| Number of patients who keep the LARC after placement \| \| 24 months \| \| rates of short interval pregnancy \| Number of patients who become pregnant after enrollment pregnancy \| 24 months \|			\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Decision Aid<br> \| Behavioral: Decision Aid<br>* Following randomization, participants will independently view the multimedia based decision aid on a provided tablet. They will also receive provider counseling. For the remainder of the pregnancy, they will receive a text message with a link to the multimedia based presentation. This will occur every 4 weeks until 12 weeks postpartum.<br>\| \| Active Comparator: Routine Care<br> \| Behavioral: Routine Care<br>* The control arm will receive routine prenatal care including provider counselling on postpartum contraceptive options.<br>\|	Use of an Educational Multimedia Tool Versus Routine Care for the Uptake of Postpartum LARC in High-Risk Pregnancies Study Overview ================= Brief Summary ----------------- The purpose of the study is to evaluate if the implementation of a multimedia based educational tool and regular reminders with shared decision-making will increase the rate of LARC uptake and retention in high risk pregnancy patients within 12 weeks of delivery and to study the rates of retention of LARC at 12 and 24 months and short-interval pregnancy rates. Detailed Description ----------------- This study will include 380 women aged 18-50 enrolled between 28 weeks gestation and postpartum day #1 who have a pregnancy that is considered high-risk. After consent, participants will be randomized to either routine care or multimedia based intervention. The intervention will include an investigator created decision aid presented at the time of randomization and reminder texts until 12 weeks postpartum. The primary objective is to evaluate the rate of LARC uptake and retention within 12 weeks of delivery. Secondary objectives include i) the retention of LARC at 12 and 24 months and ii) short-interval pregnancy rates. Official Title ----------------- Use of an Educational Multimedia Tool Versus Routine Care for the Uptake of Postpartum LARC in High-Risk Pregnancies (SUSTAIN): A Randomized Clinical Trial Conditions ----------------- Pregnancy, High Risk, Contraception Intervention / Treatment ----------------- * Behavioral: Decision Aid * Behavioral: Routine Care Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Aged 13-50 years old High risk pregnancy due to either maternal medical conditions or obstetric/neonatal complications Exclusion Criteria: Planned cesarean hysterectomy Unable to provide informed consent in either English or Spanish Unable to provide reliable cell phone access for the study duration Not willing to provide follow-up for two years Ages Eligible for Study ----------------- Minimum Age: 13 Years Maximum Age: 50 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Decision Aid<br> \| Behavioral: Decision Aid<br>* Following randomization, participants will independently view the multimedia based decision aid on a provided tablet. They will also receive provider counseling. For the remainder of the pregnancy, they will receive a text message with a link to the multimedia based presentation. This will occur every 4 weeks until 12 weeks postpartum.<br>\| \| Active Comparator: Routine Care<br> \| Behavioral: Routine Care<br>* The control arm will receive routine prenatal care including provider counselling on postpartum contraceptive options.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Rate of initial LARC utilization \| Number of subjects who elect to have LARC procedure between the 2 arms \| 12 weeks postpartum (12 weeks) \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of patients who keep the LARC after placement \| \| 12 months \| \| Number of patients who keep the LARC after placement \| \| 24 months \| \| rates of short interval pregnancy \| Number of patients who become pregnant after enrollment pregnancy \| 24 months \|
NCT05101486	A Study of an Ad26.RSV.PreF-based Regimen at the End of Shelf-life in Adults Aged 60 to 75 Years	The purpose of this study is to demonstrate non-inferiority in terms of humoral immune responses of Ad26.RSV.preF-based study vaccine lots representative of different aged vaccine in comparison to a non-aged Ad26.RSV.preF-based study vaccine lot.		A Randomized, Double-blind Phase 3 Study to Assess the Immunogenicity and Safety of an Ad26.RSV.PreF-based Regimen at the End of Shelf-life in Adults Aged 60 to 75 Years	Respiratory Syncytial Virus Prevention	* Biological: Ad26.RSV.PreF-based Vaccine	Inclusion Criteria:~Before randomization, a participant must be: a) postmenopausal (postmenopausal state is defined as no menses for 12 months without an alternative medical cause); and b) not intending to conceive by any methods~From the time of vaccination through 3 months after vaccination, agrees not to donate blood~In the investigator's clinical judgment, a participant must be in stable health at the time of vaccination. Participants may have underlying illnesses such as hypertension, congestive heart failure, chronic obstructive pulmonary disease, Type 2 diabetes, hyperlipoproteinemia, or hypothyroidism, as long as their symptoms and signs are stable at the time of vaccination, and these conditions receive routine follow-up by the participant's healthcare provider. Participants will be included on the basis of medical history and vital signs performed between informed consent form (ICF) signature and vaccination~Must be able to read, understand, and complete questionnaires in the electronic diary (eDiary)~Must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study~Must be able to work with smartphones/tablets/computers~Exclusion Criteria:~Known or suspected allergy or history of anaphylaxis or other serious adverse reactions to vaccines or their excipients (including specifically the excipients of the study vaccine)~Abnormal function of the immune system resulting from clinical conditions or medication~Per medical history, participant has chronic active hepatitis B or hepatitis C infection~History of acute polyneuropathy (example, Guillain-Barré syndrome) or chronic idiopathic demyelinating polyneuropathy~Has had major surgery (per the investigator's judgment) within 4 weeks before administration of the study vaccine or will not have recovered from surgery per the investigator's judgment at time of vaccination~Has had major psychiatric illness and/or drug or alcohol abuse which in the investigator's opinion would compromise the participant's safety and/or compliance with the study procedures	60 Years	75 Years	All	No	Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Geometric Mean Titers (GMTs) of Prefusion F-protein (preF) Antibodies as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) 14 Days Post Vaccination \| GMTs of pre-F antibodies as assessed by ELISA at 14 days post administration of Ad26/protein preF RSV vaccine were reported. \| 14 days post vaccination on Day 1 (Day 15) \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Respiratory Syncytial Virus (RSV) A2 Strain Neutralizing Antibody Titers at 14 Days Post Vaccination \| RSV A2 strain neutralizing antibody titers of the vaccine-induced immune response was assessed through virus neutralization assay at 14 days post administration of Ad26/protein preF RSV-based vaccine were expressed as 50 percent (%) inhibitory concentration (IC50) units. \| 14 days post vaccination on Day 1 (Day 15) \| \| Number of Participants With Solicited Local Adverse Events (AEs) for 7 Days Post Vaccination \| Number of participants with solicited local AEs 7 days post vaccination were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs were precisely defined events that participants were specifically asked about and which were noted by participants in the diary. Solicited local AEs that included injection site pain/tenderness, erythema and swelling at the study vaccine injection site, were used to assess the reactogenicity of the study vaccine and were pre-defined local (injection site). \| Up to Day 7 post vaccination on Day 1 (up to Day 8) \| \| Number of Participants With Solicited Systemic AEs for 7 Days Post Vaccination \| Number of participants with solicited systemic AEs 7 days post vaccination were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited systemic events include events such as fatigue, headache, nausea, myalgia, and pyrexia, for which participants were specifically questioned and which were noted by participants in their participant diary for 7 days post vaccination (day of vaccination and the subsequent 7 days). \| Up to Day 7 post vaccination on Day 1 (up to Day 8) \| \| Number of Participants With Unsolicited AEs for 28 Days Post Vaccination \| Number of participants with unsolicited AEs 28 days post vaccination were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs were all AEs for which the participant was not specifically questioned in the participant diary. \| Up to 28 days post vaccination on Day 1 (up to Day 29) \| \| Number of Participants With Serious Adverse Events (SAEs) Until 6 Months Post Vaccination \| Number of participants with SAEs until 6 months post vaccination were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product. \| From Day 1 up to 6 months post vaccination on Day 1 (up to Day 183) \| \| Number of Participants With Adverse Event of Special Interests (AESIs) Until 6 Months Post Vaccination \| Number of participants with AESIs until 6 months post vaccination were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Thrombosis with thrombocytopenia syndrome (TTS) was considered as an AESI. \| From Day 1 up to 6 months post vaccination on Day 1 (up to Day 183) \|			\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Group 1: Ad26.RSV.PreF-based Vaccine<br>Participants will receive a single intramuscular (IM) injection of Ad26.RSV.PreF-based vaccine on Day 1 (non-aged lot). \| Biological: Ad26.RSV.PreF-based Vaccine<br>* Ad26.RSV.PreF-based Vaccine will be administered as single IM injection.<br>\| \| Experimental: Group 2: Ad26.RSV.PreF-based Vaccine<br>Participants will receive a single IM injection of Ad26.RSV.PreF-based vaccine on Day 1 (aged lot 1). \| Biological: Ad26.RSV.PreF-based Vaccine<br>* Ad26.RSV.PreF-based Vaccine will be administered as single IM injection.<br>\| \| Experimental: Group 3: Ad26.RSV.PreF-based Vaccine<br>Participants will receive a single IM injection of Ad26.RSV.PreF-based vaccine on Day 1 (aged lot 2). \| Biological: Ad26.RSV.PreF-based Vaccine<br>* Ad26.RSV.PreF-based Vaccine will be administered as single IM injection.<br>\|	A Study of an Ad26.RSV.PreF-based Regimen at the End of Shelf-life in Adults Aged 60 to 75 Years Study Overview ================= Brief Summary ----------------- The purpose of this study is to demonstrate non-inferiority in terms of humoral immune responses of Ad26.RSV.preF-based study vaccine lots representative of different aged vaccine in comparison to a non-aged Ad26.RSV.preF-based study vaccine lot. Official Title ----------------- A Randomized, Double-blind Phase 3 Study to Assess the Immunogenicity and Safety of an Ad26.RSV.PreF-based Regimen at the End of Shelf-life in Adults Aged 60 to 75 Years Conditions ----------------- Respiratory Syncytial Virus Prevention Intervention / Treatment ----------------- * Biological: Ad26.RSV.PreF-based Vaccine Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Before randomization, a participant must be: a) postmenopausal (postmenopausal state is defined as no menses for 12 months without an alternative medical cause); and b) not intending to conceive by any methods From the time of vaccination through 3 months after vaccination, agrees not to donate blood In the investigator's clinical judgment, a participant must be in stable health at the time of vaccination. Participants may have underlying illnesses such as hypertension, congestive heart failure, chronic obstructive pulmonary disease, Type 2 diabetes, hyperlipoproteinemia, or hypothyroidism, as long as their symptoms and signs are stable at the time of vaccination, and these conditions receive routine follow-up by the participant's healthcare provider. Participants will be included on the basis of medical history and vital signs performed between informed consent form (ICF) signature and vaccination Must be able to read, understand, and complete questionnaires in the electronic diary (eDiary) Must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study Must be able to work with smartphones/tablets/computers Exclusion Criteria: Known or suspected allergy or history of anaphylaxis or other serious adverse reactions to vaccines or their excipients (including specifically the excipients of the study vaccine) Abnormal function of the immune system resulting from clinical conditions or medication Per medical history, participant has chronic active hepatitis B or hepatitis C infection History of acute polyneuropathy (example, Guillain-Barré syndrome) or chronic idiopathic demyelinating polyneuropathy Has had major surgery (per the investigator's judgment) within 4 weeks before administration of the study vaccine or will not have recovered from surgery per the investigator's judgment at time of vaccination Has had major psychiatric illness and/or drug or alcohol abuse which in the investigator's opinion would compromise the participant's safety and/or compliance with the study procedures Ages Eligible for Study ----------------- Minimum Age: 60 Years Maximum Age: 75 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Group 1: Ad26.RSV.PreF-based Vaccine<br>Participants will receive a single intramuscular (IM) injection of Ad26.RSV.PreF-based vaccine on Day 1 (non-aged lot). \| Biological: Ad26.RSV.PreF-based Vaccine<br>* Ad26.RSV.PreF-based Vaccine will be administered as single IM injection.<br>\| \| Experimental: Group 2: Ad26.RSV.PreF-based Vaccine<br>Participants will receive a single IM injection of Ad26.RSV.PreF-based vaccine on Day 1 (aged lot 1). \| Biological: Ad26.RSV.PreF-based Vaccine<br>* Ad26.RSV.PreF-based Vaccine will be administered as single IM injection.<br>\| \| Experimental: Group 3: Ad26.RSV.PreF-based Vaccine<br>Participants will receive a single IM injection of Ad26.RSV.PreF-based vaccine on Day 1 (aged lot 2). \| Biological: Ad26.RSV.PreF-based Vaccine<br>* Ad26.RSV.PreF-based Vaccine will be administered as single IM injection.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Geometric Mean Titers (GMTs) of Prefusion F-protein (preF) Antibodies as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) 14 Days Post Vaccination \| GMTs of pre-F antibodies as assessed by ELISA at 14 days post administration of Ad26/protein preF RSV vaccine were reported. \| 14 days post vaccination on Day 1 (Day 15) \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Respiratory Syncytial Virus (RSV) A2 Strain Neutralizing Antibody Titers at 14 Days Post Vaccination \| RSV A2 strain neutralizing antibody titers of the vaccine-induced immune response was assessed through virus neutralization assay at 14 days post administration of Ad26/protein preF RSV-based vaccine were expressed as 50 percent (%) inhibitory concentration (IC50) units. \| 14 days post vaccination on Day 1 (Day 15) \| \| Number of Participants With Solicited Local Adverse Events (AEs) for 7 Days Post Vaccination \| Number of participants with solicited local AEs 7 days post vaccination were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs were precisely defined events that participants were specifically asked about and which were noted by participants in the diary. Solicited local AEs that included injection site pain/tenderness, erythema and swelling at the study vaccine injection site, were used to assess the reactogenicity of the study vaccine and were pre-defined local (injection site). \| Up to Day 7 post vaccination on Day 1 (up to Day 8) \| \| Number of Participants With Solicited Systemic AEs for 7 Days Post Vaccination \| Number of participants with solicited systemic AEs 7 days post vaccination were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited systemic events include events such as fatigue, headache, nausea, myalgia, and pyrexia, for which participants were specifically questioned and which were noted by participants in their participant diary for 7 days post vaccination (day of vaccination and the subsequent 7 days). \| Up to Day 7 post vaccination on Day 1 (up to Day 8) \| \| Number of Participants With Unsolicited AEs for 28 Days Post Vaccination \| Number of participants with unsolicited AEs 28 days post vaccination were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs were all AEs for which the participant was not specifically questioned in the participant diary. \| Up to 28 days post vaccination on Day 1 (up to Day 29) \| \| Number of Participants With Serious Adverse Events (SAEs) Until 6 Months Post Vaccination \| Number of participants with SAEs until 6 months post vaccination were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product. \| From Day 1 up to 6 months post vaccination on Day 1 (up to Day 183) \| \| Number of Participants With Adverse Event of Special Interests (AESIs) Until 6 Months Post Vaccination \| Number of participants with AESIs until 6 months post vaccination were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Thrombosis with thrombocytopenia syndrome (TTS) was considered as an AESI. \| From Day 1 up to 6 months post vaccination on Day 1 (up to Day 183) \|
NCT01966588	Adverse Events and Genomics in Schizophrenia	The purpose of this study is to find genes that predict whether or not a person will develop side effects to antipsychotic medications, such as weight gain, blood sugar dysregulation, or immune cell abnormalities. We will be collecting blood samples from participants who are taking second-generation antipsychotic medications. These blood samples will be stored over the long-term in a biobank, and will be used for later genetic testing and other cell-based studies.	All data (including blood samples and medical information gathered from participants) will be labelled with each participant's unique coded identifier. Participants' identities will be matched with their coded identifier in a single, hard-copy of a Master Coding List. The maintenance and security of this list is the responsibility of the Principal Investigator.~All processing steps of the blood samples, including details of the blood draw, nucleic acid extraction, sequence library preparation, and sequence analysis will be documented in a Microsoft Excel worksheet. This worksheet will be encrypted for privacy.~Anonymized aliquots of blood samples (as well as any derived cell cultures) will be barcoded before long-term storage in a surveillance-monitored, secured freezer at -80 degrees Celsius. Samples within the freezer will be maintained via a positional numbered grid within the Laboratory Information Management System. This grid will also allow the study team to link each barcoded sample to a participant's coded identifier.~Mapped genomic sequences and other data collected from participants will be saved in password-protected folders on the UBC server. The coded sequence data will be transferred to the Department of Genetics and Genomic Sciences at Mount Sinai School of Medicine (MSSM) for further analyses. Data transfer will occur by Two Factor Identification. The MSSM secure network is Clinical Laboratory Improvement Amendments (CLIA) certified for secure handling of patient sequence data. The transfer of sequence data between UBC and MSSM will be performed under a material transfer agreement which requires that 1) all data and analysis be confined within the secure, password-protected database defined by UBC, 2) not distributed to any third party, and 3) both raw and analyzed data be destroyed from the MSSM monthly. This study is not required to comply with any U.S. federal regulations, as the group in MSSM will not have access to any identifying information about our participants.	Genomic Biomarkers of Adverse Events Arising From Antipsychotic Drug Therapy	Adverse Effect of Other Antipsychotics and Neuroleptics	* Other: Blood samples for whole genomic/transcriptomic sequencing * Other: UKU Side Effect Rating Scale	Inclusion Criteria:~Must be taking an antipsychotic medication (no limit on treatment duration)~Exclusion Criteria:~None	null	null	All	No		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Concentration of whole-genome and/or transcriptome variants predicting weight gain, or glucose or lipid dysregulations in whole blood (ng/uL). \| \| Anytime during a participant's course of treatment with second-generation antipsychotics (expected average of approximately 1 year after starting treatments) \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Concentration of whole-genome and/or transcriptome variants predicting immune effects of clozapine monotherapy in whole blood (ng/uL). \| \| Baseline (at time of enrolment; expected average of approximately 1 year after starting treatment), 3 months after baseline, and 1 year after baseline (with possibility of further follow-up) \|	Antipsychotic agents, Adverse effects, Genomics, Transcriptome		\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Metabolic Arm<br>Blood samples for whole genomic/transcriptomic sequencing; administration of the UKU Side Effect Rating Scale. \| Other: Blood samples for whole genomic/transcriptomic sequencing<br>* Participants in the Metabolic Arm will receive one blood draw, while participants in the Neutropenia Arm will receive a total of three blood draws: one at baseline, another 3 months later, and one 1 year later, with the possibility of further follow-up.<br>Other: UKU Side Effect Rating Scale<br>* Clinician-rated scale of psychic, neurological, autonomic, and other side effects related to psychotropic drugs; ratings are based on a 10-30 minute interview with each participant.<br>* Other names: Udvalg for Kliniske Undersøgelser;\| \| Neutropenia/Immune System Arm<br>Blood samples for whole genomic/transcriptomic sequencing \| Other: Blood samples for whole genomic/transcriptomic sequencing<br>* Participants in the Metabolic Arm will receive one blood draw, while participants in the Neutropenia Arm will receive a total of three blood draws: one at baseline, another 3 months later, and one 1 year later, with the possibility of further follow-up.<br>\|	Adverse Events and Genomics in Schizophrenia Study Overview ================= Brief Summary ----------------- The purpose of this study is to find genes that predict whether or not a person will develop side effects to antipsychotic medications, such as weight gain, blood sugar dysregulation, or immune cell abnormalities. We will be collecting blood samples from participants who are taking second-generation antipsychotic medications. These blood samples will be stored over the long-term in a biobank, and will be used for later genetic testing and other cell-based studies. Detailed Description ----------------- All data (including blood samples and medical information gathered from participants) will be labelled with each participant's unique coded identifier. Participants' identities will be matched with their coded identifier in a single, hard-copy of a Master Coding List. The maintenance and security of this list is the responsibility of the Principal Investigator. All processing steps of the blood samples, including details of the blood draw, nucleic acid extraction, sequence library preparation, and sequence analysis will be documented in a Microsoft Excel worksheet. This worksheet will be encrypted for privacy. Anonymized aliquots of blood samples (as well as any derived cell cultures) will be barcoded before long-term storage in a surveillance-monitored, secured freezer at -80 degrees Celsius. Samples within the freezer will be maintained via a positional numbered grid within the Laboratory Information Management System. This grid will also allow the study team to link each barcoded sample to a participant's coded identifier. Mapped genomic sequences and other data collected from participants will be saved in password-protected folders on the UBC server. The coded sequence data will be transferred to the Department of Genetics and Genomic Sciences at Mount Sinai School of Medicine (MSSM) for further analyses. Data transfer will occur by Two Factor Identification. The MSSM secure network is Clinical Laboratory Improvement Amendments (CLIA) certified for secure handling of patient sequence data. The transfer of sequence data between UBC and MSSM will be performed under a material transfer agreement which requires that 1) all data and analysis be confined within the secure, password-protected database defined by UBC, 2) not distributed to any third party, and 3) both raw and analyzed data be destroyed from the MSSM monthly. This study is not required to comply with any U.S. federal regulations, as the group in MSSM will not have access to any identifying information about our participants. Official Title ----------------- Genomic Biomarkers of Adverse Events Arising From Antipsychotic Drug Therapy Conditions ----------------- Adverse Effect of Other Antipsychotics and Neuroleptics Intervention / Treatment ----------------- * Other: Blood samples for whole genomic/transcriptomic sequencing * Other: UKU Side Effect Rating Scale Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Must be taking an antipsychotic medication (no limit on treatment duration) Exclusion Criteria: None Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Metabolic Arm<br>Blood samples for whole genomic/transcriptomic sequencing; administration of the UKU Side Effect Rating Scale. \| Other: Blood samples for whole genomic/transcriptomic sequencing<br>* Participants in the Metabolic Arm will receive one blood draw, while participants in the Neutropenia Arm will receive a total of three blood draws: one at baseline, another 3 months later, and one 1 year later, with the possibility of further follow-up.<br>Other: UKU Side Effect Rating Scale<br>* Clinician-rated scale of psychic, neurological, autonomic, and other side effects related to psychotropic drugs; ratings are based on a 10-30 minute interview with each participant.<br>* Other names: Udvalg for Kliniske Undersøgelser;\| \| Neutropenia/Immune System Arm<br>Blood samples for whole genomic/transcriptomic sequencing \| Other: Blood samples for whole genomic/transcriptomic sequencing<br>* Participants in the Metabolic Arm will receive one blood draw, while participants in the Neutropenia Arm will receive a total of three blood draws: one at baseline, another 3 months later, and one 1 year later, with the possibility of further follow-up.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Concentration of whole-genome and/or transcriptome variants predicting weight gain, or glucose or lipid dysregulations in whole blood (ng/uL). \| \| Anytime during a participant's course of treatment with second-generation antipsychotics (expected average of approximately 1 year after starting treatments) \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Concentration of whole-genome and/or transcriptome variants predicting immune effects of clozapine monotherapy in whole blood (ng/uL). \| \| Baseline (at time of enrolment; expected average of approximately 1 year after starting treatment), 3 months after baseline, and 1 year after baseline (with possibility of further follow-up) \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Antipsychotic agents, Adverse effects, Genomics, Transcriptome
NCT01896375	Gutkha Pan Masala Ban Impact Study in Mumbai	Present study is conducted on Gutkha and Pan Masala users to find out the impact of ban on them. It will also try to find out awareness about ban and source of information for the same. Availability of Gutkha and Pan Masala in post ban period will also be assessed.	Background: Based on the various reports indicating health hazards of gutka and pan masala there are various efforts to ban the production, consumption, sale, storage and transportation of these products by various states in India. The situation had gone to such an extent that government had no other option than to ban these products. In India gutka is classed as a food item and falls within the purview of Prevention of Food Adulteration act. The Central Committee on Food Standards (CCFS) had already reported a complete ban to the Central Government a decade ago itself. The reasons unanimously given by CCFS for a complete ban on Gutka were 1) Children are getting addicted to these products in large numbers; 2) Users develop Oral Submucous Fibrosis and cancer over a relatively shorter duration and die earlier compared to smokers; 3) Women prefer smokeless tobacco due to social disapproval of their smoking and therefore may be particularly vulnerable to gutka addiction. Tamil Nadu had banned Gutka in 2001 itself. Andhra Pradesh, Goa, Maharashtra & Rajasthan had also followed the same in August 2002.4 Subsequently following some legal battles ban on Gutka in Maharashtra was lifted. But now following the example of eight other states in India, Government of Maharashtra has finally banned the manufacture, storage, distribution or sale of Gutka and Pan masala, containing either tobacco and/or nicotine or Magnesium Carbonate as ingredients by whatsoever name these are available in the market and any other products marketed separately to constitute as Gutka and Pan Masala, etc. as final products from July 19, 2012.8 The appeal filed by some manufacturers in Bombay High Court has been quashed and the ban is to continue now unless it is reversed by the Supreme Court of India. Sensing the possibility of Supreme Court (SC) appeal by gutka and pan masala manufacturers the Government of Maharashtra has already filed an caveat there so that there plea will be heard first by SC before passing any order in this matter.~There is a large population addicted to Gutkha and pan-masala all over India. We would like to study the impact of this ban on the users of this product and on the tobacco vendors. Even if the ban is reversed by the Supreme Court, we would still like to study its impact in the interim period when the ban was imposed.~Rationale: Seeing the addictive potential of the contents of gutka and pan masala, it will be interesting to record the effect of ban of these products on the regular consumers. Whether they have stopped the consumption or are still getting the products (by smuggled routes) is an important issue. If they have shifted to other tobacco products, it will be important to study the shift pattern. If at all some withdrawal symptoms are reported by them, it will be helpful to record it so as to devise our cessation strategies. If the previous regular consumers have stopped the consumption of gutka and pan masala because of ban, it is positive sign in support of legal ban for the maintenance of proper public health. The response of gutka and pan masala users to the ban has to be studied. To what extent they have accepted the ban and what reaction they are giving are important issues to be studied. In depth analysis of all these points will be helpful in the development of further public health strategy as far as use of gutka and pan masala is concerned.~The second aspect of this study is to investigate the response and implications of tobacco vendors to the ban. In last few years there was tremendous increase in vendors of tobacco especially Gutka and Pan-masala. These products being cheaply available were marketed in almost all corners of cities and villages. Even public transport vehicle were also flooded by the presence of many street vendors. Ultimately all these vendors were working as the merchants of deadly tobacco products. So the study of the response of these people to ban is an issue of interest. The implication of the ban on them if studied in depth can help us to devise some strategy for their rehabilitation and preventive programmes to deter them from indulging into such type of business. We may also get some newer insights to strengthen the ban.~Aim and Objectives:~To assess the knowledge of gutkha and pan-masala users regarding the ban~To assess the awareness regarding health hazards of gutkha and pan masala among the users~To investigate the effectiveness with which the gutkha and pan masala ban has been implemented~To determine the impact of gutkha and pan masala ban on previous users in terms of availability, reduction of use, quitting, switch over to other tobacco products, cost of available products etc.~To understand the perception of gutkha and pan masala among users regarding the ban.~To record any personal positive or negative experience (e.g. health effects) that the user experienced after the ban.~To assess the perception of tobacco vendors regarding the ban.~To understand the financial implications of the ban on the vendors~To record if the vendors still sell gutkha and pan-masala and the details regarding the same (source, brands, costing etc.)~To record if the tobacco vendors themselves were gutka and pan masala users and their tobacco related behaviour after the ban.~To observe if there are empty sachets of Gutkha/ pan masala lying near the shops of tobacco vendors~Secondary Objective:~1. To record the prevalence of gutkha and pan-masala use in low socio economic community in Mumbai suburbs (before the ban was imposed).~Methodology:~Study type : Cross sectional study Study area : PMGP area - Pocket No. 6, Mankhurd, Mumbai Low socio-economic community in suburbs of Mumbai Total population: Around 6000 Inclusion criteria : For survey: All tobacco users Part I - All the persons (≥ 18 years) using gutkha and/or pan masala (at the time of implementation of ban) in the selected community.~Part-II All tobacco vendors (≥ 18 years) in the selected locality Exclusion criteria : Those dead, shifted out of the area, unwilling to give consent and severely ill will be excluded Sample size : The selected community PMGP area - Pocket No. 6, Mankhurd has a total population of around 6000, with 1100 tobacco users (as documented in the previous departmental program) will be surveyed to enlist the gutka and pan-masala users who are the eligible participants for the Part I of the trial (Expected about 75-90). For Part II of the trial all tobacco vendors in the PMGP area - Pocket No. 6, Mankhurd will be invited for participation. (Expected about 10) Study duration : Three months Study tool : Two separate Pre-designed and pre-tested questionnaires to be administered by trained Medical Social Workers, one for the gutka and pan-masala users and the other for the tobacco vendors.~Statistical analysis : The data entry will be done by EDP Technicians in SPSS software version 19. Data errors will be checked. The compiled data will be analysed with the help of Stata software. The qualitative data will be analysed with the help of Non parametric tests. The effects of the ban on change in tobacco habit and various factors responsible for the same will be analysed using univariate and multivariate logistic regression analysis.~Technical manpower:~Medical Social Workers: 2 EDP Technician: 1~The present study is proposed to be conducted at PMGP area (Pocket No.6), which is one of the clusters of the mobile outreach programme of the department of Preventive Oncology. Under this programme women are screened for breast, cervix and oral cavity cancers. A list of male and female tobacco users in this area will be made available from the previous program data. This area is being selected for the present trial since our observation suggests that the prevalence of tobacco usage among both men and women is high in this area though the data inputting is still on-going. The project will be carried out even if the ban is lifted by the Supreme Court to understand the behaviour of the gutka and pan-masala users in the interim period.~At first all the important stakeholders in the concerned issue will be identified.viz Community leaders, NGOs, health care providers etc. The plan to establish community rapport with the help of these stakeholders for the current project will be developed. Then required staff members will be recruited. They will be given necessary training at Preventive Oncology Department. Pre-designed proforma will be pilot tested in community and necessary changes will be made. Maps of the households are available from our previous program. However, extensive mapping of the tobacco vendors in the area and detailed micro-plan to implement the project will be undertaken. Suitable time of the day will be identified for interview so as to maximise the response rate.~The Medical Social workers will undertake house to house visits only to houses of male and female tobacco users in the community (as identified in the previous project). The list of the same will be made available to them from the previous program data. The MSWs will conduct a short survey to identify the Gutkha and Pan-masala users amongst this population (at the time of implementation of the ban). They will be taken into confidence and explained about the objectives and methods of the study. They will then be invited to participate in the trial and a written informed consent in local language will be obtained from them. Left hand thumb impression will be obtained from those who are illiterates. A person from the same community will be invited to witness the procedure of informed consent and will sign as an impartial witness. Help of a translator will be taken whenever necessary. The invited participants will be given the patient information sheet. Only after obtaining the informed consent the participants will be enrolled in the trial and will be interviewed with the help of pre-designed and pre-tested proforma questionnaire. A pamphlet containing information regarding the health hazards of tobacco in both pictoral form and written in local language will be given to the participant after the interview.~The second aspect of the study deals with the response and implications of the ban on the tobacco vendors. Here all the tobacco vendors in the same selected community PMGP area (Pocket No.6) will be mapped and enumerated by MSWs. After initial interaction with them, suitable time of the day will be selected to interview them again to get the maximum possible response. After explaining the purpose of the study, they will then be invited to participate in the trial. A written informed consent in local language will be obtained from them. Left hand thumb impression will be obtained from those who are illiterates. A person from the same community will be invited to witness the procedure of informed consent and will sign as an impartial witness. Help of a translator will be taken whenever necessary. The invited participants will be given the patient information sheet. Only after obtaining the informed consent the participants will be enrolled in the trial. They will be interviewed using another set of questionnaire so as to understand their response and implications to the ban. Also observational survey will be made in the surrounding area to see if there are gutkha/ pan masala packets in the shop, direct or surrogate advertisements nearby, empty sachets of Gutkha and pan masala lying in the nearby area etc.~The data collection will be completed in six months time. Data analysis will be done and logical interpretations will be drawn and publicized so as to develop further strategies for advocacy in support of the ban.	Impact of 'Gutkha and Pan Masala Ban' in the State of Maharashtra on Users and Vendors	AODE on Coworker		Inclusion Criteria:~For survey : All tobacco users~Part I-All the persons (≥ 18 years) using gutkha and/or pan masala (at the time of implementation of ban) in the selected community.~Part-II All tobacco vendors (≥ 18 years) in the selected locality~Exclusion Criteria:~Those dead, shifted out of the area, unwilling to give consent and severely ill	18 Years	null	All	No		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Gutkha or Pan Masala Habit Quit \| The person who has quit consuming Gutkha / Pan Masala (has not consumed it at least for a month) after 3 months will be considered as quitter of the habit. \| After 3 months \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Decrease in consumption of Gutkha and / or Pan Masala \| Verbal assessment will be done to enquire about reduction in consumption of Gutkha / Pan Masala after 3 months from the date of ban i. e. 19th July 2012 as compared to his / her consumption habit pripor to the enforcement of ban \| After 3 months \|	Gutkha, Pan masala ban, Legislation, Smokeless tobacco			Gutkha Pan Masala Ban Impact Study in Mumbai Study Overview ================= Brief Summary ----------------- Present study is conducted on Gutkha and Pan Masala users to find out the impact of ban on them. It will also try to find out awareness about ban and source of information for the same. Availability of Gutkha and Pan Masala in post ban period will also be assessed. Detailed Description ----------------- Background: Based on the various reports indicating health hazards of gutka and pan masala there are various efforts to ban the production, consumption, sale, storage and transportation of these products by various states in India. The situation had gone to such an extent that government had no other option than to ban these products. In India gutka is classed as a food item and falls within the purview of Prevention of Food Adulteration act. The Central Committee on Food Standards (CCFS) had already reported a complete ban to the Central Government a decade ago itself. The reasons unanimously given by CCFS for a complete ban on Gutka were 1) Children are getting addicted to these products in large numbers; 2) Users develop Oral Submucous Fibrosis and cancer over a relatively shorter duration and die earlier compared to smokers; 3) Women prefer smokeless tobacco due to social disapproval of their smoking and therefore may be particularly vulnerable to gutka addiction. Tamil Nadu had banned Gutka in 2001 itself. Andhra Pradesh, Goa, Maharashtra & Rajasthan had also followed the same in August 2002.4 Subsequently following some legal battles ban on Gutka in Maharashtra was lifted. But now following the example of eight other states in India, Government of Maharashtra has finally banned the manufacture, storage, distribution or sale of Gutka and Pan masala, containing either tobacco and/or nicotine or Magnesium Carbonate as ingredients by whatsoever name these are available in the market and any other products marketed separately to constitute as Gutka and Pan Masala, etc. as final products from July 19, 2012.8 The appeal filed by some manufacturers in Bombay High Court has been quashed and the ban is to continue now unless it is reversed by the Supreme Court of India. Sensing the possibility of Supreme Court (SC) appeal by gutka and pan masala manufacturers the Government of Maharashtra has already filed an caveat there so that there plea will be heard first by SC before passing any order in this matter. There is a large population addicted to Gutkha and pan-masala all over India. We would like to study the impact of this ban on the users of this product and on the tobacco vendors. Even if the ban is reversed by the Supreme Court, we would still like to study its impact in the interim period when the ban was imposed. Rationale: Seeing the addictive potential of the contents of gutka and pan masala, it will be interesting to record the effect of ban of these products on the regular consumers. Whether they have stopped the consumption or are still getting the products (by smuggled routes) is an important issue. If they have shifted to other tobacco products, it will be important to study the shift pattern. If at all some withdrawal symptoms are reported by them, it will be helpful to record it so as to devise our cessation strategies. If the previous regular consumers have stopped the consumption of gutka and pan masala because of ban, it is positive sign in support of legal ban for the maintenance of proper public health. The response of gutka and pan masala users to the ban has to be studied. To what extent they have accepted the ban and what reaction they are giving are important issues to be studied. In depth analysis of all these points will be helpful in the development of further public health strategy as far as use of gutka and pan masala is concerned. The second aspect of this study is to investigate the response and implications of tobacco vendors to the ban. In last few years there was tremendous increase in vendors of tobacco especially Gutka and Pan-masala. These products being cheaply available were marketed in almost all corners of cities and villages. Even public transport vehicle were also flooded by the presence of many street vendors. Ultimately all these vendors were working as the merchants of deadly tobacco products. So the study of the response of these people to ban is an issue of interest. The implication of the ban on them if studied in depth can help us to devise some strategy for their rehabilitation and preventive programmes to deter them from indulging into such type of business. We may also get some newer insights to strengthen the ban. Aim and Objectives: To assess the knowledge of gutkha and pan-masala users regarding the ban To assess the awareness regarding health hazards of gutkha and pan masala among the users To investigate the effectiveness with which the gutkha and pan masala ban has been implemented To determine the impact of gutkha and pan masala ban on previous users in terms of availability, reduction of use, quitting, switch over to other tobacco products, cost of available products etc. To understand the perception of gutkha and pan masala among users regarding the ban. To record any personal positive or negative experience (e.g. health effects) that the user experienced after the ban. To assess the perception of tobacco vendors regarding the ban. To understand the financial implications of the ban on the vendors To record if the vendors still sell gutkha and pan-masala and the details regarding the same (source, brands, costing etc.) To record if the tobacco vendors themselves were gutka and pan masala users and their tobacco related behaviour after the ban. To observe if there are empty sachets of Gutkha/ pan masala lying near the shops of tobacco vendors Secondary Objective: 1. To record the prevalence of gutkha and pan-masala use in low socio economic community in Mumbai suburbs (before the ban was imposed). Methodology: Study type : Cross sectional study Study area : PMGP area - Pocket No. 6, Mankhurd, Mumbai Low socio-economic community in suburbs of Mumbai Total population: Around 6000 Inclusion criteria : For survey: All tobacco users Part I - All the persons (≥ 18 years) using gutkha and/or pan masala (at the time of implementation of ban) in the selected community. Part-II All tobacco vendors (≥ 18 years) in the selected locality Exclusion criteria : Those dead, shifted out of the area, unwilling to give consent and severely ill will be excluded Sample size : The selected community PMGP area - Pocket No. 6, Mankhurd has a total population of around 6000, with 1100 tobacco users (as documented in the previous departmental program) will be surveyed to enlist the gutka and pan-masala users who are the eligible participants for the Part I of the trial (Expected about 75-90). For Part II of the trial all tobacco vendors in the PMGP area - Pocket No. 6, Mankhurd will be invited for participation. (Expected about 10) Study duration : Three months Study tool : Two separate Pre-designed and pre-tested questionnaires to be administered by trained Medical Social Workers, one for the gutka and pan-masala users and the other for the tobacco vendors. Statistical analysis : The data entry will be done by EDP Technicians in SPSS software version 19. Data errors will be checked. The compiled data will be analysed with the help of Stata software. The qualitative data will be analysed with the help of Non parametric tests. The effects of the ban on change in tobacco habit and various factors responsible for the same will be analysed using univariate and multivariate logistic regression analysis. Technical manpower: Medical Social Workers: 2 EDP Technician: 1 The present study is proposed to be conducted at PMGP area (Pocket No.6), which is one of the clusters of the mobile outreach programme of the department of Preventive Oncology. Under this programme women are screened for breast, cervix and oral cavity cancers. A list of male and female tobacco users in this area will be made available from the previous program data. This area is being selected for the present trial since our observation suggests that the prevalence of tobacco usage among both men and women is high in this area though the data inputting is still on-going. The project will be carried out even if the ban is lifted by the Supreme Court to understand the behaviour of the gutka and pan-masala users in the interim period. At first all the important stakeholders in the concerned issue will be identified.viz Community leaders, NGOs, health care providers etc. The plan to establish community rapport with the help of these stakeholders for the current project will be developed. Then required staff members will be recruited. They will be given necessary training at Preventive Oncology Department. Pre-designed proforma will be pilot tested in community and necessary changes will be made. Maps of the households are available from our previous program. However, extensive mapping of the tobacco vendors in the area and detailed micro-plan to implement the project will be undertaken. Suitable time of the day will be identified for interview so as to maximise the response rate. The Medical Social workers will undertake house to house visits only to houses of male and female tobacco users in the community (as identified in the previous project). The list of the same will be made available to them from the previous program data. The MSWs will conduct a short survey to identify the Gutkha and Pan-masala users amongst this population (at the time of implementation of the ban). They will be taken into confidence and explained about the objectives and methods of the study. They will then be invited to participate in the trial and a written informed consent in local language will be obtained from them. Left hand thumb impression will be obtained from those who are illiterates. A person from the same community will be invited to witness the procedure of informed consent and will sign as an impartial witness. Help of a translator will be taken whenever necessary. The invited participants will be given the patient information sheet. Only after obtaining the informed consent the participants will be enrolled in the trial and will be interviewed with the help of pre-designed and pre-tested proforma questionnaire. A pamphlet containing information regarding the health hazards of tobacco in both pictoral form and written in local language will be given to the participant after the interview. The second aspect of the study deals with the response and implications of the ban on the tobacco vendors. Here all the tobacco vendors in the same selected community PMGP area (Pocket No.6) will be mapped and enumerated by MSWs. After initial interaction with them, suitable time of the day will be selected to interview them again to get the maximum possible response. After explaining the purpose of the study, they will then be invited to participate in the trial. A written informed consent in local language will be obtained from them. Left hand thumb impression will be obtained from those who are illiterates. A person from the same community will be invited to witness the procedure of informed consent and will sign as an impartial witness. Help of a translator will be taken whenever necessary. The invited participants will be given the patient information sheet. Only after obtaining the informed consent the participants will be enrolled in the trial. They will be interviewed using another set of questionnaire so as to understand their response and implications to the ban. Also observational survey will be made in the surrounding area to see if there are gutkha/ pan masala packets in the shop, direct or surrogate advertisements nearby, empty sachets of Gutkha and pan masala lying in the nearby area etc. The data collection will be completed in six months time. Data analysis will be done and logical interpretations will be drawn and publicized so as to develop further strategies for advocacy in support of the ban. Official Title ----------------- Impact of 'Gutkha and Pan Masala Ban' in the State of Maharashtra on Users and Vendors Conditions ----------------- AODE on Coworker Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: For survey : All tobacco users Part I-All the persons (≥ 18 years) using gutkha and/or pan masala (at the time of implementation of ban) in the selected community. Part-II All tobacco vendors (≥ 18 years) in the selected locality Exclusion Criteria: Those dead, shifted out of the area, unwilling to give consent and severely ill Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Gutkha or Pan Masala Habit Quit \| The person who has quit consuming Gutkha / Pan Masala (has not consumed it at least for a month) after 3 months will be considered as quitter of the habit. \| After 3 months \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Decrease in consumption of Gutkha and / or Pan Masala \| Verbal assessment will be done to enquire about reduction in consumption of Gutkha / Pan Masala after 3 months from the date of ban i. e. 19th July 2012 as compared to his / her consumption habit pripor to the enforcement of ban \| After 3 months \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Gutkha, Pan masala ban, Legislation, Smokeless tobacco
NCT00855426	Diagnostic Protocol Of Painful Hip	Nondisplaced hip fractures may be radiographically occult and require MRI or single photon emission CT bone scintigraphy for accurate diagnosis. Both examinations are expensive and are not readily available in many hospitals. Ultrasound (US) examination is relatively inexpensive and preliminary data had demonstrated its efficacy in detecting occult fractures in other sites. Our objective is to evaluate US examination as a screening tool for occult hip fractures in posttraumatic painful hips in the elderly.		null	Hip Fracture		Inclusion Criteria:~Men and women above 40 years old~Trauma to the hip .~Extreme difficulty in walking or inability to step on the leg, following sensitivity in the hip joint area after local pressure or in a movement.~X ray of the pelvis aimed to the suspected hip joint (including AP lateral position and internal rotation) does not demonstrate fracture in the joint or the pelvis.~Exclusion Criteria:~1. None	40 Years	85 Years	All	No		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \|			Hip Fractures, Femoral Fractures, Fractures, Bone, Wounds and Injuries, Hip Injuries, Leg Injuries		Diagnostic Protocol Of Painful Hip Study Overview ================= Brief Summary ----------------- Nondisplaced hip fractures may be radiographically occult and require MRI or single photon emission CT bone scintigraphy for accurate diagnosis. Both examinations are expensive and are not readily available in many hospitals. Ultrasound (US) examination is relatively inexpensive and preliminary data had demonstrated its efficacy in detecting occult fractures in other sites. Our objective is to evaluate US examination as a screening tool for occult hip fractures in posttraumatic painful hips in the elderly. Conditions ----------------- Hip Fracture Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Men and women above 40 years old Trauma to the hip . Extreme difficulty in walking or inability to step on the leg, following sensitivity in the hip joint area after local pressure or in a movement. X ray of the pelvis aimed to the suspected hip joint (including AP lateral position and internal rotation) does not demonstrate fracture in the joint or the pelvis. Exclusion Criteria: 1. None Ages Eligible for Study ----------------- Minimum Age: 40 Years Maximum Age: 85 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \|
NCT04338152	Family-Focused Therapy for Individuals at High Clinical Risk for Psychosis: A Confirmatory Efficacy Trial	The present study is a confirmatory efficacy trial of Family Focused Therapy for youth at clinical high risk for psychosis (FFT-CHR). This trial is sponsored by seven mature CHR clinical research programs from the North American Prodrome Longitudinal Study (NAPLS). The young clinical high risk sample (N = 220 youth ages 13-25) is to be followed at 6-month intervals for 18 months.	This randomized, single blind trial will compare outcomes from a 6-month FFT-CHR intervention and a control condition (enhanced care, or EC) matched to the FFT-CHR in duration (6 months) and access to a clinician. Participants families in FFT-CHR are provided 18 family sessions augmented by a therapy app with content and surveys, while participants in the EC condition are provided three family sessions plus five monthly individual support and case management sessions. Duration of therapy sessions is one hour.~Main Goals of FFT-CHR (Experimental Treatment)~To assist young clients and their family in: developing a common understanding of CHR symptoms; recognizing early signs of escalating symptoms; practicing individual and family coping strategies; and pre-planning family responses to any escalation in symptoms. When families have poor understanding of CHR symptoms and strategies for their management, this can fuel stressful home dynamics and contribute to youth withdrawal and decompensation.~For the youth and their family members to learn to express more constructive messages during their interactions, particularly regarding highly charged topics such as curbing risky behaviors and management of the offspring's symptoms.~For youth and family members to practice skills for resolving family or extrafamilial conflicts (usually those related to the youth's functioning) through effective communication and problem solving~The control condition, Enhanced Care (EC) shares the psychoeducation goal of FFT-CHR but is more oriented toward skill-training for the individual patient. Whereas it does not offer the same level of opportunity for families to build communication and problem-solving skills, the family is actively involved in helping the individual develop a relapse prevention plan. Monthly individual sessions focus on the development of individual coping skills such as symptom tracking and problem-solving. Both conditions require families to submit real-time mobile app surveys to assist with progress tracking.~Study Aims~The primary clinical outcomes are prodromal positive symptom scores examined immediately after treatment (6 months) and at 18 months. Secondary outcomes are time to remission of positive symptoms and psychosocial functioning over 18 months. Temporal relationships between early changes in treatment targets and later changes in symptoms or psychosocial functioning will also be examined.~Primary Hypotheses~FFT-CHR (vs. EC) will be associated with greater improvement in positive symptoms by end of therapy and follow-up (6 and 18 months), and greater high-risk syndrome remission and better psychosocial functioning at 18 months~FFT-CHR (vs. EC) will be associated with greater improvement in family communication and problem solving at 6 months~FFT-CHR (vs. EC) will be associated with greater improvement in youth-perceived parental criticism at 6 months. In turn, improvements in family communication, problem-solving and youths' perceptions of criticism will be associated with downstream improvements in the youths' primary outcomes (positive symptoms) and secondary outcomes (time to remission and psychosocial functioning) over 18 months. Thus, improvements in family functioning are hypothesized to mediate the relationship between treatment condition (FFT-CHR, EC) and changes in primary and secondary outcomes in the individual with CHR syndrome.~CHR individuals with higher baseline risk of conversion are hypothesized to improve more on family communication over 6 months and primary and secondary outcomes over 18 months in FFT-CHR than in EC.	Family-Focused Therapy for Individuals at High Clinical Risk for Psychosis: A Confirmatory Efficacy Trial	Psychotic Disorders, Prodromal Symptoms, Prodromal Schizophrenia, Psychosis, Family	* Behavioral: Family Focused Therapy for Clinical High Risk Youth (FFT-CHR) * Behavioral: Enhanced Care (EC)	Inclusion Criteria~Participants must be able to understand and sign an informed consent (or assent for minors) document in English;~Youth has at least one parent or legal guardian who participants sees often enough (minimum 4 hours/week) that family intervention is sensible, who is English-speaking, and who consents to study participation and treatment sessions; and~Youth currently meets criteria for clinical high-risk (CHR) for psychosis, with attenuated positive symptoms that have begun or worsened in the past 12 months, genetic risk and deterioration, or brief intermittent psychotic symptoms. Eligible participants may meet DSM-5 criteria for any non-psychotic disorder (e.g. major depression, anxiety disorders, ADHD), as long as the disorder does not clearly account for the presence of psychosis risk symptoms.~Exclusion Criteria~Current or lifetime Axis 1 psychotic disorder by DSM-5 criteria~Impaired intellectual functioning (IQ<70)~Unwilling or unable to taper individual therapy to monthly by start of treatment~Past or current history of a clinically significant medical or central nervous system disorder that may contribute to CHR symptoms or confound assessment~Severe substance or alcohol use disorder within the past 6 months, and/or substance use (including cannabis) is causally related to recent onset of CHR symptoms so as to confound prodromal diagnostic determination.~If either an exclusionary medical condition or an incidental medical condition is suspected, the participant will be advised to consult with their physician or will be referred to a specialist. Eligibility for the trial will be reconsidered if the medical condition has been treated to remission and the subject still meets CHR criteria.	13 Years	25 Years	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: FFT-CHR assists families with (1) recognizing the youth's psychosis risk symptoms and warning signs of escalating risk, (2) understanding vulnerability to psychosis and interventions, and (3) operating effectively as a unit. The manual includes session instructions and handouts.~The Enhanced care (EC) condition has also been manualized and tested as a family educational treatment in CHR and bipolar youth. The 3 weekly sessions involve an abridged form of FFT-CHR psychoeducation. Then the youth has monthly individual sessions focused on applying the prevention plan and nondirective problem-solving of conflicts. The clinician serves as case manager.~See further description below. Masking: Single	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| The Structured Interview for Psychosis-risk Syndromes Scale of Prodromal Symptoms (SOPS) \| The change from baseline to follow-up in Total Scale of Prodromal Symptoms (SOPS) Positive scores (sum of items 1 to 5) will be significantly greater in clinical high-risk patients assigned to FFT-CHR vs. EC. Total SOPS scores range from 0-30, with higher scores indicating more severe symptoms. In FFT-CHR (versus EC), rates of remission of prodromal symptoms will be higher and rates of conversion to psychosis will be lower over 18 months. \| 0, 6, 12, and 18 months \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Perceived Criticism Scale \| Measures adolescent perceived criticism from parent(s) during treatment (highest sum score for two items rated 1-10 each, with higher scores indicating more perceived criticism), as well as parental self-rated criticism of their child (highest sum score for either parent for the 2 items rated 1-10) \| 0, 6, 12, and 18 months \| \| Family Interactional Assessment Task \| Measures proportion of constructive vs. conflictual parent/offspring and offspring/parent communication. Scores are derived from a 10-minute live interaction sample and transcript, with each speaking turn rated on communication dimensions. Proportional scores range from 0 - 1.0, with higher scores indicating a greater proportion of conflictual (or constructive) communication \| 0 and 6 months \| \| Appraisal of Family Interactions \| Perceived frequency of constructive/calm and critical/conflictual interactions in each parent/offspring pairing. Sum of 5 items (1-10 scales) filled out by parent(s)/youth about the frequency of critical-conflictual and calm-constructive interactions and the level of distress experienced in these interactions, with higher scores indicating more of the behavior (conflict, constructive communication or distress) \| 0, 6, 12, and 18 months \| \| Global Functioning: Social Scale; Global Functioning: Role Scale \| Independent evaluator rated social functioning and school/job functioning scales based on set interview questions and assessment data. Both scales capture level of functioning for the recent month, rated from 1-10, with higher scores indicating better functioning. \| 0, 6, 12, and 18 months \| \| Global Assessment of Functioning Scale from the Structured Interview for Psychosis-risk Syndromes \| Independent evaluator rating of combined symptom and psychosocial functioning. 1-100 point scale captures current functioning and highest/lowest functioning since previous assessment point. Higher scores indicate better functioning. \| 0, 6, 12, and 18 months \| \| Calgary Depression Scale for Schizophrenia \| Depression severity score based on 9-item evaluator interview (0-3 severity scores for each item). Combined total depression score, where higher scores indicate more depression. \| 0, 6, 12, and 18 months \| \| The Alcohol and Drug Use Scale \| Independent evaluator rating of frequency of use and level of impairment from alcohol and substance use in the recent month, based on combined youth and parent reports. Higher scores indicate more substance or alcohol use. \| 0, 6, 12, and 18 months \|	Family Therapy, Family Focused Therapy, Prodromal psychosis, Clinical High Risk	Prodromal Symptoms, Schizophrenia, Psychotic Disorders, Mental Disorders, Schizophrenia Spectrum and Other Psychotic Disorders	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: FFT-CHR<br>Family-Focused Therapy for Clinical High-Risk Individuals \| Behavioral: Family Focused Therapy for Clinical High Risk Youth (FFT-CHR)<br>* Family-Focused Therapy (FFT) has been tested in randomized trials involving persons with bipolar disorder, depression, and clinical high-risk syndromes. FFT-CHR provides families with psychoeducation (sessions 1-6) about prodromal symptoms and the role of the family in helping maintain stability. Clients are supported in building coping skills and monitoring thoughts, perceptions, and mood. The family formulates a prevention action plan to prevent prodromal symptoms from escalating into full episodes. Communication training (sessions 7-13) teaches families to express positive and negative feelings, listen actively, make positive requests for change, and communicate clearly through role-playing and between-session practice. In problem solving (sessions 14-18) participants learn to break down problems into smaller ones, evaluate pros/cons, and choose solutions to implement.<br>\| \| Active Comparator: Enhanced Care<br>Enhanced Care Psychoeducation for Clinical High-Risk Individuals \| Behavioral: Enhanced Care (EC)<br>* Enhanced care (EC) has been tested as a family educational treatment in CHR and bipolar youth. The first 3 sessions of EC involve the CHR person and family (parents, siblings) and cover the same content as the psychoeducational module of FFT in abridged form. The objective of these sessions is to develop a prevention action plan. Then, the CHR person is offered monthly individual sessions with the same clinician over the next 5 months, for a total of 8 sessions over 6 months. The individual sessions focus on applying the prevention action plan when symptoms emerge, and supportive, nondirective problem-solving regarding areas of conflict with family, with peers or in the educational or occupational arena. The clinician also serves as case manager.<br>\|	Family-Focused Therapy for Individuals at High Clinical Risk for Psychosis: A Confirmatory Efficacy Trial Study Overview ================= Brief Summary ----------------- The present study is a confirmatory efficacy trial of Family Focused Therapy for youth at clinical high risk for psychosis (FFT-CHR). This trial is sponsored by seven mature CHR clinical research programs from the North American Prodrome Longitudinal Study (NAPLS). The young clinical high risk sample (N = 220 youth ages 13-25) is to be followed at 6-month intervals for 18 months. Detailed Description ----------------- This randomized, single blind trial will compare outcomes from a 6-month FFT-CHR intervention and a control condition (enhanced care, or EC) matched to the FFT-CHR in duration (6 months) and access to a clinician. Participants families in FFT-CHR are provided 18 family sessions augmented by a therapy app with content and surveys, while participants in the EC condition are provided three family sessions plus five monthly individual support and case management sessions. Duration of therapy sessions is one hour. Main Goals of FFT-CHR (Experimental Treatment) To assist young clients and their family in: developing a common understanding of CHR symptoms; recognizing early signs of escalating symptoms; practicing individual and family coping strategies; and pre-planning family responses to any escalation in symptoms. When families have poor understanding of CHR symptoms and strategies for their management, this can fuel stressful home dynamics and contribute to youth withdrawal and decompensation. For the youth and their family members to learn to express more constructive messages during their interactions, particularly regarding highly charged topics such as curbing risky behaviors and management of the offspring's symptoms. For youth and family members to practice skills for resolving family or extrafamilial conflicts (usually those related to the youth's functioning) through effective communication and problem solving The control condition, Enhanced Care (EC) shares the psychoeducation goal of FFT-CHR but is more oriented toward skill-training for the individual patient. Whereas it does not offer the same level of opportunity for families to build communication and problem-solving skills, the family is actively involved in helping the individual develop a relapse prevention plan. Monthly individual sessions focus on the development of individual coping skills such as symptom tracking and problem-solving. Both conditions require families to submit real-time mobile app surveys to assist with progress tracking. Study Aims The primary clinical outcomes are prodromal positive symptom scores examined immediately after treatment (6 months) and at 18 months. Secondary outcomes are time to remission of positive symptoms and psychosocial functioning over 18 months. Temporal relationships between early changes in treatment targets and later changes in symptoms or psychosocial functioning will also be examined. Primary Hypotheses FFT-CHR (vs. EC) will be associated with greater improvement in positive symptoms by end of therapy and follow-up (6 and 18 months), and greater high-risk syndrome remission and better psychosocial functioning at 18 months FFT-CHR (vs. EC) will be associated with greater improvement in family communication and problem solving at 6 months FFT-CHR (vs. EC) will be associated with greater improvement in youth-perceived parental criticism at 6 months. In turn, improvements in family communication, problem-solving and youths' perceptions of criticism will be associated with downstream improvements in the youths' primary outcomes (positive symptoms) and secondary outcomes (time to remission and psychosocial functioning) over 18 months. Thus, improvements in family functioning are hypothesized to mediate the relationship between treatment condition (FFT-CHR, EC) and changes in primary and secondary outcomes in the individual with CHR syndrome. CHR individuals with higher baseline risk of conversion are hypothesized to improve more on family communication over 6 months and primary and secondary outcomes over 18 months in FFT-CHR than in EC. Official Title ----------------- Family-Focused Therapy for Individuals at High Clinical Risk for Psychosis: A Confirmatory Efficacy Trial Conditions ----------------- Psychotic Disorders, Prodromal Symptoms, Prodromal Schizophrenia, Psychosis, Family Intervention / Treatment ----------------- * Behavioral: Family Focused Therapy for Clinical High Risk Youth (FFT-CHR) * Behavioral: Enhanced Care (EC) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria Participants must be able to understand and sign an informed consent (or assent for minors) document in English; Youth has at least one parent or legal guardian who participants sees often enough (minimum 4 hours/week) that family intervention is sensible, who is English-speaking, and who consents to study participation and treatment sessions; and Youth currently meets criteria for clinical high-risk (CHR) for psychosis, with attenuated positive symptoms that have begun or worsened in the past 12 months, genetic risk and deterioration, or brief intermittent psychotic symptoms. Eligible participants may meet DSM-5 criteria for any non-psychotic disorder (e.g. major depression, anxiety disorders, ADHD), as long as the disorder does not clearly account for the presence of psychosis risk symptoms. Exclusion Criteria Current or lifetime Axis 1 psychotic disorder by DSM-5 criteria Impaired intellectual functioning (IQ<70) Unwilling or unable to taper individual therapy to monthly by start of treatment Past or current history of a clinically significant medical or central nervous system disorder that may contribute to CHR symptoms or confound assessment Severe substance or alcohol use disorder within the past 6 months, and/or substance use (including cannabis) is causally related to recent onset of CHR symptoms so as to confound prodromal diagnostic determination. If either an exclusionary medical condition or an incidental medical condition is suspected, the participant will be advised to consult with their physician or will be referred to a specialist. Eligibility for the trial will be reconsidered if the medical condition has been treated to remission and the subject still meets CHR criteria. Ages Eligible for Study ----------------- Minimum Age: 13 Years Maximum Age: 25 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: FFT-CHR assists families with (1) recognizing the youth's psychosis risk symptoms and warning signs of escalating risk, (2) understanding vulnerability to psychosis and interventions, and (3) operating effectively as a unit. The manual includes session instructions and handouts. The Enhanced care (EC) condition has also been manualized and tested as a family educational treatment in CHR and bipolar youth. The 3 weekly sessions involve an abridged form of FFT-CHR psychoeducation. Then the youth has monthly individual sessions focused on applying the prevention plan and nondirective problem-solving of conflicts. The clinician serves as case manager. See further description below. Masking: Single Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: FFT-CHR<br>Family-Focused Therapy for Clinical High-Risk Individuals \| Behavioral: Family Focused Therapy for Clinical High Risk Youth (FFT-CHR)<br>* Family-Focused Therapy (FFT) has been tested in randomized trials involving persons with bipolar disorder, depression, and clinical high-risk syndromes. FFT-CHR provides families with psychoeducation (sessions 1-6) about prodromal symptoms and the role of the family in helping maintain stability. Clients are supported in building coping skills and monitoring thoughts, perceptions, and mood. The family formulates a prevention action plan to prevent prodromal symptoms from escalating into full episodes. Communication training (sessions 7-13) teaches families to express positive and negative feelings, listen actively, make positive requests for change, and communicate clearly through role-playing and between-session practice. In problem solving (sessions 14-18) participants learn to break down problems into smaller ones, evaluate pros/cons, and choose solutions to implement.<br>\| \| Active Comparator: Enhanced Care<br>Enhanced Care Psychoeducation for Clinical High-Risk Individuals \| Behavioral: Enhanced Care (EC)<br>* Enhanced care (EC) has been tested as a family educational treatment in CHR and bipolar youth. The first 3 sessions of EC involve the CHR person and family (parents, siblings) and cover the same content as the psychoeducational module of FFT in abridged form. The objective of these sessions is to develop a prevention action plan. Then, the CHR person is offered monthly individual sessions with the same clinician over the next 5 months, for a total of 8 sessions over 6 months. The individual sessions focus on applying the prevention action plan when symptoms emerge, and supportive, nondirective problem-solving regarding areas of conflict with family, with peers or in the educational or occupational arena. The clinician also serves as case manager.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| The Structured Interview for Psychosis-risk Syndromes Scale of Prodromal Symptoms (SOPS) \| The change from baseline to follow-up in Total Scale of Prodromal Symptoms (SOPS) Positive scores (sum of items 1 to 5) will be significantly greater in clinical high-risk patients assigned to FFT-CHR vs. EC. Total SOPS scores range from 0-30, with higher scores indicating more severe symptoms. In FFT-CHR (versus EC), rates of remission of prodromal symptoms will be higher and rates of conversion to psychosis will be lower over 18 months. \| 0, 6, 12, and 18 months \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Perceived Criticism Scale \| Measures adolescent perceived criticism from parent(s) during treatment (highest sum score for two items rated 1-10 each, with higher scores indicating more perceived criticism), as well as parental self-rated criticism of their child (highest sum score for either parent for the 2 items rated 1-10) \| 0, 6, 12, and 18 months \| \| Family Interactional Assessment Task \| Measures proportion of constructive vs. conflictual parent/offspring and offspring/parent communication. Scores are derived from a 10-minute live interaction sample and transcript, with each speaking turn rated on communication dimensions. Proportional scores range from 0 - 1.0, with higher scores indicating a greater proportion of conflictual (or constructive) communication \| 0 and 6 months \| \| Appraisal of Family Interactions \| Perceived frequency of constructive/calm and critical/conflictual interactions in each parent/offspring pairing. Sum of 5 items (1-10 scales) filled out by parent(s)/youth about the frequency of critical-conflictual and calm-constructive interactions and the level of distress experienced in these interactions, with higher scores indicating more of the behavior (conflict, constructive communication or distress) \| 0, 6, 12, and 18 months \| \| Global Functioning: Social Scale; Global Functioning: Role Scale \| Independent evaluator rated social functioning and school/job functioning scales based on set interview questions and assessment data. Both scales capture level of functioning for the recent month, rated from 1-10, with higher scores indicating better functioning. \| 0, 6, 12, and 18 months \| \| Global Assessment of Functioning Scale from the Structured Interview for Psychosis-risk Syndromes \| Independent evaluator rating of combined symptom and psychosocial functioning. 1-100 point scale captures current functioning and highest/lowest functioning since previous assessment point. Higher scores indicate better functioning. \| 0, 6, 12, and 18 months \| \| Calgary Depression Scale for Schizophrenia \| Depression severity score based on 9-item evaluator interview (0-3 severity scores for each item). Combined total depression score, where higher scores indicate more depression. \| 0, 6, 12, and 18 months \| \| The Alcohol and Drug Use Scale \| Independent evaluator rating of frequency of use and level of impairment from alcohol and substance use in the recent month, based on combined youth and parent reports. Higher scores indicate more substance or alcohol use. \| 0, 6, 12, and 18 months \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Family Therapy, Family Focused Therapy, Prodromal psychosis, Clinical High Risk
NCT01860274	Meshed Vein Graft Patency Trial - VEST	The study hypothesis is that a meshed conduit made of safen vein allows a better patency at mid-long term than a safen vein alone.~To test this hypothesis the investigators plan a prospective, randomized study, comparing grafts to the diagonal, in cases of vessel diameter under 1.5mm. A control angiography will be performed one year after the operation.		External Mesh of Vein Grafts In Coronary Artery Bypass Grating: Early Patency and Clinical Outcome	Coronary Artery Disease	* Device: External Mesh for vein grafts	Inclusion Criteria:~Clinical Indication for elective Coronary Artery Bypass Grafting with at least one vein graft~Coronary artery with critical stenosis (over 70%)~Exclusion Criteria:~-	null	null	All	No	Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Patency \| Patency of graft at CT Scan \| 6 to 12 months \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Major Adverse Cardiac and Cerebrovascular Events (MACCE) \| \| 60 months \| \| Vein graft lumen uniformity \| \| 6 to 12 months \|	Mesh, Graft, Patency	Coronary Artery Disease, Coronary Disease, Myocardial Ischemia, Heart Diseases, Cardiovascular Diseases, Arteriosclerosis, Arterial Occlusive Diseases, Vascular Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: External Mesh<br> \| Device: External Mesh for vein grafts<br> <br> \|	Meshed Vein Graft Patency Trial - VEST Study Overview ================= Brief Summary ----------------- The study hypothesis is that a meshed conduit made of safen vein allows a better patency at mid-long term than a safen vein alone. To test this hypothesis the investigators plan a prospective, randomized study, comparing grafts to the diagonal, in cases of vessel diameter under 1.5mm. A control angiography will be performed one year after the operation. Official Title ----------------- External Mesh of Vein Grafts In Coronary Artery Bypass Grating: Early Patency and Clinical Outcome Conditions ----------------- Coronary Artery Disease Intervention / Treatment ----------------- * Device: External Mesh for vein grafts Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Clinical Indication for elective Coronary Artery Bypass Grafting with at least one vein graft Coronary artery with critical stenosis (over 70%) Exclusion Criteria: - Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: External Mesh<br> \| Device: External Mesh for vein grafts<br> <br> \| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Patency \| Patency of graft at CT Scan \| 6 to 12 months \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Major Adverse Cardiac and Cerebrovascular Events (MACCE) \| \| 60 months \| \| Vein graft lumen uniformity \| \| 6 to 12 months \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Mesh, Graft, Patency
NCT02317081	Axetis Inert Coronary Stent System First In Man Clinical Investigation (AXETIS FIM)	Prospective, multicenter, single arm study, to assess the feasibility and safety of the Axetis Inert Stent for treatment of patients with de novo coronary artery stenosis in native vessels.	Prospective, multicenter, open-label and single arm study, conducted in 3 interventional cardiology centers in The Netherlands. The objective is to assess the feasibility and safety of the Axetis Inert Stent for treatment of patients with de novo coronary artery stenosis in native vessels. In total, 35 patients will be enrolled. All patients will be treated with Axetis Inert Coronary Stent System. All patients will undergo repeat angiography at 6 months follow-up. Quantitative coronary angiography (QCA) assessment will be performed at baseline (pre- and post-procedure) and at 6 months follow-up. All patients will undergo Optical coherence Tomography (OCT) investigation at baseline (post procedure) and at 6 months follow-up. The primary endpoint is in-stent Late Lumen Loss (LLL) at 6 months after stent implantation as assessed by off-line QCA. Clinical follow-up will occur at 6 and 12 months post-stent implantation.	Axetis Inert Coronary Stent System First In Man Clinical Investigation (AXETIS FIM)	Native Coronary Artery Stenosis	* Device: Axetis Inert Coronary Stents	Inclusion Criteria:~18 to 85 years~Evidence of myocardial ischemia without elevatedTroponin / cardiac biomarkers (e.g.~stable or unstable angina, silent ischemia demonstrated by positive territorial functional study). NSTEMI patients are allowed, as long as Troponin is within the normal limits before the start of the procedure.~The patient has a planned intervention of up to two de-novo lesions in two different vessels (previously untreated vessels)~Lesion must have a visually estimated diameter stenosis of ≥50% and <100%.~Lesion length must be ≤ 28 mm~RVD must be between 2.4 and 3.8 mm~Written informed consent~The patient and the patient's physician agree to the follow-up visits including angiographic follow-up and OCT control at 6 months~Exclusion Criteria:~Evidence of ongoing acute myocardial infarction in ECG and or elevated cardiac biomarkers prior to procedure.~LVEF <30%~Platelet count <100,000 cells/mm3 or >400,000 cells/mm3, a WBC of <3,000 cells/mm3, or documented or suspected liver disease (including laboratory evidence of hepatitis)~Known renal insufficiency (e.g., eGFR <60 ml/kg/m2 or serum creatinine level of >2.5 mg/dL, or subject on dialysis)~History of bleeding diathesis or coagulopathy~The patient is a recipient of a heart transplant~Known hypersensitivity or contraindication to aspirin, heparin, antiplatelet medication specified for use in the study (clopidogrel, prasugrel, ticagrelor and ticlopidine) or stainless steel~Other medical illness (e.g. cancer, stroke with neurological deficiency) or known history of substance abuse (alcohol, cocaine, heroin etc.) as per physician judgment that may cause non-compliance with the protocol or confound the data interpretation or is associated with a limited life expectancy~Pregnant or breastfeeding woman or woman in fertile period not taking adequate contraceptives~Severe tortuous, calcified or angulated coronary anatomy of the study vessel that in the opinion of the investigator would result in suboptimal imaging or excessive risk of complication from placement of an OCT catheter~Target lesion in left main stem.~Target lesion involves a side branch > 2.0mm in diameter~Aorto-ostial target lesion (within 3 mm of the aorta junction).~Total occlusion or TIMI flow 1, prior to wire crossing~The target vessel contains visible thrombus~Restenotic lesion~Target vessel with previously placed stent or with graft~Located within an arterial or saphenous vein graft~Treatment of more than 1 lesion in one vessel, or treatment of more than two lesions	18 Years	85 Years	All	No	Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| In-stent Late Lumen Loss (LLL) assessed by off-line QCA \| \| 6 months after stent implantation \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Acute Lumen gain \| Angiographic endpoint MLD (mm); Diameter Stenosis (%); Binary Restenosis (DS ≥50%) \| Post intervention (1 hour) \| \| Acute area gain \| Optical coherence tomography end point \| Post intervention (1 hour) \| \| Percent Acute device success \| Device-oriented Composite Endpoints (DoCE) at 6 months and 12 months (DoCE is defined as Cardiac Death, MI not clearly attributable to a nonintervention vessel, and clinically-indicated Target Lesion Revascularization and its individual components) Stent thrombosis according to the ARC definitions up to 12 months follow-up \| 1 day post intervention \| \| late lumen loss \| Angiographic endpoint \| 6 months after intervention \| \| maximal neointimal thickness \| OCT \| 6 months after intervention \| \| Percent procedural success \| \| post intervention (1 hour) \| \| Number of adverse cardiac events \| clinical endpoint \| 12 months after intervention \|		Coronary Stenosis, Coronary Disease, Myocardial Ischemia, Heart Diseases, Cardiovascular Diseases, Vascular Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Axetis Inert Coronary Stents<br>Axetis Inert Coronary Stents for de novo coronary lesion \| Device: Axetis Inert Coronary Stents<br>* de novo coronary artery stenosis in native vessels<br>\|	Axetis Inert Coronary Stent System First In Man Clinical Investigation (AXETIS FIM) Study Overview ================= Brief Summary ----------------- Prospective, multicenter, single arm study, to assess the feasibility and safety of the Axetis Inert Stent for treatment of patients with de novo coronary artery stenosis in native vessels. Detailed Description ----------------- Prospective, multicenter, open-label and single arm study, conducted in 3 interventional cardiology centers in The Netherlands. The objective is to assess the feasibility and safety of the Axetis Inert Stent for treatment of patients with de novo coronary artery stenosis in native vessels. In total, 35 patients will be enrolled. All patients will be treated with Axetis Inert Coronary Stent System. All patients will undergo repeat angiography at 6 months follow-up. Quantitative coronary angiography (QCA) assessment will be performed at baseline (pre- and post-procedure) and at 6 months follow-up. All patients will undergo Optical coherence Tomography (OCT) investigation at baseline (post procedure) and at 6 months follow-up. The primary endpoint is in-stent Late Lumen Loss (LLL) at 6 months after stent implantation as assessed by off-line QCA. Clinical follow-up will occur at 6 and 12 months post-stent implantation. Official Title ----------------- Axetis Inert Coronary Stent System First In Man Clinical Investigation (AXETIS FIM) Conditions ----------------- Native Coronary Artery Stenosis Intervention / Treatment ----------------- * Device: Axetis Inert Coronary Stents Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: 18 to 85 years Evidence of myocardial ischemia without elevatedTroponin / cardiac biomarkers (e.g. stable or unstable angina, silent ischemia demonstrated by positive territorial functional study). NSTEMI patients are allowed, as long as Troponin is within the normal limits before the start of the procedure. The patient has a planned intervention of up to two de-novo lesions in two different vessels (previously untreated vessels) Lesion must have a visually estimated diameter stenosis of ≥50% and <100%. Lesion length must be ≤ 28 mm RVD must be between 2.4 and 3.8 mm Written informed consent The patient and the patient's physician agree to the follow-up visits including angiographic follow-up and OCT control at 6 months Exclusion Criteria: Evidence of ongoing acute myocardial infarction in ECG and or elevated cardiac biomarkers prior to procedure. LVEF <30% Platelet count <100,000 cells/mm3 or >400,000 cells/mm3, a WBC of <3,000 cells/mm3, or documented or suspected liver disease (including laboratory evidence of hepatitis) Known renal insufficiency (e.g., eGFR <60 ml/kg/m2 or serum creatinine level of >2.5 mg/dL, or subject on dialysis) History of bleeding diathesis or coagulopathy The patient is a recipient of a heart transplant Known hypersensitivity or contraindication to aspirin, heparin, antiplatelet medication specified for use in the study (clopidogrel, prasugrel, ticagrelor and ticlopidine) or stainless steel Other medical illness (e.g. cancer, stroke with neurological deficiency) or known history of substance abuse (alcohol, cocaine, heroin etc.) as per physician judgment that may cause non-compliance with the protocol or confound the data interpretation or is associated with a limited life expectancy Pregnant or breastfeeding woman or woman in fertile period not taking adequate contraceptives Severe tortuous, calcified or angulated coronary anatomy of the study vessel that in the opinion of the investigator would result in suboptimal imaging or excessive risk of complication from placement of an OCT catheter Target lesion in left main stem. Target lesion involves a side branch > 2.0mm in diameter Aorto-ostial target lesion (within 3 mm of the aorta junction). Total occlusion or TIMI flow 1, prior to wire crossing The target vessel contains visible thrombus Restenotic lesion Target vessel with previously placed stent or with graft Located within an arterial or saphenous vein graft Treatment of more than 1 lesion in one vessel, or treatment of more than two lesions Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 85 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Axetis Inert Coronary Stents<br>Axetis Inert Coronary Stents for de novo coronary lesion \| Device: Axetis Inert Coronary Stents<br>* de novo coronary artery stenosis in native vessels<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| In-stent Late Lumen Loss (LLL) assessed by off-line QCA \| \| 6 months after stent implantation \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Acute Lumen gain \| Angiographic endpoint MLD (mm); Diameter Stenosis (%); Binary Restenosis (DS ≥50%) \| Post intervention (1 hour) \| \| Acute area gain \| Optical coherence tomography end point \| Post intervention (1 hour) \| \| Percent Acute device success \| Device-oriented Composite Endpoints (DoCE) at 6 months and 12 months (DoCE is defined as Cardiac Death, MI not clearly attributable to a nonintervention vessel, and clinically-indicated Target Lesion Revascularization and its individual components) Stent thrombosis according to the ARC definitions up to 12 months follow-up \| 1 day post intervention \| \| late lumen loss \| Angiographic endpoint \| 6 months after intervention \| \| maximal neointimal thickness \| OCT \| 6 months after intervention \| \| Percent procedural success \| \| post intervention (1 hour) \| \| Number of adverse cardiac events \| clinical endpoint \| 12 months after intervention \|
