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NCT00817635
|
A Study to Evaluate the Efficacy and Safety of LCI699 Compared to Placebo in Participants With Resistant Hypertension
|
This study assessed the blood pressure effect, safety and tolerability of LCI699 compared to placebo and eplerenone in participants with resistant hypertension.
|
A Phase II, Randomized, Double-blind, Placebo and Active Controlled, Parallel Group, Multi-center, Dose Ranging Study to Evaluate the Efficacy and Safety of LCI699 Compared to Placebo After 8 Weeks Treatment in Patients With Resistant Hypertension
|
Hypertension
|
* Drug: LCI699
* Drug: Eplerenone
* Drug: LCI699-matching Placebo
* Drug: Eplerenone-matching Placebo
|
Inclusion criteria:~Diagnosis of hypertension with mean sitting systolic blood pressure (MSSBP) ≥140 millimeters of mercury (mmHg) and <180 mmHg~Stable on a three-drug regimen (including a diuretic) for at least 4 weeks for the treatment of resistant hypertension~Male and female participants 18 to 75 years of age~Exclusion criteria:~Recent history of myocardial infarction (MI), heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack~Clinically significant electrocardiography (ECG) findings related to cardiac conduction defects~Type 1 diabetes or uncontrolled type 2 diabetes (haemoglobin A1c [HbA1c] >9%)~Malignancies within the last 5 years (excluding basal cell skin cancer)~Other protocol-defined inclusion/exclusion criteria may apply.
|
18 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in MSSBP at Week 8 Last Observation Carried Forward (LOCF) | Arterial blood pressure (BP) determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in the MSSBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from Baseline in MSSBP was analyzed using an analysis of covariance model (ANCOVA) with treatment and country as factors and Baseline MSSBP as a covariate. | Baseline, Week 8 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in MSDBP at Week 8 LOCF | Arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in the MSDBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from Baseline in MSDBP was analyzed using an ANCOVA with treatment and country as factors and Baseline MSDBP as a covariate. | Baseline, Week 8 |
| Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8, as Measured by Office Blood Pressure (OBP) | MSSBP response was defined as the percentage of participants with a MSSBP <140 mmHg or a >=20 mmHg reduction from baseline reduction from baseline. MSSBP control was defined as the percentage of participants with a MSSBP <140 mmHg for non-diabetic participants and <130mHg for diabetic participants. | Week 8 |
| Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8, as Measured by OBP | MSDBP response was defined as the percentage of participants with a MSDBP <90 mmHg or a >=10 mmHg reduction from baseline. MSDBP control was defined as the percentage of participants with a MSDBP <90 mmHg for non-diabetic participants and <80mHg for diabetic participants. | Week 8 |
| Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSSBP at Week 8 | Arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in the MSSBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from Baseline in MSSBP was analyzed using an ANCOVA with treatment and country as factors and Baseline MSSBP as a covariate. | Baseline, Week 8 |
| Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSDBP at Week 8 | Arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in the MSDBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from Baseline in MSDBP was analyzed using an ANCOVA with treatment and country as factors and Baseline MSDBP as a covariate. | Baseline, Week 8 |
| Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Systolic Blood Pressure (SBP) at Week 8 LOCF, as Measured by Ambulatory Blood Pressure Measurement (ABPM) | An ABPM measured a participant's blood pressure over a 24-hour period including daytime and nighttime readings, using an automated validated monitoring device from Baseline to Week 8. The 24-hour SBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24-hour period. The change from Baseline in SBP was analyzed using ANCOVA with treatment and country as factors and Baseline MSSBP as a covariate. | Baseline, Week 8 |
| Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM | An ABPM measured a participant's blood pressure over a 24-hour period including daytime and nighttime readings, using an automated validated monitoring device from Baseline to Week 8. The 24-hour DBP was calculated by taking the mean of all ambulatory diastolic blood pressure readings for the 24-hour period. The change from Baseline in DBP was analyzed using an ANCOVA with treatment and country as factors and Baseline MSDBP as a covariate. | Baseline, Week 8 |
| Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime SBP in LCI699 1mg QD Versus LCI699 0.5mg BID Arm at Week 4, as Measured by ABPM | An ABPM measured a participant's blood pressure over a 24-hour period including daytime and nighttime readings using an automated validated monitoring device from Baseline to Week 4. The 24-hour SBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24-hour period. The change from Baseline in SBP was analyzed using an ANCOVA with treatment and country as factors and Baseline MSDBP as a covariate. | Baseline, Week 4 |
| Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime DBP in LCI699 1mg QD Versus LCI699 0.5mg BID Arm at Week 4, as Measured by ABPM | An ABPM measured a participant's blood pressure over a 24-hour period including daytime and nighttime readings using an automated validated monitoring device from Baseline to Week 4. The 24-hour DBP was calculated by taking the mean of all ambulatory diastolic blood pressure readings for the 24-hour period. The change from Baseline in DBP was analyzed using an ANCOVA with treatment and country as factors and Baseline MSDBP as a covariate. | Baseline, Week 4 |
| Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality. Hyperkalemia was defined as potassium level >5.5 millimoles per liter (mmol/L). It is the medical term that describes a potassium level that's higher than normal. Hyponatremia was defined as sodium level <135 mmol/L. It is the medical term that describes a sodium level that's lesser than normal. | AEs, Hyperkalemia, and Hyponatremia: From start of the study drug treatment up to 10 weeks; SAE: From signing of the informed consent up to 10 weeks |
| Number of Participants With Cortisol Levels Below 500 Nmol/L at 1 Hour After Adrenocorticotropic Hormone (ACTH) Injection at Week 8 | Serum cortisol concentrations at 1 hour after injection were measured to assess the maximum stimulated cortisol level achieved. Potential adrenal suppression was indicated if the serum cortisol concentration was <500 nanomoles per liter (nmol/L) at 1 hour after the injection. | 1-hour post-dose at Week 8 |
| Percent Change From Baseline in Renin-Angiotensin-Aldosterone-System (RAAS) Biomarker: Plasma Aldosterone (PA) in LCI699 Compared to Eplerenone 50 mg at Week 8 LOCF | Percent change from Baseline was analyzed by ANCOVA model using PA values measured at Baseline and Week 8 LOCF, with treatment and country as factors and Baseline value as the covariate. Negative percent change from Baseline shows improvement. | Baseline, Week 8 |
| Percent Change From Baseline in RAAS Biomarker: Plasma Renin Activity (PRA) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF | Percent change from Baseline was analyzed by ANCOVA model using plasma renin values measured at Baseline and Week 8 LOCF, with treatment and country as factors and Baseline value as the covariate. Negative percent change from Baseline shows improvement. | Baseline, Week 8 |
| Percent Change From Baseline in RAAS Biomarker: Active Renin (ARC) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF | Percent change from Baseline was analyzed by ANCOVA model using active renin values measured at Baseline and Week 8 LOCF, with treatment and country as factors and Baseline value as the covariate. Negative percent change from Baseline shows improvement. | Baseline, Week 8 |
| Percent Change From Baseline in RAAS Biomarker: Ratio of PA to PRA in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF | Percent change from Baseline was analyzed by ANCOVA model using percent ratio of PA to PRA values measured at Baseline and Week 8 LOCF, with treatment and country as factors and Baseline value as the covariate. Negative percent change from Baseline shows improvement. | Baseline, Week 8 |
|
Blood Pressure, Hypertension, Resistant Hypertension
|
Eplerenone, Mineralocorticoid Receptor Antagonists, Hormone Antagonists, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs, Diuretics, Potassium Sparing, Diuretics, Natriuretic Agents, Antihypertensive Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LCI699 0.25 mg BID<br>Following a 2-week placebo run-in period, participants received LCI699 0.25 mg, capsules, orally, twice daily (BID), with or without food for up to 8 weeks. | Drug: LCI699<br>* LCI699 oral capsules<br>|
| Experimental: LCI699 1 mg QD<br>Following a 2-week placebo run-in period, participants received LCI699 1 mg, capsules, orally, once daily (QD), with or without food for up to 8 weeks. | Drug: LCI699<br>* LCI699 oral capsules<br>|
| Experimental: LCI699 0.5 mg followed by LCI699 1 mg BID<br>Following a 2-week placebo run-in period, participants received LCI699 0.5 mg, capsules, orally, BID, with or without food for up to 4 weeks, followed by LCI699 1 mg, capsules, orally, BID with or without food for up to 4 weeks. | Drug: LCI699<br>* LCI699 oral capsules<br>|
| Active Comparator: Eplerenone 50 mg BID<br>Following a 2-week placebo run-in period, participants received eplerenone 50 mg, capsules, orally, BID, with or without food for up to 8 weeks. | Drug: Eplerenone<br>* Eplerenone oral capsules<br>|
| Placebo Comparator: Placebo<br>For a 2-week placebo run-in period, followed by 8 weeks of the treatment period, participants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food. | Drug: LCI699-matching Placebo<br>* LCI699-matching placebo oral capsules<br>Drug: Eplerenone-matching Placebo<br>* Eplerenone-matching placebo oral capsules<br>|
|
A Study to Evaluate the Efficacy and Safety of LCI699 Compared to Placebo in Participants With Resistant Hypertension
Study Overview
=================
Brief Summary
-----------------
This study assessed the blood pressure effect, safety and tolerability of LCI699 compared to placebo and eplerenone in participants with resistant hypertension.