NCT04805593	Clinical Investigation of the WaveLight® EX500 Excimer Laser	The purpose of this study is to collect efficacy and safety data on the WaveLight EX500 excimer laser system for the correction of hyperopia with and without astigmatism by laser in situ keratomileusis (LASIK) treatment.	Qualified subjects will receive LASIK treatment in both eyes and be followed for 1 year. Subjects will be asked to attend a total of 9 visits (Screening, Surgery, Day 1, Week 1, Month 1, Month 3, Month 6, Month 9, and Year 1). Total expected duration of subject participation is approximately 1 year.	Clinical Investigation of the WaveLight® EX500 Excimer Laser for Hyperopic LASIK	Hyperopia, Hyperopic Astigmatism	* Device: WaveLight EX500 excimer laser system * Procedure: LASIK	Key Inclusion Criteria:~Intended to treat bilaterally;~Hyperopia with or without astigmatism as specified in the protocol;~Stable vision as specified in the protocol;~Other protocol-defined inclusion criteria may apply.~Key Exclusion Criteria:~Glaucoma;~Cataracts;~Previous eye surgery;~Intent to have monovision treatment;~Other protocol-defined exclusion criteria may apply.	18 Years	null	All	No	Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Percentage of eyes with manifest refraction spherical equivalent (MRSE) within ±0.50 diopter (D) at refractive stability \| A manifest refraction (manual refraction) will be performed using a phoropter. The spherical equivalent will be calculated by adding the sum of the sphere power with half of the cylinder power. Refractive stability is defined as the latter of two postoperative manifest refractions performed at least 3 months apart (or at 3 months after surgery when compared with the 1-month visit) that meets all the protocol-specified stability requirements. \| Preoperative, up to Month 12 \| \| Percentage of eyes with MRSE within ±1.00 D at refractive stability \| A manifest refraction (manual refraction) will be performed using a phoropter. The spherical equivalent will be calculated by adding the sum of the sphere power with half of the cylinder power. Refractive stability is defined as the latter of two postoperative manifest refractions performed at least 3 months apart (or at 3 months after surgery when compared with the 1-month visit) that meets all the protocol-specified stability requirements. \| Preoperative, up to Month 12 \| \| Percentage of eyes experiencing ocular adverse events (AEs) \| An AE is defined as any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in subjects, users, or other persons, whether or not related to the investigational medical device (test product). Ocular adverse events will be collected for this outcome measure. \| Up to Month 12 \|		LASIK, Refractive errors	Astigmatism, Hyperopia, Refractive Errors, Eye Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: WaveLight EX500 excimer laser system<br>Laser-assisted in situ keratomileusis (LASIK) surgery using the WaveLight EX500 excimer laser system \| Device: WaveLight EX500 excimer laser system<br>* FDA approved stationary scanning-spot excimer laser system used during refractive surgery for the treatment of myopia, myopic astigmatism, hyperopia, hyperopic astigmatism, and mixed astigmatism. For this clinical study, the Wavefront Optimized (WFO) Ablation profile of the WaveLight EX500 excimer laser system will be used for bilateral LASIK treatment of hyperopia with and without astigmatism.<br>Procedure: LASIK<br>* Procedure that reshapes the front part of the eye (cornea) so that light traveling through it is properly focused on the back part of the eye (retina). The procedure will be performed using the WaveLight EX500 excimer laser system.<br>\|	Clinical Investigation of the WaveLight® EX500 Excimer Laser Study Overview ================= Brief Summary ----------------- The purpose of this study is to collect efficacy and safety data on the WaveLight EX500 excimer laser system for the correction of hyperopia with and without astigmatism by laser in situ keratomileusis (LASIK) treatment. Detailed Description ----------------- Qualified subjects will receive LASIK treatment in both eyes and be followed for 1 year. Subjects will be asked to attend a total of 9 visits (Screening, Surgery, Day 1, Week 1, Month 1, Month 3, Month 6, Month 9, and Year 1). Total expected duration of subject participation is approximately 1 year. Official Title ----------------- Clinical Investigation of the WaveLight® EX500 Excimer Laser for Hyperopic LASIK Conditions ----------------- Hyperopia, Hyperopic Astigmatism Intervention / Treatment ----------------- * Device: WaveLight EX500 excimer laser system * Procedure: LASIK Participation Criteria ================= Eligibility Criteria ----------------- Key Inclusion Criteria: Intended to treat bilaterally; Hyperopia with or without astigmatism as specified in the protocol; Stable vision as specified in the protocol; Other protocol-defined inclusion criteria may apply. Key Exclusion Criteria: Glaucoma; Cataracts; Previous eye surgery; Intent to have monovision treatment; Other protocol-defined exclusion criteria may apply. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: WaveLight EX500 excimer laser system<br>Laser-assisted in situ keratomileusis (LASIK) surgery using the WaveLight EX500 excimer laser system \| Device: WaveLight EX500 excimer laser system<br>* FDA approved stationary scanning-spot excimer laser system used during refractive surgery for the treatment of myopia, myopic astigmatism, hyperopia, hyperopic astigmatism, and mixed astigmatism. For this clinical study, the Wavefront Optimized (WFO) Ablation profile of the WaveLight EX500 excimer laser system will be used for bilateral LASIK treatment of hyperopia with and without astigmatism.<br>Procedure: LASIK<br>* Procedure that reshapes the front part of the eye (cornea) so that light traveling through it is properly focused on the back part of the eye (retina). The procedure will be performed using the WaveLight EX500 excimer laser system.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Percentage of eyes with manifest refraction spherical equivalent (MRSE) within ±0.50 diopter (D) at refractive stability \| A manifest refraction (manual refraction) will be performed using a phoropter. The spherical equivalent will be calculated by adding the sum of the sphere power with half of the cylinder power. Refractive stability is defined as the latter of two postoperative manifest refractions performed at least 3 months apart (or at 3 months after surgery when compared with the 1-month visit) that meets all the protocol-specified stability requirements. \| Preoperative, up to Month 12 \| \| Percentage of eyes with MRSE within ±1.00 D at refractive stability \| A manifest refraction (manual refraction) will be performed using a phoropter. The spherical equivalent will be calculated by adding the sum of the sphere power with half of the cylinder power. Refractive stability is defined as the latter of two postoperative manifest refractions performed at least 3 months apart (or at 3 months after surgery when compared with the 1-month visit) that meets all the protocol-specified stability requirements. \| Preoperative, up to Month 12 \| \| Percentage of eyes experiencing ocular adverse events (AEs) \| An AE is defined as any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in subjects, users, or other persons, whether or not related to the investigational medical device (test product). Ocular adverse events will be collected for this outcome measure. \| Up to Month 12 \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- LASIK, Refractive errors
NCT02457832	Motor Training in PD	The purpose of this research study is to learn more about brain activity when individuals with and without Parkinson disease (PD) move their lower limbs. The investigators also want to see if and how two different types of partnered dance affect brain activity in individuals with and without PD. Testing will take place at the Atlanta VA Medical Center and at Emory University. The investigators expect to enroll about 140 people for this study over a five-year period.	Persons with Parkinson's disease (PD) have impaired mobility, which adversely affects their quality of life. The effectiveness of adapted tango dance, in which participants both lead (internally guide: IG) and follow (externally guide: EG) movement has been shown. To improve outcomes in those with PD, the underlying brain mechanisms for both motor impairments and improvement must be studied. IG and EG movements have distinct brain activity patterns. Individuals with PD have trouble with IG movement but this problem is helped by strategies used while leading. During following, participants with PD can use many external cues, which helps movement in PD, because EG tasks bypass the basal ganglia, the part of the brain affected by PD. In older persons with PD, the investigators aim to:~determine brain activation patterns during IG and EG foot movement.~look into effects of IG and EG training on brain activation along with mobility improvements.~The investigators will begin with a functional Magnetic Resonance Imaging test in a scanner. The investigators will look at brain area correlates of a clinically-used foot-tapping task, during IG and EG conditions in older persons with and without PD. Then, the investigators will assess the relative effectiveness of IG versus EG training during an adapted tango class, compared to a group that participates in health education, for improved mobility and foot tapping. Participants with PD will be assessed for disease severity. They will receive tests of outcome measures while OFF and ON PD-specific medications at the following time points:~1 week before training~1 week after training~1 month after training Participants must attend 20 lessons of IG or EG adapted tango in 12 weeks, taught by an experienced instructor. In the functional MRI (fMRI) scanner, the investigators will assess participants for improved foot tapping after training. The investigators will also look at changes in activation in specific brain circuits along with training effects upon mobility.~The long-term goal is to improve motor training as much as possible for persons with PD by understanding foot movement brain circuitry in PD as well as brain changes in circuitry through which training is effective. This work proposes to illumine information about brain function that is very important to continued progress in rehabilitative care of persons with PD.	Optimizing Motor Training in Parkinson Disease Through Neural Mechanisms (NEURODEGEN)	Parkinson Disease	* Behavioral: Adapted Tango Dancing * Behavioral: Behavioral Control (BC) Condition	Inclusion Criteria:~Age 40 - 70 years~Willingness to spend 1-h in a scanner~Able to walk with or without an assistive device 10 feet~Best corrected/aided acuity better than 20/70 in the better eye~Absence of dementia or vascular cognitive impairment~Absence of primary memory deficits~Exclusion Criteria:~Deep brain stimulator implants, Metallic implants, fragments, or pacemakers~Montreal Cognitive Assessment (MocA) score < 24~Pure-tone threshold sensitivity > 40 dB~Peripheral neuropathy~Untreated Major Depression~History of stroke, or traumatic brain injury	40 Years	null	All	Accepts Healthy Volunteers	Primary Purpose: Supportive Care Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Percent signal change \| For the IG and EG tasks for the MRI, the investigators want to determine and distinguish circuits involved in IG and EG foot-tapping networks in participants with and without PD. \| 12 weeks \| \| Connectivity strength \| Changes in average connectivity strength across striatal-thalamo-cortical (STC) and cerebello-thalamo-cortical (CTC) circuits, as measured by average cross correlation coefficient between the seed regions of the circuits. \| 12 weeks \|		Magnetic Resonance Imaging, Neurology, Neurosciences, Physical Medicine, Parkinson Disease, Rehabilitation	Parkinson Disease, Parkinsonian Disorders, Basal Ganglia Diseases, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Movement Disorders, Synucleinopathies, Neurodegenerative Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Internal guidance training (IG)<br>Adapted tango dancing is a sophisticated, yet accessible system of tactile communication that conveys motor intentions and goals between a leader and follower. Those in IG training will choose direction, timing and amplitude of each successive step, and will communicate this information to their partner through moving their frame and center of mass. \| Behavioral: Adapted Tango Dancing<br>* Composed of simple steps, tango involves frequent movement initiation and cessation, multi-directional perturbations and varied rhythms. Participants focus on trunk control and stepping strategies, coordination, somatosensory awareness, attention to partner, path of movement, and aesthetics. Sessions will begin with a typical dance class warm-up consisting of breathing, limbering and postural alignment to upbeat music. Novel step elements will be introduced every class period. Those with PD will partner with an individual without PD. After novel step introduction, the instructor will present rhythmic training, which is indispensable to partnered dancing. Participants will learn 'typical' rhythms from tango and Latin dances, based upon the system of quicks (Q) and slows (S), ubiquitously used in ballroom dance training to understand the temporal relationship of movement to music.<br>\| \| Experimental: Externally guided training (EG)<br>Those in EG will learn to attend to sensory cues for movement direction, timing and amplitude of steps, communicated from their partner to them via the frame and center of mass. The 'follower' will wait to receive the movement cue before moving. \| Behavioral: Adapted Tango Dancing<br>* Composed of simple steps, tango involves frequent movement initiation and cessation, multi-directional perturbations and varied rhythms. Participants focus on trunk control and stepping strategies, coordination, somatosensory awareness, attention to partner, path of movement, and aesthetics. Sessions will begin with a typical dance class warm-up consisting of breathing, limbering and postural alignment to upbeat music. Novel step elements will be introduced every class period. Those with PD will partner with an individual without PD. After novel step introduction, the instructor will present rhythmic training, which is indispensable to partnered dancing. Participants will learn 'typical' rhythms from tango and Latin dances, based upon the system of quicks (Q) and slows (S), ubiquitously used in ballroom dance training to understand the temporal relationship of movement to music.<br>\| \| Active Comparator: Behavioral Control (BC)<br>BC participants will attend group health education sessions adapted to the needs of individuals with PD, about pharmacological management, nutrition, sleep disorders, cognitive deficits, bereavement coping, mobility, balance and home safety. Participants in this training will be instructed not to change their habitual exercise routines. After completing health education, participants will be assigned to an IG or EG training class but will not undergo evaluations. \| Behavioral: Behavioral Control (BC) Condition<br>* Group health education sessions adapted to the needs of individuals with PD, about pharmacological management, nutrition, sleep disorders, cognitive deficits, bereavement coping, mobility, balance and home safety.<br>\| \| No Intervention: Normal Control (NC)<br>Age-matched controls without Parkinson's disease will come in for a single assessment including MRI. \| \|	Motor Training in PD Study Overview ================= Brief Summary ----------------- The purpose of this research study is to learn more about brain activity when individuals with and without Parkinson disease (PD) move their lower limbs. The investigators also want to see if and how two different types of partnered dance affect brain activity in individuals with and without PD. Testing will take place at the Atlanta VA Medical Center and at Emory University. The investigators expect to enroll about 140 people for this study over a five-year period. Detailed Description ----------------- Persons with Parkinson's disease (PD) have impaired mobility, which adversely affects their quality of life. The effectiveness of adapted tango dance, in which participants both lead (internally guide: IG) and follow (externally guide: EG) movement has been shown. To improve outcomes in those with PD, the underlying brain mechanisms for both motor impairments and improvement must be studied. IG and EG movements have distinct brain activity patterns. Individuals with PD have trouble with IG movement but this problem is helped by strategies used while leading. During following, participants with PD can use many external cues, which helps movement in PD, because EG tasks bypass the basal ganglia, the part of the brain affected by PD. In older persons with PD, the investigators aim to: determine brain activation patterns during IG and EG foot movement. look into effects of IG and EG training on brain activation along with mobility improvements. The investigators will begin with a functional Magnetic Resonance Imaging test in a scanner. The investigators will look at brain area correlates of a clinically-used foot-tapping task, during IG and EG conditions in older persons with and without PD. Then, the investigators will assess the relative effectiveness of IG versus EG training during an adapted tango class, compared to a group that participates in health education, for improved mobility and foot tapping. Participants with PD will be assessed for disease severity. They will receive tests of outcome measures while OFF and ON PD-specific medications at the following time points: 1 week before training 1 week after training 1 month after training Participants must attend 20 lessons of IG or EG adapted tango in 12 weeks, taught by an experienced instructor. In the functional MRI (fMRI) scanner, the investigators will assess participants for improved foot tapping after training. The investigators will also look at changes in activation in specific brain circuits along with training effects upon mobility. The long-term goal is to improve motor training as much as possible for persons with PD by understanding foot movement brain circuitry in PD as well as brain changes in circuitry through which training is effective. This work proposes to illumine information about brain function that is very important to continued progress in rehabilitative care of persons with PD. Official Title ----------------- Optimizing Motor Training in Parkinson Disease Through Neural Mechanisms (NEURODEGEN) Conditions ----------------- Parkinson Disease Intervention / Treatment ----------------- * Behavioral: Adapted Tango Dancing * Behavioral: Behavioral Control (BC) Condition Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age 40 - 70 years Willingness to spend 1-h in a scanner Able to walk with or without an assistive device 10 feet Best corrected/aided acuity better than 20/70 in the better eye Absence of dementia or vascular cognitive impairment Absence of primary memory deficits Exclusion Criteria: Deep brain stimulator implants, Metallic implants, fragments, or pacemakers Montreal Cognitive Assessment (MocA) score < 24 Pure-tone threshold sensitivity > 40 dB Peripheral neuropathy Untreated Major Depression History of stroke, or traumatic brain injury Ages Eligible for Study ----------------- Minimum Age: 40 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Supportive Care Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Internal guidance training (IG)<br>Adapted tango dancing is a sophisticated, yet accessible system of tactile communication that conveys motor intentions and goals between a leader and follower. Those in IG training will choose direction, timing and amplitude of each successive step, and will communicate this information to their partner through moving their frame and center of mass. \| Behavioral: Adapted Tango Dancing<br>* Composed of simple steps, tango involves frequent movement initiation and cessation, multi-directional perturbations and varied rhythms. Participants focus on trunk control and stepping strategies, coordination, somatosensory awareness, attention to partner, path of movement, and aesthetics. Sessions will begin with a typical dance class warm-up consisting of breathing, limbering and postural alignment to upbeat music. Novel step elements will be introduced every class period. Those with PD will partner with an individual without PD. After novel step introduction, the instructor will present rhythmic training, which is indispensable to partnered dancing. Participants will learn 'typical' rhythms from tango and Latin dances, based upon the system of quicks (Q) and slows (S), ubiquitously used in ballroom dance training to understand the temporal relationship of movement to music.<br>\| \| Experimental: Externally guided training (EG)<br>Those in EG will learn to attend to sensory cues for movement direction, timing and amplitude of steps, communicated from their partner to them via the frame and center of mass. The 'follower' will wait to receive the movement cue before moving. \| Behavioral: Adapted Tango Dancing<br>* Composed of simple steps, tango involves frequent movement initiation and cessation, multi-directional perturbations and varied rhythms. Participants focus on trunk control and stepping strategies, coordination, somatosensory awareness, attention to partner, path of movement, and aesthetics. Sessions will begin with a typical dance class warm-up consisting of breathing, limbering and postural alignment to upbeat music. Novel step elements will be introduced every class period. Those with PD will partner with an individual without PD. After novel step introduction, the instructor will present rhythmic training, which is indispensable to partnered dancing. Participants will learn 'typical' rhythms from tango and Latin dances, based upon the system of quicks (Q) and slows (S), ubiquitously used in ballroom dance training to understand the temporal relationship of movement to music.<br>\| \| Active Comparator: Behavioral Control (BC)<br>BC participants will attend group health education sessions adapted to the needs of individuals with PD, about pharmacological management, nutrition, sleep disorders, cognitive deficits, bereavement coping, mobility, balance and home safety. Participants in this training will be instructed not to change their habitual exercise routines. After completing health education, participants will be assigned to an IG or EG training class but will not undergo evaluations. \| Behavioral: Behavioral Control (BC) Condition<br>* Group health education sessions adapted to the needs of individuals with PD, about pharmacological management, nutrition, sleep disorders, cognitive deficits, bereavement coping, mobility, balance and home safety.<br>\| \| No Intervention: Normal Control (NC)<br>Age-matched controls without Parkinson's disease will come in for a single assessment including MRI. \| \| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Percent signal change \| For the IG and EG tasks for the MRI, the investigators want to determine and distinguish circuits involved in IG and EG foot-tapping networks in participants with and without PD. \| 12 weeks \| \| Connectivity strength \| Changes in average connectivity strength across striatal-thalamo-cortical (STC) and cerebello-thalamo-cortical (CTC) circuits, as measured by average cross correlation coefficient between the seed regions of the circuits. \| 12 weeks \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Magnetic Resonance Imaging, Neurology, Neurosciences, Physical Medicine, Parkinson Disease, Rehabilitation
NCT04425629	Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Adult and Pediatric Patients With COVID-19	Phase 1~To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo~To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral load of SARS-CoV-2~Phase 2~• To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral load of SARS-CoV-2~Phase 3~Cohort 1 (≥18 Years Old, Not Pregnant at Randomization)~• To evaluate the clinical efficacy of REGN10933+REGN10987 compared to placebo as measured by COVID-19-related hospitalizations or all-cause death~Cohort 2 (<18 Years Old, Not Pregnant at Randomization)~To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo~To further characterize the concentrations of REGN10933 and REGN10987 in serum over time~Cohort 3 (Pregnant at Randomization) • To evaluate the safety and tolerability of REGN10933+REGN10987		A Master Protocol Assessing the Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Patients With COVID-19	COVID-19	* Drug: casirivimab+imdevimab combination therapy	Key Inclusion Criteria:~Has SARS-CoV-2-positive diagnostic test (from a sample collected ≤72 hours prior to randomization, using a validated SARS-CoV-2 antigen, RT-PCR, or other molecular diagnostic assay, and an appropriate sample such as nasopharyngeal [NP], nasal, oropharyngeal [OP], or saliva)~Has symptoms consistent with COVID-19, as determined by the investigator, with onset ≤7 days before randomization~Maintains O2 saturation ≥93% on room air~Is able to understand and complete study-related questionnaires (patients aged ≥12 years only)~Key Exclusion Criteria:~Was admitted to a hospital for COVID-19 prior to randomization, or is hospitalized (inpatient) for any reason at randomization~Has participated, or is participating, in a clinical research study evaluating COVID-19 convalescent plasma, mAbs against SARS-CoV-2 (eg, bamlanivimab), or intravenous immunoglobulin (IVIG) within 3 months or within 5 half-lives of the investigational product (whichever is longer) prior to the screening visit~Prior, current, or planned future use of any of the following treatments: COVID-19 convalescent plasma, mAbs against SARS-CoV-2 (eg, bamlanivimab), IVIG (any indication), systemic corticosteroids (any indication), or COVID-19 treatments (authorized, approved, or investigational)~Prior use (prior to randomization), current use (at randomization) or planned use (within 90 days of study drug administration or per current CDC recommendations, as applicable) of any authorized or approved vaccine for COVID-19~Has participated, is participating or plans to participate in a clinical research study evaluation any authorized, approved or investigational vaccine for COVID-19~NOTE: Other Protocol defined Inclusion/Exclusion criteria apply	null	null	All	No	Primary Purpose: Treatment Intervention Model: Single Group Assignment Interventional Model Description: Phase 1/Phase 2/Phase 3 Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3] \| Primary:~Phase 1, Phase 3 (Cohort 2 and Cohort 3)~Secondary:~Phase 2, Phase 3 (Cohort 1) \| Through Day 29 \| \| Number of Participants With Infusion-related Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) \| Primary:~Phase 1, Phase 3 (Cohort 2 and Cohort 3)~Secondary:~Phase 2, Phase 3 (Cohort 1) \| Through Day 4 \| \| Number of Participants With Hypersensitivity Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) \| Primary:~Phase 1, Phase 3 (Cohort 2 and Cohort 3)~Secondary:~Phase 2, Phase 3 (Cohort 1) \| Through Day 29 \| \| Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Day 7, as Measured by Quantitative Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) in Nasopharyngeal (NP) Swab Samples (Ph1, Ph2) \| Primary:~Phase 1, Phase 2 \| Baseline up to Day 7 \| \| Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death (Ph3 Cohort 1- 1.2g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death (Ph3 Cohort 1 - 2.4g vs Placebo) \| Primary:~Phase 3 (Cohort 1) \| Through Day 29 \| \| Concentration of REGN10983 + REGN10987 in Serum Over Time (Ph3 Cohort 2) \| Phase 3 Cohort 2~[Nominal Sampling Time] = [Clinical Study Time (Visit Day - 1)] \| Up to Nominal Sampling Day 28 \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 1.2g vs Placebo) \| Phase 3 Cohort 1 \| Up to Day 29 \| \| Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 2.4g vs Placebo) \| Phase 3 (Cohort 1) \| Through Day 29 \| \| Proportion of Participants With ≥1 COVID-19-related Hospitalization or All-cause Death From Day 4 Through Day 29 (Ph3 Cohort 1 - 1.2g vs. Placebo) \| Phase 3 (Cohort 1) \| Day 4 thru Day 29 \| \| Proportion of Participants With ≥1 COVID-19-related Hospitalization or All-cause Death From Day 4 Through Day 29 (Ph3 Cohort 1 - 2.4g vs. Placebo) \| Phase 3 (Cohort 1) \| From Day 4 Through Day 29 \| \| Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs (Next Phase 2 Cohort) \| Next Phase 2 Symptomatic \| Day 5, Day 7, Day 15, Day 29 \| \| Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Post-baseline Study Days (Ph1, Ph2) \| Phase 1, Phase 2 \| Day 1 to Day 29 \| \| Percentage of Participants With ≥1 COVID-19-related Medically-attended Visit Through Day 29 (Ph1, Ph2) \| Phase 1, Phase 2 \| Through Day 29 \| \| Percentage of Participants With ≥1 COVID-19 Related Hospitalization, Emergency Room, or Urgent Care Visit Through Day 29 (Ph1, Ph2) \| Phase 1, Phase 2 \| Through Day 29 \| \| Time to First Onset of Symptoms Consistent With COVID-19 (Phase 2 Asymptomatic Cohort Only) \| Phase 2 Only \| Up to Day 29 \| \| Proportion of Participants With ≥1 COVID-19-related Hospitalization, Emergency Room Visit, or All-cause Death (Ph3 Cohort 1) - Placebo vs. 1.2g IV \| Phase 3 Cohort 1 - Placebo vs. 1.2 g IV \| Through Day 29 \| \| Proportion of Participants With ≥1 COVID-19-related Hospitalization, Emergency Room Visit, or All-cause Death (Ph3 Cohort 1) - Placebo vs. 2.4g IV \| Phase 3 (Cohort 1) \| Through day 29 \| \| Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) \| Secondary:~Phase 1, Phase 2, Phase 3 (Cohort 1 and Cohort 3) - Symptomatic Participants~[Nominal Sampling Time] = [Clinical Study Time (Visit Day - 1)] \| Up to Nominal Sampling Day 28 \| \| Assessment of Pharmacokinetic (PK) Parameter: Maximum Serum Concentration Observed (Cmax) of REGN10933+REGN10987 (Phase 1) \| Phase 1 Only \| Through Day 29 \| \| Assessment of PK Parameter: Time to Cmax (Tmax) for REGN10933+REGN10987 (Phase 1) \| Phase 1 Only \| Through Day 29 \| \| Assessment of PK Parameter: Area Under the Curve (AUC) Computed From Time Zero to Day 28 Concentration (AUC 0-28) for REGN10933+REGN10987 (Phase 1) \| Phase 1 Only \| Through Day 29 \| \| Immunogenicity as Measured by Anti-drug (ADA) to REGN10933 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1) \| Phase 1, Phase 2, Phase 3 (Cohort 1) - Pooled Symptomatic Participants \| Through Day 29 \| \| Immunogenicity as Measured by Anti-drug (ADA) to REGN10933 (Ph3 Cohort 2 - Cohort 3) \| Symptomatic Participants Phase 3 Cohort 2 Participants Phase 3 Cohort 3 Participants \| Through Day 29 \| \| Immunogenicity as Measured by ADA to REGN10987 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1) \| Phase 1, Phase 2, Phase 3 (Cohort 1) - Pooled Symptomatic Participants \| Through Day 29 \| \| Immunogenicity as Measured by ADA to REGN10987 (Ph3 Cohort 2 and Cohort 3) \| Symptomatic Participants Phase 3 Cohort 2 Participants Phase 3 Cohort 3 Participants \| Through Day 29 \| \| Immunogenicity as Measured by Neutralizing Antibodies (NAbs) to REGN10933 (Ph3 Cohort 2, Ph3 Cohort 3) \| Symptomatic Participants Phase 3 Cohort 2 Participants Phase 3 Cohort 3 Participants~(TE&TB+;NAb+) = TE = Treatment-emergent; TB = Treatment-boosted; NAb+ = Positive in NAb assay \| Through Day 29 \| \| Immunogenicity as Measured by NAbs to REGN10987 (Ph3 Cohort 2 - Cohort 3) \| Phase 3 Cohort 2 Participants Phase 3 Cohort 3 Participants~(TE&TB+;NAb+) = TE = Treatment-emergent; TB = Treatment-boosted; NAb+ = Positive in NAb assay \| Through Day 29 \| \| Number of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death (Phase 3 Cohort 2) \| Phase 3 (Cohort 2) \| Through Day 29 \| \| Percentage of Participants With ≥1 COVID-19-related Medically-attended Visit (Phase 1, Phase 2) \| Phase 1, Phase 2 Medically-attended Visits include Hospitalizations, ER visits, Urgent Care Clinic visits, Outpatient/physician office/telemedicine visits \| Through Day 29 \| \| Percentage of Participants With ≥2 COVID-19-related Medically-attended Visit - (Ph3 Cohort 1) - Placebo vs. 1.2g IV \| Phase 3 (Cohort 1) \| Through Day 29 \| \| Percentage of Participants With ≥2 COVID-19-related Medically-attended Visit - (Ph3 Cohort 1) - Placebo vs. 2.4g IV \| Phase 3 Cohort 1 \| Through Day 29 \| \| Total Number of COVID-19-related Medically-attended Visits (Phase 1 and Phase 2) \| Phase 1 and Phase 2 \| Through Day 29 \| \| Assessment of Pharmacokinetic (PK) Parameter: Maximum Serum Concentration Observed (Cmax) of REGN10933 and REGN10987 (Phase 1 Only) \| Phase 1 Only \| Through Day 29 \| \| Assessment of PK Parameter: Cmax-to-dose Ratio (Cmax/Dose) of REGN10933 and REGN10987 (Phase 1 Only) \| Phase 1 Only \| Though Day 29 \| \| Assessment of PK Parameter: Time to Cmax (Tmax) for REGN10933 and REGN10987 (Phase 1 Only) \| Phase 1 Only \| Through Day 29 \| \| Assessment of PK Parameter: Area Under the Curve (AUC) Computed From Time Zero to the Time of the Last Positive Concentration (AUClast) for REGN10933 - (Phase 1 Only) \| Phase 1 Only - Tlast (Time of last quantifiable concentration) \| Through Day 29 \| \| Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death From Day 4 Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo) \| Phase 3 Cohort 1 \| Day 4 Through Day 29 \| \| Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death From Day 4 Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo) \| Phase 3 Cohort 1 \| Day 4 Through Day 29 \| \| Proportion of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit or All-cause Death Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Proportion of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit or All-cause Death Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Number of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit or All-cause Death Through Day 29 (Phase 3 Cohort 2) \| Phase 3 (Cohort 2) \| Through Day 29 \| \| Proportion of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit by Type of Visit Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Proportion of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit by Type of Visit Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Total Number of COVID-19-related Medically-attended Visits by Type of Visit Through Day 29 (Phase 3 Cohort 2) \| Phase 3 (Cohort 2) \| Through Day 29 \| \| Cumulative Incidence Percentage of Patients With COVID-19-related Hospitalization or All-cause Death Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Cumulative Incidence Percentage of Patients With COVID-19-related Hospitalization or All-cause Death Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Cumulative Incidence Percentage of Patients With COVID-19-related Hospitalization, Emergency Room (ER) or All-cause Death Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Cumulative Incidence Percentage of Patients With COVID-19-related Hospitalization, Emergency Room (ER) or All-cause Death Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Cumulative Incidence Percentage of Patients With COVID-19-related Medically-attended Visit or All-cause Death Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Cumulative Incidence Percentage of Patients With COVID-19-related Medically-attended Visit or All-cause Death Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Proportion of Participants Requiring Supplemental Oxygen Due to COVID-19 by Day 29 (Ph3 Cohort 1- 1.2g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Proportion of Participants Requiring Supplemental Oxygen Due to COVID-19 by Day 29 (Ph3 Cohort 1- 2.4g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 1.2g \| Phase 3 Cohort 1 \| by Day 29, Day 120, and Day 169 \| \| Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 2.4g \| Phase 3 Cohort 1 Placebo vs. 2.4g IV \| by Day 29, Day 120, and Day 169 \| \| Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only) \| Next Phase 2 Only \| Through Day 29 \| \| Correlation of RT-qPCR Results Over Time Between Different Sample Types (NP, Nasal, and Saliva) - (Phase 1 Only) \| Phase 1 Only \| Up to Day 29 \| \| Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasal Swabs - (Phase 1 Only) \| Phase 1 Only \| Baseline Up To Day 29 \| \| Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Saliva Samples - (Phase 1 Only) \| Phase 1 Only \| Baseline Up to Day 29 \| \| Concordance of RT-qPCR Results Over Time Between Different Sample Types (NP, Nasal, and Saliva) - (Phase 1 Only) \| Phase 1 Only \| Up To Day 29 \| \| Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL), as Measured by RT-qPCR in Saliva Samples - (Phase 1) \| Phase 1 Only \| Baseline up to Day 22 \| \| Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only) \| Phase 2 Only \| Through Day 29 \| \| Duration of Symptoms Consistent With COVID-19 (Phase 2 Only) \| Phase 2 Only \| Through Day 29 \| \| Time to First Onset of Symptoms Consistent With COVID-19 (Phase 2 Asymptomatic Cohort Only) \| Phase 2 Only \| Through Day 29 \| \| Number of Participants Admitted to a Hospital Due to COVID-19 (Phase 1, Phase 2) \| Phase 1, Phase 2 \| Through Day 29 \| \| Time to Negative RT-qPCR in All Tested Samples With no Subsequent Positive RT-qPCR in Any Tested Samples - (Phase 1 Only) \| Phase 1 Only \| Through Day 29 \| \| Proportion of Participants With All-cause Mortality (Phase 2 Asymptomatic) \| Phase 2 Asymptomatic \| Through Day 29 \| \| Time to All-cause Death (Ph3 Cohort 1- 1.2g vs Placebo) \| Phase 3 Cohort 1 (1.2g IV) \| Through Day 169 \| \| Time to All-cause Death (Ph3 Cohort 1- 2.4g vs Placebo) \| Phase 3 Cohort 1 (2.4g IV) \| Through Day 169 \| \| Time to All-cause Death (Phase 3 Cohort 2) \| Phase 3 (Cohort 2) \| Through Day 29 \| \| Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Ph3 Cohort 1- 1.2g vs Placebo) \| \| Through Day 29 \| \| Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Ph3 Cohort 1- 2.4g vs Placebo) \| \| Through Day 29 \| \| Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Phase 3 Cohort 2) \| Phase 3 (Cohort 2) \| Through Day 29 \| \| Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 1 - 1.2g vs. Placebo) \| Phase 3 Cohort 1 \| Baseline up to Day 29 \| \| Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 1 - 2.4g vs. Placebo) \| Phase 3 Cohort 1 \| Baseline up to Day 29 \| \| Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 2) \| Phase 3 Cohort 2 \| Baseline up to Day 29 \| \| Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL), as Measured by Quantitative Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) in Nasopharyngeal (NP) Swab Samples (Ph3 Cohort 1) \| Phase 3 (Cohort 1) \| Baseline to Day 7 \| \| Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL), as Measured by Quantitative Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) in Nasopharyngeal (NP) Swab Samples (Ph3 Cohort 2) \| Phase 3 (Cohort 2) \| Baseline to Day 7 \| \| Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only) \| Next Phase 2 Symptomatic \| Day 0, Day 5, Day 7, Day 15, Day 29 \| \| Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only) \| Next Phase 2 Symptomatic \| Day 0, Day 5, Day 7, Day 15, Day 29 \| \| Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 1) Placebo vs. 1.2g IV \| Phase 3 (Cohort 1) \| Through Day 29 \| \| Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 1) Placebo vs. 2.4g IV \| Phase 3 (Cohort 1) \| Through Day 29 \| \| Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 2) \| Phase 3 (Cohort 2) \| Through Day 29 \| \| Number of Days of Hospitalization Due to COVID-19 (Phase 2 Asymptomatic) \| Phase 2 Only \| Up to Day 29 \| \| Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 1) Placebo vs. 1.2g IV \| Phase 3 (Cohort 1) \| Through Day 29 \| \| Percentage of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 1) Placebo vs. 2.4g IV \| Phase 3 (Cohort 1) \| Through Day 29 \| \| Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 2) \| Phase 3 (Cohort 2) \| Through Day 29 \| \| Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Next Phase 2) #87 \| Next Phase 2 \| Through Day 29 \| \| Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 1) Placebo vs. 1.2g \| Phase 3 Cohort 1 \| Through Day 29 \| \| Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 1) Placebo vs. 2.4g \| Phase 3 Cohort 1 \| Through Day 29 \| \| Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 2) \| Phase 3 Cohort 2 \| Through Day 29 \|	Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), coronavirus	Casirivimab and imdevimab drug combination, Antiviral Agents, Anti-Infective Agents	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: casirivimab+imdevimab low dose<br>Low dose or body-weight equivalent for those under 18 years of age. \| Drug: casirivimab+imdevimab combination therapy<br>* Administered intravenously (IV) single dose<br>* Other names: Ronapreve™;\|	Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Adult and Pediatric Patients With COVID-19 Study Overview ================= Brief Summary ----------------- Phase 1 To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral load of SARS-CoV-2 Phase 2 • To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral load of SARS-CoV-2 Phase 3 Cohort 1 (≥18 Years Old, Not Pregnant at Randomization) • To evaluate the clinical efficacy of REGN10933+REGN10987 compared to placebo as measured by COVID-19-related hospitalizations or all-cause death Cohort 2 (<18 Years Old, Not Pregnant at Randomization) To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo To further characterize the concentrations of REGN10933 and REGN10987 in serum over time Cohort 3 (Pregnant at Randomization) • To evaluate the safety and tolerability of REGN10933+REGN10987 Official Title ----------------- A Master Protocol Assessing the Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Patients With COVID-19 Conditions ----------------- COVID-19 Intervention / Treatment ----------------- * Drug: casirivimab+imdevimab combination therapy Participation Criteria ================= Eligibility Criteria ----------------- Key Inclusion Criteria: Has SARS-CoV-2-positive diagnostic test (from a sample collected ≤72 hours prior to randomization, using a validated SARS-CoV-2 antigen, RT-PCR, or other molecular diagnostic assay, and an appropriate sample such as nasopharyngeal [NP], nasal, oropharyngeal [OP], or saliva) Has symptoms consistent with COVID-19, as determined by the investigator, with onset ≤7 days before randomization Maintains O2 saturation ≥93% on room air Is able to understand and complete study-related questionnaires (patients aged ≥12 years only) Key Exclusion Criteria: Was admitted to a hospital for COVID-19 prior to randomization, or is hospitalized (inpatient) for any reason at randomization Has participated, or is participating, in a clinical research study evaluating COVID-19 convalescent plasma, mAbs against SARS-CoV-2 (eg, bamlanivimab), or intravenous immunoglobulin (IVIG) within 3 months or within 5 half-lives of the investigational product (whichever is longer) prior to the screening visit Prior, current, or planned future use of any of the following treatments: COVID-19 convalescent plasma, mAbs against SARS-CoV-2 (eg, bamlanivimab), IVIG (any indication), systemic corticosteroids (any indication), or COVID-19 treatments (authorized, approved, or investigational) Prior use (prior to randomization), current use (at randomization) or planned use (within 90 days of study drug administration or per current CDC recommendations, as applicable) of any authorized or approved vaccine for COVID-19 Has participated, is participating or plans to participate in a clinical research study evaluation any authorized, approved or investigational vaccine for COVID-19 NOTE: Other Protocol defined Inclusion/Exclusion criteria apply Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Interventional Model Description: Phase 1/Phase 2/Phase 3 Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: casirivimab+imdevimab low dose<br>Low dose or body-weight equivalent for those under 18 years of age. \| Drug: casirivimab+imdevimab combination therapy<br>* Administered intravenously (IV) single dose<br>* Other names: Ronapreve™;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3] \| Primary: Phase 1, Phase 3 (Cohort 2 and Cohort 3) Secondary: Phase 2, Phase 3 (Cohort 1) \| Through Day 29 \| \| Number of Participants With Infusion-related Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) \| Primary: Phase 1, Phase 3 (Cohort 2 and Cohort 3) Secondary: Phase 2, Phase 3 (Cohort 1) \| Through Day 4 \| \| Number of Participants With Hypersensitivity Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) \| Primary: Phase 1, Phase 3 (Cohort 2 and Cohort 3) Secondary: Phase 2, Phase 3 (Cohort 1) \| Through Day 29 \| \| Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Day 7, as Measured by Quantitative Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) in Nasopharyngeal (NP) Swab Samples (Ph1, Ph2) \| Primary: Phase 1, Phase 2 \| Baseline up to Day 7 \| \| Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death (Ph3 Cohort 1- 1.2g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death (Ph3 Cohort 1 - 2.4g vs Placebo) \| Primary: Phase 3 (Cohort 1) \| Through Day 29 \| \| Concentration of REGN10983 + REGN10987 in Serum Over Time (Ph3 Cohort 2) \| Phase 3 Cohort 2 [Nominal Sampling Time] = [Clinical Study Time (Visit Day - 1)] \| Up to Nominal Sampling Day 28 \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 1.2g vs Placebo) \| Phase 3 Cohort 1 \| Up to Day 29 \| \| Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 2.4g vs Placebo) \| Phase 3 (Cohort 1) \| Through Day 29 \| \| Proportion of Participants With ≥1 COVID-19-related Hospitalization or All-cause Death From Day 4 Through Day 29 (Ph3 Cohort 1 - 1.2g vs. Placebo) \| Phase 3 (Cohort 1) \| Day 4 thru Day 29 \| \| Proportion of Participants With ≥1 COVID-19-related Hospitalization or All-cause Death From Day 4 Through Day 29 (Ph3 Cohort 1 - 2.4g vs. Placebo) \| Phase 3 (Cohort 1) \| From Day 4 Through Day 29 \| \| Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs (Next Phase 2 Cohort) \| Next Phase 2 Symptomatic \| Day 5, Day 7, Day 15, Day 29 \| \| Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Post-baseline Study Days (Ph1, Ph2) \| Phase 1, Phase 2 \| Day 1 to Day 29 \| \| Percentage of Participants With ≥1 COVID-19-related Medically-attended Visit Through Day 29 (Ph1, Ph2) \| Phase 1, Phase 2 \| Through Day 29 \| \| Percentage of Participants With ≥1 COVID-19 Related Hospitalization, Emergency Room, or Urgent Care Visit Through Day 29 (Ph1, Ph2) \| Phase 1, Phase 2 \| Through Day 29 \| \| Time to First Onset of Symptoms Consistent With COVID-19 (Phase 2 Asymptomatic Cohort Only) \| Phase 2 Only \| Up to Day 29 \| \| Proportion of Participants With ≥1 COVID-19-related Hospitalization, Emergency Room Visit, or All-cause Death (Ph3 Cohort 1) - Placebo vs. 1.2g IV \| Phase 3 Cohort 1 - Placebo vs. 1.2 g IV \| Through Day 29 \| \| Proportion of Participants With ≥1 COVID-19-related Hospitalization, Emergency Room Visit, or All-cause Death (Ph3 Cohort 1) - Placebo vs. 2.4g IV \| Phase 3 (Cohort 1) \| Through day 29 \| \| Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) \| Secondary: Phase 1, Phase 2, Phase 3 (Cohort 1 and Cohort 3) - Symptomatic Participants [Nominal Sampling Time] = [Clinical Study Time (Visit Day - 1)] \| Up to Nominal Sampling Day 28 \| \| Assessment of Pharmacokinetic (PK) Parameter: Maximum Serum Concentration Observed (Cmax) of REGN10933+REGN10987 (Phase 1) \| Phase 1 Only \| Through Day 29 \| \| Assessment of PK Parameter: Time to Cmax (Tmax) for REGN10933+REGN10987 (Phase 1) \| Phase 1 Only \| Through Day 29 \| \| Assessment of PK Parameter: Area Under the Curve (AUC) Computed From Time Zero to Day 28 Concentration (AUC 0-28) for REGN10933+REGN10987 (Phase 1) \| Phase 1 Only \| Through Day 29 \| \| Immunogenicity as Measured by Anti-drug (ADA) to REGN10933 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1) \| Phase 1, Phase 2, Phase 3 (Cohort 1) - Pooled Symptomatic Participants \| Through Day 29 \| \| Immunogenicity as Measured by Anti-drug (ADA) to REGN10933 (Ph3 Cohort 2 - Cohort 3) \| Symptomatic Participants Phase 3 Cohort 2 Participants Phase 3 Cohort 3 Participants \| Through Day 29 \| \| Immunogenicity as Measured by ADA to REGN10987 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1) \| Phase 1, Phase 2, Phase 3 (Cohort 1) - Pooled Symptomatic Participants \| Through Day 29 \| \| Immunogenicity as Measured by ADA to REGN10987 (Ph3 Cohort 2 and Cohort 3) \| Symptomatic Participants Phase 3 Cohort 2 Participants Phase 3 Cohort 3 Participants \| Through Day 29 \| \| Immunogenicity as Measured by Neutralizing Antibodies (NAbs) to REGN10933 (Ph3 Cohort 2, Ph3 Cohort 3) \| Symptomatic Participants Phase 3 Cohort 2 Participants Phase 3 Cohort 3 Participants (TE&TB+;NAb+) = TE = Treatment-emergent; TB = Treatment-boosted; NAb+ = Positive in NAb assay \| Through Day 29 \| \| Immunogenicity as Measured by NAbs to REGN10987 (Ph3 Cohort 2 - Cohort 3) \| Phase 3 Cohort 2 Participants Phase 3 Cohort 3 Participants (TE&TB+;NAb+) = TE = Treatment-emergent; TB = Treatment-boosted; NAb+ = Positive in NAb assay \| Through Day 29 \| \| Number of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death (Phase 3 Cohort 2) \| Phase 3 (Cohort 2) \| Through Day 29 \| \| Percentage of Participants With ≥1 COVID-19-related Medically-attended Visit (Phase 1, Phase 2) \| Phase 1, Phase 2 Medically-attended Visits include Hospitalizations, ER visits, Urgent Care Clinic visits, Outpatient/physician office/telemedicine visits \| Through Day 29 \| \| Percentage of Participants With ≥2 COVID-19-related Medically-attended Visit - (Ph3 Cohort 1) - Placebo vs. 1.2g IV \| Phase 3 (Cohort 1) \| Through Day 29 \| \| Percentage of Participants With ≥2 COVID-19-related Medically-attended Visit - (Ph3 Cohort 1) - Placebo vs. 2.4g IV \| Phase 3 Cohort 1 \| Through Day 29 \| \| Total Number of COVID-19-related Medically-attended Visits (Phase 1 and Phase 2) \| Phase 1 and Phase 2 \| Through Day 29 \| \| Assessment of Pharmacokinetic (PK) Parameter: Maximum Serum Concentration Observed (Cmax) of REGN10933 and REGN10987 (Phase 1 Only) \| Phase 1 Only \| Through Day 29 \| \| Assessment of PK Parameter: Cmax-to-dose Ratio (Cmax/Dose) of REGN10933 and REGN10987 (Phase 1 Only) \| Phase 1 Only \| Though Day 29 \| \| Assessment of PK Parameter: Time to Cmax (Tmax) for REGN10933 and REGN10987 (Phase 1 Only) \| Phase 1 Only \| Through Day 29 \| \| Assessment of PK Parameter: Area Under the Curve (AUC) Computed From Time Zero to the Time of the Last Positive Concentration (AUClast) for REGN10933 - (Phase 1 Only) \| Phase 1 Only - Tlast (Time of last quantifiable concentration) \| Through Day 29 \| \| Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death From Day 4 Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo) \| Phase 3 Cohort 1 \| Day 4 Through Day 29 \| \| Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death From Day 4 Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo) \| Phase 3 Cohort 1 \| Day 4 Through Day 29 \| \| Proportion of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit or All-cause Death Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Proportion of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit or All-cause Death Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Number of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit or All-cause Death Through Day 29 (Phase 3 Cohort 2) \| Phase 3 (Cohort 2) \| Through Day 29 \| \| Proportion of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit by Type of Visit Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Proportion of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit by Type of Visit Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Total Number of COVID-19-related Medically-attended Visits by Type of Visit Through Day 29 (Phase 3 Cohort 2) \| Phase 3 (Cohort 2) \| Through Day 29 \| \| Cumulative Incidence Percentage of Patients With COVID-19-related Hospitalization or All-cause Death Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Cumulative Incidence Percentage of Patients With COVID-19-related Hospitalization or All-cause Death Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Cumulative Incidence Percentage of Patients With COVID-19-related Hospitalization, Emergency Room (ER) or All-cause Death Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Cumulative Incidence Percentage of Patients With COVID-19-related Hospitalization, Emergency Room (ER) or All-cause Death Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Cumulative Incidence Percentage of Patients With COVID-19-related Medically-attended Visit or All-cause Death Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Cumulative Incidence Percentage of Patients With COVID-19-related Medically-attended Visit or All-cause Death Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Proportion of Participants Requiring Supplemental Oxygen Due to COVID-19 by Day 29 (Ph3 Cohort 1- 1.2g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Proportion of Participants Requiring Supplemental Oxygen Due to COVID-19 by Day 29 (Ph3 Cohort 1- 2.4g vs Placebo) \| Phase 3 Cohort 1 \| Through Day 29 \| \| Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 1.2g \| Phase 3 Cohort 1 \| by Day 29, Day 120, and Day 169 \| \| Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 2.4g \| Phase 3 Cohort 1 Placebo vs. 2.4g IV \| by Day 29, Day 120, and Day 169 \| \| Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only) \| Next Phase 2 Only \| Through Day 29 \| \| Correlation of RT-qPCR Results Over Time Between Different Sample Types (NP, Nasal, and Saliva) - (Phase 1 Only) \| Phase 1 Only \| Up to Day 29 \| \| Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasal Swabs - (Phase 1 Only) \| Phase 1 Only \| Baseline Up To Day 29 \| \| Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Saliva Samples - (Phase 1 Only) \| Phase 1 Only \| Baseline Up to Day 29 \| \| Concordance of RT-qPCR Results Over Time Between Different Sample Types (NP, Nasal, and Saliva) - (Phase 1 Only) \| Phase 1 Only \| Up To Day 29 \| \| Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL), as Measured by RT-qPCR in Saliva Samples - (Phase 1) \| Phase 1 Only \| Baseline up to Day 22 \| \| Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only) \| Phase 2 Only \| Through Day 29 \| \| Duration of Symptoms Consistent With COVID-19 (Phase 2 Only) \| Phase 2 Only \| Through Day 29 \| \| Time to First Onset of Symptoms Consistent With COVID-19 (Phase 2 Asymptomatic Cohort Only) \| Phase 2 Only \| Through Day 29 \| \| Number of Participants Admitted to a Hospital Due to COVID-19 (Phase 1, Phase 2) \| Phase 1, Phase 2 \| Through Day 29 \| \| Time to Negative RT-qPCR in All Tested Samples With no Subsequent Positive RT-qPCR in Any Tested Samples - (Phase 1 Only) \| Phase 1 Only \| Through Day 29 \| \| Proportion of Participants With All-cause Mortality (Phase 2 Asymptomatic) \| Phase 2 Asymptomatic \| Through Day 29 \| \| Time to All-cause Death (Ph3 Cohort 1- 1.2g vs Placebo) \| Phase 3 Cohort 1 (1.2g IV) \| Through Day 169 \| \| Time to All-cause Death (Ph3 Cohort 1- 2.4g vs Placebo) \| Phase 3 Cohort 1 (2.4g IV) \| Through Day 169 \| \| Time to All-cause Death (Phase 3 Cohort 2) \| Phase 3 (Cohort 2) \| Through Day 29 \| \| Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Ph3 Cohort 1- 1.2g vs Placebo) \| \| Through Day 29 \| \| Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Ph3 Cohort 1- 2.4g vs Placebo) \| \| Through Day 29 \| \| Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Phase 3 Cohort 2) \| Phase 3 (Cohort 2) \| Through Day 29 \| \| Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 1 - 1.2g vs. Placebo) \| Phase 3 Cohort 1 \| Baseline up to Day 29 \| \| Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 1 - 2.4g vs. Placebo) \| Phase 3 Cohort 1 \| Baseline up to Day 29 \| \| Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 2) \| Phase 3 Cohort 2 \| Baseline up to Day 29 \| \| Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL), as Measured by Quantitative Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) in Nasopharyngeal (NP) Swab Samples (Ph3 Cohort 1) \| Phase 3 (Cohort 1) \| Baseline to Day 7 \| \| Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL), as Measured by Quantitative Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) in Nasopharyngeal (NP) Swab Samples (Ph3 Cohort 2) \| Phase 3 (Cohort 2) \| Baseline to Day 7 \| \| Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only) \| Next Phase 2 Symptomatic \| Day 0, Day 5, Day 7, Day 15, Day 29 \| \| Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only) \| Next Phase 2 Symptomatic \| Day 0, Day 5, Day 7, Day 15, Day 29 \| \| Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 1) Placebo vs. 1.2g IV \| Phase 3 (Cohort 1) \| Through Day 29 \| \| Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 1) Placebo vs. 2.4g IV \| Phase 3 (Cohort 1) \| Through Day 29 \| \| Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 2) \| Phase 3 (Cohort 2) \| Through Day 29 \| \| Number of Days of Hospitalization Due to COVID-19 (Phase 2 Asymptomatic) \| Phase 2 Only \| Up to Day 29 \| \| Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 1) Placebo vs. 1.2g IV \| Phase 3 (Cohort 1) \| Through Day 29 \| \| Percentage of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 1) Placebo vs. 2.4g IV \| Phase 3 (Cohort 1) \| Through Day 29 \| \| Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 2) \| Phase 3 (Cohort 2) \| Through Day 29 \| \| Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Next Phase 2) #87 \| Next Phase 2 \| Through Day 29 \| \| Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 1) Placebo vs. 1.2g \| Phase 3 Cohort 1 \| Through Day 29 \| \| Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 1) Placebo vs. 2.4g \| Phase 3 Cohort 1 \| Through Day 29 \| \| Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 2) \| Phase 3 Cohort 2 \| Through Day 29 \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), coronavirus
NCT03703297	Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy	This is a Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center, International Study of Durvalumab or Durvalumab and Tremelimumab as Consolidation Treatment for Patients with LS-SCLC Who Have Not Progressed Following Concurrent Chemoradiation Therapy		A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center, International Study of Durvalumab or Durvalumab and Tremelimumab as Consolidation Treatment for Patients With Limited Stage Small Cell Lung Cancer Who Have Not Progressed Following Concurrent Chemoradiation Therapy (ADRIATIC)	Small Cell Lung Cancer	* Drug: Durvalumab * Drug: Tremelimumab * Other: Placebo	Inclusion criteria:~Histologically or cytologically documented limited-stage small cell lung cancer (stage I-III).~Received 4 cycles of chemotherapy concurrent with radiotherapy, which must be completed within 1 to 42 days prior to randomization and the first dose of IP. Chemotherapy must contain platinum and IV etoposide. Radiotherapy must be either total 60-66 Gy over 6 weeks for the standard QD regimen or total 45 Gy over 3 weeks for hyperfractionated BD schedules.~PCI may be delivered at the discretion of investigator and local standard of care, and must be conducted after the end of cCRT and completed between 1 to 42 days to first dose of IP.~4 .Have not progressed following definitive concurrent chemoradiation 5 .Life expectancy ≥ 12 weeks at Day 1. 6. ECOG 0 or 1 at enrolment.~Exclusion criteria:~Extensive-stage SCLC~Active or prior documented autoimmune or inflammatory disorders~Uncontrolled intercurrent illness, including but not limited to interstitial lung disease.~Active infection including tuberculosis, HIV, hepatitis B and C~Patients who received sequential chemotherapy and radiotherapy (no overlap of RT with chemotherapy)	18 Years	130 Years	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Progression-free survival (PFS) \| To assess the efficacy of Durvalumab monotherapy vs Placebo in terms of PFS \| Approximately 6 years \| \| Overall Survival (OS) \| To assess the efficacy of Durvalumab monotherapy vs Placebo in terms of OS \| Approximately 6 years \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Overall Survival (OS) \| To assess the efficacy of Durvalumab & Tremelimumab combination therapy vs Placebo in terms of OS \| Approximately 6 years \| \| Objective Response Rate (ORR) \| \| Approximately 6 years \| \| Progression-free survival PFS \| To assess the efficacy of durvalumab and tremelimumab combination therapy compared to placebo in terms of PFS \| Approximately 6 years \| \| Progression-free survival at 18 months (PFS18) \| \| Approximately 6 years \| \| Progression-free survival at 24 months (PFS24) \| \| Approximately 6 years \| \| Time to death or distant metastasis (TTDM) \| \| Approximately 6 years \| \| Proportion of patients alive at 24 months (OS24) \| \| Approximately 6 years \| \| Proportion of patients alive at and 36 months (OS36) \| \| Approximately 6 years \| \| Time from randomization to second progression (PFS2) \| \| Approximately 6 years \| \| To assess symptoms and health-related QoL in patients treated withdurvalumab or durvalumab and tremelimumab combination therapy compared to placebo using the EORTC QLQ-C30 v3 \| \| Approximately 6 years \| \| To assess the PK of durvalumab and tremelimumab in blood (peak trough concentration) \| \| Approximately 6 years \| \| Presence of anti-drug antibodies (ADA) for durvalumab and tremelimumab (confirmatory results: positive or negative) \| \| Approximately 6 years \| \| PD-L1 expression in tumor and/or immune cells relative to response/efficacy outcomes (PFS, OS & ORR). \| To investigate the relationship between PDL1 expression & spatial distribution with Durva (mono) therapy & Durva+Treme (combination) therapy \| Approximately 6 years \| \| To assess symptoms and health-related QoL in patients treated withdurvalumab or durvalumab and tremelimumab combination therapy compared to placebo using the EORTC QLQ-LC13 \| \| Approximately 6 years \|	Small Cell Lung Cancer, SCLC, LS-SCLC, Limited Stage, Carcinoma, Lung Cancer	Tremelimumab, Antineoplastic Agents, Immunological, Antineoplastic Agents, Durvalumab	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Durvalumab + Placebo<br>Durvalumab monotherapy: Durvalumab (1500 mg intravenous [IV]) q4w in combination with placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with placebo saline solution. \| Drug: Durvalumab<br>* Durvalumab IV (intravenous infusion)<br>* Other names: MEDI4736;Other: Placebo<br>* Placebo IV (intravenous infusion)<br>\| \| Experimental: Durvalumab + Tremelimumab<br>Durvalumab in combination with tremelimumab: Durvalumab (1500 mg IV) q4w in combination with tremelimumab (75 mg IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with tremelimumab. \| Drug: Durvalumab<br>* Durvalumab IV (intravenous infusion)<br>* Other names: MEDI4736;Drug: Tremelimumab<br>* Tremelimumab IV (intravenous infusion)<br>\| \| Placebo Comparator: Placebo + Placebo<br>Placebo: Placebo saline solution (IV) q4w in combination with a second placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by a single placebo saline solution q4w. The first placebo saline solution monotherapy dose q4w will be 4 weeks after the final dose of the 2 placebo saline solutions in combination. \| Other: Placebo<br>* Placebo IV (intravenous infusion)<br>\|	Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy Study Overview ================= Brief Summary ----------------- This is a Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center, International Study of Durvalumab or Durvalumab and Tremelimumab as Consolidation Treatment for Patients with LS-SCLC Who Have Not Progressed Following Concurrent Chemoradiation Therapy Official Title ----------------- A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center, International Study of Durvalumab or Durvalumab and Tremelimumab as Consolidation Treatment for Patients With Limited Stage Small Cell Lung Cancer Who Have Not Progressed Following Concurrent Chemoradiation Therapy (ADRIATIC) Conditions ----------------- Small Cell Lung Cancer Intervention / Treatment ----------------- * Drug: Durvalumab * Drug: Tremelimumab * Other: Placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion criteria: Histologically or cytologically documented limited-stage small cell lung cancer (stage I-III). Received 4 cycles of chemotherapy concurrent with radiotherapy, which must be completed within 1 to 42 days prior to randomization and the first dose of IP. Chemotherapy must contain platinum and IV etoposide. Radiotherapy must be either total 60-66 Gy over 6 weeks for the standard QD regimen or total 45 Gy over 3 weeks for hyperfractionated BD schedules. PCI may be delivered at the discretion of investigator and local standard of care, and must be conducted after the end of cCRT and completed between 1 to 42 days to first dose of IP. 4 .Have not progressed following definitive concurrent chemoradiation 5 .Life expectancy ≥ 12 weeks at Day 1. 6. ECOG 0 or 1 at enrolment. Exclusion criteria: Extensive-stage SCLC Active or prior documented autoimmune or inflammatory disorders Uncontrolled intercurrent illness, including but not limited to interstitial lung disease. Active infection including tuberculosis, HIV, hepatitis B and C Patients who received sequential chemotherapy and radiotherapy (no overlap of RT with chemotherapy) Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 130 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Durvalumab + Placebo<br>Durvalumab monotherapy: Durvalumab (1500 mg intravenous [IV]) q4w in combination with placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with placebo saline solution. \| Drug: Durvalumab<br>* Durvalumab IV (intravenous infusion)<br>* Other names: MEDI4736;Other: Placebo<br>* Placebo IV (intravenous infusion)<br>\| \| Experimental: Durvalumab + Tremelimumab<br>Durvalumab in combination with tremelimumab: Durvalumab (1500 mg IV) q4w in combination with tremelimumab (75 mg IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with tremelimumab. \| Drug: Durvalumab<br>* Durvalumab IV (intravenous infusion)<br>* Other names: MEDI4736;Drug: Tremelimumab<br>* Tremelimumab IV (intravenous infusion)<br>\| \| Placebo Comparator: Placebo + Placebo<br>Placebo: Placebo saline solution (IV) q4w in combination with a second placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by a single placebo saline solution q4w. The first placebo saline solution monotherapy dose q4w will be 4 weeks after the final dose of the 2 placebo saline solutions in combination. \| Other: Placebo<br>* Placebo IV (intravenous infusion)<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Progression-free survival (PFS) \| To assess the efficacy of Durvalumab monotherapy vs Placebo in terms of PFS \| Approximately 6 years \| \| Overall Survival (OS) \| To assess the efficacy of Durvalumab monotherapy vs Placebo in terms of OS \| Approximately 6 years \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Overall Survival (OS) \| To assess the efficacy of Durvalumab & Tremelimumab combination therapy vs Placebo in terms of OS \| Approximately 6 years \| \| Objective Response Rate (ORR) \| \| Approximately 6 years \| \| Progression-free survival PFS \| To assess the efficacy of durvalumab and tremelimumab combination therapy compared to placebo in terms of PFS \| Approximately 6 years \| \| Progression-free survival at 18 months (PFS18) \| \| Approximately 6 years \| \| Progression-free survival at 24 months (PFS24) \| \| Approximately 6 years \| \| Time to death or distant metastasis (TTDM) \| \| Approximately 6 years \| \| Proportion of patients alive at 24 months (OS24) \| \| Approximately 6 years \| \| Proportion of patients alive at and 36 months (OS36) \| \| Approximately 6 years \| \| Time from randomization to second progression (PFS2) \| \| Approximately 6 years \| \| To assess symptoms and health-related QoL in patients treated withdurvalumab or durvalumab and tremelimumab combination therapy compared to placebo using the EORTC QLQ-C30 v3 \| \| Approximately 6 years \| \| To assess the PK of durvalumab and tremelimumab in blood (peak trough concentration) \| \| Approximately 6 years \| \| Presence of anti-drug antibodies (ADA) for durvalumab and tremelimumab (confirmatory results: positive or negative) \| \| Approximately 6 years \| \| PD-L1 expression in tumor and/or immune cells relative to response/efficacy outcomes (PFS, OS & ORR). \| To investigate the relationship between PDL1 expression & spatial distribution with Durva (mono) therapy & Durva+Treme (combination) therapy \| Approximately 6 years \| \| To assess symptoms and health-related QoL in patients treated withdurvalumab or durvalumab and tremelimumab combination therapy compared to placebo using the EORTC QLQ-LC13 \| \| Approximately 6 years \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Small Cell Lung Cancer, SCLC, LS-SCLC, Limited Stage, Carcinoma, Lung Cancer
NCT01721395	Effect of Agave Syrup, Placebo, and No Treatment on Nocturnal Cough and Sleep Quality for Coughing Infants/Toddlers and Their Parents	Cough is a frequent symptom in children and infants and is one of the most common reasons parents visit a healthcare provider for their child. The US Food and Drug Administration has issued a warning that over-the-counter cough and cold medicines including antihistamines, decongestants, anti-tussives, and expectorants should not be administered to children younger than 2 years of age due not only to lack of proven efficacy, but also because of important safety concerns. Honey, another method of soothing cough cannot be used in children <1 year due to concerns for infantile botulism. A preparation from agave syrup has been created to address the need for an infant cough syrup. Although no studies have formally evaluated the use of agave nectar for nocturnal cough associated with Upper Respiratory Infections, the demulcent effect and sweet taste of agave nectar may provide some relief from cough in children.		Effect of Agave Syrup, Placebo, and No Treatment on Nocturnal Cough and Sleep Quality for Coughing Infants/Toddlers and Their Parents	Cough	* Dietary Supplement: Agave Syrup	Inclusion Criteria:~Otherwise healthy male or female infant who is 2 to <48 months of age.~presents with a non-specific acute cough for 7 or fewer days' duration.~Parents/legal authorized representative reporting at least moderate cough and cold symptoms.~Parent/legal authorized representative was in the home with the child on the night prior to enrollment and plans to be in the home with the child on the night when study treatment will be administered~Parent/legal authorized representative who is willing and able to comply with study requirements.~Exclusion Criteria:~Previous participation in this clinical trial~Gestational age at birth <35 weeks.~Signs or symptoms of a more treatable disease (eg, asthma, pneumonia, laryngotracheobronchitis, sinusitis, allergic rhinitis).~Diagnosis of influenza, bronchiolitis or respiratory syncytial virus (RSV).~History of reactive airways disease, asthma, or chronic lung disease.~Use of any medication or honey to treat cough within 6 hours of bedtime on the evening prior to or on the day of enrollment.~Presence of any significant disease including immunodeficiency, hepatic, renal,cardiovascular, or hematologic disease or any other health condition that, in the opinion of the investigator, would preclude participation in the study.~Known allergy to agave nectar or grape flavoring	2 Months	48 Months	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Efficacy:Change in Cough Frequency based on parent responses to the Pediatric Cough Questionnaire \| Change from baseline in cough frequency between the first night and the end of the second night. Parents/caregivers will complete a Pediatric Cough Questionnaire (a subjective parent report of cough) using a 0-6 point Likert scale with 0=not at all to 6=extremely often to assess frequency of cough. The same parent/caregiver that completed the questionnaire in the clinic will be asked to complete the questionnaire during the follow-up telephone call. \| Baseline (night 1) and End of night 2 \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Efficacy: Change in Response to Other symptom responses on the Pediatric Cough Questionnaire(parental report) \| Change from baseline (night 1) and the end of the second night for each of the remaining questionnaire items pertaining to cough and cold symptoms and the symptoms affect on sleep.~Parents/caregivers will complete a Pediatric Cough Questionnaire (a subjective parent report of cold symptoms) using a 0-6 point Likert scale with 0=not at all to 6=extremely often to assess cold symptoms.~severity of cough~bothersome nature of cough~how much the cough affected the child's and parent's/caregiver's ability to sleep~severity of stuffy nose~severity of runny nose The same parent/caregiver that completed the questionnaire in the clinic will be asked to complete the questionnaire during the follow-up telephone call. \| Change from Baseline (night 1) to End of Second Night \|	Cough, Nocturnal Cough, Agave, Sleep Quality, Childhood cough	Cough, Respiration Disorders, Respiratory Tract Diseases, Signs and Symptoms, Respiratory	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Placebo Comparator: Colored, Flavored water<br>The placebo will be colored to approximate the reddish amber color of the agave syrup. The placebo will use the same flavoring used in the agave syrup. The placebo will be created in a GMP facility \| Dietary Supplement: Agave Syrup<br> <br> * Other names: Zarbee's Naturals Agave Baby Cough Syrup;\| \| Experimental: Agave Syrup<br>The formulation of pasteurized agave syrup consists of pasteurized agave syrup and natural flavoring. \| Dietary Supplement: Agave Syrup<br> <br> * Other names: Zarbee's Naturals Agave Baby Cough Syrup;\| \| Sham Comparator: Air-filled oral syringe<br>Air-filled oral syringe to match experimental and placebo arm \| Dietary Supplement: Agave Syrup<br> <br> * Other names: Zarbee's Naturals Agave Baby Cough Syrup;\|	Effect of Agave Syrup, Placebo, and No Treatment on Nocturnal Cough and Sleep Quality for Coughing Infants/Toddlers and Their Parents Study Overview ================= Brief Summary ----------------- Cough is a frequent symptom in children and infants and is one of the most common reasons parents visit a healthcare provider for their child. The US Food and Drug Administration has issued a warning that over-the-counter cough and cold medicines including antihistamines, decongestants, anti-tussives, and expectorants should not be administered to children younger than 2 years of age due not only to lack of proven efficacy, but also because of important safety concerns. Honey, another method of soothing cough cannot be used in children <1 year due to concerns for infantile botulism. A preparation from agave syrup has been created to address the need for an infant cough syrup. Although no studies have formally evaluated the use of agave nectar for nocturnal cough associated with Upper Respiratory Infections, the demulcent effect and sweet taste of agave nectar may provide some relief from cough in children. Official Title ----------------- Effect of Agave Syrup, Placebo, and No Treatment on Nocturnal Cough and Sleep Quality for Coughing Infants/Toddlers and Their Parents Conditions ----------------- Cough Intervention / Treatment ----------------- * Dietary Supplement: Agave Syrup Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Otherwise healthy male or female infant who is 2 to <48 months of age. presents with a non-specific acute cough for 7 or fewer days' duration. Parents/legal authorized representative reporting at least moderate cough and cold symptoms. Parent/legal authorized representative was in the home with the child on the night prior to enrollment and plans to be in the home with the child on the night when study treatment will be administered Parent/legal authorized representative who is willing and able to comply with study requirements. Exclusion Criteria: Previous participation in this clinical trial Gestational age at birth <35 weeks. Signs or symptoms of a more treatable disease (eg, asthma, pneumonia, laryngotracheobronchitis, sinusitis, allergic rhinitis). Diagnosis of influenza, bronchiolitis or respiratory syncytial virus (RSV). History of reactive airways disease, asthma, or chronic lung disease. Use of any medication or honey to treat cough within 6 hours of bedtime on the evening prior to or on the day of enrollment. Presence of any significant disease including immunodeficiency, hepatic, renal,cardiovascular, or hematologic disease or any other health condition that, in the opinion of the investigator, would preclude participation in the study. Known allergy to agave nectar or grape flavoring Ages Eligible for Study ----------------- Minimum Age: 2 Months Maximum Age: 48 Months Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Placebo Comparator: Colored, Flavored water<br>The placebo will be colored to approximate the reddish amber color of the agave syrup. The placebo will use the same flavoring used in the agave syrup. The placebo will be created in a GMP facility \| Dietary Supplement: Agave Syrup<br> <br> * Other names: Zarbee's Naturals Agave Baby Cough Syrup;\| \| Experimental: Agave Syrup<br>The formulation of pasteurized agave syrup consists of pasteurized agave syrup and natural flavoring. \| Dietary Supplement: Agave Syrup<br> <br> * Other names: Zarbee's Naturals Agave Baby Cough Syrup;\| \| Sham Comparator: Air-filled oral syringe<br>Air-filled oral syringe to match experimental and placebo arm \| Dietary Supplement: Agave Syrup<br> <br> * Other names: Zarbee's Naturals Agave Baby Cough Syrup;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Efficacy:Change in Cough Frequency based on parent responses to the Pediatric Cough Questionnaire \| Change from baseline in cough frequency between the first night and the end of the second night. Parents/caregivers will complete a Pediatric Cough Questionnaire (a subjective parent report of cough) using a 0-6 point Likert scale with 0=not at all to 6=extremely often to assess frequency of cough. The same parent/caregiver that completed the questionnaire in the clinic will be asked to complete the questionnaire during the follow-up telephone call. \| Baseline (night 1) and End of night 2 \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Efficacy: Change in Response to Other symptom responses on the Pediatric Cough Questionnaire(parental report) \| Change from baseline (night 1) and the end of the second night for each of the remaining questionnaire items pertaining to cough and cold symptoms and the symptoms affect on sleep. Parents/caregivers will complete a Pediatric Cough Questionnaire (a subjective parent report of cold symptoms) using a 0-6 point Likert scale with 0=not at all to 6=extremely often to assess cold symptoms. severity of cough bothersome nature of cough how much the cough affected the child's and parent's/caregiver's ability to sleep severity of stuffy nose severity of runny nose The same parent/caregiver that completed the questionnaire in the clinic will be asked to complete the questionnaire during the follow-up telephone call. \| Change from Baseline (night 1) to End of Second Night \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Cough, Nocturnal Cough, Agave, Sleep Quality, Childhood cough
NCT05056155	Systane Complete Multi-symptom Relief	The purpose of this study is to demonstrate effective symptom relief with the use of Systane Complete among subjects with dry eye disease (DED).	Subjects will be expected to attend a screening/baseline visit and one additional visit at Day 28 (± 2 days), with a telephone call visit conducted at Day 14 (± 2 days). Individual duration of subject participation will be approximately 28 days.	Systane Complete Multi-symptom Relief	Dry Eye Disease	* Other: Systane Complete	Key Inclusion Criteria:~Able to understand and sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form.~Willing and able to attend all study visits as required per protocol.~Have dry eye symptoms as specified in the protocol.~Willing to discontinue use of all habitual artificial tear supplements for the entire study duration.~Other protocol-defined inclusion criteria may apply.~Key Exclusion Criteria:~Ocular conditions as specified in the protocol.~Contact lens use within one week prior to screening visit.~Use of medications as specified in the protocol.~Pregnant or breast feeding.~Other protocol-defined exclusion criteria may apply.	18 Years	null	All	No	Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change from Baseline at Day 28 in IDEEL-SB Question Sore \| The Impact of Dry Eye on Everyday Life - Symptoms Bother (IDEEL-SB) is a patient-reported outcome measures questionnaire designed to assess symptoms of dry eye disease. Subjects will respond to the question, OVER THE LAST TWO WEEKS, how much did the following symptom bother you: Sore Eyes? using a 0-4 Likert-type scale, where 0 = I did not have this symptom/Not applicable and 4 = Very Much. A negative change value will represent perceived improvement. \| Baseline (Day 0), Day 28 \| \| Change from Baseline at Day 28 in IDEEL-SB Question Stinging \| Subjects will respond to the question, OVER THE LAST TWO WEEKS, how much did the following symptom bother you: Stinging Eyes? using a 0-4 Likert-type scale, where 0 = I did not have this symptom/Not applicable and 4 = Very Much. A negative change value will represent perceived improvement. \| Baseline (Day 0), Day 28 \| \| Change from Baseline at Day 28 in IDEEL-SB Question Burning \| Subjects will respond to the question, OVER THE LAST TWO WEEKS, how much did the following symptom bother you: Burning Eyes? using a 0-4 Likert-type scale, where 0 = I did not have this symptom/Not applicable and 4 = Very Much. A negative change value will represent perceived improvement. \| Baseline (Day 0), Day 28 \| \| Change from Baseline at Day 28 in IDEEL-SB Question Tired Eyes \| Subjects will respond to the question, OVER THE LAST TWO WEEKS, how much did the following symptom bother you: Tired Eyes? using a 0-4 Likert-type scale, where 0 = I did not have this symptom/Not applicable and 4 = Very Much. A negative change value will represent perceived improvement. \| Baseline (Day 0), Day 28 \| \| Change from Baseline at Day 28 in DEQ-5 Question Watery \| The Dry Eye Questionnaire-5 (DEQ-5) is a patient-reported outcome measures questionnaire designed to assess symptoms of dry eye disease. Subjects will respond to the question, During a typical day in the past month, how often did your eyes look or feel excessively watery? using a 0-4 Likert-type scale, where 0 = Never and 4 = Constantly. A negative change value will represent perceived improvement. \| Baseline (Day 0), Day 28 \|		Eye drops	Lubricant Eye Drops, Ophthalmic Solutions, Pharmaceutical Solutions	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Systane Complete<br>First dose of Systane Complete in both eyes on Day 0, followed by Systane Complete self-administered 4 times daily for 28 days \| Other: Systane Complete<br>* Propylene glycol 0.6% eye drops for replenishing deficiencies in both the lipid and aqueous layers of the tear film<br>* Other names: Systane® Complete Lubricant Eye Drops;\|	Systane Complete Multi-symptom Relief Study Overview ================= Brief Summary ----------------- The purpose of this study is to demonstrate effective symptom relief with the use of Systane Complete among subjects with dry eye disease (DED). Detailed Description ----------------- Subjects will be expected to attend a screening/baseline visit and one additional visit at Day 28 (± 2 days), with a telephone call visit conducted at Day 14 (± 2 days). Individual duration of subject participation will be approximately 28 days. Official Title ----------------- Systane Complete Multi-symptom Relief Conditions ----------------- Dry Eye Disease Intervention / Treatment ----------------- * Other: Systane Complete Participation Criteria ================= Eligibility Criteria ----------------- Key Inclusion Criteria: Able to understand and sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form. Willing and able to attend all study visits as required per protocol. Have dry eye symptoms as specified in the protocol. Willing to discontinue use of all habitual artificial tear supplements for the entire study duration. Other protocol-defined inclusion criteria may apply. Key Exclusion Criteria: Ocular conditions as specified in the protocol. Contact lens use within one week prior to screening visit. Use of medications as specified in the protocol. Pregnant or breast feeding. Other protocol-defined exclusion criteria may apply. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Systane Complete<br>First dose of Systane Complete in both eyes on Day 0, followed by Systane Complete self-administered 4 times daily for 28 days \| Other: Systane Complete<br>* Propylene glycol 0.6% eye drops for replenishing deficiencies in both the lipid and aqueous layers of the tear film<br>* Other names: Systane® Complete Lubricant Eye Drops;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change from Baseline at Day 28 in IDEEL-SB Question Sore \| The Impact of Dry Eye on Everyday Life - Symptoms Bother (IDEEL-SB) is a patient-reported outcome measures questionnaire designed to assess symptoms of dry eye disease. Subjects will respond to the question, OVER THE LAST TWO WEEKS, how much did the following symptom bother you: Sore Eyes? using a 0-4 Likert-type scale, where 0 = I did not have this symptom/Not applicable and 4 = Very Much. A negative change value will represent perceived improvement. \| Baseline (Day 0), Day 28 \| \| Change from Baseline at Day 28 in IDEEL-SB Question Stinging \| Subjects will respond to the question, OVER THE LAST TWO WEEKS, how much did the following symptom bother you: Stinging Eyes? using a 0-4 Likert-type scale, where 0 = I did not have this symptom/Not applicable and 4 = Very Much. A negative change value will represent perceived improvement. \| Baseline (Day 0), Day 28 \| \| Change from Baseline at Day 28 in IDEEL-SB Question Burning \| Subjects will respond to the question, OVER THE LAST TWO WEEKS, how much did the following symptom bother you: Burning Eyes? using a 0-4 Likert-type scale, where 0 = I did not have this symptom/Not applicable and 4 = Very Much. A negative change value will represent perceived improvement. \| Baseline (Day 0), Day 28 \| \| Change from Baseline at Day 28 in IDEEL-SB Question Tired Eyes \| Subjects will respond to the question, OVER THE LAST TWO WEEKS, how much did the following symptom bother you: Tired Eyes? using a 0-4 Likert-type scale, where 0 = I did not have this symptom/Not applicable and 4 = Very Much. A negative change value will represent perceived improvement. \| Baseline (Day 0), Day 28 \| \| Change from Baseline at Day 28 in DEQ-5 Question Watery \| The Dry Eye Questionnaire-5 (DEQ-5) is a patient-reported outcome measures questionnaire designed to assess symptoms of dry eye disease. Subjects will respond to the question, During a typical day in the past month, how often did your eyes look or feel excessively watery? using a 0-4 Likert-type scale, where 0 = Never and 4 = Constantly. A negative change value will represent perceived improvement. \| Baseline (Day 0), Day 28 \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Eye drops
NCT05464901	VTE and the Related Factors Associated With Higher Rates of PE After a DVT in Southwestern China	Little is known about the current management status of venous thromboembolism (VTE) in Southwestern China. We aimed to investigate the status of anticoagulant administration in VTE in Southwestern China and assess the potential predictors of deep vein thrombosis (DVT) complicated pulmonary embolism (PE). We extracted data from YiduCloud database from December 2006 to November 2018 and performed a cross-sectional survey of VTE. The demographics, laboratory tests, and anticoagulants were collected and analyzed in the logistic regression model, classification tree and Random Forest model.	We established a collaborative epidemiological work of southwestern China for our cross-sectional survey sample, which included hospitalized patients in the seven main medical centers who met the inclusion criteria. The Human Research Committee of Chongqing Medical University approved this study and waived the need for informed consent. Patients were eligible to be included in the study if they are admitted or discharged with a diagnosis of DVT or/and PE and if they ever received treatment in the seven medical centers between December 2006 to November 2018.	The Real-World Treatment Status of Venous Thromboembolism and the Related Factors Associated With Higher Rates of PE After a DVT in Southwestern China	Venous Thromboembolism; Deep Vein Thrombosis; Pulmonary Embolism; Anticoagulants		Inclusion Criteria:~- In the Chinese VTE guidelines, the diagnosis of VTE depends on a series of tests. D-dimer was used to screen for thrombosis, and limb venous ultrasound was used to diagnose DVT. CT pulmonary angiography (CTPA) or pulmonary ventilation perfusion scan was used for the diagnosis of pulmonary embolism. Through the retrieval of patient diagnosis in the database, we retrieved the basic data of all patients diagnosed as VTE during the study period.~Exclusion Criteria:~-	null	null	All	null		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| The maternal cardiac events and the neonatal complications \| Primary outcomes of interest were major adverse cardiac events (MACEs), obstetric complications and neonatal adverse clinical events (NACEs). \| 2010-2019 \|			Pulmonary Embolism, Thrombosis, Embolism, Thromboembolism, Venous Thromboembolism, Venous Thrombosis, Embolism and Thrombosis, Vascular Diseases, Cardiovascular Diseases, Lung Diseases, Respiratory Tract Diseases		VTE and the Related Factors Associated With Higher Rates of PE After a DVT in Southwestern China Study Overview ================= Brief Summary ----------------- Little is known about the current management status of venous thromboembolism (VTE) in Southwestern China. We aimed to investigate the status of anticoagulant administration in VTE in Southwestern China and assess the potential predictors of deep vein thrombosis (DVT) complicated pulmonary embolism (PE). We extracted data from YiduCloud database from December 2006 to November 2018 and performed a cross-sectional survey of VTE. The demographics, laboratory tests, and anticoagulants were collected and analyzed in the logistic regression model, classification tree and Random Forest model. Detailed Description ----------------- We established a collaborative epidemiological work of southwestern China for our cross-sectional survey sample, which included hospitalized patients in the seven main medical centers who met the inclusion criteria. The Human Research Committee of Chongqing Medical University approved this study and waived the need for informed consent. Patients were eligible to be included in the study if they are admitted or discharged with a diagnosis of DVT or/and PE and if they ever received treatment in the seven medical centers between December 2006 to November 2018. Official Title ----------------- The Real-World Treatment Status of Venous Thromboembolism and the Related Factors Associated With Higher Rates of PE After a DVT in Southwestern China Conditions ----------------- Venous Thromboembolism; Deep Vein Thrombosis; Pulmonary Embolism; Anticoagulants Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: - In the Chinese VTE guidelines, the diagnosis of VTE depends on a series of tests. D-dimer was used to screen for thrombosis, and limb venous ultrasound was used to diagnose DVT. CT pulmonary angiography (CTPA) or pulmonary ventilation perfusion scan was used for the diagnosis of pulmonary embolism. Through the retrieval of patient diagnosis in the database, we retrieved the basic data of all patients diagnosed as VTE during the study period. Exclusion Criteria: - Sexes Eligible for Study ----------------- All Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| The maternal cardiac events and the neonatal complications \| Primary outcomes of interest were major adverse cardiac events (MACEs), obstetric complications and neonatal adverse clinical events (NACEs). \| 2010-2019 \|
NCT00220519	Lactobacillus GG Supplementation During Pediatric Burn Injuries	Critical illness and the therapies that accompany it are associated with a disruption in the ecological equilibrium of the GI tract that can ultimately lead to infection. Lactobacillus GG, a probiotic, replenishes the healthy flora of the intestinal tract and may decrease the risk of diarrhea and infection during critical illness. However, little is known about the impact of probiotics following a burn injury and the mechanisms behind the proposed benefits. The hypothesis of this research is that Lactobacillus GG decreases the incidence of diarrhea and infection in burned children receiving antibiotic therapy. The specific aim of this research is to determine the impact of Lactobacillus GG on the incidence of diarrhea and infection among burned children (>20% TBSA) receiving antibiotic therapy.	Specific Aim:~Critical illness and the therapies that accompany it are associated with a disruption in the ecological equilibrium of the GI tract that can ultimately lead to infection. Lactobacillus GG, a probiotic, repletes the healthy flora of the intestinal tract and may decrease the risk of diarrhea and infection during critical illness. However, little is known about the impact of probiotics following a burn injury and the mechanisms behind the proposed benefits. The hypothesis of this research is that Lactobacillus GG decreases the incidence of diarrhea and infection in burned children receiving antibiotic therapy. The specific aim of this research is to determine the impact of Lactobacillus GG on the incidence of diarrhea and infection among burned children (>20% TBSA) receiving antibiotic therapy.~Subjects:~All subjects will be recruited from the Shriners Hospitals for Children in Boston. Patients of any age admitted to Shriners Hospitals for Children in Boston that match the following inclusion criteria will be considered for this study 1)burn wound size of at least 20% of the body surface area, 2)requires antibiotic therapy. Exclusion criteria includes: 1) < 20% total body surface area burn, 2)does not require antibiotic therapy, 3)only requires post-operative antibiotic therapy, 4)bowel obstruction, 5)milk allergy.~Study Design:~This is a randomized, double-blind, placebo-controlled trial. Patients will be randomly assigned to receive Lactobacillus GG (n = 47) or a placebo (n = 47) within 3 days of initiation of antibiotic therapy. Randomization will occur by using a computerized randomization list. A pharmacist, who is not a member of the study staff, will assign each of the 2 supplement groups a number and label the supplement bottles accordingly.~Methods:~Lactobacillus GG, a nonpathogenic microorganism, will be administered in this study. A dose of 1010 colony factor units (cfu) twice daily will be given to the experimental group (n =47). The control group will receive a placebo (n = 47) that will be identical in appearance to the probiotic. All supplements will be administered orally or via feeding tube. The study endpoint will be 10 days after antibiotic use is discontinued or patient discharge Parameters measured will include 1) the occurrence of pneumonia or infection in the wound, blood, or urine, as defined by The National Nosocomial Infection Surveillance System (A localized or systemic condition that results from adverse reaction to the presence of an infectious agent(s) or toxin(s)) and clarified by the Infection Control Nurse, 2) incidence of diarrhea defined as 3 or more loose or watery stools per 24 hours, 3) weekly weights and labs (including total protein, albumin, prealbumin and C-reactive protein) as obtained per routine care, 4) length of antibiotic use, 5) length of stay.	Lactobacillus GG Supplementation During Pediatric Burn Injuries	Burns	* Drug: Lactobacillus GG	Inclusion Criteria:~Burn wound size of at least 20% of the body surface area~Requires antibiotic therapy~Exclusion Criteria:~< 20% total body surface area burn~Does not require antibiotic therapy~Only requires post-operative antibiotic therapy~Bowel obstruction~Milk allergy	null	18 Years	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Infection \| \| Daily \| \| Diarrhea \| \| Daily \|			Burns, Wounds and Injuries	\| Intervention/Treatment \| \| --- \| \|Drug: Lactobacillus GG\|nan\|	Lactobacillus GG Supplementation During Pediatric Burn Injuries Study Overview ================= Brief Summary ----------------- Critical illness and the therapies that accompany it are associated with a disruption in the ecological equilibrium of the GI tract that can ultimately lead to infection. Lactobacillus GG, a probiotic, replenishes the healthy flora of the intestinal tract and may decrease the risk of diarrhea and infection during critical illness. However, little is known about the impact of probiotics following a burn injury and the mechanisms behind the proposed benefits. The hypothesis of this research is that Lactobacillus GG decreases the incidence of diarrhea and infection in burned children receiving antibiotic therapy. The specific aim of this research is to determine the impact of Lactobacillus GG on the incidence of diarrhea and infection among burned children (>20% TBSA) receiving antibiotic therapy. Detailed Description ----------------- Specific Aim: Critical illness and the therapies that accompany it are associated with a disruption in the ecological equilibrium of the GI tract that can ultimately lead to infection. Lactobacillus GG, a probiotic, repletes the healthy flora of the intestinal tract and may decrease the risk of diarrhea and infection during critical illness. However, little is known about the impact of probiotics following a burn injury and the mechanisms behind the proposed benefits. The hypothesis of this research is that Lactobacillus GG decreases the incidence of diarrhea and infection in burned children receiving antibiotic therapy. The specific aim of this research is to determine the impact of Lactobacillus GG on the incidence of diarrhea and infection among burned children (>20% TBSA) receiving antibiotic therapy. Subjects: All subjects will be recruited from the Shriners Hospitals for Children in Boston. Patients of any age admitted to Shriners Hospitals for Children in Boston that match the following inclusion criteria will be considered for this study 1)burn wound size of at least 20% of the body surface area, 2)requires antibiotic therapy. Exclusion criteria includes: 1) < 20% total body surface area burn, 2)does not require antibiotic therapy, 3)only requires post-operative antibiotic therapy, 4)bowel obstruction, 5)milk allergy. Study Design: This is a randomized, double-blind, placebo-controlled trial. Patients will be randomly assigned to receive Lactobacillus GG (n = 47) or a placebo (n = 47) within 3 days of initiation of antibiotic therapy. Randomization will occur by using a computerized randomization list. A pharmacist, who is not a member of the study staff, will assign each of the 2 supplement groups a number and label the supplement bottles accordingly. Methods: Lactobacillus GG, a nonpathogenic microorganism, will be administered in this study. A dose of 1010 colony factor units (cfu) twice daily will be given to the experimental group (n =47). The control group will receive a placebo (n = 47) that will be identical in appearance to the probiotic. All supplements will be administered orally or via feeding tube. The study endpoint will be 10 days after antibiotic use is discontinued or patient discharge Parameters measured will include 1) the occurrence of pneumonia or infection in the wound, blood, or urine, as defined by The National Nosocomial Infection Surveillance System (A localized or systemic condition that results from adverse reaction to the presence of an infectious agent(s) or toxin(s)) and clarified by the Infection Control Nurse, 2) incidence of diarrhea defined as 3 or more loose or watery stools per 24 hours, 3) weekly weights and labs (including total protein, albumin, prealbumin and C-reactive protein) as obtained per routine care, 4) length of antibiotic use, 5) length of stay. Official Title ----------------- Lactobacillus GG Supplementation During Pediatric Burn Injuries Conditions ----------------- Burns Intervention / Treatment ----------------- * Drug: Lactobacillus GG Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Burn wound size of at least 20% of the body surface area Requires antibiotic therapy Exclusion Criteria: < 20% total body surface area burn Does not require antibiotic therapy Only requires post-operative antibiotic therapy Bowel obstruction Milk allergy Ages Eligible for Study ----------------- Maximum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple Arms and Interventions \| Intervention/Treatment \| \| --- \| \|Drug: Lactobacillus GG\|nan\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Infection \| \| Daily \| \| Diarrhea \| \| Daily \|