Official Title
-----------------
A Phase II, Randomized, Double-blind, Placebo and Active Controlled, Parallel Group, Multi-center, Dose Ranging Study to Evaluate the Efficacy and Safety of LCI699 Compared to Placebo After 8 Weeks Treatment in Patients With Resistant Hypertension
Conditions
-----------------
Hypertension
Intervention / Treatment
-----------------
* Drug: LCI699
* Drug: Eplerenone
* Drug: LCI699-matching Placebo
* Drug: Eplerenone-matching Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Diagnosis of hypertension with mean sitting systolic blood pressure (MSSBP) ≥140 millimeters of mercury (mmHg) and <180 mmHg Stable on a three-drug regimen (including a diuretic) for at least 4 weeks for the treatment of resistant hypertension Male and female participants 18 to 75 years of age Exclusion criteria: Recent history of myocardial infarction (MI), heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack Clinically significant electrocardiography (ECG) findings related to cardiac conduction defects Type 1 diabetes or uncontrolled type 2 diabetes (haemoglobin A1c [HbA1c] >9%) Malignancies within the last 5 years (excluding basal cell skin cancer) Other protocol-defined inclusion/exclusion criteria may apply.
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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LCI699 0.25 mg BID<br>Following a 2-week placebo run-in period, participants received LCI699 0.25 mg, capsules, orally, twice daily (BID), with or without food for up to 8 weeks. | Drug: LCI699<br>* LCI699 oral capsules<br>|
| Experimental: LCI699 1 mg QD<br>Following a 2-week placebo run-in period, participants received LCI699 1 mg, capsules, orally, once daily (QD), with or without food for up to 8 weeks. | Drug: LCI699<br>* LCI699 oral capsules<br>|
| Experimental: LCI699 0.5 mg followed by LCI699 1 mg BID<br>Following a 2-week placebo run-in period, participants received LCI699 0.5 mg, capsules, orally, BID, with or without food for up to 4 weeks, followed by LCI699 1 mg, capsules, orally, BID with or without food for up to 4 weeks. | Drug: LCI699<br>* LCI699 oral capsules<br>|
| Active Comparator: Eplerenone 50 mg BID<br>Following a 2-week placebo run-in period, participants received eplerenone 50 mg, capsules, orally, BID, with or without food for up to 8 weeks. | Drug: Eplerenone<br>* Eplerenone oral capsules<br>|
| Placebo Comparator: Placebo<br>For a 2-week placebo run-in period, followed by 8 weeks of the treatment period, participants received LCI699-matching placebo or eplerenone-matching placebo, capsules, orally, QD or BID, with or without food. | Drug: LCI699-matching Placebo<br>* LCI699-matching placebo oral capsules<br>Drug: Eplerenone-matching Placebo<br>* Eplerenone-matching placebo oral capsules<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in MSSBP at Week 8 Last Observation Carried Forward (LOCF) | Arterial blood pressure (BP) determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in the MSSBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from Baseline in MSSBP was analyzed using an analysis of covariance model (ANCOVA) with treatment and country as factors and Baseline MSSBP as a covariate. | Baseline, Week 8 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in MSDBP at Week 8 LOCF | Arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in the MSDBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from Baseline in MSDBP was analyzed using an ANCOVA with treatment and country as factors and Baseline MSDBP as a covariate. | Baseline, Week 8 |
| Percentage of Participants With a MSSBP Response and MSSBP Control at Week 8, as Measured by Office Blood Pressure (OBP) | MSSBP response was defined as the percentage of participants with a MSSBP <140 mmHg or a >=20 mmHg reduction from baseline reduction from baseline. MSSBP control was defined as the percentage of participants with a MSSBP <140 mmHg for non-diabetic participants and <130mHg for diabetic participants. | Week 8 |
| Percentage of Participants With a MSDBP Response and MSDBP Control at Week 8, as Measured by OBP | MSDBP response was defined as the percentage of participants with a MSDBP <90 mmHg or a >=10 mmHg reduction from baseline. MSDBP control was defined as the percentage of participants with a MSDBP <90 mmHg for non-diabetic participants and <80mHg for diabetic participants. | Week 8 |
| Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSSBP at Week 8 | Arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in the MSSBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from Baseline in MSSBP was analyzed using an ANCOVA with treatment and country as factors and Baseline MSSBP as a covariate. | Baseline, Week 8 |
| Dose/Exposure BP Response Relationship of LCI699, as Measured by Change From Baseline in MSDBP at Week 8 | Arterial BP determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in the MSDBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from Baseline in MSDBP was analyzed using an ANCOVA with treatment and country as factors and Baseline MSDBP as a covariate. | Baseline, Week 8 |
| Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Systolic Blood Pressure (SBP) at Week 8 LOCF, as Measured by Ambulatory Blood Pressure Measurement (ABPM) | An ABPM measured a participant's blood pressure over a 24-hour period including daytime and nighttime readings, using an automated validated monitoring device from Baseline to Week 8. The 24-hour SBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24-hour period. The change from Baseline in SBP was analyzed using ANCOVA with treatment and country as factors and Baseline MSSBP as a covariate. | Baseline, Week 8 |
| Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime Diastolic Blood Pressure (DBP) at Week 8 LOCF, as Measured by ABPM | An ABPM measured a participant's blood pressure over a 24-hour period including daytime and nighttime readings, using an automated validated monitoring device from Baseline to Week 8. The 24-hour DBP was calculated by taking the mean of all ambulatory diastolic blood pressure readings for the 24-hour period. The change from Baseline in DBP was analyzed using an ANCOVA with treatment and country as factors and Baseline MSDBP as a covariate. | Baseline, Week 8 |
| Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime SBP in LCI699 1mg QD Versus LCI699 0.5mg BID Arm at Week 4, as Measured by ABPM | An ABPM measured a participant's blood pressure over a 24-hour period including daytime and nighttime readings using an automated validated monitoring device from Baseline to Week 4. The 24-hour SBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24-hour period. The change from Baseline in SBP was analyzed using an ANCOVA with treatment and country as factors and Baseline MSDBP as a covariate. | Baseline, Week 4 |
| Change From Baseline in Mean 24 Hours, Mean Daytime and Mean Nighttime DBP in LCI699 1mg QD Versus LCI699 0.5mg BID Arm at Week 4, as Measured by ABPM | An ABPM measured a participant's blood pressure over a 24-hour period including daytime and nighttime readings using an automated validated monitoring device from Baseline to Week 4. The 24-hour DBP was calculated by taking the mean of all ambulatory diastolic blood pressure readings for the 24-hour period. The change from Baseline in DBP was analyzed using an ANCOVA with treatment and country as factors and Baseline MSDBP as a covariate. | Baseline, Week 4 |
| Number of Participants With Adverse Event (AEs), Serious Adverse Events (SAEs), Hyperkalemia, and Hyponatremia | An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality. Hyperkalemia was defined as potassium level >5.5 millimoles per liter (mmol/L). It is the medical term that describes a potassium level that's higher than normal. Hyponatremia was defined as sodium level <135 mmol/L. It is the medical term that describes a sodium level that's lesser than normal. | AEs, Hyperkalemia, and Hyponatremia: From start of the study drug treatment up to 10 weeks; SAE: From signing of the informed consent up to 10 weeks |
| Number of Participants With Cortisol Levels Below 500 Nmol/L at 1 Hour After Adrenocorticotropic Hormone (ACTH) Injection at Week 8 | Serum cortisol concentrations at 1 hour after injection were measured to assess the maximum stimulated cortisol level achieved. Potential adrenal suppression was indicated if the serum cortisol concentration was <500 nanomoles per liter (nmol/L) at 1 hour after the injection. | 1-hour post-dose at Week 8 |
| Percent Change From Baseline in Renin-Angiotensin-Aldosterone-System (RAAS) Biomarker: Plasma Aldosterone (PA) in LCI699 Compared to Eplerenone 50 mg at Week 8 LOCF | Percent change from Baseline was analyzed by ANCOVA model using PA values measured at Baseline and Week 8 LOCF, with treatment and country as factors and Baseline value as the covariate. Negative percent change from Baseline shows improvement. | Baseline, Week 8 |
| Percent Change From Baseline in RAAS Biomarker: Plasma Renin Activity (PRA) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF | Percent change from Baseline was analyzed by ANCOVA model using plasma renin values measured at Baseline and Week 8 LOCF, with treatment and country as factors and Baseline value as the covariate. Negative percent change from Baseline shows improvement. | Baseline, Week 8 |
| Percent Change From Baseline in RAAS Biomarker: Active Renin (ARC) in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF | Percent change from Baseline was analyzed by ANCOVA model using active renin values measured at Baseline and Week 8 LOCF, with treatment and country as factors and Baseline value as the covariate. Negative percent change from Baseline shows improvement. | Baseline, Week 8 |
| Percent Change From Baseline in RAAS Biomarker: Ratio of PA to PRA in LCI699 Compared to Eplerenone 50mg at Week 8 LOCF | Percent change from Baseline was analyzed by ANCOVA model using percent ratio of PA to PRA values measured at Baseline and Week 8 LOCF, with treatment and country as factors and Baseline value as the covariate. Negative percent change from Baseline shows improvement. | Baseline, Week 8 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Blood Pressure, Hypertension, Resistant Hypertension
|
|
NCT00212121
|
Radiation Dose Intensity Study in Breast Cancer in Young Women
|
hypothesis: 10 Gy additional boost to the tumor bed will yield an increase in local control at 10 years from 88% to 93%, with still acceptable cosmesis.
|
Title of the study:~Radiation dose intensity study in breast cancer in young women: a randomized phase III trial of additional dose to the tumor bed.~Background and aim of the study:~Several studies showed that breast conserving therapy (BCT) yields similar survival rates as mastectomy. BCT consists of lumpectomy followed by whole breast radiotherapy (WBRT). Three studies showed that an additional dose to the tumor bed, after 50 Gy WBRT, reduces the local recurrence rate (LRR). The largest of these 3 studies was a recent EORTC trial, which also showed that young age was an independent risk factor for LR after BCT.~In patients < 51 years of age, the LR rate was reduced with 50% after a 66 Gy dose to the tumor bed, compared to 50 Gy (5-year LRR 12% vs 5.9%, p < 0.02). However, the LRR in young women was still quite high (> 1% per year). Therefore the first aim of the study is to investigate whether an additional boost dose to the tumorbed (26 Gy) reduces the LRR further. Therefore, we will compare the effect of a low boost dose (16 Gy) with the effect of a high boost dose (26 Gy) on the LRR, but also on the cosmetic outcome.~The second, very important aim of this study is to investigate whether we can find genetic or protein profiles that correlate with LRR, lymph node metastases, distant metastases, survival, radiosensitivity, and age. For this purpose we will obtain frozen tumor material and blood samples of as many patients as possible.~Population, study design, intervention:~Patients younger than 51 years of age, with stage T1-2N01-2aM0 breast cancer, and where the tumor can be locally excised with acceptable cosmetic result, will be randomized between a 16 Gy boost dose to the tumorbed and a 26 Gy boost dose to the tumor bed, after 50 Gy WBRT. Patients will be stratified based on age, tumor size, lymph node metastases, estrogen receptor status, interstitial or external boost irradiation, and institution. In principle frozen tumor samples and blood samples will be stored of each patient.~Endpoints and statistics:~The primary endpoint is LRR are 10 years. The secondary endpoint is cosmetic result, which will be quantified using digitized color photographs. In addition, patients will be asked to give their opinion about the cosmetic result using standardized questionnaires.~To find an increase in the local control rate of 88% to 93% at 10 year, with a power of 80% and a significance level of 5%, 580 patients will be included in each treatment arm.~Side studies:~An extremely important aspect of this trial is to obtain fresh tumor material and blood samples. These will be used to determine genetic and protein profiles aimed at finding subgroups based on these profiles, which may take more or less advantage of the additional radiation treatment.
|
Radiation Dose Intensity Study in Breast Cancer in Young Women: a Randomized Phase III Trial of Additional Dose to the Tumor Bed
|
Breast Cancer
|
* Radiation: high dose boost
* Procedure: boost
|
Inclusion criteria:~Age 50 years or younger.~Histological diagnosis of invasive mammary cancer including all subtypes of invasive adenocarcinoma.~Tumor location and extension imaged prior to surgery using at least mammography and ultrasound.~Unicentric tumors and multifocal tumors removed using a wide local excision; microscopic radical resection (focally involved margins allowed, defined as:~any DCIS or invasive carcinoma in 3 or fewer low-power fields (using a x 4 objective and a x 10 ocular lens, which has a diameter of 5 mm per low-power microscopic fields).~Sentinel lymph node biopsy and/or axillary lymph node dissection has been performed.~Breast cancer stage: pT1-2pN0-2a M0.~No treatment is allowed prior to surgery (no neoadjuvant chemotherapy, no neoadjuvant hormonal therapy, no pre-operative radiotherapy).~In cases where no adjuvant chemotherapy is given, wide local excision has been performed < 10 weeks before the start of radiotherapy.~In cases where adjuvant chemotherapy is given immediately after surgery, wide local excision has been performed < 6 months before the start of radiotherapy, and chemotherapy should be completed < 6 weeks before the start of radiotherapy.~In cases where hormonal treatment is planned, this is given after completion of the radiotherapy.~No previous history or synchronous malignant tumor in the other breast, previous history of malignant disease, except adequately treated carcinoma in situ of the cervix or basal cell carcinoma of the skin.~ECOG performance scale 2 or less.~Exclusion criteria:~Residual microcalcifications on mammogram.~All histological types of malignancies other than invasive adenocarcinoma.~In situ carcinoma of the breast, without invasive tumor.~Concurrent pregnancy.~Multicentric tumors, and multifocal. tumors excised using multiple excisions * Invasive breast cancer in both breasts.