NCT03480438	Treatment of Older Patients With B-precursor ALL With Sequential Dose Reduced Chemotherapy and Blinatumomab	The trial proposed here attempts to reduce induction chemotherapy to phase I of standard induction in patients with B-precursor ALL. Induction phase II will be replaced by blinatumomab.~The initial treatment phase is followed by sequential chemotherapy and further blinatumomab cycles.	Blinatumomab is a bispecific single-chain antibody construct designed to link B cells and T cells resulting in T-cell activation and a cytotoxic T-cell response against CD19 expressing cells. In Phase II-III clinical trials 43-69 % of the patients treated with blinatumomab in relapsed/refractory ALL with poor prognostic features, achieved a complete hematologic remission and around 80 % of these obtained a molecular remission as well. Blinatumomab thus has demonstrated significant antileukemic activity in relapsed/refractory adult ALL. The ultimate goal for optimised management of adult ALL is to integrate targeted compounds with known single-drug activity into first-line treatment.	Phase II Trial for the Treatment of Older Patients With Newly Diagnosed CD19 Positive, Ph/BCR-ABL Negative B-precursor Acute Lymphoblastic Leukemia With Sequential Dose Reduced Chemotherapy and Blinatumomab (EWALL-BOLD)	B-Precursor ALL	* Drug: Blinatumomab	Inclusion Criteria:~Patients with newly diagnosed CD19 positive B-precursor ALL~Greater than 25 % blasts in bone marrow~Eastern Cooperative Oncology Group (ECOG) performance status <= 2~Charlson comorbidity score <= 2~Age > 55 and < 75 years at the time of informed consent~Renal and hepatic function as defined below:~AST (SGOT), ALT(SGPT) and AP < 5x upper limit of normal (UNL) (unless related to leukemic liver infiltration by investigator assessment)~Total bilirubin < 1.5x ULN (unless related to Gilbert's Meulengracht disease)~Creatinine < 1.5x ULN~Creatinine clearance >= 50 mL/min (e.g. calculated according Cockroft & Gault)~Negative pregnancy test in women of childbearing potential~Ability to understand and willingness to sign a written informed consent~For Germany: Participation in the registry of the German Multicenter Study Group for Adult ALL (GMALL)~Exclusion Criteria:~Antileukemic pretreatment (GMALL prephase with dexamethasone and cyclophosphamide allowed)~History of malignancy other than ALL within 5 years prior to start of protocol-specified therapy with the exception of:~Malignancy treated with curative intent and with no known active disease present for 2 years before enrollment and felt to be at low risk for recurrence by the treating physician including~Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease~Adequately treated cervical carcinoma in situ without evidence of disease~Adequately treated breast ductal carcinoma in situ without evidence of disease~Prostatic intraepithelial neoplasia without evidence of prostate cancer~History or presence of clinically relevant (per investigator's assessment) CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome or psychosis~Active ALL in the CNS confirmed by CSF analysis) or testes (clinical diagnosis) or other extramedullary involvement; non-bulky lymph node (< 7.5 cm diameter) involvement will be accepted~Current autoimmune disease or history of autoimmune disease with potential CNS involvement~Known exclusion criteria to recommended chemotherapy~Known positivity of HIV, hepatitis B (HbsAG) or hepatitis C virus (anti-HCV)~Subject received prior anti-CD19 therapy~Live vaccination within 2 weeks before the start of study treatment~Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation:~Subject has known sensitivity to immunoglobulins or any of the products or components to be administered during dosing~Currently receiving treatment in another investigational device or drug study or less than 30 days since ending treatment on another investigational device or drug study(s). Thirty days is calculated from day 1 of protocol-specified therapy~Subject likely to not be available to complete all protocol-required study visits or procedures, including follow-up visits, and/or to comply with all required study procedures to the best of the subject's and investigator's knowledge~History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator would pose a risk to subject safety of interfere with the study evaluation, procedures or completion~Woman of childbearing potential and is not willing to use a highly effective method of contraception while receiving study treatment and for an additional 3 months after the last dose of study treatment~Male who has a female partner of childbearing potential, and is not willing to use 2 highly effective forms of contraception while receiving protocol-specified therapy and for at least an additional 3 months after the last dose of protocol-specified therapy.	56 Years	74 Years	All	No	Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Hematologic and MRD response after induction therapy \| Proportion of patients achieving a complete hematologic remission and a complete molecular remission (MRD response or complete MRD response) after induction therapy defined as one cycle of chemotherapy and one cycle of blinatumomab \| after induction therapy (up to 8 weeks) \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Overall Survival \| Probability of overall survival at 1 year after start of therapy \| 1 year after start of therapy \| \| Adverse Events \| Rate and grade of adverse events (AE) according to CTC-AE in induction phase I, blinatumomab induction and during blinatumomab cycle I, II and III \| continuously until end-of-core-study (week 43) \| \| MRD response after induction and consolidation \| Proportion of patients who achieve a MRD response or a complete MRD response after induction consolidation \| after induction and consolidation (up to 35 weeks) \| \| Time to MRD relapse \| Time to MRD relapse after prior achievement of MRD response or complete MRD response \| continuously until end of maintenance therapy (up to 27 months) \| \| Continuous complete remission \| Probability of continuous complete remission at 1 year \| 1 year after start of therapy \| \| Relapse free survival \| Probability of relapse free survival at 1 year \| 1 year after start of therapy \| \| Event-free survival \| Probability of event-free survival at 1 year \| 1 year after start of therapy \| \| Relapse localisation \| Proportion of different relapse localisation in relation to total number of relapses \| In case of relapse, continuously until end of maintenance therapy (up to 27 months) \| \| Quality of life \| Quality of life measures (EORTC=European Organisation for Research and Treatment of Cancer standard scales) at different time-points during induction and consolidation; this is a multidimensional questionnaire with different scales per item such als functional scale, global health status and symptoms. Details are outlined in respective manuals (https://qol.eortc.org/manuals/) \| until end of maintenance therapy (up to 27 months) \| \| Treatment deviation 1 \| Rate of treatment interruptions \| until end of treatment (up to 39 weeks) \| \| Treatment deviation 2 \| Duration of treatment interruptions \| until end of treatment (up to 39 weeks) \| \| Treatment deviation 3 \| Dose reductions \| until end of treatment (up to 39 weeks) \| \| Treatment deviation 4 \| Mitigation strategies \| until end of treatment (up to 39 weeks) \| \| Treatment deviation 5 \| Rate of withdrawals \| until end of treatment (up to 39 weeks) \|		Blinatumomab, Antineoplastic Agents	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Blinatumomab<br>Patients will receive blinatumomab at a dose of 28 μg/day as continuous intravenous infusion at constant flow rate for four weeks defined as one treatment cycle. Up to four cycles will be performed.~In case of defined toxicities, the dose of blinatumomab may be reduced to 9 μg/day. \| Drug: Blinatumomab<br>* Patients will receive standard of care chemotherapy before blinatumomab, between blinatumomab cycles and after blinatumomab.<br>* Other names: blincyto;\|	Treatment of Older Patients With B-precursor ALL With Sequential Dose Reduced Chemotherapy and Blinatumomab Study Overview ================= Brief Summary ----------------- The trial proposed here attempts to reduce induction chemotherapy to phase I of standard induction in patients with B-precursor ALL. Induction phase II will be replaced by blinatumomab. The initial treatment phase is followed by sequential chemotherapy and further blinatumomab cycles. Detailed Description ----------------- Blinatumomab is a bispecific single-chain antibody construct designed to link B cells and T cells resulting in T-cell activation and a cytotoxic T-cell response against CD19 expressing cells. In Phase II-III clinical trials 43-69 % of the patients treated with blinatumomab in relapsed/refractory ALL with poor prognostic features, achieved a complete hematologic remission and around 80 % of these obtained a molecular remission as well. Blinatumomab thus has demonstrated significant antileukemic activity in relapsed/refractory adult ALL. The ultimate goal for optimised management of adult ALL is to integrate targeted compounds with known single-drug activity into first-line treatment. Official Title ----------------- Phase II Trial for the Treatment of Older Patients With Newly Diagnosed CD19 Positive, Ph/BCR-ABL Negative B-precursor Acute Lymphoblastic Leukemia With Sequential Dose Reduced Chemotherapy and Blinatumomab (EWALL-BOLD) Conditions ----------------- B-Precursor ALL Intervention / Treatment ----------------- * Drug: Blinatumomab Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients with newly diagnosed CD19 positive B-precursor ALL Greater than 25 % blasts in bone marrow Eastern Cooperative Oncology Group (ECOG) performance status <= 2 Charlson comorbidity score <= 2 Age > 55 and < 75 years at the time of informed consent Renal and hepatic function as defined below: AST (SGOT), ALT(SGPT) and AP < 5x upper limit of normal (UNL) (unless related to leukemic liver infiltration by investigator assessment) Total bilirubin < 1.5x ULN (unless related to Gilbert's Meulengracht disease) Creatinine < 1.5x ULN Creatinine clearance >= 50 mL/min (e.g. calculated according Cockroft & Gault) Negative pregnancy test in women of childbearing potential Ability to understand and willingness to sign a written informed consent For Germany: Participation in the registry of the German Multicenter Study Group for Adult ALL (GMALL) Exclusion Criteria: Antileukemic pretreatment (GMALL prephase with dexamethasone and cyclophosphamide allowed) History of malignancy other than ALL within 5 years prior to start of protocol-specified therapy with the exception of: Malignancy treated with curative intent and with no known active disease present for 2 years before enrollment and felt to be at low risk for recurrence by the treating physician including Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated cervical carcinoma in situ without evidence of disease Adequately treated breast ductal carcinoma in situ without evidence of disease Prostatic intraepithelial neoplasia without evidence of prostate cancer History or presence of clinically relevant (per investigator's assessment) CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome or psychosis Active ALL in the CNS confirmed by CSF analysis) or testes (clinical diagnosis) or other extramedullary involvement; non-bulky lymph node (< 7.5 cm diameter) involvement will be accepted Current autoimmune disease or history of autoimmune disease with potential CNS involvement Known exclusion criteria to recommended chemotherapy Known positivity of HIV, hepatitis B (HbsAG) or hepatitis C virus (anti-HCV) Subject received prior anti-CD19 therapy Live vaccination within 2 weeks before the start of study treatment Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation: Subject has known sensitivity to immunoglobulins or any of the products or components to be administered during dosing Currently receiving treatment in another investigational device or drug study or less than 30 days since ending treatment on another investigational device or drug study(s). Thirty days is calculated from day 1 of protocol-specified therapy Subject likely to not be available to complete all protocol-required study visits or procedures, including follow-up visits, and/or to comply with all required study procedures to the best of the subject's and investigator's knowledge History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator would pose a risk to subject safety of interfere with the study evaluation, procedures or completion Woman of childbearing potential and is not willing to use a highly effective method of contraception while receiving study treatment and for an additional 3 months after the last dose of study treatment Male who has a female partner of childbearing potential, and is not willing to use 2 highly effective forms of contraception while receiving protocol-specified therapy and for at least an additional 3 months after the last dose of protocol-specified therapy. Ages Eligible for Study ----------------- Minimum Age: 56 Years Maximum Age: 74 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Blinatumomab<br>Patients will receive blinatumomab at a dose of 28 μg/day as continuous intravenous infusion at constant flow rate for four weeks defined as one treatment cycle. Up to four cycles will be performed. In case of defined toxicities, the dose of blinatumomab may be reduced to 9 μg/day. \| Drug: Blinatumomab<br>* Patients will receive standard of care chemotherapy before blinatumomab, between blinatumomab cycles and after blinatumomab.<br>* Other names: blincyto;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Hematologic and MRD response after induction therapy \| Proportion of patients achieving a complete hematologic remission and a complete molecular remission (MRD response or complete MRD response) after induction therapy defined as one cycle of chemotherapy and one cycle of blinatumomab \| after induction therapy (up to 8 weeks) \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Overall Survival \| Probability of overall survival at 1 year after start of therapy \| 1 year after start of therapy \| \| Adverse Events \| Rate and grade of adverse events (AE) according to CTC-AE in induction phase I, blinatumomab induction and during blinatumomab cycle I, II and III \| continuously until end-of-core-study (week 43) \| \| MRD response after induction and consolidation \| Proportion of patients who achieve a MRD response or a complete MRD response after induction consolidation \| after induction and consolidation (up to 35 weeks) \| \| Time to MRD relapse \| Time to MRD relapse after prior achievement of MRD response or complete MRD response \| continuously until end of maintenance therapy (up to 27 months) \| \| Continuous complete remission \| Probability of continuous complete remission at 1 year \| 1 year after start of therapy \| \| Relapse free survival \| Probability of relapse free survival at 1 year \| 1 year after start of therapy \| \| Event-free survival \| Probability of event-free survival at 1 year \| 1 year after start of therapy \| \| Relapse localisation \| Proportion of different relapse localisation in relation to total number of relapses \| In case of relapse, continuously until end of maintenance therapy (up to 27 months) \| \| Quality of life \| Quality of life measures (EORTC=European Organisation for Research and Treatment of Cancer standard scales) at different time-points during induction and consolidation; this is a multidimensional questionnaire with different scales per item such als functional scale, global health status and symptoms. Details are outlined in respective manuals (https://qol.eortc.org/manuals/) \| until end of maintenance therapy (up to 27 months) \| \| Treatment deviation 1 \| Rate of treatment interruptions \| until end of treatment (up to 39 weeks) \| \| Treatment deviation 2 \| Duration of treatment interruptions \| until end of treatment (up to 39 weeks) \| \| Treatment deviation 3 \| Dose reductions \| until end of treatment (up to 39 weeks) \| \| Treatment deviation 4 \| Mitigation strategies \| until end of treatment (up to 39 weeks) \| \| Treatment deviation 5 \| Rate of withdrawals \| until end of treatment (up to 39 weeks) \|
NCT01671878	Glucose and Insulin Responses to Test Foods	In this study, postprandial glucose and insulin responses of different foods will be measured in individuals with varying body weight.		Characterization of the Postprandial Glucose and Insulin Responses to Test Foods in Lean and Overweight Subjects	Glucose Response, Insulin Response	* Other: Reference Glucose * Other: Test Food 1 (Cereal) * Other: Test Food 2 (Biscuit)	Inclusion Criteria:~Participants will be non-smoking males or non-pregnant females aged 20-45y, with normal glycemia and in good health. A total of 12 participants will be included, where approximately half will be male & half female, and half normal weight (BMI > 19.0 and < 25.0) and half overweight but not obese (BMI > 25.0 and < 30). Thus, no fewer than 5 male, 5 female, 5 normal weight and 5 overweight but not obese subjects will be included. Additional inclusion criteria will include:~Absence of diabetes, impaired glucose tolerance and impaired fasting glucose, defined as having a fasting plasma glucose < 5.6 mmol/L (100 mg/dL) AND plasma glucose levels < 7.8 mmol/L (140 mg/dL) 2h after consumption of a 50 g glucose drink (OGTT will be administered during the screening visit)~Systolic blood pressure 100-150 mmHg inclusive~Diastolic blood pressure 60-90 mmHg inclusive~Resting heart rate 50-90 beats/min inclusive after 3 minute rest~Able to refrain from eating legumes and drinking alcohol the day before each test session~Fasting triglycerides < 2.0 mmol/L (178 mg/dL)~Fasting HDL cholesterol > 0.9 mmol/L (35 mg/dL) for males and > 1.1mmol/L (42 mg/dL) for females~Fasting LDL cholesterol < 5.0 mmol/L (193 mg/dL)~AST and ALT < 120% of upper limit of normal (ULN)~hsCRP < 10 mg/L~Urea and creatinine < 150% ULN~Exclusion Criteria:~failure to meet any one of the inclusion criteria~age less than 18 or over 45 years~known history or AIDS, hepatitis, diabetes or a heart condition~participants using medications or with any condition which might, in the opinion of Dr. Wolever, the president of GI Testing, either: 1) make participation dangerous to the subject or to others, or 2) affect the results~participants who cannot or will not comply with the experimental procedures or do not follow GI Labs safety guidelines.~Food allergies of any kind~General anaesthesia in the month prior to inclusion.~Smokers	18 Years	45 Years	All	Accepts Healthy Volunteers	Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Postprandial Glucose Response \| \| 3 hours \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Postprandial Insulin Response \| \| 3 hours \|			\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Other: Reference Glucose<br>Glucose standard \| Other: Reference Glucose<br> <br> \| \| Experimental: Test Food 1<br>Cereal \| Other: Test Food 1 (Cereal)<br> <br> \| \| Experimental: Test Food 2<br>Biscuit \| Other: Test Food 2 (Biscuit)<br> <br> \|	Glucose and Insulin Responses to Test Foods Study Overview ================= Brief Summary ----------------- In this study, postprandial glucose and insulin responses of different foods will be measured in individuals with varying body weight. Official Title ----------------- Characterization of the Postprandial Glucose and Insulin Responses to Test Foods in Lean and Overweight Subjects Conditions ----------------- Glucose Response, Insulin Response Intervention / Treatment ----------------- * Other: Reference Glucose * Other: Test Food 1 (Cereal) * Other: Test Food 2 (Biscuit) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Participants will be non-smoking males or non-pregnant females aged 20-45y, with normal glycemia and in good health. A total of 12 participants will be included, where approximately half will be male & half female, and half normal weight (BMI > 19.0 and < 25.0) and half overweight but not obese (BMI > 25.0 and < 30). Thus, no fewer than 5 male, 5 female, 5 normal weight and 5 overweight but not obese subjects will be included. Additional inclusion criteria will include: Absence of diabetes, impaired glucose tolerance and impaired fasting glucose, defined as having a fasting plasma glucose < 5.6 mmol/L (100 mg/dL) AND plasma glucose levels < 7.8 mmol/L (140 mg/dL) 2h after consumption of a 50 g glucose drink (OGTT will be administered during the screening visit) Systolic blood pressure 100-150 mmHg inclusive Diastolic blood pressure 60-90 mmHg inclusive Resting heart rate 50-90 beats/min inclusive after 3 minute rest Able to refrain from eating legumes and drinking alcohol the day before each test session Fasting triglycerides < 2.0 mmol/L (178 mg/dL) Fasting HDL cholesterol > 0.9 mmol/L (35 mg/dL) for males and > 1.1mmol/L (42 mg/dL) for females Fasting LDL cholesterol < 5.0 mmol/L (193 mg/dL) AST and ALT < 120% of upper limit of normal (ULN) hsCRP < 10 mg/L Urea and creatinine < 150% ULN Exclusion Criteria: failure to meet any one of the inclusion criteria age less than 18 or over 45 years known history or AIDS, hepatitis, diabetes or a heart condition participants using medications or with any condition which might, in the opinion of Dr. Wolever, the president of GI Testing, either: 1) make participation dangerous to the subject or to others, or 2) affect the results participants who cannot or will not comply with the experimental procedures or do not follow GI Labs safety guidelines. Food allergies of any kind General anaesthesia in the month prior to inclusion. Smokers Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 45 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Other: Reference Glucose<br>Glucose standard \| Other: Reference Glucose<br> <br> \| \| Experimental: Test Food 1<br>Cereal \| Other: Test Food 1 (Cereal)<br> <br> \| \| Experimental: Test Food 2<br>Biscuit \| Other: Test Food 2 (Biscuit)<br> <br> \| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Postprandial Glucose Response \| \| 3 hours \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Postprandial Insulin Response \| \| 3 hours \|
NCT01625039	Impact of Employee Wellness Programme	The introduction of a wellness programme for workers employed in a clothing factory will improve quality of life, pain, attendance at work and levels of physical activity.	Introduction: The prevalence of health risk behaviours is growing amongst South African employees. Health risk behaviours have been identified as a major contributor to reduced health related quality of life (HRQoL) and the increase prevalence of non-communicable diseases. Worksite wellness programmes promise to promote behaviour changes amongst employees and to improve their HRQoL.~Aims: The aim of this study was to evaluate the short-term efficacy of an employee wellness programme on HRQoL, health behaviour change, levels of self efficacy, pain intensity, body mass index (BMI) and absenteeism amongst clothing and textile manufacturing employees.~Methods: The study was a randomised control trial consisting of 80 participants from three clothing manufacturing companies in South Africa. The experimental group was subjected to a wellness programme based on the principles of cognitive behaviour therapy (CBT) as well as weekly supervised exercise classes over six weeks. The control group received a once-off health promotion talk and various educational pamphlets, with no further intervention. Measurements were recorded at baseline and at six weeks post-intervention. Outcome measures used included the EQ-5D, Brief Pain Inventory-SF, Stanford Exercise Behaviours Scale, Stanford Self-Efficacy Scale, Stanford Self-Rated Health Scale, BMI and absenteeism.~Data Analysis: All the data were analysed with the Statistica-8 software program. Although t-tests are the most commonly used statistical method for evaluating the differences in the means between two groups (e.g. control and experimental), it assumes that the variable is normally distributed. Thus, because the ordinal data were not normally distributed, non-parametric tests were used to evaluate the differences in the medians between the two groups and to determine the level of significance. The Sign test was used in place of the paired t-test to determine the within group changes. The Mann-Whitney U test was used in place of the independent t-test to determine the difference between the two groups.	The Impact of an Employee Wellness Programme in Clothing/Textile Manufacturing Companies: A Randomised Control Trial	Obesity	* Behavioral: Employee wellness programme * Behavioral: Comparator (Once off educational session and educational materials)	Inclusion Criteria:~All factory workers who volunteered to take part in the study~Exclusion Criteria:~Subjects were excluded from the study if they reported uncontrolled diabetes and hypertension, coronary heart disease or any other illness that rendered participation in the exercise component unsafe.	18 Years	60 Years	All	Accepts Healthy Volunteers	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| EQ-5D \| Generic Health Related Quality of Life measure \| Baseline, change in EQ-5D at 6 weeks \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Stanford Exercise Behaviour Scale \| Self reported participation in different forms of physical exercise \| Baseline, change in stanford exercise behaviour at 6 weeks \| \| Body Mass Index \| Measurement of height and weight using standardized scales. \| Baseline, Change in BMI at 6 weeks \| \| Absenteeism from work \| Scrutiny of attendance records \| All absenteeism during the six weeks prior, during the six weeks of intervention and six weeks post intervention \|	Occupational health, cognitive behavioural therapy, physiotherapy, physical activity		\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Intervention<br>Participated in weekly educational workshops \| Behavioral: Employee wellness programme<br>* The experimental group was subjected to a wellness programme based on the principles of cognitive behaviour therapy (CBT) as well as weekly supervised exercise classes over six weeks.<br>* Other names: Exercise classes;\| \| Active Comparator: Control group<br>Received once off educational session and materials \| Behavioral: Comparator (Once off educational session and educational materials)<br>* Once off educational session and educational materials<br>* Other names: Health education;\|	Impact of Employee Wellness Programme Study Overview ================= Brief Summary ----------------- The introduction of a wellness programme for workers employed in a clothing factory will improve quality of life, pain, attendance at work and levels of physical activity. Detailed Description ----------------- Introduction: The prevalence of health risk behaviours is growing amongst South African employees. Health risk behaviours have been identified as a major contributor to reduced health related quality of life (HRQoL) and the increase prevalence of non-communicable diseases. Worksite wellness programmes promise to promote behaviour changes amongst employees and to improve their HRQoL. Aims: The aim of this study was to evaluate the short-term efficacy of an employee wellness programme on HRQoL, health behaviour change, levels of self efficacy, pain intensity, body mass index (BMI) and absenteeism amongst clothing and textile manufacturing employees. Methods: The study was a randomised control trial consisting of 80 participants from three clothing manufacturing companies in South Africa. The experimental group was subjected to a wellness programme based on the principles of cognitive behaviour therapy (CBT) as well as weekly supervised exercise classes over six weeks. The control group received a once-off health promotion talk and various educational pamphlets, with no further intervention. Measurements were recorded at baseline and at six weeks post-intervention. Outcome measures used included the EQ-5D, Brief Pain Inventory-SF, Stanford Exercise Behaviours Scale, Stanford Self-Efficacy Scale, Stanford Self-Rated Health Scale, BMI and absenteeism. Data Analysis: All the data were analysed with the Statistica-8 software program. Although t-tests are the most commonly used statistical method for evaluating the differences in the means between two groups (e.g. control and experimental), it assumes that the variable is normally distributed. Thus, because the ordinal data were not normally distributed, non-parametric tests were used to evaluate the differences in the medians between the two groups and to determine the level of significance. The Sign test was used in place of the paired t-test to determine the within group changes. The Mann-Whitney U test was used in place of the independent t-test to determine the difference between the two groups. Official Title ----------------- The Impact of an Employee Wellness Programme in Clothing/Textile Manufacturing Companies: A Randomised Control Trial Conditions ----------------- Obesity Intervention / Treatment ----------------- * Behavioral: Employee wellness programme * Behavioral: Comparator (Once off educational session and educational materials) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: All factory workers who volunteered to take part in the study Exclusion Criteria: Subjects were excluded from the study if they reported uncontrolled diabetes and hypertension, coronary heart disease or any other illness that rendered participation in the exercise component unsafe. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 60 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Intervention<br>Participated in weekly educational workshops \| Behavioral: Employee wellness programme<br>* The experimental group was subjected to a wellness programme based on the principles of cognitive behaviour therapy (CBT) as well as weekly supervised exercise classes over six weeks.<br>* Other names: Exercise classes;\| \| Active Comparator: Control group<br>Received once off educational session and materials \| Behavioral: Comparator (Once off educational session and educational materials)<br>* Once off educational session and educational materials<br>* Other names: Health education;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| EQ-5D \| Generic Health Related Quality of Life measure \| Baseline, change in EQ-5D at 6 weeks \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Stanford Exercise Behaviour Scale \| Self reported participation in different forms of physical exercise \| Baseline, change in stanford exercise behaviour at 6 weeks \| \| Body Mass Index \| Measurement of height and weight using standardized scales. \| Baseline, Change in BMI at 6 weeks \| \| Absenteeism from work \| Scrutiny of attendance records \| All absenteeism during the six weeks prior, during the six weeks of intervention and six weeks post intervention \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Occupational health, cognitive behavioural therapy, physiotherapy, physical activity
NCT03018379	Body Composition, Dietary Behaviors, Energy Expenditure and Physical Activity Among Moroccan Schoolchildren and Adolescents	Considering the increasing public health concern the obesity in Morocco, the aim of the present study was to use isotope techniques to assess body fat, total energy expenditure and physical activity to inform design and improve interventions for the prevention and control of obesity and related health risks such as diabetes and elevated blood pressure among children and adolescents. Specific objectives of the trial: 1. Determine the extent of obesity and physical activity levels in children and adolescents to design effective interventions in the school setting. 2.Propose alternative field based techniques for assessing body composition and physical activity that could be used in largescale situation assessments and in assessing interventions to address obesity and risk related health care. * For body composition: BMI z-score, waist circumference, waist measurement at height. * For physical activity: Questionnaire, Accelerometers 3. To identify factors contributing to the development of obesity and related health risks in schoolchildren and adolescents. 4. Collaborate with stakeholders (government, schools and / or colleges, communities and development partners) in designing interventions to address obesity and health risks. 5. To recommend to stakeholders the most effective interventions in schools to prevent and combat obesity and health risks in children and adolescents.		Assessment Study of Body Composition, Energy Expenditure and Physical Activity to Inform Design and Improve Interventions for the Prevention and Control of Obesity and Related Health Risks Among Schoolchildren and Adolescent Aged 8 to 14 Years in Morocco	Body Composition, Physical Activity		Inclusion Criteria:~Apparently healthy~Aged between 8 to 14 years old~Exclusion Criteria:~Hypo or hypervolemic conditions including diet~Diuretics and oedema~Private schools~Rural area	8 Years	14 Years	All	Accepts Healthy Volunteers		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Assessment of body composition using deuterium dilution technique \| Each participant provided a predose saliva sample. The postdose sample was collected from 3h to 4h after the administration of the dose. \| 1 year \| \| Assessment of energy expenditure using isotopes dilution techniques \| Each participant provided a predose urine sample. The postdose urine samples were collected after 3h to 4h and on days 3, 7 and 14. \| 1 year \| \| Assessment of physical activity levels using accelerometry triaxial (GT3X+) \| \| 2 years 6 months \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Assessment of dietary intake using 24h recall questionnaire \| \| 6 months \| \| Assessment of physical activity levels using physical activity questionnaire for children (PAQ-C) \| \| 2 years 6 months \|	Obesity, Body composition, energy expenditure, sedentarity, dietary behaviors		\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Assessment of body composition<br>The collection of the samples and the analyses were undertaken according to the guidelines of the International Atomic Energy Agency. In brief, after having emptied the bladder, each participant provided a predose saliva sample using a cotton ball.A 99.8 % deuterium dose of 0.5 g per kg body weight was given orally to the participant. The postdose sample was collected from 3h to 4h after the administration of the dose. The saliva samples were stored at 20°C until analysis by Fourier transform infrared spectroscopy (FTIR). \| \| \| Assessment of energy expenditure<br>Each participant provided a predose urine sample. A dose of doubly labelled water 2.625 ml per kg body weight was given orally to the participant.~The post dose sample was collected at 3h to 4h , and on days 3, 7 and 14 after dosing. An aliquot of those samples were stored at 20°C in tightly sealed containers until analysis by isotope-ratio mass spectrometry (IRMS). \| \| \| Assessment of physical activity<br>The participants were instructed to wear the accelerometer triaxial (GT3X+) attached to an elasticized belt around the waist, once they woke up until bed time at night for 7 consecutive days and to remove the accelerometer any time they were to perform activities that involve the use of water and when going to bed. \| \|	Body Composition, Dietary Behaviors, Energy Expenditure and Physical Activity Among Moroccan Schoolchildren and Adolescents Study Overview ================= Brief Summary ----------------- Considering the increasing public health concern the obesity in Morocco, the aim of the present study was to use isotope techniques to assess body fat, total energy expenditure and physical activity to inform design and improve interventions for the prevention and control of obesity and related health risks such as diabetes and elevated blood pressure among children and adolescents. Specific objectives of the trial: 1. Determine the extent of obesity and physical activity levels in children and adolescents to design effective interventions in the school setting. 2.Propose alternative field based techniques for assessing body composition and physical activity that could be used in largescale situation assessments and in assessing interventions to address obesity and risk related health care. * For body composition: BMI z-score, waist circumference, waist measurement at height. * For physical activity: Questionnaire, Accelerometers 3. To identify factors contributing to the development of obesity and related health risks in schoolchildren and adolescents. 4. Collaborate with stakeholders (government, schools and / or colleges, communities and development partners) in designing interventions to address obesity and health risks. 5. To recommend to stakeholders the most effective interventions in schools to prevent and combat obesity and health risks in children and adolescents. Official Title ----------------- Assessment Study of Body Composition, Energy Expenditure and Physical Activity to Inform Design and Improve Interventions for the Prevention and Control of Obesity and Related Health Risks Among Schoolchildren and Adolescent Aged 8 to 14 Years in Morocco Conditions ----------------- Body Composition, Physical Activity Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Apparently healthy Aged between 8 to 14 years old Exclusion Criteria: Hypo or hypervolemic conditions including diet Diuretics and oedema Private schools Rural area Ages Eligible for Study ----------------- Minimum Age: 8 Years Maximum Age: 14 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Assessment of body composition<br>The collection of the samples and the analyses were undertaken according to the guidelines of the International Atomic Energy Agency. In brief, after having emptied the bladder, each participant provided a predose saliva sample using a cotton ball.A 99.8 % deuterium dose of 0.5 g per kg body weight was given orally to the participant. The postdose sample was collected from 3h to 4h after the administration of the dose. The saliva samples were stored at 20°C until analysis by Fourier transform infrared spectroscopy (FTIR). \| \| \| Assessment of energy expenditure<br>Each participant provided a predose urine sample. A dose of doubly labelled water 2.625 ml per kg body weight was given orally to the participant. The post dose sample was collected at 3h to 4h , and on days 3, 7 and 14 after dosing. An aliquot of those samples were stored at 20°C in tightly sealed containers until analysis by isotope-ratio mass spectrometry (IRMS). \| \| \| Assessment of physical activity<br>The participants were instructed to wear the accelerometer triaxial (GT3X+) attached to an elasticized belt around the waist, once they woke up until bed time at night for 7 consecutive days and to remove the accelerometer any time they were to perform activities that involve the use of water and when going to bed. \| \| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Assessment of body composition using deuterium dilution technique \| Each participant provided a predose saliva sample. The postdose sample was collected from 3h to 4h after the administration of the dose. \| 1 year \| \| Assessment of energy expenditure using isotopes dilution techniques \| Each participant provided a predose urine sample. The postdose urine samples were collected after 3h to 4h and on days 3, 7 and 14. \| 1 year \| \| Assessment of physical activity levels using accelerometry triaxial (GT3X+) \| \| 2 years 6 months \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Assessment of dietary intake using 24h recall questionnaire \| \| 6 months \| \| Assessment of physical activity levels using physical activity questionnaire for children (PAQ-C) \| \| 2 years 6 months \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Obesity, Body composition, energy expenditure, sedentarity, dietary behaviors
NCT02839278	Biological Evaluation of a Novel Anti-inflammatory Treatment in Immune-mediated Inflammatory Diseases	The aim of the study is to investigate in vitro the impact of a novel anti-inflammatory treatment on costimulatory molecules expressed on monocytes.		Biological Evaluation of a Novel Anti-inflammatory Treatment in Immune-mediated Inflammatory Diseases	Inflammation	* Biological: Blood sample	Inclusion Criteria:~Immune-mediated inflammatory disease (non-ST segment elevation myocardial infarction, Rheumatoid arthritis, Chronic obstructive pulmonary disease, Idiopathic pulmonary fibrosis, Crohn's disease, Ulcerative colitis, Cystic fibrosis, Psoriasis, Multiple sclerosis or major depressive episode)~Patient able to understand the reason of the study~Patient not opposed to the conservation of biological samples for scientific research~Exclusion Criteria:~Pregnant woman~Subject without health insurance	18 Years	85 Years	All	No	Primary Purpose: Basic Science Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Expression of costimulatory molecules CD86, CD80, CD40 and class II (HLA-DR) on monocytes \| \| 24 months \|		Immunomodulation	Inflammation, Pathologic Processes	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Immune-mediated inflammatory disease<br>Patients with an immune-mediated inflammatory disease. A blood sample is achieved at T0 (no follow-up). \| Biological: Blood sample<br> <br> \|	Biological Evaluation of a Novel Anti-inflammatory Treatment in Immune-mediated Inflammatory Diseases Study Overview ================= Brief Summary ----------------- The aim of the study is to investigate in vitro the impact of a novel anti-inflammatory treatment on costimulatory molecules expressed on monocytes. Official Title ----------------- Biological Evaluation of a Novel Anti-inflammatory Treatment in Immune-mediated Inflammatory Diseases Conditions ----------------- Inflammation Intervention / Treatment ----------------- * Biological: Blood sample Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Immune-mediated inflammatory disease (non-ST segment elevation myocardial infarction, Rheumatoid arthritis, Chronic obstructive pulmonary disease, Idiopathic pulmonary fibrosis, Crohn's disease, Ulcerative colitis, Cystic fibrosis, Psoriasis, Multiple sclerosis or major depressive episode) Patient able to understand the reason of the study Patient not opposed to the conservation of biological samples for scientific research Exclusion Criteria: Pregnant woman Subject without health insurance Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 85 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Basic Science Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Immune-mediated inflammatory disease<br>Patients with an immune-mediated inflammatory disease. A blood sample is achieved at T0 (no follow-up). \| Biological: Blood sample<br> <br> \| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Expression of costimulatory molecules CD86, CD80, CD40 and class II (HLA-DR) on monocytes \| \| 24 months \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Immunomodulation
NCT01994746	Efficacy and Safety of Nasal Glucagon for Treatment of Hypoglycemia in Adults	The purpose of this study is to assess the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and safety of 3 milligrams (mg) glucagon (glucagon nasal powder) administered nasally compared with commercially available glucagon given by intramuscular injection.	Each glucagon dosing visit was conducted after an overnight fast of at least 8 h with a starting plasma glucose >= 90 mg/dL. Hypoglycemia was induced by an intravenous (IV) infusion of regular insulin diluted in normal saline during the clinic visit. Five minutes after stopping the insulin infusion (once the plasma glucose was <60 mg/dL), participants were treated with either a 3 mg glucagon dose nasally or 1 mg of glucagon administered by intramuscular (IM) injection.~After a wash-out period of 7 days or more, participants returned to the clinic and the procedure repeated with each participant crossed over to the other treatment. As such, each participant underwent two episodes of insulin-induced hypoglycemia in random order and received glucagon nasal powder during one episode and commercially available glucagon (GlucaGen, Novo Nordisk) by IM injection during the other episode.	Efficacy and Safety of Nasal Glucagon for Treatment of Insulin Induced Hypoglycemia in Adults With Diabetes	Diabetes Mellitus, Type 1	* Drug: Nasal Glucagon * Drug: Intramuscular Glucagon	Inclusion Criteria:~To be eligible, the following inclusion criteria must be met:~Clinical diagnosis of either type 1 diabetes receiving daily insulin since the time of diagnosis for at least 2 years or type 2 diabetes receiving multiple daily insulin doses for at least 2 years~At least 18.0 years of age and less than 65.0 years~Body mass index (BMI) greater than or equal to 20.0 and below or equal to 35.0 kilograms per meter squared (kg/m²)~Weighs at least 50 kg (110 pounds)~Females must meet one of the following criteria:~Of childbearing potential but agree to use an accepted contraceptive regimen as described in the study procedure manual throughout the entire duration of the study (from the screening until study completion)~Of non-childbearing potential, defined as a female who has had a hysterectomy or tubal ligation, is clinically considered infertile or is in a menopausal state (at least 1 year without menses)~In good general health with no conditions that could influence the outcome of the trial, and in the judgment of the Investigator is a good candidate for the study based on review of available medical history, physical examination and clinical laboratory evaluations~Willingness to adhere to the study requirements~Exclusion Criteria:~An individual is not eligible if any of the following exclusion criteria are present:~Females who are pregnant according to a positive urine pregnancy test, actively attempting to get pregnant, or are lactating~History of hypersensitivity to glucagon or any related products or severe hypersensitivity reactions (such as angioedema) to any drugs~Presence of cardiovascular, gastrointestinal, liver or kidney disease, or any other conditions which in the judgment of the investigator could interfere with the absorption, distribution, metabolism or excretion of drugs or could potentiate or predispose to undesired effects~History of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma.~History of an episode of severe hypoglycemia (as defined by an episode that required third party assistance for treatment) in the 1 month prior to enrolling in the study~Use of daily systemic beta-blocker, indomethacin, warfarin or anticholinergic drugs~History of epilepsy or seizure disorder~Regularly consumes 3 or more alcoholic beverages per day~Use of an Investigational Product in another clinical trial within the past 30 days~Donated 225 milliliters (mL) or more of blood in the previous 8 weeks before the first glucagon dosing	18 Years	64 Years	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Increase in Plasma Glucose Level to >=70mg/dL or an Increase of >=20mg/dL From Glucose Nadir \| Increase in blood glucose to ≥70 mg/dL or an increase of ≥20 mg/dL from glucose nadir within 30 minutes after receiving study glucagon, without receiving additional actions to increase the blood glucose level defines treatment success. Due to the residual activity of circulating insulin, glucose nadir was defined as the minimum glucose measurement at the time of, or within 10 minutes following glucagon administration. \| Within 30 minutes after receiving glucagon at both dosing visits (glucose was measured at pre-dose; 5, 10, 15, 20, 25, and 30 minutes following glucagon administration) \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Nasal and Non-nasal Effects/Symptoms \| Symptoms of runny nose, nasal congestion and/or itching, sneezing, watery and/or itchy eyes, redness of eyes, and itching of ears and/or throat were assessed. This was done via the Nasal Non-nasal Score Questionnaire. Each of the 9 symptoms is assigned an integer value from 0 to 3; higher values indicate more severe symptoms (a score of 0 indicates no symptoms). The reported results indicate the cohort median out of a possible maximum value of 27 (summing all 9 questions for each subject and reporting the median/IQR across participants). \| Pre-dose; 15, 30, 60, and 90 post glucagon administration \| \| Recovery From Symptoms of Hypoglycemia \| Recovery from hypoglycemia symptoms were assessed using the Edinburgh Hypoglycemia Scale. The Edinburgh Hypoglycemia Symptom Scale measures the intensity of 15 commonly experienced hypoglycemic symptoms on a 7-point Likert scale (1 = not present, 7 = very intense). The higher the score, the more intense the hypoglycemia symptoms. The sum of each symptom score would yield a range of 15 to 105 (i.e., 15 x 7 =105). The total score was calculated as the sum of each symptom score minus 15, and summarized at each time point by treatment group. \| Pre-dose;15, 30, 45 and 60 minutes following administration of glucagon \| \| Time From Glucagon Administration to Blood Glucose >/=70 mg/dL or an Increase ≥20 mg/dL in Blood Glucose From Nadir \| The mean time from glucagon administration to blood glucose >/=70 mg/dL or an increase ≥20 mg/dL in blood glucose from nadir. \| Pre-dose; 5, 10, 15, 20, 25, and 30 minutes following glucagon administration \| \| Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Baseline-Adjusted Glucagon \| \| Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration \| \| Maximum Change From Baseline Concentration (Cmax) of Glucagon \| \| Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration \| \| Time to Maximum Change From Baseline Concentration (Tmax) of Glucagon \| \| Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration \| \| Area Under the Effect Concentration Time Curve (AUEC0-1.5) of Baseline-Adjusted Glucose From Time Zero up to 90 Minutes \| \| Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration \| \| Maximum Change From Baseline Concentration (Cmax) of Glucose \| \| Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration \| \| Time to Maximum Change From Baseline Concentration (Tmax) of Glucose \| \| Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration \|		Glucagon, Glucagon-Like Peptide 1, Gastrointestinal Agents, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs, Incretins	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Nasal Glucagon<br>At one visit, a glucagon dose of 3 mg was administered in a nostril with a prefilled delivery device that delivers a single dose upon activation. \| Drug: Nasal Glucagon<br> <br> * Other names: LY900018;\| \| Active Comparator: Intramuscular Glucagon<br>At a separate visit, 1 mg of glucagon was administered into the deltoid muscle of the non-dominant arm (intramuscular [IM]). \| Drug: Intramuscular Glucagon<br> <br> * Other names: GlucaGen HypoKit;\|	Efficacy and Safety of Nasal Glucagon for Treatment of Hypoglycemia in Adults Study Overview ================= Brief Summary ----------------- The purpose of this study is to assess the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and safety of 3 milligrams (mg) glucagon (glucagon nasal powder) administered nasally compared with commercially available glucagon given by intramuscular injection. Detailed Description ----------------- Each glucagon dosing visit was conducted after an overnight fast of at least 8 h with a starting plasma glucose >= 90 mg/dL. Hypoglycemia was induced by an intravenous (IV) infusion of regular insulin diluted in normal saline during the clinic visit. Five minutes after stopping the insulin infusion (once the plasma glucose was <60 mg/dL), participants were treated with either a 3 mg glucagon dose nasally or 1 mg of glucagon administered by intramuscular (IM) injection. After a wash-out period of 7 days or more, participants returned to the clinic and the procedure repeated with each participant crossed over to the other treatment. As such, each participant underwent two episodes of insulin-induced hypoglycemia in random order and received glucagon nasal powder during one episode and commercially available glucagon (GlucaGen, Novo Nordisk) by IM injection during the other episode. Official Title ----------------- Efficacy and Safety of Nasal Glucagon for Treatment of Insulin Induced Hypoglycemia in Adults With Diabetes Conditions ----------------- Diabetes Mellitus, Type 1 Intervention / Treatment ----------------- * Drug: Nasal Glucagon * Drug: Intramuscular Glucagon Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: To be eligible, the following inclusion criteria must be met: Clinical diagnosis of either type 1 diabetes receiving daily insulin since the time of diagnosis for at least 2 years or type 2 diabetes receiving multiple daily insulin doses for at least 2 years At least 18.0 years of age and less than 65.0 years Body mass index (BMI) greater than or equal to 20.0 and below or equal to 35.0 kilograms per meter squared (kg/m²) Weighs at least 50 kg (110 pounds) Females must meet one of the following criteria: Of childbearing potential but agree to use an accepted contraceptive regimen as described in the study procedure manual throughout the entire duration of the study (from the screening until study completion) Of non-childbearing potential, defined as a female who has had a hysterectomy or tubal ligation, is clinically considered infertile or is in a menopausal state (at least 1 year without menses) In good general health with no conditions that could influence the outcome of the trial, and in the judgment of the Investigator is a good candidate for the study based on review of available medical history, physical examination and clinical laboratory evaluations Willingness to adhere to the study requirements Exclusion Criteria: An individual is not eligible if any of the following exclusion criteria are present: Females who are pregnant according to a positive urine pregnancy test, actively attempting to get pregnant, or are lactating History of hypersensitivity to glucagon or any related products or severe hypersensitivity reactions (such as angioedema) to any drugs Presence of cardiovascular, gastrointestinal, liver or kidney disease, or any other conditions which in the judgment of the investigator could interfere with the absorption, distribution, metabolism or excretion of drugs or could potentiate or predispose to undesired effects History of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma. History of an episode of severe hypoglycemia (as defined by an episode that required third party assistance for treatment) in the 1 month prior to enrolling in the study Use of daily systemic beta-blocker, indomethacin, warfarin or anticholinergic drugs History of epilepsy or seizure disorder Regularly consumes 3 or more alcoholic beverages per day Use of an Investigational Product in another clinical trial within the past 30 days Donated 225 milliliters (mL) or more of blood in the previous 8 weeks before the first glucagon dosing Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 64 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Nasal Glucagon<br>At one visit, a glucagon dose of 3 mg was administered in a nostril with a prefilled delivery device that delivers a single dose upon activation. \| Drug: Nasal Glucagon<br> <br> * Other names: LY900018;\| \| Active Comparator: Intramuscular Glucagon<br>At a separate visit, 1 mg of glucagon was administered into the deltoid muscle of the non-dominant arm (intramuscular [IM]). \| Drug: Intramuscular Glucagon<br> <br> * Other names: GlucaGen HypoKit;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Increase in Plasma Glucose Level to >=70mg/dL or an Increase of >=20mg/dL From Glucose Nadir \| Increase in blood glucose to ≥70 mg/dL or an increase of ≥20 mg/dL from glucose nadir within 30 minutes after receiving study glucagon, without receiving additional actions to increase the blood glucose level defines treatment success. Due to the residual activity of circulating insulin, glucose nadir was defined as the minimum glucose measurement at the time of, or within 10 minutes following glucagon administration. \| Within 30 minutes after receiving glucagon at both dosing visits (glucose was measured at pre-dose; 5, 10, 15, 20, 25, and 30 minutes following glucagon administration) \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Nasal and Non-nasal Effects/Symptoms \| Symptoms of runny nose, nasal congestion and/or itching, sneezing, watery and/or itchy eyes, redness of eyes, and itching of ears and/or throat were assessed. This was done via the Nasal Non-nasal Score Questionnaire. Each of the 9 symptoms is assigned an integer value from 0 to 3; higher values indicate more severe symptoms (a score of 0 indicates no symptoms). The reported results indicate the cohort median out of a possible maximum value of 27 (summing all 9 questions for each subject and reporting the median/IQR across participants). \| Pre-dose; 15, 30, 60, and 90 post glucagon administration \| \| Recovery From Symptoms of Hypoglycemia \| Recovery from hypoglycemia symptoms were assessed using the Edinburgh Hypoglycemia Scale. The Edinburgh Hypoglycemia Symptom Scale measures the intensity of 15 commonly experienced hypoglycemic symptoms on a 7-point Likert scale (1 = not present, 7 = very intense). The higher the score, the more intense the hypoglycemia symptoms. The sum of each symptom score would yield a range of 15 to 105 (i.e., 15 x 7 =105). The total score was calculated as the sum of each symptom score minus 15, and summarized at each time point by treatment group. \| Pre-dose;15, 30, 45 and 60 minutes following administration of glucagon \| \| Time From Glucagon Administration to Blood Glucose >/=70 mg/dL or an Increase ≥20 mg/dL in Blood Glucose From Nadir \| The mean time from glucagon administration to blood glucose >/=70 mg/dL or an increase ≥20 mg/dL in blood glucose from nadir. \| Pre-dose; 5, 10, 15, 20, 25, and 30 minutes following glucagon administration \| \| Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Baseline-Adjusted Glucagon \| \| Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration \| \| Maximum Change From Baseline Concentration (Cmax) of Glucagon \| \| Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration \| \| Time to Maximum Change From Baseline Concentration (Tmax) of Glucagon \| \| Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration \| \| Area Under the Effect Concentration Time Curve (AUEC0-1.5) of Baseline-Adjusted Glucose From Time Zero up to 90 Minutes \| \| Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration \| \| Maximum Change From Baseline Concentration (Cmax) of Glucose \| \| Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration \| \| Time to Maximum Change From Baseline Concentration (Tmax) of Glucose \| \| Pre-dose; 5, 10, 15, 20, 25, 30, 40, 50, 60 and 90 minutes following glucagon administration \|
NCT04759430	The Effects of Telerehabilitation and Supervised Stabilization Exercises in Individuals With Nonspecific Chronic Low Back Pain	This study aims to investigate the effects of telerehabilitation and supervised stabilization exercises on pain, functionality, kinesophobia and quality of life in individuals with non-specific chronic low back pain. 72 individuals who voluntarily agree to participate in the study will be included. This study divides the patients in three groups: the supervised group: face-to-face stabilization exercises are applied, the telerehabilitation group: treatment through online meetings, and the control group: patients will do home-based exercises that prescribed by physiothrerapist. Evaluations will be made by the same physiotherapist. The researcher who will make the measurements in this study will not know which treatment program was applied to the participants. In this study, The same stabilization exercises will be applied in three different groups. Ten different stabilization exercises will be applied to the participants. Exercises will be performed for 20-30 minutes in each session, three times a week, for four weeks in total, twelve sessions. Clinical and demographic data of the 72 people participating in the study will be taken before treatment. Participants will also fill out questionnaires before and after the treatment that involve; the Oswestry Disability Index to measure(ODI) daily life activity limitations; the Visual Analogue Scale(VAS) for assessing the intensity of pain; Tampa Scale for Kinesiophobia(TSK) to assess fear of movement; and the Short Form(SF-36) in order to assess self-perceived health-related quality of life. Statistical analysis is going to be used in this research through the SPSS 20.0 package program.	Today, low back pain is one of the most common health problems in the world in which create a considerable individual, social and financial burden on the society. Low back pain is classified as specific and nonspecific. While, 10 percent of the paints are suffered from specific low back pain, non-specific low back pain is occured in approximately 90 percent of the population. If low back pain persists for six weeks, it is classified as acute back pain, subacute back pain between six weeks and three months, and chronic low back pain if it lasts for more than three months.~Chronic low back pain (CLBP) is a complex problem that continues for a long time without a cause and is the most common in the musculoskeletal system, leading to disability. Individuals with CLBP have a lower quality of life than the general population. It causes individuals to decrease their activities due to pain and prepares the ground for the continuation of pain. Lack of movement caused by pain in individuals; It negatively affects the quality of life by triggering the continuation of symptoms, causing a decrease in functional levels, limitation in daily life activities, problems in family and work life. There are many physical, psychological and social factors that cause low back pain to become chronic. Age, race, occupation, obesity, smoking, alcohol consumption and stress are the most important factors that trigger the chronicity of low back pain. The effectiveness of a multidisciplinary treatment program and determination of risk factors in the management of CLBP is known. Treatment approaches include medical treatment, surgical treatment and physiotherapy applications. In physiotherapy programs, patient education, back schools, electrotherapy applications, traction, massage, superficial heat applications, corsets and exercise approaches are used. Stretching exercises, trunk flexion-extension exercises, resistantce exercises, stabilization exercises are the main exercise approaches used to cope with low back pain. In addition to exercises performed under the supervision of a physiotherapist, home exercise programs are also provided for low back pain. Stabilization exercises have various benefits on the musculoskeletal system. Stabilization exercises that aim to protect and support the spine by regenerating muscle control, applied in muscle activation losses caused by injury or degenerative changes, increase strength and flexibility. Stabilization exercise has been reported to be effective in reducing pain and improving functional disability in patients with nonspecific CLBP, improving individuals psychologically and also increasing the quality of life of patients. Stabilization exercises have been found to be effective in increasing the cross-sectional area of the lumbar multifidus muscle, which is one of the muscles needed to maintain the proper stability of the spine.~Today, in line with technological developments, the use of common information processing, sensor networks, three-dimensional (3D) computer graphics, internet and mobile phone applications in healthcare services is widespread. Telerehabilitation refers to the provision of rehabilitation services through information and communication technologies. Clinically this term; covers a range of rehabilitation and habilitation services including assessment, monitoring, prevention, response, control, training, consultation and counseling. Along with telerehabilitation, rehabilitation practices can be applied in health centers as well as homes, schools or community-based work sites. Mostly, there are studies in the literature regarding its use in musculoskeletal disorders, coronary heart disease, some types of cancer, type 2 diabetes, hypertension and physically disabled individuals. Due to the social distance and isolation, which are the effects of the covid-19, which spread in a short time in our country and all over the world, there are disruptions in individuals' continuing their treatment. Telerehabilitation allows one-to-one physiotherapist-patient meetings without the need for contact and provides flexibility to patients in terms of time. Exercise is one of the treatments that physiotherapists can give using telerehabilitation. With the applications made with telerehabilitation, individuals are provided to take an active role in their own rehabilitation and individuals can have the ability to manage themselves.	The Effects of Telerehabilitation and Supervised Stabilization Exercises on Pain, Functionality, Kinesiophobia and Quality of Life in Individuals With Nonspecific Chronic Low Back Pain: A Single Blind Randomized Controlled Trial	Low Back Pain	* Other: Supervised Group * Other: Telerehabilitation group	Inclusion Criteria:~Having non-specific chronic low back pain~Non-specific chronic low back pain ⩾three months~Being over the age of 18~Score of ⩾4 on the Roland-Morris Disability Questionnaire (RMQ)~Agree to voluntarily participate in the research~Exclusion Criteria:~Presence of lumbar stenosis~Presence of clinical signs or symptoms of radiculopathy~Diagnosis of spondylolisthesis~Diagnosis of fibromyalgia~Treatment with corticosteroids or other drugs in the previous two weeks~History of spinal surgery~Presence of central or peripheral system pathology (i.e. stroke, peripheral nerve etc.)~Have received a physiotherapy treatment for low back pain before 6 months	18 Years	null	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: The individuals are randomly allocated into supervised group, telerehabilitation group and control group Masking: Single	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Oswestry Disability Index(ODI) \| The Oswestry Disability Index(ODI) is an extremely important tool that researchers and disability evaluators use to measure a patient's permanent functional disability. The test is considered the 'gold standard' of low back functional outcome tools. Scores between 0-5 are given for each question on the scale consisting of 10 questions. Questions are on travel, social life, sex life, sleeping, standing, sitting, walking, lifting things and personal precautions. Maximum score is 50, minimum score is 0. \| Change between baseline and 4 weeks \| \| Visual Analogue Scale(VAS) \| The Visual Analog Scale (VAS) is a scale used to determine the intensity of pain experienced by individuals. It consists of a line approximately 10-15 cm long; the patient is asked to mark his pain level on the line between the two endpoints. The distance between 'no pain at all' and the mark then defines the subject's pain the left side means no pain with 0 points, while the right side means 10 points the worst pain ever. \| Change between baseline and 4 weeks \| \| Tampa Scale for Kinesiophobia(TSK) \| The Tampa Scale of Kinesiophobiais (TSK) is 17 items a self-reporting questionnaire based on evaluation of fear of movement, fear of physical activity, and fear avoidance. It was first developed to distinguish between non-excessive fear and phobia in patients with chronic musculoskeletal pain, specifically the fear of movement in patients with chronic low back pain then widely used for different parts of the body. The questionnaire using 4 points to assess that are based on; the model of fear-avoidance, fear of work-related activities, fear of movement, and fear of re-injury.(1 = Strongly Disagree, 4 = Strongly Agree).The total score of the scale range from 17-68, where 17 means no kinesiophobia, 68 means severe kinesiophobia. \| Change between baseline and 4 weeks \| \| Short Form(SF-36) \| The 36-Item Short Form Survey (SF-36) is an oft-used, well-researched, self-reported measure of health. It comprises 36 questions which cover eight domains of health:1) Limitations in physical activities because of health problems 2) Limitations in social activities because of physical or emotional problems 3) Limitations in usual role activities because of physical health problems 4) Bodily pain 5) General mental health (psychological distress and well-being) 6) Limitations in usual role activities because of emotional problems 7) Vitality (energy and fatigue) 8) General health perceptions. The SF-36 is often used as a measure of a person or population's quality of life (QOL). In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. \| Change between baseline and 4 weeks \|		low back pain, chronic pain, exercise, quality of life, telerehabilitation	Back Pain, Low Back Pain, Pain, Neurologic Manifestations	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Supervised Group<br>24 individuals will participate in the Supervised group. Patients in the supervised group will be treated individually by the researcher at the hospital. During the application, individuals will apply ten different stabilization exercises in company with a physiotherapist. Exercises will be applied under the supervision of a physiotherapist in the center where the work will be done for 20-30 minutes in each session, three days a week, for a total of 12 sessions for four weeks. The exercises program to be applied to the participants in the group is listed below: Supine position; Abdominal bracing, while continuing the abdominal bracing; heel slides, bridging, 90 degrees hip flexion. Quadruped position; Abdominal bracing while continuing the abdominal bracing; single arm lift, single leg lift, cross-arm leg raises activities. Standing position; Abdominal bracing. \| Other: Supervised Group<br>* Individuals will apply ten different stabilization exercises in company with a physiotherapist.<br>\| \| Experimental: Telerehabilitation Group<br>24 individuals will participate in the Telerehabilitation group. Patients in the telerehabilitation group will attend the treatment from their homes. The exercises will be performed online with the patient by the researcher physiotherapist and supervised through the video conference or phone. The same stabilization exercises will be applied to the participants in the supervised group. Exercises will be applied for 20-30 minutes in each session, three days a week, for a total of 12 sessions for four weeks. \| Other: Telerehabilitation group<br>* Same stabilization exercises will be performed online with the patient by the researcher physiotherapist and supervised through the video conference or phone.<br>\| \| No Intervention: Control Group<br> \| \|	The Effects of Telerehabilitation and Supervised Stabilization Exercises in Individuals With Nonspecific Chronic Low Back Pain Study Overview ================= Brief Summary ----------------- This study aims to investigate the effects of telerehabilitation and supervised stabilization exercises on pain, functionality, kinesophobia and quality of life in individuals with non-specific chronic low back pain. 72 individuals who voluntarily agree to participate in the study will be included. This study divides the patients in three groups: the supervised group: face-to-face stabilization exercises are applied, the telerehabilitation group: treatment through online meetings, and the control group: patients will do home-based exercises that prescribed by physiothrerapist. Evaluations will be made by the same physiotherapist. The researcher who will make the measurements in this study will not know which treatment program was applied to the participants. In this study, The same stabilization exercises will be applied in three different groups. Ten different stabilization exercises will be applied to the participants. Exercises will be performed for 20-30 minutes in each session, three times a week, for four weeks in total, twelve sessions. Clinical and demographic data of the 72 people participating in the study will be taken before treatment. Participants will also fill out questionnaires before and after the treatment that involve; the Oswestry Disability Index to measure(ODI) daily life activity limitations; the Visual Analogue Scale(VAS) for assessing the intensity of pain; Tampa Scale for Kinesiophobia(TSK) to assess fear of movement; and the Short Form(SF-36) in order to assess self-perceived health-related quality of life. Statistical analysis is going to be used in this research through the SPSS 20.0 package program. Detailed Description ----------------- Today, low back pain is one of the most common health problems in the world in which create a considerable individual, social and financial burden on the society. Low back pain is classified as specific and nonspecific. While, 10 percent of the paints are suffered from specific low back pain, non-specific low back pain is occured in approximately 90 percent of the population. If low back pain persists for six weeks, it is classified as acute back pain, subacute back pain between six weeks and three months, and chronic low back pain if it lasts for more than three months. Chronic low back pain (CLBP) is a complex problem that continues for a long time without a cause and is the most common in the musculoskeletal system, leading to disability. Individuals with CLBP have a lower quality of life than the general population. It causes individuals to decrease their activities due to pain and prepares the ground for the continuation of pain. Lack of movement caused by pain in individuals; It negatively affects the quality of life by triggering the continuation of symptoms, causing a decrease in functional levels, limitation in daily life activities, problems in family and work life. There are many physical, psychological and social factors that cause low back pain to become chronic. Age, race, occupation, obesity, smoking, alcohol consumption and stress are the most important factors that trigger the chronicity of low back pain. The effectiveness of a multidisciplinary treatment program and determination of risk factors in the management of CLBP is known. Treatment approaches include medical treatment, surgical treatment and physiotherapy applications. In physiotherapy programs, patient education, back schools, electrotherapy applications, traction, massage, superficial heat applications, corsets and exercise approaches are used. Stretching exercises, trunk flexion-extension exercises, resistantce exercises, stabilization exercises are the main exercise approaches used to cope with low back pain. In addition to exercises performed under the supervision of a physiotherapist, home exercise programs are also provided for low back pain. Stabilization exercises have various benefits on the musculoskeletal system. Stabilization exercises that aim to protect and support the spine by regenerating muscle control, applied in muscle activation losses caused by injury or degenerative changes, increase strength and flexibility. Stabilization exercise has been reported to be effective in reducing pain and improving functional disability in patients with nonspecific CLBP, improving individuals psychologically and also increasing the quality of life of patients. Stabilization exercises have been found to be effective in increasing the cross-sectional area of the lumbar multifidus muscle, which is one of the muscles needed to maintain the proper stability of the spine. Today, in line with technological developments, the use of common information processing, sensor networks, three-dimensional (3D) computer graphics, internet and mobile phone applications in healthcare services is widespread. Telerehabilitation refers to the provision of rehabilitation services through information and communication technologies. Clinically this term; covers a range of rehabilitation and habilitation services including assessment, monitoring, prevention, response, control, training, consultation and counseling. Along with telerehabilitation, rehabilitation practices can be applied in health centers as well as homes, schools or community-based work sites. Mostly, there are studies in the literature regarding its use in musculoskeletal disorders, coronary heart disease, some types of cancer, type 2 diabetes, hypertension and physically disabled individuals. Due to the social distance and isolation, which are the effects of the covid-19, which spread in a short time in our country and all over the world, there are disruptions in individuals' continuing their treatment. Telerehabilitation allows one-to-one physiotherapist-patient meetings without the need for contact and provides flexibility to patients in terms of time. Exercise is one of the treatments that physiotherapists can give using telerehabilitation. With the applications made with telerehabilitation, individuals are provided to take an active role in their own rehabilitation and individuals can have the ability to manage themselves. Official Title ----------------- The Effects of Telerehabilitation and Supervised Stabilization Exercises on Pain, Functionality, Kinesiophobia and Quality of Life in Individuals With Nonspecific Chronic Low Back Pain: A Single Blind Randomized Controlled Trial Conditions ----------------- Low Back Pain Intervention / Treatment ----------------- * Other: Supervised Group * Other: Telerehabilitation group Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Having non-specific chronic low back pain Non-specific chronic low back pain ⩾three months Being over the age of 18 Score of ⩾4 on the Roland-Morris Disability Questionnaire (RMQ) Agree to voluntarily participate in the research Exclusion Criteria: Presence of lumbar stenosis Presence of clinical signs or symptoms of radiculopathy Diagnosis of spondylolisthesis Diagnosis of fibromyalgia Treatment with corticosteroids or other drugs in the previous two weeks History of spinal surgery Presence of central or peripheral system pathology (i.e. stroke, peripheral nerve etc.) Have received a physiotherapy treatment for low back pain before 6 months Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: The individuals are randomly allocated into supervised group, telerehabilitation group and control group Masking: Single Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Supervised Group<br>24 individuals will participate in the Supervised group. Patients in the supervised group will be treated individually by the researcher at the hospital. During the application, individuals will apply ten different stabilization exercises in company with a physiotherapist. Exercises will be applied under the supervision of a physiotherapist in the center where the work will be done for 20-30 minutes in each session, three days a week, for a total of 12 sessions for four weeks. The exercises program to be applied to the participants in the group is listed below: Supine position; Abdominal bracing, while continuing the abdominal bracing; heel slides, bridging, 90 degrees hip flexion. Quadruped position; Abdominal bracing while continuing the abdominal bracing; single arm lift, single leg lift, cross-arm leg raises activities. Standing position; Abdominal bracing. \| Other: Supervised Group<br>* Individuals will apply ten different stabilization exercises in company with a physiotherapist.<br>\| \| Experimental: Telerehabilitation Group<br>24 individuals will participate in the Telerehabilitation group. Patients in the telerehabilitation group will attend the treatment from their homes. The exercises will be performed online with the patient by the researcher physiotherapist and supervised through the video conference or phone. The same stabilization exercises will be applied to the participants in the supervised group. Exercises will be applied for 20-30 minutes in each session, three days a week, for a total of 12 sessions for four weeks. \| Other: Telerehabilitation group<br>* Same stabilization exercises will be performed online with the patient by the researcher physiotherapist and supervised through the video conference or phone.<br>\| \| No Intervention: Control Group<br> \| \| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Oswestry Disability Index(ODI) \| The Oswestry Disability Index(ODI) is an extremely important tool that researchers and disability evaluators use to measure a patient's permanent functional disability. The test is considered the 'gold standard' of low back functional outcome tools. Scores between 0-5 are given for each question on the scale consisting of 10 questions. Questions are on travel, social life, sex life, sleeping, standing, sitting, walking, lifting things and personal precautions. Maximum score is 50, minimum score is 0. \| Change between baseline and 4 weeks \| \| Visual Analogue Scale(VAS) \| The Visual Analog Scale (VAS) is a scale used to determine the intensity of pain experienced by individuals. It consists of a line approximately 10-15 cm long; the patient is asked to mark his pain level on the line between the two endpoints. The distance between 'no pain at all' and the mark then defines the subject's pain the left side means no pain with 0 points, while the right side means 10 points the worst pain ever. \| Change between baseline and 4 weeks \| \| Tampa Scale for Kinesiophobia(TSK) \| The Tampa Scale of Kinesiophobiais (TSK) is 17 items a self-reporting questionnaire based on evaluation of fear of movement, fear of physical activity, and fear avoidance. It was first developed to distinguish between non-excessive fear and phobia in patients with chronic musculoskeletal pain, specifically the fear of movement in patients with chronic low back pain then widely used for different parts of the body. The questionnaire using 4 points to assess that are based on; the model of fear-avoidance, fear of work-related activities, fear of movement, and fear of re-injury.(1 = Strongly Disagree, 4 = Strongly Agree).The total score of the scale range from 17-68, where 17 means no kinesiophobia, 68 means severe kinesiophobia. \| Change between baseline and 4 weeks \| \| Short Form(SF-36) \| The 36-Item Short Form Survey (SF-36) is an oft-used, well-researched, self-reported measure of health. It comprises 36 questions which cover eight domains of health:1) Limitations in physical activities because of health problems 2) Limitations in social activities because of physical or emotional problems 3) Limitations in usual role activities because of physical health problems 4) Bodily pain 5) General mental health (psychological distress and well-being) 6) Limitations in usual role activities because of emotional problems 7) Vitality (energy and fatigue) 8) General health perceptions. The SF-36 is often used as a measure of a person or population's quality of life (QOL). In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. \| Change between baseline and 4 weeks \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- low back pain, chronic pain, exercise, quality of life, telerehabilitation
NCT04055753	Study to Assess TOPO2A as a Biomarker for Sensitivity to Doxorubicin/Doxil in Soft Tissue Sarcoma	The primary aim of this study is to determine the utility of TOPO2A as a biomarker for sensitivity to doxorubicin or its derivatives. Patients whose planned therapy is doxorucibin or doxil single agent may be enrolled into this trial. In light of its recent FDA approval and differing mechanism of action, patients receiving olaratumab along with doxorubicin will be eligible for this study.~Doxorucibin will be administered at standard 21-day intervals. Doxil will be administered at standard 28-day intervals. Response to therapy will be assessed using standard RECIST criteria every 2 cycles. Patients will continue on study until disease progression, prohibitive toxicity or completion of cumulative dose of 450 mg/m2 of either agent. Overall survival will be assessed every 3 months for 1 year, every 6 months in year 2 and, annually until death.		A Study to Assess Topoisomerase II Alpha (TOPO2A) as a Biomarker for Sensitivity to Doxorubicin/Doxil in Soft Tissue Sarcoma	Soft Tissue Sarcoma	* Drug: Doxil * Drug: Doxorubicin	Inclusion Criteria:~Patients must consent to providing tumor tissue prior to initiation of therapy if sufficient archival tissue is not available. Archival tissue is permitted if no other anticancer treatment was given after the tissue was obtained (not including surgery or radiation). If a biopsy is required, the treating physician should ensure that this can be done safely.~Patients with STS will be eligible for the trial if their next planned chemotherapy will include single agent doxorubicin or doxil. Patients who will be receiving concomitant therapy with olaratumab will be allowed to participate.~Sarcoma subtypes of angiosarcoma, epithelioid sarcoma, leiomyosarcoma, fibrosarcoma, myxofibrosarcoma, synovial sarcoma, pleomorphic rhabdomyosarcoma, undifferentiated pleomorphic sarcoma, liposarcoma (excluding well-differentiated) and malignant peripheral nerve sheath tumor will be included. These are subtypes for which a targeted therapy is not standard of care. All other subtypes will be included on a case by case basis as determined by the principle investigator.~≥ 18 years of age.~Ability to understand and willingness to sign a written informed consent and HIPPA document~Measurable disease by RECIST 1.1 criteria (at least one target lesion outside of previous radiation fields or progressed within a previous radiation field).~Life expectancy of at least 3 months.~All women of childbearing potential must have a negative serum pregnancy test and all subjects must agree to use effective means of contraception (surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose. Post-menopausal women must meet the criteria of 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >35 mIU/ml (IU/L).~Patients must have normal organ and marrow function as defined below~Absolute neutrophil count > 1,500/mcL~Platelets > 100,000/mcL~Total bilirubin ≤ 1.5 X upper limit of normal (ULN)~AST/ALT (SGOT/SGPT) ≤ 3 X institutional normal limits; if liver metastases are present then ≤ 5 X ULN are allowed~Exclusion Criteria:~Patients may not be receiving any other investigational agents, chemotherapy, radiation therapy or hormonal therapy (i.e. aromatase inhibitors for leiomyosarcoma), with the exception of olaratumab~Pregnant or breast feeding women.~Any concomitant medical issue that in the opinion of the treating physician would confound survival from sarcoma (e.g. other active cancer, symptomatic brain metastases, cardiac conditions).	18 Years	null	All	No		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Best overall response \| best response recorded from the start of the treatment until disease progression/recurrence \| 6 years \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Overall survival \| defined as the time from initiation of treatment until death from any cause \| 6 years \|		Doxorubicin, Antibiotics, Antineoplastic, Antineoplastic Agents, Topoisomerase II Inhibitors, Topoisomerase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Doxorubicin<br> \| Drug: Doxorubicin<br>* Doxorubicin 75 mg/m2, IV over 5-15 min OR Continuous infusion over 48-72 hours<br>\| \| Doxil<br> \| Drug: Doxil<br>* Doxil 50 mg/m2, as per institutional standard<br>\|	Study to Assess TOPO2A as a Biomarker for Sensitivity to Doxorubicin/Doxil in Soft Tissue Sarcoma Study Overview ================= Brief Summary ----------------- The primary aim of this study is to determine the utility of TOPO2A as a biomarker for sensitivity to doxorubicin or its derivatives. Patients whose planned therapy is doxorucibin or doxil single agent may be enrolled into this trial. In light of its recent FDA approval and differing mechanism of action, patients receiving olaratumab along with doxorubicin will be eligible for this study. Doxorucibin will be administered at standard 21-day intervals. Doxil will be administered at standard 28-day intervals. Response to therapy will be assessed using standard RECIST criteria every 2 cycles. Patients will continue on study until disease progression, prohibitive toxicity or completion of cumulative dose of 450 mg/m2 of either agent. Overall survival will be assessed every 3 months for 1 year, every 6 months in year 2 and, annually until death. Official Title ----------------- A Study to Assess Topoisomerase II Alpha (TOPO2A) as a Biomarker for Sensitivity to Doxorubicin/Doxil in Soft Tissue Sarcoma Conditions ----------------- Soft Tissue Sarcoma Intervention / Treatment ----------------- * Drug: Doxil * Drug: Doxorubicin Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients must consent to providing tumor tissue prior to initiation of therapy if sufficient archival tissue is not available. Archival tissue is permitted if no other anticancer treatment was given after the tissue was obtained (not including surgery or radiation). If a biopsy is required, the treating physician should ensure that this can be done safely. Patients with STS will be eligible for the trial if their next planned chemotherapy will include single agent doxorubicin or doxil. Patients who will be receiving concomitant therapy with olaratumab will be allowed to participate. Sarcoma subtypes of angiosarcoma, epithelioid sarcoma, leiomyosarcoma, fibrosarcoma, myxofibrosarcoma, synovial sarcoma, pleomorphic rhabdomyosarcoma, undifferentiated pleomorphic sarcoma, liposarcoma (excluding well-differentiated) and malignant peripheral nerve sheath tumor will be included. These are subtypes for which a targeted therapy is not standard of care. All other subtypes will be included on a case by case basis as determined by the principle investigator. ≥ 18 years of age. Ability to understand and willingness to sign a written informed consent and HIPPA document Measurable disease by RECIST 1.1 criteria (at least one target lesion outside of previous radiation fields or progressed within a previous radiation field). Life expectancy of at least 3 months. All women of childbearing potential must have a negative serum pregnancy test and all subjects must agree to use effective means of contraception (surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose. Post-menopausal women must meet the criteria of 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >35 mIU/ml (IU/L). Patients must have normal organ and marrow function as defined below Absolute neutrophil count > 1,500/mcL Platelets > 100,000/mcL Total bilirubin ≤ 1.5 X upper limit of normal (ULN) AST/ALT (SGOT/SGPT) ≤ 3 X institutional normal limits; if liver metastases are present then ≤ 5 X ULN are allowed Exclusion Criteria: Patients may not be receiving any other investigational agents, chemotherapy, radiation therapy or hormonal therapy (i.e. aromatase inhibitors for leiomyosarcoma), with the exception of olaratumab Pregnant or breast feeding women. Any concomitant medical issue that in the opinion of the treating physician would confound survival from sarcoma (e.g. other active cancer, symptomatic brain metastases, cardiac conditions). Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Doxorubicin<br> \| Drug: Doxorubicin<br>* Doxorubicin 75 mg/m2, IV over 5-15 min OR Continuous infusion over 48-72 hours<br>\| \| Doxil<br> \| Drug: Doxil<br>* Doxil 50 mg/m2, as per institutional standard<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Best overall response \| best response recorded from the start of the treatment until disease progression/recurrence \| 6 years \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Overall survival \| defined as the time from initiation of treatment until death from any cause \| 6 years \|
NCT05016843	The Study of Internet-delivered, Transdiagnostic Treatments for Anxiety and Depression	Anxiety and depression are common psychiatric disorders, resulting in suffering and impaired functioning for the individual. Today, most psychological treatments are disorder specific, even tough comorbidity between depression and anxiety and different anxiety disorders is rule rather than exception. Transdiagnostic treatments target the common features between depression and anxiety disorders and has shown to be as effective as disorder specific treatments in reducing symptoms of the disorders. Unified protocol and Affect phobia treatment are two types of transdiagnostic treatments that, to our knowledge, never been compared in research before. Internet-administered treatment presents a promising way to increase availability of psychotherapeutic interventions such as transdiagnostic treatments. However, questions regarding the optimal treatment length and level of support remain unanswered. The aim of this study is to examine two internet-administered transdiagnostic treatments and their effect on anxiety and depression, and to investigate the impact of treatment length and access to a moderated forum.~The study will investigate three factors: type of transdiagnostic treatment, length of treatment and whether patients have access to a moderated forum or not. 2400 participants with anxiety and/or depression will be randomly assigned to one of 12 subgroups and subsequently offered treatment based on differing combinations of the previously mentioned factors (200 participants/arm). The treatment conditions are internet-administered cognitive, behavioral treatment (CBT) Unified protocol and the psychodynamic Affect phobia treatment as well as a waitlist control group. Participants will also be randomized to either 8 or 16 weeks of treatment and access to a moderated forum or not.~Primary outcome measures will be the Patient Health Questionnaire, the Generalized Anxiety Disorder 7-item scale and the Brief Quality of Life scale. Negative effects of treatment will also be assessed. In addition to pre- and post-treatment measurements, the study includes one mid-treatment and three follow-up assessments (6, 12 and 24 months).		The Study of Internet-delivered, Transdiagnostic Treatments for Anxiety and Depression (TRAnsdiagnostisk BEhandling (Elektronisk))	Anxiety Disorders, Depression	* Behavioral: Treatment condition: Internet-administered Unified protocol * Behavioral: Treatment condition: Internet-administered Affect phobia treatment * Other: Treatment condition: Waitlist control * Other: Treatment length: 8 weeks * Other: Treatment length: 16 weeks * Other: Access to a moderated forum * Other: No access to a moderated forum	Inclusion Criteria:~Be able to read and write Swedish,~access to a mobile phone/computer,~18 years or older,~GAD-7 ≥ 5 and/or~PHQ-9 ≥ 10.~Exclusion Criteria:~Partaking in other psychological treatment,~has started or adjusted treatment with psychopharmacological drugs for anxiety, worry or depression within the nearest month,~severe depression (PHQ-9 ≥ 20) or suicidal (PHQ-9, item 9>2).	18 Years	null	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Factorial Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Patient Health Questionnaire 9-item scale (PHQ-9) \| The PHQ-9 features nine items for assessing depression in a clinical context and screening of depression in the general population. \| Through study completion, an average of 2 years. \| \| Generalised Anxiety Disorder 7- item scale (GAD-7) \| The GAD-7 features seven items for assessing anxiety and screening for generalized anxiety disorder. \| Through study completion, an average of 2 years. \| \| Brunnsviken Brief Quality of Life Scale (BBQ) \| The BBQ features 12 items concerning 6 areas of life rated on importance and satisfaction. \| Through study completion, an average of 2 years. \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| The Personality Inventory for DSM Short Form (PID-5) \| The PID-5 is a self-rated measure of personality-related problems featuring 25 items. \| Baseline only. \| \| Negative Effects Questionnaire (NEQ) \| The NEQ measures unwanted effects of treatments. \| At post-treatment only (which is week 8 or 16 depending on treatment allocation). \| \| Reflective Functioning Questionnaire 8 (RFQ-8) \| RFQ features 8 items assessing the ability to understand mental states of the self and others. \| Through study completion, an average of 2 years. \|		Depression, Depressive Disorder, Anxiety Disorders, Behavioral Symptoms, Mood Disorders, Mental Disorders	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: CBT, 8 weeks and access to forum.<br> \| Behavioral: Treatment condition: Internet-administered Unified protocol<br>* Treatment condition:~The cognitive, behavioral treatment Unified protocol is a transdiagnostic treatment for anxiety and depression. Participants are taught five techniques in order to find new and more helpful ways to react to hindering thoughts and feelings: mindfulness, cognitive flexibility, identify and reduce behavioral avoidance, increase willingness to experience physiological sensations and exposure. The intervention is delivered online through a secure platform. Modules consist of text and the participants can work with the material whenever they wish to. Participants gain access to a new treatment modul every week.<br>Other: Treatment length: 8 weeks<br>* Participants will partake in their treatment condition for 8 weeks.<br>Other: Access to a moderated forum<br>* During their treatment, participants will have access to a discussion forum moderated by a clinician. Participants are encouraged to discuss questions and experiences related to their treatment condition.<br>\| \| Experimental: CBT, 16 weeks and access to forum.<br> \| Behavioral: Treatment condition: Internet-administered Unified protocol<br>* Treatment condition:~The cognitive, behavioral treatment Unified protocol is a transdiagnostic treatment for anxiety and depression. Participants are taught five techniques in order to find new and more helpful ways to react to hindering thoughts and feelings: mindfulness, cognitive flexibility, identify and reduce behavioral avoidance, increase willingness to experience physiological sensations and exposure. The intervention is delivered online through a secure platform. Modules consist of text and the participants can work with the material whenever they wish to. Participants gain access to a new treatment modul every week.<br>Other: Treatment length: 16 weeks<br>* Participants will partake in their treatment condition for 16 weeks.<br>Other: No access to a moderated forum<br>* Participants will not have access to a moderated forum, hence their treatment is self-guided.<br>\| \| Experimental: CBT, 8 weeks and no access to forum.<br> \| Behavioral: Treatment condition: Internet-administered Unified protocol<br>* Treatment condition:~The cognitive, behavioral treatment Unified protocol is a transdiagnostic treatment for anxiety and depression. Participants are taught five techniques in order to find new and more helpful ways to react to hindering thoughts and feelings: mindfulness, cognitive flexibility, identify and reduce behavioral avoidance, increase willingness to experience physiological sensations and exposure. The intervention is delivered online through a secure platform. Modules consist of text and the participants can work with the material whenever they wish to. Participants gain access to a new treatment modul every week.<br>Other: Treatment length: 8 weeks<br>* Participants will partake in their treatment condition for 8 weeks.<br>Other: No access to a moderated forum<br>* Participants will not have access to a moderated forum, hence their treatment is self-guided.<br>\| \| Experimental: CBT, 16 weeks and no access to forum.<br> \| Behavioral: Treatment condition: Internet-administered Unified protocol<br>* Treatment condition:~The cognitive, behavioral treatment Unified protocol is a transdiagnostic treatment for anxiety and depression. Participants are taught five techniques in order to find new and more helpful ways to react to hindering thoughts and feelings: mindfulness, cognitive flexibility, identify and reduce behavioral avoidance, increase willingness to experience physiological sensations and exposure. The intervention is delivered online through a secure platform. Modules consist of text and the participants can work with the material whenever they wish to. Participants gain access to a new treatment modul every week.<br>Other: Treatment length: 16 weeks<br>* Participants will partake in their treatment condition for 16 weeks.<br>Other: Access to a moderated forum<br>* During their treatment, participants will have access to a discussion forum moderated by a clinician. Participants are encouraged to discuss questions and experiences related to their treatment condition.<br>\| \| Experimental: Psychodynamic therapy, 8 weeks and access to forum.<br> \| Behavioral: Treatment condition: Internet-administered Affect phobia treatment<br>* The aim of psychodynamic Affect phobia treatment is for the patient to reach an intellectual and emotional understanding of his/hers problems. The goal of the treatment is for participants to decrease emotional avoidance and start to approach emotions and increase emotional awareness. Participants are taught this through linking their symptoms to their emotional avoidance, observe frequent and maladaptive patterns in relationships and see how these are linked to emotional avoidance. The intervention is delivered online through a secure platform. Modules consist of text and the participants can work with the material whenever they wish to. Participants gain access to a new treatment modul every week.<br>Other: Treatment length: 8 weeks<br>* Participants will partake in their treatment condition for 8 weeks.<br>Other: Access to a moderated forum<br>* During their treatment, participants will have access to a discussion forum moderated by a clinician. Participants are encouraged to discuss questions and experiences related to their treatment condition.<br>\| \| Experimental: Psychodynamic therapy, 16 weeks and access to forum.<br> \| Behavioral: Treatment condition: Internet-administered Affect phobia treatment<br>* The aim of psychodynamic Affect phobia treatment is for the patient to reach an intellectual and emotional understanding of his/hers problems. The goal of the treatment is for participants to decrease emotional avoidance and start to approach emotions and increase emotional awareness. Participants are taught this through linking their symptoms to their emotional avoidance, observe frequent and maladaptive patterns in relationships and see how these are linked to emotional avoidance. The intervention is delivered online through a secure platform. Modules consist of text and the participants can work with the material whenever they wish to. Participants gain access to a new treatment modul every week.<br>Other: Treatment length: 16 weeks<br>* Participants will partake in their treatment condition for 16 weeks.<br>Other: Access to a moderated forum<br>* During their treatment, participants will have access to a discussion forum moderated by a clinician. Participants are encouraged to discuss questions and experiences related to their treatment condition.<br>\| \| Experimental: Psychodynamic therapy, 8 weeks and no access to forum.<br> \| Behavioral: Treatment condition: Internet-administered Affect phobia treatment<br>* The aim of psychodynamic Affect phobia treatment is for the patient to reach an intellectual and emotional understanding of his/hers problems. The goal of the treatment is for participants to decrease emotional avoidance and start to approach emotions and increase emotional awareness. Participants are taught this through linking their symptoms to their emotional avoidance, observe frequent and maladaptive patterns in relationships and see how these are linked to emotional avoidance. The intervention is delivered online through a secure platform. Modules consist of text and the participants can work with the material whenever they wish to. Participants gain access to a new treatment modul every week.<br>Other: Treatment length: 8 weeks<br>* Participants will partake in their treatment condition for 8 weeks.<br>Other: No access to a moderated forum<br>* Participants will not have access to a moderated forum, hence their treatment is self-guided.<br>\| \| Experimental: Psychodynamic therapy, 16 weeks and no access to forum.<br> \| Behavioral: Treatment condition: Internet-administered Affect phobia treatment<br>* The aim of psychodynamic Affect phobia treatment is for the patient to reach an intellectual and emotional understanding of his/hers problems. The goal of the treatment is for participants to decrease emotional avoidance and start to approach emotions and increase emotional awareness. Participants are taught this through linking their symptoms to their emotional avoidance, observe frequent and maladaptive patterns in relationships and see how these are linked to emotional avoidance. The intervention is delivered online through a secure platform. Modules consist of text and the participants can work with the material whenever they wish to. Participants gain access to a new treatment modul every week.<br>Other: Treatment length: 16 weeks<br>* Participants will partake in their treatment condition for 16 weeks.<br>Other: No access to a moderated forum<br>* Participants will not have access to a moderated forum, hence their treatment is self-guided.<br>\| \| Experimental: Waitlist, 8 weeks and access to forum.<br> \| Other: Treatment condition: Waitlist control<br>* The waitlist condition is a control condition without any intervention.<br>Other: Treatment length: 8 weeks<br>* Participants will partake in their treatment condition for 8 weeks.<br>Other: Access to a moderated forum<br>* During their treatment, participants will have access to a discussion forum moderated by a clinician. Participants are encouraged to discuss questions and experiences related to their treatment condition.<br>\| \| Experimental: Waitlist, 16 weeks and access to forum.<br> \| Other: Treatment condition: Waitlist control<br>* The waitlist condition is a control condition without any intervention.<br>Other: Treatment length: 16 weeks<br>* Participants will partake in their treatment condition for 16 weeks.<br>Other: Access to a moderated forum<br>* During their treatment, participants will have access to a discussion forum moderated by a clinician. Participants are encouraged to discuss questions and experiences related to their treatment condition.<br>\| \| Experimental: Waitlist, 8 weeks and no access to forum.<br> \| Other: Treatment condition: Waitlist control<br>* The waitlist condition is a control condition without any intervention.<br>Other: Treatment length: 8 weeks<br>* Participants will partake in their treatment condition for 8 weeks.<br>Other: No access to a moderated forum<br>* Participants will not have access to a moderated forum, hence their treatment is self-guided.<br>\| \| Experimental: Waitlist, 16 weeks and no access to forum.<br> \| Other: Treatment condition: Waitlist control<br>* The waitlist condition is a control condition without any intervention.<br>Other: Treatment length: 16 weeks<br>* Participants will partake in their treatment condition for 16 weeks.<br>Other: No access to a moderated forum<br>* Participants will not have access to a moderated forum, hence their treatment is self-guided.<br>\|	The Study of Internet-delivered, Transdiagnostic Treatments for Anxiety and Depression Study Overview ================= Brief Summary ----------------- Anxiety and depression are common psychiatric disorders, resulting in suffering and impaired functioning for the individual. Today, most psychological treatments are disorder specific, even tough comorbidity between depression and anxiety and different anxiety disorders is rule rather than exception. Transdiagnostic treatments target the common features between depression and anxiety disorders and has shown to be as effective as disorder specific treatments in reducing symptoms of the disorders. Unified protocol and Affect phobia treatment are two types of transdiagnostic treatments that, to our knowledge, never been compared in research before. Internet-administered treatment presents a promising way to increase availability of psychotherapeutic interventions such as transdiagnostic treatments. However, questions regarding the optimal treatment length and level of support remain unanswered. The aim of this study is to examine two internet-administered transdiagnostic treatments and their effect on anxiety and depression, and to investigate the impact of treatment length and access to a moderated forum. The study will investigate three factors: type of transdiagnostic treatment, length of treatment and whether patients have access to a moderated forum or not. 2400 participants with anxiety and/or depression will be randomly assigned to one of 12 subgroups and subsequently offered treatment based on differing combinations of the previously mentioned factors (200 participants/arm). The treatment conditions are internet-administered cognitive, behavioral treatment (CBT) Unified protocol and the psychodynamic Affect phobia treatment as well as a waitlist control group. Participants will also be randomized to either 8 or 16 weeks of treatment and access to a moderated forum or not. Primary outcome measures will be the Patient Health Questionnaire, the Generalized Anxiety Disorder 7-item scale and the Brief Quality of Life scale. Negative effects of treatment will also be assessed. In addition to pre- and post-treatment measurements, the study includes one mid-treatment and three follow-up assessments (6, 12 and 24 months). Official Title ----------------- The Study of Internet-delivered, Transdiagnostic Treatments for Anxiety and Depression (TRAnsdiagnostisk BEhandling (Elektronisk)) Conditions ----------------- Anxiety Disorders, Depression Intervention / Treatment ----------------- * Behavioral: Treatment condition: Internet-administered Unified protocol * Behavioral: Treatment condition: Internet-administered Affect phobia treatment * Other: Treatment condition: Waitlist control * Other: Treatment length: 8 weeks * Other: Treatment length: 16 weeks * Other: Access to a moderated forum * Other: No access to a moderated forum Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Be able to read and write Swedish, access to a mobile phone/computer, 18 years or older, GAD-7 ≥ 5 and/or PHQ-9 ≥ 10. Exclusion Criteria: Partaking in other psychological treatment, has started or adjusted treatment with psychopharmacological drugs for anxiety, worry or depression within the nearest month, severe depression (PHQ-9 ≥ 20) or suicidal (PHQ-9, item 9>2). Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Factorial Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: CBT, 8 weeks and access to forum.<br> \| Behavioral: Treatment condition: Internet-administered Unified protocol<br>* Treatment condition: The cognitive, behavioral treatment Unified protocol is a transdiagnostic treatment for anxiety and depression. Participants are taught five techniques in order to find new and more helpful ways to react to hindering thoughts and feelings: mindfulness, cognitive flexibility, identify and reduce behavioral avoidance, increase willingness to experience physiological sensations and exposure. The intervention is delivered online through a secure platform. Modules consist of text and the participants can work with the material whenever they wish to. Participants gain access to a new treatment modul every week.<br>Other: Treatment length: 8 weeks<br>* Participants will partake in their treatment condition for 8 weeks.<br>Other: Access to a moderated forum<br>* During their treatment, participants will have access to a discussion forum moderated by a clinician. Participants are encouraged to discuss questions and experiences related to their treatment condition.<br>\| \| Experimental: CBT, 16 weeks and access to forum.<br> \| Behavioral: Treatment condition: Internet-administered Unified protocol<br>* Treatment condition: The cognitive, behavioral treatment Unified protocol is a transdiagnostic treatment for anxiety and depression. Participants are taught five techniques in order to find new and more helpful ways to react to hindering thoughts and feelings: mindfulness, cognitive flexibility, identify and reduce behavioral avoidance, increase willingness to experience physiological sensations and exposure. The intervention is delivered online through a secure platform. Modules consist of text and the participants can work with the material whenever they wish to. Participants gain access to a new treatment modul every week.<br>Other: Treatment length: 16 weeks<br>* Participants will partake in their treatment condition for 16 weeks.<br>Other: No access to a moderated forum<br>* Participants will not have access to a moderated forum, hence their treatment is self-guided.<br>\| \| Experimental: CBT, 8 weeks and no access to forum.<br> \| Behavioral: Treatment condition: Internet-administered Unified protocol<br>* Treatment condition: The cognitive, behavioral treatment Unified protocol is a transdiagnostic treatment for anxiety and depression. Participants are taught five techniques in order to find new and more helpful ways to react to hindering thoughts and feelings: mindfulness, cognitive flexibility, identify and reduce behavioral avoidance, increase willingness to experience physiological sensations and exposure. The intervention is delivered online through a secure platform. Modules consist of text and the participants can work with the material whenever they wish to. Participants gain access to a new treatment modul every week.<br>Other: Treatment length: 8 weeks<br>* Participants will partake in their treatment condition for 8 weeks.<br>Other: No access to a moderated forum<br>* Participants will not have access to a moderated forum, hence their treatment is self-guided.<br>\| \| Experimental: CBT, 16 weeks and no access to forum.<br> \| Behavioral: Treatment condition: Internet-administered Unified protocol<br>* Treatment condition: The cognitive, behavioral treatment Unified protocol is a transdiagnostic treatment for anxiety and depression. Participants are taught five techniques in order to find new and more helpful ways to react to hindering thoughts and feelings: mindfulness, cognitive flexibility, identify and reduce behavioral avoidance, increase willingness to experience physiological sensations and exposure. The intervention is delivered online through a secure platform. Modules consist of text and the participants can work with the material whenever they wish to. Participants gain access to a new treatment modul every week.<br>Other: Treatment length: 16 weeks<br>* Participants will partake in their treatment condition for 16 weeks.<br>Other: Access to a moderated forum<br>* During their treatment, participants will have access to a discussion forum moderated by a clinician. Participants are encouraged to discuss questions and experiences related to their treatment condition.<br>\| \| Experimental: Psychodynamic therapy, 8 weeks and access to forum.<br> \| Behavioral: Treatment condition: Internet-administered Affect phobia treatment<br>* The aim of psychodynamic Affect phobia treatment is for the patient to reach an intellectual and emotional understanding of his/hers problems. The goal of the treatment is for participants to decrease emotional avoidance and start to approach emotions and increase emotional awareness. Participants are taught this through linking their symptoms to their emotional avoidance, observe frequent and maladaptive patterns in relationships and see how these are linked to emotional avoidance. The intervention is delivered online through a secure platform. Modules consist of text and the participants can work with the material whenever they wish to. Participants gain access to a new treatment modul every week.<br>Other: Treatment length: 8 weeks<br>* Participants will partake in their treatment condition for 8 weeks.<br>Other: Access to a moderated forum<br>* During their treatment, participants will have access to a discussion forum moderated by a clinician. Participants are encouraged to discuss questions and experiences related to their treatment condition.<br>\| \| Experimental: Psychodynamic therapy, 16 weeks and access to forum.<br> \| Behavioral: Treatment condition: Internet-administered Affect phobia treatment<br>* The aim of psychodynamic Affect phobia treatment is for the patient to reach an intellectual and emotional understanding of his/hers problems. The goal of the treatment is for participants to decrease emotional avoidance and start to approach emotions and increase emotional awareness. Participants are taught this through linking their symptoms to their emotional avoidance, observe frequent and maladaptive patterns in relationships and see how these are linked to emotional avoidance. The intervention is delivered online through a secure platform. Modules consist of text and the participants can work with the material whenever they wish to. Participants gain access to a new treatment modul every week.<br>Other: Treatment length: 16 weeks<br>* Participants will partake in their treatment condition for 16 weeks.<br>Other: Access to a moderated forum<br>* During their treatment, participants will have access to a discussion forum moderated by a clinician. Participants are encouraged to discuss questions and experiences related to their treatment condition.<br>\| \| Experimental: Psychodynamic therapy, 8 weeks and no access to forum.<br> \| Behavioral: Treatment condition: Internet-administered Affect phobia treatment<br>* The aim of psychodynamic Affect phobia treatment is for the patient to reach an intellectual and emotional understanding of his/hers problems. The goal of the treatment is for participants to decrease emotional avoidance and start to approach emotions and increase emotional awareness. Participants are taught this through linking their symptoms to their emotional avoidance, observe frequent and maladaptive patterns in relationships and see how these are linked to emotional avoidance. The intervention is delivered online through a secure platform. Modules consist of text and the participants can work with the material whenever they wish to. Participants gain access to a new treatment modul every week.<br>Other: Treatment length: 8 weeks<br>* Participants will partake in their treatment condition for 8 weeks.<br>Other: No access to a moderated forum<br>* Participants will not have access to a moderated forum, hence their treatment is self-guided.<br>\| \| Experimental: Psychodynamic therapy, 16 weeks and no access to forum.<br> \| Behavioral: Treatment condition: Internet-administered Affect phobia treatment<br>* The aim of psychodynamic Affect phobia treatment is for the patient to reach an intellectual and emotional understanding of his/hers problems. The goal of the treatment is for participants to decrease emotional avoidance and start to approach emotions and increase emotional awareness. Participants are taught this through linking their symptoms to their emotional avoidance, observe frequent and maladaptive patterns in relationships and see how these are linked to emotional avoidance. The intervention is delivered online through a secure platform. Modules consist of text and the participants can work with the material whenever they wish to. Participants gain access to a new treatment modul every week.<br>Other: Treatment length: 16 weeks<br>* Participants will partake in their treatment condition for 16 weeks.<br>Other: No access to a moderated forum<br>* Participants will not have access to a moderated forum, hence their treatment is self-guided.<br>\| \| Experimental: Waitlist, 8 weeks and access to forum.<br> \| Other: Treatment condition: Waitlist control<br>* The waitlist condition is a control condition without any intervention.<br>Other: Treatment length: 8 weeks<br>* Participants will partake in their treatment condition for 8 weeks.<br>Other: Access to a moderated forum<br>* During their treatment, participants will have access to a discussion forum moderated by a clinician. Participants are encouraged to discuss questions and experiences related to their treatment condition.<br>\| \| Experimental: Waitlist, 16 weeks and access to forum.<br> \| Other: Treatment condition: Waitlist control<br>* The waitlist condition is a control condition without any intervention.<br>Other: Treatment length: 16 weeks<br>* Participants will partake in their treatment condition for 16 weeks.<br>Other: Access to a moderated forum<br>* During their treatment, participants will have access to a discussion forum moderated by a clinician. Participants are encouraged to discuss questions and experiences related to their treatment condition.<br>\| \| Experimental: Waitlist, 8 weeks and no access to forum.<br> \| Other: Treatment condition: Waitlist control<br>* The waitlist condition is a control condition without any intervention.<br>Other: Treatment length: 8 weeks<br>* Participants will partake in their treatment condition for 8 weeks.<br>Other: No access to a moderated forum<br>* Participants will not have access to a moderated forum, hence their treatment is self-guided.<br>\| \| Experimental: Waitlist, 16 weeks and no access to forum.<br> \| Other: Treatment condition: Waitlist control<br>* The waitlist condition is a control condition without any intervention.<br>Other: Treatment length: 16 weeks<br>* Participants will partake in their treatment condition for 16 weeks.<br>Other: No access to a moderated forum<br>* Participants will not have access to a moderated forum, hence their treatment is self-guided.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Patient Health Questionnaire 9-item scale (PHQ-9) \| The PHQ-9 features nine items for assessing depression in a clinical context and screening of depression in the general population. \| Through study completion, an average of 2 years. \| \| Generalised Anxiety Disorder 7- item scale (GAD-7) \| The GAD-7 features seven items for assessing anxiety and screening for generalized anxiety disorder. \| Through study completion, an average of 2 years. \| \| Brunnsviken Brief Quality of Life Scale (BBQ) \| The BBQ features 12 items concerning 6 areas of life rated on importance and satisfaction. \| Through study completion, an average of 2 years. \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| The Personality Inventory for DSM Short Form (PID-5) \| The PID-5 is a self-rated measure of personality-related problems featuring 25 items. \| Baseline only. \| \| Negative Effects Questionnaire (NEQ) \| The NEQ measures unwanted effects of treatments. \| At post-treatment only (which is week 8 or 16 depending on treatment allocation). \| \| Reflective Functioning Questionnaire 8 (RFQ-8) \| RFQ features 8 items assessing the ability to understand mental states of the self and others. \| Through study completion, an average of 2 years. \|
NCT00102687	Alternative Dosing Regimens of Subcutaneous Azacitidine for Myelodysplastic Syndromes	The purpose of this study is to determine if azacitidine, combined with Best Supportive Care (BSC), is effective in treating myelodysplastic syndromes (MDS) when given according to a different doses and dosing schedules.	Comparison/Control Interventions: The comparison is azacitidine at different doses and schedules.~Duration of Intervention: Treatment lasted for a maximum of 18 cycles, which is up to 24 months.	A Multicenter, Randomized, Open-Label Study Comparing Three Alternative Dosing Regimens of Subcutaneous Azacitidine Plus Best Supportive Care for the Treatment of Myelodysplastic Syndromes	Myelodysplastic Syndromes	* Drug: azacitidine	Inclusion Criteria:~Diagnosis of refractory anemia, refractory anemia with ringed sideroblasts and at least one of the following: a)Anemia with hemoglobin <110g/L and requires at least 1 unit packed red blood cell transfusions every 28 days; b)Thrombocytopenia with platelet counts <100 x 10^9/L; or c)Neutropenia with absolute neutrophil count <1.5 x 10^9/L.~OR, Refractory anemia with excess blasts or refractory anemia with excess blast in transformation, according to the French-American-British classification system for MDS.~At least 18 years of age.~Have a life expectancy of >7 months.~Unlikely to proceed to bone marrow or stem cell transplantation therapy following remission.~Have serum bilirubin levels less than or equal to 1.5 times the upper limit of the normal (ULN) range for the laboratory.~Have serum glutamic-oxaloacetic transaminase (aspartate aminotransferase) or serum glutamic-pyruvic transaminase (alanine aminotransferase) levels less than or equal to 2 x ULN.~Have serum creatinine levels less than or equal to 1.5 x ULN.~Exclusion Criteria:~Secondary MDS.~Prior treatment with azacitidine.~Any prior history of Acute Myeloid Leukemia (AML).~Malignant or metastatic disease within the previous 12 months.~Uncorrected red cell folate deficiency or vitamin B12 deficiency.~Hepatic tumors.~Radiation, chemotherapy, or cytotoxic therapy for non-MDS conditions in the previous 12 months.~Known or suspected hypersensitivity to azacitidine or mannitol.~Prior transplantation or cytotoxic therapy to treat MDS. Prior use of Revlimid and Thalomid allowed after 30 day washout.~Serious medical illness likely to limit survival to less than or equal to 7 months.~Treatment with androgenic hormones during the previous 14 days~Active viral infection with known human immunodeficiency virus or vial hepatitis Type B or C.~Treatment with other investigational drugs with the previous 30 days.	18 Years	null	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period. \| Participant counts by best hematological response; complete remission(CR) is better than a partial remission(PR) which is better than stable disease(SD).~Investigator determined responses followed IWG 2000 criteria for MDS CR: repeat bone marrow show <5% myeloblasts, and peripheral blood evaluations lasting >=2 months of hemoglobin(>110 g/L), neutrophils(>=1.5x10^9/L), platelets(>=100x10^9/L), blasts (0%) and no dysplasia PR is the same as CR for peripheral blood: bone marrow shows blasts decrease by >=50% or a less advanced FAB classification from pretreatment (see Population Descrip) \| Day 1 (randomization) to 6 months \| \| Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period. \| IWG 2000 Criteria: Pretreatment=hemoglobin <110g/L or RBC transfusion-dependence, platelet count <100x10^9/L or platelet transfusion dependence, absolute neutrophil count <1.5x10^9/L.~Erythroid response: Major->20g/L increase in hemoglobin or transfusion independence. Minor- 10-20g/L increase in hemoglobin or >=50% decrease in transfusion requirements.~Platelet response: Major-absolute increase of platelet count by >=30x10^9/L or platelet transfusion independence. Minor->=50% increase in platelet count with net increase >10x10^9/L but <30x10^9/L.~(continued in Population Description) \| Day 1 (randomization) to 6 months \| \| Number of Participants With Overall Best Hematologic Response and Hematologic Improvement Based on IWG 2000 Criteria For MDS During the Initial Study Period \| Number of participants whose best hematological outcome was either complete remission (CR), partial remission (PR) (as determined by the investigator), or any hematologic improvement (based on the IWG 2000 criteria for MDS). See previous outcomes for detailed definitions. \| Day 1 (randomization) to 6 months \| \| Number of Participants Who Improved or Maintained The Hematologic Response From the Initial Study Period (Based on IWG 2000 Criteria For MDS) During the Maintenance Period \| Hematologic response during the maintenance period are compared to the response in the initial study period. Initial response could have been a complete remission, a partial remission, stable disease or a hematologic improvement. Maintenance period best response is after randomization to a maintenance arm for those randomized, and is after the start of cycle 7 for those remaining on initial period treatment throughout the study. \| 24 months \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Baseline Hemoglobin Values \| The median values for hemoglobin based on blood tests performed on study day 1 (prior to study treatment) constitute a baseline measure for hemoglobin. Baseline values are used to compare to values following treatment. \| Day 1 (randomization) \| \| Change From Baseline in Hemoglobin at End of Initial Study Period (6 Months) \| The difference between hemoglobin values at the end of the initial study period minus the hemoglobin values at baseline. \| 6 months \| \| Change From Baseline in Hemoglobin at the End of the Maintenance Study Period \| The difference between hemoglobin values at the end of the maintenance study period minus the hemoglobin values at baseline. \| 24 months \| \| Baseline Platelet Values \| The median values for platelets based on blood tests performed on study day 1 (prior to study treatment) constitute a baseline measure for platelets. Baseline values are used to compare to values following treatment. \| Day 1 (randomization) \| \| Change From Baseline in Platelets at the End of Initial Study Period (6 Months) \| The difference between platelet values at the end of the initial study period minus the platelet values at baseline. \| 6 months \| \| Change From Baseline in Platelets at the End of the Maintenance Study Period (Month 24) \| The difference between platelet values at the end of the maintenance study period minus the platelet values at baseline. \| 24 months \| \| Baseline Absolute Neutrophil Count (ANC) Values \| The median values for ANC based on blood tests performed on study day 1 (prior to study treatment) constitute a baseline measure for ANC. Baseline values are used to compare to values following treatment. \| Day 1 (randomization) \| \| Change From Baseline in Absolute Neutrophil Count (ANC) at the End of Initial Study Period (6 Months) \| The difference between ANC values at the end of the initial study period minus the ANC values at baseline. \| 6 months \| \| Change From Baseline in Absolute Neutrophil Count (ANC) at the End of the Maintenance Study Period (Month 24) \| The difference between ANC values at the end of the maintenance study period minus the ANC values at baseline. \| 24 months \| \| Red Blood Cell (RBC) Transfusion Status at Baseline and End of Initial Study Period (6 Months) \| Shift table comparing the RBC transfusion status of patients at the end of the initial study period to the transfusion status at baseline. \| 6 months \| \| Platelet Transfusion Status at Baseline and End of Initial Study Period (6 Months) \| Shift table comparing the platelet transfusion status of patients at the end of the initial study period to the transfusion status at baseline. \| 6 months \| \| Red Blood Cell (RBC) Transfusion Status at Baseline and End of Maintenance Study Period (24 Months) \| Shift table comparing the RBC transfusion status of patients at the end of the maintenance study period to the transfusion status at baseline. \| 24 months \| \| Platelet Transfusion Status at Baseline and End of Maintenance Study Period (24 Months) \| Shift table comparing the platelet transfusion status of patients at the end of the maintenance study period to the transfusion status at baseline. \| 24 months \| \| Change From Baseline in the Number of Infections Requiring Treatment With IV Antibiotics Per Treatment Cycle (28 Days) for the Initial Study Period \| Baseline uses the average number of infections requiring IV antibiotic treatment from the 28 days prior to and including the day of first dose to an initial treatment arm. Initial study period values total the number of infections requiring IV antibiotic treatment divided by the number of treatment cycles (each cycle is approximately one month). \| 6 months \| \| Change From Baseline in the Number of Infections Requiring Treatment With IV Antibiotics Per Treatment Cycle (28 Days) for the Maintenance Study Period \| Baseline uses the average number of infections requiring IV antibiotic treatment from the 28 days prior to and including the day of first dose to an initial treatment arm. Maintenance study period values total the number of infections requiring IV antibiotic treatment divided by the number of treatment cycles (each cycle is approximately one month). \| 24 months \|		Azacitidine, Antimetabolites, Antineoplastic, Antimetabolites, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents, Enzyme Inhibitors	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Aza-5<br>Azacitidine administered subcutaneously at 75mg/m^2 for 5 days on a 28 day cycle. \| Drug: azacitidine<br>* Azacitidine is administered subcutaneously~Total of 18 cycles on treatment or early discontinuation.<br>\| \| Experimental: Aza-5-2-2<br>Azacitidine administered subcutaneously at 75mg/m^2 for 5days with 2 days off, then for an additional 2 days, on a 28 day cycle. \| Drug: azacitidine<br>* Azacitidine is administered subcutaneously~Total of 18 cycles on treatment or early discontinuation.<br>\| \| Experimental: Aza-5-2-5<br>Azacitidine administered subcutaneously at 50mg/m^2 for 5 days with 2 days off, then for an additional 5 days, on a 28 day cycle. \| Drug: azacitidine<br>* Azacitidine is administered subcutaneously~Total of 18 cycles on treatment or early discontinuation.<br>\| \| Experimental: Maintenance Aza 5 days q 4 weeks<br>Azacitidine administered subcutaneously at 75mg/m^2 for 5 days every 4 weeks. \| Drug: azacitidine<br>* Azacitidine is administered subcutaneously~Total of 18 cycles on treatment or early discontinuation.<br>\| \| Experimental: Maintenance Aza 5 days q 6 weeks<br>Azacitidine administered subcutaneously at 75mg/m^2 for 5 days every 6 weeks. \| Drug: azacitidine<br>* Azacitidine is administered subcutaneously~Total of 18 cycles on treatment or early discontinuation.<br>\|	Alternative Dosing Regimens of Subcutaneous Azacitidine for Myelodysplastic Syndromes Study Overview ================= Brief Summary ----------------- The purpose of this study is to determine if azacitidine, combined with Best Supportive Care (BSC), is effective in treating myelodysplastic syndromes (MDS) when given according to a different doses and dosing schedules. Detailed Description ----------------- Comparison/Control Interventions: The comparison is azacitidine at different doses and schedules. Duration of Intervention: Treatment lasted for a maximum of 18 cycles, which is up to 24 months. Official Title ----------------- A Multicenter, Randomized, Open-Label Study Comparing Three Alternative Dosing Regimens of Subcutaneous Azacitidine Plus Best Supportive Care for the Treatment of Myelodysplastic Syndromes Conditions ----------------- Myelodysplastic Syndromes Intervention / Treatment ----------------- * Drug: azacitidine Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Diagnosis of refractory anemia, refractory anemia with ringed sideroblasts and at least one of the following: a)Anemia with hemoglobin <110g/L and requires at least 1 unit packed red blood cell transfusions every 28 days; b)Thrombocytopenia with platelet counts <100 x 10^9/L; or c)Neutropenia with absolute neutrophil count <1.5 x 10^9/L. OR, Refractory anemia with excess blasts or refractory anemia with excess blast in transformation, according to the French-American-British classification system for MDS. At least 18 years of age. Have a life expectancy of >7 months. Unlikely to proceed to bone marrow or stem cell transplantation therapy following remission. Have serum bilirubin levels less than or equal to 1.5 times the upper limit of the normal (ULN) range for the laboratory. Have serum glutamic-oxaloacetic transaminase (aspartate aminotransferase) or serum glutamic-pyruvic transaminase (alanine aminotransferase) levels less than or equal to 2 x ULN. Have serum creatinine levels less than or equal to 1.5 x ULN. Exclusion Criteria: Secondary MDS. Prior treatment with azacitidine. Any prior history of Acute Myeloid Leukemia (AML). Malignant or metastatic disease within the previous 12 months. Uncorrected red cell folate deficiency or vitamin B12 deficiency. Hepatic tumors. Radiation, chemotherapy, or cytotoxic therapy for non-MDS conditions in the previous 12 months. Known or suspected hypersensitivity to azacitidine or mannitol. Prior transplantation or cytotoxic therapy to treat MDS. Prior use of Revlimid and Thalomid allowed after 30 day washout. Serious medical illness likely to limit survival to less than or equal to 7 months. Treatment with androgenic hormones during the previous 14 days Active viral infection with known human immunodeficiency virus or vial hepatitis Type B or C. Treatment with other investigational drugs with the previous 30 days. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Aza-5<br>Azacitidine administered subcutaneously at 75mg/m^2 for 5 days on a 28 day cycle. \| Drug: azacitidine<br>* Azacitidine is administered subcutaneously Total of 18 cycles on treatment or early discontinuation.<br>\| \| Experimental: Aza-5-2-2<br>Azacitidine administered subcutaneously at 75mg/m^2 for 5days with 2 days off, then for an additional 2 days, on a 28 day cycle. \| Drug: azacitidine<br>* Azacitidine is administered subcutaneously Total of 18 cycles on treatment or early discontinuation.<br>\| \| Experimental: Aza-5-2-5<br>Azacitidine administered subcutaneously at 50mg/m^2 for 5 days with 2 days off, then for an additional 5 days, on a 28 day cycle. \| Drug: azacitidine<br>* Azacitidine is administered subcutaneously Total of 18 cycles on treatment or early discontinuation.<br>\| \| Experimental: Maintenance Aza 5 days q 4 weeks<br>Azacitidine administered subcutaneously at 75mg/m^2 for 5 days every 4 weeks. \| Drug: azacitidine<br>* Azacitidine is administered subcutaneously Total of 18 cycles on treatment or early discontinuation.<br>\| \| Experimental: Maintenance Aza 5 days q 6 weeks<br>Azacitidine administered subcutaneously at 75mg/m^2 for 5 days every 6 weeks. \| Drug: azacitidine<br>* Azacitidine is administered subcutaneously Total of 18 cycles on treatment or early discontinuation.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period. \| Participant counts by best hematological response; complete remission(CR) is better than a partial remission(PR) which is better than stable disease(SD). Investigator determined responses followed IWG 2000 criteria for MDS CR: repeat bone marrow show <5% myeloblasts, and peripheral blood evaluations lasting >=2 months of hemoglobin(>110 g/L), neutrophils(>=1.5x10^9/L), platelets(>=100x10^9/L), blasts (0%) and no dysplasia PR is the same as CR for peripheral blood: bone marrow shows blasts decrease by >=50% or a less advanced FAB classification from pretreatment (see Population Descrip) \| Day 1 (randomization) to 6 months \| \| Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period. \| IWG 2000 Criteria: Pretreatment=hemoglobin <110g/L or RBC transfusion-dependence, platelet count <100x10^9/L or platelet transfusion dependence, absolute neutrophil count <1.5x10^9/L. Erythroid response: Major->20g/L increase in hemoglobin or transfusion independence. Minor- 10-20g/L increase in hemoglobin or >=50% decrease in transfusion requirements. Platelet response: Major-absolute increase of platelet count by >=30x10^9/L or platelet transfusion independence. Minor->=50% increase in platelet count with net increase >10x10^9/L but <30x10^9/L. (continued in Population Description) \| Day 1 (randomization) to 6 months \| \| Number of Participants With Overall Best Hematologic Response and Hematologic Improvement Based on IWG 2000 Criteria For MDS During the Initial Study Period \| Number of participants whose best hematological outcome was either complete remission (CR), partial remission (PR) (as determined by the investigator), or any hematologic improvement (based on the IWG 2000 criteria for MDS). See previous outcomes for detailed definitions. \| Day 1 (randomization) to 6 months \| \| Number of Participants Who Improved or Maintained The Hematologic Response From the Initial Study Period (Based on IWG 2000 Criteria For MDS) During the Maintenance Period \| Hematologic response during the maintenance period are compared to the response in the initial study period. Initial response could have been a complete remission, a partial remission, stable disease or a hematologic improvement. Maintenance period best response is after randomization to a maintenance arm for those randomized, and is after the start of cycle 7 for those remaining on initial period treatment throughout the study. \| 24 months \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Baseline Hemoglobin Values \| The median values for hemoglobin based on blood tests performed on study day 1 (prior to study treatment) constitute a baseline measure for hemoglobin. Baseline values are used to compare to values following treatment. \| Day 1 (randomization) \| \| Change From Baseline in Hemoglobin at End of Initial Study Period (6 Months) \| The difference between hemoglobin values at the end of the initial study period minus the hemoglobin values at baseline. \| 6 months \| \| Change From Baseline in Hemoglobin at the End of the Maintenance Study Period \| The difference between hemoglobin values at the end of the maintenance study period minus the hemoglobin values at baseline. \| 24 months \| \| Baseline Platelet Values \| The median values for platelets based on blood tests performed on study day 1 (prior to study treatment) constitute a baseline measure for platelets. Baseline values are used to compare to values following treatment. \| Day 1 (randomization) \| \| Change From Baseline in Platelets at the End of Initial Study Period (6 Months) \| The difference between platelet values at the end of the initial study period minus the platelet values at baseline. \| 6 months \| \| Change From Baseline in Platelets at the End of the Maintenance Study Period (Month 24) \| The difference between platelet values at the end of the maintenance study period minus the platelet values at baseline. \| 24 months \| \| Baseline Absolute Neutrophil Count (ANC) Values \| The median values for ANC based on blood tests performed on study day 1 (prior to study treatment) constitute a baseline measure for ANC. Baseline values are used to compare to values following treatment. \| Day 1 (randomization) \| \| Change From Baseline in Absolute Neutrophil Count (ANC) at the End of Initial Study Period (6 Months) \| The difference between ANC values at the end of the initial study period minus the ANC values at baseline. \| 6 months \| \| Change From Baseline in Absolute Neutrophil Count (ANC) at the End of the Maintenance Study Period (Month 24) \| The difference between ANC values at the end of the maintenance study period minus the ANC values at baseline. \| 24 months \| \| Red Blood Cell (RBC) Transfusion Status at Baseline and End of Initial Study Period (6 Months) \| Shift table comparing the RBC transfusion status of patients at the end of the initial study period to the transfusion status at baseline. \| 6 months \| \| Platelet Transfusion Status at Baseline and End of Initial Study Period (6 Months) \| Shift table comparing the platelet transfusion status of patients at the end of the initial study period to the transfusion status at baseline. \| 6 months \| \| Red Blood Cell (RBC) Transfusion Status at Baseline and End of Maintenance Study Period (24 Months) \| Shift table comparing the RBC transfusion status of patients at the end of the maintenance study period to the transfusion status at baseline. \| 24 months \| \| Platelet Transfusion Status at Baseline and End of Maintenance Study Period (24 Months) \| Shift table comparing the platelet transfusion status of patients at the end of the maintenance study period to the transfusion status at baseline. \| 24 months \| \| Change From Baseline in the Number of Infections Requiring Treatment With IV Antibiotics Per Treatment Cycle (28 Days) for the Initial Study Period \| Baseline uses the average number of infections requiring IV antibiotic treatment from the 28 days prior to and including the day of first dose to an initial treatment arm. Initial study period values total the number of infections requiring IV antibiotic treatment divided by the number of treatment cycles (each cycle is approximately one month). \| 6 months \| \| Change From Baseline in the Number of Infections Requiring Treatment With IV Antibiotics Per Treatment Cycle (28 Days) for the Maintenance Study Period \| Baseline uses the average number of infections requiring IV antibiotic treatment from the 28 days prior to and including the day of first dose to an initial treatment arm. Maintenance study period values total the number of infections requiring IV antibiotic treatment divided by the number of treatment cycles (each cycle is approximately one month). \| 24 months \|
NCT02173158	Efficacy and Safety of Lomitapide in Japanese Patients With HoFH on Concurrent Lipid-Lowering Therapy	Study to Evaluate the Efficacy and Safety of Lomitapide in Japanese Patients with Homozygous Familial Hypercholesterolemia (HoFH) on Concurrent Lipid-Lowering Therapy.	This is a Phase 3, single-arm, open-label, multicenter clinical trial to evaluate both the efficacy and long-term safety of lomitapide in Japanese patients with HoFH receiving maximally-tolerated, stable lipid-lowering therapy. This study is comprised of a run-in period, a primary 26-week Efficacy Phase, and a 30-week Safety Phase.	A Phase 3, Single-Arm, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of Lomitapide in Japanese Patients With Homozygous Familial Hypercholesterolemia (HoFH) on Concurrent Lipid-Lowering Therapy	Familial Hypercholesterolemia - Homozygous	* Drug: lomitapide	Inclusion Criteria:~Japanese male and female patients aged ≥ 18 years of age who are receiving maximally tolerated, stable, lipid-lowering therapy~Diagnosis of functional HoFH~Body weight ≥ 40 kg and < 136 kg~Negative pregnancy test at screening~Exclusion Criteria:~Uncontrolled hypertension~History of chronic renal insufficiency~History of biopsy proven cirrhosis or abnormal liver function tests (LFTs) at screening~Any major surgical procedure occurring < 3 months prior to the screening visit~Cardiac insufficiency~Previous organ transplantation~History of a non-skin malignancy within the previous 3 years~Patients who are not able to limit their alcohol intake~Participation in an investigational drug study within 6 weeks prior to the screening visit~Known significant gastrointestinal bowel disease~Nursing mothers~Serious or unstable medical or psychological conditions~Requirement for certain prohibited medications known to be potentially hepatotoxic~Use of strong or moderate inhibitors of CYP3A4~Use of simvastatin at doses >10 mg per day~Documented diagnosis of any liver disease	18 Years	null	All	No	Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Percent Change in LDL-C \| Mean percent change from baseline \| Baseline to Week 26 \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change in Total Cholesterol \| Mean percent change from baseline \| Baseline to Week 56 \| \| Change in Apo B \| Mean percent change from baseline \| Baseline to Week 56 \| \| Change in Triglycerides \| Mean percent change from baseline \| Baseline to Week 56 \| \| Change in Non-HDL-C \| Mean percent change from baseline \| Baseline to Week 56 \| \| Change in VLDL-C \| Mean percent change from baseline \| Baseline to Week 56 \| \| Change in Lp(a) \| Mean percent change from baseline \| Baseline to Week 56 \| \| Change in HDL-C \| Mean percent change from baseline \| Baseline to Week 56 \| \| Change in Apo AI \| Mean percent change from baseline \| Baseline to Week 56 \| \| Change in LDL-C \| Mean percent change from baseline \| Baseline to Week 56 \|		Hyperlipoproteinemia Type II, Homozygous Familial Hypercholesterolemia, Hypercholesterolemia, Hyperlipidemias, Dyslipidemias, Lipid Metabolism Disorders, Metabolic Diseases, Lipid Metabolism, Inborn Errors, Metabolism, Inborn Errors, Genetic Diseases, Inborn, Hyperlipoproteinemias	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: lomitapide<br>Maximum tolerated dose of lomitapide (up to 60mg/day) in addition to existing lipid lowering therapy including plasmapheresis or lipid apheresis. \| Drug: lomitapide<br> <br> * Other names: Juxtapid, Lojuxta;\|	Efficacy and Safety of Lomitapide in Japanese Patients With HoFH on Concurrent Lipid-Lowering Therapy Study Overview ================= Brief Summary ----------------- Study to Evaluate the Efficacy and Safety of Lomitapide in Japanese Patients with Homozygous Familial Hypercholesterolemia (HoFH) on Concurrent Lipid-Lowering Therapy. Detailed Description ----------------- This is a Phase 3, single-arm, open-label, multicenter clinical trial to evaluate both the efficacy and long-term safety of lomitapide in Japanese patients with HoFH receiving maximally-tolerated, stable lipid-lowering therapy. This study is comprised of a run-in period, a primary 26-week Efficacy Phase, and a 30-week Safety Phase. Official Title ----------------- A Phase 3, Single-Arm, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of Lomitapide in Japanese Patients With Homozygous Familial Hypercholesterolemia (HoFH) on Concurrent Lipid-Lowering Therapy Conditions ----------------- Familial Hypercholesterolemia - Homozygous Intervention / Treatment ----------------- * Drug: lomitapide Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Japanese male and female patients aged ≥ 18 years of age who are receiving maximally tolerated, stable, lipid-lowering therapy Diagnosis of functional HoFH Body weight ≥ 40 kg and < 136 kg Negative pregnancy test at screening Exclusion Criteria: Uncontrolled hypertension History of chronic renal insufficiency History of biopsy proven cirrhosis or abnormal liver function tests (LFTs) at screening Any major surgical procedure occurring < 3 months prior to the screening visit Cardiac insufficiency Previous organ transplantation History of a non-skin malignancy within the previous 3 years Patients who are not able to limit their alcohol intake Participation in an investigational drug study within 6 weeks prior to the screening visit Known significant gastrointestinal bowel disease Nursing mothers Serious or unstable medical or psychological conditions Requirement for certain prohibited medications known to be potentially hepatotoxic Use of strong or moderate inhibitors of CYP3A4 Use of simvastatin at doses >10 mg per day Documented diagnosis of any liver disease Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: lomitapide<br>Maximum tolerated dose of lomitapide (up to 60mg/day) in addition to existing lipid lowering therapy including plasmapheresis or lipid apheresis. \| Drug: lomitapide<br> <br> * Other names: Juxtapid, Lojuxta;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Percent Change in LDL-C \| Mean percent change from baseline \| Baseline to Week 26 \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Change in Total Cholesterol \| Mean percent change from baseline \| Baseline to Week 56 \| \| Change in Apo B \| Mean percent change from baseline \| Baseline to Week 56 \| \| Change in Triglycerides \| Mean percent change from baseline \| Baseline to Week 56 \| \| Change in Non-HDL-C \| Mean percent change from baseline \| Baseline to Week 56 \| \| Change in VLDL-C \| Mean percent change from baseline \| Baseline to Week 56 \| \| Change in Lp(a) \| Mean percent change from baseline \| Baseline to Week 56 \| \| Change in HDL-C \| Mean percent change from baseline \| Baseline to Week 56 \| \| Change in Apo AI \| Mean percent change from baseline \| Baseline to Week 56 \| \| Change in LDL-C \| Mean percent change from baseline \| Baseline to Week 56 \|
NCT03686722	Effect of Co-administration of Metformin and Daclatasvir on the Pharmacokinetis and Pharmacodynamics of Metformin	A Randomized,Two-period, Crossover Study to Determine the Possibility of Drug-drug Interaction After Co-administration of Metformin and Daclatasvir Where Twenty Eligible Adult Subjects Will be Randomized to Receive Either Metformin Only and/or Metformin Co-administered With Daclatasvir to measure primary outcomes including pharmacokinetics parameters as: Maximum drug concentration in plasma(Cmax), Area under the Plasma concentration Versus Time Curve from time 0 to 12 hours(AUC0-12), Clearance(CL)	Study Design:~A randomized, one-way, single blinded, two-period, crossover study in adult human healthy egyptian volunteers~Methodology:~period (I): Group A:10 volunteers will receive 500 mg Metformin twice daily on day 1-4 then 1000mg metformin twice on day 5-7~GroupB:10 volunteers will receive 500 mg Metformin twice daily + Daclatasvir (DCV) 60 mg once daily on day 1-4 then 1000mg metformin twice daily+DCV 60 mg once daily on day 5-7~period (II): Group A:10 volunteers will receive 500 mg Metformin twice daily + Daclatasvir (DCV) 60 mg once daily on day 1-4 then 1000mg metformin twice daily+DCV 60 mg once daily on day 5-7~Group B:10 volunteers will receive 500 mg Metformin twice daily on day 1-4 then 1000mg metformin twice daily on day 5-7~All drug administration will be followed by 240 ml of water after at least 10 hours fasting prior to administration.~The two treatment periods will be separated by a one week washout period~Blood Sampling will be collected at a pre-dosing and at 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12 hours Urine samples will be collected for metformin analysis from 0 to 12 hours after drug administration.~A 75 g Oral glucose tolerance test(OGTT) will be carried out by ingestion of 75g glucose in 240ml water 2-hours post dosing and blood samples for determining glucose concentration during OGTTs were collected immediately before and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, and 3 hours after glucose ingestion.~Blood samples will be collected from each volunteer prior to drug administration (blank) at the predetermined sampling intervals after drug administration in ethylene diamine tetra-acetic acid(kEDTA) containing tubes.~These samples will be centrifuged and the plasma harvested and stored at -80°C until assay.	Effect of Co-administration of Metformin and Daclatasvir on the Pharmacokinetics and Pharmacodynamics of Metformin	Diabetes Mellitus, Type 2, Hepatitis C, Drug Interactions	* Drug: Metformin * Drug: Daclatasvir	Inclusion Criteria:~Subject is at least 18-55 years at screening.~Subject has a Body Mass Index of 18 to 35 kg/m2.~Subject are non smokers or moderate smokers(not more than 10 cigarettes per day)~Subjects is willing to participate and give their final written consent prior to the commencement of the study procedures~Subject is in good age-appropriate health condition as established by medical history, physical examination, and results of biochemistry, hematology and urine analysis testing within 4 weeks prior to study.~Subject has a normal blood pressure and pulse rate, according to the reference normal ranges.~Exclusion Criteria:~Treatment with any known enzyme-inducing/inhibiting agents prior to the start of the study and throughout the study.~Subjects who have taken any medication two weeks preceding of the trial starting date.~Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.~Any prior surgery of the gastrointestinal tract that may interfere with drug absorption.~Gastrointestinal diseases.~Renal diseases.~Cardiovascular diseases specially transient ischemic attacks and cardiac dysrhythmia .~Pancreatic disease including diabetes.~Hepatic diseases as hepatic failure, cirrhosis, galactose intolerance, fructose intolerance, glycogen storage diseases~Hematological disease or pulmonary disease~Abnormal laboratory values.~Subjects who have donated blood or who have been involved in a drug study within 6 weeks preceding the start of the study.~Positive HIV test.~History of or current abuse of drugs, alcohol or solvents.~Endocrine disorders as Pheochromocytoma, Addison disease, glucagon deficiency, carcinomas, extrahepatic tumors~Autoimmune disorders as Graves disease~Central nervous system (CNS) disorders	18 Years	55 Years	Male	Accepts Healthy Volunteers	Primary Purpose: Other Allocation: Randomized Intervention Model: Crossover Assignment Interventional Model Description: Twenty Eligible Adult Subjects Will be Randomized Equally into two Groups: A and B To Receive Either:~Group (A):10 subjects will receive 500 mg Metformin twice daily on day 1-4 then 1000mg metformin twice on day 5-7 Group (B):10 subjects will receive 500 mg co-administered daily with Daclatasvir 60 mg once daily on day 1-4 then 1000mg Metformin co-administered twice daily with Daclatasvir 60 mg once daily on day 5-7 Masking: Double	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| (AUC0→12) \| Area under the plasma concentration-time curve measured in (nanogram(ng).hr/ml) \| From first sampling interval(time zero) up to 12 hours \| \| Area under the plasma concentration-time curve from time 0 to infinity (AUC0→∞) \| Area under the plasma concentration-time curve from time 0 to infinity measured in(ng.hr/ml) \| From first sampling interval up to infinity \| \| Area under the plasma concentration-time curve from time 0 to tau(AUC0→tau) \| Area under the plasma concentration-time curve from time 0 to tau measured in(ng.hr/ml) \| From first sampling interval up to dosing interval(Tau) \| \| Maximum drug concentration in plasma at steady state(Cpss) \| Maximum drug concentration in plasma at steady state measured in (ng/ml) \| Time corresponding to maximum drug concentration in plasma at steady state \| \| Half life( t½) of drug in plasma \| Half life of drug measured in Hours(hr) \| Up to 12 hours \| \| Mean residence time of drug(MRT) \| Mean residence time of drug in plasma measured in (hr) \| From first sampling interval up to 12 hours \| \| steady state Clearance of drug(CLss) \| steady state Clearance of drug measured in (ml/min) \| From first sampling interval up to 12 hours \| \| Renal Clearance of drug(CLr) \| Renal Clearance of drug measured in (ml/min) \| From first sampling interval up to 12 hours \| \| Cumulative amount of drug eliminated in urine (Ae) \| Cumulative amount of drug eliminated in urine measured in (microgram(ug)/ml) \| From first sampling interval up to 12 hours \| \| Maximum excretion rate (Urate max) \| Maximum excretion rate for the drug measured in (milligram(mg)/hr) \| From first sampling interval up to 12 hours \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Blood Glucose(BG) levels \| Blood glucose levels measured in (mg/dl) \| up to 3 hours \| \| Area under the BG-time curve(AUG)0-3hr \| Area under the BG-time curve measured in (mg.hr/dl) \| up to 3 hours \| \| Maximum Glucose concentration(Gmax) \| Maximum Glucose concentration measured in (mg/dl) \| up to 3 hours \|		Metformin, Hypoglycemic Agents, Physiological Effects of Drugs	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Metformin<br>Subjects administered Metformin 500mg(Glucophage tablets) twice daily till day(4) then Metformin 1000mg twice daily till day(7) \| Drug: Metformin<br>* Metformin is used primarly in treatment of diabetes type II<br>\| \| Experimental: Metformin and Daclatasvir<br>Subjects Coadministered Metformin 500mg(Glucophage tablets) twice daily and Daclatasvir 60mg tablets once daily till day (4) then Metformin 1000mg twice daily and Daclatasvir 60mg tablets once daily till Day(7) \| Drug: Metformin<br>* Metformin is used primarly in treatment of diabetes type II<br>Drug: Daclatasvir<br>* Daclatsvir is a direct acting antiviral drug<br>\|	Effect of Co-administration of Metformin and Daclatasvir on the Pharmacokinetis and Pharmacodynamics of Metformin Study Overview ================= Brief Summary ----------------- A Randomized,Two-period, Crossover Study to Determine the Possibility of Drug-drug Interaction After Co-administration of Metformin and Daclatasvir Where Twenty Eligible Adult Subjects Will be Randomized to Receive Either Metformin Only and/or Metformin Co-administered With Daclatasvir to measure primary outcomes including pharmacokinetics parameters as: Maximum drug concentration in plasma(Cmax), Area under the Plasma concentration Versus Time Curve from time 0 to 12 hours(AUC0-12), Clearance(CL) Detailed Description ----------------- Study Design: A randomized, one-way, single blinded, two-period, crossover study in adult human healthy egyptian volunteers Methodology: period (I): Group A:10 volunteers will receive 500 mg Metformin twice daily on day 1-4 then 1000mg metformin twice on day 5-7 GroupB:10 volunteers will receive 500 mg Metformin twice daily + Daclatasvir (DCV) 60 mg once daily on day 1-4 then 1000mg metformin twice daily+DCV 60 mg once daily on day 5-7 period (II): Group A:10 volunteers will receive 500 mg Metformin twice daily + Daclatasvir (DCV) 60 mg once daily on day 1-4 then 1000mg metformin twice daily+DCV 60 mg once daily on day 5-7 Group B:10 volunteers will receive 500 mg Metformin twice daily on day 1-4 then 1000mg metformin twice daily on day 5-7 All drug administration will be followed by 240 ml of water after at least 10 hours fasting prior to administration. The two treatment periods will be separated by a one week washout period Blood Sampling will be collected at a pre-dosing and at 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12 hours Urine samples will be collected for metformin analysis from 0 to 12 hours after drug administration. A 75 g Oral glucose tolerance test(OGTT) will be carried out by ingestion of 75g glucose in 240ml water 2-hours post dosing and blood samples for determining glucose concentration during OGTTs were collected immediately before and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, and 3 hours after glucose ingestion. Blood samples will be collected from each volunteer prior to drug administration (blank) at the predetermined sampling intervals after drug administration in ethylene diamine tetra-acetic acid(kEDTA) containing tubes. These samples will be centrifuged and the plasma harvested and stored at -80°C until assay. Official Title ----------------- Effect of Co-administration of Metformin and Daclatasvir on the Pharmacokinetics and Pharmacodynamics of Metformin Conditions ----------------- Diabetes Mellitus, Type 2, Hepatitis C, Drug Interactions Intervention / Treatment ----------------- * Drug: Metformin * Drug: Daclatasvir Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Subject is at least 18-55 years at screening. Subject has a Body Mass Index of 18 to 35 kg/m2. Subject are non smokers or moderate smokers(not more than 10 cigarettes per day) Subjects is willing to participate and give their final written consent prior to the commencement of the study procedures Subject is in good age-appropriate health condition as established by medical history, physical examination, and results of biochemistry, hematology and urine analysis testing within 4 weeks prior to study. Subject has a normal blood pressure and pulse rate, according to the reference normal ranges. Exclusion Criteria: Treatment with any known enzyme-inducing/inhibiting agents prior to the start of the study and throughout the study. Subjects who have taken any medication two weeks preceding of the trial starting date. Documented history of sensitivity/idiosyncrasy to medicinal products or excipients. Any prior surgery of the gastrointestinal tract that may interfere with drug absorption. Gastrointestinal diseases. Renal diseases. Cardiovascular diseases specially transient ischemic attacks and cardiac dysrhythmia . Pancreatic disease including diabetes. Hepatic diseases as hepatic failure, cirrhosis, galactose intolerance, fructose intolerance, glycogen storage diseases Hematological disease or pulmonary disease Abnormal laboratory values. Subjects who have donated blood or who have been involved in a drug study within 6 weeks preceding the start of the study. Positive HIV test. History of or current abuse of drugs, alcohol or solvents. Endocrine disorders as Pheochromocytoma, Addison disease, glucagon deficiency, carcinomas, extrahepatic tumors Autoimmune disorders as Graves disease Central nervous system (CNS) disorders Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 55 Years Sexes Eligible for Study ----------------- Male Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Other Allocation: Randomized Intervention Model: Crossover Assignment Interventional Model Description: Twenty Eligible Adult Subjects Will be Randomized Equally into two Groups: A and B To Receive Either: Group (A):10 subjects will receive 500 mg Metformin twice daily on day 1-4 then 1000mg metformin twice on day 5-7 Group (B):10 subjects will receive 500 mg co-administered daily with Daclatasvir 60 mg once daily on day 1-4 then 1000mg Metformin co-administered twice daily with Daclatasvir 60 mg once daily on day 5-7 Masking: Double Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Metformin<br>Subjects administered Metformin 500mg(Glucophage tablets) twice daily till day(4) then Metformin 1000mg twice daily till day(7) \| Drug: Metformin<br>* Metformin is used primarly in treatment of diabetes type II<br>\| \| Experimental: Metformin and Daclatasvir<br>Subjects Coadministered Metformin 500mg(Glucophage tablets) twice daily and Daclatasvir 60mg tablets once daily till day (4) then Metformin 1000mg twice daily and Daclatasvir 60mg tablets once daily till Day(7) \| Drug: Metformin<br>* Metformin is used primarly in treatment of diabetes type II<br>Drug: Daclatasvir<br>* Daclatsvir is a direct acting antiviral drug<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| (AUC0→12) \| Area under the plasma concentration-time curve measured in (nanogram(ng).hr/ml) \| From first sampling interval(time zero) up to 12 hours \| \| Area under the plasma concentration-time curve from time 0 to infinity (AUC0→∞) \| Area under the plasma concentration-time curve from time 0 to infinity measured in(ng.hr/ml) \| From first sampling interval up to infinity \| \| Area under the plasma concentration-time curve from time 0 to tau(AUC0→tau) \| Area under the plasma concentration-time curve from time 0 to tau measured in(ng.hr/ml) \| From first sampling interval up to dosing interval(Tau) \| \| Maximum drug concentration in plasma at steady state(Cpss) \| Maximum drug concentration in plasma at steady state measured in (ng/ml) \| Time corresponding to maximum drug concentration in plasma at steady state \| \| Half life( t½) of drug in plasma \| Half life of drug measured in Hours(hr) \| Up to 12 hours \| \| Mean residence time of drug(MRT) \| Mean residence time of drug in plasma measured in (hr) \| From first sampling interval up to 12 hours \| \| steady state Clearance of drug(CLss) \| steady state Clearance of drug measured in (ml/min) \| From first sampling interval up to 12 hours \| \| Renal Clearance of drug(CLr) \| Renal Clearance of drug measured in (ml/min) \| From first sampling interval up to 12 hours \| \| Cumulative amount of drug eliminated in urine (Ae) \| Cumulative amount of drug eliminated in urine measured in (microgram(ug)/ml) \| From first sampling interval up to 12 hours \| \| Maximum excretion rate (Urate max) \| Maximum excretion rate for the drug measured in (milligram(mg)/hr) \| From first sampling interval up to 12 hours \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Blood Glucose(BG) levels \| Blood glucose levels measured in (mg/dl) \| up to 3 hours \| \| Area under the BG-time curve(AUG)0-3hr \| Area under the BG-time curve measured in (mg.hr/dl) \| up to 3 hours \| \| Maximum Glucose concentration(Gmax) \| Maximum Glucose concentration measured in (mg/dl) \| up to 3 hours \|
NCT01097603	Larsen & Toubro (L&T) Noninvasive Blood Pressure Module Performance Validation	To validate accuracy of the readings of noninvasive blood pressure (NIBP) module with sphygmomanometer as per the requirements of AAMI SP10:2002. This study is for adult and pediatric population.		L&T Noninvasive Blood Pressure Module Performance Validation	Blood Pressure		Subjects: Healthy volunteers~Inclusion Criteria:~Healthy subjects~Age between 1 - 60 yrs~Both genders~Consenting for the study~Exclusion Criteria:~Subjects suffering from cardiorespiratory, neurological or endocrinal disorders~Subjects with alcohol abuse/dependance~Female subjects who are pregnant or lactating~Subjects with pace maker implantations~Subjects: Diseased subjects~Inclusion Criteria:~Patients of hypertensive, ICU and in patients of different diseases~Age between 1 - 80 yrs~Both genders~Consenting for the study~Exclusion Criteria:~Healthy volunteers	1 Year	80 Years	All	Accepts Healthy Volunteers		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \|		Non-Invasive Blood Pressure			Larsen & Toubro (L&T) Noninvasive Blood Pressure Module Performance Validation Study Overview ================= Brief Summary ----------------- To validate accuracy of the readings of noninvasive blood pressure (NIBP) module with sphygmomanometer as per the requirements of AAMI SP10:2002. This study is for adult and pediatric population. Official Title ----------------- L&T Noninvasive Blood Pressure Module Performance Validation Conditions ----------------- Blood Pressure Participation Criteria ================= Eligibility Criteria ----------------- Subjects: Healthy volunteers Inclusion Criteria: Healthy subjects Age between 1 - 60 yrs Both genders Consenting for the study Exclusion Criteria: Subjects suffering from cardiorespiratory, neurological or endocrinal disorders Subjects with alcohol abuse/dependance Female subjects who are pregnant or lactating Subjects with pace maker implantations Subjects: Diseased subjects Inclusion Criteria: Patients of hypertensive, ICU and in patients of different diseases Age between 1 - 80 yrs Both genders Consenting for the study Exclusion Criteria: Healthy volunteers Ages Eligible for Study ----------------- Minimum Age: 1 Year Maximum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Non-Invasive Blood Pressure
NCT03187743	Personalised Pharmacological Approach to the Tapering of Corticosteroid Doses in Systemic Lupus Patients Treated With Prednisone	This research study is a multicentre prospective pharmacokinetic study. The clinical and biological data will be collected in the framework of a prospective study. The drug to be evaluated is a glucocorticoid routinely used to treat Systemic lupus erythematosus (SLE) patient. Initial dose of prednisone must be oral and at least 0.5mg/Kg/day, but the precise dosage and the tapering regimen will be determined according to the clinical judgment of the investigator. The duration of the research period for each patient will be 3 months. Three visits (which are all usual care visits) will be needed within the 3 months of the study for collecting data and/or blood sampling	Until now, glucocorticoids always play a leading role in the lupus treatment, and the lupus's prognosis has been greatly improved by the treatment of serious flare-ups with a combination of high-dose corticosteroids and immunosuppressants, notably mycophenolate mofetil (MMF) together with hydroxychloroquine (Plaquenil), survival at 10 years being 70 to 90%. However, corticosteroid treatment is also a major cause of morbidity and mortality, and with 60 years of experience, consensus about appropriate dosages, route of administration and tapering regimes has not been reached. In addition, there is a large variability in clinical response to corticosteroid therapy which may be attributed to heterogeneity of SLE, drugs interaction or to environmental and genetic factors, especially to polymorphism of the MDR (multi-drug resistance) -1 and NR3C1 (glucocorticoid nuclear receptor subfamily 3, group C, member 1). There are no previous studies investigating the role of MDR-1 and NR3C1 genes polymorphisms in the response to corticosteroids in lupus patients Drug monitoring of immunosuppressive drugs has been largely explored in renal transplantation and in a lesser extend in SLE (especially for mycophenolic acid). Relationship between prednisolone PK and clinical efficacy/toxicity have been also shown previously especially in renal transplant population. In patients with SLE, only two small series (8 children, 25 adults) have explored this relationship, and suggested that SLE activity and corticosteroid toxicity might be related to prednisolone AUC. Thus, limited data suggest that prednisone monitoring may optimize treatment efficacy and minimize adverse events.~The DECOR study will aim :~to search for relationship between prednisolone PK and SLE disease activity in a large series of patients in order to improve the rational of prednisone doses in lupus patients~to identify pharmacogenetic factors influencing the response to steroid in order to identify patients sharing a high probability of being responders or resistant to corticosteroids.~This approach could be applied to all inflammatory diseases requiring prolonged corticosteroid treatment, and thus, be a major progress in the use of this old treatment.	Personalised Pharmacological Approach to the Tapering of Corticosteroid Doses in Systemic Lupus Patients Treated With Prednisone	Lupus Erythematosus, Systemic	* Other: Blood samples	Inclusion Criteria:~Patient aged ≥ 6 years~Patient who met the American College of Rheumatology criteria (ACR) or the Systemic Lupus International Collaborating Clinics Classification (SLICC) for systemic lupus erythematosus.~Patients needs (re)initiation of oral prednisone regimen at least at 0.5 mg/Kg/d(or >30mg/d for patients >60 kg) in combination with mycophenolate mofetyl or mycofenolic acid or cyclophosphamide at usual dose including :~i) patient who receives bolus of methylprednisolone the week before and/or the week after inclusion for treating the lupus flare ii) patient who was previously treated by a low-prednisone dose (≤ 7.5 mg/d in patients ≥ 60 kg and ≤ 0.1 mg/kd/d in patient < 60 kg).~iii) patient who was previously treated by prednisone ≥ 0,5 mg/kg/d (or >30mg/d for patients >60 kg) but stopped since at least one month before inclusion~Patient with stable doses of other immunosuppressive or biological drugs before inclusion (at least 15 days for Imurel, Methotrexate, Tacrolimus ; at least 6 months for Rituximab, Belimumab) and during the 3 months of patient participation in the study.~Signed informed consent form by the patient (if aged ≥ 18 years), or by the parents / legal guardian and patient's agreement (if aged < 18 years)~Patient affiliated to the health insurance system~Exclusion Criteria:~Patient presents contraindications to corticosteroids~Patient presents contraindications to MMF, mycofenolic acid or cyclophosphamide for patient receiving immunosupressor~Patient cannot be treated by oral way~Patient whose physician has planned to stop prednisone in less than 3 months~Patient (or parents for minor) are unable to give a written informed consent for physical or psychical reasons~Patient disagrees with the study	6 Years	null	All	No	Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| SELENA-SLEDAI score \| \| 3 months \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Primary parameters : volume of distribution \| To study the pharmacokinetics of prednisolone in a population of patients with SLE \| Day 0, 1 month, 3 months \| \| Primary parameters : elimination clearance \| To study the pharmacokinetics of prednisolone in a population of patients with SLE \| Day 0, 1 month, 3 months \| \| Primary parameters : absorption constant \| To study the pharmacokinetics of prednisolone in a population of patients with SLE \| Day 0, 1 month, 3 months \| \| Secondary parameters : trough concentration \| To study the pharmacokinetics of prednisolone in a population of patients with SLE \| Day 0, 1 month, 3 months \| \| Secondary parameters : maximum concentration \| To study the pharmacokinetics of prednisolone in a population of patients with SLE \| Day 0, 1 month, 3 months \| \| Secondary parameters : Area Under Curve (AUC) \| To study the pharmacokinetics of prednisolone in a population of patients with SLE \| Day 0, 1 month, 3 months \| \| Secondary parameters : elimination half-life \| To study the pharmacokinetics of prednisolone in a population of patients with SLE \| Day 0, 1 month, 3 months \| \| Occurrence of adverse events \| \| 3 months \|	Lupus erythematosus, Systemic, Corticosteroid, Prednisone, Pharmacokinetics	Lupus Erythematosus, Systemic, Connective Tissue Diseases, Autoimmune Diseases, Immune System Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Pharmacokinetics/dynamics<br>Blood samples at 3 visits \| Other: Blood samples<br>* Blood samples at 3 visits :~V0 : - 5 mL in heparin tube / Pharmacokinetics + Gene Expression Analysis~V1 : - 5 mL in heparin tube / sample (2 to 5 samples) Pharmacokinetics + Pharmacogenetics + Gene Expression Analysis~V2 : - 5 mL in heparin tube / Pharmacokinetics + Gene Expression Analysis and - 5 mL in EDTA tube / DNA bank<br>\|	Personalised Pharmacological Approach to the Tapering of Corticosteroid Doses in Systemic Lupus Patients Treated With Prednisone Study Overview ================= Brief Summary ----------------- This research study is a multicentre prospective pharmacokinetic study. The clinical and biological data will be collected in the framework of a prospective study. The drug to be evaluated is a glucocorticoid routinely used to treat Systemic lupus erythematosus (SLE) patient. Initial dose of prednisone must be oral and at least 0.5mg/Kg/day, but the precise dosage and the tapering regimen will be determined according to the clinical judgment of the investigator. The duration of the research period for each patient will be 3 months. Three visits (which are all usual care visits) will be needed within the 3 months of the study for collecting data and/or blood sampling Detailed Description ----------------- Until now, glucocorticoids always play a leading role in the lupus treatment, and the lupus's prognosis has been greatly improved by the treatment of serious flare-ups with a combination of high-dose corticosteroids and immunosuppressants, notably mycophenolate mofetil (MMF) together with hydroxychloroquine (Plaquenil), survival at 10 years being 70 to 90%. However, corticosteroid treatment is also a major cause of morbidity and mortality, and with 60 years of experience, consensus about appropriate dosages, route of administration and tapering regimes has not been reached. In addition, there is a large variability in clinical response to corticosteroid therapy which may be attributed to heterogeneity of SLE, drugs interaction or to environmental and genetic factors, especially to polymorphism of the MDR (multi-drug resistance) -1 and NR3C1 (glucocorticoid nuclear receptor subfamily 3, group C, member 1). There are no previous studies investigating the role of MDR-1 and NR3C1 genes polymorphisms in the response to corticosteroids in lupus patients Drug monitoring of immunosuppressive drugs has been largely explored in renal transplantation and in a lesser extend in SLE (especially for mycophenolic acid). Relationship between prednisolone PK and clinical efficacy/toxicity have been also shown previously especially in renal transplant population. In patients with SLE, only two small series (8 children, 25 adults) have explored this relationship, and suggested that SLE activity and corticosteroid toxicity might be related to prednisolone AUC. Thus, limited data suggest that prednisone monitoring may optimize treatment efficacy and minimize adverse events. The DECOR study will aim : to search for relationship between prednisolone PK and SLE disease activity in a large series of patients in order to improve the rational of prednisone doses in lupus patients to identify pharmacogenetic factors influencing the response to steroid in order to identify patients sharing a high probability of being responders or resistant to corticosteroids. This approach could be applied to all inflammatory diseases requiring prolonged corticosteroid treatment, and thus, be a major progress in the use of this old treatment. Official Title ----------------- Personalised Pharmacological Approach to the Tapering of Corticosteroid Doses in Systemic Lupus Patients Treated With Prednisone Conditions ----------------- Lupus Erythematosus, Systemic Intervention / Treatment ----------------- * Other: Blood samples Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patient aged ≥ 6 years Patient who met the American College of Rheumatology criteria (ACR) or the Systemic Lupus International Collaborating Clinics Classification (SLICC) for systemic lupus erythematosus. Patients needs (re)initiation of oral prednisone regimen at least at 0.5 mg/Kg/d(or >30mg/d for patients >60 kg) in combination with mycophenolate mofetyl or mycofenolic acid or cyclophosphamide at usual dose including : i) patient who receives bolus of methylprednisolone the week before and/or the week after inclusion for treating the lupus flare ii) patient who was previously treated by a low-prednisone dose (≤ 7.5 mg/d in patients ≥ 60 kg and ≤ 0.1 mg/kd/d in patient < 60 kg). iii) patient who was previously treated by prednisone ≥ 0,5 mg/kg/d (or >30mg/d for patients >60 kg) but stopped since at least one month before inclusion Patient with stable doses of other immunosuppressive or biological drugs before inclusion (at least 15 days for Imurel, Methotrexate, Tacrolimus ; at least 6 months for Rituximab, Belimumab) and during the 3 months of patient participation in the study. Signed informed consent form by the patient (if aged ≥ 18 years), or by the parents / legal guardian and patient's agreement (if aged < 18 years) Patient affiliated to the health insurance system Exclusion Criteria: Patient presents contraindications to corticosteroids Patient presents contraindications to MMF, mycofenolic acid or cyclophosphamide for patient receiving immunosupressor Patient cannot be treated by oral way Patient whose physician has planned to stop prednisone in less than 3 months Patient (or parents for minor) are unable to give a written informed consent for physical or psychical reasons Patient disagrees with the study Ages Eligible for Study ----------------- Minimum Age: 6 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Pharmacokinetics/dynamics<br>Blood samples at 3 visits \| Other: Blood samples<br>* Blood samples at 3 visits : V0 : - 5 mL in heparin tube / Pharmacokinetics + Gene Expression Analysis V1 : - 5 mL in heparin tube / sample (2 to 5 samples) Pharmacokinetics + Pharmacogenetics + Gene Expression Analysis V2 : - 5 mL in heparin tube / Pharmacokinetics + Gene Expression Analysis and - 5 mL in EDTA tube / DNA bank<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| SELENA-SLEDAI score \| \| 3 months \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Primary parameters : volume of distribution \| To study the pharmacokinetics of prednisolone in a population of patients with SLE \| Day 0, 1 month, 3 months \| \| Primary parameters : elimination clearance \| To study the pharmacokinetics of prednisolone in a population of patients with SLE \| Day 0, 1 month, 3 months \| \| Primary parameters : absorption constant \| To study the pharmacokinetics of prednisolone in a population of patients with SLE \| Day 0, 1 month, 3 months \| \| Secondary parameters : trough concentration \| To study the pharmacokinetics of prednisolone in a population of patients with SLE \| Day 0, 1 month, 3 months \| \| Secondary parameters : maximum concentration \| To study the pharmacokinetics of prednisolone in a population of patients with SLE \| Day 0, 1 month, 3 months \| \| Secondary parameters : Area Under Curve (AUC) \| To study the pharmacokinetics of prednisolone in a population of patients with SLE \| Day 0, 1 month, 3 months \| \| Secondary parameters : elimination half-life \| To study the pharmacokinetics of prednisolone in a population of patients with SLE \| Day 0, 1 month, 3 months \| \| Occurrence of adverse events \| \| 3 months \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Lupus erythematosus, Systemic, Corticosteroid, Prednisone, Pharmacokinetics
NCT03623074	Control of Myopia Using Novel Spectacle Lens Designs	Randomized, controlled, multisite, subject-and observer-masked, 3-arm parallel group clinical trial of 36-month duration to evaluate the safety and efficacy of a novel spectacle lens design in reducing the progression of juvenile myopia.		Efficacy and Safety Study of Novel Spectacle Lens Designs to Control of Myopia	Juvenile Myopia	* Device: Novel spectacle lens design * Device: Spectacle lenses	Inclusion Criteria:~Children 6-10 years of age (day prior to 10th birthday) at time of informed consent/assent~SER error between -0.75 and -4.50 D~SER power between the two eyes must be less than or equal to 1.50 D~Willingness to participate in the trial for 3 years without content lens wear~Exclusion Criteria:~Previous or current use of contact lenses~Previous or current use of bifocals, progressive addition spectacles lenses~Previous or current use of myopia control treatment~Astigmatism worse then -1.25 DC in either eye	6 Years	10 Years	All	Accepts Healthy Volunteers	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Axial length \| Change in axial length from baseline \| 36 Months \| \| Spherical equivalent refraction \| Change in spherical equivalent refraction from baseline \| 36 Months \|		Myopia	Myopia, Refractive Errors, Eye Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Test Arm 1<br>Single vision, impact-resistant spectacle lenses \| Device: Novel spectacle lens design<br>* Use of lenses may reduce the rate of progression of juvenile myopia<br>\| \| Experimental: Test Arm 2<br>Single vision, impact-resistant spectacle lenses \| Device: Novel spectacle lens design<br>* Use of lenses may reduce the rate of progression of juvenile myopia<br>\| \| Other: Test Arm 3<br>Single vision, impact-resistant spectacle lenses \| Device: Spectacle lenses<br>* Use of lenses may reduce the rate of progression of juvenile myopia<br>\|	Control of Myopia Using Novel Spectacle Lens Designs Study Overview ================= Brief Summary ----------------- Randomized, controlled, multisite, subject-and observer-masked, 3-arm parallel group clinical trial of 36-month duration to evaluate the safety and efficacy of a novel spectacle lens design in reducing the progression of juvenile myopia. Official Title ----------------- Efficacy and Safety Study of Novel Spectacle Lens Designs to Control of Myopia Conditions ----------------- Juvenile Myopia Intervention / Treatment ----------------- * Device: Novel spectacle lens design * Device: Spectacle lenses Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Children 6-10 years of age (day prior to 10th birthday) at time of informed consent/assent SER error between -0.75 and -4.50 D SER power between the two eyes must be less than or equal to 1.50 D Willingness to participate in the trial for 3 years without content lens wear Exclusion Criteria: Previous or current use of contact lenses Previous or current use of bifocals, progressive addition spectacles lenses Previous or current use of myopia control treatment Astigmatism worse then -1.25 DC in either eye Ages Eligible for Study ----------------- Minimum Age: 6 Years Maximum Age: 10 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Test Arm 1<br>Single vision, impact-resistant spectacle lenses \| Device: Novel spectacle lens design<br>* Use of lenses may reduce the rate of progression of juvenile myopia<br>\| \| Experimental: Test Arm 2<br>Single vision, impact-resistant spectacle lenses \| Device: Novel spectacle lens design<br>* Use of lenses may reduce the rate of progression of juvenile myopia<br>\| \| Other: Test Arm 3<br>Single vision, impact-resistant spectacle lenses \| Device: Spectacle lenses<br>* Use of lenses may reduce the rate of progression of juvenile myopia<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Axial length \| Change in axial length from baseline \| 36 Months \| \| Spherical equivalent refraction \| Change in spherical equivalent refraction from baseline \| 36 Months \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Myopia
NCT04192201	A Real-world Study for Patients With Multiple Pulmonary Ground-glass Nodules	The purpose of this study is to actively monitor patients with multiple pulmonary Ground-glass Nodules (GGNs), in order to provide evidence for multiple GGNs treatment.	Multiple pulmonary GGNs are very commonly identified particularly as increasing numbers of CT scans are performed as part of routine lung cancer screening. At the same time, the ideal solution for these cases continues to be debated. This aim of this study is to learn more about the effects of multiple factors on outcome of multiple pulmonary GGNs, such as patients' clinical characteristics, CT features and different pathological types. Furthermore, the optimal timing of surgery and the effect of different surgical choices on the prognosis of patients with multiple GGNs will be investigated.	A Real-world Study for Patients With Multiple Pulmonary Ground-glass Nodules	Multiple Pulmonary Nodules		Inclusion Criteria:~Age greater than 18 years~Have two or more GGNs on CT imaging~Diameter of GGNs > 5mm and ≤ 3cm~GGNs must be greater than half ground glass~Exclusion Criteria:~patients who have a history of lung cancer~patients who have undergone chemotherapy, radiotherapy or targeted therapy before surgery~pregnant women	18 Years	null	All	No		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| 5-year overall survival [Time Frame: From date of the recruitment, assessed up to 60 months] \| 5-year overall survival \| October 31, 2024 \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| 5-year Progression-Free-Survival [Time Frame: From date of the recruitment, assessed up to 60 months] \| 5-year Progression-Free-Survival \| October 31, 2024 \| \| Recurrence-free survival [Time Frame: From date of the recruitment, assessed up to 60 months] \| Recurrence-free survival \| October 31, 2024 \|	Lung Neoplasms, Multiple Pulmonary Nodules	Multiple Pulmonary Nodules, Lung Neoplasms, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, Neoplasms, Lung Diseases, Respiratory Tract Diseases		A Real-world Study for Patients With Multiple Pulmonary Ground-glass Nodules Study Overview ================= Brief Summary ----------------- The purpose of this study is to actively monitor patients with multiple pulmonary Ground-glass Nodules (GGNs), in order to provide evidence for multiple GGNs treatment. Detailed Description ----------------- Multiple pulmonary GGNs are very commonly identified particularly as increasing numbers of CT scans are performed as part of routine lung cancer screening. At the same time, the ideal solution for these cases continues to be debated. This aim of this study is to learn more about the effects of multiple factors on outcome of multiple pulmonary GGNs, such as patients' clinical characteristics, CT features and different pathological types. Furthermore, the optimal timing of surgery and the effect of different surgical choices on the prognosis of patients with multiple GGNs will be investigated. Official Title ----------------- A Real-world Study for Patients With Multiple Pulmonary Ground-glass Nodules Conditions ----------------- Multiple Pulmonary Nodules Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age greater than 18 years Have two or more GGNs on CT imaging Diameter of GGNs > 5mm and ≤ 3cm GGNs must be greater than half ground glass Exclusion Criteria: patients who have a history of lung cancer patients who have undergone chemotherapy, radiotherapy or targeted therapy before surgery pregnant women Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| 5-year overall survival [Time Frame: From date of the recruitment, assessed up to 60 months] \| 5-year overall survival \| October 31, 2024 \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| 5-year Progression-Free-Survival [Time Frame: From date of the recruitment, assessed up to 60 months] \| 5-year Progression-Free-Survival \| October 31, 2024 \| \| Recurrence-free survival [Time Frame: From date of the recruitment, assessed up to 60 months] \| Recurrence-free survival \| October 31, 2024 \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Lung Neoplasms, Multiple Pulmonary Nodules