|
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 |
| --- | --- | --- |
| Local control at 10 yr | | at every follow up visit (< 2 months after last radiation treatment and thereafter yearly |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cosmetic outcome | | prior to radiotherapy, 1 year after radiotherapy and thereafter every 3 years |
|
breast cancer, radiotherapy, microarrays
|
Breast Neoplasms, Neoplasms by Site, Neoplasms, Breast Diseases, Skin Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>low dose boost (16 Gy) | Radiation: high dose boost<br>* high dose boost<br>Procedure: boost<br>* low dose versus high dose<br>|
| Experimental: 2<br>high boost (26 Gy) | Radiation: high dose boost<br>* high dose boost<br>Procedure: boost<br>* low dose versus high dose<br>|
|
Radiation Dose Intensity Study in Breast Cancer in Young Women
Study Overview
=================
Brief Summary
-----------------
hypothesis: 10 Gy additional boost to the tumor bed will yield an increase in local control at 10 years from 88% to 93%, with still acceptable cosmesis.
Detailed Description
-----------------
Title of the study: Radiation dose intensity study in breast cancer in young women: a randomized phase III trial of additional dose to the tumor bed. Background and aim of the study: Several studies showed that breast conserving therapy (BCT) yields similar survival rates as mastectomy. BCT consists of lumpectomy followed by whole breast radiotherapy (WBRT). Three studies showed that an additional dose to the tumor bed, after 50 Gy WBRT, reduces the local recurrence rate (LRR). The largest of these 3 studies was a recent EORTC trial, which also showed that young age was an independent risk factor for LR after BCT. In patients < 51 years of age, the LR rate was reduced with 50% after a 66 Gy dose to the tumor bed, compared to 50 Gy (5-year LRR 12% vs 5.9%, p < 0.02). However, the LRR in young women was still quite high (> 1% per year). Therefore the first aim of the study is to investigate whether an additional boost dose to the tumorbed (26 Gy) reduces the LRR further. Therefore, we will compare the effect of a low boost dose (16 Gy) with the effect of a high boost dose (26 Gy) on the LRR, but also on the cosmetic outcome. The second, very important aim of this study is to investigate whether we can find genetic or protein profiles that correlate with LRR, lymph node metastases, distant metastases, survival, radiosensitivity, and age. For this purpose we will obtain frozen tumor material and blood samples of as many patients as possible. Population, study design, intervention: Patients younger than 51 years of age, with stage T1-2N01-2aM0 breast cancer, and where the tumor can be locally excised with acceptable cosmetic result, will be randomized between a 16 Gy boost dose to the tumorbed and a 26 Gy boost dose to the tumor bed, after 50 Gy WBRT. Patients will be stratified based on age, tumor size, lymph node metastases, estrogen receptor status, interstitial or external boost irradiation, and institution. In principle frozen tumor samples and blood samples will be stored of each patient. Endpoints and statistics: The primary endpoint is LRR are 10 years. The secondary endpoint is cosmetic result, which will be quantified using digitized color photographs. In addition, patients will be asked to give their opinion about the cosmetic result using standardized questionnaires. To find an increase in the local control rate of 88% to 93% at 10 year, with a power of 80% and a significance level of 5%, 580 patients will be included in each treatment arm. Side studies: An extremely important aspect of this trial is to obtain fresh tumor material and blood samples. These will be used to determine genetic and protein profiles aimed at finding subgroups based on these profiles, which may take more or less advantage of the additional radiation treatment.
Official Title
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Radiation Dose Intensity Study in Breast Cancer in Young Women: a Randomized Phase III Trial of Additional Dose to the Tumor Bed
Conditions
-----------------
Breast Cancer
Intervention / Treatment
-----------------
* Radiation: high dose boost
* Procedure: boost
Participation Criteria
=================
Eligibility Criteria
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Inclusion criteria: Age 50 years or younger. Histological diagnosis of invasive mammary cancer including all subtypes of invasive adenocarcinoma. Tumor location and extension imaged prior to surgery using at least mammography and ultrasound. Unicentric tumors and multifocal tumors removed using a wide local excision; microscopic radical resection (focally involved margins allowed, defined as: any DCIS or invasive carcinoma in 3 or fewer low-power fields (using a x 4 objective and a x 10 ocular lens, which has a diameter of 5 mm per low-power microscopic fields). Sentinel lymph node biopsy and/or axillary lymph node dissection has been performed. Breast cancer stage: pT1-2pN0-2a M0. No treatment is allowed prior to surgery (no neoadjuvant chemotherapy, no neoadjuvant hormonal therapy, no pre-operative radiotherapy). In cases where no adjuvant chemotherapy is given, wide local excision has been performed < 10 weeks before the start of radiotherapy. In cases where adjuvant chemotherapy is given immediately after surgery, wide local excision has been performed < 6 months before the start of radiotherapy, and chemotherapy should be completed < 6 weeks before the start of radiotherapy. In cases where hormonal treatment is planned, this is given after completion of the radiotherapy. No previous history or synchronous malignant tumor in the other breast, previous history of malignant disease, except adequately treated carcinoma in situ of the cervix or basal cell carcinoma of the skin. ECOG performance scale 2 or less. Exclusion criteria: Residual microcalcifications on mammogram. All histological types of malignancies other than invasive adenocarcinoma. In situ carcinoma of the breast, without invasive tumor. Concurrent pregnancy. Multicentric tumors, and multifocal. tumors excised using multiple excisions * Invasive breast cancer in both breasts.
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: 1<br>low dose boost (16 Gy) | Radiation: high dose boost<br>* high dose boost<br>Procedure: boost<br>* low dose versus high dose<br>|
| Experimental: 2<br>high boost (26 Gy) | Radiation: high dose boost<br>* high dose boost<br>Procedure: boost<br>* low dose versus high dose<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local control at 10 yr | | at every follow up visit (< 2 months after last radiation treatment and thereafter yearly |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cosmetic outcome | | prior to radiotherapy, 1 year after radiotherapy and thereafter every 3 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
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breast cancer, radiotherapy, microarrays
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NCT04901858
|
Knee Aspiration and High Definition MRI for ACL Injury
|
The aim of this pilot study is to understand the biological changes that occur within the knee joint following injury to the anterior cruciate ligament (ACL). This will be achieved through aspiration and analysis of the haemarthrosis which fills the knee following injury. The study will look at inflammatory and healing responses using DNA, RNA and protein analysis.~This, combined with high resolution imaging of the knee and surrounding soft tissue structures, may enable a more patient specific approach to treatment of ACL injury.