NCT02743455	A Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of MVA-BN Yellow Fever Vaccine With and Without Montanide ISA-720 Adjuvant in 18-45 Year Old Healthy Volunteers	This study is a multi-center, double-blind, placebo-controlled, Phase I study to evaluate the safety, reactogenicity, tolerability, and immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) in Flavivirus-naive healthy male and non-pregnant female adult subjects. There are six dose groups in this study. Subjects who have never received a licensed or investigational smallpox vaccine will be randomized to Groups 1-5 and vaccine administration and follow-up will be conducted in a double-blinded fashion. Subjects who have previously received two, 1 x 10^8 TCID50 doses of Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) between 19 and 45 days apart by s ubcutaneous (SC) or intramuscular (IM) routes will be enrolled in Group 6 and will be dosed open-label. Since this is a first in human, phase I study, a sentinel cohort will be utilized. The first two subjects (1st sentinel group) one at each clinical site will be randomized to Group 2 or 3 and vaccinated with MVA-BN-YF with or without Montanide ISA 720 adjuvant (ISA 720). Subjects and study personnel will be blinded as to whether ISA 720 was administered. The primary objectives are the: 1) assessment of the safety, tolerability, and reactogenicity of MVA-BN-YF vaccine administered with or without ISA 720; 2) comparison of the safety, tolerability, and reactogenicity of MVA-BN-YF vaccine administered with or without ISA 720 with Yellow Fever Vaccine (YF-VAX) and MVA-BN.	This study is a multi-center, double-blind, placebo-controlled, Phase I study to evaluate the safety, reactogenicity, tolerability, and immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) in Flavivirus-naive healthy male and non-pregnant female adult subjects. There are six dose groups in this study. Subjects who have never received a licensed or investigational smallpox vaccine will be randomized to Groups 1-5 and vaccine administration and follow-up will be conducted in a double-blinded fashion. Subjects who have previously received two, 1 x 10^8 TCID50 doses of Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) between 19 and 45 days apart by subcutaneous (SC) or intramuscular (IM) routes will be enrolled in Group 6 and will be dosed open-label. Since this is a first in human, phase I study, a sentinel cohort will be utilized. The first two subjects (1st sentinel group) one at each clinical site will be randomized to Group 2 or 3 and vaccinated with MVA-BN-YF with or without Montanide ISA 720 adjuvant (ISA 720). Subjects and study personnel will be blinded as to whether ISA 720 was administered. Subjects will be monitored for safety for one day, and if no pre-defined halting rule is met then two additional subjects (2nd sentinel group) one at each clinical site will be assigned to the group the previous subject was not assigned to. These subjects will be vaccinated and monitored as above. A total of 4 sentinel subjects will be vaccinated. The primary objectives are the: 1) assessment of the safety, tolerability, and reactogenicity of MVA-BN-YF vaccine administered with or without ISA 720; 2) comparison of the safety, tolerability, and reactogenicity of MVA-BN-YF vaccine administered with or without ISA 720 with Yellow Fever Vaccine (YF-VAX) and MVA-BN. The secondary objectives are the: 1) assessment of the immunogenicity against the MVA-BN backbone and Yellow Fever Virus (YF) antigen insert of MVA-BN-YF with and without ISA 720 as assessed by kinetics of the immune responses, seroconversion rates, and peak Geometric Mean Titer (GMT); 2) assessment of the impact of previous MVA-BN vaccination on peak immune responses to YF antigen in MVA-BN-YF; 3) comparison of the peak immunogenicity against YF antigen of 1 or 2 doses of MVA-BN-YF with or without ISA 720 with YF-VAX; 4) comparison of the peak immunogenicity against the MVA-BN backbone of 1 or 2 doses of MVA-BN-YF with or without ISA 720 with MVA-BN; 5) assessment of durability of immune response to YF antigen and MVA-BN at 6 months after 2nd vaccination or placebo administration.	A Phase I, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of MVA-BN Yellow Fever Vaccine With and Without Montanide ISA 720 Adjuvant in 18-45 Year Old Healthy Adults	Yellow Fever, Yellow Fever Immunisation	* Drug: ISA-720 * Biological: MVA Smallpox Vaccine * Biological: MVA-BN Yellow Fever Vaccine * Other: Placebo * Other: Placebo * Biological: YF Vax 17D Strain	Inclusion Criteria:~Must be a male or female at least 18 to < / = 45 years old at the time of screening.~Must be able to read and provide written consent and complete the Informed Consent.~Must have a body mass index (BMI) > / = 18.5 and < 35.0 kg/m^2.~Must be in good health on the basis of physical examination, vital signs, medical history, safety laboratories, and the investigator's clinical judgment. Safety laboratory normal ranges will be those used by the reference clinical lab. Protocol-specific criteria for individual subjects are listed in criteria #6~The clinical laboratory evaluations that will be graded as laboratory Adverse Events (AEs) and be considered for the Study or Individual Halting Rules are those which are included in the laboratory toxicity grading scales.~Vital signs must be in normal ranges. If a subject has elevated systolic or diastolic blood pressure, subject may rest for 10 minutes in a quiet room and then the blood pressure may be retaken once.~For Group 6: subjects must have documented previous vaccination with MVA-BN. In order to be enrolled, a subject has to have received two 1x10^8 TCID50 doses of MVA-BN 19-45 days apart subcutaneous (SC) or intramuscular (IM) as part of participation in DMID vaccine trials 11-0021 or 09-0002. First dose must have been administered no earlier than 2010.~Must have acceptable* laboratory criteria within 28 days before enrollment.~Acceptable lab parameters include:~Hemoglobin: women: > 11.0 g/dL; men > 12.5 g/dL~White blood cell count: > 3,700 cells/mm^3 but < 11,000 cells/mm^3~Platelets: > 125,000 but < 375,000 per mm^3~Urine dipstick (clean urine sample): protein < 1+, glucose negative~Alanine aminotransferase and aspartate aminotransferase (ALT, AST) < 1.25 x institutional upper limit of normal~Blood urea nitrogen (BUN) < / = 1 x institutional upper limit of normal~Total bilirubin < 1.25x institutional upper limit of normal.~Serum creatinine < / = 1 x institutional upper limit of normal~If laboratory screening tests are out of range, repeat of screening tests is permitted once, provided there is an alternative explanation for the out of range value.~Women of childbearing potential must have a negative serum pregnancy test at screening and negative urine pregnancy tests prior to each vaccination.~Women of childbearing potential must have an acceptable method of contraception from 28 days prior to the 1st vaccination until at least 60 days after the 2nd vaccination.~Acceptable methods of contraception include the following:~-Prescription oral contraceptives, contraceptive injections, intrauterine device (IUD), implants, vaginal ring, double-barrier method, contraceptive patch, male partner sterilization, abstinence (defined as refraining from heterosexual intercourse during participation in the study [from 28 days before the first vaccination until at least 60 days after the last vaccination]). Women of non-childbearing potential, defined as postmenopausal (any age with amenorrhea for = / > 12 months without other known or suspected cause for amenorrhea, or surgically sterile (hysterectomy, bilateral tubal ligation, obilateral oophorectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with documented confirmation test at least 3 months after the procedure), are not required to use the birth control methods.~Female subjects must agree to not donate eggs (ova, oocytes) from the start of screening onwards until at least 60 days after the last vaccination.~Male subjects who have not had a vasectomy and is sexually active with a woman of childbearing potential must agree to use an acceptable measure of birth control from 28 days prior to 1st vaccination until at least 60 days after the last vaccination.~Acceptable methods of birth control include the following:~Abstinence (defined as refraining from heterosexual intercourse with a female partner of childbearing potential during participation in the study [from 28 days before the first vaccination until at least 60 days after the last vaccination].~A double-barrier method of birth control, such as condom with spermicidal foam/gel/film/cream/suppository and partner with occlusive cap (diaphragm, cervical/vault caps).~In case the female partner is using an acceptable method of birth control (see Inclusion Criterion #8), a single-barrier method of birth control for the male subject is acceptable.~Male subjects must agree to not donate sperm from the start of screening onwards until at least 60 days after the last vaccination.~Must be available and willing to participate for the duration of the study visits and follow-up.~Must have a means to be contacted by telephone.~Exclusion Criteria:~Was ever vaccinated with a licensed or investigational YF vaccine or was diagnosed with YF infection or disease.~Includes YF-VAX, Stamaril, or Bio-Manguinhos yellow fever vaccine. Subject's verbal history will suffice.~Was ever vaccinated with a licensed or investigational Flavivirus vaccine.~Including Japanese encephalitis virus (JEV) vaccine or an investigational Flavivirus vaccine including dengue virus (DENV) or West Nile virus vaccine, or has been diagnosed with an illness caused by a Flavivirus including DENV, West Nile virus (WNV), JEV, St. Louis encephalitis, or tick-borne encephalitis virus (TBEV). Subject's verbal history will suffice.~Positive serology for HIV, Hepatitis C virus, or Hepatitis B surface antigen.~Positive serology to Dengue, Yellow Fever, or West Nile virus.~Plans to travel to a Yellow-Fever endemic area during the course of the study or travel to a Yellow-Fever endemic area within 30 days of screening.~Subjects who have a recent travel to a Yellow Fever endemic area may screen if they have returned to the U.S. 30 or more days prior to the screening visit. Refer to the CDC Yellow Fever map for countries/regions at risk for Yellow Fever virus infection. http://www.cdc.gov/yellowfever/maps/~Was ever vaccinated with a licensed or investigational smallpox vaccine with the exception of subjects in Group 6.~Includes Dryvax, Acam2000, LC 16 m8, MVA-based vaccine candidate or licensed vaccines, and Imvamune or Imvanex.~-EXCEPTION: Group 6 should have had two 1 x 10^8 TCID 50 doses of MVA-BN 19-45 days apart SC or IM as part of participation in DMID vaccine trials 11-0021 or 09-0002. First dose must have been administered no earlier than 2010.~Has known allergy or history of anaphylaxis or other serious adverse reaction to a vaccine or vaccine products.~Including egg products, aminoglycosides, gelatin, sorbitol, tris (hydroxymethyl)-amino methane (THAM), or any of the constituents of the study vaccines.~Has severe allergy or anaphylaxis to latex.~Participants in Group 6 will not be exposed to latex and so may have history of severe allergy or anaphylaxis to latex.~Has an acute illness or temperature > / = 38.0 degrees Celsius on Day 1 or Day 29.~Subjects with fever or acute illness on the Day of vaccination may be re-assessed and enrolled if healthy or only minor residual symptoms remain within 3 days.~Female subjects who are pregnant or breast-feeding, or planning to become pregnant while enrolled in the study.~Has history of chronic or acute severe neurologic condition.~Including history of seizure disorder or epilepsy, history of Guillain-Barre syndrome, Bell's palsy, meningitis, or disease with any focal neurologic deficits.~Has history of thymus disorder including myasthenia gravis, thymoma or prior thymectomy.~Has history of autoimmune disease, or clinically significant cardiac, pulmonary, hepatic, rheumatologic, or renal disease by history, physical examination, and/or laboratory studies.~Includes the conditions and diagnoses defined as AESI.~Has history of malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure.~Subjects with a history of skin cancer must not be vaccinated at the previous tumor site.~Has known or suspected congenital or acquired immunodeficiency, or recent history or current use of immunosuppressive therapy.~Anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term (at least 2 weeks within the previous 3 months) systemic corticosteroids therapy (at a dose of at least 0.5 mg/kg/day). Intranasal or topical prednisone (or equivalent) are allowed.~Is post-organ and/or stem cell transplant whether or not on chronic immunosuppressive therapy.~Had major surgery (per the investigator's judgment) within the 4 weeks prior to study entry or planned major surgery during the course of the study.~Has personal history of recurring migraines (every 6 months or more often) or on prescription medication for treatment of recurring headaches or migraines.~Has history of cardiac disease.~Myocarditis, pericarditis, cardiomyopathy, transient ischemic attack or stroke, myocardial infarction, angina, coronary artery disease, congestive heart failure, clinically significant arrhythmia. Includes any arrhythmia requiring medication, treatment, or clinical follow-up.~Has electrocardiogram (ECG) with clinically significant findings, or features that would interfere with the assessment of myocarditis/pericarditis.~Including any of the following:~Conduction disturbance (complete left or complete right bundle branch block or nonspecific intraventricular conduction disturbance with QRS = / > 120 ms, PR interval > 219 ms, any second-or third-degree atrioventricular block, or prolongation of the QT interval corrected according to Bazett's formula [QTcB] [> 450 ms]).~Significant repolarization (ST-segment or T-wave) abnormality.~Significant atrial or ventricular arrhythmia; frequent atrial or ventricular ectopy (e.g., frequent premature atrial contractions, 2 premature ventricular contractions in a row).~ST-elevation consistent with ischemia or evidence of past or evolving myocardial infarction.~Has history of diabetes mellitus type 1 or type 2, including cases controlled with diet alone.~-Note: history of isolated gestational diabetes is not an exclusion criterion.~Has history of thyroidectomy, or thyroid disease requiring medication during the last 12 months.~Has history of hypertension even if medically controlled.~-Note: Vital signs must be normal by protocol toxicity grading scale or determined to be normal-variant by investigator. In the event of an abnormal heart rate or blood pressure due to physiological variation or activity, the subject may rest for 10 minutes in a quiet room, and then blood pressure and/or heart rate may be re-measured. Repeated vital signs may be used to determine eligibility.~Received live attenuated vaccines from 30 days before Day 1 until 30 days after the 2nd vaccination.~Received killed or inactivated vaccines from 14 days before Day 1 until 14 days after the 2nd vaccination.~Received experimental therapeutic agents within 3 months prior to the first study vaccination or plans to receive any experimental therapeutic agents during the course of the study.~Is currently participating or plans to participate in another clinical study which would involve receipt of the following:~An investigational product, blood drawing, or an invasive medical procedure that would require administration of anesthetics or intravenous dyes or removal of tissue during the study.~-Includes endoscopy, bronchoscopy, or administration of IV contrast.~Received blood products or immunoglobulin in the 3 months before study entry or planned use during the course of the study.~Donated a unit of blood within 8 weeks before Day 1 or plans to donate blood during the course of the study.~Has major psychiatric illness during the past 12 months that in the opinion of the investigator would preclude participation.~Has current alcohol use or current or past abuse of recreational or narcotic drugs by history as judged by the investigator to potentially interfere with study adherence.~Has a history of chronic urticaria (recurrent hives).~Has tattoos, scars, or other marks on both deltoid areas which would, in the opinion of the investigator, interfere with assessment of the vaccination site.~Is a study site employee or staff who are paid entirely or partially by/through the OCRR contract for the trial, or staff who are supervised by the PI or Sub-Investigators.~*Including the Principal Investigator (PI), sub-Investigators listed in Form FDA 1572 or Investigator of Record Form.~In the opinion of the investigator cannot communicate reliably, is unlikely to adhere to the requirements of the study, or has any condition which would limit the subject's ability to complete the study.	18 Years	45 Years	All	Accepts Healthy Volunteers	Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Comparison of Grade 3 local, systemic or laboratory toxicities, continuous Grade 2 or greater local reactogenicity \| \| Day 1 through Day 8 \| \| Comparison of Grade 3 local, systemic or laboratory toxicities, continuous Grade 2 or greater local reactogenicity \| \| Day 29 through Day 36 \| \| Number of adverse events of special interest (AESIs) considered related to study vaccination in Group 1 \| \| Day 1 through Day 394 \| \| Number of adverse events of special interest (AESIs) considered related to study vaccination in Group 2 \| \| Day 1 through Day 394 \| \| Number of adverse events of special interest (AESIs) considered related to study vaccination in Group 3 \| \| Day 1 through Day 394 \| \| Number of adverse events of special interest (AESIs) considered related to study vaccination in Group 4 \| \| Day 1 through Day 394 \| \| Number of adverse events of special interest (AESIs) considered related to study vaccination in Group 5 \| \| Day 1 through Day 394 \| \| Number of adverse events of special interest (AESIs) considered related to study vaccination in Group 6 \| \| Day 1 through Day 394 \| \| Number of adverse events of special interest (AESIs) considered related to study vaccination overall \| \| Day 1 through Day 394 \| \| Number of related adverse events of special interest (AESIs) \| \| Day 1 through Day 394 \| \| Number of related serious adverse events (SAEs) \| \| Day 1 through Day 394 \| \| Number of serious adverse events (SAEs) considered related to study vaccination in Group 1 \| \| Day 1 through Day 394 \| \| Number of serious adverse events (SAEs) considered related to study vaccination in Group 2 \| \| Day 1 through Day 394 \| \| Number of serious adverse events (SAEs) considered related to study vaccination in Group 3 \| \| Day 1 through Day 394 \| \| Number of serious adverse events (SAEs) considered related to study vaccination in Group 4 \| \| Day 1 through Day 394 \| \| Number of serious adverse events (SAEs) considered related to study vaccination in Group 5 \| \| Day 1 through Day 394 \| \| Number of serious adverse events (SAEs) considered related to study vaccination in Group 6 \| \| Day 1 through Day 394 \| \| Number of serious adverse events (SAEs) considered related to study vaccination overall \| \| Day 1 through Day 394 \| \| Number of subjects with new onset of a chronic medical condition in Group 1 \| \| Day 1 through Day 394 \| \| Number of subjects with new onset of a chronic medical condition in Group 2 \| \| Day 1 through Day 394 \| \| Number of subjects with new onset of a chronic medical condition in Group 3 \| \| Day 1 through Day 394 \| \| Number of subjects with new onset of a chronic medical condition in Group 4 \| \| Day 1 through Day 394 \| \| Number of subjects with new onset of a chronic medical condition in Group 5 \| \| Day 1 through Day 394 \| \| Number of subjects with new onset of a chronic medical condition in Group 6 \| \| Day 1 through Day 394 \| \| Number of subjects with new onset of a chronic medical condition overall \| \| Day 1 through Day 394 \| \| Number of subjects with unsolicited vaccine-related adverse events (AEs) in Group 1 \| \| Day 1 through Day 57 \| \| Number of subjects with unsolicited vaccine-related adverse events (AEs) in Group 2 \| \| Day 1 through Day 57 \| \| Number of subjects with unsolicited vaccine-related adverse events (AEs) in Group 3 \| \| Day 1 through Day 57 \| \| Number of subjects with unsolicited vaccine-related adverse events (AEs) in Group 4 \| \| Day 1 through Day 57 \| \| Number of subjects with unsolicited vaccine-related adverse events (AEs) in Group 5 \| \| Day 1 through Day 57 \| \| Number of subjects with unsolicited vaccine-related adverse events (AEs) in Group 6 \| \| Day 1 through Day 57 \| \| Number of subjects with unsolicited vaccine-related adverse events (AEs) overall \| \| Day 1 through Day 57 \| \| Number of vaccine-related laboratory adverse events (AEs) in Group 1 \| \| Day 1 through Day 57 \| \| Number of vaccine-related laboratory adverse events (AEs) in Group 2 \| \| Day 1 through Day 57 \| \| Number of vaccine-related laboratory adverse events (AEs) in Group 3 \| \| Day 1 through Day 57 \| \| Number of vaccine-related laboratory adverse events (AEs) in Group 4 \| \| Day 1 through Day 57 \| \| Number of vaccine-related laboratory adverse events (AEs) in Group 5 \| \| Day 1 through Day 57 \| \| Number of vaccine-related laboratory adverse events (AEs) in Group 6 \| \| Day 1 through Day 57 \| \| Number of withdrawals or discontinuation of vaccinations due to any reason \| \| Day 1 through Day 394 \| \| Occurrence of solicited injection site reactogenicity events in Group 1 \| \| Day 1 through Day 8 \| \| Occurrence of solicited injection site reactogenicity events in Group 1 \| \| Day 29 through Day 36 \| \| Occurrence of solicited injection site reactogenicity events in Group 2 \| \| Day 1 through Day 8 \| \| Occurrence of solicited injection site reactogenicity events in Group 2 \| \| Day 29 through Day 36 \| \| Occurrence of solicited injection site reactogenicity events in Group 3 \| \| Day 1 through Day 8 \| \| Occurrence of solicited injection site reactogenicity events in Group 3 \| \| Day 29 through Day 36 \| \| Occurrence of solicited injection site reactogenicity events in Group 4 \| \| Day 1 through Day 8 \| \| Occurrence of solicited injection site reactogenicity events in Group 4 \| \| Day 29 through Day 36 \| \| Occurrence of solicited injection site reactogenicity events in Group 5 \| \| Day 1 through Day 8 \| \| Occurrence of solicited injection site reactogenicity events in Group 5 \| \| Day 29 through Day 36 \| \| Occurrence of solicited injection site reactogenicity events in Group 6 \| \| Day 1 through Day 8 \| \| Occurrence of solicited injection site reactogenicity events in Group 6 \| \| Day 29 through Day 36 \| \| Occurrence of solicited injection site reactogenicity events overall \| \| Day 1 through Day 8 \| \| Occurrence of solicited injection site reactogenicity events overall \| \| Day 29 through Day 36 \| \| Occurrence of solicited systemic reactogenicity events in Group 1 \| \| Day 1 through Day 8 \| \| Occurrence of solicited systemic reactogenicity events in Group 1 \| \| Day 29 through Day 36 \| \| Occurrence of solicited systemic reactogenicity events in Group 2 \| \| Day 1 through Day 8 \| \| Occurrence of solicited systemic reactogenicity events in Group 2 \| \| Day 29 through Day 36 \| \| Occurrence of solicited systemic reactogenicity events in Group 3 \| \| Day 1 through Day 8 \| \| Occurrence of solicited systemic reactogenicity events in Group 3 \| \| Day 29 through Day 36 \| \| Occurrence of solicited systemic reactogenicity events in Group 4 \| \| Day 1 through Day 8 \| \| Occurrence of solicited systemic reactogenicity events in Group 4 \| \| Day 29 through Day 36 \| \| Occurrence of solicited systemic reactogenicity events in Group 5 \| \| Day 1 through Day 8 \| \| Occurrence of solicited systemic reactogenicity events in Group 5 \| \| Day 29 through Day 36 \| \| Occurrence of solicited systemic reactogenicity events in Group 6 \| \| Day 1 through Day 8 \| \| Occurrence of solicited systemic reactogenicity events in Group 6 \| \| Day 29 through Day 36 \| \| Occurrence of solicited systemic reactogenicity events overall \| \| Day 1 through Day 8 \| \| Occurrence of solicited systemic reactogenicity events overall \| \| Day 29 through Day 36 \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Comparison of geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 1 and Group 2 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 1 and Group 3 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 1 and Group 4 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 1 and Group 2 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 1 and Group 3 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 1 and Group 4 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to YF between Group 5 and Group 2 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to YF between Group 5 and Group 3 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to YF between Group 5 and Group 4 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to YF between Group 5 and Group 6 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to YF between Group 6 and Group 2 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to YF between Group 6 and Group 3 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to YF between Group 6 and Group 4 \| \| Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 1 and Group 2 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 1 and Group 3 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 1 and Group 4 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 2 and Group 3 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 2 and Group 4 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 3 and Group 4 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 1 and Group 2 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 1 and Group 3 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 1 and Group 4 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 2 and Group 3 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 2 and Group 4 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 3 and Group 4 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 2 and Group 3 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 2 and Group 3 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 2 and Group 4 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 2 and Group 4 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 2 and Group 5 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 2 and Group 5 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 2 and Group 6 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 2 and Group 6 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 3 and Group 4 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 3 and Group 4 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 3 and Group 5 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 3 and Group 5 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 3 and Group 6 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 3 and Group 6 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 4 and Group 5 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 4 and Group 5 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 4 and Group 6 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 4 and Group 6 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 5 and Group 6 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 5 and Group 6 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination with MVA-BN-YF in Group 6 compared to Group 2 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination with MVA-BN-YF in Group 6 compared to Group 2 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination with MVA-BN-YF in Group 6 compared to Group 3 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination with MVA-BN-YF in Group 6 compared to Group 3 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination with MVA-BN-YF in Group 6 compared to Group 4 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination with MVA-BN-YF in Group 6 compared to Group 4 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 2 and Group 3 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 2 and Group 4 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 2 and Group 5 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 2 and Group 6 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 3 and Group 4 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 3 and Group 5 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 3 and Group 6 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 4 and Group 5 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 4 and Group 6 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 5 and Group 6 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 1 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 2 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 3 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 4 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 6 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 1 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 2 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 3 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 4 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 6 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to YF in Group 2 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to YF in Group 3 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to YF in Group 4 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to YF in Group 5 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to YF in Group 6 \| \| Day 1 through Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 1 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 1 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 1 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 1 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 1 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 1 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 1 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 2 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 2 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 2 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 2 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 2 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 2 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 2 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 3 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 3 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 3 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 3 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 3 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 3 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 3 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 4 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 4 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 4 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 4 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 4 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 4 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 4 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 6 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 6 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 6 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 6 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 6 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 6 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 6 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 1 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 1 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 1 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 1 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 1 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 1 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 1 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 2 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 2 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 2 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 2 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 2 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 2 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 2 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 3 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 3 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 3 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 3 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 3 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 3 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 3 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 4 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 4 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 4 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 4 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 4 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 4 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 4 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 6 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 6 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 6 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 6 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 6 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 6 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 6 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 2 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 2 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 2 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 2 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 2 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 2 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 2 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 3 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 3 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 3 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 3 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 3 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 3 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 3 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 4 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 4 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 4 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 4 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 4 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 4 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 4 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 5 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 5 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 5 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 5 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 5 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 5 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 5 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 6 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 6 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 6 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 6 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 6 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 6 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 6 \| \| Day 57 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 1 \| \| Day 1 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 1 \| \| Day 15 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 1 \| \| Day 211 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 1 \| \| Day 22 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 1 \| \| Day 29 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 1 \| \| Day 36 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 1 \| \| Day 43 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 1 \| \| Day 50 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 1 \| \| Day 57 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 2 \| \| Day 1 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 2 \| \| Day 15 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 2 \| \| Day 211 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 2 \| \| Day 22 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 2 \| \| Day 29 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 2 \| \| Day 36 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 2 \| \| Day 43 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 2 \| \| Day 50 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 2 \| \| Day 57 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 3 \| \| Day 1 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 3 \| \| Day 15 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 3 \| \| Day 211 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 3 \| \| Day 22 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 3 \| \| Day 29 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 3 \| \| Day 36 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 3 \| \| Day 43 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 3 \| \| Day 50 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 3 \| \| Day 57 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 4 \| \| Day 1 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 4 \| \| Day 15 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 4 \| \| Day 211 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 4 \| \| Day 22 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 4 \| \| Day 29 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 4 \| \| Day 36 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 4 \| \| Day 43 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 4 \| \| Day 50 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 4 \| \| Day 57 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 2 \| \| Day 1 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 2 \| \| Day 15 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 2 \| \| Day 211 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 2 \| \| Day 22 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 2 \| \| Day 29 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 2 \| \| Day 36 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 2 \| \| Day 43 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 2 \| \| Day 50 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 2 \| \| Day 57 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 3 \| \| Day 1 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 3 \| \| Day 15 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 3 \| \| Day 211 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 3 \| \| Day 22 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 3 \| \| Day 29 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 3 \| \| Day 36 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 3 \| \| Day 43 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 3 \| \| Day 50 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 3 \| \| Day 57 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 4 \| \| Day 1 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 4 \| \| Day 15 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 4 \| \| Day 211 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 4 \| \| Day 22 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 4 \| \| Day 29 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 4 \| \| Day 36 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 4 \| \| Day 43 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 4 \| \| Day 50 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 4 \| \| Day 57 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 5 \| \| Day 1 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 5 \| \| Day 15 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 5 \| \| Day 211 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 5 \| \| Day 22 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 5 \| \| Day 29 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 5 \| \| Day 36 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 5 \| \| Day 43 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 5 \| \| Day 50 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 5 \| \| Day 57 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 6 \| \| Day 1 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 6 \| \| Day 15 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 6 \| \| Day 211 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 6 \| \| Day 22 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 6 \| \| Day 29 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 6 \| \| Day 36 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 6 \| \| Day 43 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 6 \| \| Day 50 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 6 \| \| Day 57 \|	Fever, Immunogenicity, MVA-BN, Reactogenicity, Vaccine, Yellow	Vaccines, Immunologic Factors, Physiological Effects of Drugs	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Group 1<br>Subjects will receive 1.0x10^8 TCID50 of MVA-BN as two doses subcutaneously on Day 1 and Day 29. N=15 \| Biological: MVA Smallpox Vaccine<br>* Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine (MVA BN(R)) is a purified live vaccine will be used as an active comparator.<br>\| \| Experimental: Group 2<br>Subjects will receive 1.0x10^8 TCID50 of MVA-BN-YF as two doses intramuscularly on Day 1 and Day 29. N=15 \| Biological: MVA-BN Yellow Fever Vaccine<br>* Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) clinical trial material is manufactured in CEF cells derived from Specific Pathogen Free (SPF) eggs in a bioreactor culture using serum free medium.<br>\| \| Experimental: Group 3<br>Subjects will receive 1.0x10^8 TCID50 of MVA-BN-YF + ISA 720 as two doses intramuscularly on Day 1 and Day 29. N=15 \| Drug: ISA-720<br>* The vaccine adjuvant ISA 720 will be used with Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) as vaccine adjuvant with a depot effect. This comprises slow release of antigen at the injection site, protection of antigen against degradation and strong stimulation of the immune response.<br>Biological: MVA-BN Yellow Fever Vaccine<br>* Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) clinical trial material is manufactured in CEF cells derived from Specific Pathogen Free (SPF) eggs in a bioreactor culture using serum free medium.<br>\| \| Experimental: Group 4<br>Subjects will receive 1.0x10^8 TCID50 of MVA-BN-YF + ISA 720 as a single dose intramuscularly on Day 1 and matching placebo on Day 29. N=15 \| Drug: ISA-720<br>* The vaccine adjuvant ISA 720 will be used with Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) as vaccine adjuvant with a depot effect. This comprises slow release of antigen at the injection site, protection of antigen against degradation and strong stimulation of the immune response.<br>Biological: MVA-BN Yellow Fever Vaccine<br>* Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) clinical trial material is manufactured in CEF cells derived from Specific Pathogen Free (SPF) eggs in a bioreactor culture using serum free medium.<br>Other: Placebo<br>* 0.9% Sodium Chloride Injection, USP is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection.<br>\| \| Active Comparator: Group 5<br>Subjects will receive = / > 4.74 log10 PFU of YF-Vax as a single dose subcutaneously on Day 1 and matching placebo on Day 29. N=15 \| Other: Placebo<br>* 0.9% Sodium Chloride Injection, USP is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection.<br>Biological: YF Vax 17D Strain<br>* Yellow Fever Vaccine (YF-VAX) is a vaccine prepared by culturing the 17D-204 strain of yellow fever virus in living avian leucosis virus-free (ALV-free) chicken embryos. Will be used as an active comparator.<br>\| \| Experimental: Group 6<br>Subjects with prior receipt of MVA-BN will receive 1.0x10^8 TCID50 of MVA-BN-YF as two doses intramuscularly on Day 1 and Day 29. N=15 \| Biological: MVA-BN Yellow Fever Vaccine<br>* Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) clinical trial material is manufactured in CEF cells derived from Specific Pathogen Free (SPF) eggs in a bioreactor culture using serum free medium.<br>\|	A Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of MVA-BN Yellow Fever Vaccine With and Without Montanide ISA-720 Adjuvant in 18-45 Year Old Healthy Volunteers Study Overview ================= Brief Summary ----------------- This study is a multi-center, double-blind, placebo-controlled, Phase I study to evaluate the safety, reactogenicity, tolerability, and immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) in Flavivirus-naive healthy male and non-pregnant female adult subjects. There are six dose groups in this study. Subjects who have never received a licensed or investigational smallpox vaccine will be randomized to Groups 1-5 and vaccine administration and follow-up will be conducted in a double-blinded fashion. Subjects who have previously received two, 1 x 10^8 TCID50 doses of Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) between 19 and 45 days apart by s ubcutaneous (SC) or intramuscular (IM) routes will be enrolled in Group 6 and will be dosed open-label. Since this is a first in human, phase I study, a sentinel cohort will be utilized. The first two subjects (1st sentinel group) one at each clinical site will be randomized to Group 2 or 3 and vaccinated with MVA-BN-YF with or without Montanide ISA 720 adjuvant (ISA 720). Subjects and study personnel will be blinded as to whether ISA 720 was administered. The primary objectives are the: 1) assessment of the safety, tolerability, and reactogenicity of MVA-BN-YF vaccine administered with or without ISA 720; 2) comparison of the safety, tolerability, and reactogenicity of MVA-BN-YF vaccine administered with or without ISA 720 with Yellow Fever Vaccine (YF-VAX) and MVA-BN. Detailed Description ----------------- This study is a multi-center, double-blind, placebo-controlled, Phase I study to evaluate the safety, reactogenicity, tolerability, and immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) in Flavivirus-naive healthy male and non-pregnant female adult subjects. There are six dose groups in this study. Subjects who have never received a licensed or investigational smallpox vaccine will be randomized to Groups 1-5 and vaccine administration and follow-up will be conducted in a double-blinded fashion. Subjects who have previously received two, 1 x 10^8 TCID50 doses of Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) between 19 and 45 days apart by subcutaneous (SC) or intramuscular (IM) routes will be enrolled in Group 6 and will be dosed open-label. Since this is a first in human, phase I study, a sentinel cohort will be utilized. The first two subjects (1st sentinel group) one at each clinical site will be randomized to Group 2 or 3 and vaccinated with MVA-BN-YF with or without Montanide ISA 720 adjuvant (ISA 720). Subjects and study personnel will be blinded as to whether ISA 720 was administered. Subjects will be monitored for safety for one day, and if no pre-defined halting rule is met then two additional subjects (2nd sentinel group) one at each clinical site will be assigned to the group the previous subject was not assigned to. These subjects will be vaccinated and monitored as above. A total of 4 sentinel subjects will be vaccinated. The primary objectives are the: 1) assessment of the safety, tolerability, and reactogenicity of MVA-BN-YF vaccine administered with or without ISA 720; 2) comparison of the safety, tolerability, and reactogenicity of MVA-BN-YF vaccine administered with or without ISA 720 with Yellow Fever Vaccine (YF-VAX) and MVA-BN. The secondary objectives are the: 1) assessment of the immunogenicity against the MVA-BN backbone and Yellow Fever Virus (YF) antigen insert of MVA-BN-YF with and without ISA 720 as assessed by kinetics of the immune responses, seroconversion rates, and peak Geometric Mean Titer (GMT); 2) assessment of the impact of previous MVA-BN vaccination on peak immune responses to YF antigen in MVA-BN-YF; 3) comparison of the peak immunogenicity against YF antigen of 1 or 2 doses of MVA-BN-YF with or without ISA 720 with YF-VAX; 4) comparison of the peak immunogenicity against the MVA-BN backbone of 1 or 2 doses of MVA-BN-YF with or without ISA 720 with MVA-BN; 5) assessment of durability of immune response to YF antigen and MVA-BN at 6 months after 2nd vaccination or placebo administration. Official Title ----------------- A Phase I, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of MVA-BN Yellow Fever Vaccine With and Without Montanide ISA 720 Adjuvant in 18-45 Year Old Healthy Adults Conditions ----------------- Yellow Fever, Yellow Fever Immunisation Intervention / Treatment ----------------- * Drug: ISA-720 * Biological: MVA Smallpox Vaccine * Biological: MVA-BN Yellow Fever Vaccine * Other: Placebo * Other: Placebo * Biological: YF Vax 17D Strain Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Must be a male or female at least 18 to < / = 45 years old at the time of screening. Must be able to read and provide written consent and complete the Informed Consent. Must have a body mass index (BMI) > / = 18.5 and < 35.0 kg/m^2. Must be in good health on the basis of physical examination, vital signs, medical history, safety laboratories, and the investigator's clinical judgment. Safety laboratory normal ranges will be those used by the reference clinical lab. Protocol-specific criteria for individual subjects are listed in criteria #6 The clinical laboratory evaluations that will be graded as laboratory Adverse Events (AEs) and be considered for the Study or Individual Halting Rules are those which are included in the laboratory toxicity grading scales. Vital signs must be in normal ranges. If a subject has elevated systolic or diastolic blood pressure, subject may rest for 10 minutes in a quiet room and then the blood pressure may be retaken once. For Group 6: subjects must have documented previous vaccination with MVA-BN. In order to be enrolled, a subject has to have received two 1x10^8 TCID50 doses of MVA-BN 19-45 days apart subcutaneous (SC) or intramuscular (IM) as part of participation in DMID vaccine trials 11-0021 or 09-0002. First dose must have been administered no earlier than 2010. Must have acceptable* laboratory criteria within 28 days before enrollment. Acceptable lab parameters include: Hemoglobin: women: > 11.0 g/dL; men > 12.5 g/dL White blood cell count: > 3,700 cells/mm^3 but < 11,000 cells/mm^3 Platelets: > 125,000 but < 375,000 per mm^3 Urine dipstick (clean urine sample): protein < 1+, glucose negative Alanine aminotransferase and aspartate aminotransferase (ALT, AST) < 1.25 x institutional upper limit of normal Blood urea nitrogen (BUN) < / = 1 x institutional upper limit of normal Total bilirubin < 1.25x institutional upper limit of normal. Serum creatinine < / = 1 x institutional upper limit of normal If laboratory screening tests are out of range, repeat of screening tests is permitted once, provided there is an alternative explanation for the out of range value. Women of childbearing potential must have a negative serum pregnancy test at screening and negative urine pregnancy tests prior to each vaccination. Women of childbearing potential must have an acceptable method of contraception from 28 days prior to the 1st vaccination until at least 60 days after the 2nd vaccination. Acceptable methods of contraception include the following: -Prescription oral contraceptives, contraceptive injections, intrauterine device (IUD), implants, vaginal ring, double-barrier method, contraceptive patch, male partner sterilization, abstinence (defined as refraining from heterosexual intercourse during participation in the study [from 28 days before the first vaccination until at least 60 days after the last vaccination]). Women of non-childbearing potential, defined as postmenopausal (any age with amenorrhea for = / > 12 months without other known or suspected cause for amenorrhea, or surgically sterile (hysterectomy, bilateral tubal ligation, obilateral oophorectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with documented confirmation test at least 3 months after the procedure), are not required to use the birth control methods. Female subjects must agree to not donate eggs (ova, oocytes) from the start of screening onwards until at least 60 days after the last vaccination. Male subjects who have not had a vasectomy and is sexually active with a woman of childbearing potential must agree to use an acceptable measure of birth control from 28 days prior to 1st vaccination until at least 60 days after the last vaccination. Acceptable methods of birth control include the following: Abstinence (defined as refraining from heterosexual intercourse with a female partner of childbearing potential during participation in the study [from 28 days before the first vaccination until at least 60 days after the last vaccination]. A double-barrier method of birth control, such as condom with spermicidal foam/gel/film/cream/suppository and partner with occlusive cap (diaphragm, cervical/vault caps). In case the female partner is using an acceptable method of birth control (see Inclusion Criterion #8), a single-barrier method of birth control for the male subject is acceptable. Male subjects must agree to not donate sperm from the start of screening onwards until at least 60 days after the last vaccination. Must be available and willing to participate for the duration of the study visits and follow-up. Must have a means to be contacted by telephone. Exclusion Criteria: Was ever vaccinated with a licensed or investigational YF vaccine or was diagnosed with YF infection or disease. Includes YF-VAX, Stamaril, or Bio-Manguinhos yellow fever vaccine. Subject's verbal history will suffice. Was ever vaccinated with a licensed or investigational Flavivirus vaccine. Including Japanese encephalitis virus (JEV) vaccine or an investigational Flavivirus vaccine including dengue virus (DENV) or West Nile virus vaccine, or has been diagnosed with an illness caused by a Flavivirus including DENV, West Nile virus (WNV), JEV, St. Louis encephalitis, or tick-borne encephalitis virus (TBEV). Subject's verbal history will suffice. Positive serology for HIV, Hepatitis C virus, or Hepatitis B surface antigen. Positive serology to Dengue, Yellow Fever, or West Nile virus. Plans to travel to a Yellow-Fever endemic area during the course of the study or travel to a Yellow-Fever endemic area within 30 days of screening. Subjects who have a recent travel to a Yellow Fever endemic area may screen if they have returned to the U.S. 30 or more days prior to the screening visit. Refer to the CDC Yellow Fever map for countries/regions at risk for Yellow Fever virus infection. http://www.cdc.gov/yellowfever/maps/ Was ever vaccinated with a licensed or investigational smallpox vaccine with the exception of subjects in Group 6. Includes Dryvax, Acam2000, LC 16 m8, MVA-based vaccine candidate or licensed vaccines, and Imvamune or Imvanex. -EXCEPTION: Group 6 should have had two 1 x 10^8 TCID 50 doses of MVA-BN 19-45 days apart SC or IM as part of participation in DMID vaccine trials 11-0021 or 09-0002. First dose must have been administered no earlier than 2010. Has known allergy or history of anaphylaxis or other serious adverse reaction to a vaccine or vaccine products. Including egg products, aminoglycosides, gelatin, sorbitol, tris (hydroxymethyl)-amino methane (THAM), or any of the constituents of the study vaccines. Has severe allergy or anaphylaxis to latex. Participants in Group 6 will not be exposed to latex and so may have history of severe allergy or anaphylaxis to latex. Has an acute illness or temperature > / = 38.0 degrees Celsius on Day 1 or Day 29. Subjects with fever or acute illness on the Day of vaccination may be re-assessed and enrolled if healthy or only minor residual symptoms remain within 3 days. Female subjects who are pregnant or breast-feeding, or planning to become pregnant while enrolled in the study. Has history of chronic or acute severe neurologic condition. Including history of seizure disorder or epilepsy, history of Guillain-Barre syndrome, Bell's palsy, meningitis, or disease with any focal neurologic deficits. Has history of thymus disorder including myasthenia gravis, thymoma or prior thymectomy. Has history of autoimmune disease, or clinically significant cardiac, pulmonary, hepatic, rheumatologic, or renal disease by history, physical examination, and/or laboratory studies. Includes the conditions and diagnoses defined as AESI. Has history of malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure. Subjects with a history of skin cancer must not be vaccinated at the previous tumor site. Has known or suspected congenital or acquired immunodeficiency, or recent history or current use of immunosuppressive therapy. Anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term (at least 2 weeks within the previous 3 months) systemic corticosteroids therapy (at a dose of at least 0.5 mg/kg/day). Intranasal or topical prednisone (or equivalent) are allowed. Is post-organ and/or stem cell transplant whether or not on chronic immunosuppressive therapy. Had major surgery (per the investigator's judgment) within the 4 weeks prior to study entry or planned major surgery during the course of the study. Has personal history of recurring migraines (every 6 months or more often) or on prescription medication for treatment of recurring headaches or migraines. Has history of cardiac disease. Myocarditis, pericarditis, cardiomyopathy, transient ischemic attack or stroke, myocardial infarction, angina, coronary artery disease, congestive heart failure, clinically significant arrhythmia. Includes any arrhythmia requiring medication, treatment, or clinical follow-up. Has electrocardiogram (ECG) with clinically significant findings, or features that would interfere with the assessment of myocarditis/pericarditis. Including any of the following: Conduction disturbance (complete left or complete right bundle branch block or nonspecific intraventricular conduction disturbance with QRS = / > 120 ms, PR interval > 219 ms, any second-or third-degree atrioventricular block, or prolongation of the QT interval corrected according to Bazett's formula [QTcB] [> 450 ms]). Significant repolarization (ST-segment or T-wave) abnormality. Significant atrial or ventricular arrhythmia; frequent atrial or ventricular ectopy (e.g., frequent premature atrial contractions, 2 premature ventricular contractions in a row). ST-elevation consistent with ischemia or evidence of past or evolving myocardial infarction. Has history of diabetes mellitus type 1 or type 2, including cases controlled with diet alone. -Note: history of isolated gestational diabetes is not an exclusion criterion. Has history of thyroidectomy, or thyroid disease requiring medication during the last 12 months. Has history of hypertension even if medically controlled. -Note: Vital signs must be normal by protocol toxicity grading scale or determined to be normal-variant by investigator. In the event of an abnormal heart rate or blood pressure due to physiological variation or activity, the subject may rest for 10 minutes in a quiet room, and then blood pressure and/or heart rate may be re-measured. Repeated vital signs may be used to determine eligibility. Received live attenuated vaccines from 30 days before Day 1 until 30 days after the 2nd vaccination. Received killed or inactivated vaccines from 14 days before Day 1 until 14 days after the 2nd vaccination. Received experimental therapeutic agents within 3 months prior to the first study vaccination or plans to receive any experimental therapeutic agents during the course of the study. Is currently participating or plans to participate in another clinical study which would involve receipt of the following: An investigational product, blood drawing, or an invasive medical procedure that would require administration of anesthetics or intravenous dyes or removal of tissue during the study. -Includes endoscopy, bronchoscopy, or administration of IV contrast. Received blood products or immunoglobulin in the 3 months before study entry or planned use during the course of the study. Donated a unit of blood within 8 weeks before Day 1 or plans to donate blood during the course of the study. Has major psychiatric illness during the past 12 months that in the opinion of the investigator would preclude participation. Has current alcohol use or current or past abuse of recreational or narcotic drugs by history as judged by the investigator to potentially interfere with study adherence. Has a history of chronic urticaria (recurrent hives). Has tattoos, scars, or other marks on both deltoid areas which would, in the opinion of the investigator, interfere with assessment of the vaccination site. Is a study site employee or staff who are paid entirely or partially by/through the OCRR contract for the trial, or staff who are supervised by the PI or Sub-Investigators. Including the Principal Investigator (PI), sub-Investigators listed in Form FDA 1572 or Investigator of Record Form. In the opinion of the investigator cannot communicate reliably, is unlikely to adhere to the requirements of the study, or has any condition which would limit the subject's ability to complete the study. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 45 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Group 1<br>Subjects will receive 1.0x10^8 TCID50 of MVA-BN as two doses subcutaneously on Day 1 and Day 29. N=15 \| Biological: MVA Smallpox Vaccine<br> Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine (MVA BN(R)) is a purified live vaccine will be used as an active comparator.<br>\| \| Experimental: Group 2<br>Subjects will receive 1.0x10^8 TCID50 of MVA-BN-YF as two doses intramuscularly on Day 1 and Day 29. N=15 \| Biological: MVA-BN Yellow Fever Vaccine<br>* Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) clinical trial material is manufactured in CEF cells derived from Specific Pathogen Free (SPF) eggs in a bioreactor culture using serum free medium.<br>\| \| Experimental: Group 3<br>Subjects will receive 1.0x10^8 TCID50 of MVA-BN-YF + ISA 720 as two doses intramuscularly on Day 1 and Day 29. N=15 \| Drug: ISA-720<br>* The vaccine adjuvant ISA 720 will be used with Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) as vaccine adjuvant with a depot effect. This comprises slow release of antigen at the injection site, protection of antigen against degradation and strong stimulation of the immune response.<br>Biological: MVA-BN Yellow Fever Vaccine<br>* Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) clinical trial material is manufactured in CEF cells derived from Specific Pathogen Free (SPF) eggs in a bioreactor culture using serum free medium.<br>\| \| Experimental: Group 4<br>Subjects will receive 1.0x10^8 TCID50 of MVA-BN-YF + ISA 720 as a single dose intramuscularly on Day 1 and matching placebo on Day 29. N=15 \| Drug: ISA-720<br>* The vaccine adjuvant ISA 720 will be used with Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) as vaccine adjuvant with a depot effect. This comprises slow release of antigen at the injection site, protection of antigen against degradation and strong stimulation of the immune response.<br>Biological: MVA-BN Yellow Fever Vaccine<br>* Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) clinical trial material is manufactured in CEF cells derived from Specific Pathogen Free (SPF) eggs in a bioreactor culture using serum free medium.<br>Other: Placebo<br>* 0.9% Sodium Chloride Injection, USP is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection.<br>\| \| Active Comparator: Group 5<br>Subjects will receive = / > 4.74 log10 PFU of YF-Vax as a single dose subcutaneously on Day 1 and matching placebo on Day 29. N=15 \| Other: Placebo<br>* 0.9% Sodium Chloride Injection, USP is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection.<br>Biological: YF Vax 17D Strain<br>* Yellow Fever Vaccine (YF-VAX) is a vaccine prepared by culturing the 17D-204 strain of yellow fever virus in living avian leucosis virus-free (ALV-free) chicken embryos. Will be used as an active comparator.<br>\| \| Experimental: Group 6<br>Subjects with prior receipt of MVA-BN will receive 1.0x10^8 TCID50 of MVA-BN-YF as two doses intramuscularly on Day 1 and Day 29. N=15 \| Biological: MVA-BN Yellow Fever Vaccine<br>* Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) clinical trial material is manufactured in CEF cells derived from Specific Pathogen Free (SPF) eggs in a bioreactor culture using serum free medium.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Comparison of Grade 3 local, systemic or laboratory toxicities, continuous Grade 2 or greater local reactogenicity \| \| Day 1 through Day 8 \| \| Comparison of Grade 3 local, systemic or laboratory toxicities, continuous Grade 2 or greater local reactogenicity \| \| Day 29 through Day 36 \| \| Number of adverse events of special interest (AESIs) considered related to study vaccination in Group 1 \| \| Day 1 through Day 394 \| \| Number of adverse events of special interest (AESIs) considered related to study vaccination in Group 2 \| \| Day 1 through Day 394 \| \| Number of adverse events of special interest (AESIs) considered related to study vaccination in Group 3 \| \| Day 1 through Day 394 \| \| Number of adverse events of special interest (AESIs) considered related to study vaccination in Group 4 \| \| Day 1 through Day 394 \| \| Number of adverse events of special interest (AESIs) considered related to study vaccination in Group 5 \| \| Day 1 through Day 394 \| \| Number of adverse events of special interest (AESIs) considered related to study vaccination in Group 6 \| \| Day 1 through Day 394 \| \| Number of adverse events of special interest (AESIs) considered related to study vaccination overall \| \| Day 1 through Day 394 \| \| Number of related adverse events of special interest (AESIs) \| \| Day 1 through Day 394 \| \| Number of related serious adverse events (SAEs) \| \| Day 1 through Day 394 \| \| Number of serious adverse events (SAEs) considered related to study vaccination in Group 1 \| \| Day 1 through Day 394 \| \| Number of serious adverse events (SAEs) considered related to study vaccination in Group 2 \| \| Day 1 through Day 394 \| \| Number of serious adverse events (SAEs) considered related to study vaccination in Group 3 \| \| Day 1 through Day 394 \| \| Number of serious adverse events (SAEs) considered related to study vaccination in Group 4 \| \| Day 1 through Day 394 \| \| Number of serious adverse events (SAEs) considered related to study vaccination in Group 5 \| \| Day 1 through Day 394 \| \| Number of serious adverse events (SAEs) considered related to study vaccination in Group 6 \| \| Day 1 through Day 394 \| \| Number of serious adverse events (SAEs) considered related to study vaccination overall \| \| Day 1 through Day 394 \| \| Number of subjects with new onset of a chronic medical condition in Group 1 \| \| Day 1 through Day 394 \| \| Number of subjects with new onset of a chronic medical condition in Group 2 \| \| Day 1 through Day 394 \| \| Number of subjects with new onset of a chronic medical condition in Group 3 \| \| Day 1 through Day 394 \| \| Number of subjects with new onset of a chronic medical condition in Group 4 \| \| Day 1 through Day 394 \| \| Number of subjects with new onset of a chronic medical condition in Group 5 \| \| Day 1 through Day 394 \| \| Number of subjects with new onset of a chronic medical condition in Group 6 \| \| Day 1 through Day 394 \| \| Number of subjects with new onset of a chronic medical condition overall \| \| Day 1 through Day 394 \| \| Number of subjects with unsolicited vaccine-related adverse events (AEs) in Group 1 \| \| Day 1 through Day 57 \| \| Number of subjects with unsolicited vaccine-related adverse events (AEs) in Group 2 \| \| Day 1 through Day 57 \| \| Number of subjects with unsolicited vaccine-related adverse events (AEs) in Group 3 \| \| Day 1 through Day 57 \| \| Number of subjects with unsolicited vaccine-related adverse events (AEs) in Group 4 \| \| Day 1 through Day 57 \| \| Number of subjects with unsolicited vaccine-related adverse events (AEs) in Group 5 \| \| Day 1 through Day 57 \| \| Number of subjects with unsolicited vaccine-related adverse events (AEs) in Group 6 \| \| Day 1 through Day 57 \| \| Number of subjects with unsolicited vaccine-related adverse events (AEs) overall \| \| Day 1 through Day 57 \| \| Number of vaccine-related laboratory adverse events (AEs) in Group 1 \| \| Day 1 through Day 57 \| \| Number of vaccine-related laboratory adverse events (AEs) in Group 2 \| \| Day 1 through Day 57 \| \| Number of vaccine-related laboratory adverse events (AEs) in Group 3 \| \| Day 1 through Day 57 \| \| Number of vaccine-related laboratory adverse events (AEs) in Group 4 \| \| Day 1 through Day 57 \| \| Number of vaccine-related laboratory adverse events (AEs) in Group 5 \| \| Day 1 through Day 57 \| \| Number of vaccine-related laboratory adverse events (AEs) in Group 6 \| \| Day 1 through Day 57 \| \| Number of withdrawals or discontinuation of vaccinations due to any reason \| \| Day 1 through Day 394 \| \| Occurrence of solicited injection site reactogenicity events in Group 1 \| \| Day 1 through Day 8 \| \| Occurrence of solicited injection site reactogenicity events in Group 1 \| \| Day 29 through Day 36 \| \| Occurrence of solicited injection site reactogenicity events in Group 2 \| \| Day 1 through Day 8 \| \| Occurrence of solicited injection site reactogenicity events in Group 2 \| \| Day 29 through Day 36 \| \| Occurrence of solicited injection site reactogenicity events in Group 3 \| \| Day 1 through Day 8 \| \| Occurrence of solicited injection site reactogenicity events in Group 3 \| \| Day 29 through Day 36 \| \| Occurrence of solicited injection site reactogenicity events in Group 4 \| \| Day 1 through Day 8 \| \| Occurrence of solicited injection site reactogenicity events in Group 4 \| \| Day 29 through Day 36 \| \| Occurrence of solicited injection site reactogenicity events in Group 5 \| \| Day 1 through Day 8 \| \| Occurrence of solicited injection site reactogenicity events in Group 5 \| \| Day 29 through Day 36 \| \| Occurrence of solicited injection site reactogenicity events in Group 6 \| \| Day 1 through Day 8 \| \| Occurrence of solicited injection site reactogenicity events in Group 6 \| \| Day 29 through Day 36 \| \| Occurrence of solicited injection site reactogenicity events overall \| \| Day 1 through Day 8 \| \| Occurrence of solicited injection site reactogenicity events overall \| \| Day 29 through Day 36 \| \| Occurrence of solicited systemic reactogenicity events in Group 1 \| \| Day 1 through Day 8 \| \| Occurrence of solicited systemic reactogenicity events in Group 1 \| \| Day 29 through Day 36 \| \| Occurrence of solicited systemic reactogenicity events in Group 2 \| \| Day 1 through Day 8 \| \| Occurrence of solicited systemic reactogenicity events in Group 2 \| \| Day 29 through Day 36 \| \| Occurrence of solicited systemic reactogenicity events in Group 3 \| \| Day 1 through Day 8 \| \| Occurrence of solicited systemic reactogenicity events in Group 3 \| \| Day 29 through Day 36 \| \| Occurrence of solicited systemic reactogenicity events in Group 4 \| \| Day 1 through Day 8 \| \| Occurrence of solicited systemic reactogenicity events in Group 4 \| \| Day 29 through Day 36 \| \| Occurrence of solicited systemic reactogenicity events in Group 5 \| \| Day 1 through Day 8 \| \| Occurrence of solicited systemic reactogenicity events in Group 5 \| \| Day 29 through Day 36 \| \| Occurrence of solicited systemic reactogenicity events in Group 6 \| \| Day 1 through Day 8 \| \| Occurrence of solicited systemic reactogenicity events in Group 6 \| \| Day 29 through Day 36 \| \| Occurrence of solicited systemic reactogenicity events overall \| \| Day 1 through Day 8 \| \| Occurrence of solicited systemic reactogenicity events overall \| \| Day 29 through Day 36 \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Comparison of geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 1 and Group 2 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 1 and Group 3 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 1 and Group 4 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 1 and Group 2 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 1 and Group 3 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 1 and Group 4 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to YF between Group 5 and Group 2 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to YF between Group 5 and Group 3 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to YF between Group 5 and Group 4 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to YF between Group 5 and Group 6 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to YF between Group 6 and Group 2 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to YF between Group 6 and Group 3 \| \| Day 211 \| \| Comparison of geometric mean titer (GMT) (as measured by PRNT) to YF between Group 6 and Group 4 \| \| Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 1 and Group 2 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 1 and Group 3 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 1 and Group 4 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 2 and Group 3 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 2 and Group 4 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 3 and Group 4 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 1 and Group 2 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 1 and Group 3 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 1 and Group 4 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 2 and Group 3 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 2 and Group 4 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 3 and Group 4 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 2 and Group 3 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 2 and Group 3 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 2 and Group 4 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 2 and Group 4 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 2 and Group 5 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 2 and Group 5 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 2 and Group 6 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 2 and Group 6 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 3 and Group 4 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 3 and Group 4 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 3 and Group 5 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 3 and Group 5 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 3 and Group 6 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 3 and Group 6 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 4 and Group 5 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 4 and Group 5 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 4 and Group 6 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 4 and Group 6 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 5 and Group 6 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination between Group 5 and Group 6 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination with MVA-BN-YF in Group 6 compared to Group 2 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination with MVA-BN-YF in Group 6 compared to Group 2 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination with MVA-BN-YF in Group 6 compared to Group 3 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination with MVA-BN-YF in Group 6 compared to Group 3 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination with MVA-BN-YF in Group 6 compared to Group 4 \| \| Day 15 through Day 22 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF after vaccination with MVA-BN-YF in Group 6 compared to Group 4 \| \| Day 36 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 2 and Group 3 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 2 and Group 4 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 2 and Group 5 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 2 and Group 6 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 3 and Group 4 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 3 and Group 5 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 3 and Group 6 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 4 and Group 5 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 4 and Group 6 \| \| Day 1 through Day 211 \| \| Comparison of peak geometric mean titer (GMT) (as measured by PRNT) to YF between Group 5 and Group 6 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 1 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 2 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 3 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 4 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 6 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 1 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 2 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 3 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 4 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 6 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to YF in Group 2 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to YF in Group 3 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to YF in Group 4 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to YF in Group 5 \| \| Day 1 through Day 211 \| \| Peak geometric mean titer (GMT) (as measured by PRNT) to YF in Group 6 \| \| Day 1 through Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 1 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 1 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 1 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 1 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 1 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 1 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 1 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 2 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 2 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 2 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 2 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 2 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 2 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 2 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 3 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 3 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 3 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 3 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 3 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 3 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 3 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 4 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 4 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 4 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 4 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 4 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 4 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 4 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 6 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 6 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 6 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 6 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 6 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 6 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by ELISA) to MVA-BN in Group 6 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 1 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 1 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 1 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 1 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 1 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 1 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 1 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 2 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 2 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 2 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 2 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 2 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 2 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 2 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 3 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 3 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 3 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 3 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 3 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 3 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 3 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 4 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 4 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 4 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 4 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 4 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 4 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 4 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 6 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 6 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 6 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 6 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 6 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 6 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to VACV-WR in Group 6 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 2 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 2 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 2 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 2 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 2 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 2 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 2 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 3 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 3 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 3 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 3 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 3 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 3 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 3 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 4 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 4 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 4 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 4 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 4 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 4 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 4 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 5 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 5 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 5 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 5 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 5 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 5 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 5 \| \| Day 57 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 6 \| \| Day 15 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 6 \| \| Day 211 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 6 \| \| Day 22 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 6 \| \| Day 36 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 6 \| \| Day 43 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 6 \| \| Day 50 \| \| Per-visit geometric mean titer (GMT) (as measured by PRNT) to YF in Group 6 \| \| Day 57 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 1 \| \| Day 1 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 1 \| \| Day 15 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 1 \| \| Day 211 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 1 \| \| Day 22 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 1 \| \| Day 29 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 1 \| \| Day 36 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 1 \| \| Day 43 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 1 \| \| Day 50 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 1 \| \| Day 57 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 2 \| \| Day 1 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 2 \| \| Day 15 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 2 \| \| Day 211 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 2 \| \| Day 22 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 2 \| \| Day 29 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 2 \| \| Day 36 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 2 \| \| Day 43 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 2 \| \| Day 50 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 2 \| \| Day 57 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 3 \| \| Day 1 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 3 \| \| Day 15 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 3 \| \| Day 211 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 3 \| \| Day 22 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 3 \| \| Day 29 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 3 \| \| Day 36 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 3 \| \| Day 43 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 3 \| \| Day 50 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 3 \| \| Day 57 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 4 \| \| Day 1 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 4 \| \| Day 15 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 4 \| \| Day 211 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 4 \| \| Day 22 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 4 \| \| Day 29 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 4 \| \| Day 36 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 4 \| \| Day 43 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 4 \| \| Day 50 \| \| Proportion of subjects seroconverting to MVA-BN (VACV-WR PRNT defined as PRNT50 = / > 2 and MVA-BN ELISA defined as titer = / > 50 or = / > 2-fold rise in ELISA antibody responses compared with baseline if baseline ELISA titer = / > 50) in Group 4 \| \| Day 57 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 2 \| \| Day 1 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 2 \| \| Day 15 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 2 \| \| Day 211 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 2 \| \| Day 22 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 2 \| \| Day 29 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 2 \| \| Day 36 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 2 \| \| Day 43 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 2 \| \| Day 50 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 2 \| \| Day 57 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 3 \| \| Day 1 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 3 \| \| Day 15 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 3 \| \| Day 211 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 3 \| \| Day 22 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 3 \| \| Day 29 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 3 \| \| Day 36 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 3 \| \| Day 43 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 3 \| \| Day 50 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 3 \| \| Day 57 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 4 \| \| Day 1 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 4 \| \| Day 15 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 4 \| \| Day 211 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 4 \| \| Day 22 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 4 \| \| Day 29 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 4 \| \| Day 36 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 4 \| \| Day 43 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 4 \| \| Day 50 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 4 \| \| Day 57 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 5 \| \| Day 1 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 5 \| \| Day 15 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 5 \| \| Day 211 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 5 \| \| Day 22 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 5 \| \| Day 29 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 5 \| \| Day 36 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 5 \| \| Day 43 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 5 \| \| Day 50 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 5 \| \| Day 57 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 6 \| \| Day 1 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 6 \| \| Day 15 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 6 \| \| Day 211 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 6 \| \| Day 22 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 6 \| \| Day 29 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 6 \| \| Day 36 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 6 \| \| Day 43 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 6 \| \| Day 50 \| \| Proportion of subjects seroconverting to YF (defined as PRNT50 titer = / > 20 or = / > 4-fold increase in neutralizing antibody responses to YF compared with baseline if baseline PRNT50 titer = / > 20) in Group 6 \| \| Day 57 \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Fever, Immunogenicity, MVA-BN, Reactogenicity, Vaccine, Yellow
NCT03641053	Honey Versus Povidone-iodine on Laceration Wounds	This study evaluates healing time in usage of honey and povidone-iodine over paraffin gauze as dressings in the treatment of acute laceration wounds. In Indonesia, especially in rural area, where most of the resources is limited and modern dressings are expensive and hard-to-find. The investigators tried to find an alternative which was easier to find and could act as a substitute of modern wound dressing.~The hypothesis of this study is honey and povidone-iodine could be a good substitute (or equal to) to paraffin gauze on acute laceration wounds.~Honey is chosen because of its versatility and already well-known to be used as a chronic wound dressing. Povidone-iodine was chosen as another alternative because it is still one of the most used substance in rural area as a wound dressing, but there is not enough study to support the usage of this substance. Paraffin gauze was chosen as a representative of modern wound dressing because it fulfilled the standard of wound dressing on acute wound, which is non-adherent and also moist.	The investigator's team consists of five members, each have their own specific tasks and divided by two groups, which are ER group (first time encounter, informed consent, and intervention) and polyclinic group (routine wound care). All of the data are primary data. Data registry were taken by the team without involving any other party. Any intervention done to the participants were also done only by the team(suturing, wound care). Appointment for routine wound care was also made by contacting the participant through their cellphone numbers which were collected when they come to the ER.~The data of each of the participant was registered on a form which was pre-made by the investigators. It recorded the identity of the patient, history taking, physical examination, and also to record more detailed information about our intervention, such as the amount of stitches and how many and what kind of resources that have been spent on the participant.~Every sample will be categorized into 3 randomized groups of intervention; honey, povidone-iodine, and paraffin gauze, which will also be categorized by location of their wound; face and neck, upper extremity, and lower extremity. Participants on each intervention group are distributed evenly using stratified block randomization. Photos of the wound will be taken before and after the wound is cleaned, and after the wound has been sutured. Every patient will be asked to attend a predetermined schedule for wound care assessment. The wound will be evaluated by photos before and after the wound is cleaned, debrided, or have its sutures removed. Parameter of evaluation will be duration of wound healing per anatomical region, infection, cleanliness of wound, odor, exudate level, pain, itch, and total cost of wound care.~Every paper consists of participants' data that were collected on colored maps based on the intervention group (red: povidone-iodine, yellow: honey, blue: paraffin). At the end of the study, three of the team's members converted the data to be analyzed using Microsoft Excel and SPSS.~The investigators prepared beforehand the Standard Operational Procedures regarding any possibilities of adverse events, such as lidocaine toxicity and honey hypersensitivity and were already approved by the hospital's committee.~The investigators determined the target of the sample size with the total sample of 36 participants, distributed evenly based on intervention groups and wounds' location using stratified block randomization	Comparison of Honey and Povidone-iodine in Wound Healing on Acute Laceration Wounds: A Randomized Controlled Trial Study	Laceration Face, Wound Heal, Wounds and Injuries, Laceration Arm, Laceration of Leg	* Other: Honey * Other: Povidone-iodine * Other: Paraffin gauze	Inclusion Criteria:~Every patient that admits to the emergency department with:~An acute open traumatic wound~Agrees to a voluntary agreement for informed consent~To be treated in an outpatient setting~Exclusion Criteria:~Human factor:~Patient under the age of 10 and over 60 years old~Systemic conditions (diabetes mellitus, hypertension, liver' kidney disease)~Signs of infection~Consuming steroids and / or antibiotics~History of keloid~History of drug and / or alcohol abuse~Under treatment for chemotherapy or immunocompromised~Pregnant~History of allergy towards amoxicillin and / or ibuprofen~Wound factor:~Acute Open Traumatic Wound that has occured after than 12 hours of admittance to the emergency department~Open fracture~Suspicion of contamination from the mechanism of attaining the wound (human or animal bite, body fluids such as faeces, saliva, urine, sperm, or vaginal secretion)~Penetration trauma (stab wound, gunshot wound, or a joint-affected wound)~Signs of wound infection~More than one wound in the same anatomical region~Possess a chronic wound caused by underlying disease other than trauma~Wound with exposed tendon and/ or bone~Wound length dimension no less than 1 cm and no more than 10 cm.~Hypersensitivity to honey~Does not attend to scheduled wound care assesment control~Sample's wish to not be involved anymore with the research at any phase	10 Years	60 Years	All	Accepts Healthy Volunteers	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: A three-arm parallel assignment where one group receives honey, the second group receives povidone-iodine, and the third group receives paraffin gauze as wound dressing. Masking: Single	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Wound healing time \| Measured by days, when was all of the sutures completely removed and the wound is completely approximated. We followed the guideline from American Academy of Family Physicians for timing for suture removal, so we will not remove the suture before the recommended time \| 28 days/4 weeks; day 0 is the day of the event. The participants was chosen very carefully by our strict eligibility criteria, so the investigators expect that the wound will heal on acute period \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Infection \| Measured using the infection signs from Delphi Criteria \| 28 days/4 weeks; day 0 is the day of the event. The participants was chosen very carefully by our strict eligibility criteria, so the investigators expect that the wound will heal on acute period \| \| Pain level \| measured using Numeral Rating Scale from 0-10, asked from the onset of the wound and every routine wound care \| 28 days/4 weeks; day 0 is the day of the event. The participants was chosen very carefully by our strict eligibility criteria, so the investigators expect that the wound will heal on acute period \| \| Itchiness \| Measured using Numeral Rating Scale from 0-10, asked from the onset of the wound and every routine wound care \| 28 days/4 weeks; day 0 is the day of the event. The participants was chosen very carefully by our strict eligibility criteria, so the investigators expect that the wound will heal on acute period \| \| Odor \| Measured using Verbal Rating Scale, consists of 4 level of odor (no odor, slight odor, medium odor, strong odor), asked from the onset of the wound and every routine wound care \| 28 days/4 weeks; day 0 is the day of the event. The participants was chosen very carefully by our strict eligibility criteria, so the investigators expect that the wound will heal on acute period \| \| Exudate \| Measured in grams, using digital scale with the precision of 3 digits. We measured the gauze which will be used and the one which is already on top the wound, from the onset of the wound and every routine wound care \| 28 days/4 weeks; day 0 is the day of the event. The participants was chosen very carefully by our strict eligibility criteria, so the investigators expect that the wound will heal on acute period \| \| Cleanliness \| Measured using images taken from the whole photographs of the wound. This parameter was measured using less clean, cleaner, unchanged cleanliness. statistically using Cohen's kappa score to reach the agreement of the evaluation of this parameter \| 28 days/4 weeks; day 0 is the day of the event. The participants was chosen very carefully by our strict eligibility criteria, so the investigators expect that the wound will heal on acute period \| \| Cost \| Measured by counting the cost of every material used for the participant \| 28 days/4 weeks; day 0 is the day of the event. The participants was chosen very carefully by our strict eligibility criteria, so the investigators expect that the wound will heal on acute period \|	honey, povidone-iodine, randomized control trial, wound healing	Iodine, Povidone-Iodine, Povidone, Anti-Infective Agents, Local, Anti-Infective Agents, Trace Elements, Micronutrients, Physiological Effects of Drugs, Plasma Substitutes, Blood Substitutes	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Honey<br>0.05 cc of honey (Madu Nusantara®) per 1 cm of laceration, given every predetermined wound care schedule \| Other: Honey<br>* Substance is given topically after the wound has been sutured<br>* Other names: Madu Nusantara®;\| \| Active Comparator: Povidone-iodine<br>0.05 cc of povidone-iodine per 1 cm of laceration, given every predetermined wound care schedule \| Other: Povidone-iodine<br>* Substance is given topically after the wound has been sutured<br>* Other names: OneMed® povidone-iodine 10%;\| \| Active Comparator: Paraffin gauze<br>1 layer of paraffin gauze, given every predetermined wound care schedule \| Other: Paraffin gauze<br>* Substance is given topically after the wound has been sutured<br>* Other names: Cuticell® Classic Paraffin Gauze;\|	Honey Versus Povidone-iodine on Laceration Wounds Study Overview ================= Brief Summary ----------------- This study evaluates healing time in usage of honey and povidone-iodine over paraffin gauze as dressings in the treatment of acute laceration wounds. In Indonesia, especially in rural area, where most of the resources is limited and modern dressings are expensive and hard-to-find. The investigators tried to find an alternative which was easier to find and could act as a substitute of modern wound dressing. The hypothesis of this study is honey and povidone-iodine could be a good substitute (or equal to) to paraffin gauze on acute laceration wounds. Honey is chosen because of its versatility and already well-known to be used as a chronic wound dressing. Povidone-iodine was chosen as another alternative because it is still one of the most used substance in rural area as a wound dressing, but there is not enough study to support the usage of this substance. Paraffin gauze was chosen as a representative of modern wound dressing because it fulfilled the standard of wound dressing on acute wound, which is non-adherent and also moist. Detailed Description ----------------- The investigator's team consists of five members, each have their own specific tasks and divided by two groups, which are ER group (first time encounter, informed consent, and intervention) and polyclinic group (routine wound care). All of the data are primary data. Data registry were taken by the team without involving any other party. Any intervention done to the participants were also done only by the team(suturing, wound care). Appointment for routine wound care was also made by contacting the participant through their cellphone numbers which were collected when they come to the ER. The data of each of the participant was registered on a form which was pre-made by the investigators. It recorded the identity of the patient, history taking, physical examination, and also to record more detailed information about our intervention, such as the amount of stitches and how many and what kind of resources that have been spent on the participant. Every sample will be categorized into 3 randomized groups of intervention; honey, povidone-iodine, and paraffin gauze, which will also be categorized by location of their wound; face and neck, upper extremity, and lower extremity. Participants on each intervention group are distributed evenly using stratified block randomization. Photos of the wound will be taken before and after the wound is cleaned, and after the wound has been sutured. Every patient will be asked to attend a predetermined schedule for wound care assessment. The wound will be evaluated by photos before and after the wound is cleaned, debrided, or have its sutures removed. Parameter of evaluation will be duration of wound healing per anatomical region, infection, cleanliness of wound, odor, exudate level, pain, itch, and total cost of wound care. Every paper consists of participants' data that were collected on colored maps based on the intervention group (red: povidone-iodine, yellow: honey, blue: paraffin). At the end of the study, three of the team's members converted the data to be analyzed using Microsoft Excel and SPSS. The investigators prepared beforehand the Standard Operational Procedures regarding any possibilities of adverse events, such as lidocaine toxicity and honey hypersensitivity and were already approved by the hospital's committee. The investigators determined the target of the sample size with the total sample of 36 participants, distributed evenly based on intervention groups and wounds' location using stratified block randomization Official Title ----------------- Comparison of Honey and Povidone-iodine in Wound Healing on Acute Laceration Wounds: A Randomized Controlled Trial Study Conditions ----------------- Laceration Face, Wound Heal, Wounds and Injuries, Laceration Arm, Laceration of Leg Intervention / Treatment ----------------- * Other: Honey * Other: Povidone-iodine * Other: Paraffin gauze Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Every patient that admits to the emergency department with: An acute open traumatic wound Agrees to a voluntary agreement for informed consent To be treated in an outpatient setting Exclusion Criteria: Human factor: Patient under the age of 10 and over 60 years old Systemic conditions (diabetes mellitus, hypertension, liver' kidney disease) Signs of infection Consuming steroids and / or antibiotics History of keloid History of drug and / or alcohol abuse Under treatment for chemotherapy or immunocompromised Pregnant History of allergy towards amoxicillin and / or ibuprofen Wound factor: Acute Open Traumatic Wound that has occured after than 12 hours of admittance to the emergency department Open fracture Suspicion of contamination from the mechanism of attaining the wound (human or animal bite, body fluids such as faeces, saliva, urine, sperm, or vaginal secretion) Penetration trauma (stab wound, gunshot wound, or a joint-affected wound) Signs of wound infection More than one wound in the same anatomical region Possess a chronic wound caused by underlying disease other than trauma Wound with exposed tendon and/ or bone Wound length dimension no less than 1 cm and no more than 10 cm. Hypersensitivity to honey Does not attend to scheduled wound care assesment control Sample's wish to not be involved anymore with the research at any phase Ages Eligible for Study ----------------- Minimum Age: 10 Years Maximum Age: 60 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: A three-arm parallel assignment where one group receives honey, the second group receives povidone-iodine, and the third group receives paraffin gauze as wound dressing. Masking: Single Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Honey<br>0.05 cc of honey (Madu Nusantara®) per 1 cm of laceration, given every predetermined wound care schedule \| Other: Honey<br>* Substance is given topically after the wound has been sutured<br>* Other names: Madu Nusantara®;\| \| Active Comparator: Povidone-iodine<br>0.05 cc of povidone-iodine per 1 cm of laceration, given every predetermined wound care schedule \| Other: Povidone-iodine<br>* Substance is given topically after the wound has been sutured<br>* Other names: OneMed® povidone-iodine 10%;\| \| Active Comparator: Paraffin gauze<br>1 layer of paraffin gauze, given every predetermined wound care schedule \| Other: Paraffin gauze<br>* Substance is given topically after the wound has been sutured<br>* Other names: Cuticell® Classic Paraffin Gauze;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Wound healing time \| Measured by days, when was all of the sutures completely removed and the wound is completely approximated. We followed the guideline from American Academy of Family Physicians for timing for suture removal, so we will not remove the suture before the recommended time \| 28 days/4 weeks; day 0 is the day of the event. The participants was chosen very carefully by our strict eligibility criteria, so the investigators expect that the wound will heal on acute period \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Infection \| Measured using the infection signs from Delphi Criteria \| 28 days/4 weeks; day 0 is the day of the event. The participants was chosen very carefully by our strict eligibility criteria, so the investigators expect that the wound will heal on acute period \| \| Pain level \| measured using Numeral Rating Scale from 0-10, asked from the onset of the wound and every routine wound care \| 28 days/4 weeks; day 0 is the day of the event. The participants was chosen very carefully by our strict eligibility criteria, so the investigators expect that the wound will heal on acute period \| \| Itchiness \| Measured using Numeral Rating Scale from 0-10, asked from the onset of the wound and every routine wound care \| 28 days/4 weeks; day 0 is the day of the event. The participants was chosen very carefully by our strict eligibility criteria, so the investigators expect that the wound will heal on acute period \| \| Odor \| Measured using Verbal Rating Scale, consists of 4 level of odor (no odor, slight odor, medium odor, strong odor), asked from the onset of the wound and every routine wound care \| 28 days/4 weeks; day 0 is the day of the event. The participants was chosen very carefully by our strict eligibility criteria, so the investigators expect that the wound will heal on acute period \| \| Exudate \| Measured in grams, using digital scale with the precision of 3 digits. We measured the gauze which will be used and the one which is already on top the wound, from the onset of the wound and every routine wound care \| 28 days/4 weeks; day 0 is the day of the event. The participants was chosen very carefully by our strict eligibility criteria, so the investigators expect that the wound will heal on acute period \| \| Cleanliness \| Measured using images taken from the whole photographs of the wound. This parameter was measured using less clean, cleaner, unchanged cleanliness. statistically using Cohen's kappa score to reach the agreement of the evaluation of this parameter \| 28 days/4 weeks; day 0 is the day of the event. The participants was chosen very carefully by our strict eligibility criteria, so the investigators expect that the wound will heal on acute period \| \| Cost \| Measured by counting the cost of every material used for the participant \| 28 days/4 weeks; day 0 is the day of the event. The participants was chosen very carefully by our strict eligibility criteria, so the investigators expect that the wound will heal on acute period \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- honey, povidone-iodine, randomized control trial, wound healing
NCT02760888	Oral Tramadol Versus Diclofenac For Pain Relief Before Outpatient Hysteroscopy:	The purpose of this study is there difference between the effect of Tramadol orally and Diclofenac orally with respect to : analgesic efficacy during diagnostic hysteroscopy in nulliparous women.	This prospective double-blind, randomized, clinical trial, will be conducted at Ain Shams University Maternity Hospital- Early Cancer Detection Unite [ECDU].~Patients fulfilling inclusion and exclusion criteria will be divided into three groups.~Group A (study group) Include 34 patients who will receive Tramadol 100mg orally 1 hour before the procedure.~Group B (study group) Include 34 patients who will receive Diclofenac 100mg orally 1 hour before the procedure.~Group C (control group) Include 34 patients who will receive a placebo.~Pain will evaluate on two separate occasion: immediately after the procedure and 15 minutes after procedure using a 100mm line visual analog scale.	Oral Tramadol Versus Diclofenac For Pain Relief Before Outpatient Hysteroscopy: A Randomized Controlled Trial	Pain, Procedure	* Drug: Tramadol * Drug: Diclofenac * Drug: Placebo	Inclusion Criteria:~BMI raging between (18.5 - 30 ).~Scheduled for diagnostic hysteroscopy only.~All of them should have given informed written consent.~Exclusion Criteria:~Any contraindication to hysteroscopy (e.g. suspected pregnancy, genital tract infection).~Receiving any other form of analgesia.~Patients with known cervical stenosis, polyps and ulcers.~Previous cervical surgery.~Patients who are planning to have invasive intrauterine therapeutic interventions during the hysteroscopy.~known sensitivity to non-steroidal anti-inflammatory and opioids drugs.~Known gastritis or peptic ulcer or cardiac disease or Respiratory dysfunction.~Unwilling to comply with the protocol, and Participation in another clinical trial in the last three months prior to the start of this study	18 Years	35 Years	Female	No	Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Pain during the procedure \| Pain will be assessed using a visual analogue scale immediatly after inserting the hysterscopy \| intraoperative \| \| pain after the procedure \| 15 minutes after procedure using a 100mm line visual analog scale \| 15 minutes after completing the procedure \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Adverse effect and difficulties \| Recorded in Case Record Form \| 24 hours \|		Diclofenac, Tramadol, Anti-Inflammatory Agents, Non-Steroidal, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anti-Inflammatory Agents, Antirheumatic Agents, Cyclooxygenase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Analgesics, Opioid, Narcotics, Central Nervous System Depressants	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Tramadol<br>Women will receive oral tramadol 100 mg 1 hour before the procedure \| Drug: Tramadol<br>* Women will receive a oral Tramadol 100mg 1 hour before the procedure<br>\| \| Active Comparator: Diclofenac<br>Women will receive 100 mg diclofenac 1 hour before the procedure \| Drug: Diclofenac<br>* Women will receive oral Diclofenac 100mg 1 hour before the procedure<br>\| \| Placebo Comparator: Placebo<br>Women will receive a placebo 1 hour before the procedure \| Drug: Placebo<br>* Women will receive a Placebo 1 hour before the procedure<br>\|	Oral Tramadol Versus Diclofenac For Pain Relief Before Outpatient Hysteroscopy: Study Overview ================= Brief Summary ----------------- The purpose of this study is there difference between the effect of Tramadol orally and Diclofenac orally with respect to : analgesic efficacy during diagnostic hysteroscopy in nulliparous women. Detailed Description ----------------- This prospective double-blind, randomized, clinical trial, will be conducted at Ain Shams University Maternity Hospital- Early Cancer Detection Unite [ECDU]. Patients fulfilling inclusion and exclusion criteria will be divided into three groups. Group A (study group) Include 34 patients who will receive Tramadol 100mg orally 1 hour before the procedure. Group B (study group) Include 34 patients who will receive Diclofenac 100mg orally 1 hour before the procedure. Group C (control group) Include 34 patients who will receive a placebo. Pain will evaluate on two separate occasion: immediately after the procedure and 15 minutes after procedure using a 100mm line visual analog scale. Official Title ----------------- Oral Tramadol Versus Diclofenac For Pain Relief Before Outpatient Hysteroscopy: A Randomized Controlled Trial Conditions ----------------- Pain, Procedure Intervention / Treatment ----------------- * Drug: Tramadol * Drug: Diclofenac * Drug: Placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: BMI raging between (18.5 - 30 ). Scheduled for diagnostic hysteroscopy only. All of them should have given informed written consent. Exclusion Criteria: Any contraindication to hysteroscopy (e.g. suspected pregnancy, genital tract infection). Receiving any other form of analgesia. Patients with known cervical stenosis, polyps and ulcers. Previous cervical surgery. Patients who are planning to have invasive intrauterine therapeutic interventions during the hysteroscopy. known sensitivity to non-steroidal anti-inflammatory and opioids drugs. Known gastritis or peptic ulcer or cardiac disease or Respiratory dysfunction. Unwilling to comply with the protocol, and Participation in another clinical trial in the last three months prior to the start of this study Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 35 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Tramadol<br>Women will receive oral tramadol 100 mg 1 hour before the procedure \| Drug: Tramadol<br>* Women will receive a oral Tramadol 100mg 1 hour before the procedure<br>\| \| Active Comparator: Diclofenac<br>Women will receive 100 mg diclofenac 1 hour before the procedure \| Drug: Diclofenac<br>* Women will receive oral Diclofenac 100mg 1 hour before the procedure<br>\| \| Placebo Comparator: Placebo<br>Women will receive a placebo 1 hour before the procedure \| Drug: Placebo<br>* Women will receive a Placebo 1 hour before the procedure<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Pain during the procedure \| Pain will be assessed using a visual analogue scale immediatly after inserting the hysterscopy \| intraoperative \| \| pain after the procedure \| 15 minutes after procedure using a 100mm line visual analog scale \| 15 minutes after completing the procedure \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Adverse effect and difficulties \| Recorded in Case Record Form \| 24 hours \|
NCT02779283	Personalized Kinase Inhibitor Therapy Combined With Chemotherapy in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia	This phase IB trial studies the feasibility of using a functional laboratory based study to determine how well the test can be used to select personalized kinase inhibitor therapy in combination with standard chemotherapy in treating patients with newly diagnosed acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). It also evaluates safety and potential efficacy. Kinase inhibitor is a type of substance that blocks an enzyme called a kinase. Human cells have many different kinase enzymes, and they help control important cell functions. Certain kinases are more active in some types of cancer cells and blocking them may help keep the cancer cells from growing. Testing samples of blood from patients with AML and ALL in the laboratory with kinase inhibitors may help determine which kinase inhibitor has more activity against cancer cells and which one should be combined with standard of care chemotherapy. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving a personalized kinase inhibitor therapy combined with standard chemotherapy may be a better treatment for AML and ALL.	PRIMARY OBJECTIVES:~I. Determine feasibility of using an in vitro small molecule inhibitor screen to select kinase inhibitors to add to standard chemotherapy induction in AML or ALL.~SECONDARY OBJECTIVES:~I. Determine the safety and tolerability of the addition of the kinase inhibitors when added to standard chemotherapy induction.~II. Evaluate overall objective response rates at completion of induction therapy.~III. Evaluate need for re-induction at day 14 (+/- 3 days) for AML. IV. Evaluate sensitivity to kinase inhibitors using our in vitro small molecule inhibitor screen in newly diagnosed AML/ALL.~V. Determine twelve-month overall survival.~TERTIARY OBJECTIVES:~I. Perform next-generation mutational analysis in primary leukemia samples from study subjects at baseline to establish a panel of known mutations for each subject and at the time of bone marrow recovery after induction chemotherapy to measure residual disease and evaluate utility of next-generation sequencing as a method compared to flow cytometry for minimal residual disease (MRD).~II. Evaluate pharmacokinetics for each individual kinase inhibitor. III. Determine if there is a cytogenetic or other risk group that has a higher rate of treatment failure or inability to obtain results from the small molecule inhibitor screen.~OUTLINE: Patients are assigned to 1 of 2 arms.~ARM I (AML): Patients receive cytarabine intravenously (IV) continuously over 24 hours on days 1-7, and idarubicin IV over 30 minutes on days 1-3.~ARM II (ALL) CYCLE A: Patients receive cyclophosphamide IV over 3 hours twice daily (BID) on days 1-3, vincristine sulfate IV on days 4 and 11, doxorubicin hydrochloride IV on day 4, dexamethasone PO on days 1-4 and 11-14, and rituximab IV on day 1 and 11 (day 11 only of course 1). Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.~ARM II (ALL) CYCLE B: Patients receive cytarabine IV over 2 hours BID on days 2-3, methotrexate IV over 2-22 hours on day 1, methylprednisolone sodium succinate IV BID on days 1-3, leucovorin calcium IV every 6 hours until methotrexate level is < 0.05 uM and rituximab IV on days 1 and 8. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.~In all arms, based on the results of the kinase inhibitor assay, patients receive either sorafenib tosylate PO BID, sunitinib malate PO daily, dasatinib PO daily, ponatinib hydrochloride PO daily, ruxolitinib phosphate or idelalisib PO BID on days 8-28 in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed up at 4-6 weeks, and then for a minimum of 1 year.	A Phase Ib Feasibility Study of Personalized Kinase Inhibitor Therapy Combined With Induction in Acute Leukemias Who Exhibit In Vitro Kinase Inhibitor Sensitivity	Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia	* Drug: Cyclophosphamide * Drug: Cytarabine * Drug: Dasatinib * Drug: Dexamethasone * Drug: Doxorubicin Hydrochloride * Drug: Idarubicin * Drug: Idelalisib * Device: In Vitro Kinase Inhibitor Assay * Drug: Leucovorin Calcium * Drug: Methotrexate * Drug: Methylprednisolone Sodium Succinate * Drug: Ponatinib Hydrochloride * Biological: Rituximab * Drug: Ruxolitinib Phosphate * Drug: Sorafenib Tosylate * Drug: Sunitinib Malate * Drug: Vincristine Sulfate	Inclusion Criteria:~Patients must have histologically confirmed AML or ALL, excluding acute promyelocytic leukemia (APL); for histological confirmation, a bone marrow biopsy and aspirate must be reviewed at Oregon Health & Science University (OHSU)~Patients must have newly diagnosed AML or ALL without previous treatment; hydroxyurea will be allowed to control peripheral blast count as clinically indicated but would need to be stopped prior to initiation of tyrosine kinase inhibitor [TKI]); all-trans retinoic acid (ATRA) is permitted during the period prior to ruling out a diagnosis of APL; previous radiation treatment is allowable; patients must be deemed eligible for treatment with cytotoxic induction chemotherapy with cytarabine and idarubicin for AML or hyper-cyclophosphamide, dexamethasone, doxorubicin, vincristine sulfate (CVAD) for ALL; patients newly diagnosed with ALL must have received no prior treatment for their ALL with the exception of steroids (i.e. prednisone, dexamethasone); intrathecal methotrexate or cytarabine, allowed prior to and throughout the enrollment period for AML and ALL~Subjects must be aged between >= 18 years and =< 64 for AML and > 40 and =< 64 for ALL~Eastern Cooperative Oncology Group (ECOG) performance status =< 2~Total bilirubin < 2.0 x institutional upper limit of normal (ULN)~Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN and thought to be due to hepatocellular dysfunction~Potassium > lower limit of normal (LLN) or correctable with supplements prior to first dose of study medication~Magnesium > LLN or correctable with supplements prior to first dose of study medication~Total calcium (corrected for serum albumin) >= LLN or correctable with supplements prior to first dose of study medication~Serum amylase and lipase =< 1.5 x institutional ULN~International normalized ratio (INR) =< 2.0 or correctable to 2.0 with vitamin K therapy~Corrected QT (QTc) =< 450 msec. for men or QTc =< 470 msec. for women~Creatinine < 2.0 x ULN~No clinically significant uncontrolled infections as determined by investigator~Patients must be able to take oral medications~Persons of reproductive potential must agree to an adequate method of contraception throughout treatment and for at least 4 weeks after study drug is stopped~Women of childbearing potential must have a negative serum or urine pregnancy test within 8 days prior to start of study drug administration~Patients must be willing to accept blood product transfusions~Ability to understand and the willingness to sign a written informed consent document and Health Insurance Portability and Accountability Act (HIPAA) documentation~DRUG-SPECIFIC INCLUSION CRITERIA~DASATINIB~Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of study drug~Women must not be breastfeeding~WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug, plus 30 days (duration of ovulatory cycle) for a total of 30 days post-treatment completion~Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug plus 90 days (duration of sperm turnover) for a total of 90 days post-treatment completion~Azoospermic males and WOCBP, who are not heterosexually active, are exempt from contraceptive requirements; however, WOCBP must still undergo pregnancy testing~Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of unexpected pregnancy; investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective contraception; highly effective methods of contraception have a failure rate of < 1% when used consistently and correctly~At a minimum, subjects must agree to the use of two methods of contraception, with one method being highly effective and the other method being either highly effective or less effective~Exclusion Criteria:~Newly diagnosed AML patients who are identified with FLT3-ITD or tyrosine kinase domain (TKD) point mutation in the codon for an aspartate (D835) or an isoleucine (I836) residue~Patients with a diagnosis of Philadelphia chromosome (Ph)+ ALL are not eligible~Subjects who are currently receiving any other investigational agents~History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent or other agents used in the study~Drugs that affect the cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) systems are allowed but should be used with caution depending on specific kinase inhibitor used~All outside study medications and supplements will be reviewed and monitored by the inpatient pharmacy team; patients will be discouraged from taking herbals and additional supplements~Patients should not be prescribed concomitant medications that may contribute to prolonged QTc without consultation with the chemotherapy pharmacist; additional ECGs should be done at the investigator?s discretion to ensure the subject?s safety; drugs that are generally accepted to increase the risk of Torsades de Pointes, include (but not limited to):~Quinidine, procainamide, disopyramide~Amiodarone, ibutilide, dofetilide, sotalol~Erythromycin, clarithromycin~Chlorpromazine, mesoridazine, thioridazine, pimozide~Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine~Left ventricular ejection fraction < 50%~Uncontrolled intercurrent illness including but not limited to, symptomatic New York Heart Association (NYHA) class III congestive heart failure, uncontrolled angina pectoris, myocardial infarction or stroke within 6 months prior to enrollment, or psychiatric illness/social situations that would limit compliance with study requirements~Patients with a known human immunodeficiency virus (HIV) diagnosis are excluded from the study~History of hypersensitivity to any of the kinase inhibitors included in this study~Pregnant or lactating women are excluded from the study~Diagnosed congenital long QT syndrome~Any history of significant bleeding disorder unrelated to cancer, including any congenital bleeding disorder or any acquired bleeding disorder within one year of start of study~Any history of clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation or torsade de pointes)~Patients must not have clinically significant malabsorption syndrome or history~All patients must discontinue anti-platelet agents or anticoagulants 7 days prior to initiation of study drug~All patients with unhealed wounds or fistulas should not be given vascular endothelial growth factor (VEGF) inhibiting TKIs~DRUG-SPECIFIC EXCLUSION CRITERIA~PONATINIB~Patients with cytogenetically ?favorable risk' AML (core-binding factor leukemias) will not be enrolled on the ponatinib arm; testing with cytogenetics and fluorescence in situ hybridization (FISH) can establish this subtype within 7 days of the diagnostic bone marrow biopsy~History of acute pancreatitis within 1 year of study or history of chronic pancreatitis~Uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL)~Any history of myocardial infarction, stroke, or revascularization~Any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism with the exception of upper Extremity/Line associated deep vein thrombosis (DVTs) which are adequately treated (line removed and/or patient anti-coagulated)~Uncontrolled hypertension (diastolic blood pressure > 90 mm Hg; systolic > 140 mm Hg); patients with hypertension should be under treatment on study entry to effect blood pressure control~DASATINIB~Any history of second or third degree heart block (may be eligible if the subject currently has a pacemaker)~Known pulmonary arterial hypertension~Patients may not have clinically significant pleural or pericardial effusion per provider discretion~SORAFENIB~Major surgery, open biopsy, or significant traumatic injury within 30 days~Non-healing wound, ulcer, or bone fracture~Thrombotic or embolic venous or arterial events, such as cerebrovascular accident, including transient ischemic attacks, arterial thrombosis, deep vein thrombosis and pulmonary embolism within the past 6 months~Upper Extremity/Line associated DVTs which are adequately treated (line removed and/or patient anticoagulated) are eligible~Uncontrolled hypertension~Active bleeding during screening~Hypersensitivity to sorafenib~Idelalisib~Ongoing drug-induced liver injury, chronic active hepatitis C (hepatitis C virus [HCV]), chronic active hepatitis B (hepatitis B virus [HBV]), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, portal hypertension, or history of autoimmune hepatitis~Ongoing symptomatic pneumonitis~Ongoing inflammatory bowel disease or autoimmune colitis~Ongoing cytomegalovirus (CMV) infection, treatment, or prophylaxis within the past 28 days prior to the screening test for active CMV~History of serious allergic reaction including anaphylaxis and epidermal necrolysis~Ruxolitinib~Chronic active hepatitis C (HCV)	18 Years	64 Years	All	No	Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Proportion of subjects who start a targeted drug \| A proportion of subjects whose targeted drug is identified and who start the kinase-inhibitor drug on day 8 will be estimated among all screened subjects along with the 95% confidence interval using the feasibility analysis set. \| On day 8 \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Incidence of any grade 3 or higher dose limiting toxicity graded (DLT) according to Common Terminology Criteria for Adverse Events version 4.0 \| DLT events will be tabulated and summarized. The incidence of DLT and its 95% confidence interval will be provided for the entire safety analysis set as well as for each targeted drug separately. \| Up to 6 weeks post-treatment \| \| Overall objective response rates defined as morphologic, cytogenetic and molecular complete response (CR) rates at the end of induction period \| The proportion and its 95% confidence interval will be provided for morphologic CR rate, cytogenetic CR rate, and molecular CR rate at the end of induction period. The descriptive statistics (mean, standard deviation, median, minimum and maximum) will be provided for % blasts at day 14 (+/- 3 days) for acute myeloid leukemia or show signs of disease progression requiring alternative treatment (re-induction) during the 21 day targeted treatment period (days 8-28) for acute lymphoblastic leukemia. The proportion and its 95% confidence interval will be provided for the proportion of patients who show sensitivity to each of the study drugs (i.e., IC50 < 20% of median IC50). \| At 14 days post-induction treatment \| \| Proportion of patients who show sensitivity to each of the study kinase inhibitors \| Measured as half maximal inhibitory concentration (IC50) < 20% of median IC50. \| Baseline \| \| Overall survival \| Kaplan-Meier method will be used to estimate overall survival. \| From date of the first treatment assessed up to 1 year \|		Calcium, Dietary, Leucovorin, Folic Acid, Cytarabine, Dexamethasone, Methylprednisolone, Methylprednisolone Acetate, Methylprednisolone Hemisuccinate, Prednisolone, Prednisolone acetate, Dexamethasone acetate, Cyclophosphamide, Rituximab, Doxorubicin, Liposomal doxorubicin, Methotrexate, Vincristine, Sorafenib, Sunitinib, Dasatinib, Idarubicin, Ponatinib, Idelalisib, Antineoplastic Agents, Immunological, Antibodies, Immunoglobulins, Antibodies, Monoclonal, Prednisolone hemisuccinate, Prednisolone phosphate, BB 1101, Calcium, Levoleucovorin, Immunosuppressive Agents, Immunologic Factors, Physiological Effects of Drugs, Antirheumatic Agents, Antineoplastic Agents, Alkylating, Alkylating Agents, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents, Myeloablative Agonists, Anti-Inflammatory Agents, Antiemetics, Autonomic Agents, Peripheral Nervous System Agents, Gastrointestinal Agents, Glucocorticoids, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Antineoplastic Agents, Hormonal, Antibiotics, Antineoplastic, Topoisomerase II Inhibitors, Topoisomerase Inhibitors, Enzyme Inhibitors, Calcium-Regulating Hormones and Agents, Bone Density Conservation Agents, Abortifacient Agents, Nonsteroidal, Abortifacient Agents, Reproductive Control Agents, Antimetabolites, Antineoplastic, Antimetabolites, Dermatologic Agents, Folic Acid Antagonists, Nucleic Acid Synthesis Inhibitors, Antiviral Agents, Anti-Infective Agents, Antidotes, Protective Agents, Vitamin B Complex, Vitamins, Micronutrients, Antineoplastic Agents, Phytogenic, Tubulin Modulators, Antimitotic Agents, Mitosis Modulators, Protein Kinase Inhibitors, Neuroprotective Agents, Angiogenesis Inhibitors, Angiogenesis Modulating Agents, Growth Substances, Growth Inhibitors, Hematinics, Protease Inhibitors	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Arm I (AML)<br>Patients receive cytarabine IV continuously over 24 hours on days 1-7, and idarubicin IV over 30 minutes on days 1-3.Patients receive cyclophosphamide IV over 3 hours twice daily (BID) on days 1-3, vincristine sulfate IV on days 4 and 11, doxorubicin hydrochloride IV on day 4, dexamethasone PO on days 1-4 and 11-14, and rituximab IV on day 1 and 11 (day 11 only of course 1). Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Based on the results of the kinase inhibitor assay (In Vitro Kinase Inhibitor Assay), patients receive either sorafenib tosylate PO BID, sunitinib malate PO daily, dasatinib PO daily, ponatinib hydrochloride PO daily, ruxolitinib phosphate or idelalisib PO BID on days 8-28 in the absence of disease progression or unacceptable toxicity. \| Drug: Cytarabine<br>* Given IV<br>* Other names: WR-28453;Drug: Dasatinib<br>* Given PO<br>* Other names: Sprycel;Drug: Idarubicin<br>* Given IV<br>* Other names: 4-DMDR;Drug: Idelalisib<br>* Given PO<br>* Other names: Zydelig;Device: In Vitro Kinase Inhibitor Assay<br>* Correlative studies<br>* Other names: Laboratory Biomarker Analysis;Drug: Ponatinib Hydrochloride<br>* Given PO<br>* Other names: Iclusig;Drug: Ruxolitinib Phosphate<br>* Given PO<br>* Other names: Jakafi;Drug: Sorafenib Tosylate<br>* Given PO<br>* Other names: sorafenib;Drug: Sunitinib Malate<br>* Given PO<br>* Other names: Sutent;\| \| Experimental: Arm II (ALL)<br>Patients receive cytarabine IV over 2 hours BID on days 2-3, methotrexate IV over 2-22 hours on day 1, methylprednisolone sodium succinate IV BID on days 1-3, leucovorin calcium IV every 6 hours until methotrexate level is < 0.05 uM and rituximab IV on days 1 and 8. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Based on the results of the kinase inhibitor assay (In Vitro Kinase Inhibitor Assay), patients receive either sorafenib tosylate PO BID, sunitinib malate PO daily, dasatinib PO daily, ponatinib hydrochloride PO daily, ruxolitinib phosphate or idelalisib PO BID on days 8-28 in the absence of disease progression or unacceptable toxicity. \| Drug: Cyclophosphamide<br>* Given IV<br>* Other names: WR- 138719;Drug: Cytarabine<br>* Given IV<br>* Other names: WR-28453;Drug: Dasatinib<br>* Given PO<br>* Other names: Sprycel;Drug: Dexamethasone<br>* Given PO<br>* Other names: Visumetazone;Drug: Doxorubicin Hydrochloride<br>* Given IV<br>* Other names: Rubex;Drug: Idelalisib<br>* Given PO<br>* Other names: Zydelig;Device: In Vitro Kinase Inhibitor Assay<br>* Correlative studies<br>* Other names: Laboratory Biomarker Analysis;Drug: Leucovorin Calcium<br>* Given IV<br>* Other names: Wellcovorin;Drug: Methotrexate<br>* Given IV<br>* Other names: WR-19039;Drug: Methylprednisolone Sodium Succinate<br>* Given IV<br>* Other names: Solu-Medrone;Drug: Ponatinib Hydrochloride<br>* Given PO<br>* Other names: Iclusig;Biological: Rituximab<br>* Given IV<br>* Other names: RTXM83;Drug: Ruxolitinib Phosphate<br>* Given PO<br>* Other names: Jakafi;Drug: Sorafenib Tosylate<br>* Given PO<br>* Other names: sorafenib;Drug: Sunitinib Malate<br>* Given PO<br>* Other names: Sutent;Drug: Vincristine Sulfate<br>* Given IV<br>* Other names: Vincristine, sulfate;\|	Personalized Kinase Inhibitor Therapy Combined With Chemotherapy in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia Study Overview ================= Brief Summary ----------------- This phase IB trial studies the feasibility of using a functional laboratory based study to determine how well the test can be used to select personalized kinase inhibitor therapy in combination with standard chemotherapy in treating patients with newly diagnosed acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). It also evaluates safety and potential efficacy. Kinase inhibitor is a type of substance that blocks an enzyme called a kinase. Human cells have many different kinase enzymes, and they help control important cell functions. Certain kinases are more active in some types of cancer cells and blocking them may help keep the cancer cells from growing. Testing samples of blood from patients with AML and ALL in the laboratory with kinase inhibitors may help determine which kinase inhibitor has more activity against cancer cells and which one should be combined with standard of care chemotherapy. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving a personalized kinase inhibitor therapy combined with standard chemotherapy may be a better treatment for AML and ALL. Detailed Description ----------------- PRIMARY OBJECTIVES: I. Determine feasibility of using an in vitro small molecule inhibitor screen to select kinase inhibitors to add to standard chemotherapy induction in AML or ALL. SECONDARY OBJECTIVES: I. Determine the safety and tolerability of the addition of the kinase inhibitors when added to standard chemotherapy induction. II. Evaluate overall objective response rates at completion of induction therapy. III. Evaluate need for re-induction at day 14 (+/- 3 days) for AML. IV. Evaluate sensitivity to kinase inhibitors using our in vitro small molecule inhibitor screen in newly diagnosed AML/ALL. V. Determine twelve-month overall survival. TERTIARY OBJECTIVES: I. Perform next-generation mutational analysis in primary leukemia samples from study subjects at baseline to establish a panel of known mutations for each subject and at the time of bone marrow recovery after induction chemotherapy to measure residual disease and evaluate utility of next-generation sequencing as a method compared to flow cytometry for minimal residual disease (MRD). II. Evaluate pharmacokinetics for each individual kinase inhibitor. III. Determine if there is a cytogenetic or other risk group that has a higher rate of treatment failure or inability to obtain results from the small molecule inhibitor screen. OUTLINE: Patients are assigned to 1 of 2 arms. ARM I (AML): Patients receive cytarabine intravenously (IV) continuously over 24 hours on days 1-7, and idarubicin IV over 30 minutes on days 1-3. ARM II (ALL) CYCLE A: Patients receive cyclophosphamide IV over 3 hours twice daily (BID) on days 1-3, vincristine sulfate IV on days 4 and 11, doxorubicin hydrochloride IV on day 4, dexamethasone PO on days 1-4 and 11-14, and rituximab IV on day 1 and 11 (day 11 only of course 1). Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. ARM II (ALL) CYCLE B: Patients receive cytarabine IV over 2 hours BID on days 2-3, methotrexate IV over 2-22 hours on day 1, methylprednisolone sodium succinate IV BID on days 1-3, leucovorin calcium IV every 6 hours until methotrexate level is < 0.05 uM and rituximab IV on days 1 and 8. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. In all arms, based on the results of the kinase inhibitor assay, patients receive either sorafenib tosylate PO BID, sunitinib malate PO daily, dasatinib PO daily, ponatinib hydrochloride PO daily, ruxolitinib phosphate or idelalisib PO BID on days 8-28 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 4-6 weeks, and then for a minimum of 1 year. Official Title ----------------- A Phase Ib Feasibility Study of Personalized Kinase Inhibitor Therapy Combined With Induction in Acute Leukemias Who Exhibit In Vitro Kinase Inhibitor Sensitivity Conditions ----------------- Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia Intervention / Treatment ----------------- * Drug: Cyclophosphamide * Drug: Cytarabine * Drug: Dasatinib * Drug: Dexamethasone * Drug: Doxorubicin Hydrochloride * Drug: Idarubicin * Drug: Idelalisib * Device: In Vitro Kinase Inhibitor Assay * Drug: Leucovorin Calcium * Drug: Methotrexate * Drug: Methylprednisolone Sodium Succinate * Drug: Ponatinib Hydrochloride * Biological: Rituximab * Drug: Ruxolitinib Phosphate * Drug: Sorafenib Tosylate * Drug: Sunitinib Malate * Drug: Vincristine Sulfate Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients must have histologically confirmed AML or ALL, excluding acute promyelocytic leukemia (APL); for histological confirmation, a bone marrow biopsy and aspirate must be reviewed at Oregon Health & Science University (OHSU) Patients must have newly diagnosed AML or ALL without previous treatment; hydroxyurea will be allowed to control peripheral blast count as clinically indicated but would need to be stopped prior to initiation of tyrosine kinase inhibitor [TKI]); all-trans retinoic acid (ATRA) is permitted during the period prior to ruling out a diagnosis of APL; previous radiation treatment is allowable; patients must be deemed eligible for treatment with cytotoxic induction chemotherapy with cytarabine and idarubicin for AML or hyper-cyclophosphamide, dexamethasone, doxorubicin, vincristine sulfate (CVAD) for ALL; patients newly diagnosed with ALL must have received no prior treatment for their ALL with the exception of steroids (i.e. prednisone, dexamethasone); intrathecal methotrexate or cytarabine, allowed prior to and throughout the enrollment period for AML and ALL Subjects must be aged between >= 18 years and =< 64 for AML and > 40 and =< 64 for ALL Eastern Cooperative Oncology Group (ECOG) performance status =< 2 Total bilirubin < 2.0 x institutional upper limit of normal (ULN) Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN and thought to be due to hepatocellular dysfunction Potassium > lower limit of normal (LLN) or correctable with supplements prior to first dose of study medication Magnesium > LLN or correctable with supplements prior to first dose of study medication Total calcium (corrected for serum albumin) >= LLN or correctable with supplements prior to first dose of study medication Serum amylase and lipase =< 1.5 x institutional ULN International normalized ratio (INR) =< 2.0 or correctable to 2.0 with vitamin K therapy Corrected QT (QTc) =< 450 msec. for men or QTc =< 470 msec. for women Creatinine < 2.0 x ULN No clinically significant uncontrolled infections as determined by investigator Patients must be able to take oral medications Persons of reproductive potential must agree to an adequate method of contraception throughout treatment and for at least 4 weeks after study drug is stopped Women of childbearing potential must have a negative serum or urine pregnancy test within 8 days prior to start of study drug administration Patients must be willing to accept blood product transfusions Ability to understand and the willingness to sign a written informed consent document and Health Insurance Portability and Accountability Act (HIPAA) documentation DRUG-SPECIFIC INCLUSION CRITERIA DASATINIB Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of study drug Women must not be breastfeeding WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug, plus 30 days (duration of ovulatory cycle) for a total of 30 days post-treatment completion Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug plus 90 days (duration of sperm turnover) for a total of 90 days post-treatment completion Azoospermic males and WOCBP, who are not heterosexually active, are exempt from contraceptive requirements; however, WOCBP must still undergo pregnancy testing Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of unexpected pregnancy; investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective contraception; highly effective methods of contraception have a failure rate of < 1% when used consistently and correctly At a minimum, subjects must agree to the use of two methods of contraception, with one method being highly effective and the other method being either highly effective or less effective Exclusion Criteria: Newly diagnosed AML patients who are identified with FLT3-ITD or tyrosine kinase domain (TKD) point mutation in the codon for an aspartate (D835) or an isoleucine (I836) residue Patients with a diagnosis of Philadelphia chromosome (Ph)+ ALL are not eligible Subjects who are currently receiving any other investigational agents History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent or other agents used in the study Drugs that affect the cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) systems are allowed but should be used with caution depending on specific kinase inhibitor used All outside study medications and supplements will be reviewed and monitored by the inpatient pharmacy team; patients will be discouraged from taking herbals and additional supplements Patients should not be prescribed concomitant medications that may contribute to prolonged QTc without consultation with the chemotherapy pharmacist; additional ECGs should be done at the investigator?s discretion to ensure the subject?s safety; drugs that are generally accepted to increase the risk of Torsades de Pointes, include (but not limited to): Quinidine, procainamide, disopyramide Amiodarone, ibutilide, dofetilide, sotalol Erythromycin, clarithromycin Chlorpromazine, mesoridazine, thioridazine, pimozide Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine Left ventricular ejection fraction < 50% Uncontrolled intercurrent illness including but not limited to, symptomatic New York Heart Association (NYHA) class III congestive heart failure, uncontrolled angina pectoris, myocardial infarction or stroke within 6 months prior to enrollment, or psychiatric illness/social situations that would limit compliance with study requirements Patients with a known human immunodeficiency virus (HIV) diagnosis are excluded from the study History of hypersensitivity to any of the kinase inhibitors included in this study Pregnant or lactating women are excluded from the study Diagnosed congenital long QT syndrome Any history of significant bleeding disorder unrelated to cancer, including any congenital bleeding disorder or any acquired bleeding disorder within one year of start of study Any history of clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation or torsade de pointes) Patients must not have clinically significant malabsorption syndrome or history All patients must discontinue anti-platelet agents or anticoagulants 7 days prior to initiation of study drug All patients with unhealed wounds or fistulas should not be given vascular endothelial growth factor (VEGF) inhibiting TKIs DRUG-SPECIFIC EXCLUSION CRITERIA PONATINIB Patients with cytogenetically ?favorable risk' AML (core-binding factor leukemias) will not be enrolled on the ponatinib arm; testing with cytogenetics and fluorescence in situ hybridization (FISH) can establish this subtype within 7 days of the diagnostic bone marrow biopsy History of acute pancreatitis within 1 year of study or history of chronic pancreatitis Uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL) Any history of myocardial infarction, stroke, or revascularization Any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism with the exception of upper Extremity/Line associated deep vein thrombosis (DVTs) which are adequately treated (line removed and/or patient anti-coagulated) Uncontrolled hypertension (diastolic blood pressure > 90 mm Hg; systolic > 140 mm Hg); patients with hypertension should be under treatment on study entry to effect blood pressure control DASATINIB Any history of second or third degree heart block (may be eligible if the subject currently has a pacemaker) Known pulmonary arterial hypertension Patients may not have clinically significant pleural or pericardial effusion per provider discretion SORAFENIB Major surgery, open biopsy, or significant traumatic injury within 30 days Non-healing wound, ulcer, or bone fracture Thrombotic or embolic venous or arterial events, such as cerebrovascular accident, including transient ischemic attacks, arterial thrombosis, deep vein thrombosis and pulmonary embolism within the past 6 months Upper Extremity/Line associated DVTs which are adequately treated (line removed and/or patient anticoagulated) are eligible Uncontrolled hypertension Active bleeding during screening Hypersensitivity to sorafenib Idelalisib Ongoing drug-induced liver injury, chronic active hepatitis C (hepatitis C virus [HCV]), chronic active hepatitis B (hepatitis B virus [HBV]), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, portal hypertension, or history of autoimmune hepatitis Ongoing symptomatic pneumonitis Ongoing inflammatory bowel disease or autoimmune colitis Ongoing cytomegalovirus (CMV) infection, treatment, or prophylaxis within the past 28 days prior to the screening test for active CMV History of serious allergic reaction including anaphylaxis and epidermal necrolysis Ruxolitinib Chronic active hepatitis C (HCV) Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 64 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Arm I (AML)<br>Patients receive cytarabine IV continuously over 24 hours on days 1-7, and idarubicin IV over 30 minutes on days 1-3.Patients receive cyclophosphamide IV over 3 hours twice daily (BID) on days 1-3, vincristine sulfate IV on days 4 and 11, doxorubicin hydrochloride IV on day 4, dexamethasone PO on days 1-4 and 11-14, and rituximab IV on day 1 and 11 (day 11 only of course 1). Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Based on the results of the kinase inhibitor assay (In Vitro Kinase Inhibitor Assay), patients receive either sorafenib tosylate PO BID, sunitinib malate PO daily, dasatinib PO daily, ponatinib hydrochloride PO daily, ruxolitinib phosphate or idelalisib PO BID on days 8-28 in the absence of disease progression or unacceptable toxicity. \| Drug: Cytarabine<br>* Given IV<br>* Other names: WR-28453;Drug: Dasatinib<br>* Given PO<br>* Other names: Sprycel;Drug: Idarubicin<br>* Given IV<br>* Other names: 4-DMDR;Drug: Idelalisib<br>* Given PO<br>* Other names: Zydelig;Device: In Vitro Kinase Inhibitor Assay<br>* Correlative studies<br>* Other names: Laboratory Biomarker Analysis;Drug: Ponatinib Hydrochloride<br>* Given PO<br>* Other names: Iclusig;Drug: Ruxolitinib Phosphate<br>* Given PO<br>* Other names: Jakafi;Drug: Sorafenib Tosylate<br>* Given PO<br>* Other names: sorafenib;Drug: Sunitinib Malate<br>* Given PO<br>* Other names: Sutent;\| \| Experimental: Arm II (ALL)<br>Patients receive cytarabine IV over 2 hours BID on days 2-3, methotrexate IV over 2-22 hours on day 1, methylprednisolone sodium succinate IV BID on days 1-3, leucovorin calcium IV every 6 hours until methotrexate level is < 0.05 uM and rituximab IV on days 1 and 8. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Based on the results of the kinase inhibitor assay (In Vitro Kinase Inhibitor Assay), patients receive either sorafenib tosylate PO BID, sunitinib malate PO daily, dasatinib PO daily, ponatinib hydrochloride PO daily, ruxolitinib phosphate or idelalisib PO BID on days 8-28 in the absence of disease progression or unacceptable toxicity. \| Drug: Cyclophosphamide<br>* Given IV<br>* Other names: WR- 138719;Drug: Cytarabine<br>* Given IV<br>* Other names: WR-28453;Drug: Dasatinib<br>* Given PO<br>* Other names: Sprycel;Drug: Dexamethasone<br>* Given PO<br>* Other names: Visumetazone;Drug: Doxorubicin Hydrochloride<br>* Given IV<br>* Other names: Rubex;Drug: Idelalisib<br>* Given PO<br>* Other names: Zydelig;Device: In Vitro Kinase Inhibitor Assay<br>* Correlative studies<br>* Other names: Laboratory Biomarker Analysis;Drug: Leucovorin Calcium<br>* Given IV<br>* Other names: Wellcovorin;Drug: Methotrexate<br>* Given IV<br>* Other names: WR-19039;Drug: Methylprednisolone Sodium Succinate<br>* Given IV<br>* Other names: Solu-Medrone;Drug: Ponatinib Hydrochloride<br>* Given PO<br>* Other names: Iclusig;Biological: Rituximab<br>* Given IV<br>* Other names: RTXM83;Drug: Ruxolitinib Phosphate<br>* Given PO<br>* Other names: Jakafi;Drug: Sorafenib Tosylate<br>* Given PO<br>* Other names: sorafenib;Drug: Sunitinib Malate<br>* Given PO<br>* Other names: Sutent;Drug: Vincristine Sulfate<br>* Given IV<br>* Other names: Vincristine, sulfate;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Proportion of subjects who start a targeted drug \| A proportion of subjects whose targeted drug is identified and who start the kinase-inhibitor drug on day 8 will be estimated among all screened subjects along with the 95% confidence interval using the feasibility analysis set. \| On day 8 \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Incidence of any grade 3 or higher dose limiting toxicity graded (DLT) according to Common Terminology Criteria for Adverse Events version 4.0 \| DLT events will be tabulated and summarized. The incidence of DLT and its 95% confidence interval will be provided for the entire safety analysis set as well as for each targeted drug separately. \| Up to 6 weeks post-treatment \| \| Overall objective response rates defined as morphologic, cytogenetic and molecular complete response (CR) rates at the end of induction period \| The proportion and its 95% confidence interval will be provided for morphologic CR rate, cytogenetic CR rate, and molecular CR rate at the end of induction period. The descriptive statistics (mean, standard deviation, median, minimum and maximum) will be provided for % blasts at day 14 (+/- 3 days) for acute myeloid leukemia or show signs of disease progression requiring alternative treatment (re-induction) during the 21 day targeted treatment period (days 8-28) for acute lymphoblastic leukemia. The proportion and its 95% confidence interval will be provided for the proportion of patients who show sensitivity to each of the study drugs (i.e., IC50 < 20% of median IC50). \| At 14 days post-induction treatment \| \| Proportion of patients who show sensitivity to each of the study kinase inhibitors \| Measured as half maximal inhibitory concentration (IC50) < 20% of median IC50. \| Baseline \| \| Overall survival \| Kaplan-Meier method will be used to estimate overall survival. \| From date of the first treatment assessed up to 1 year \|
NCT01699646	Cadiotocography Combined With ST-analysis Versus Cardiotocography Combined With Scalp-pH	Hypothesis:~STAN monitoring will reduce the number of interventions because of suspected fetal asphyxia and reduce the number of newborns with metabolic acidosis.~Primary endpoint:~1) Frequency of metabolic acidosis in the two groups, defined by pH in umbilical cord artery < 7.05 and standard base excess <-10.~Secondary endpoints:~Number of intervention (VE and caesarean section) in the two groups~Number of pH measurements in the two groups~Number of neonates admitted to the neonatal department because of suspected asphyxia in the two groups~The aim of fetal surveillance is to identify those fetuses at risk for developing damage in newborn to term or long term damage caused by lack of oxygen during birth process. Approximately 1/10 of all cases of paralysis due to brain damage (cerebral palsy) is believed to be caused by lack of oxygen during birth. These can be avoided if the investigators intervene actively in the birth before damage occurs.~CardioTocoGraphy (CTG = detection of fetal heart rate pattern and maternal uterine contractions via electrodes on the maternal abdomen and fetal scalp) is a widely used method of fetal surveillance. However, it can be difficult to interpret a CTG, and uncertainty in CTG interpretation may therefore lead to increase in the number of deliveries with vacuum suction and caesarean section. Interpretation of CTG can be improved by analyzing the acidity of a blood sample taken from the skin of the fetal scalp. Such a scalp pH analysis shows indirectly the fetus gets enough oxygen. Scalp pH measurement requires expertise and requires repeated measurements if the abnormal heart rate pattern persists. This method is the normal routine at the maternity ward at Hvidovre Hospital / Roskilde County Hospital.~The problem seems to be partially alleviated by using a newly developed method for fetal surveillance called STAN (ST analysis). By STAN continuously recorded both CTG and fetal ECG (electrocardiography = recording of the electrical heart activity). Simultaneously analyzes a portion of the fetal ECG, namely ST-part because hypoxia leads to changes in it. The technique is easy to use, since it only requires one electrode on the fetal scalp that is placed in the same way as in ordinary CTG registration.	The value of STAN (ST analysis) was assessed in 2 randomized trials and shows: 1) A reduction in the incidence of severe hypoxia in fetuses during labor and 2) A reduction in frequency of redemption with suction and caesarean section due to lack of oxygen during the birth process.~Within the last year however, there is substantial new information regarding. STAN. The Swedish Social Board has published a newsletter (17) which describes a possible risk of birth of asphyxiated children, some died and others have cerebral palsy. A new Finnish study (18) suggests that there may be an increased risk of (moderate) acidosis after using STAN.~The above has led to considerable debate, not just in Sweden but also throughout Europe. This has led to the Swedish, Danish (Newsletter 1, Annex 1b) and the common Nordic reference group for STAN orally has announced new clinical guidelines for STAN application. A recently held workshop in Utrecht, Holland will generate joint European guideline, these will be sought published. Against this background it has been necessary to develop new guidelines for the complement of scalp pH in the STAN arm of this project (Annex 1a)~Common to the above studies is that there is consistently applied scalp pH before STAN monitoring begins. It is therefore important to elucidate whether, through the use of STAN monitoring is needed (more than 1) FBS - and if so to what extent FBS is required.~STAN method currently winning widespread in Denmark and internationally (FDA has just approved), notwithstanding that it is not scientifically proven that fetal monitoring with STAN is better than the current monitoring method with scalp pH measurement. It is therefore important to get this resolved in a randomized study in the relative expensive STAN apparatus introduced in several places in Denmark.~This study will provide an opportunity to highlight these issues and can prepare on our way to use STAN to prevent or significantly reduce these risks and thus justify continued STAN use or the continued spread of STAN should not by advised.~If STAN by our method proves to be comparable with clean scalps pH measurement as an adjunct to CTG, it will be a significant advance in fetal monitoring technology, taking thus will have a primarily non-invasive, safe and continuous method cause less inconvenience to both mother and child.~The study was approved by the Ethical nominee directors.~The study will include all women > 18 years in labour with a fetus in the cephalic presentation with a gestational age of more than 36 weeks + 0, where there is the monitoring with CTG.~Women who develop CTG changes that are interpreted as abnormal (according to STAN (FIGO)-guidelines and the scalp pH is normal, could be included in the study. Women will be randomised by telephone(electronic)to surveillance with eighter STAN monitoring or with CTG and scalp pH. In the latter group STAN results will be blinded (hidden) for later analysis.~There are estimated to be 1200 women in the study and the study is expected to run for 2-3 years, preceded by a pilotproject.~During the pilot project we will follow the department's usual procedures for monitoring, but to CTG using the STAN device with blinded/concealed ST analysis. There is expected to be 100 patients in the pilotproject. The aim is to investigate whether the calculations in the survey stick and simultaneously train staff at the maternity ward in STAN equipment and procedures and make them familiar with the work.~The advantage in conducting the study at the maternity ward at Hvidovre hospital is that it is the largest birthplace in Denmark with nearly 6,000 births annually, with perhaps the highest use of scalp pH measurements during labor. In addition, nearly 3,000 births annually at Roskilde County Hospital, a total of 9,500 births. In addition, department and project managers areexperienced in scientific studies on fetal monitoring.~Project participants have on their own initiative, initiated this project and has no financial interest in the instrument companies that produce the used equipment/ appliances/ monitors.~The project has been allocated 2.5 million DKr in funding for the project from Elsass Foundation, a private foundation with no financial interest in the project equipment/ appliances/ monitors.	Cardiotocography Combined With ST-analysis Versus Cardiotocography Combined With Scalp-pH in Deliveries With Abnormal CTG - A Randomised Trial	Metabolic Acidosis of Newborn	* Device: Neoventa S 21 ST-ANalysis of fetal heart * Procedure: CTG + FBS	Inclusion Criteria:~intermediate or abnormal CTG and~Normal fetal scalp-pH > or = 7,25~Exclusion Criteria:~preterminal CTG~Fetal arrythmias or A-V block~Severe fetal malformations (known)~Amnionitis (temp > 38,5 degr. celcius)~maternal Hepatitis B/C or HIV	18 Years	50 Years	Female	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Frequency of metabolic acidosis in the 2 groups, defined by pH < 7,05 and SBE < -10 in the umbilical artery \| We will do a minimum 2 year follow-up on the children \| within 1 hour \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Does STAN reduce number of admissions to NICU and/or HIE \| Number of neonates admitted to NICU because of suspected asphyxia in the two groups. There will also be a minimun of 2 years of follow-up in these children \| 2 years after termination of study \| \| Does STAN reduce number of interventions in delivery(vacuum or section) \| \| 1 year after termination of study \|	CTG, Intrapartum fetal surveillance, cardiotocography, STAN, ST-Analysis, metabolic acidosis in umbilical artery, operative delivery	Acidosis, Acid-Base Imbalance, Metabolic Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: CTG + FBS<br>intrapartum surveillance with CTG+FBS \| Procedure: CTG + FBS<br>* Cardiotocography and fetal blood sampling on/from fetal skalp<br>* Other names: Cardiotocography and fetal blood sampling (scalp-pH);\| \| Active Comparator: Neoventa S 21 ST-ANalysis of fetal heart<br>intrapartum surveillance with CTG + STAN \| Device: Neoventa S 21 ST-ANalysis of fetal heart<br>* Application of gold-trace scalp electrode<br>* Other names: Cardiotocography and ST-ANalysis;\|	Cadiotocography Combined With ST-analysis Versus Cardiotocography Combined With Scalp-pH Study Overview ================= Brief Summary ----------------- Hypothesis: STAN monitoring will reduce the number of interventions because of suspected fetal asphyxia and reduce the number of newborns with metabolic acidosis. Primary endpoint: 1) Frequency of metabolic acidosis in the two groups, defined by pH in umbilical cord artery < 7.05 and standard base excess <-10. Secondary endpoints: Number of intervention (VE and caesarean section) in the two groups Number of pH measurements in the two groups Number of neonates admitted to the neonatal department because of suspected asphyxia in the two groups The aim of fetal surveillance is to identify those fetuses at risk for developing damage in newborn to term or long term damage caused by lack of oxygen during birth process. Approximately 1/10 of all cases of paralysis due to brain damage (cerebral palsy) is believed to be caused by lack of oxygen during birth. These can be avoided if the investigators intervene actively in the birth before damage occurs. CardioTocoGraphy (CTG = detection of fetal heart rate pattern and maternal uterine contractions via electrodes on the maternal abdomen and fetal scalp) is a widely used method of fetal surveillance. However, it can be difficult to interpret a CTG, and uncertainty in CTG interpretation may therefore lead to increase in the number of deliveries with vacuum suction and caesarean section. Interpretation of CTG can be improved by analyzing the acidity of a blood sample taken from the skin of the fetal scalp. Such a scalp pH analysis shows indirectly the fetus gets enough oxygen. Scalp pH measurement requires expertise and requires repeated measurements if the abnormal heart rate pattern persists. This method is the normal routine at the maternity ward at Hvidovre Hospital / Roskilde County Hospital. The problem seems to be partially alleviated by using a newly developed method for fetal surveillance called STAN (ST analysis). By STAN continuously recorded both CTG and fetal ECG (electrocardiography = recording of the electrical heart activity). Simultaneously analyzes a portion of the fetal ECG, namely ST-part because hypoxia leads to changes in it. The technique is easy to use, since it only requires one electrode on the fetal scalp that is placed in the same way as in ordinary CTG registration. Detailed Description ----------------- The value of STAN (ST analysis) was assessed in 2 randomized trials and shows: 1) A reduction in the incidence of severe hypoxia in fetuses during labor and 2) A reduction in frequency of redemption with suction and caesarean section due to lack of oxygen during the birth process. Within the last year however, there is substantial new information regarding. STAN. The Swedish Social Board has published a newsletter (17) which describes a possible risk of birth of asphyxiated children, some died and others have cerebral palsy. A new Finnish study (18) suggests that there may be an increased risk of (moderate) acidosis after using STAN. The above has led to considerable debate, not just in Sweden but also throughout Europe. This has led to the Swedish, Danish (Newsletter 1, Annex 1b) and the common Nordic reference group for STAN orally has announced new clinical guidelines for STAN application. A recently held workshop in Utrecht, Holland will generate joint European guideline, these will be sought published. Against this background it has been necessary to develop new guidelines for the complement of scalp pH in the STAN arm of this project (Annex 1a) Common to the above studies is that there is consistently applied scalp pH before STAN monitoring begins. It is therefore important to elucidate whether, through the use of STAN monitoring is needed (more than 1) FBS - and if so to what extent FBS is required. STAN method currently winning widespread in Denmark and internationally (FDA has just approved), notwithstanding that it is not scientifically proven that fetal monitoring with STAN is better than the current monitoring method with scalp pH measurement. It is therefore important to get this resolved in a randomized study in the relative expensive STAN apparatus introduced in several places in Denmark. This study will provide an opportunity to highlight these issues and can prepare on our way to use STAN to prevent or significantly reduce these risks and thus justify continued STAN use or the continued spread of STAN should not by advised. If STAN by our method proves to be comparable with clean scalps pH measurement as an adjunct to CTG, it will be a significant advance in fetal monitoring technology, taking thus will have a primarily non-invasive, safe and continuous method cause less inconvenience to both mother and child. The study was approved by the Ethical nominee directors. The study will include all women > 18 years in labour with a fetus in the cephalic presentation with a gestational age of more than 36 weeks + 0, where there is the monitoring with CTG. Women who develop CTG changes that are interpreted as abnormal (according to STAN (FIGO)-guidelines and the scalp pH is normal, could be included in the study. Women will be randomised by telephone(electronic)to surveillance with eighter STAN monitoring or with CTG and scalp pH. In the latter group STAN results will be blinded (hidden) for later analysis. There are estimated to be 1200 women in the study and the study is expected to run for 2-3 years, preceded by a pilotproject. During the pilot project we will follow the department's usual procedures for monitoring, but to CTG using the STAN device with blinded/concealed ST analysis. There is expected to be 100 patients in the pilotproject. The aim is to investigate whether the calculations in the survey stick and simultaneously train staff at the maternity ward in STAN equipment and procedures and make them familiar with the work. The advantage in conducting the study at the maternity ward at Hvidovre hospital is that it is the largest birthplace in Denmark with nearly 6,000 births annually, with perhaps the highest use of scalp pH measurements during labor. In addition, nearly 3,000 births annually at Roskilde County Hospital, a total of 9,500 births. In addition, department and project managers areexperienced in scientific studies on fetal monitoring. Project participants have on their own initiative, initiated this project and has no financial interest in the instrument companies that produce the used equipment/ appliances/ monitors. The project has been allocated 2.5 million DKr in funding for the project from Elsass Foundation, a private foundation with no financial interest in the project equipment/ appliances/ monitors. Official Title ----------------- Cardiotocography Combined With ST-analysis Versus Cardiotocography Combined With Scalp-pH in Deliveries With Abnormal CTG - A Randomised Trial Conditions ----------------- Metabolic Acidosis of Newborn Intervention / Treatment ----------------- * Device: Neoventa S 21 ST-ANalysis of fetal heart * Procedure: CTG + FBS Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: intermediate or abnormal CTG and Normal fetal scalp-pH > or = 7,25 Exclusion Criteria: preterminal CTG Fetal arrythmias or A-V block Severe fetal malformations (known) Amnionitis (temp > 38,5 degr. celcius) maternal Hepatitis B/C or HIV Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 50 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: CTG + FBS<br>intrapartum surveillance with CTG+FBS \| Procedure: CTG + FBS<br>* Cardiotocography and fetal blood sampling on/from fetal skalp<br>* Other names: Cardiotocography and fetal blood sampling (scalp-pH);\| \| Active Comparator: Neoventa S 21 ST-ANalysis of fetal heart<br>intrapartum surveillance with CTG + STAN \| Device: Neoventa S 21 ST-ANalysis of fetal heart<br>* Application of gold-trace scalp electrode<br>* Other names: Cardiotocography and ST-ANalysis;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Frequency of metabolic acidosis in the 2 groups, defined by pH < 7,05 and SBE < -10 in the umbilical artery \| We will do a minimum 2 year follow-up on the children \| within 1 hour \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Does STAN reduce number of admissions to NICU and/or HIE \| Number of neonates admitted to NICU because of suspected asphyxia in the two groups. There will also be a minimun of 2 years of follow-up in these children \| 2 years after termination of study \| \| Does STAN reduce number of interventions in delivery(vacuum or section) \| \| 1 year after termination of study \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- CTG, Intrapartum fetal surveillance, cardiotocography, STAN, ST-Analysis, metabolic acidosis in umbilical artery, operative delivery
NCT00003979	CHS 828 in Treating Patients With Solid Tumors	RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Phase I trial to study the effectiveness of CHS 828 in treating patients who have solid tumors.	OBJECTIVES:~Determine the maximum tolerated dose of oral CHS 828 in patients with solid tumors.~Determine the qualitative and quantitative toxic effects of this regimen in these patients.~Determine a safe dose of this regimen for phase II evaluation.~Determine the pharmacokinetic profile of this regimen in these patients.~Determine any antitumor activity in these patients.~OUTLINE: Patients receive oral CHS 828 every 3 weeks. Treatment continues for at least 2 courses in the absence of disease progression or unacceptable toxicity.~Cohorts of 3-6 patients receive escalating doses of CHS 828 until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose at which 2 of 6 patients experience dose limiting toxicity.~Patients are followed for up to 4 weeks.~PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 12 months.	Phase I and Pharmacokinetics Study to Determine the Safety of CHS 828 in Patients With a Solid Tumor on a Single Oral Dose Repeated Every 3 Weeks	Unspecified Adult Solid Tumor, Protocol Specific	* Drug: CHS 828	DISEASE CHARACTERISTICS:~Histologically or cytologically confirmed solid tumor not amenable to standard therapy~No symptomatic brain or leptomeningeal involvement~PATIENT CHARACTERISTICS:~Age:~18 and over~Performance status:~WHO 0-2~Life expectancy:~At least 3 months~Hematopoietic:~WBC at least 4,000/mm^3~Platelet count at least 100,000/mm^3~Hepatic:~Bilirubin less than 1.5 mg/dL~Other liver function tests no greater than 2 times upper limit of normal (unless related to liver metastases)~Renal:~Creatinine no greater than 1.4 mg/dL~Other:~Not pregnant or nursing~Fertile patients must use effective contraception~No active bacterial infection~No other nonmalignant disease~No alcoholism, drug addiction, or psychiatric disorders~Able to take oral medication~PRIOR CONCURRENT THERAPY:~Biologic therapy:~At least 4 weeks since prior immunotherapy~Chemotherapy:~At least 4 weeks since prior chemotherapy (6 weeks since nitrosoureas)~No other concurrent chemotherapy~Endocrine therapy:~Not specified~Radiotherapy:~At least 4 weeks since prior radiotherapy (6 weeks since extensive radiotherapy)~No concurrent radiotherapy (except palliative radiotherapy)~Surgery:~Not specified~Other:~No other concurrent investigational drugs~No other concurrent antitumor drugs	18 Years	null	All	No	Primary Purpose: Treatment	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \|		unspecified adult solid tumor, protocol specific	Neoplasms	\| Intervention/Treatment \| \| --- \| \|Drug: CHS 828\|nan\|	CHS 828 in Treating Patients With Solid Tumors Study Overview ================= Brief Summary ----------------- RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of CHS 828 in treating patients who have solid tumors. Detailed Description ----------------- OBJECTIVES: Determine the maximum tolerated dose of oral CHS 828 in patients with solid tumors. Determine the qualitative and quantitative toxic effects of this regimen in these patients. Determine a safe dose of this regimen for phase II evaluation. Determine the pharmacokinetic profile of this regimen in these patients. Determine any antitumor activity in these patients. OUTLINE: Patients receive oral CHS 828 every 3 weeks. Treatment continues for at least 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of CHS 828 until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose at which 2 of 6 patients experience dose limiting toxicity. Patients are followed for up to 4 weeks. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 12 months. Official Title ----------------- Phase I and Pharmacokinetics Study to Determine the Safety of CHS 828 in Patients With a Solid Tumor on a Single Oral Dose Repeated Every 3 Weeks Conditions ----------------- Unspecified Adult Solid Tumor, Protocol Specific Intervention / Treatment ----------------- * Drug: CHS 828 Participation Criteria ================= Eligibility Criteria ----------------- DISEASE CHARACTERISTICS: Histologically or cytologically confirmed solid tumor not amenable to standard therapy No symptomatic brain or leptomeningeal involvement PATIENT CHARACTERISTICS: Age: 18 and over Performance status: WHO 0-2 Life expectancy: At least 3 months Hematopoietic: WBC at least 4,000/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin less than 1.5 mg/dL Other liver function tests no greater than 2 times upper limit of normal (unless related to liver metastases) Renal: Creatinine no greater than 1.4 mg/dL Other: Not pregnant or nursing Fertile patients must use effective contraception No active bacterial infection No other nonmalignant disease No alcoholism, drug addiction, or psychiatric disorders Able to take oral medication PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior immunotherapy Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks since nitrosoureas) No other concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since prior radiotherapy (6 weeks since extensive radiotherapy) No concurrent radiotherapy (except palliative radiotherapy) Surgery: Not specified Other: No other concurrent investigational drugs No other concurrent antitumor drugs Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Arms and Interventions \| Intervention/Treatment \| \| --- \| \|Drug: CHS 828\|nan\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- unspecified adult solid tumor, protocol specific
NCT03040362	Absorption, Metabolism and Excretion of [14C]-Lasmiditan - Single Oral Dose Administration	This study will be an open-label, nonrandomized, absorption, metabolism, and excretion study of [14C]-lasmiditan administered as a 200-milligrams (mg) (approximately 100 microcuries[µCi]) oral solution to 8 healthy males and females, following at least a 10 hour fast from food to assess the pharmacokinetics (PK), metabolism, and routes and extent of elimination of a single oral dose of 200 mg (approximately 100 µCi) [14C] lasmiditan in healthy males and females.		A Phase 1 Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-Lasmiditan Following Single Oral Dose Administration in Healthy Male and Female Subjects	Healthy	* Drug: [14C]-lasmiditan	Inclusion Criteria:~Males and females, between 18 and 60 years of age, inclusive, at Screening~Have a body mass index range of 18.5 to 32.0 kilograms per meter squared (kg/m²), inclusive, at Screening~In good health, determined by no clinically significant findings from medical history, 12 lead electrocardiogram (ECG), and vital signs measurements at Screening or Check-in (Day 1) as determined by the Investigator (or designee)~Clinical laboratory evaluations (including clinical chemistry panel [fasted at least 10 hours], hematology/complete blood count [CBC], and urinalysis [UA]; within the reference range for the test laboratory at Screening and Check-in, unless deemed not clinically significant by the Investigator (or designee)~Negative test for selected drugs of abuse at Screening (does not include alcohol) and at Check-in (does include alcohol)~Negative hepatitis panel (including hepatitis B surface antigen and hepatitis C virus antibody and negative human immunodeficiency virus (HIV) antibody screens~Females must be nonpregnant, nonlactating, and either postmenopausal (defined as no menstrual period for at least 12 months and confirmed by a serum follicle-stimulating hormone (FSH) level of ≥40 milli-international units (mIU/mL), surgically sterile (e.g., bilateral oophorectomy, salpingectomy, and/or hysterectomy) for at least 90 days prior to Screening, or must have undergone bilateral tubal ligation and agree to use effective contraception. For all females, the pregnancy test results must be negative at Screening and Check-in~Males will be surgically sterile for at least 90 days prior to Screening or when sexually-active with female partners of child-bearing potential will agree to use contraception from Check-in until 90 days following Discharge. Male participants must also be willing to refrain from donating sperm from Check-in until 90 days following Discharge~Able to comprehend and willing to sign an informed consent form (ICF)~A minimum of 1 to 2 bowel movements per day~Exclusion Criteria:~Significant history or clinical manifestation of any metabolic, allergic, infectious, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder (as determined by the Investigator [or designee]) prior to Check-in~History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee) prior to Check-in~History of stomach or intestinal surgery or resection that could alter absorption or excretion of orally administered drugs prior to Check-in, except that cholecystectomy, appendectomy, and hernia repair will be allowed if it was not associated with complications~History or presence of an abnormal ECG that, in the Investigator's (or designee's) opinion, is clinically significant at Screening or Check-in~History of orthostatic hypotension with or without syncope~A sustained seated systolic blood pressure >150 millimeters of mercury (mmHg) or <90 mmHg or a diastolic blood pressure >90 mmHg or <50 mmHg at Screening or Check in. Blood pressure may be retested twice at intervals of 5 minutes. The out of range blood pressure values will be considered sustained if either the systolic or diastolic blood pressures are outside the stated limits after these 3 assessments~History of alcoholism or drug addiction within 1 year prior to Check-in~Use of any tobacco- or nicotine-containing products (including but not limited to cigarettes, e-cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to Check-in, or positive cotinine screen at Screening or Check-in~Participation in more than 1 other radiolabeled investigational study drug trial within 12 months prior to Check-in. The previous radiolabeled study drug must have been received more than 6 months prior to Check-in for this study and the total exposure from this study and the previous study will be within the recommended levels considered safe, per United States (US) Title 21 Code of Federal Regulations (CFR) 361.1 (e.g., less than 5,000 millirem [mrem] whole body annual exposure)~Exposure to significant radiation (e.g., serial x-ray or computed tomography scans, barium meal, current employment in a job requiring radiation exposure monitoring) within 12 months prior to Check-in~Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 5 half-lives (if known) or 30 days prior to Check-in, whichever is longer~Use of any prescription medications/products within 14 days prior to Check-in, unless deemed acceptable by the Investigator (or designee)~Use of any over-the-counter, nonprescription preparations (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) within 7 days prior to Check-in, unless deemed acceptable by the Investigator (or designee)~Poor peripheral venous access prior to Check-in~Donation of whole blood from 56 days prior to Screening through Discharge, inclusive, or of plasma from 30 days prior to Screening through Discharge, inclusive~Receipt of blood products within 2 months prior to Check-in~Participant is at imminent risk of suicide (positive response to question 4 or 5 on the baseline Columbia-Suicide Severity Rating Scale (C-SSRS) or had a suicide attempt within 6 months prior to Screening~Any acute or chronic condition that, in the opinion of the Investigator (or designee), would limit the particpant's ability to complete or participate in this clinical study~Any other unspecified reason that, in the opinion of the Investigator (or designee) or Sponsor, makes the participant unsuitable for enrollment	18 Years	60 Years	All	Accepts Healthy Volunteers	Primary Purpose: Basic Science Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) \| Maximum observed concentration based on plasma concentrations of lasmiditan. \| Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours post-dose \| \| Pharmacokinetics: Time of Maximum Observed Plasma Concentration (Tmax) \| Time to maximum concentration based on plasma concentrations of lasmiditan. \| Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours pos-tdose \| \| Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Tlast (AUC[0-tlast]) \| Area under concentration time curve (AUC) from Hour 0 to the last measurable concentration based on plasma concentrations of lasmiditan. \| Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours post-dose \| \| AUC Time Zero to Infinity (AUC0-∞) Blood/Plasma Ratio \| AUC time zero to infinity (0-∞) of total radioactivity in blood/AUC0-∞ of total radioactivity in plasma. \| Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours post-dose \| \| AUC Time Zero to Infinity (AUC0-∞) Plasma Lasmiditan/Total Radioactivity Ratio \| AUC time zero to infinity (0-∞) of lasmiditan in plasma/AUC0-∞ of total radioactivity in plasma. \| Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours pos-tdose \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Pharmacokinetics - Cumulative Amount of Lasmiditan and Its Metabolites Excreted in Urine \| Amount of Lasmiditan and its metabolites (M3, M7, M8, (S,R)-M18, and (S,S)-M18) excreted in urine (Aeu) over sampling interval. \| Pre-dose (-12 to 0 hours) and intervals: 0 to 6, 6 to 12, 12 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, 144 to 168, and 168 to 192 hours post-dose \| \| Percentage of Lasmiditan Recovered in Urine, Relative to Dose Administered \| Percentage of lasmiditan recovered in urine (%UR), relative to dose administered calculated as %UR = 100 (amount of lasmiditan excreted in urine over a sampling interval (Aeu)/dose). \| Pre-dose (-12 to 0 hours) and intervals: 0 to 6, 6 to 12, 12 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, 144 to 168, and 168 to 192 hours post-dose \| \| Renal Clearance (CLR) \| Renal clearance is the volume of plasma completely cleared of lasmiditan by the kidneys per unit time and calculated as CLR = Aeu/AUC0-x (where Aeu = amount of lasmiditan excreted in urine over a sampling interval; x is the last interval collected; for lasmiditan only). \| Pre-dose (-12 to 0 hours) and intervals: 0 to 6, 6 to 12, 12 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, 144 to 168, and 168 to 192 hours post-dose \| \| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) \| Safety assessed from time of consent through end of study (up to 49 days). A summary of all reported serious adverse events (SAE) and other adverse events regardless of causality are provided in the Adverse Events module of this record. \| Up to 49 days \|		Lasmiditan, Serotonin Receptor Agonists, Serotonin Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Physiological Effects of Drugs	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: [14C]-lasmiditan<br>[14C]-lasmiditan administered as a 200 mg (approximately 100 µCi) oral solution \| Drug: [14C]-lasmiditan<br>* [14C]-lasmiditan as a 200 mg (approximately 100 µCi) oral solution<br>* Other names: LY573144;\|	Absorption, Metabolism and Excretion of [14C]-Lasmiditan - Single Oral Dose Administration Study Overview ================= Brief Summary ----------------- This study will be an open-label, nonrandomized, absorption, metabolism, and excretion study of [14C]-lasmiditan administered as a 200-milligrams (mg) (approximately 100 microcuries[µCi]) oral solution to 8 healthy males and females, following at least a 10 hour fast from food to assess the pharmacokinetics (PK), metabolism, and routes and extent of elimination of a single oral dose of 200 mg (approximately 100 µCi) [14C] lasmiditan in healthy males and females. Official Title ----------------- A Phase 1 Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-Lasmiditan Following Single Oral Dose Administration in Healthy Male and Female Subjects Conditions ----------------- Healthy Intervention / Treatment ----------------- * Drug: [14C]-lasmiditan Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Males and females, between 18 and 60 years of age, inclusive, at Screening Have a body mass index range of 18.5 to 32.0 kilograms per meter squared (kg/m²), inclusive, at Screening In good health, determined by no clinically significant findings from medical history, 12 lead electrocardiogram (ECG), and vital signs measurements at Screening or Check-in (Day 1) as determined by the Investigator (or designee) Clinical laboratory evaluations (including clinical chemistry panel [fasted at least 10 hours], hematology/complete blood count [CBC], and urinalysis [UA]; within the reference range for the test laboratory at Screening and Check-in, unless deemed not clinically significant by the Investigator (or designee) Negative test for selected drugs of abuse at Screening (does not include alcohol) and at Check-in (does include alcohol) Negative hepatitis panel (including hepatitis B surface antigen and hepatitis C virus antibody and negative human immunodeficiency virus (HIV) antibody screens Females must be nonpregnant, nonlactating, and either postmenopausal (defined as no menstrual period for at least 12 months and confirmed by a serum follicle-stimulating hormone (FSH) level of ≥40 milli-international units (mIU/mL), surgically sterile (e.g., bilateral oophorectomy, salpingectomy, and/or hysterectomy) for at least 90 days prior to Screening, or must have undergone bilateral tubal ligation and agree to use effective contraception. For all females, the pregnancy test results must be negative at Screening and Check-in Males will be surgically sterile for at least 90 days prior to Screening or when sexually-active with female partners of child-bearing potential will agree to use contraception from Check-in until 90 days following Discharge. Male participants must also be willing to refrain from donating sperm from Check-in until 90 days following Discharge Able to comprehend and willing to sign an informed consent form (ICF) A minimum of 1 to 2 bowel movements per day Exclusion Criteria: Significant history or clinical manifestation of any metabolic, allergic, infectious, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder (as determined by the Investigator [or designee]) prior to Check-in History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee) prior to Check-in History of stomach or intestinal surgery or resection that could alter absorption or excretion of orally administered drugs prior to Check-in, except that cholecystectomy, appendectomy, and hernia repair will be allowed if it was not associated with complications History or presence of an abnormal ECG that, in the Investigator's (or designee's) opinion, is clinically significant at Screening or Check-in History of orthostatic hypotension with or without syncope A sustained seated systolic blood pressure >150 millimeters of mercury (mmHg) or <90 mmHg or a diastolic blood pressure >90 mmHg or <50 mmHg at Screening or Check in. Blood pressure may be retested twice at intervals of 5 minutes. The out of range blood pressure values will be considered sustained if either the systolic or diastolic blood pressures are outside the stated limits after these 3 assessments History of alcoholism or drug addiction within 1 year prior to Check-in Use of any tobacco- or nicotine-containing products (including but not limited to cigarettes, e-cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to Check-in, or positive cotinine screen at Screening or Check-in Participation in more than 1 other radiolabeled investigational study drug trial within 12 months prior to Check-in. The previous radiolabeled study drug must have been received more than 6 months prior to Check-in for this study and the total exposure from this study and the previous study will be within the recommended levels considered safe, per United States (US) Title 21 Code of Federal Regulations (CFR) 361.1 (e.g., less than 5,000 millirem [mrem] whole body annual exposure) Exposure to significant radiation (e.g., serial x-ray or computed tomography scans, barium meal, current employment in a job requiring radiation exposure monitoring) within 12 months prior to Check-in Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 5 half-lives (if known) or 30 days prior to Check-in, whichever is longer Use of any prescription medications/products within 14 days prior to Check-in, unless deemed acceptable by the Investigator (or designee) Use of any over-the-counter, nonprescription preparations (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) within 7 days prior to Check-in, unless deemed acceptable by the Investigator (or designee) Poor peripheral venous access prior to Check-in Donation of whole blood from 56 days prior to Screening through Discharge, inclusive, or of plasma from 30 days prior to Screening through Discharge, inclusive Receipt of blood products within 2 months prior to Check-in Participant is at imminent risk of suicide (positive response to question 4 or 5 on the baseline Columbia-Suicide Severity Rating Scale (C-SSRS) or had a suicide attempt within 6 months prior to Screening Any acute or chronic condition that, in the opinion of the Investigator (or designee), would limit the particpant's ability to complete or participate in this clinical study Any other unspecified reason that, in the opinion of the Investigator (or designee) or Sponsor, makes the participant unsuitable for enrollment Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 60 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Basic Science Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: [14C]-lasmiditan<br>[14C]-lasmiditan administered as a 200 mg (approximately 100 µCi) oral solution \| Drug: [14C]-lasmiditan<br>* [14C]-lasmiditan as a 200 mg (approximately 100 µCi) oral solution<br>* Other names: LY573144;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) \| Maximum observed concentration based on plasma concentrations of lasmiditan. \| Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours post-dose \| \| Pharmacokinetics: Time of Maximum Observed Plasma Concentration (Tmax) \| Time to maximum concentration based on plasma concentrations of lasmiditan. \| Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours pos-tdose \| \| Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Tlast (AUC[0-tlast]) \| Area under concentration time curve (AUC) from Hour 0 to the last measurable concentration based on plasma concentrations of lasmiditan. \| Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours post-dose \| \| AUC Time Zero to Infinity (AUC0-∞) Blood/Plasma Ratio \| AUC time zero to infinity (0-∞) of total radioactivity in blood/AUC0-∞ of total radioactivity in plasma. \| Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours post-dose \| \| AUC Time Zero to Infinity (AUC0-∞) Plasma Lasmiditan/Total Radioactivity Ratio \| AUC time zero to infinity (0-∞) of lasmiditan in plasma/AUC0-∞ of total radioactivity in plasma. \| Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours pos-tdose \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Pharmacokinetics - Cumulative Amount of Lasmiditan and Its Metabolites Excreted in Urine \| Amount of Lasmiditan and its metabolites (M3, M7, M8, (S,R)-M18, and (S,S)-M18) excreted in urine (Aeu) over sampling interval. \| Pre-dose (-12 to 0 hours) and intervals: 0 to 6, 6 to 12, 12 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, 144 to 168, and 168 to 192 hours post-dose \| \| Percentage of Lasmiditan Recovered in Urine, Relative to Dose Administered \| Percentage of lasmiditan recovered in urine (%UR), relative to dose administered calculated as %UR = 100 (amount of lasmiditan excreted in urine over a sampling interval (Aeu)/dose). \| Pre-dose (-12 to 0 hours) and intervals: 0 to 6, 6 to 12, 12 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, 144 to 168, and 168 to 192 hours post-dose \| \| Renal Clearance (CLR) \| Renal clearance is the volume of plasma completely cleared of lasmiditan by the kidneys per unit time and calculated as CLR = Aeu/AUC0-x (where Aeu = amount of lasmiditan excreted in urine over a sampling interval; x is the last interval collected; for lasmiditan only). \| Pre-dose (-12 to 0 hours) and intervals: 0 to 6, 6 to 12, 12 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, 144 to 168, and 168 to 192 hours post-dose \| \| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) \| Safety assessed from time of consent through end of study (up to 49 days). A summary of all reported serious adverse events (SAE) and other adverse events regardless of causality are provided in the Adverse Events module of this record. \| Up to 49 days \|