|
Pilot Study Into the Structural Local Molecular Environment Following an ACL Injury
|
ACL Injury
|
* Diagnostic Test: Aspiration of haemarthrosis and high definition MRI
|
Inclusion Criteria:~Diagnosis of ACL injury confirmed by MRI~All participants must have the capacity to provide informed consent to participate~Participants must be able to comply with required study visit~Exclusion Criteria:~Participants outside of the specified age range~Participants who do not have the mental capacity to make informed decisions~Participants who have meniscal pathology or other injuries requiring urgent surgery
|
18 Years
|
30 Years
|
All
|
No
|
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pattern of injury on High Definition MRI measured by comparison with 3t MRI images | Outcome will illustrate any additional benefit of high definition MRI | Last visit, usually 28 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of acute inflammatory mediators measured by NanoString molecular analysis | | Last visit, usually 28 days |
|
Wounds and Injuries, Anterior Cruciate Ligament Injuries, Knee Injuries, Leg Injuries
|
| Intervention/Treatment |
| --- |
|Diagnostic Test: Aspiration of haemarthrosis and high definition MRI|Aspiration of haemarthrosis and high definition MRI|
|
Knee Aspiration and High Definition MRI for ACL Injury
Study Overview
=================
Brief Summary
-----------------
The aim of this pilot study is to understand the biological changes that occur within the knee joint following injury to the anterior cruciate ligament (ACL). This will be achieved through aspiration and analysis of the haemarthrosis which fills the knee following injury. The study will look at inflammatory and healing responses using DNA, RNA and protein analysis. This, combined with high resolution imaging of the knee and surrounding soft tissue structures, may enable a more patient specific approach to treatment of ACL injury.
Official Title
-----------------
Pilot Study Into the Structural Local Molecular Environment Following an ACL Injury
Conditions
-----------------
ACL Injury
Intervention / Treatment
-----------------
* Diagnostic Test: Aspiration of haemarthrosis and high definition MRI
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of ACL injury confirmed by MRI All participants must have the capacity to provide informed consent to participate Participants must be able to comply with required study visit Exclusion Criteria: Participants outside of the specified age range Participants who do not have the mental capacity to make informed decisions Participants who have meniscal pathology or other injuries requiring urgent surgery
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 30 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Intervention/Treatment |
| --- |
|Diagnostic Test: Aspiration of haemarthrosis and high definition MRI|Aspiration of haemarthrosis and high definition MRI|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pattern of injury on High Definition MRI measured by comparison with 3t MRI images | Outcome will illustrate any additional benefit of high definition MRI | Last visit, usually 28 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of acute inflammatory mediators measured by NanoString molecular analysis | | Last visit, usually 28 days |
|
||
NCT01634555
|
A Study to Assess the Pharmacokinetics of Ramucirumab (IMC-1121B) in Combination With FOLFIRI
|
The purpose of this study is to assess the effect of concomitant ramucirumab (IMC-1121B) on the pharmacokinetics of irinotecan and its metabolite SN-38 when coadministered with folinic acid and 5-fluorouracil, in participants with advanced malignant solid tumors resistant to standard therapy or for which no standard therapy is available.
|
A Study to Evaluate the Potential of Concomitant Ramucirumab to Affect the Pharmacokinetics of Irinotecan and Its Metabolite SN-38 When Coadministered With Folinic Acid and 5 Fluorouracil in Patients With Advanced Malignant Solid Tumors
|
Solid Tumors
|
* Biological: Ramucirumab (IMC-1121B)
* Drug: Irinotecan
* Drug: Folinic acid
* Drug: 5-Fluorouracil
|
Inclusion Criteria:~Has histologic or cytologic documentation of a malignant solid tumor~Has an advanced solid tumor that is resistant to standard therapy or for which no standard therapy is available~Has resolution to Grade ≤1, per the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v. 4.0), of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy~Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2~Has adequate hematologic, coagulation, and hepatic function~Has serum creatinine ≤ 1.5 x upper limit of normal (ULN)~Urinary protein is <2+ on dipstick or routine urinalysis (UA) at study entry~Women with childbearing potential must have a negative serum or urine pregnancy test~Eligible participants of reproductive potential (both sexes) agree to use adequate method of contraception during the study period and for 12 weeks after the last dose of study medication~Exclusion Criteria:~Has received a therapeutic monoclonal antibody within the last 42 days~Has received cytotoxic chemotherapy within the last 21 days~Has received radiotherapy within the last 14 days~Are currently enrolled in, or discontinued within the last 14 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study~Has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism during the last 3 months~Has an uncontrolled illness, including, but not limited to uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders~Has experienced any arterial thromboembolic event within the last 6 months~Has known leptomeningeal disease or brain metastases or uncontrolled spinal cord compression~Has an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy~Has known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness~Has received a prior organ or transplantation~Has undergone major surgery within the last 28 days~Has had a serious nonhealing wound, ulcer, or bone fracture within the last 28 days~Has an elective or planned major surgery to be performed during the course of the trial~Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection, Crohn's disease, ulcerative colitis, or chronic diarrhea~Has experienced a Grade 3 or higher bleeding event within the last 3 months~Has a known history or clinical evidence of Gilbert's Syndrome, or is known to have any of the following genotypes: uridine diphosphate glucuronosyltransferase isoform 1A1 (UGT1A1)*6/*6, UGT1A1*28/*28, or UGT1A1*6/*28~Has received clinically relevant inhibitors or inducers of cytochrome P (CYP) 450 CYP3A4/5 or CYP2C9 and/or isoenzymes within the last 3 weeks~Has cirrhosis at a level of Child-Pugh B (or worse), or cirrhosis and a history of hepatic encephalopathy, or ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Dose-Normalized Area Under the Concentration Versus Time Curve of Irinotecan and Its Metabolite SN-38 From Time Zero to Infinity [AUC(0-∞)] in Cycle 1 | Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose. Data presented are Geometric Least Squares (Geo LS) means. Geo LS means were adjusted for cycle, participant and random error. | Cycle 1: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion |
| Pharmacokinetics: Dose-Normalized AUC(0-∞) of Irinotecan and Its Metabolite SN-38 in Cycle 2 | Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose. Data presented are Geo LS means. Geo LS means were adjusted for cycle, participant and random error. | Cycle 2: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion |
| Pharmacokinetics: Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Irinotecan and Its Metabolite SN-38 in Cycle 1 | Dose-normalized Cmax was calculated from Cmax divided by the dose. Data presented are Geo LS means. Geo LS means were adjusted for cycle, participant and random error. | Cycle 1: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion |
| Pharmacokinetics: Dose-Normalized Cmax of Irinotecan and Its Metabolite SN-38 in Cycle 2 | Dose-normalized Cmax was calculated from Cmax divided by the dose. Data presented are Geo LS means. Geo LS means were adjusted for cycle, participant and random error. | Cycle 2: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Cmax of Ramucirumab (IMC-1121B) | | Cycle 2: -2, -1, -0.5, 0, 2, 3, 4, 5, 8, 10, 25, 48, 72, 96, 168, 264, 336 hours post-ramucirumab (IMC-1121B) infusion |
| Number of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA) | Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group. | Up To 2 Years |
|
Advanced Malignant Solid Tumors
|
Vitamins, Leucovorin, Folic Acid, Fluorouracil, Irinotecan, Ramucirumab, Levoleucovorin, Antimetabolites, Molecular Mechanisms of Pharmacological Action, Antimetabolites, Antineoplastic, Antineoplastic Agents, Immunosuppressive Agents, Immunologic Factors, Physiological Effects of Drugs, Topoisomerase I Inhibitors, Topoisomerase Inhibitors, Enzyme Inhibitors, Antidotes, Protective Agents, Vitamin B Complex, Micronutrients, Hematinics
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ramucirumab (IMC-1121B) and FOLFIRI<br>Treatment is sequential, Ramucirumab (IMC-1121B) will be administered before FOLFIRI ((Irinotecan + Folinic acid + 5-Fluorouracil). FOLFIRI will be administered each cycle and Ramucirumab (IMC-1121B) will be administered beginning from Cycle 2 (2-week cycle). | Biological: Ramucirumab (IMC-1121B)<br>* Ramucirumab (IMC-1121B) 8 milligrams per kilogram (mg/kg), administered as an intravenous (IV) infusion on Day 1 of each 2-week cycle (except Cycle 1)<br>* Other names: LY3009806;Drug: Irinotecan<br>* 180 milligrams per square meter (mg/m²) administered IV on Day 1 of each cycle<br>Drug: Folinic acid<br>* 400 mg/m² administered IV on Day 1 of each cycle<br>Drug: 5-Fluorouracil<br>* 400 mg/m² bolus over 2 to 4 minutes administered IV on Day 1 of each cycle, followed by 2400 mg/m² administered IV over 46 to 48 hours on Days 1 and 2 of each cycle<br>|
|
A Study to Assess the Pharmacokinetics of Ramucirumab (IMC-1121B) in Combination With FOLFIRI
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the effect of concomitant ramucirumab (IMC-1121B) on the pharmacokinetics of irinotecan and its metabolite SN-38 when coadministered with folinic acid and 5-fluorouracil, in participants with advanced malignant solid tumors resistant to standard therapy or for which no standard therapy is available.