NCT02323646	Safety and Efficacy of Telapristone Acetate (Proellex®) Administered Vaginally for the Treatment of Uterine Fibroids	The primary objective of this study is to determine the safety and efficacy of two vaginal doses of Proellex® administered for up to 2 courses of treatment (18 weeks each), each separated by an Off-Drug Interval (ODI), to premenopausal women with symptomatic uterine fibroids.		A Phase 2, Multi-Center, Parallel Design, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of 6 and 12 mg Proellex® (Telapristone Acetate) Administered Vaginally in the Treatment of Premenopausal Women With Confirmed Symptomatic Uterine Fibroids	Uterine Fibroids	* Drug: Placebo * Drug: Telapristone Acetate	Inclusion Criteria:~Adult females between 18 and 47 years.~Have a history of at least 3 regular menstrual cycles in which menorrhagia is due to uterine fibroids.~Must have uterine fibroids.~Agreement not to attempt to become pregnant during the trial.~Agreement to use only sanitary pads provided throughout the course of the study, tampon use is prohibited .~Ability to complete a daily Participant diary and study procedures in compliance with the protocol.~Have a negative pregnancy test at the Screening and Baseline visits, and subsequent study visits.~A Body Mass Index (BMI) between 18 and 45 inclusive.~Menstrual blood loss > 80 milliliters (mL) by alkaline hematin assay.~Exclusion Criteria:~Post-menopausal woman, defined as either; six (6) months or more (immediately prior to screening visit) without a menstrual period, or prior hysterectomy and/or oophorectomy.~Pregnant or lactating or is attempting or expecting to become pregnant during the entire study period.~Received an investigational drug in the 30 days prior to the screening for this study.~History of Polycystic Ovarian Syndrome (PCOS).~Concurrent use of any testosterone, progestin, androgen, estrogen, anabolic steroids, Dihydroepiandrosterone (DHEA) or hormonal products for at least 2 weeks prior to screening and during the study.~Use of oral contraceptives in the preceding 30 days. Use of Depo-Provera® in the preceding 10 months.~Use of Gonadotropin Releasing Hormone (GnRHas) (e.g. Lupron Depot) within 3 months of the first dose of study drug (Lupron Depot must have a wash-out period of 3 months).~Has an Intra Uterine device (IUD) in place.~Known or suspected carcinoma of the breast or reproductive organs.~Recent history (within past 6 months) of alcoholism or drug abuse.~Clinically significant abnormal findings on screening examination and laboratory assessments or any condition which in the opinion of the investigator would interfere with the participant's ability to comply with the study instructions or endanger the participant if she took part in the study.	18 Years	47 Years	Female	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Percentage of Participants in Amenorrhea at the End of Treatment Course 1 \| Amenorrhea was defined as any 28-day period during treatment (not including the ODI) without a bleeding intensity score >1. Participants were provided with a daily diary and Pictorial Blood Loss Assessment Chart (PBAC) to record information about the menstrual blood loss (MBL). Bleeding intensity was graded on a 5-point scale where: 1=spotting to 5=heavy bleeding. \| At the end of 18-weeks Treatment Course 1 \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Percentage of Participants in Amenorrhea at the End of Treatment Course 2 \| Amenorrhea was defined as any 28-day period during treatment (not including the ODI) without a bleeding intensity score >1 after 2 courses of treatment. Participants were provided with a daily diary and (PBAC) to record information about the MBL. Bleeding intensity was graded on a 5-point scale where: 1=spotting to 5=heavy bleeding. \| At the end of 18-weeks Treatment Course 2 \| \| Percentage Change in PBAC Scores From Baseline to the End of Treatment Courses 1 and 2 \| Uterine bleeding was assessed with the use of the PBAC, a validated self-reporting method to estimate menstrual blood loss. Participants recorded daily the number of tampons and towels used and the degree to which individual items were soiled with blood (plus small or large clots). Pictorial scores range from score 1 for slightly stained tampon/towel, 5 for a partially stained tampon/towel, 10 for a completely saturated tampon, 20 for a completely saturated towel, and 5 for each episode of flooding and for each blood clot larger than a quarter in size. Total score can range from 0 (no bleeding) to >500. Higher scores indicate more bleeding. Lower scores indicate less bleeding. A negative change from Baseline indicates improvement (reduction in bleeding). \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1 and the end of 18-weeks Treatment Course 2 \| \| Percentage Change in Transformed Total Uterine Fibroid System Quality of Life Survey System Severity (UFS-SSS) Score From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit \| UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. Each question was answered on a 5-point scale where 1=Not at all to 5=A very great deal. The sum of the total scores was transformed to a range of 0=no symptoms (best) to 100=most severe symptoms (worst). A negative percentage change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit \| \| Percentage Change in the Individual UFS-SSS Subscale Score Question 1 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit \| UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 1: During the previous 3 months how distressed were you by heavy bleeding during your menstrual period? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit \| \| Percentage Change in the Individual UFS-SSS Subscale Score Question 2 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit \| UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 2: During the previous 3 months how distressed were you by passing blood clots during your menstrual period? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit \| \| Percentage Change in the Individual UFS-SSS Subscale Score Question 3 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit \| UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 3: During the previous 3 months how distressed were you by fluctuation in the duration of your menstrual period compared to your previous cycle? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit \| \| Percentage Change in the Individual UFS-SSS Subscale Score Question 4 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit \| UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 4: During the previous 3 months how distressed were you by fluctuation in the length of your monthly cycle compared to your previous cycles? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit \| \| Percentage Change in the Individual UFS-SSS Subscale Score Question 5 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit \| UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 5: During the previous 3 months how distressed were you by feeling tightness or pressure in your pelvic area? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit \| \| Percentage Change in the Individual UFS-SSS Subscale Score Question 6 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit \| UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 6: During the previous 3 months how distressed were you by frequent urination during the daytime hours? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit \| \| Percentage Change in the Individual UFS-SSS Subscale Score Question 7 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit \| UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 7: During the previous 3 months how distressed were you by frequent nighttime urination? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit \| \| Percentage Change in the Individual UFS-SSS Subscale Score Question 8 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit \| UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 8: During the previous 3 months how distressed were you by feeling fatigued? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit \| \| Percentage Change in Total Uterine Fibroid Volume From Baseline to the End of Treatment Courses 1 and 2 \| The total uterine fibroid volume was measured by Magnetic Resonance Imaging (MRI). A negative change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1 and the end of 18-weeks Treatment Course 2 \|	uterine fibroids, leiomyoma, fibroid tumor, fibroma	Leiomyoma, Myofibroma, Neoplasms, Muscle Tissue, Neoplasms, Connective and Soft Tissue, Neoplasms by Histologic Type, Neoplasms, Neoplasms, Connective Tissue, Connective Tissue Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Placebo Comparator: Placebo<br>Following the baseline assessment no treatment period, matching placebo, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI. \| Drug: Placebo<br>* Matching placebo, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI.<br>\| \| Experimental: Telapristone Acetate 6 mg<br>Following the baseline assessment no treatment period, telapristone acetate 6 milligrams (mg), vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI. \| Drug: Telapristone Acetate<br>* Telapristone acetate, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI.<br>* Other names: Proellex®;\| \| Experimental: Telapristone Acetate 12 mg<br>Following the baseline assessment no treatment period, telapristone acetate 12mg, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI. \| Drug: Telapristone Acetate<br>* Telapristone acetate, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI.<br>* Other names: Proellex®;\|	Safety and Efficacy of Telapristone Acetate (Proellex®) Administered Vaginally for the Treatment of Uterine Fibroids Study Overview ================= Brief Summary ----------------- The primary objective of this study is to determine the safety and efficacy of two vaginal doses of Proellex® administered for up to 2 courses of treatment (18 weeks each), each separated by an Off-Drug Interval (ODI), to premenopausal women with symptomatic uterine fibroids. Official Title ----------------- A Phase 2, Multi-Center, Parallel Design, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of 6 and 12 mg Proellex® (Telapristone Acetate) Administered Vaginally in the Treatment of Premenopausal Women With Confirmed Symptomatic Uterine Fibroids Conditions ----------------- Uterine Fibroids Intervention / Treatment ----------------- * Drug: Placebo * Drug: Telapristone Acetate Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Adult females between 18 and 47 years. Have a history of at least 3 regular menstrual cycles in which menorrhagia is due to uterine fibroids. Must have uterine fibroids. Agreement not to attempt to become pregnant during the trial. Agreement to use only sanitary pads provided throughout the course of the study, tampon use is prohibited . Ability to complete a daily Participant diary and study procedures in compliance with the protocol. Have a negative pregnancy test at the Screening and Baseline visits, and subsequent study visits. A Body Mass Index (BMI) between 18 and 45 inclusive. Menstrual blood loss > 80 milliliters (mL) by alkaline hematin assay. Exclusion Criteria: Post-menopausal woman, defined as either; six (6) months or more (immediately prior to screening visit) without a menstrual period, or prior hysterectomy and/or oophorectomy. Pregnant or lactating or is attempting or expecting to become pregnant during the entire study period. Received an investigational drug in the 30 days prior to the screening for this study. History of Polycystic Ovarian Syndrome (PCOS). Concurrent use of any testosterone, progestin, androgen, estrogen, anabolic steroids, Dihydroepiandrosterone (DHEA) or hormonal products for at least 2 weeks prior to screening and during the study. Use of oral contraceptives in the preceding 30 days. Use of Depo-Provera® in the preceding 10 months. Use of Gonadotropin Releasing Hormone (GnRHas) (e.g. Lupron Depot) within 3 months of the first dose of study drug (Lupron Depot must have a wash-out period of 3 months). Has an Intra Uterine device (IUD) in place. Known or suspected carcinoma of the breast or reproductive organs. Recent history (within past 6 months) of alcoholism or drug abuse. Clinically significant abnormal findings on screening examination and laboratory assessments or any condition which in the opinion of the investigator would interfere with the participant's ability to comply with the study instructions or endanger the participant if she took part in the study. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 47 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Placebo Comparator: Placebo<br>Following the baseline assessment no treatment period, matching placebo, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI. \| Drug: Placebo<br>* Matching placebo, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI.<br>\| \| Experimental: Telapristone Acetate 6 mg<br>Following the baseline assessment no treatment period, telapristone acetate 6 milligrams (mg), vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI. \| Drug: Telapristone Acetate<br>* Telapristone acetate, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI.<br>* Other names: Proellex®;\| \| Experimental: Telapristone Acetate 12 mg<br>Following the baseline assessment no treatment period, telapristone acetate 12mg, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI. \| Drug: Telapristone Acetate<br>* Telapristone acetate, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI.<br>* Other names: Proellex®;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Percentage of Participants in Amenorrhea at the End of Treatment Course 1 \| Amenorrhea was defined as any 28-day period during treatment (not including the ODI) without a bleeding intensity score >1. Participants were provided with a daily diary and Pictorial Blood Loss Assessment Chart (PBAC) to record information about the menstrual blood loss (MBL). Bleeding intensity was graded on a 5-point scale where: 1=spotting to 5=heavy bleeding. \| At the end of 18-weeks Treatment Course 1 \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Percentage of Participants in Amenorrhea at the End of Treatment Course 2 \| Amenorrhea was defined as any 28-day period during treatment (not including the ODI) without a bleeding intensity score >1 after 2 courses of treatment. Participants were provided with a daily diary and (PBAC) to record information about the MBL. Bleeding intensity was graded on a 5-point scale where: 1=spotting to 5=heavy bleeding. \| At the end of 18-weeks Treatment Course 2 \| \| Percentage Change in PBAC Scores From Baseline to the End of Treatment Courses 1 and 2 \| Uterine bleeding was assessed with the use of the PBAC, a validated self-reporting method to estimate menstrual blood loss. Participants recorded daily the number of tampons and towels used and the degree to which individual items were soiled with blood (plus small or large clots). Pictorial scores range from score 1 for slightly stained tampon/towel, 5 for a partially stained tampon/towel, 10 for a completely saturated tampon, 20 for a completely saturated towel, and 5 for each episode of flooding and for each blood clot larger than a quarter in size. Total score can range from 0 (no bleeding) to >500. Higher scores indicate more bleeding. Lower scores indicate less bleeding. A negative change from Baseline indicates improvement (reduction in bleeding). \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1 and the end of 18-weeks Treatment Course 2 \| \| Percentage Change in Transformed Total Uterine Fibroid System Quality of Life Survey System Severity (UFS-SSS) Score From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit \| UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. Each question was answered on a 5-point scale where 1=Not at all to 5=A very great deal. The sum of the total scores was transformed to a range of 0=no symptoms (best) to 100=most severe symptoms (worst). A negative percentage change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit \| \| Percentage Change in the Individual UFS-SSS Subscale Score Question 1 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit \| UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 1: During the previous 3 months how distressed were you by heavy bleeding during your menstrual period? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit \| \| Percentage Change in the Individual UFS-SSS Subscale Score Question 2 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit \| UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 2: During the previous 3 months how distressed were you by passing blood clots during your menstrual period? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit \| \| Percentage Change in the Individual UFS-SSS Subscale Score Question 3 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit \| UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 3: During the previous 3 months how distressed were you by fluctuation in the duration of your menstrual period compared to your previous cycle? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit \| \| Percentage Change in the Individual UFS-SSS Subscale Score Question 4 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit \| UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 4: During the previous 3 months how distressed were you by fluctuation in the length of your monthly cycle compared to your previous cycles? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit \| \| Percentage Change in the Individual UFS-SSS Subscale Score Question 5 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit \| UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 5: During the previous 3 months how distressed were you by feeling tightness or pressure in your pelvic area? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit \| \| Percentage Change in the Individual UFS-SSS Subscale Score Question 6 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit \| UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 6: During the previous 3 months how distressed were you by frequent urination during the daytime hours? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit \| \| Percentage Change in the Individual UFS-SSS Subscale Score Question 7 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit \| UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 7: During the previous 3 months how distressed were you by frequent nighttime urination? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit \| \| Percentage Change in the Individual UFS-SSS Subscale Score Question 8 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit \| UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 8: During the previous 3 months how distressed were you by feeling fatigued? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1, the end of 18-weeks Treatment Course 2 and the Course 2 Week 24 Follow-up Visit \| \| Percentage Change in Total Uterine Fibroid Volume From Baseline to the End of Treatment Courses 1 and 2 \| The total uterine fibroid volume was measured by Magnetic Resonance Imaging (MRI). A negative change from Baseline indicates improvement. \| Baseline (No treatment period) to the end of 18-weeks Treatment Course 1 and the end of 18-weeks Treatment Course 2 \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- uterine fibroids, leiomyoma, fibroid tumor, fibroma
NCT03499730	Does Midazolam Affect Postoperative Pain?	To investigate whether midazolam has any effect on postoperative pain in outpatient surgery, the investigators will assess the impact of different midazolam doses on pain scores 24h, 7 days and 3 months after open inguinal hernia repair.~The investigators hypothesize that patients being administered higher midazolam doses will refer more pain.	Systemic midazolam prescribed perioperatively might have impact on pain, with studies suggesting antinociceptive and hyperalgesic effects. Anxiety might be a confounder in this association. In order to investigate the effect of midazolam on postoperative pain, a prospective cohort study will be conducted in four Portuguese ambulatory surgery units. A convenience sample with consecutive design will include patients admitted for open inguinal hernia repair. After anxiety and pain evaluation, a tailored dose of midazolam will be administered as premedication according to the anesthetist's best judgement within each unit's protocol (routine care; this dose may be null). Subsequent anesthesia and analgesia will be standardized. Postoperative pain will be blindly assessed by telephone interviews at 24h, 7 days, and 3 months. Statistical analysis will be performed separately for each gender, centre and type of anesthesia, adjusting for preoperative anxiety and other confounding variables with multivariate analysis.~The investigators intend to clarify the relation between anxiety, preoperative midazolam and postoperative pain.	Does Preoperative Midazolam Dose Affect Postoperative Pain? - a Multicentric Observational Study in Open Inguinal Hernia Repair	Pain, Postoperative	* Drug: Midazolam injection	Inclusion Criteria:~- adults proposed for open inguinal hernia repair in Portuguese ambulatory surgery units~Exclusion Criteria:~psychiatric disorders~alcoholism~illiteracy or poor understanding of the Portuguese language~history of chronic pain under opioids~recurrent surgery	18 Years	null	All	No		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Postoperative pain \| Pain numeric rating scale (NRS) 0-10 \| 24h after surgery \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Postoperative pain \| Pain NRS \| 7 days after surgery \| \| Postoperative pain \| Pain NRS \| 3 months after surgery \| \| Patient satisfaction \| NRS \| 7 days after surgery \| \| Patient satisfaction \| NRS \| 3 months after surgery \| \| Analgesic consumption \| Total analgesic drugs taken in a time period \| 24h after surgery \| \| Analgesic consumption \| Total analgesic drugs taken in a time period \| 7 days after surgery \| \| Adverse events \| Number of patients with adverse events like bleeding, nausea, uncontrolled pain \| 7 days after surgery \| \| Global surgery recovery index \| Global surgery recovery index \| 3 months after surgery \|	Midazolam, Inguinal hernia	Midazolam, Adjuvants, Anesthesia, Hypnotics and Sedatives, Central Nervous System Depressants, Physiological Effects of Drugs, Anti-Anxiety Agents, Tranquilizing Agents, Psychotropic Drugs, Anesthetics, Intravenous, Anesthetics, General, Anesthetics, GABA Modulators, GABA Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action	\| Intervention/Treatment \| \| --- \| \|Drug: Midazolam injection\|The dose of preoperative midazolam is the predictor variable and will be registered as a continuous variable in a single cohort.\|	Does Midazolam Affect Postoperative Pain? Study Overview ================= Brief Summary ----------------- To investigate whether midazolam has any effect on postoperative pain in outpatient surgery, the investigators will assess the impact of different midazolam doses on pain scores 24h, 7 days and 3 months after open inguinal hernia repair. The investigators hypothesize that patients being administered higher midazolam doses will refer more pain. Detailed Description ----------------- Systemic midazolam prescribed perioperatively might have impact on pain, with studies suggesting antinociceptive and hyperalgesic effects. Anxiety might be a confounder in this association. In order to investigate the effect of midazolam on postoperative pain, a prospective cohort study will be conducted in four Portuguese ambulatory surgery units. A convenience sample with consecutive design will include patients admitted for open inguinal hernia repair. After anxiety and pain evaluation, a tailored dose of midazolam will be administered as premedication according to the anesthetist's best judgement within each unit's protocol (routine care; this dose may be null). Subsequent anesthesia and analgesia will be standardized. Postoperative pain will be blindly assessed by telephone interviews at 24h, 7 days, and 3 months. Statistical analysis will be performed separately for each gender, centre and type of anesthesia, adjusting for preoperative anxiety and other confounding variables with multivariate analysis. The investigators intend to clarify the relation between anxiety, preoperative midazolam and postoperative pain. Official Title ----------------- Does Preoperative Midazolam Dose Affect Postoperative Pain? - a Multicentric Observational Study in Open Inguinal Hernia Repair Conditions ----------------- Pain, Postoperative Intervention / Treatment ----------------- * Drug: Midazolam injection Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: - adults proposed for open inguinal hernia repair in Portuguese ambulatory surgery units Exclusion Criteria: psychiatric disorders alcoholism illiteracy or poor understanding of the Portuguese language history of chronic pain under opioids recurrent surgery Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions \| Intervention/Treatment \| \| --- \| \|Drug: Midazolam injection\|The dose of preoperative midazolam is the predictor variable and will be registered as a continuous variable in a single cohort.\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Postoperative pain \| Pain numeric rating scale (NRS) 0-10 \| 24h after surgery \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Postoperative pain \| Pain NRS \| 7 days after surgery \| \| Postoperative pain \| Pain NRS \| 3 months after surgery \| \| Patient satisfaction \| NRS \| 7 days after surgery \| \| Patient satisfaction \| NRS \| 3 months after surgery \| \| Analgesic consumption \| Total analgesic drugs taken in a time period \| 24h after surgery \| \| Analgesic consumption \| Total analgesic drugs taken in a time period \| 7 days after surgery \| \| Adverse events \| Number of patients with adverse events like bleeding, nausea, uncontrolled pain \| 7 days after surgery \| \| Global surgery recovery index \| Global surgery recovery index \| 3 months after surgery \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Midazolam, Inguinal hernia
NCT01876251	A Study Evaluating The PF-03084014 In Combination With Docetaxel In Patients With Advanced Breast Cancer	This study is aimed to determine the tolerability of the PF-03084014 plus docetaxel combination in patients with advanced breast cancer. Preliminary information about the efficacy of the combination will also be collected.		Phase 1b Study Of Docetaxel + Pf 03084014 In Metastatic Or Locally Recurrent/Advanced Triple Negative Breast Cancer	Breast Cancer Metastatic	* Drug: PF-03084014 * Drug: PF-03084014 * Drug: PF-03084014 * Drug: Docetaxel * Drug: Docetaxel	Inclusion Criteria:~Diagnosis of breast cancer with evidence of a) metastatic or b) locally recurrent/advanced disease.~Exclusion Criteria:~Prior treatment with a gamma secretase inhibitors or other Notch signaling inhibitors.	18 Years	null	Female	No	Primary Purpose: Treatment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Participants With Dose-limiting Toxicities (DLTs) in Cycle 1 \| Any DLT event in Cycle 1: Grade 4 neutropenia lasting more than (>)7 days; febrile neutropenia (Grade more than or equal to [>=] 3 and body temperature >=38.5 degrees Celsius); Grade >=3 neutropenic infection; Grade >=3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia without bleeding; Grade >=3 toxicities (except those that had not been maximally treated); Grade 3 prolongation of time from electrocardiogram (ECG) Q wave to the end of the T wave corresponding to electrical systole (QT) corrected for heart rate (QTc) which persisted after correction of reversible causes; delay of 2 weeks in receiving next scheduled cycle due to persisting treatment-related toxicities; and failure to deliver at least 80% of planned dose during first cycle due to treatment-related toxicities. \| Cycle 1 Days 1-21 \| \| Progression-free Survival (PFS) at 6 Months - Expansion Cohort \| The period from study entry until disease progression, death or date of last contact. Assessment of response was made using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. \| Baseline till 6 months post-dose \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Participants With All Causality and Treatment-related Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs \| An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent AEs (TEAEs) are defined as newly occurring AEs or those worsening after first dose. AEs comprised both SAEs and non-SAEs. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Causality assessment was made by the investigator. Grading was per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening, Grade 5=death related to AE. \| Baseline up to 28-35 days after treatment discontinuation (up to Day 280) \| \| Number of Participants With Laboratory Abnormalities \| Number of participants with laboratory test abnormalities without regard to baseline abnormality. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick). \| Baseline up to 28-35 days after treatment discontinuation (up to Day 280) \| \| Percentage of Participants With Objective Response (OR) \| OR was based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [<] 10 millimeters [mm]). No new lesions. PR was defined as more than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. \| Baseline, every 6 weeks from Cycle 2 onwards up to 26 months \| \| Area Under the Concentration-time Curve (AUC) From Time 0 to Time of Last Measured Concentration (AUClast) of PF-03084014 in Dose-finding Cohort \| Serum PF-03084014 pharmacokinetic (PK) parameters were calculated following twice daily (BID) doses of PF-03084014 given alone (Cycle 1 Day 21) and in combination with docetaxel (Cycle 1 Day 2 and Cycle 2 Day 1). \| Cycle (C) 1 Days (D) 1, 2, 8, and 21; Day 1 of subsequent cycles and at EOT (max reached: Cycle 12) \| \| AUClast and AUC From Time 0 Extrapolated to Infinite Time (AUCinf) of Docetaxel in Dose-finding Cohort \| Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1) \| C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) \| \| Maximum Serum or Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of PF-03084014 in Dose-finding Cohort \| Serum PF-03084014 PK parameters were calculated following BID doses of PF-03084014 given alone (Cycle 1 Day 21) and in combination with docetaxel (Cycle 1 Day 2 and Cycle 2 Day 1) \| C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) \| \| Cmax of Docetaxel in Dose-finding Cohort \| Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1) \| C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) \| \| Time to Cmax (Tmax) of PF-03084014 in Dose-finding Cohort \| Serum PF-03084014 PK parameters were calculated following BID doses of PF-03084014 given alone (Cycle 1 Day 21) and in combination with docetaxel (Cycle 1 Day 2 and Cycle 2 Day 1) \| C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) \| \| Tmax of Docetaxel in Dose-finding Cohort \| Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1) \| C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) \| \| Systemic Clearance (CL) of Docetaxel in Dose-finding Cohort \| Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1) \| C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) \| \| Terminal Half-life (t1/2) of Docetaxel in Dose-finding Cohort \| Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1) \| C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) \| \| Volume of Distribution (Vss) of Docetaxel in Dose-finding Cohort \| Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1) \| C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) \| \| AUClast of PF-03084014 in the Expansion Cohort \| \| C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12) \| \| Cmax of PF-03084014 in the Expansion Cohort \| \| C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12) \| \| Tmax of PF-03084014 in the Expansion Cohort \| \| C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12) \| \| Ctrough of PF-03084014 in the Expansion Cohort \| \| C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12) \| \| Duration of Response (DR) \| Duration of response (DR) defined as time from start of first documented objective tumor response [Complete Response (CR) or Partial Response (PR)] to first documented objective tumor progression or death due to any cause, whichever occurs first. DR = (the end date for DR minus first subsequent confirmed CR or PR plus 1) divided by 7.02. CR: disappearance of all target lesions. PR: at least 30% decrease in the sum of diameters of target lesions. \| Baseline up to 28-35 days after treatment discontinuation (up to Day 280) \| \| Number of Participants With QTc Values Meeting Categorical Summarization Criteria \| Criteria for categorical summarization of the time corresponding to the beginning of depolarization to repolarization of the ventricles (QT) corrected for heart rate (QTc) using Bazett's correction (QTcB) or Fridericia's correction (QTcF) included: maximum QTcB or QTcF less than or equal to (<=) 450 milliseconds (msec), 450 to <=480 msec, 480 to <=500 msec, more than (>) 500 msec; maximum QTcB or QTcF changes (increases/decreases) from baseline (BL) less than (<) 30 msec, 30 to <60 msec, more than or equal to (>=) 60 msec. \| Screening, C1D1, C1D21, Day 1 of subsequent cycles, and EOT (maximum reached: C12) \| \| Percentage Change From Baseline in Notch 1 to 4 Ribonucleic Acid (RNA) in Blood \| As PF-03084014 acts on the Notch pathway as an inhibitor, it is of interest to investigate its effects, if any, on the Notch family of receptors, mainly Notch 1-4. \| C1D1, C1D2, C1D8, C1D21 and EOT (maximum reached: C12) \|	Breast cancer metastatic, docetaxel, PF-03084014	Docetaxel, Nirogacestat, Antineoplastic Agents, Tubulin Modulators, Antimitotic Agents, Mitosis Modulators, Molecular Mechanisms of Pharmacological Action, Gamma Secretase Inhibitors and Modulators, Enzyme Inhibitors	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: PF-03084014 plus docetaxel<br>PF 03084014 will be administered orally, continuously, twice daily at doses from 80 to 150 mg in combination with docetaxel given every 3 weeks at doses from 75 to 100 mg/m^2 \| Drug: PF-03084014<br>* Tablet, 10 mg, twice a day<br>Drug: PF-03084014<br>* Tablet, 50 mg, twice a day<br>Drug: PF-03084014<br>* Tablet, 100 mg, twice a day<br>Drug: Docetaxel<br>* Solution for IV infusion 75 mg/m^2, every 3 weeks<br>* Other names: Taxotere;Drug: Docetaxel<br>* Solution for IV infusion 100 mg/m^2, every 3 weeks<br>\|	A Study Evaluating The PF-03084014 In Combination With Docetaxel In Patients With Advanced Breast Cancer Study Overview ================= Brief Summary ----------------- This study is aimed to determine the tolerability of the PF-03084014 plus docetaxel combination in patients with advanced breast cancer. Preliminary information about the efficacy of the combination will also be collected. Official Title ----------------- Phase 1b Study Of Docetaxel + Pf 03084014 In Metastatic Or Locally Recurrent/Advanced Triple Negative Breast Cancer Conditions ----------------- Breast Cancer Metastatic Intervention / Treatment ----------------- * Drug: PF-03084014 * Drug: PF-03084014 * Drug: PF-03084014 * Drug: Docetaxel * Drug: Docetaxel Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Diagnosis of breast cancer with evidence of a) metastatic or b) locally recurrent/advanced disease. Exclusion Criteria: Prior treatment with a gamma secretase inhibitors or other Notch signaling inhibitors. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: PF-03084014 plus docetaxel<br>PF 03084014 will be administered orally, continuously, twice daily at doses from 80 to 150 mg in combination with docetaxel given every 3 weeks at doses from 75 to 100 mg/m^2 \| Drug: PF-03084014<br>* Tablet, 10 mg, twice a day<br>Drug: PF-03084014<br>* Tablet, 50 mg, twice a day<br>Drug: PF-03084014<br>* Tablet, 100 mg, twice a day<br>Drug: Docetaxel<br>* Solution for IV infusion 75 mg/m^2, every 3 weeks<br>* Other names: Taxotere;Drug: Docetaxel<br>* Solution for IV infusion 100 mg/m^2, every 3 weeks<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Participants With Dose-limiting Toxicities (DLTs) in Cycle 1 \| Any DLT event in Cycle 1: Grade 4 neutropenia lasting more than (>)7 days; febrile neutropenia (Grade more than or equal to [>=] 3 and body temperature >=38.5 degrees Celsius); Grade >=3 neutropenic infection; Grade >=3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia without bleeding; Grade >=3 toxicities (except those that had not been maximally treated); Grade 3 prolongation of time from electrocardiogram (ECG) Q wave to the end of the T wave corresponding to electrical systole (QT) corrected for heart rate (QTc) which persisted after correction of reversible causes; delay of 2 weeks in receiving next scheduled cycle due to persisting treatment-related toxicities; and failure to deliver at least 80% of planned dose during first cycle due to treatment-related toxicities. \| Cycle 1 Days 1-21 \| \| Progression-free Survival (PFS) at 6 Months - Expansion Cohort \| The period from study entry until disease progression, death or date of last contact. Assessment of response was made using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. \| Baseline till 6 months post-dose \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Number of Participants With All Causality and Treatment-related Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs \| An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent AEs (TEAEs) are defined as newly occurring AEs or those worsening after first dose. AEs comprised both SAEs and non-SAEs. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Causality assessment was made by the investigator. Grading was per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening, Grade 5=death related to AE. \| Baseline up to 28-35 days after treatment discontinuation (up to Day 280) \| \| Number of Participants With Laboratory Abnormalities \| Number of participants with laboratory test abnormalities without regard to baseline abnormality. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick). \| Baseline up to 28-35 days after treatment discontinuation (up to Day 280) \| \| Percentage of Participants With Objective Response (OR) \| OR was based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [<] 10 millimeters [mm]). No new lesions. PR was defined as more than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. \| Baseline, every 6 weeks from Cycle 2 onwards up to 26 months \| \| Area Under the Concentration-time Curve (AUC) From Time 0 to Time of Last Measured Concentration (AUClast) of PF-03084014 in Dose-finding Cohort \| Serum PF-03084014 pharmacokinetic (PK) parameters were calculated following twice daily (BID) doses of PF-03084014 given alone (Cycle 1 Day 21) and in combination with docetaxel (Cycle 1 Day 2 and Cycle 2 Day 1). \| Cycle (C) 1 Days (D) 1, 2, 8, and 21; Day 1 of subsequent cycles and at EOT (max reached: Cycle 12) \| \| AUClast and AUC From Time 0 Extrapolated to Infinite Time (AUCinf) of Docetaxel in Dose-finding Cohort \| Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1) \| C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) \| \| Maximum Serum or Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of PF-03084014 in Dose-finding Cohort \| Serum PF-03084014 PK parameters were calculated following BID doses of PF-03084014 given alone (Cycle 1 Day 21) and in combination with docetaxel (Cycle 1 Day 2 and Cycle 2 Day 1) \| C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) \| \| Cmax of Docetaxel in Dose-finding Cohort \| Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1) \| C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) \| \| Time to Cmax (Tmax) of PF-03084014 in Dose-finding Cohort \| Serum PF-03084014 PK parameters were calculated following BID doses of PF-03084014 given alone (Cycle 1 Day 21) and in combination with docetaxel (Cycle 1 Day 2 and Cycle 2 Day 1) \| C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) \| \| Tmax of Docetaxel in Dose-finding Cohort \| Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1) \| C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) \| \| Systemic Clearance (CL) of Docetaxel in Dose-finding Cohort \| Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1) \| C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) \| \| Terminal Half-life (t1/2) of Docetaxel in Dose-finding Cohort \| Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1) \| C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) \| \| Volume of Distribution (Vss) of Docetaxel in Dose-finding Cohort \| Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1) \| C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) \| \| AUClast of PF-03084014 in the Expansion Cohort \| \| C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12) \| \| Cmax of PF-03084014 in the Expansion Cohort \| \| C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12) \| \| Tmax of PF-03084014 in the Expansion Cohort \| \| C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12) \| \| Ctrough of PF-03084014 in the Expansion Cohort \| \| C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12) \| \| Duration of Response (DR) \| Duration of response (DR) defined as time from start of first documented objective tumor response [Complete Response (CR) or Partial Response (PR)] to first documented objective tumor progression or death due to any cause, whichever occurs first. DR = (the end date for DR minus first subsequent confirmed CR or PR plus 1) divided by 7.02. CR: disappearance of all target lesions. PR: at least 30% decrease in the sum of diameters of target lesions. \| Baseline up to 28-35 days after treatment discontinuation (up to Day 280) \| \| Number of Participants With QTc Values Meeting Categorical Summarization Criteria \| Criteria for categorical summarization of the time corresponding to the beginning of depolarization to repolarization of the ventricles (QT) corrected for heart rate (QTc) using Bazett's correction (QTcB) or Fridericia's correction (QTcF) included: maximum QTcB or QTcF less than or equal to (<=) 450 milliseconds (msec), 450 to <=480 msec, 480 to <=500 msec, more than (>) 500 msec; maximum QTcB or QTcF changes (increases/decreases) from baseline (BL) less than (<) 30 msec, 30 to <60 msec, more than or equal to (>=) 60 msec. \| Screening, C1D1, C1D21, Day 1 of subsequent cycles, and EOT (maximum reached: C12) \| \| Percentage Change From Baseline in Notch 1 to 4 Ribonucleic Acid (RNA) in Blood \| As PF-03084014 acts on the Notch pathway as an inhibitor, it is of interest to investigate its effects, if any, on the Notch family of receptors, mainly Notch 1-4. \| C1D1, C1D2, C1D8, C1D21 and EOT (maximum reached: C12) \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Breast cancer metastatic, docetaxel, PF-03084014
NCT04198766	Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)	This is a Phase 1/2, open-label, non-randomized, 4-part Phase 1 trial to determine the safety profile and identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of INBRX 106 administered as a single agent or in combination with the anti-PD-1 checkpoint inhibitor (CPI) pembrolizumab (Keytruda).		An Open-Label, Multicenter, First-in-Human, Dose-Escalation, Multicohort, Phase 1/2 Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors	Solid Tumor, Non-Small Cell Lung Cancer, Melanoma, Head and Neck Cancer, Gastric Cancer, Renal Cell Carcinoma, Urothelial Carcinoma	* Drug: INBRX-106 - Hexavalent OX40 agonist antibody * Drug: Pembrolizumab 200 mg * Drug: Pembrolizumab 400 mg	Select Inclusion Criteria:~Males or females aged ≥18 years.~Parts 1 and 3 (escalation cohorts): Subjects with locally advanced or metastatic non resectable solid tumors, whose disease has progressed despite all standard therapies or for whom no further standard or clinically acceptable therapy exists.~Part 2 (single-agent expansion cohort): Subjects with NSCLC, melanoma, HNSCC, G/GEA, RCC, or TCC, with locally advanced or metastatic, non-resectable disease, which has progressed despite all standard therapies including CPI or for whom no standard or clinically acceptable therapy exists.~Part 4 (expansion cohorts in combination with pembrolizumab): Subjects with melanoma (all types), HNSCC, G/GEA, RCC, TCC, NSCLC, or MSI-high, TMB-high, MMR-deficient tumors, with locally advanced or metastatic, non resectable disease, which is either CPI-naive (melanoma, HNSCC, NPC) or progressed despite all standard therapies including CPI (NSCLC, RCC, TCC, uveal melanoma, MSI-high, TMB-high, or MMR-deficient solid tumors) or for whom no standard or clinically acceptable therapy exists.~All subjects with non-squamous NSCLC must have documentation of absence of tumor activating EGFR mutations and absence of ALK gene rearrangements.~PD-L1 by IHC (22C3): Parts 1 and 3: IHC optional. Part 2: IHC result mandatory but any score allowed. Part 4: Combined Positive Score (CPS) ≥ 1% (or Tumor Proportion Score ≥50% for NSCLC; for TMB-high tumors, any TPS% is allowed).~Adequate hematologic, coagulation, hepatic and renal function and ECOG score as defined per protocol.~Select Exclusion Criteria:~Prior exposure to OX40 agonists.~Receipt of any investigational product or any approved anticancer drug(s) or biological product(s) within 4 weeks prior to the first dose of study drug with certain exceptions.~Hematologic malignancies (e.g., ALL, AML, MDS, CLL, CML, NHL, Hodgkin's lymphoma and multiple myeloma)~Prior or concurrent malignancies. Exception: Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessments of INBRX-106.~Known or active primary central nervous system (CNS) tumors, leptomeningeal disease and CNS metastases. Exception: Subjects with previously treated, asymptomatic, and clinically stable CNS metastases may be allowed study entry if certain criteria apply.~Grade ≥ 3 immune-related adverse events (irAEs) or irAE that lead to discontinuation of prior immunotherapy. Some exceptions as defined per protocol apply.~Active autoimmune disease or documented history of autoimmune disease that required systemic steroids or other immunosuppressive medications. Certain exceptions as defined in protocol apply.~Treatment with systemic immunosuppressive medications within 4 weeks prior to the first dose of study drug. Certain exceptions as defined in protocol apply.~History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection for Parts 1 and 3. Exceptions as defined in protocol for expansion cohorts will apply.~Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment with steroids or other immunosuppressive medications.~Clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heart disease < 3 months; left ventricular ejection fraction (LVEF) < 50%; New York Heart Association (NYHA) Class III or IV congestive heart failure; or uncontrolled hypertension.~Active, hemodynamically significant pulmonary embolism within 3 months prior to enrollment on this trial.~Major surgery within 4 weeks prior to enrollment on this trial.~Anti-infectious drug treatments (i.e., antibiotics) within 4 weeks prior to the first dose of study drug.~Prior organ allograft transplantations or allogeneic peripheral blood stem cell (PBSC) or bone marrow (BM) transplantation.~Additional in- and exclusion criteria per protocol.	18 Years	null	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Sequential Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Frequency of adverse events of INBRX-106 as single agent and in combination with pembrolizumab \| Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0 \| 2-4 years \| \| Severity of adverse events of INBRX-106 as single agent and in combination with pembrolizumab \| Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0 \| 2-4 years \| \| MTD and/or RP2D of INBRX-106 as single agent and in combination with pembrolizumab \| Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of INBRX-106 and INBRX-106 in combination with pembrolizumab \| 2-4 years \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Area under the serum concentration time curve (AUC) of INBRX-106 \| Area under the serum concentration time curve (AUC) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined. \| 2-4 years \| \| Maximum observed serum concentration (Cmax) of INBRX-106 \| Maximum observed serum concentration (Cmax) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined. \| 2-4 years \| \| Trough observed serum concentration (Ctrough) of INBRX-106 \| Trough observed serum concentration (Ctrough) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined. \| 2-4 years \| \| Time to Cmax (Tmax) of INBRX-106 \| Time to Cmax (Tmax) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined. \| 2-4 years \| \| Immunogenicity of INBRX-106 \| Frequency of anti-drug antibodies (ADA) against INBRX-106 as a single agent and in combination with pembrolizumab will be determined. \| 2-4 years \|	Phase 1 and Phase 2, Phase 1 and Phase 2 Clinical Trial, Solid Tumors, Melanoma, Head and Neck Cancer, Stomach Cancer, Gastric Cancer, Lung Cancer, Non-Small Cell Lung Cancer, Kidney Cancer, Renal Cell Carcinoma, Bladder Cancer, Urothelial Carcinoma, OX40, PD-1, Pembrolizumab, Keytruda	Pembrolizumab, Antibodies, Immunologic Factors, Physiological Effects of Drugs, Antineoplastic Agents, Immunological, Antineoplastic Agents, Immune Checkpoint Inhibitors, Molecular Mechanisms of Pharmacological Action	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Part 1 INBRX-106 Escalation<br>INBRX-106 will be escalated in subjects with locally advanced or metastatic solid tumors. \| Drug: INBRX-106 - Hexavalent OX40 agonist antibody<br>* The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).<br>\| \| Experimental: Part 3 INBRX-106 Escalation in Combination with Pembrolizumab<br>INBRX-106 will be escalated, in combination with pembrolizumab, in subjects with locally advanced or metastatic solid tumors. \| Drug: INBRX-106 - Hexavalent OX40 agonist antibody<br>* The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).<br>Drug: Pembrolizumab 200 mg<br>* Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.<br>* Other names: Keytruda;\| \| Experimental: Part 4 INBRX-106 Expansion in Combination with Pembrolizumab<br>Subjects with melanoma (any type), head and neck squamous cell carcinoma (non-nasopharyngeal), nasopharyngeal carcinoma, MSI-high, TMB-high or MMR-deficient tumors, will be treated with INBRX-106 in combination with 200mg pembrolizumab IV every 3 weeks. \| Drug: INBRX-106 - Hexavalent OX40 agonist antibody<br>* The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).<br>Drug: Pembrolizumab 200 mg<br>* Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.<br>* Other names: Keytruda;\| \| Active Comparator: Part 4 Pembrolizumab Expansion Arm, Randomized<br>Subjects with non-small cell lung cancer will be treated with 200 mg pembrolizumab IV every 3 weeks \| Drug: Pembrolizumab 200 mg<br>* Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.<br>* Other names: Keytruda;\| \| Experimental: Part 4 INBRX-106 Expansion in Combination with Pembrolizumab in NSCLC, Randomized<br>Subjects with non-small cell lung cancer will be treated with alternating every 6 weeks dosing of INBRX-106 0.3 mg/kg Q6W and 400 mg pembrolizumab IV \| Drug: INBRX-106 - Hexavalent OX40 agonist antibody<br>* The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).<br>Drug: Pembrolizumab 400 mg<br>* Pembrolizumab 400 mg by IV infusion given on Day 1 of alternating 21-day cycles (every 6 weeks)<br>* Other names: Keytruda;\| \| Experimental: Part 4 INBRX-106 Expansion in Combination with Pembrolizumab in NSCLC; Randomized<br>Subjects with non-small cell lung cancer will be given a 0.3 mg/kg priming dose of INBRX-106 in cycle 1, followed by 0.1 mg/kg INBRX-106 and 200 mg pembrolizumab IV every 3 weeks in subsequent cycles \| Drug: INBRX-106 - Hexavalent OX40 agonist antibody<br>* The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).<br>Drug: Pembrolizumab 200 mg<br>* Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.<br>* Other names: Keytruda;\| \| Experimental: Part 2 INBRX-106 Escalation in NSCLC<br>Subjects with non-small cell carcinoma relapsed or refractory to prior checkpoint inhibitor (CPI) therapy will be treated with INBRX-106 \| Drug: INBRX-106 - Hexavalent OX40 agonist antibody<br>* The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).<br>\| \| Experimental: Part 2 INBRX-106 Escalation in Various Solid Tumor Types<br>Subjects with melanoma (any type), head and neck squamous cell carcinoma, renal cell carcinoma, urothelial carcinoma or MSI/TMB-high tumors that are relapsed or refractory to prior checkpoint inhibitor (CPI) therapy will be treated with INBRX-106 \| Drug: INBRX-106 - Hexavalent OX40 agonist antibody<br>* The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).<br>\| \| Experimental: Part 4 INBRX-106 Expansion with Pembrolizumab in Uveal Melanoma<br>Subjects with ocular (uveal) melanoma who are relapsed or refractory to checkpoint inhibitor (CPI) therapy will be treated with INBRX-106 and 200 mg pembrolizumab IV every 3 weeks \| Drug: INBRX-106 - Hexavalent OX40 agonist antibody<br>* The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).<br>Drug: Pembrolizumab 200 mg<br>* Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.<br>* Other names: Keytruda;\| \| Experimental: Part 4 INBRX-106 Expansion with Pembrolizumab in MSI-high, TMB-high or MMR-deficient tumors<br>Subjects with solid tumors that have confirmed MSI-high, TMB-high or MMR-deficient states who are relapsed or refractory to checkpoint inhibitor (CPI) therapy will be treated with INBRX-106 and 200 mg pembrolizumab IV every 3 weeks \| Drug: INBRX-106 - Hexavalent OX40 agonist antibody<br>* The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).<br>Drug: Pembrolizumab 200 mg<br>* Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.<br>* Other names: Keytruda;\|	Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist) Study Overview ================= Brief Summary ----------------- This is a Phase 1/2, open-label, non-randomized, 4-part Phase 1 trial to determine the safety profile and identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of INBRX 106 administered as a single agent or in combination with the anti-PD-1 checkpoint inhibitor (CPI) pembrolizumab (Keytruda). Official Title ----------------- An Open-Label, Multicenter, First-in-Human, Dose-Escalation, Multicohort, Phase 1/2 Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors Conditions ----------------- Solid Tumor, Non-Small Cell Lung Cancer, Melanoma, Head and Neck Cancer, Gastric Cancer, Renal Cell Carcinoma, Urothelial Carcinoma Intervention / Treatment ----------------- * Drug: INBRX-106 - Hexavalent OX40 agonist antibody * Drug: Pembrolizumab 200 mg * Drug: Pembrolizumab 400 mg Participation Criteria ================= Eligibility Criteria ----------------- Select Inclusion Criteria: Males or females aged ≥18 years. Parts 1 and 3 (escalation cohorts): Subjects with locally advanced or metastatic non resectable solid tumors, whose disease has progressed despite all standard therapies or for whom no further standard or clinically acceptable therapy exists. Part 2 (single-agent expansion cohort): Subjects with NSCLC, melanoma, HNSCC, G/GEA, RCC, or TCC, with locally advanced or metastatic, non-resectable disease, which has progressed despite all standard therapies including CPI or for whom no standard or clinically acceptable therapy exists. Part 4 (expansion cohorts in combination with pembrolizumab): Subjects with melanoma (all types), HNSCC, G/GEA, RCC, TCC, NSCLC, or MSI-high, TMB-high, MMR-deficient tumors, with locally advanced or metastatic, non resectable disease, which is either CPI-naive (melanoma, HNSCC, NPC) or progressed despite all standard therapies including CPI (NSCLC, RCC, TCC, uveal melanoma, MSI-high, TMB-high, or MMR-deficient solid tumors) or for whom no standard or clinically acceptable therapy exists. All subjects with non-squamous NSCLC must have documentation of absence of tumor activating EGFR mutations and absence of ALK gene rearrangements. PD-L1 by IHC (22C3): Parts 1 and 3: IHC optional. Part 2: IHC result mandatory but any score allowed. Part 4: Combined Positive Score (CPS) ≥ 1% (or Tumor Proportion Score ≥50% for NSCLC; for TMB-high tumors, any TPS% is allowed). Adequate hematologic, coagulation, hepatic and renal function and ECOG score as defined per protocol. Select Exclusion Criteria: Prior exposure to OX40 agonists. Receipt of any investigational product or any approved anticancer drug(s) or biological product(s) within 4 weeks prior to the first dose of study drug with certain exceptions. Hematologic malignancies (e.g., ALL, AML, MDS, CLL, CML, NHL, Hodgkin's lymphoma and multiple myeloma) Prior or concurrent malignancies. Exception: Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessments of INBRX-106. Known or active primary central nervous system (CNS) tumors, leptomeningeal disease and CNS metastases. Exception: Subjects with previously treated, asymptomatic, and clinically stable CNS metastases may be allowed study entry if certain criteria apply. Grade ≥ 3 immune-related adverse events (irAEs) or irAE that lead to discontinuation of prior immunotherapy. Some exceptions as defined per protocol apply. Active autoimmune disease or documented history of autoimmune disease that required systemic steroids or other immunosuppressive medications. Certain exceptions as defined in protocol apply. Treatment with systemic immunosuppressive medications within 4 weeks prior to the first dose of study drug. Certain exceptions as defined in protocol apply. History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection for Parts 1 and 3. Exceptions as defined in protocol for expansion cohorts will apply. Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment with steroids or other immunosuppressive medications. Clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heart disease < 3 months; left ventricular ejection fraction (LVEF) < 50%; New York Heart Association (NYHA) Class III or IV congestive heart failure; or uncontrolled hypertension. Active, hemodynamically significant pulmonary embolism within 3 months prior to enrollment on this trial. Major surgery within 4 weeks prior to enrollment on this trial. Anti-infectious drug treatments (i.e., antibiotics) within 4 weeks prior to the first dose of study drug. Prior organ allograft transplantations or allogeneic peripheral blood stem cell (PBSC) or bone marrow (BM) transplantation. Additional in- and exclusion criteria per protocol. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Sequential Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Part 1 INBRX-106 Escalation<br>INBRX-106 will be escalated in subjects with locally advanced or metastatic solid tumors. \| Drug: INBRX-106 - Hexavalent OX40 agonist antibody<br>* The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).<br>\| \| Experimental: Part 3 INBRX-106 Escalation in Combination with Pembrolizumab<br>INBRX-106 will be escalated, in combination with pembrolizumab, in subjects with locally advanced or metastatic solid tumors. \| Drug: INBRX-106 - Hexavalent OX40 agonist antibody<br>* The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).<br>Drug: Pembrolizumab 200 mg<br>* Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.<br>* Other names: Keytruda;\| \| Experimental: Part 4 INBRX-106 Expansion in Combination with Pembrolizumab<br>Subjects with melanoma (any type), head and neck squamous cell carcinoma (non-nasopharyngeal), nasopharyngeal carcinoma, MSI-high, TMB-high or MMR-deficient tumors, will be treated with INBRX-106 in combination with 200mg pembrolizumab IV every 3 weeks. \| Drug: INBRX-106 - Hexavalent OX40 agonist antibody<br>* The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).<br>Drug: Pembrolizumab 200 mg<br>* Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.<br>* Other names: Keytruda;\| \| Active Comparator: Part 4 Pembrolizumab Expansion Arm, Randomized<br>Subjects with non-small cell lung cancer will be treated with 200 mg pembrolizumab IV every 3 weeks \| Drug: Pembrolizumab 200 mg<br>* Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.<br>* Other names: Keytruda;\| \| Experimental: Part 4 INBRX-106 Expansion in Combination with Pembrolizumab in NSCLC, Randomized<br>Subjects with non-small cell lung cancer will be treated with alternating every 6 weeks dosing of INBRX-106 0.3 mg/kg Q6W and 400 mg pembrolizumab IV \| Drug: INBRX-106 - Hexavalent OX40 agonist antibody<br>* The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).<br>Drug: Pembrolizumab 400 mg<br>* Pembrolizumab 400 mg by IV infusion given on Day 1 of alternating 21-day cycles (every 6 weeks)<br>* Other names: Keytruda;\| \| Experimental: Part 4 INBRX-106 Expansion in Combination with Pembrolizumab in NSCLC; Randomized<br>Subjects with non-small cell lung cancer will be given a 0.3 mg/kg priming dose of INBRX-106 in cycle 1, followed by 0.1 mg/kg INBRX-106 and 200 mg pembrolizumab IV every 3 weeks in subsequent cycles \| Drug: INBRX-106 - Hexavalent OX40 agonist antibody<br>* The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).<br>Drug: Pembrolizumab 200 mg<br>* Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.<br>* Other names: Keytruda;\| \| Experimental: Part 2 INBRX-106 Escalation in NSCLC<br>Subjects with non-small cell carcinoma relapsed or refractory to prior checkpoint inhibitor (CPI) therapy will be treated with INBRX-106 \| Drug: INBRX-106 - Hexavalent OX40 agonist antibody<br>* The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).<br>\| \| Experimental: Part 2 INBRX-106 Escalation in Various Solid Tumor Types<br>Subjects with melanoma (any type), head and neck squamous cell carcinoma, renal cell carcinoma, urothelial carcinoma or MSI/TMB-high tumors that are relapsed or refractory to prior checkpoint inhibitor (CPI) therapy will be treated with INBRX-106 \| Drug: INBRX-106 - Hexavalent OX40 agonist antibody<br>* The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).<br>\| \| Experimental: Part 4 INBRX-106 Expansion with Pembrolizumab in Uveal Melanoma<br>Subjects with ocular (uveal) melanoma who are relapsed or refractory to checkpoint inhibitor (CPI) therapy will be treated with INBRX-106 and 200 mg pembrolizumab IV every 3 weeks \| Drug: INBRX-106 - Hexavalent OX40 agonist antibody<br>* The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).<br>Drug: Pembrolizumab 200 mg<br>* Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.<br>* Other names: Keytruda;\| \| Experimental: Part 4 INBRX-106 Expansion with Pembrolizumab in MSI-high, TMB-high or MMR-deficient tumors<br>Subjects with solid tumors that have confirmed MSI-high, TMB-high or MMR-deficient states who are relapsed or refractory to checkpoint inhibitor (CPI) therapy will be treated with INBRX-106 and 200 mg pembrolizumab IV every 3 weeks \| Drug: INBRX-106 - Hexavalent OX40 agonist antibody<br>* The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).<br>Drug: Pembrolizumab 200 mg<br>* Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.<br>* Other names: Keytruda;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Frequency of adverse events of INBRX-106 as single agent and in combination with pembrolizumab \| Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0 \| 2-4 years \| \| Severity of adverse events of INBRX-106 as single agent and in combination with pembrolizumab \| Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0 \| 2-4 years \| \| MTD and/or RP2D of INBRX-106 as single agent and in combination with pembrolizumab \| Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of INBRX-106 and INBRX-106 in combination with pembrolizumab \| 2-4 years \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Area under the serum concentration time curve (AUC) of INBRX-106 \| Area under the serum concentration time curve (AUC) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined. \| 2-4 years \| \| Maximum observed serum concentration (Cmax) of INBRX-106 \| Maximum observed serum concentration (Cmax) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined. \| 2-4 years \| \| Trough observed serum concentration (Ctrough) of INBRX-106 \| Trough observed serum concentration (Ctrough) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined. \| 2-4 years \| \| Time to Cmax (Tmax) of INBRX-106 \| Time to Cmax (Tmax) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined. \| 2-4 years \| \| Immunogenicity of INBRX-106 \| Frequency of anti-drug antibodies (ADA) against INBRX-106 as a single agent and in combination with pembrolizumab will be determined. \| 2-4 years \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Phase 1 and Phase 2, Phase 1 and Phase 2 Clinical Trial, Solid Tumors, Melanoma, Head and Neck Cancer, Stomach Cancer, Gastric Cancer, Lung Cancer, Non-Small Cell Lung Cancer, Kidney Cancer, Renal Cell Carcinoma, Bladder Cancer, Urothelial Carcinoma, OX40, PD-1, Pembrolizumab, Keytruda
NCT04492163	Open-Label Pilot Study of OPTUNE® With High Density Transducer Arrays for the Treatment of Recurrent GBM	This is a prospective, open-label, single arm, historical control pilot study aimed to test the effectiveness and safety of TTFields delivered through high intensity arrays in recurrent glioblastoma.~The Optune® System is an investigational , portable, battery operated medical device in this study delivering 200 kHz TTFields to the brain using high intensity transducer arrays for the treatment of patients at the age of 18 years or older with first or second recurrence of Glioblastoma Multiforme (GBM)	Optune® is a medical device that has been approved for the treatment of recurrent and newly diagnosed glioblastoma (GBM) by the Food and Drug Administration (FDA) in the United States. Optune® has obtained a CE mark in Europe for recurrent and newly diagnosed GBM.~TTFields intensity has been shown to be positively correlated with patient outcome. The new transducer array design is expected to reduce skin heating and thus enable delivery of higher TTFields intensities while keeping the safety profile of the treatment unchanged.~The purpose of the study is to test if delivering TTFields using high intensity transducer arrays for recurrent GBM significantly improves the clinical outcome of patients, compared to using the standard transducer arrays.~The study will enroll 25 patients.~All patients included in this clinical investigation are patients with histologically confirmed diagnosis of GBM with first or second radiological disease progression per RANO criteria.~In addition, all patients must meet all eligibility criteria.~Baseline assessments will be performed to confirm patient eligibility in the study.~Enrolled patients will be treated continuously with the device until disease progression per RANO criteria or 18 months (the earlier of the two) unless any of the treatment discontinuation conditions described under criteria for patient withdrawal or termination are met.~Concurrent brain directed antitumor therapy or procedures beyond TTFields is prohibited.~TTFields treatment will start within 28 days following signing the informed consent.~After the initial visit, subjects will continue treatment at home, while pursuing normal daily routines. Subjects are required to use the device for at least 18 hours a day. Short breaks in treatment for personal hygiene and other personal needs is allowed. Total usage time will be recorded and provided to the sponsor.~Subjects will be required to return to the clinic every 4 weeks and every 8 weeks after first 12 visits, until disease progression. At each study visit an examination by a physician and a routine laboratory examination will be performed.~A contrast enhanced MRI of the head will be performed at baseline and every 4 weeks for the first 24 weeks and then at least every 12 weeks, until disease progression.~A post-treatment termination visit will be performed approximately 30 days after discontinuation of TTfields treatment or disease progression (the latter of the two).~Following disease progression, subjects will be contacted once per month by telephone to answer basic questions about their health status.~Pathological analysis of GBM tumor samples, which may be obtained prior and during the study period, will be performed based on subjects' consent to have an experimental pathological examination of their tumors.	EF-33: An Open-Label Pilot Study of OPTUNE® (TTFields, 200 Khz) With High Density Transducer Arrays for the Treatment of Recurrent Glioblastoma	Glioblastoma Multiforme	* Device: TTFields	Inclusion Criteria:~Histologically confirmed diagnosis of GBM according to WHO classification criteria.~Age ≥ 18 years~Not a candidate for further radiotherapy or additional resection of residual tumor.~Patients with first or second radiological disease progression per RANO criteria documented by MRI within 4 weeks prior to starting therapy with the following restriction: disease progression must be either growth of the enhancing lesion or a new lesion.~Karnofsky performance status ≥ 70~Life expectancy ≥ least 3 months~Participants of childbearing age must use highly effective contraception. An effective method of birth control is defined as one that results in a failure rate of less than 1% per year when used consistently and correctly. The Investigator must approve the selected method, and may consult with a gynecologist as needed.~All patients must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.~Treatment start date at least 4 weeks out from brain surgery chemotherapy or irradiation therapy.~Exclusion Criteria:~Infratentorial or leptomeningeal disease~Treatment with Optune® (for newly diagnosed or recurrent disease) prior to enrollment.~Participation in another clinical treatment study during screening and treatment phase of the study.~Pregnancy or breast-feeding.~Significant co-morbidities at baseline, as determined by the investigator:~Thrombocytopenia (platelet count < 100 x 103/μL)~Neutropenia (absolute neutrophil count < 1 x 103/μL)~CTC grade 4 non-hematological Toxicity (except for alopecia, nausea, vomiting)~Significant liver function impairment - AST or ALT > 3 times the upper limit of normal~Total bilirubin > 1.5 x upper limit of normal~Significant renal impairment (serum creatinine > 1.7 mg/dL, or > 150 µmol/l)~History of any psychiatric condition that might impair patient's ability to understand or comply with the requirements of the study or to provide consent~Implanted pacemaker, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.~Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness)~Admitted to an institution by administrative or court order.~Known allergies to medical adhesives or hydrogel~-	18 Years	null	All	No	Primary Purpose: Treatment Intervention Model: Single Group Assignment Interventional Model Description: Single group assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Progression free survival (PFS) \| PFS will be measured from the date of enrollment to date of progression (in months) based on RANO citeria. \| 18 Months \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Overall Survival (OS) \| Survival will be measured from date of enrollment until date of death. \| 18 Months \| \| Progression Free Survival at 6 months (PFS6) \| The analysis will be estimated proportions of patients who are progression-free at 6 months based on the RANO criteria following the time of enrollment. \| 18 Months \| \| 1-year and 2-year survival rates \| The analyses will be performed based on estimated proportions of patients who are alive at one and two years following enrollment. \| 24 Months \| \| Overall radiological response \| The percentage of patients who had either complete response or partial response per RANO criteria following enrollment \| 18 Months \| \| Severity and frequency of adverse events \| The analyses will be performed based on the incidence, severity, frequency of adverse events, and their association with study treatments \| 18 Months \| \| Pathological changes in resected GBM tumors following study treatment \| Pathological changes in the tumors of patients who consented to have pathological analysis of their tumors and also underwent another surgical resection while on the study \| 18 Months \| \| Dependence of Progression Free Survival on TTFields dose delivered to the tumor bed \| \| 18 months \| \| Dependence of Overall Survival on TTFields dose delivered to the tumor bed \| \| 18 months \|	Glioblastoma Multiforme, Recurrent Glioblastoma, GBM, Treatment, Minimal Toxicity, TTFields, Tumor Treating Fields, NovoCure	Glioblastoma, Astrocytoma, Glioma, Neoplasms, Neuroepithelial, Neuroectodermal Tumors, Neoplasms, Germ Cell and Embryonal, Neoplasms by Histologic Type, Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms, Nerve Tissue	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Experimental: TTFields<br>Patients receive continuous TTFields treatment using the Optune® System with high intensity transducer arrays. \| Device: TTFields<br>* TTFields treatment will consist of wearing four electrically insulated electrode arrays on the head. The treatment enables the patient to maintain regular daily routine.~Other Names:~• TTFields<br>\|	Open-Label Pilot Study of OPTUNE® With High Density Transducer Arrays for the Treatment of Recurrent GBM Study Overview ================= Brief Summary ----------------- This is a prospective, open-label, single arm, historical control pilot study aimed to test the effectiveness and safety of TTFields delivered through high intensity arrays in recurrent glioblastoma. The Optune® System is an investigational , portable, battery operated medical device in this study delivering 200 kHz TTFields to the brain using high intensity transducer arrays for the treatment of patients at the age of 18 years or older with first or second recurrence of Glioblastoma Multiforme (GBM) Detailed Description ----------------- Optune® is a medical device that has been approved for the treatment of recurrent and newly diagnosed glioblastoma (GBM) by the Food and Drug Administration (FDA) in the United States. Optune® has obtained a CE mark in Europe for recurrent and newly diagnosed GBM. TTFields intensity has been shown to be positively correlated with patient outcome. The new transducer array design is expected to reduce skin heating and thus enable delivery of higher TTFields intensities while keeping the safety profile of the treatment unchanged. The purpose of the study is to test if delivering TTFields using high intensity transducer arrays for recurrent GBM significantly improves the clinical outcome of patients, compared to using the standard transducer arrays. The study will enroll 25 patients. All patients included in this clinical investigation are patients with histologically confirmed diagnosis of GBM with first or second radiological disease progression per RANO criteria. In addition, all patients must meet all eligibility criteria. Baseline assessments will be performed to confirm patient eligibility in the study. Enrolled patients will be treated continuously with the device until disease progression per RANO criteria or 18 months (the earlier of the two) unless any of the treatment discontinuation conditions described under criteria for patient withdrawal or termination are met. Concurrent brain directed antitumor therapy or procedures beyond TTFields is prohibited. TTFields treatment will start within 28 days following signing the informed consent. After the initial visit, subjects will continue treatment at home, while pursuing normal daily routines. Subjects are required to use the device for at least 18 hours a day. Short breaks in treatment for personal hygiene and other personal needs is allowed. Total usage time will be recorded and provided to the sponsor. Subjects will be required to return to the clinic every 4 weeks and every 8 weeks after first 12 visits, until disease progression. At each study visit an examination by a physician and a routine laboratory examination will be performed. A contrast enhanced MRI of the head will be performed at baseline and every 4 weeks for the first 24 weeks and then at least every 12 weeks, until disease progression. A post-treatment termination visit will be performed approximately 30 days after discontinuation of TTfields treatment or disease progression (the latter of the two). Following disease progression, subjects will be contacted once per month by telephone to answer basic questions about their health status. Pathological analysis of GBM tumor samples, which may be obtained prior and during the study period, will be performed based on subjects' consent to have an experimental pathological examination of their tumors. Official Title ----------------- EF-33: An Open-Label Pilot Study of OPTUNE® (TTFields, 200 Khz) With High Density Transducer Arrays for the Treatment of Recurrent Glioblastoma Conditions ----------------- Glioblastoma Multiforme Intervention / Treatment ----------------- * Device: TTFields Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Histologically confirmed diagnosis of GBM according to WHO classification criteria. Age ≥ 18 years Not a candidate for further radiotherapy or additional resection of residual tumor. Patients with first or second radiological disease progression per RANO criteria documented by MRI within 4 weeks prior to starting therapy with the following restriction: disease progression must be either growth of the enhancing lesion or a new lesion. Karnofsky performance status ≥ 70 Life expectancy ≥ least 3 months Participants of childbearing age must use highly effective contraception. An effective method of birth control is defined as one that results in a failure rate of less than 1% per year when used consistently and correctly. The Investigator must approve the selected method, and may consult with a gynecologist as needed. All patients must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted. Treatment start date at least 4 weeks out from brain surgery chemotherapy or irradiation therapy. Exclusion Criteria: Infratentorial or leptomeningeal disease Treatment with Optune® (for newly diagnosed or recurrent disease) prior to enrollment. Participation in another clinical treatment study during screening and treatment phase of the study. Pregnancy or breast-feeding. Significant co-morbidities at baseline, as determined by the investigator: Thrombocytopenia (platelet count < 100 x 103/μL) Neutropenia (absolute neutrophil count < 1 x 103/μL) CTC grade 4 non-hematological Toxicity (except for alopecia, nausea, vomiting) Significant liver function impairment - AST or ALT > 3 times the upper limit of normal Total bilirubin > 1.5 x upper limit of normal Significant renal impairment (serum creatinine > 1.7 mg/dL, or > 150 µmol/l) History of any psychiatric condition that might impair patient's ability to understand or comply with the requirements of the study or to provide consent Implanted pacemaker, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias. Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness) Admitted to an institution by administrative or court order. Known allergies to medical adhesives or hydrogel - Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Interventional Model Description: Single group assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Experimental: TTFields<br>Patients receive continuous TTFields treatment using the Optune® System with high intensity transducer arrays. \| Device: TTFields<br>* TTFields treatment will consist of wearing four electrically insulated electrode arrays on the head. The treatment enables the patient to maintain regular daily routine. Other Names: • TTFields<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Progression free survival (PFS) \| PFS will be measured from the date of enrollment to date of progression (in months) based on RANO citeria. \| 18 Months \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Overall Survival (OS) \| Survival will be measured from date of enrollment until date of death. \| 18 Months \| \| Progression Free Survival at 6 months (PFS6) \| The analysis will be estimated proportions of patients who are progression-free at 6 months based on the RANO criteria following the time of enrollment. \| 18 Months \| \| 1-year and 2-year survival rates \| The analyses will be performed based on estimated proportions of patients who are alive at one and two years following enrollment. \| 24 Months \| \| Overall radiological response \| The percentage of patients who had either complete response or partial response per RANO criteria following enrollment \| 18 Months \| \| Severity and frequency of adverse events \| The analyses will be performed based on the incidence, severity, frequency of adverse events, and their association with study treatments \| 18 Months \| \| Pathological changes in resected GBM tumors following study treatment \| Pathological changes in the tumors of patients who consented to have pathological analysis of their tumors and also underwent another surgical resection while on the study \| 18 Months \| \| Dependence of Progression Free Survival on TTFields dose delivered to the tumor bed \| \| 18 months \| \| Dependence of Overall Survival on TTFields dose delivered to the tumor bed \| \| 18 months \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Glioblastoma Multiforme, Recurrent Glioblastoma, GBM, Treatment, Minimal Toxicity, TTFields, Tumor Treating Fields, NovoCure
NCT03126279	fMRI and Central Sensitization in Chronic Knee Osteoarthritis. A Pre and Post TKR Study	Painful osteoarthritis (OA) is the 4th largest cause of disability in the UK. Preoperative temporal summation, a measure of central pain facilitation, has been shown to predict postoperative pain after total knee replacement surgery (TKR). The assessment of the brain's response to noxious stimuli using non-invasive functional MRI (fMRI) may be key in identifying imaging biomarkers within the brain that map central sensitization changes seen in OA. fMRI may help explain why up to 20% of patients undergoing TKR surgery develop persistent post-operative pain. To test these concepts the study aims to functionally characterise the brain activity related to temporal summation of pain in healthy individuals and OA patients using a novel fMRI cuff algometer. Assessment of outcomes in terms of pain and function will be performed 6 months post TKR surgery		Predicting Chronic Post TKR Pain by Assessing Central Sensitisation Using Functional Brain MRI	Osteoarthritis, Pain, Postoperative Pain, Surgery	* Procedure: Total Knee Replacement Surgery	Inclusion Criteria:~OA Group~Unilateral Knee OA No previous knee surgery Able to give informed consent Age > 40 years~- Healthy Volunteers Group~No OA or knee pain Able to give informed consent Age > 40 years~Exclusion Criteria:~-OA Group~Major medical, psychiatric, neurological Cx Other chronic pain condition (fibromyalgia) Contraindications to MRI Active Cancer Neuropathic drug treatment~-Healthy Volunteers Group~Pregnancy Lower limb pain or previous knee surgery Contraindications to MRI Active Cancer Major medical, psychiatric, neurological condition	40 Years	null	All	Accepts Healthy Volunteers		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Brain activity related to temporal summation of pain in healthy individuals and OA patients using a novel fMRI cuff algometer. \| Using BOLD fMRI we aim to assess the difference in neural brain activity between patients with chronic knee OA pain and a group of healthy volunteers and to assess the reversal of this activity pattern 6 months post TKR surgery \| 6 months post total knee replacement surgery \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Assessment of knee pain using the Visual Analogue Scale for Pain (0-10) \| Pain using visual analogue scale \| 6 months post total knee replacement surgery \| \| Assessment of improvement in the Oxford Knee Score \| pain and function outcome measure \| 6 months post total knee replacement surgery \| \| Assessment of change in healthy related quality of life measure using the EQ5D-5L questionnaire \| quality of life index measure \| 6 months post total knee replacement \|	Pain, Osteoarthritis, Postoperative Pain	Musculoskeletal Diseases, Rheumatic Diseases, Pain, Osteoarthritis, Pain, Postoperative, Arthritis, Joint Diseases, Postoperative Complications, Pathologic Processes, Neurologic Manifestations	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Preoperative Chronic Knee OA Patients<br>Patients will be recruited from orthopaedic preoperative clinics from those awaiting total knee replacement surgery. \| Procedure: Total Knee Replacement Surgery<br>* All chronic knee osteoarthritis patients will be recruited as they are on the NHS waiting list for a total knee replacement. Only this group will undergo the procedure<br>* Other names: Total;\| \| Healthy Volunteers<br>Healthy volunteers will be recruited that are aged match to our OA patient cohort so meaningful comparisons regarding brain activity and pain sensitisation characteristics can be assessed. \| \|	fMRI and Central Sensitization in Chronic Knee Osteoarthritis. A Pre and Post TKR Study Study Overview ================= Brief Summary ----------------- Painful osteoarthritis (OA) is the 4th largest cause of disability in the UK. Preoperative temporal summation, a measure of central pain facilitation, has been shown to predict postoperative pain after total knee replacement surgery (TKR). The assessment of the brain's response to noxious stimuli using non-invasive functional MRI (fMRI) may be key in identifying imaging biomarkers within the brain that map central sensitization changes seen in OA. fMRI may help explain why up to 20% of patients undergoing TKR surgery develop persistent post-operative pain. To test these concepts the study aims to functionally characterise the brain activity related to temporal summation of pain in healthy individuals and OA patients using a novel fMRI cuff algometer. Assessment of outcomes in terms of pain and function will be performed 6 months post TKR surgery Official Title ----------------- Predicting Chronic Post TKR Pain by Assessing Central Sensitisation Using Functional Brain MRI Conditions ----------------- Osteoarthritis, Pain, Postoperative Pain, Surgery Intervention / Treatment ----------------- * Procedure: Total Knee Replacement Surgery Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: OA Group Unilateral Knee OA No previous knee surgery Able to give informed consent Age > 40 years - Healthy Volunteers Group No OA or knee pain Able to give informed consent Age > 40 years Exclusion Criteria: -OA Group Major medical, psychiatric, neurological Cx Other chronic pain condition (fibromyalgia) Contraindications to MRI Active Cancer Neuropathic drug treatment -Healthy Volunteers Group Pregnancy Lower limb pain or previous knee surgery Contraindications to MRI Active Cancer Major medical, psychiatric, neurological condition Ages Eligible for Study ----------------- Minimum Age: 40 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Preoperative Chronic Knee OA Patients<br>Patients will be recruited from orthopaedic preoperative clinics from those awaiting total knee replacement surgery. \| Procedure: Total Knee Replacement Surgery<br>* All chronic knee osteoarthritis patients will be recruited as they are on the NHS waiting list for a total knee replacement. Only this group will undergo the procedure<br>* Other names: Total;\| \| Healthy Volunteers<br>Healthy volunteers will be recruited that are aged match to our OA patient cohort so meaningful comparisons regarding brain activity and pain sensitisation characteristics can be assessed. \| \| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Brain activity related to temporal summation of pain in healthy individuals and OA patients using a novel fMRI cuff algometer. \| Using BOLD fMRI we aim to assess the difference in neural brain activity between patients with chronic knee OA pain and a group of healthy volunteers and to assess the reversal of this activity pattern 6 months post TKR surgery \| 6 months post total knee replacement surgery \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Assessment of knee pain using the Visual Analogue Scale for Pain (0-10) \| Pain using visual analogue scale \| 6 months post total knee replacement surgery \| \| Assessment of improvement in the Oxford Knee Score \| pain and function outcome measure \| 6 months post total knee replacement surgery \| \| Assessment of change in healthy related quality of life measure using the EQ5D-5L questionnaire \| quality of life index measure \| 6 months post total knee replacement \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Pain, Osteoarthritis, Postoperative Pain
NCT04290364	Early Palliative Care in Pancreatic Cancer - a Quasi-experimental Study	The aim of the proposed study is to understand the palliative care needs of patients with pancreatic cancer, to investigate whether early palliative care can improve patient outcomes and reduce use of health care services, and to understand the psychological health of carers and their satisfaction with care.~A quasi-experimental design is used, introducing palliative care for patients with pancreatic cancer within three weeks from diagnosis. The patients are recruited in Dept. of Surgery, Hospital of North Zealand, which covers the northern catchment area of the Capital Region of Copenhagen, Denmark. Patients are seen by the palliative care team on home-visits every four weeks throughout their trajectory, and quality of life is evaluated using the following quality of life questionnaires (QLQs): European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients receiving palliative care (EORTC QLQ-C15-PAL), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Pancreatic Cancer Patients (EORTC QLQ-PAN26), and Hospital Anxiety and Depression Scale (HADS). For carers, mental health is evaluated using HADS and satisfaction with care is evaluated using the Family Caregivers' Satisfaction With Palliative Care in Advanced Cancer Questionnaire (FAMCARE-2).~The primary outcome is health care service use (acute hospital admissions, days in hospital). Secondary outcomes are survival and place of death. Data are compared with historical control patients treated in the same hospital before introduction of early palliative care. These outcomes are readily available from patient records and are expected to carry a very low risk of bias.~Palliative care needs at referral in the study group will be compared with palliative care needs in the subgroup of historical control patients referred to palliative care on-demand.~For outcomes where unbiased historical control data are not available a prospective observational approach is used. These include symptom burden, weight, psychological health and satisfaction with care.~The minimum sample size needed to show a clinically significant decrease in acute hospital admissions is 70, 35 participating in the prospective study and 35 historical control patients. The study will include 40-50 patients and their carers from September 2019 to September 2020.	Study design~All patients with symptoms compatible with pancreatic cancer living in the northern catchment area of the Capital Region of Copenhagen, Denmark, are referred to Dept. of Surgery, Hospital of North Zealand for further investigations. Cases diagnosed with pancreatic cancer are discussed at a regional Multi-Disciplinary-Team (MDT) conference and either referred for surgery or chemotherapy or receive best supportive care in Dept. of Surgery. The Palliative Care Unit at Hospital of North Zealand covers the same geographical area with 310,000 inhabitants.~Patients referred to Dept. of Surgery and diagnosed with pancreatic cancer are offered participation in this study. All participants will receive home-visits from the palliative care team every four weeks, starting within three weeks from diagnosis and until end-of-life or cure without residual palliative needs.~The study design chosen is a quasi-experimental design using historical control patients for the primary outcome: use of health care services (acute hospital admissions, days in hospital) and the secondary outcomes: survival and place of death. The historical control patients were diagnosed before the introduction of early palliative care. The outcomes are readily available from patient records and are expected to carry a very low risk of registration bias. Palliative care needs at referral in the study group will be compared with palliative care needs in the subgroup of historical control patients referred to palliative care on-demand.~Demographic data will be collected for participants and historical controls to evaluate if any selection bias or other systematic differences exist between the groups.~For outcomes where unbiased historical control data are not available a prospective observational approach is used. These include symptom burden, psychological health and satisfaction with care.~The study will include 40-50 patients and their carers from September 2019 to September 2020.~Recruitment and informed consent~Recruitment to this project will take place in Dept. of Surgery, Hospital of North Zealand to which all patients suspected of having pancreatic cancer and living in the northern catchment area of the Capital Region of Copenhagen will be referred for further investigations. The patients will be informed about their diagnosis by the responsible surgeon in the outpatient clinic in an undisturbed environment. The patients will then be informed about the possibility of participation in the present study. They will receive both oral and written information about the project and will be allowed enough time to consider participation before deciding, as long as it allows contact to the palliative care team within three weeks from diagnosis. It is expected that most patients will come to Dept. of Surgery with a family member or friend, as they are aware that they will receive the results from the investigations performed. However, patients will be informed that they have a right to come back for further information about the protocol accompanied by a family member or any other person they want to bring. They will meet either a surgeon or a palliative care physician who can give further information and answer any possible questions at this meeting.~Written informed consent will be obtained before any protocol related procedures are performed.~Carers will receive separate oral and written information either on the same day as the patient or when meeting the palliative care team on the first visit. Carers will sign a separate consent form if they want to participate in the study. Carers have the same rights as the patients regarding time for consideration and further information before signing the consent form.~Palliative Care Intervention~Patients and carers will be seen on home-visits. The first time they will meet a doctor and usually also a nurse, while follow-up home-visits can be undertaken by either a doctor or a nurse. Home-visits are scheduled every four weeks. Patients can contact a doctor or a specialised nurse on weekdays for consultation. The palliative care nurse will contact a palliative care physician if needed for change of treatment or other reasons. Palliative care is offered in parallel with any specific cancer treatment given.~The patients will receive standard palliative care including treatment of symptoms (e.g. pain, nausea, weight loss, loss of appetite, diarrhoea or fatigue), psychosocial support, physiotherapy, nutritional counselling and advance care planning, depending on their needs. The palliative care team comprises physicians, nurses, a physiotherapist and a chaplain. Patients and/or carers scoring 8 or more on HADS for anxiety and/or depression will be advised to be referred to a psychologist via their general practitioner.~Change from standard of care~Patients with pancreatic cancer are normally referred to palliative care when the surgeon, oncologist or general practitioner taking care of them find that they are not able to meet their palliative care needs, or if the patients and their families request a referral. Most patients are referred late in their trajectory and only half of the patients are referred. We do not know whether patients not referred to palliative care in the routine setting have palliative care needs, whether they are met by other physicians or whether they have unsolved palliative care needs.~Patients accepting inclusion in the project will get specialised palliative care throughout their trajectory, within three weeks after diagnosis until end-of-life or cure without residual palliative care needs.~Both patients participating in the project and patients referred on-demand will receive four-weekly visits in their homes. Patients participating in the project are guaranteed that the first visit will take place within three weeks after diagnosis, whereas patients referred on-demand might have to wait longer before they meet the palliative care team.	Early Palliative Care for Patients With Pancreatic Cancer - Health Care Service Use and Quality of Life - a Quasi-experimental Study Using Historical Controls	Pancreatic Cancer	* Other: Palliative care	Inclusion Criteria:~Adults newly diagnosed with pancreatic cancer in Dept. of Surgery, Hospital of North Zealand, Denmark~Caregivers involved in care or practical help~Exclusion Criteria:~Inability to take an active part in answering questionnaires	18 Years	null	All	No		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Use of healthcare services \| Number of acute hospital admissions and number of days in hospital \| Until death or end of study, an average of 8 months \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Survival \| Survival \| Until death or end of study, an average of 8 months \| \| Quality of life: EORTC QLQ-C15-PAL \| Quality of life measured using the questionnaire: EORTC QLQ-C15-PAL \| Four-weekly until death or end of study, an average of 8 months \| \| Quality of life: EORTC QLQ-PAN26 \| Quality of life measured using the questionnaire: EORTC QLQ-PAN26 \| Four-weekly until death or end of study, an average of 8 months \| \| Anxiety and/or depression \| Anxiety and/or depression measured using the questionnaire: HADS \| Four-weekly until death or end of study, an average of 8 months \| \| Change in weight \| Weight in kilos \| Four-weekly until death or end of study, an average of 8 months \| \| Preferred and actual place of death \| Advance care planning (where patients prefer to die) and the actual place of death \| Until death or end of study, an average of 8 months \| \| Carer satisfaction with palliative care \| Carer satisfaction with palliative care measured using the questionnaire: FAMCARE-2 \| Three-monthly. The last time is at a follow-up visit after the patient has died, or at end of study, an average of 10 months \|	Palliative care	Pancreatic Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Endocrine Gland Neoplasms, Digestive System Diseases, Pancreatic Diseases, Endocrine System Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Prospective cohort<br>Patients newly diagnosed with pancreatic cancer included in the prospective part of the study \| Other: Palliative care<br>* The patients in the prospective part of the study are seen on home-visits and offered standard palliative care within three weeks of diagnosis.<br>\| \| Retrospective cohort<br>Patients diagnosed with pancreatic cancer before early palliative care was introduced (historical control patients) \| \|	Early Palliative Care in Pancreatic Cancer - a Quasi-experimental Study Study Overview ================= Brief Summary ----------------- The aim of the proposed study is to understand the palliative care needs of patients with pancreatic cancer, to investigate whether early palliative care can improve patient outcomes and reduce use of health care services, and to understand the psychological health of carers and their satisfaction with care. A quasi-experimental design is used, introducing palliative care for patients with pancreatic cancer within three weeks from diagnosis. The patients are recruited in Dept. of Surgery, Hospital of North Zealand, which covers the northern catchment area of the Capital Region of Copenhagen, Denmark. Patients are seen by the palliative care team on home-visits every four weeks throughout their trajectory, and quality of life is evaluated using the following quality of life questionnaires (QLQs): European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients receiving palliative care (EORTC QLQ-C15-PAL), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Pancreatic Cancer Patients (EORTC QLQ-PAN26), and Hospital Anxiety and Depression Scale (HADS). For carers, mental health is evaluated using HADS and satisfaction with care is evaluated using the Family Caregivers' Satisfaction With Palliative Care in Advanced Cancer Questionnaire (FAMCARE-2). The primary outcome is health care service use (acute hospital admissions, days in hospital). Secondary outcomes are survival and place of death. Data are compared with historical control patients treated in the same hospital before introduction of early palliative care. These outcomes are readily available from patient records and are expected to carry a very low risk of bias. Palliative care needs at referral in the study group will be compared with palliative care needs in the subgroup of historical control patients referred to palliative care on-demand. For outcomes where unbiased historical control data are not available a prospective observational approach is used. These include symptom burden, weight, psychological health and satisfaction with care. The minimum sample size needed to show a clinically significant decrease in acute hospital admissions is 70, 35 participating in the prospective study and 35 historical control patients. The study will include 40-50 patients and their carers from September 2019 to September 2020. Detailed Description ----------------- Study design All patients with symptoms compatible with pancreatic cancer living in the northern catchment area of the Capital Region of Copenhagen, Denmark, are referred to Dept. of Surgery, Hospital of North Zealand for further investigations. Cases diagnosed with pancreatic cancer are discussed at a regional Multi-Disciplinary-Team (MDT) conference and either referred for surgery or chemotherapy or receive best supportive care in Dept. of Surgery. The Palliative Care Unit at Hospital of North Zealand covers the same geographical area with 310,000 inhabitants. Patients referred to Dept. of Surgery and diagnosed with pancreatic cancer are offered participation in this study. All participants will receive home-visits from the palliative care team every four weeks, starting within three weeks from diagnosis and until end-of-life or cure without residual palliative needs. The study design chosen is a quasi-experimental design using historical control patients for the primary outcome: use of health care services (acute hospital admissions, days in hospital) and the secondary outcomes: survival and place of death. The historical control patients were diagnosed before the introduction of early palliative care. The outcomes are readily available from patient records and are expected to carry a very low risk of registration bias. Palliative care needs at referral in the study group will be compared with palliative care needs in the subgroup of historical control patients referred to palliative care on-demand. Demographic data will be collected for participants and historical controls to evaluate if any selection bias or other systematic differences exist between the groups. For outcomes where unbiased historical control data are not available a prospective observational approach is used. These include symptom burden, psychological health and satisfaction with care. The study will include 40-50 patients and their carers from September 2019 to September 2020. Recruitment and informed consent Recruitment to this project will take place in Dept. of Surgery, Hospital of North Zealand to which all patients suspected of having pancreatic cancer and living in the northern catchment area of the Capital Region of Copenhagen will be referred for further investigations. The patients will be informed about their diagnosis by the responsible surgeon in the outpatient clinic in an undisturbed environment. The patients will then be informed about the possibility of participation in the present study. They will receive both oral and written information about the project and will be allowed enough time to consider participation before deciding, as long as it allows contact to the palliative care team within three weeks from diagnosis. It is expected that most patients will come to Dept. of Surgery with a family member or friend, as they are aware that they will receive the results from the investigations performed. However, patients will be informed that they have a right to come back for further information about the protocol accompanied by a family member or any other person they want to bring. They will meet either a surgeon or a palliative care physician who can give further information and answer any possible questions at this meeting. Written informed consent will be obtained before any protocol related procedures are performed. Carers will receive separate oral and written information either on the same day as the patient or when meeting the palliative care team on the first visit. Carers will sign a separate consent form if they want to participate in the study. Carers have the same rights as the patients regarding time for consideration and further information before signing the consent form. Palliative Care Intervention Patients and carers will be seen on home-visits. The first time they will meet a doctor and usually also a nurse, while follow-up home-visits can be undertaken by either a doctor or a nurse. Home-visits are scheduled every four weeks. Patients can contact a doctor or a specialised nurse on weekdays for consultation. The palliative care nurse will contact a palliative care physician if needed for change of treatment or other reasons. Palliative care is offered in parallel with any specific cancer treatment given. The patients will receive standard palliative care including treatment of symptoms (e.g. pain, nausea, weight loss, loss of appetite, diarrhoea or fatigue), psychosocial support, physiotherapy, nutritional counselling and advance care planning, depending on their needs. The palliative care team comprises physicians, nurses, a physiotherapist and a chaplain. Patients and/or carers scoring 8 or more on HADS for anxiety and/or depression will be advised to be referred to a psychologist via their general practitioner. Change from standard of care Patients with pancreatic cancer are normally referred to palliative care when the surgeon, oncologist or general practitioner taking care of them find that they are not able to meet their palliative care needs, or if the patients and their families request a referral. Most patients are referred late in their trajectory and only half of the patients are referred. We do not know whether patients not referred to palliative care in the routine setting have palliative care needs, whether they are met by other physicians or whether they have unsolved palliative care needs. Patients accepting inclusion in the project will get specialised palliative care throughout their trajectory, within three weeks after diagnosis until end-of-life or cure without residual palliative care needs. Both patients participating in the project and patients referred on-demand will receive four-weekly visits in their homes. Patients participating in the project are guaranteed that the first visit will take place within three weeks after diagnosis, whereas patients referred on-demand might have to wait longer before they meet the palliative care team. Official Title ----------------- Early Palliative Care for Patients With Pancreatic Cancer - Health Care Service Use and Quality of Life - a Quasi-experimental Study Using Historical Controls Conditions ----------------- Pancreatic Cancer Intervention / Treatment ----------------- * Other: Palliative care Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Adults newly diagnosed with pancreatic cancer in Dept. of Surgery, Hospital of North Zealand, Denmark Caregivers involved in care or practical help Exclusion Criteria: Inability to take an active part in answering questionnaires Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Prospective cohort<br>Patients newly diagnosed with pancreatic cancer included in the prospective part of the study \| Other: Palliative care<br>* The patients in the prospective part of the study are seen on home-visits and offered standard palliative care within three weeks of diagnosis.<br>\| \| Retrospective cohort<br>Patients diagnosed with pancreatic cancer before early palliative care was introduced (historical control patients) \| \| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Use of healthcare services \| Number of acute hospital admissions and number of days in hospital \| Until death or end of study, an average of 8 months \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Survival \| Survival \| Until death or end of study, an average of 8 months \| \| Quality of life: EORTC QLQ-C15-PAL \| Quality of life measured using the questionnaire: EORTC QLQ-C15-PAL \| Four-weekly until death or end of study, an average of 8 months \| \| Quality of life: EORTC QLQ-PAN26 \| Quality of life measured using the questionnaire: EORTC QLQ-PAN26 \| Four-weekly until death or end of study, an average of 8 months \| \| Anxiety and/or depression \| Anxiety and/or depression measured using the questionnaire: HADS \| Four-weekly until death or end of study, an average of 8 months \| \| Change in weight \| Weight in kilos \| Four-weekly until death or end of study, an average of 8 months \| \| Preferred and actual place of death \| Advance care planning (where patients prefer to die) and the actual place of death \| Until death or end of study, an average of 8 months \| \| Carer satisfaction with palliative care \| Carer satisfaction with palliative care measured using the questionnaire: FAMCARE-2 \| Three-monthly. The last time is at a follow-up visit after the patient has died, or at end of study, an average of 10 months \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Palliative care
NCT04298801	Does the Implementation of Nurse-driven HIV Screening for Key Populations in the Emergency Departments Limit Undiagnosed Infections in the Paris Metropolitan Area? DEPIST Trial (ANRS 14055)	In France, 40% of newly diagnosed HIV infections are concentrated in the Paris metropolitan area.~Two key populations are mainly concerned: persons born in a foreign country and men who have sex with men. The randomized trial ANRS DICI-VIH (2014-2015) showed that nurse-driven HIV screening for key populations, supported by research staff, in 8 emergency departments (EDs) of the region, was effective in addition to diagnostic testing. The strategy advocated by the WHO and the recent French recommendations support the proposal of screening for key populations in the EDs. Thus, it is important to evaluate the impact and the feasibility of the implementation of this strategy on a large scale.~The aim is to evaluate the impact of a wide implementation of nurse-driven HIV screening by rapid test in key populations combined with usual physician-directed diagnostic testing (intervention strategy) compared to diagnostic testing alone (control strategy) in the usual practice of the EDs.~The strategies will be compared during two periods in 18 EDs of Paris metropolitan area following a stepped-wedge cluster randomized trial.~During intervention period, nurses will suggest performing an HIV rapid test to patients belonging to key populations according to the answers to a self-administered questionnaire.	Background:~In France, 40% of newly diagnosed HIV infections are concentrated in the Paris metropolitan area.~Two key populations are mainly concerned: persons born in a foreign country and men who have sex with men. The randomized trial ANRS DICI-VIH (2014-2015) showed that nurse-driven HIV screening for key populations, supported by research staff, in 8 emergency departments (EDs) of the region, was effective in addition to diagnostic testing. The strategy advocated by the WHO and the recent French recommendations of the National Health Authority (HAS) and expert group support the proposal of screening for key populations in the EDs. Thus, it is important to evaluate the impact and the feasibility of the implementation of this strategy on a large scale in a context where local institutions are taking initiatives to curb the epidemic (Pour une Ile-de-France sans sida, Vers Paris sans sida).~Our hypothesis is that nurse-driven HIV screening for key populations can be integrated to the consultants' care pathway as usual practice of the ED and assured over the long term in the Paris metropolitan area; this strategy combined with physician-directed diagnostic testing could reduce undiagnosed infections and help control the epidemic.~Primary objective:~The primary objective is to evaluate the impact of a wide implementation of nurse-driven HIV screening by rapid test in key populations combined with usual physician-directed diagnostic testing (intervention strategy) compared to diagnostic testing alone (control strategy) in the usual practice of the EDs.~Patients aged 18 to 64 years and visiting a participating ED for reasons other than a potential exposure to HIV within less than 48 hours will be included.~The primary outcome is the proportion of new HIV diagnoses among included patients.~Secondary objectives are to :~evaluate the feasibility of nurse-driven screening and its long-term implementation,~evaluate the effectiveness of the screening process used by the caregivers, particularly the use of an electronic questionnaire, and by the patients as well as the acceptability,~compare newly diagnosed HIV+ patients in the two groups in terms of :~linkage to follow up care,~proportions of patients who had a CD4 cell count greater or equal to 500 or 350 cells/µL and no HIV-related symptoms and proportions of patients with acute HIV infection.~estimate through modelling the number of new HIV diagnoses for different levels of coverage of the screening strategy in the Paris metropolitan area.~Methods The strategies will be compared in 18 EDs of Paris metropolitan area during two periods. The start of the intervention strategy will be randomly allocated for each ED following a stepped-wedge cluster randomized trial.~EDs are selected according to the proportion of patients belonging to key populations in the patients they receive (data from two previous studies).~During intervention period, nurses will suggest performing an HIV rapid test to patients belonging to key populations according to the answers to a self-administered questionnaire.~The intervention period will last 3 to 11 months and the control period 0 to 8 months. Patients will participate up to 1 month if a follow-up is needed.	Does the Implementation of Nurse-driven HIV Screening for Key Populations in the Emergency Departments Limit Undiagnosed Infections in the Paris Metropolitan Area?	Hiv, Nurse's Role	* Procedure: Nurse-driven HIV screening for key populations combined with usual physician-directed diagnostic testing * Other: Physician-directed diagnostic testing	Inclusion Criteria:~- Patients aged 18 to 64 years and visiting a participating ED for reasons other than a potential exposure to HIV within less than 48 hours~Exclusion Criteria:~- Not applicable	18 Years	64 Years	All	No	Primary Purpose: Screening Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Proportion of new HIV diagnoses among included patients. \| \| At the end of the expected total duration of the inclusion period: 11 months in each ED \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Feasibility of the screening strategy and its implementation \| Feasibility of the screening strategy and its implementation based on:~proportion of distributed and completed self-administered questionnaires among the patients included and among the patients able to participate who were not known to be HIV positive,~the proportion of rapid tests offered by nurses among patients belonging to key populations,~the proportion of patients screened by nurses among patients who were offered a rapid test and among patients belonging to high-risk groups . \| At the end of the expected total duration of the inclusion period: 11 months in each ED \| \| Effectiveness of the screening processes used by the caregivers, particularly the integration of the electronic questionnaire, and used by the patients as well as acceptability \| \| At the end of the expected total duration of the inclusion period: 11 months in each ED \| \| Proportions of patients with a new diagnosis \| Proportions of patients with a new diagnosis who had:~a follow up visit with an infectious disease specialist within 1 month,~a CD4 cell count greater or equal to 500 or 350/µL and no HIV-related symptoms,~an acute HIV infection. \| At the end of the expected total duration of the inclusion period: 11 months in each ED \| \| Estimation through modelling of the number of new HIV diagnoses for different levels of coverage of the screening strategy in the Paris metropolitan area. \| \| At the end of the expected total duration of the inclusion period: 11 months in each ED \|	Emergency service, Hospital, HIV, Mass screening, Nurses, Prevention and control, Key populations, Targeted screening	Emergencies, Disease Attributes, Pathologic Processes	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Nurse-driven HIV screening for key populations+UD<br>Nurse-driven HIV screening for key populations combined with usual physician-directed diagnostic testing (UD) \| Procedure: Nurse-driven HIV screening for key populations combined with usual physician-directed diagnostic testing<br>* A self-administered questionnaire on HIV exposure factors will be offered to all patients of ages 18-64 able to complete it. This questionnaire will be available in a paper-based format, electronic format on the patient phone or can be conducted verbally by the nurse. According to the answers, the nurses will suggest performing a rapid test to patients belonging to key populations. A finger-stick rapid HIV test will be performed and results will be disclosed by the nurse assisted by a physician if necessary.~If needed, a follow-up visit with an infectious disease specialist will be scheduled within 72 hours.<br>Other: Physician-directed diagnostic testing<br>* Throughout the intervention, physicians will prescribe HIV tests to patients with HIV-related symptoms, following usual practice.<br>\| \| Active Comparator: Physician-directed diagnostic testing alone<br> \| Other: Physician-directed diagnostic testing<br>* Throughout the intervention, physicians will prescribe HIV tests to patients with HIV-related symptoms, following usual practice.<br>\|	Does the Implementation of Nurse-driven HIV Screening for Key Populations in the Emergency Departments Limit Undiagnosed Infections in the Paris Metropolitan Area? DEPIST Trial (ANRS 14055) Study Overview ================= Brief Summary ----------------- In France, 40% of newly diagnosed HIV infections are concentrated in the Paris metropolitan area. Two key populations are mainly concerned: persons born in a foreign country and men who have sex with men. The randomized trial ANRS DICI-VIH (2014-2015) showed that nurse-driven HIV screening for key populations, supported by research staff, in 8 emergency departments (EDs) of the region, was effective in addition to diagnostic testing. The strategy advocated by the WHO and the recent French recommendations support the proposal of screening for key populations in the EDs. Thus, it is important to evaluate the impact and the feasibility of the implementation of this strategy on a large scale. The aim is to evaluate the impact of a wide implementation of nurse-driven HIV screening by rapid test in key populations combined with usual physician-directed diagnostic testing (intervention strategy) compared to diagnostic testing alone (control strategy) in the usual practice of the EDs. The strategies will be compared during two periods in 18 EDs of Paris metropolitan area following a stepped-wedge cluster randomized trial. During intervention period, nurses will suggest performing an HIV rapid test to patients belonging to key populations according to the answers to a self-administered questionnaire. Detailed Description ----------------- Background: In France, 40% of newly diagnosed HIV infections are concentrated in the Paris metropolitan area. Two key populations are mainly concerned: persons born in a foreign country and men who have sex with men. The randomized trial ANRS DICI-VIH (2014-2015) showed that nurse-driven HIV screening for key populations, supported by research staff, in 8 emergency departments (EDs) of the region, was effective in addition to diagnostic testing. The strategy advocated by the WHO and the recent French recommendations of the National Health Authority (HAS) and expert group support the proposal of screening for key populations in the EDs. Thus, it is important to evaluate the impact and the feasibility of the implementation of this strategy on a large scale in a context where local institutions are taking initiatives to curb the epidemic (Pour une Ile-de-France sans sida, Vers Paris sans sida). Our hypothesis is that nurse-driven HIV screening for key populations can be integrated to the consultants' care pathway as usual practice of the ED and assured over the long term in the Paris metropolitan area; this strategy combined with physician-directed diagnostic testing could reduce undiagnosed infections and help control the epidemic. Primary objective: The primary objective is to evaluate the impact of a wide implementation of nurse-driven HIV screening by rapid test in key populations combined with usual physician-directed diagnostic testing (intervention strategy) compared to diagnostic testing alone (control strategy) in the usual practice of the EDs. Patients aged 18 to 64 years and visiting a participating ED for reasons other than a potential exposure to HIV within less than 48 hours will be included. The primary outcome is the proportion of new HIV diagnoses among included patients. Secondary objectives are to : evaluate the feasibility of nurse-driven screening and its long-term implementation, evaluate the effectiveness of the screening process used by the caregivers, particularly the use of an electronic questionnaire, and by the patients as well as the acceptability, compare newly diagnosed HIV+ patients in the two groups in terms of : linkage to follow up care, proportions of patients who had a CD4 cell count greater or equal to 500 or 350 cells/µL and no HIV-related symptoms and proportions of patients with acute HIV infection. estimate through modelling the number of new HIV diagnoses for different levels of coverage of the screening strategy in the Paris metropolitan area. Methods The strategies will be compared in 18 EDs of Paris metropolitan area during two periods. The start of the intervention strategy will be randomly allocated for each ED following a stepped-wedge cluster randomized trial. EDs are selected according to the proportion of patients belonging to key populations in the patients they receive (data from two previous studies). During intervention period, nurses will suggest performing an HIV rapid test to patients belonging to key populations according to the answers to a self-administered questionnaire. The intervention period will last 3 to 11 months and the control period 0 to 8 months. Patients will participate up to 1 month if a follow-up is needed. Official Title ----------------- Does the Implementation of Nurse-driven HIV Screening for Key Populations in the Emergency Departments Limit Undiagnosed Infections in the Paris Metropolitan Area? Conditions ----------------- Hiv, Nurse's Role Intervention / Treatment ----------------- * Procedure: Nurse-driven HIV screening for key populations combined with usual physician-directed diagnostic testing * Other: Physician-directed diagnostic testing Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: - Patients aged 18 to 64 years and visiting a participating ED for reasons other than a potential exposure to HIV within less than 48 hours Exclusion Criteria: - Not applicable Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 64 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Screening Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Nurse-driven HIV screening for key populations+UD<br>Nurse-driven HIV screening for key populations combined with usual physician-directed diagnostic testing (UD) \| Procedure: Nurse-driven HIV screening for key populations combined with usual physician-directed diagnostic testing<br>* A self-administered questionnaire on HIV exposure factors will be offered to all patients of ages 18-64 able to complete it. This questionnaire will be available in a paper-based format, electronic format on the patient phone or can be conducted verbally by the nurse. According to the answers, the nurses will suggest performing a rapid test to patients belonging to key populations. A finger-stick rapid HIV test will be performed and results will be disclosed by the nurse assisted by a physician if necessary. If needed, a follow-up visit with an infectious disease specialist will be scheduled within 72 hours.<br>Other: Physician-directed diagnostic testing<br>* Throughout the intervention, physicians will prescribe HIV tests to patients with HIV-related symptoms, following usual practice.<br>\| \| Active Comparator: Physician-directed diagnostic testing alone<br> \| Other: Physician-directed diagnostic testing<br>* Throughout the intervention, physicians will prescribe HIV tests to patients with HIV-related symptoms, following usual practice.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Proportion of new HIV diagnoses among included patients. \| \| At the end of the expected total duration of the inclusion period: 11 months in each ED \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Feasibility of the screening strategy and its implementation \| Feasibility of the screening strategy and its implementation based on: proportion of distributed and completed self-administered questionnaires among the patients included and among the patients able to participate who were not known to be HIV positive, the proportion of rapid tests offered by nurses among patients belonging to key populations, the proportion of patients screened by nurses among patients who were offered a rapid test and among patients belonging to high-risk groups . \| At the end of the expected total duration of the inclusion period: 11 months in each ED \| \| Effectiveness of the screening processes used by the caregivers, particularly the integration of the electronic questionnaire, and used by the patients as well as acceptability \| \| At the end of the expected total duration of the inclusion period: 11 months in each ED \| \| Proportions of patients with a new diagnosis \| Proportions of patients with a new diagnosis who had: a follow up visit with an infectious disease specialist within 1 month, a CD4 cell count greater or equal to 500 or 350/µL and no HIV-related symptoms, an acute HIV infection. \| At the end of the expected total duration of the inclusion period: 11 months in each ED \| \| Estimation through modelling of the number of new HIV diagnoses for different levels of coverage of the screening strategy in the Paris metropolitan area. \| \| At the end of the expected total duration of the inclusion period: 11 months in each ED \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Emergency service, Hospital, HIV, Mass screening, Nurses, Prevention and control, Key populations, Targeted screening
NCT03331185	Changes of Soft and Hard Tissues After Alveolar Ridge Preservation: Freeze-dried Bone Allograft vs. L-PRF Clot	A Clinical Trial to study the effectiveness between two, tooth socket grafting materials namely, Freeze Dried Bone Allograft (human derived bone particles) and Leukocytic-Platelet Rich Fibrin (the patient's own centrifuged blood).~The purpose of this study is to compare the effects (good and bad) of Bone Allograft to Platelet Rich Fibrin to see which material would be the most effective in maintaining the volume of the gum and bone of the jaw during the healing phase as well as minimizing the amount of pain and/or swelling following tooth extraction.	A prospective,randomized clinical trial will be conducted to determine whether L-PRF, compared to freeze dried bone allograft, will result in comparable volumetric shrinkage of the alveolar ridge and overlying keratinized tissue, following extraction of teeth and socket grafting.~This trial aims at obtaining information to determine which material would provide a superior clinical result, as well as reporting on patient related outcomes. The participants will be randomly assigned to two groups. The surgical procedure will be performed by one of five calibrated periodontal residents.~Patients will be followed for 2 weeks post-operatively by the same resident, to monitor the healing process and to assess for any complications.~Randomization will be achieved using a computerized randomization scheme and will be assigned to one of two groups and allocated by means of a sealed envelope opened on the day of surgery communicated to the surgeon during the surgery by a supervising faculty member. Participants will be block-randomized for each of the 5 operators for balance.~Anesthesia will be achieved and soft tissue measurements will be obtained using a periodontal probe. An atraumatic extraction technique will be performed to allow for minimal disturbance of the soft and hard tissue architecture.~The extraction socket walls are then assessed and any defects in socket measured with a periodontal probe. Group A: Full thickness mucoperiosteal pouch is created up to ~3mm apical of the bony crest of the socket with a periosteal elevator. The socket is incrementally filled with mineralized cortical freeze-dried bone allograft and condensed. Group B: Socket is pouched as in group A followed by venipuncture of the antecubital vein with 21G needle and collection of 4-6 vials (10ml each) of venous blood without any additive or anticoagulant. The vials are centrifuged for 12 minutes at 2700 rpm to form L-PRF clots. The socket is incrementally filled with the clots and condensed.~Following socket fill, both groups will have the grafts covered by dense polytetrafluoroethylene membrane. The membrane is trimmed and adapted with the borders tucked 2-3mm underneath the gingival tissues. Tissues, graft and membrane are stabilized with 5/0 PTFE sutures.~The patients will also receive a pain VAS questionnaire evaluating the post-operative pain 1 and 7 days following surgery. A CBCT with the radiographic stent will be taken within 72 hours of the surgery.~7 days post-op: Sutures will be removed if deemed suitable. The VAS questionnaire will be collected.~6 weeks post op: d-PTFE membrane will be retrieved and discarded using tissue forceps. Alginate impressions will be taken for a surgical guide.~11 weeks post op: Second CBCT will be taken with radiographic surgical stent. Images obtained will be used to analyze and compare the ridge dimensions to those obtained at baseline as well as for surgical implant planning.~12 weeks post op: Soft tissue measurement with periodontal probe and floss spanned over edentulous site from buccal to lingual mucogingival junction. Implant placement will be done per standard procedure. A 2.5mm diameter trephine drill will be used to harvest a bone core for histologic analysis. The bone core will be immediately submerged in a solution of 10% neutral buffered formalin. Osteotomies and implant placement will be done following the manufacturer's protocol. Depending on the buccal bone and soft tissue thickness, ancillary soft tissue augmentation, bone augmentation or combination of these procedures may be indicated. The patient will be followed up and referred to the restorative dentist as per standard procedure. Photographs will be taken at every visit.	Dimensional Changes of Soft and Hard Tissues Following Alveolar Ridge Preservation: Freeze-dried Bone Allograft vs. L-PRF Clot Covered With d-PTFE Membrane: A Randomized Clinical Trial	Alveolar Bone Loss, Tooth Loss	* Biological: Freeze Dried Bone Allograft * Biological: L-PRF clot	Inclusion Criteria:~Subjects with molars or premolars indicated for extraction.~Patients that present with a post extraction class I and II socket (<30% bone loss on the buccal or lingual plate, measured from the most coronal aspect of intact bone to the most apical aspect of the defect divided by the measurement from the most apical aspect of the defect to the apex of the socket x 100).~Patients presenting with the need for single extractions.~Patients with general good health that does not have a condition contra-indicating routine dental treatment, extraction and implant placement.~Patients that are compliant with the research protocol and methods.~Patients that have read, understood and signed an informed consent form.~Exclusion Criteria:~Extraction and ridge preservation indicated for teeth other than premolars and molars.~Patients that present with a post extraction class III socket (>30% bone loss on the buccal or lingual plate, measured from the most coronal aspect of intact bone to the most apical aspect of the defect divided by the measurement from the most apical aspect of the defect to the apex of the socket x 100)~Patients deemed eligible for immediate implant placement following extraction and intra-operative assessment by the attending supervisor.~Patients that present with an oral-antral communication, post extraction.~Patients that presents with the need for multiple, side by side extractions.~Patients with coagulation disorders, on corticosteroids, uncontrolled diabetes mellitus, or any systemic disease where periodontal surgery is contraindicated and healing may be compromised.~Pregnant and nursing women.~Patients with any contact hypersensitivity to the related materials used in the study.~Heavy tobacco users, >10 cigarettes per day.~Patients unwilling to sign consent or follow the protocol of the study.	22 Years	null	All	Accepts Healthy Volunteers	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: A prospective,randomized clinical trial will be conducted. The trial aims at obtaining information to determine which material would provide a superior clinical result, as well as reporting on patient related outcomes. 42 participants will be randomly assigned to two groups and a direct comparison will be made between the results obtained from the two groups. Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Overall Horizontal Change in Alveolar Ridge Width \| Calculated mean of post operative CBCT measurements of horizontal alveolar bone width changes following extraction and alveolar ridge preservation. \| Difference reported on horizontal changes comparing CBCT analysis 11weeks after extraction and grafting compared to CBCT following extraction and grafting \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Buccolingual Change in Width of Keratinized Soft Tissue \| Difference in post operative measurement analysis of keratinized gingiva changes following extraction and alveolar ridge preservation \| Soft tissue measurement at time of extraction and grafting and 12 weeks after extraction and grafting \| \| Post-operative Pain and Swelling \| Post-operative pain and complications measured by VAS-questionnaire obtained following extraction and grafting. The VAS-questionnaire contained the following categories to be answered 7days post-operatively: Pain, Swelling. A visual line scale of 100mm in length was provided with no pain/swelling on the one end and severe pain/swelling on the opposite end. Participants were instructed to rate their pain and swelling by marking a single line on the scale indicating the degree of pain/swelling they experienced. Markings were physically measured on the scale and converted into a score with 0 representing no pain/swelling and 1 representing severe pain/swelling. \| Measured at 7 days following extraction and grafting \|	Extraction, Alveolar Ridge Augmentation, Freeze Dried Bone Allograft, Leukocytic Platelet Rich Fibrin, Volumetric Changes, Dense Polytetrafluoroethylene Membrane	Alveolar Bone Loss, Tooth Loss, Bone Resorption, Bone Diseases, Musculoskeletal Diseases, Periodontal Atrophy, Periodontal Diseases, Mouth Diseases, Stomatognathic Diseases, Tooth Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Freeze Dried Bone Allograft<br>Socket filled with Mineralized Cortical Freeze Dried Bone Allograft \| Biological: Freeze Dried Bone Allograft<br>* Human derived bone particles used in oral and periodontal grafting procedures<br>* Other names: FDBA;\| \| Experimental: L-PRF Clot<br>Socket filled with L-PRF Clot \| Biological: L-PRF clot<br>* L-PRF is a second-generation platelet rich plasma obtained from autologous blood and contains several different growth factors, platelets and leucocytes in a complex fibrin matrix to accelerate the healing of soft and hard tissues.<br>* Other names: Leukocytic Platelet Rich Fibrin Clot;\|	Changes of Soft and Hard Tissues After Alveolar Ridge Preservation: Freeze-dried Bone Allograft vs. L-PRF Clot Study Overview ================= Brief Summary ----------------- A Clinical Trial to study the effectiveness between two, tooth socket grafting materials namely, Freeze Dried Bone Allograft (human derived bone particles) and Leukocytic-Platelet Rich Fibrin (the patient's own centrifuged blood). The purpose of this study is to compare the effects (good and bad) of Bone Allograft to Platelet Rich Fibrin to see which material would be the most effective in maintaining the volume of the gum and bone of the jaw during the healing phase as well as minimizing the amount of pain and/or swelling following tooth extraction. Detailed Description ----------------- A prospective,randomized clinical trial will be conducted to determine whether L-PRF, compared to freeze dried bone allograft, will result in comparable volumetric shrinkage of the alveolar ridge and overlying keratinized tissue, following extraction of teeth and socket grafting. This trial aims at obtaining information to determine which material would provide a superior clinical result, as well as reporting on patient related outcomes. The participants will be randomly assigned to two groups. The surgical procedure will be performed by one of five calibrated periodontal residents. Patients will be followed for 2 weeks post-operatively by the same resident, to monitor the healing process and to assess for any complications. Randomization will be achieved using a computerized randomization scheme and will be assigned to one of two groups and allocated by means of a sealed envelope opened on the day of surgery communicated to the surgeon during the surgery by a supervising faculty member. Participants will be block-randomized for each of the 5 operators for balance. Anesthesia will be achieved and soft tissue measurements will be obtained using a periodontal probe. An atraumatic extraction technique will be performed to allow for minimal disturbance of the soft and hard tissue architecture. The extraction socket walls are then assessed and any defects in socket measured with a periodontal probe. Group A: Full thickness mucoperiosteal pouch is created up to 3mm apical of the bony crest of the socket with a periosteal elevator. The socket is incrementally filled with mineralized cortical freeze-dried bone allograft and condensed. Group B: Socket is pouched as in group A followed by venipuncture of the antecubital vein with 21G needle and collection of 4-6 vials (10ml each) of venous blood without any additive or anticoagulant. The vials are centrifuged for 12 minutes at 2700 rpm to form L-PRF clots. The socket is incrementally filled with the clots and condensed. Following socket fill, both groups will have the grafts covered by dense polytetrafluoroethylene membrane. The membrane is trimmed and adapted with the borders tucked 2-3mm underneath the gingival tissues. Tissues, graft and membrane are stabilized with 5/0 PTFE sutures. The patients will also receive a pain VAS questionnaire evaluating the post-operative pain 1 and 7 days following surgery. A CBCT with the radiographic stent will be taken within 72 hours of the surgery. 7 days post-op: Sutures will be removed if deemed suitable. The VAS questionnaire will be collected. 6 weeks post op: d-PTFE membrane will be retrieved and discarded using tissue forceps. Alginate impressions will be taken for a surgical guide. 11 weeks post op: Second CBCT will be taken with radiographic surgical stent. Images obtained will be used to analyze and compare the ridge dimensions to those obtained at baseline as well as for surgical implant planning. 12 weeks post op: Soft tissue measurement with periodontal probe and floss spanned over edentulous site from buccal to lingual mucogingival junction. Implant placement will be done per standard procedure. A 2.5mm diameter trephine drill will be used to harvest a bone core for histologic analysis. The bone core will be immediately submerged in a solution of 10% neutral buffered formalin. Osteotomies and implant placement will be done following the manufacturer's protocol. Depending on the buccal bone and soft tissue thickness, ancillary soft tissue augmentation, bone augmentation or combination of these procedures may be indicated. The patient will be followed up and referred to the restorative dentist as per standard procedure. Photographs will be taken at every visit. Official Title ----------------- Dimensional Changes of Soft and Hard Tissues Following Alveolar Ridge Preservation: Freeze-dried Bone Allograft vs. L-PRF Clot Covered With d-PTFE Membrane: A Randomized Clinical Trial Conditions ----------------- Alveolar Bone Loss, Tooth Loss Intervention / Treatment ----------------- * Biological: Freeze Dried Bone Allograft * Biological: L-PRF clot Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Subjects with molars or premolars indicated for extraction. Patients that present with a post extraction class I and II socket (<30% bone loss on the buccal or lingual plate, measured from the most coronal aspect of intact bone to the most apical aspect of the defect divided by the measurement from the most apical aspect of the defect to the apex of the socket x 100). Patients presenting with the need for single extractions. Patients with general good health that does not have a condition contra-indicating routine dental treatment, extraction and implant placement. Patients that are compliant with the research protocol and methods. Patients that have read, understood and signed an informed consent form. Exclusion Criteria: Extraction and ridge preservation indicated for teeth other than premolars and molars. Patients that present with a post extraction class III socket (>30% bone loss on the buccal or lingual plate, measured from the most coronal aspect of intact bone to the most apical aspect of the defect divided by the measurement from the most apical aspect of the defect to the apex of the socket x 100) Patients deemed eligible for immediate implant placement following extraction and intra-operative assessment by the attending supervisor. Patients that present with an oral-antral communication, post extraction. Patients that presents with the need for multiple, side by side extractions. Patients with coagulation disorders, on corticosteroids, uncontrolled diabetes mellitus, or any systemic disease where periodontal surgery is contraindicated and healing may be compromised. Pregnant and nursing women. Patients with any contact hypersensitivity to the related materials used in the study. Heavy tobacco users, >10 cigarettes per day. Patients unwilling to sign consent or follow the protocol of the study. Ages Eligible for Study ----------------- Minimum Age: 22 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: A prospective,randomized clinical trial will be conducted. The trial aims at obtaining information to determine which material would provide a superior clinical result, as well as reporting on patient related outcomes. 42 participants will be randomly assigned to two groups and a direct comparison will be made between the results obtained from the two groups. Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Active Comparator: Freeze Dried Bone Allograft<br>Socket filled with Mineralized Cortical Freeze Dried Bone Allograft \| Biological: Freeze Dried Bone Allograft<br>* Human derived bone particles used in oral and periodontal grafting procedures<br>* Other names: FDBA;\| \| Experimental: L-PRF Clot<br>Socket filled with L-PRF Clot \| Biological: L-PRF clot<br>* L-PRF is a second-generation platelet rich plasma obtained from autologous blood and contains several different growth factors, platelets and leucocytes in a complex fibrin matrix to accelerate the healing of soft and hard tissues.<br>* Other names: Leukocytic Platelet Rich Fibrin Clot;\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Overall Horizontal Change in Alveolar Ridge Width \| Calculated mean of post operative CBCT measurements of horizontal alveolar bone width changes following extraction and alveolar ridge preservation. \| Difference reported on horizontal changes comparing CBCT analysis 11weeks after extraction and grafting compared to CBCT following extraction and grafting \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Buccolingual Change in Width of Keratinized Soft Tissue \| Difference in post operative measurement analysis of keratinized gingiva changes following extraction and alveolar ridge preservation \| Soft tissue measurement at time of extraction and grafting and 12 weeks after extraction and grafting \| \| Post-operative Pain and Swelling \| Post-operative pain and complications measured by VAS-questionnaire obtained following extraction and grafting. The VAS-questionnaire contained the following categories to be answered 7days post-operatively: Pain, Swelling. A visual line scale of 100mm in length was provided with no pain/swelling on the one end and severe pain/swelling on the opposite end. Participants were instructed to rate their pain and swelling by marking a single line on the scale indicating the degree of pain/swelling they experienced. Markings were physically measured on the scale and converted into a score with 0 representing no pain/swelling and 1 representing severe pain/swelling. \| Measured at 7 days following extraction and grafting \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Extraction, Alveolar Ridge Augmentation, Freeze Dried Bone Allograft, Leukocytic Platelet Rich Fibrin, Volumetric Changes, Dense Polytetrafluoroethylene Membrane
NCT03013621	Venous Congestion and Acute Renal Failure in Cardiac Surgery Postoperative	Acute renal failure (ARF) is a frequent complication in the postoperative cardiac surgery, and is a major risk factor for mortality in this context.~The right ventricular dysfunction post cardiopulmonary bypass (CPB) is also a common complication, close to 100% if one takes into account the transient dysfunction.~A recent study showed that right ventricular dysfunction and the IRA seemed related, rather on the slope of venous congestion. We wish to study this phenomenon more specifically in particular to offer reliable diagnostic markers of venous congestion.		Venous Congestion and Acute Renal Failure in Cardiac Surgery Postoperative (COVD)	Acute Renal Failure (ARF)		Inclusion Criteria:~Age: all major patient~Gender: both~Subject has signed an informed consent~IRA KDIGO stage 1 or urine output <0.5 mL / kg / h for at least 6 hours / elevation creat> 26.5μmol / L~Patient in sinus rhythm at the time of the ultrasound measurements~No diuretic since intervention~Absence of circulatory failure (low doses of catecholamines tolerated)~Extubated: absence of mechanical ventilation~Exclusion Criteria:~Chronic heart failure right~Chronic renal failure (GFR <60)~Usual treatment with high dose diuretics (furosemide> 40mg / day)~Endocarditis~Emergency surgery (aortic dissection, emergency bypass surgery) / heart surgery D / redux~Circulatory Support~ACFA / electro-paced rhythm~Inability to give informed about information (subject in emergencies, understanding of the subject of difficulty, ...)~Topic under judicial protection~Topic guardianship or curatorship~Pregnancy (women of childbearing age)~Breastfeeding	18 Years	null	All	No		\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Quantification of sonographic markers of right ventricular \| \| 1 hour after cardiac surgery \|		Renal Failure, Renal Insufficiency, Acute Renal Failure, Acute Renal Injury, Kidney Failure, Kidney Insufficiency, Acute Kidney Failure, Acute Kidney Injury, Ventricular dysfunction, Venous congestion, Renal function, Kidney function, Venous heart failure	Renal Insufficiency, Acute Kidney Injury, Hyperemia, Kidney Diseases, Urologic Diseases, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Male Urogenital Diseases, Vascular Diseases, Cardiovascular Diseases		Venous Congestion and Acute Renal Failure in Cardiac Surgery Postoperative Study Overview ================= Brief Summary ----------------- Acute renal failure (ARF) is a frequent complication in the postoperative cardiac surgery, and is a major risk factor for mortality in this context. The right ventricular dysfunction post cardiopulmonary bypass (CPB) is also a common complication, close to 100% if one takes into account the transient dysfunction. A recent study showed that right ventricular dysfunction and the IRA seemed related, rather on the slope of venous congestion. We wish to study this phenomenon more specifically in particular to offer reliable diagnostic markers of venous congestion. Official Title ----------------- Venous Congestion and Acute Renal Failure in Cardiac Surgery Postoperative (COVD) Conditions ----------------- Acute Renal Failure (ARF) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age: all major patient Gender: both Subject has signed an informed consent IRA KDIGO stage 1 or urine output <0.5 mL / kg / h for at least 6 hours / elevation creat> 26.5μmol / L Patient in sinus rhythm at the time of the ultrasound measurements No diuretic since intervention Absence of circulatory failure (low doses of catecholamines tolerated) Extubated: absence of mechanical ventilation Exclusion Criteria: Chronic heart failure right Chronic renal failure (GFR <60) Usual treatment with high dose diuretics (furosemide> 40mg / day) Endocarditis Emergency surgery (aortic dissection, emergency bypass surgery) / heart surgery D / redux Circulatory Support ACFA / electro-paced rhythm Inability to give informed about information (subject in emergencies, understanding of the subject of difficulty, ...) Topic under judicial protection Topic guardianship or curatorship Pregnancy (women of childbearing age) Breastfeeding Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Quantification of sonographic markers of right ventricular \| \| 1 hour after cardiac surgery \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Renal Failure, Renal Insufficiency, Acute Renal Failure, Acute Renal Injury, Kidney Failure, Kidney Insufficiency, Acute Kidney Failure, Acute Kidney Injury, Ventricular dysfunction, Venous congestion, Renal function, Kidney function, Venous heart failure
NCT03317184	Hand-assisted Laparoscopic Donor Nephrectomy Periumbilical Versus Pfannenstiel Incision	Despite efforts to optimize the transplantation of deceased donor kidneys, the number of available kidneys continues to fall short of the demand. Living donor kidneys have been used to overcome this shortage. Graft and patient survival is significantly higher following living donor kidney transplantation compared with deceased donor kidney transplantation. Open donor nephrectomy was the universal technique prior to the advent of laparoscopic techniques. Laparoscopic approaches have definite advantages over open surgery in terms of blood loss, postoperative pain, analgesic requirements, duration of hospital stay, and convalescence. There is some controversy regarding longer warm ischemia time, longer operative time, and increased bleeding with laparoscopic nephrectomy compared with hand-assisted laparoscopic living donor nephrectomy (HALDN). HALDN attempted to reduce warm ischemia time by using the hand port to extract the kidney instantly after dividing the blood vessels. This technique also offers tactile feedback, better manual control of bleeding, a relatively shorter learning curve, less kidney traction, faster kidney removal, and shorter warm ischemic periods. HALDN is often performed using periumbilical and Pfannenstiel incisions for hand-assisted port placement. Pfannenstiel incisions improve wound complications such as incisional hernia, cosmetic issues, and wound dehiscence. However, duration of surgery, postoperative pain score, and length of hospital stay are significantly lower in donors with periumbilical incisions.To the best of our knowledge, these two types of incision have not been compared in a randomized controlled trial in patients undergoing HALDN. Our objective is to compare the results of Pfannenstiel incision (intervention group) with periumbilical incision (control group). The return to normal physical activity will be evaluated in a clinical randomized trial using an expertise-based design.	Despite all efforts to optimize the transplantation of deceased donor kidneys, the number of available kidneys continues to fall short of demand. Living donor kidneys have been used to overcome this organ shortage. Graft and patient survival is significantly higher following living donor kidney transplantation compared with deceased donor kidney Transplantation.~The major disadvantage of using living donors is that a healthy individual must undergo a major surgical procedure to provide the organ for transplantation. The donor does not medically benefit from the procedure, but there is a medical impact on both donor and recipient. Therefore, a nephrectomy technique associated with the lowest donor risk and the best organ quality should be used during Transplantation.~Open donor nephrectomy was the universal technique before the advent of laparoscopic techniques. Laparoscopic living donor nephrectomy was introduced in 1995 and commercial ports were developed shortly after. In 1998, Wolf et al. described the hand-assisted laparoscopic living donor nephrectomy (HALDN) technique and since then it has become widely adopted. Laparoscopic methods have definite advantages over open surgery in terms of blood loss, postoperative pain, analgesic requirements, duration of hospital stay, and convalescence.~There is some controversy regarding the possibility of relatively longer warm ischemia time, longer operative time, and increased bleeding with laparoscopic nephrectomy. HALDN reduces warm ischemia time by extracting the kidney using the hand port as soon as the blood vessels are divided. This technique is associated with tactile feedback, better manual control of bleeding, relatively shorter learning curve, less kidney traction, faster kidney removal, and shorter warm ischemic periods. At present, there is no strong evidence to support the use of one laparoscopic approach in preference to the other. However, evidence suggests that HALDN is the most cost-effective method of donor surgery and achieves equivalent clinical benefits of pure laparoscopic approaches with less operative time.~HALDN is usually performed using a periumbilical or Pfannenstiel incision for hand-assisted port placement and kidney extraction. A periumbilical incision is made at the midline. In contrast, a Pfannenstiel incision is made as a slightly curved horizontal line just above the pubic symphysis. Pfannenstiel incisions improve wound complications, such as incisional hernia, cosmetic results, and wound dehiscence. However, the duration of surgery, postoperative pain score, and length of hospital stay were significantly lower in donors with periumbilical incision. The inserted hand plays a vital role in the procedure, including retraction and dissection, therefore the hand port midline incision is placed close to the periumbilical area. Dissecting the upper pole of the kidney through a Pfannenstiel incision may be difficult in morbidly obese and large donors.~Patients with Pfannenstiel incisions return to normal physical activity quicker than those with periumbilical incisions. However, to the best of our knowledge, these two different incision types in patients undergoing HALDN have not been compared in a randomized controlled trial.Our objective is to compare the return of patients to physical activity following a HALDN procedure with Pfannenstiel incision (intervention group) or periumbilical incision (control group) in a clinical randomized trial using an expertise-based design.	Hand-Assisted Laparoscopic Donor Nephrectomy PERiumbilical Versus Pfannenstiel Incision and Return to Normal Physical ACTivity: A Randomized Clinical Trial: HAPERPACT Trial	Donor Nephrectomy	* Procedure: Periumbilical incision * Procedure: Pfannenstiel incision	Inclusion Criteria:~Age > 20 years~No permanent pain therapy~Kidneys with only a single artery and vein in the graft~Informed consent for participation provided~Exclusion Criteria:~Infection or scar present precluding incision placement at one of the randomization sites~Bleeding disorders~Chronic use of immunosuppressive agents (e.g. steroids)	20 Years	null	All	Accepts Healthy Volunteers	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Expertise-based, single intuition, assessor-blinded, randomized clinical trial. Masking: Double	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Days to return to normal physical activity \| Patients will be asked to complete the Katz basic activities of daily living self-maintenance questionnaire each day for 4 weeks after the operation. This questionnaire assesses the ability to perform daily living activities (0 = no activity and 6 = normal activity). The normal physical activity is perceived as good. \| Four weeks \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Warm ischemia time \| From the time of clamping of the first renal artery in situ to flushing of the kidney with chilled solution on the back table \| One day \| \| Intraoperative complications \| From skin incision to skin closure \| One day \| \| Estimated blood loss \| From skin incision to skin closure \| One day \| \| Operating time \| From skin incision to skin closure \| One day \| \| Postoperative pain \| Severity of pain via 11-point Visual Analogue Scale (0 = no pain and 10 = unbearable distress). \| Seven days \| \| Rescue analgesic \| Total amount of analgesics required. \| Seven days \| \| Peak expiratory flow rate \| Is defined as maximum speed of expiration, as measured with a peak flow meter. \| Seven days \| \| Postoperative complications \| According to the Clavien-Dindo classification \| 60 days \| \| Length of hospital stay \| From the day of the operation until the day of discharge \| 60 days \| \| Time to return to work \| From the day of discharge and return to work \| 60 days \| \| Physical activity score \| The International Physical Activity Questionnaire, Short Form (IPAQ) will be used as an indicator of physical activity and fitness. IPAQ assesses total physical activity in the previous 7 days. Questions measure the frequency (days per week) and duration (minutes per session) of physical activity, as well as its intensity level (vigorous, moderate, walking, or sitting). Participants are categorized into one of three physical activity levels (low, moderate, high). Range is not applicable because it is a categorical variable. The high activity category is perceived as good. \| 60 days \| \| Patient satisfaction \| Patient satisfaction score via 5-point Likert scale (5 = representing strongly satisfied and 1 = representing strongly unsatisfied). \| 60 days \| \| Cosmetic score \| As defined by the Stony Brook scar scale (SBSES). The SBSES assessed five scar components: width, height, color, suture marks and overall appearance. Each component was assigned a score of 0 or 1 with a total sum range of 0 (worst) to 5 (best). \| 60 days \| \| Incisional hernia \| Defined as a fascia or muscle defect (bulging hernial sac and palpable fascia gap) at the site of the surgical incision examined by palpation and ultrasonography. \| 60 days \| \| Mortality \| Death due to any cause. \| 60 days \| \| Recipient serum creatinine level \| Serum creatinine level (mg/dL) \| 30 days \| \| Glomerular filtration rate \| GFR (mL/min/1.73 m2) calculated with 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) Formula \| 30 days \| \| Delayed graft function \| Is defined as the need for one or more hemodialysis treatments following transplantation prior to the onset of graft function. \| 30 days \| \| Primary non-function \| A recipient whose graft never functions. \| 30 days \|	Physical Activity, Pfannenstiel incision, Periumbilical incision	Surgical Wound, Wounds and Injuries	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Periumbilical incisions<br> \| Procedure: Periumbilical incision<br>* A periumbilical incision is made at the abdominal midline for hand-assisted laparoscopic donor nephrectomy.<br>\| \| Experimental: Pfannenstiel incision<br> \| Procedure: Pfannenstiel incision<br>* Pfannenstiel incision is made as a slightly curved horizontal line just above the pubic symphysis for hand-assisted laparoscopic donor nephrectomy.<br>\|	Hand-assisted Laparoscopic Donor Nephrectomy Periumbilical Versus Pfannenstiel Incision Study Overview ================= Brief Summary ----------------- Despite efforts to optimize the transplantation of deceased donor kidneys, the number of available kidneys continues to fall short of the demand. Living donor kidneys have been used to overcome this shortage. Graft and patient survival is significantly higher following living donor kidney transplantation compared with deceased donor kidney transplantation. Open donor nephrectomy was the universal technique prior to the advent of laparoscopic techniques. Laparoscopic approaches have definite advantages over open surgery in terms of blood loss, postoperative pain, analgesic requirements, duration of hospital stay, and convalescence. There is some controversy regarding longer warm ischemia time, longer operative time, and increased bleeding with laparoscopic nephrectomy compared with hand-assisted laparoscopic living donor nephrectomy (HALDN). HALDN attempted to reduce warm ischemia time by using the hand port to extract the kidney instantly after dividing the blood vessels. This technique also offers tactile feedback, better manual control of bleeding, a relatively shorter learning curve, less kidney traction, faster kidney removal, and shorter warm ischemic periods. HALDN is often performed using periumbilical and Pfannenstiel incisions for hand-assisted port placement. Pfannenstiel incisions improve wound complications such as incisional hernia, cosmetic issues, and wound dehiscence. However, duration of surgery, postoperative pain score, and length of hospital stay are significantly lower in donors with periumbilical incisions.To the best of our knowledge, these two types of incision have not been compared in a randomized controlled trial in patients undergoing HALDN. Our objective is to compare the results of Pfannenstiel incision (intervention group) with periumbilical incision (control group). The return to normal physical activity will be evaluated in a clinical randomized trial using an expertise-based design. Detailed Description ----------------- Despite all efforts to optimize the transplantation of deceased donor kidneys, the number of available kidneys continues to fall short of demand. Living donor kidneys have been used to overcome this organ shortage. Graft and patient survival is significantly higher following living donor kidney transplantation compared with deceased donor kidney Transplantation. The major disadvantage of using living donors is that a healthy individual must undergo a major surgical procedure to provide the organ for transplantation. The donor does not medically benefit from the procedure, but there is a medical impact on both donor and recipient. Therefore, a nephrectomy technique associated with the lowest donor risk and the best organ quality should be used during Transplantation. Open donor nephrectomy was the universal technique before the advent of laparoscopic techniques. Laparoscopic living donor nephrectomy was introduced in 1995 and commercial ports were developed shortly after. In 1998, Wolf et al. described the hand-assisted laparoscopic living donor nephrectomy (HALDN) technique and since then it has become widely adopted. Laparoscopic methods have definite advantages over open surgery in terms of blood loss, postoperative pain, analgesic requirements, duration of hospital stay, and convalescence. There is some controversy regarding the possibility of relatively longer warm ischemia time, longer operative time, and increased bleeding with laparoscopic nephrectomy. HALDN reduces warm ischemia time by extracting the kidney using the hand port as soon as the blood vessels are divided. This technique is associated with tactile feedback, better manual control of bleeding, relatively shorter learning curve, less kidney traction, faster kidney removal, and shorter warm ischemic periods. At present, there is no strong evidence to support the use of one laparoscopic approach in preference to the other. However, evidence suggests that HALDN is the most cost-effective method of donor surgery and achieves equivalent clinical benefits of pure laparoscopic approaches with less operative time. HALDN is usually performed using a periumbilical or Pfannenstiel incision for hand-assisted port placement and kidney extraction. A periumbilical incision is made at the midline. In contrast, a Pfannenstiel incision is made as a slightly curved horizontal line just above the pubic symphysis. Pfannenstiel incisions improve wound complications, such as incisional hernia, cosmetic results, and wound dehiscence. However, the duration of surgery, postoperative pain score, and length of hospital stay were significantly lower in donors with periumbilical incision. The inserted hand plays a vital role in the procedure, including retraction and dissection, therefore the hand port midline incision is placed close to the periumbilical area. Dissecting the upper pole of the kidney through a Pfannenstiel incision may be difficult in morbidly obese and large donors. Patients with Pfannenstiel incisions return to normal physical activity quicker than those with periumbilical incisions. However, to the best of our knowledge, these two different incision types in patients undergoing HALDN have not been compared in a randomized controlled trial.Our objective is to compare the return of patients to physical activity following a HALDN procedure with Pfannenstiel incision (intervention group) or periumbilical incision (control group) in a clinical randomized trial using an expertise-based design. Official Title ----------------- Hand-Assisted Laparoscopic Donor Nephrectomy PERiumbilical Versus Pfannenstiel Incision and Return to Normal Physical ACTivity: A Randomized Clinical Trial: HAPERPACT Trial Conditions ----------------- Donor Nephrectomy Intervention / Treatment ----------------- * Procedure: Periumbilical incision * Procedure: Pfannenstiel incision Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age > 20 years No permanent pain therapy Kidneys with only a single artery and vein in the graft Informed consent for participation provided Exclusion Criteria: Infection or scar present precluding incision placement at one of the randomization sites Bleeding disorders Chronic use of immunosuppressive agents (e.g. steroids) Ages Eligible for Study ----------------- Minimum Age: 20 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Expertise-based, single intuition, assessor-blinded, randomized clinical trial. Masking: Double Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Periumbilical incisions<br> \| Procedure: Periumbilical incision<br>* A periumbilical incision is made at the abdominal midline for hand-assisted laparoscopic donor nephrectomy.<br>\| \| Experimental: Pfannenstiel incision<br> \| Procedure: Pfannenstiel incision<br>* Pfannenstiel incision is made as a slightly curved horizontal line just above the pubic symphysis for hand-assisted laparoscopic donor nephrectomy.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Days to return to normal physical activity \| Patients will be asked to complete the Katz basic activities of daily living self-maintenance questionnaire each day for 4 weeks after the operation. This questionnaire assesses the ability to perform daily living activities (0 = no activity and 6 = normal activity). The normal physical activity is perceived as good. \| Four weeks \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Warm ischemia time \| From the time of clamping of the first renal artery in situ to flushing of the kidney with chilled solution on the back table \| One day \| \| Intraoperative complications \| From skin incision to skin closure \| One day \| \| Estimated blood loss \| From skin incision to skin closure \| One day \| \| Operating time \| From skin incision to skin closure \| One day \| \| Postoperative pain \| Severity of pain via 11-point Visual Analogue Scale (0 = no pain and 10 = unbearable distress). \| Seven days \| \| Rescue analgesic \| Total amount of analgesics required. \| Seven days \| \| Peak expiratory flow rate \| Is defined as maximum speed of expiration, as measured with a peak flow meter. \| Seven days \| \| Postoperative complications \| According to the Clavien-Dindo classification \| 60 days \| \| Length of hospital stay \| From the day of the operation until the day of discharge \| 60 days \| \| Time to return to work \| From the day of discharge and return to work \| 60 days \| \| Physical activity score \| The International Physical Activity Questionnaire, Short Form (IPAQ) will be used as an indicator of physical activity and fitness. IPAQ assesses total physical activity in the previous 7 days. Questions measure the frequency (days per week) and duration (minutes per session) of physical activity, as well as its intensity level (vigorous, moderate, walking, or sitting). Participants are categorized into one of three physical activity levels (low, moderate, high). Range is not applicable because it is a categorical variable. The high activity category is perceived as good. \| 60 days \| \| Patient satisfaction \| Patient satisfaction score via 5-point Likert scale (5 = representing strongly satisfied and 1 = representing strongly unsatisfied). \| 60 days \| \| Cosmetic score \| As defined by the Stony Brook scar scale (SBSES). The SBSES assessed five scar components: width, height, color, suture marks and overall appearance. Each component was assigned a score of 0 or 1 with a total sum range of 0 (worst) to 5 (best). \| 60 days \| \| Incisional hernia \| Defined as a fascia or muscle defect (bulging hernial sac and palpable fascia gap) at the site of the surgical incision examined by palpation and ultrasonography. \| 60 days \| \| Mortality \| Death due to any cause. \| 60 days \| \| Recipient serum creatinine level \| Serum creatinine level (mg/dL) \| 30 days \| \| Glomerular filtration rate \| GFR (mL/min/1.73 m2) calculated with 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) Formula \| 30 days \| \| Delayed graft function \| Is defined as the need for one or more hemodialysis treatments following transplantation prior to the onset of graft function. \| 30 days \| \| Primary non-function \| A recipient whose graft never functions. \| 30 days \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Physical Activity, Pfannenstiel incision, Periumbilical incision
NCT02680912	Warm Needle Acupuncture vs Needle Acupuncture	This is a two-armed randomised controlled pilot study that investigates the component efficacy of moxibustion for osteoarthritis of the knee. Participants will be randomised to receive either warm needle acupuncture or needle acupuncture. Participants and acupuncturists will be blinded to group allocation. The primary and secondary outcome measures are WOMAC and SF36 respectively. Qualitative interviews will be used to gather information on the patients' experiences and perceptions of the trial and the treatment provided.~It is hypothesised that warm needle acupuncture will lead to a greater reduction in clinical signs and symptoms than needle acupuncture.	Acupuncture Treatment~All participants will receive acupuncture. Only points local to the knee will be used. There will be 4-6 points used per knee, therefore 8 -12 needles per treatment. A record will be kept of the points used at each treatment. Both knees will be treated even if only one knee is painful. This will ensure that participants receive similar treatments.~Patients will be treated seated, as this allows better access to the relevant acupuncture points. It also helps ensure the moxibustion is carried out safely.~Participants will receive 8 treatments in the first 4 weeks (twice a week), then 4 treatments in 4 weeks (once a week).~Blinding procedures~The only difference in the procedures will be that lit cones are placed on the needles of the treatment group whilst unlit moxa cones will be placed on the needles of the control group. Smokeless moxa will be used. All patients will see the needles being inserted and the moxa cones placed on the needles by the acupuncturist. Skin guards will be placed at the base of the needle to reduce the immediate sense of heat on the surface of the skin. Similar skin guards are routinely used in acupuncture treatment to prevent any discomfort.~The acupuncturist will carry out a consultation at each session as per normal practice. After the needles have been inserted and the moxa cones have been placed on needles the acupuncturist leaves and an assistant acupuncturist enters the room. The assistant acupuncturist will place a screen in front of the patient to prevent them from seeing their knees. The assistant acupuncturist will then remove one cone at a time and light it. In the treatment group the lit cone is placed on the needle. In the control group the lit cone is place in a small dish close to the knee, a replacement unlit cone is placed on the needle. This process is repeated until all the cones are lit. The unlit cone is replaced on the needle of the control group to try and ensure they experience the same sensations as the treatment group. The use of a second acupuncturist to light the moxa ensures that the acupuncturist who carries out the consultation and inserts the needles is blinded to group allocation.	Warm Needle Acupuncture vs. Needle Acupuncture for Osteoarthritis of the Knee: A Pilot Study	Osteoarthritis, Knee	* Device: Warm needle acupuncture * Device: Needle acupuncture	Inclusion Criteria:~Chronic pain in at least one knee joint during the last six months.~At baseline the WOMAC pain score must be ≥ 3 points (on a scale of 0-10)~In addition to the knee pain at least 3 of the following 6 must be present:~Age > 50 years~Stiffness < 30 minutes~Crepitus~Bony Tenderness~Bony enlargement~No palpable warmth~(ACR 2013)~Plus~Ability to speak English~Signed consent form~Exclusion Criteria:~A systemic disease of the musculoskeletal system.~Bone tumour, bone tumour like lesions or metastasis.~Bone fracture in the lower extremities during the last three months.~Acute infection or osteonecrosis in the knee joint.~Recent sprain injury to the knee joint.~Surgery of the afflicted extremity during the last six months or planned surgery.~Ongoing cortico-steroid therapy or cortisone injections in the past six weeks.~Taking anti-coagulant medication.~Coagulopathy.~Other pain condition that compels the patient to take analgesics for more than three days during the last four weeks.~Addiction to analgesics, opiate or other drugs.~Acupuncture treatment in the past 3 months.~Dermatological disease within the acupuncture area impairing acupuncture treatment.~Pregnant or breast-feeding patients.~Inability to follow instructions or understand the consent form (insufficient command of language, dementia).~Participation in another clinical study.~Ongoing legal proceedings concerning degree of disability.	40 Years	null	All	No	Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) \| \| Change from Baseline to follow up at 16 weeks \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| SF36 (Rand) \| Health Related Quality of Life (HRQL) \| Change from Baseline to follow up at 16 weeks \|	Bi syndrome	Osteoarthritis, Osteoarthritis, Knee, Arthritis, Joint Diseases, Musculoskeletal Diseases, Rheumatic Diseases	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Warm needle acupuncture<br>Warm needle acupuncture (wenzhen; 温针) is where moxa cones are placed on the handle of the needle, after the needle has been inserted. Once lit, heat transmits along the shaft of the needle to the acupuncture point.~Moxa refers to the herb mugwort (Artemisia vulgaris) that is burnt to warm specific parts of the body, including acupuncture points. \| Device: Warm needle acupuncture<br>* There will be 4-6 points used per knee, therefore 8-12 needles per treatment. Two points will be used as the core treatment ST 35 dubi, Ex-LE 5 xiyan. Four other acu-points can also be used from the following: Ahshi painful points local to the knee (locus dolendi), ST 36 zusanli, GB 34 yanglingquan, Sp 9 yinlingquan, ST34 liangqiu, Sp 10 xuehai, GB 33 yangxiguan, LR 7 xiguan, LR 8 ququan, heding Ex-LE 2 In addition to the acupuncture needles the warm needle acupuncture group will receive moxibustion on up to 4 points. Smokeless moxa will be used.<br>\| \| Active Comparator: Basic needle acupuncture<br>Basic needle acupuncture is the use of acupuncture needles alone, without other methods of stimulation. \| Device: Needle acupuncture<br>* The point selection protocol will be exactly the same as the experimental group<br>\|	Warm Needle Acupuncture vs Needle Acupuncture Study Overview ================= Brief Summary ----------------- This is a two-armed randomised controlled pilot study that investigates the component efficacy of moxibustion for osteoarthritis of the knee. Participants will be randomised to receive either warm needle acupuncture or needle acupuncture. Participants and acupuncturists will be blinded to group allocation. The primary and secondary outcome measures are WOMAC and SF36 respectively. Qualitative interviews will be used to gather information on the patients' experiences and perceptions of the trial and the treatment provided. It is hypothesised that warm needle acupuncture will lead to a greater reduction in clinical signs and symptoms than needle acupuncture. Detailed Description ----------------- Acupuncture Treatment All participants will receive acupuncture. Only points local to the knee will be used. There will be 4-6 points used per knee, therefore 8 -12 needles per treatment. A record will be kept of the points used at each treatment. Both knees will be treated even if only one knee is painful. This will ensure that participants receive similar treatments. Patients will be treated seated, as this allows better access to the relevant acupuncture points. It also helps ensure the moxibustion is carried out safely. Participants will receive 8 treatments in the first 4 weeks (twice a week), then 4 treatments in 4 weeks (once a week). Blinding procedures The only difference in the procedures will be that lit cones are placed on the needles of the treatment group whilst unlit moxa cones will be placed on the needles of the control group. Smokeless moxa will be used. All patients will see the needles being inserted and the moxa cones placed on the needles by the acupuncturist. Skin guards will be placed at the base of the needle to reduce the immediate sense of heat on the surface of the skin. Similar skin guards are routinely used in acupuncture treatment to prevent any discomfort. The acupuncturist will carry out a consultation at each session as per normal practice. After the needles have been inserted and the moxa cones have been placed on needles the acupuncturist leaves and an assistant acupuncturist enters the room. The assistant acupuncturist will place a screen in front of the patient to prevent them from seeing their knees. The assistant acupuncturist will then remove one cone at a time and light it. In the treatment group the lit cone is placed on the needle. In the control group the lit cone is place in a small dish close to the knee, a replacement unlit cone is placed on the needle. This process is repeated until all the cones are lit. The unlit cone is replaced on the needle of the control group to try and ensure they experience the same sensations as the treatment group. The use of a second acupuncturist to light the moxa ensures that the acupuncturist who carries out the consultation and inserts the needles is blinded to group allocation. Official Title ----------------- Warm Needle Acupuncture vs. Needle Acupuncture for Osteoarthritis of the Knee: A Pilot Study Conditions ----------------- Osteoarthritis, Knee Intervention / Treatment ----------------- * Device: Warm needle acupuncture * Device: Needle acupuncture Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Chronic pain in at least one knee joint during the last six months. At baseline the WOMAC pain score must be ≥ 3 points (on a scale of 0-10) In addition to the knee pain at least 3 of the following 6 must be present: Age > 50 years Stiffness < 30 minutes Crepitus Bony Tenderness Bony enlargement No palpable warmth (ACR 2013) Plus Ability to speak English Signed consent form Exclusion Criteria: A systemic disease of the musculoskeletal system. Bone tumour, bone tumour like lesions or metastasis. Bone fracture in the lower extremities during the last three months. Acute infection or osteonecrosis in the knee joint. Recent sprain injury to the knee joint. Surgery of the afflicted extremity during the last six months or planned surgery. Ongoing cortico-steroid therapy or cortisone injections in the past six weeks. Taking anti-coagulant medication. Coagulopathy. Other pain condition that compels the patient to take analgesics for more than three days during the last four weeks. Addiction to analgesics, opiate or other drugs. Acupuncture treatment in the past 3 months. Dermatological disease within the acupuncture area impairing acupuncture treatment. Pregnant or breast-feeding patients. Inability to follow instructions or understand the consent form (insufficient command of language, dementia). Participation in another clinical study. Ongoing legal proceedings concerning degree of disability. Ages Eligible for Study ----------------- Minimum Age: 40 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: Warm needle acupuncture<br>Warm needle acupuncture (wenzhen; 温针) is where moxa cones are placed on the handle of the needle, after the needle has been inserted. Once lit, heat transmits along the shaft of the needle to the acupuncture point. Moxa refers to the herb mugwort (Artemisia vulgaris) that is burnt to warm specific parts of the body, including acupuncture points. \| Device: Warm needle acupuncture<br>* There will be 4-6 points used per knee, therefore 8-12 needles per treatment. Two points will be used as the core treatment ST 35 dubi, Ex-LE 5 xiyan. Four other acu-points can also be used from the following: Ahshi painful points local to the knee (locus dolendi), ST 36 zusanli, GB 34 yanglingquan, Sp 9 yinlingquan, ST34 liangqiu, Sp 10 xuehai, GB 33 yangxiguan, LR 7 xiguan, LR 8 ququan, heding Ex-LE 2 In addition to the acupuncture needles the warm needle acupuncture group will receive moxibustion on up to 4 points. Smokeless moxa will be used.<br>\| \| Active Comparator: Basic needle acupuncture<br>Basic needle acupuncture is the use of acupuncture needles alone, without other methods of stimulation. \| Device: Needle acupuncture<br>* The point selection protocol will be exactly the same as the experimental group<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) \| \| Change from Baseline to follow up at 16 weeks \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| SF36 (Rand) \| Health Related Quality of Life (HRQL) \| Change from Baseline to follow up at 16 weeks \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Bi syndrome
NCT01189383	IL15 Dendritic Cell Vaccine for Patients With Resected Stage III (A, B or C) or Stage IV Melanoma	The purpose of the study is to gather data on feasibility as well as immune and clinical efficacy of of a dendritic cell vaccine using IL15 in patients with resected stage III or stage IV melanoma	IL15 is a T cell growth factor that pre-clinical data overwhelmingly suggests could have a very important role in cancer immunotherapy. A desirable property for a dendritic cell vaccine directed against cancer is the ability to efficiently prime naïve, tumor associated antigen specific T cells into potent CTLs. Results of studies in healthy volunteers have shown that IL15 DCs are particularly efficient at priming functional melanoma specific CD8+ T cells. The use of IL15 in the manufacture of the DC vaccine could result in an improved immunotherapy product.	IL15-DC Vaccine in Patients With High Risk Melanoma - Exploratory Phase I/II Trial	Malignant Melanoma Stage III, Malignant Melanoma Stage IV	* Biological: IL15-DC Vaccine	Inclusion Criteria:~HLA A201 + phenotype~Biopsy-proven melanoma, Stages III (A, B and C) or stage IV.- no evidence of disease at study entry~Age: 21-75 years~ECOG performance status 0-1~Adequate marrow function~Adequate hepatic function~Adequate renal function~Written informed consent~Exclusion Criteria:~Subjects with measureable non-resectable melanoma~Subjects who have had chemotherapy less than 4 weeks before starting trial~Subjects who received IFN-a or GM-CSF less than 4 weeks before starting trial~Subjects who received IL2 less than 4 weeks before starting trial~Subjects with a baseline LDH greater than 1.1 times the ULN~Subjects who are HIV positive~Female subjects who are pregnant~Subjects who have received corticosteroids or other immunosuppressive agents less than 4 weeks before starting trial~Subjects who have asthma and/or are on treatment for asthma~Subjects with angina pectoris~Subjects with congestive heart failure~Subjects with history of autoimmune disease including lupus, rheumatoid arthritis or thyroiditis~Subjects with active infections including viral hepatitis~Subjects with a history of neoplastic disease othe than melanoma within the last 5 years~History of neoplastic disease within the last 5 years except for carcinoma in situ of the cervix, superficial bladder cancer or basal/squamous cell carcinoma of the skin.~Subjects who present with open wounds	21 Years	75 Years	All	No	Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label)	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Immune response \| \| 14 weeks \|	\| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Quality of elicited melanoma specific CD8+ T cells \| \| 14 weeks \| \| Breadth of melanoma specific immunity \| \| 24 weeks \| \| Longevity of melanoma specific CD8+ T cell immunity \| \| 24 weeks \|	Melanoma, Vaccine, Dendritic Cell, Immune response, Safety, Efficacy	Melanoma, Neuroendocrine Tumors, Neuroectodermal Tumors, Neoplasms, Germ Cell and Embryonal, Neoplasms by Histologic Type, Neoplasms, Neoplasms, Nerve Tissue, Nevi and Melanomas	\| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: IL15-DC Vaccine<br>Approximately 9 x 10^6 DCs will be injected (subcutaneously)total per vaccination visit. Patients will receive four vaccinations at weeks 0, 4, 8 and 12.At each scheduled vaccination the patient will receive a total of 3 injections, i.e., 3 mL injections at each of 3 anatomical locations.Injection sites are in upper and lower extremities. Subsequent DC injections will be rotated to different locations on the upper and lower extremities. \| Biological: IL15-DC Vaccine<br>* Autologous dendritic cells manufactured with GM-CSF, IL15 and loaded with melanoma/HIV peptides and KLH; then activated with LPS and CD40 Ligand. Approximately 9 x 10^6 DCs will be injected (subcutaneously)total per vaccination visit. Patients will receive four vaccinations at weeks 0, 4, 8 and 12. At each scheduled vaccination the patient will receive a total of 3 injections, i.e., 3 mL injections at each of 3 anatomical locations.Injection sites are in upper and lower extremities. Subsequent DC injections will be rotated to different locations on the upper and lower extremities.<br>\|	IL15 Dendritic Cell Vaccine for Patients With Resected Stage III (A, B or C) or Stage IV Melanoma Study Overview ================= Brief Summary ----------------- The purpose of the study is to gather data on feasibility as well as immune and clinical efficacy of of a dendritic cell vaccine using IL15 in patients with resected stage III or stage IV melanoma Detailed Description ----------------- IL15 is a T cell growth factor that pre-clinical data overwhelmingly suggests could have a very important role in cancer immunotherapy. A desirable property for a dendritic cell vaccine directed against cancer is the ability to efficiently prime naïve, tumor associated antigen specific T cells into potent CTLs. Results of studies in healthy volunteers have shown that IL15 DCs are particularly efficient at priming functional melanoma specific CD8+ T cells. The use of IL15 in the manufacture of the DC vaccine could result in an improved immunotherapy product. Official Title ----------------- IL15-DC Vaccine in Patients With High Risk Melanoma - Exploratory Phase I/II Trial Conditions ----------------- Malignant Melanoma Stage III, Malignant Melanoma Stage IV Intervention / Treatment ----------------- * Biological: IL15-DC Vaccine Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: HLA A201 + phenotype Biopsy-proven melanoma, Stages III (A, B and C) or stage IV.- no evidence of disease at study entry Age: 21-75 years ECOG performance status 0-1 Adequate marrow function Adequate hepatic function Adequate renal function Written informed consent Exclusion Criteria: Subjects with measureable non-resectable melanoma Subjects who have had chemotherapy less than 4 weeks before starting trial Subjects who received IFN-a or GM-CSF less than 4 weeks before starting trial Subjects who received IL2 less than 4 weeks before starting trial Subjects with a baseline LDH greater than 1.1 times the ULN Subjects who are HIV positive Female subjects who are pregnant Subjects who have received corticosteroids or other immunosuppressive agents less than 4 weeks before starting trial Subjects who have asthma and/or are on treatment for asthma Subjects with angina pectoris Subjects with congestive heart failure Subjects with history of autoimmune disease including lupus, rheumatoid arthritis or thyroiditis Subjects with active infections including viral hepatitis Subjects with a history of neoplastic disease othe than melanoma within the last 5 years History of neoplastic disease within the last 5 years except for carcinoma in situ of the cervix, superficial bladder cancer or basal/squamous cell carcinoma of the skin. Subjects who present with open wounds Ages Eligible for Study ----------------- Minimum Age: 21 Years Maximum Age: 75 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions \| Participant Group/Arm \| Intervention/Treatment \| \| --- \| --- \| \| Experimental: IL15-DC Vaccine<br>Approximately 9 x 10^6 DCs will be injected (subcutaneously)total per vaccination visit. Patients will receive four vaccinations at weeks 0, 4, 8 and 12.At each scheduled vaccination the patient will receive a total of 3 injections, i.e., 3 mL injections at each of 3 anatomical locations.Injection sites are in upper and lower extremities. Subsequent DC injections will be rotated to different locations on the upper and lower extremities. \| Biological: IL15-DC Vaccine<br>* Autologous dendritic cells manufactured with GM-CSF, IL15 and loaded with melanoma/HIV peptides and KLH; then activated with LPS and CD40 Ligand. Approximately 9 x 10^6 DCs will be injected (subcutaneously)total per vaccination visit. Patients will receive four vaccinations at weeks 0, 4, 8 and 12. At each scheduled vaccination the patient will receive a total of 3 injections, i.e., 3 mL injections at each of 3 anatomical locations.Injection sites are in upper and lower extremities. Subsequent DC injections will be rotated to different locations on the upper and lower extremities.<br>\| What is the study measuring? ----------------- Primary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Immune response \| \| 14 weeks \| Secondary Outcome Measures \| Outcome Measure \| Measure Description \| Time Frame \| \| --- \| --- \| --- \| \| Quality of elicited melanoma specific CD8+ T cells \| \| 14 weeks \| \| Breadth of melanoma specific immunity \| \| 24 weeks \| \| Longevity of melanoma specific CD8+ T cell immunity \| \| 24 weeks \| Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Melanoma, Vaccine, Dendritic Cell, Immune response, Safety, Efficacy

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