Official Title
-----------------
A Study to Evaluate the Potential of Concomitant Ramucirumab to Affect the Pharmacokinetics of Irinotecan and Its Metabolite SN-38 When Coadministered With Folinic Acid and 5 Fluorouracil in Patients With Advanced Malignant Solid Tumors
Conditions
-----------------
Solid Tumors
Intervention / Treatment
-----------------
* Biological: Ramucirumab (IMC-1121B)
* Drug: Irinotecan
* Drug: Folinic acid
* Drug: 5-Fluorouracil
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Has histologic or cytologic documentation of a malignant solid tumor Has an advanced solid tumor that is resistant to standard therapy or for which no standard therapy is available Has resolution to Grade ≤1, per the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v. 4.0), of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Has adequate hematologic, coagulation, and hepatic function Has serum creatinine ≤ 1.5 x upper limit of normal (ULN) Urinary protein is <2+ on dipstick or routine urinalysis (UA) at study entry Women with childbearing potential must have a negative serum or urine pregnancy test Eligible participants of reproductive potential (both sexes) agree to use adequate method of contraception during the study period and for 12 weeks after the last dose of study medication Exclusion Criteria: Has received a therapeutic monoclonal antibody within the last 42 days Has received cytotoxic chemotherapy within the last 21 days Has received radiotherapy within the last 14 days Are currently enrolled in, or discontinued within the last 14 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study Has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism during the last 3 months Has an uncontrolled illness, including, but not limited to uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders Has experienced any arterial thromboembolic event within the last 6 months Has known leptomeningeal disease or brain metastases or uncontrolled spinal cord compression Has an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy Has known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness Has received a prior organ or transplantation Has undergone major surgery within the last 28 days Has had a serious nonhealing wound, ulcer, or bone fracture within the last 28 days Has an elective or planned major surgery to be performed during the course of the trial Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection, Crohn's disease, ulcerative colitis, or chronic diarrhea Has experienced a Grade 3 or higher bleeding event within the last 3 months Has a known history or clinical evidence of Gilbert's Syndrome, or is known to have any of the following genotypes: uridine diphosphate glucuronosyltransferase isoform 1A1 (UGT1A1)*6/*6, UGT1A1*28/*28, or UGT1A1*6/*28 Has received clinically relevant inhibitors or inducers of cytochrome P (CYP) 450 CYP3A4/5 or CYP2C9 and/or isoenzymes within the last 3 weeks Has cirrhosis at a level of Child-Pugh B (or worse), or cirrhosis and a history of hepatic encephalopathy, or ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis
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: ramucirumab (IMC-1121B) and FOLFIRI<br>Treatment is sequential, Ramucirumab (IMC-1121B) will be administered before FOLFIRI ((Irinotecan + Folinic acid + 5-Fluorouracil). FOLFIRI will be administered each cycle and Ramucirumab (IMC-1121B) will be administered beginning from Cycle 2 (2-week cycle). | Biological: Ramucirumab (IMC-1121B)<br>* Ramucirumab (IMC-1121B) 8 milligrams per kilogram (mg/kg), administered as an intravenous (IV) infusion on Day 1 of each 2-week cycle (except Cycle 1)<br>* Other names: LY3009806;Drug: Irinotecan<br>* 180 milligrams per square meter (mg/m²) administered IV on Day 1 of each cycle<br>Drug: Folinic acid<br>* 400 mg/m² administered IV on Day 1 of each cycle<br>Drug: 5-Fluorouracil<br>* 400 mg/m² bolus over 2 to 4 minutes administered IV on Day 1 of each cycle, followed by 2400 mg/m² administered IV over 46 to 48 hours on Days 1 and 2 of each cycle<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Dose-Normalized Area Under the Concentration Versus Time Curve of Irinotecan and Its Metabolite SN-38 From Time Zero to Infinity [AUC(0-∞)] in Cycle 1 | Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose. Data presented are Geometric Least Squares (Geo LS) means. Geo LS means were adjusted for cycle, participant and random error. | Cycle 1: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion |
| Pharmacokinetics: Dose-Normalized AUC(0-∞) of Irinotecan and Its Metabolite SN-38 in Cycle 2 | Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose. Data presented are Geo LS means. Geo LS means were adjusted for cycle, participant and random error. | Cycle 2: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion |
| Pharmacokinetics: Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Irinotecan and Its Metabolite SN-38 in Cycle 1 | Dose-normalized Cmax was calculated from Cmax divided by the dose. Data presented are Geo LS means. Geo LS means were adjusted for cycle, participant and random error. | Cycle 1: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion |
| Pharmacokinetics: Dose-Normalized Cmax of Irinotecan and Its Metabolite SN-38 in Cycle 2 | Dose-normalized Cmax was calculated from Cmax divided by the dose. Data presented are Geo LS means. Geo LS means were adjusted for cycle, participant and random error. | Cycle 2: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Cmax of Ramucirumab (IMC-1121B) | | Cycle 2: -2, -1, -0.5, 0, 2, 3, 4, 5, 8, 10, 25, 48, 72, 96, 168, 264, 336 hours post-ramucirumab (IMC-1121B) infusion |
| Number of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA) | Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group. | Up To 2 Years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Advanced Malignant Solid Tumors
|
|
NCT02163499
|
Open-label Safety and Efficacy of Sodium Zirconium Cyclosilicate for up to 12 Months
|
The Open-Label Maintenance Study contains an Acute Phase, in which subjects will be dosed with ZS 10 g three times daily (tid) for 24 to 72 hours, followed by a long-term Maintenance Phase.
|
Subjects with 2 consecutive i STAT potassium values 5.1 mmol/L will enter the Acute Phase and receive ZS 10 g tid for 24 to 72 hours, depending on potassium values. Once normokalemia (i STAT potassium between 3.5 and 5.0 mmol/L, inclusive) is restored (whether after 24, 48 or 72 hours), subjects will be enrolled in the Maintenance Phase to be dosed with ZS at a starting dose of 5 g qd. Potassium (i STAT and central laboratory) will be measured weekly throughout the first month of study and every 4 weeks thereafter through Month 12. During the Maintenance Phase, the ZS dose may be increased or decreased in increments/decrements of 5 g qd up to a maximum of 15 g qd or a minimum of 5 g every other day based on i STAT potassium measurements as outlined below:~• > 5.0 mmol/L while receiving 5 g qd or 5 g every other day or > 5.5 mmol/L while receiving 10 g qd: increase ZS dose in 5 g qd increments to a maximum dose of 15 g qd~.• Between 3.0 and 3.4 mmol/L, inclusive: decrease ZS dose in 5 g qd decrements to a minimum dose of 5 g every other day; if a subject's i STAT potassium value remains between 3.0 and 3.4 mmol/L, inclusive, on the ZS 5 g every other day dose, the subject will be withdrawn from the study and receive standard of care treatment.~There is no limit to the number of dose titrations allowed. Subjects will receive up to 12 months of treatment with open-label ZS.
|
Multicenter, Multi-Dose, Open-Label Maintenance of Long-Term Safety and Efficacy of Sodium Zirconium Cyclosilicate (ZS) in Hyperkalemia
|
Hyperkalemia
|
* Drug: Sodium Zirconium Cyclosilicate
|
Inclusion Criteria:~Provision of written informed consent.~Over 18 years of age.~Two consecutive i STAT potassium values, measured 60 (+/- 15) minutes apart, both >/= 5.1 mmol/L and measured within 1 day before the first dose of ZS on Acute Phase Study Day 1.~Ability to have repeated blood draws or effective venous catheterization.~Women of childbearing potential must be using 2 forms of medically acceptable contraception (at least 1 barrier method) and have a negative pregnancy test at Acute Phase Study Day 1. Women who are surgically sterile or those who are postmenopausal for at least 2 years are not considered to be of childbearing potential.~Controlled diabetic subjects.~Exclusion Criteria:~Pseudohyperkalemia signs and symptoms, such as hemolyzed blood specimen due to excessive fist clenching to make veins prominent, difficult or traumatic venipuncture, or history of severe leukocytosis or thrombocytosis.~Subjects treated with lactulose, rifaximin, or other non-absorbed antibiotics for hyperammonemia within 7 days prior to first dose of ZS on Acute Phase Study Day 1.~Subjects treated with sodium polystyrene sulfonate (SPS; eg, Kayexalate®) or calcium polystyrene sulfonate (eg, Resonium®) within 3 days prior to first dose of ZS on Acute Phase Study Day 1.~Subjects with a life expectancy of less than 12 months.~Subjects who are severely physically or mentally incapacitated and who, in the opinion of investigator, are unable to perform the subjects' tasks associated with the protocol.~Women who are pregnant, lactating, or planning to become pregnant.~Subjects with diabetic ketoacidosis.~Presence of any condition which, in the opinion of the investigator, places the subject at undue risk or potentially jeopardizes the quality of the data to be generated.~Known hypersensitivity or previous anaphylaxis to ZS or to components thereof.~Treatment with a drug or device within the last 30 days that has not received regulatory approval at the time of study entry.~Subjects with cardiac arrhythmias that require immediate treatment.~Subjects on dialysis.~Subjects randomized into the previous ZS-002, ZS-003, ZS-004, or ZS-004E studies.~Documented GFR <15 mL/min within 90 days prior to study entry.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants With Restoration of Normal Serum Potassium (S-K) Values (3.5 to 5.0 mmol/L, Inclusive) at the End of the Acute Phase | Percentage of subjects with S-K values between 3.5 and 5.0 mmol/L, inclusive at the end of the Acute Phase - ITT Population | 72 Hours |
| Percentage of Participants With Mean S-K Values ≤ 5.1 mmol/L During Extended Dosing Phase Days 85 to 365 | Percentage of subjects with mean S-K values ≤ 5.1 mmol/L during Extended Dosing Phase - ITT Population | Study Days 85 to 365 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects With Mean S-K Between 3.5 and 5.5 mmol/L, Inclusive Months 3 to 12 | Proportion of Subjects with mean S-K between 3.5 and 5.5 mmol/L during Extended Dosing Phase - ITT Population | Study Days 85 to 365 |
| Mean S-K Levels Months 3 to 12, Months 6 to 9, and Months 9 to 12. | Mean S-K levels months 3 to 12(EP Days 85, 113, 141, 176, 211, 239, 267, 295, 330, 365 and EOS),months 6 to 9, and months 9 to 12. | Study days 85 to 365 |
|
Hyperkalemia, Water-Electrolyte Imbalance, Metabolic Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium Zirconium Cyclosilicate<br> | Drug: Sodium Zirconium Cyclosilicate<br>* Acute Phase Dosing: Sodium Zirconium Cyclosilicate 10 g three times daily (TID) for 24 to 72 Extended Dosing: Sodium Zirconium Cyclosilicate 5 g once daily (QD). Sodium Zirconium Cyclosilicate dose increased or decreased in increments/decrements of 5 g QD up to a maximum of 15 g QD or a minimum of 5 g every other day (QOD) based on i-STAT potassium measurements up to 12 months.<br>* Other names: ZS;|
|
Open-label Safety and Efficacy of Sodium Zirconium Cyclosilicate for up to 12 Months
Study Overview
=================
Brief Summary
-----------------
The Open-Label Maintenance Study contains an Acute Phase, in which subjects will be dosed with ZS 10 g three times daily (tid) for 24 to 72 hours, followed by a long-term Maintenance Phase.
Detailed Description
-----------------
Subjects with 2 consecutive i STAT potassium values 5.1 mmol/L will enter the Acute Phase and receive ZS 10 g tid for 24 to 72 hours, depending on potassium values. Once normokalemia (i STAT potassium between 3.5 and 5.0 mmol/L, inclusive) is restored (whether after 24, 48 or 72 hours), subjects will be enrolled in the Maintenance Phase to be dosed with ZS at a starting dose of 5 g qd. Potassium (i STAT and central laboratory) will be measured weekly throughout the first month of study and every 4 weeks thereafter through Month 12. During the Maintenance Phase, the ZS dose may be increased or decreased in increments/decrements of 5 g qd up to a maximum of 15 g qd or a minimum of 5 g every other day based on i STAT potassium measurements as outlined below: • > 5.0 mmol/L while receiving 5 g qd or 5 g every other day or > 5.5 mmol/L while receiving 10 g qd: increase ZS dose in 5 g qd increments to a maximum dose of 15 g qd .• Between 3.0 and 3.4 mmol/L, inclusive: decrease ZS dose in 5 g qd decrements to a minimum dose of 5 g every other day; if a subject's i STAT potassium value remains between 3.0 and 3.4 mmol/L, inclusive, on the ZS 5 g every other day dose, the subject will be withdrawn from the study and receive standard of care treatment. There is no limit to the number of dose titrations allowed. Subjects will receive up to 12 months of treatment with open-label ZS.
Official Title
-----------------
Multicenter, Multi-Dose, Open-Label Maintenance of Long-Term Safety and Efficacy of Sodium Zirconium Cyclosilicate (ZS) in Hyperkalemia
Conditions
-----------------
Hyperkalemia
Intervention / Treatment
-----------------
* Drug: Sodium Zirconium Cyclosilicate
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provision of written informed consent. Over 18 years of age. Two consecutive i STAT potassium values, measured 60 (+/- 15) minutes apart, both >/= 5.1 mmol/L and measured within 1 day before the first dose of ZS on Acute Phase Study Day 1. Ability to have repeated blood draws or effective venous catheterization. Women of childbearing potential must be using 2 forms of medically acceptable contraception (at least 1 barrier method) and have a negative pregnancy test at Acute Phase Study Day 1. Women who are surgically sterile or those who are postmenopausal for at least 2 years are not considered to be of childbearing potential. Controlled diabetic subjects. Exclusion Criteria: Pseudohyperkalemia signs and symptoms, such as hemolyzed blood specimen due to excessive fist clenching to make veins prominent, difficult or traumatic venipuncture, or history of severe leukocytosis or thrombocytosis. Subjects treated with lactulose, rifaximin, or other non-absorbed antibiotics for hyperammonemia within 7 days prior to first dose of ZS on Acute Phase Study Day 1. Subjects treated with sodium polystyrene sulfonate (SPS; eg, Kayexalate®) or calcium polystyrene sulfonate (eg, Resonium®) within 3 days prior to first dose of ZS on Acute Phase Study Day 1. Subjects with a life expectancy of less than 12 months. Subjects who are severely physically or mentally incapacitated and who, in the opinion of investigator, are unable to perform the subjects' tasks associated with the protocol. Women who are pregnant, lactating, or planning to become pregnant. Subjects with diabetic ketoacidosis. Presence of any condition which, in the opinion of the investigator, places the subject at undue risk or potentially jeopardizes the quality of the data to be generated. Known hypersensitivity or previous anaphylaxis to ZS or to components thereof. Treatment with a drug or device within the last 30 days that has not received regulatory approval at the time of study entry. Subjects with cardiac arrhythmias that require immediate treatment. Subjects on dialysis. Subjects randomized into the previous ZS-002, ZS-003, ZS-004, or ZS-004E studies. Documented GFR <15 mL/min within 90 days prior to study entry.
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: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium Zirconium Cyclosilicate<br> | Drug: Sodium Zirconium Cyclosilicate<br>* Acute Phase Dosing: Sodium Zirconium Cyclosilicate 10 g three times daily (TID) for 24 to 72 Extended Dosing: Sodium Zirconium Cyclosilicate 5 g once daily (QD). Sodium Zirconium Cyclosilicate dose increased or decreased in increments/decrements of 5 g QD up to a maximum of 15 g QD or a minimum of 5 g every other day (QOD) based on i-STAT potassium measurements up to 12 months.<br>* Other names: ZS;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants With Restoration of Normal Serum Potassium (S-K) Values (3.5 to 5.0 mmol/L, Inclusive) at the End of the Acute Phase | Percentage of subjects with S-K values between 3.5 and 5.0 mmol/L, inclusive at the end of the Acute Phase - ITT Population | 72 Hours |
| Percentage of Participants With Mean S-K Values ≤ 5.1 mmol/L During Extended Dosing Phase Days 85 to 365 | Percentage of subjects with mean S-K values ≤ 5.1 mmol/L during Extended Dosing Phase - ITT Population | Study Days 85 to 365 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects With Mean S-K Between 3.5 and 5.5 mmol/L, Inclusive Months 3 to 12 | Proportion of Subjects with mean S-K between 3.5 and 5.5 mmol/L during Extended Dosing Phase - ITT Population | Study Days 85 to 365 |
| Mean S-K Levels Months 3 to 12, Months 6 to 9, and Months 9 to 12. | Mean S-K levels months 3 to 12(EP Days 85, 113, 141, 176, 211, 239, 267, 295, 330, 365 and EOS),months 6 to 9, and months 9 to 12. | Study days 85 to 365 |
|
|
NCT04915625
|
A Prediction Model of 28-day Mortality in Septic Shock
|
This clinical study adopts the design of cohort research, selects the sepsis shock patients admitted to our hospital ICU as the research object, takes the 28-day mortality rate as the outcome index, collects the baseline data of the patient, the severity of the disease, vital signs, the main infection site, the laboratory-related index, the treatment method and other data, screens out the risk factors affecting the sepsis shock 28-day mortality rate and constructs the prediction model accordingly, analyzes the prediction model with the subject's working characteristic curve (ROC). The recognition ability of the model is calculated by the area under the ROC curve (AUC) and the ability of the model to predict 28-day mortality with SOFA and APACHE II.
|
A Prediction Model of 28-day Mortality in Septic Shock
|
Septic Shock
|
Inclusion Criteria:~Age ≥ 18 years of age, gender-neutral;~Diagnosed with sepsis shock;~ICU survives longer than 48 h;~The preservation of clinical data is complete;~Exclusion Criteria:~- Diagnosed with sepsis shock within 6 hours of emergency treatment; Combined with people with autoimmune diseases; 3. Organ transplantation or immunosuppressive treatment; 4. Severe heart, liver and kidney insufficiency; 5. Late stage of malignant tumor; 6. Maternity; 7. Referral or referral to another hospital;
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All causes of 28 days mortality | The all-cause mortality rate is measured from the time the ICU is admitted to the hospital and 28 days after admission (regardless of ICU, hospitalization or out-of-hospital mortality). | 28 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU hospitalization time | hospitalization time | 2 years |
| hospitalization mortality | | 2 years |
|
mortality, Predictive model
|
Shock, Shock, Septic, Pathologic Processes, Sepsis, Infections, Systemic Inflammatory Response Syndrome, Inflammation
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Death group<br>Retrospective observational studies | |
| Survival group<br>Retrospective observational studies | |
|
A Prediction Model of 28-day Mortality in Septic Shock
Study Overview
=================
Brief Summary
-----------------
This clinical study adopts the design of cohort research, selects the sepsis shock patients admitted to our hospital ICU as the research object, takes the 28-day mortality rate as the outcome index, collects the baseline data of the patient, the severity of the disease, vital signs, the main infection site, the laboratory-related index, the treatment method and other data, screens out the risk factors affecting the sepsis shock 28-day mortality rate and constructs the prediction model accordingly, analyzes the prediction model with the subject's working characteristic curve (ROC). The recognition ability of the model is calculated by the area under the ROC curve (AUC) and the ability of the model to predict 28-day mortality with SOFA and APACHE II.
Official Title
-----------------
A Prediction Model of 28-day Mortality in Septic Shock
Conditions
-----------------
Septic Shock
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years of age, gender-neutral; Diagnosed with sepsis shock; ICU survives longer than 48 h; The preservation of clinical data is complete; Exclusion Criteria: - Diagnosed with sepsis shock within 6 hours of emergency treatment; Combined with people with autoimmune diseases; 3. Organ transplantation or immunosuppressive treatment; 4. Severe heart, liver and kidney insufficiency; 5. Late stage of malignant tumor; 6. Maternity; 7. Referral or referral to another hospital;
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 |
| --- | --- |
| Death group<br>Retrospective observational studies | |
| Survival group<br>Retrospective observational studies | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All causes of 28 days mortality | The all-cause mortality rate is measured from the time the ICU is admitted to the hospital and 28 days after admission (regardless of ICU, hospitalization or out-of-hospital mortality). | 28 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU hospitalization time | hospitalization time | 2 years |
| hospitalization mortality | | 2 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
mortality, Predictive model
|
|||
NCT02990078
|
Non-invasive Measurement of Cerebrovascular Reactivity After Traumatic Brain Injury
|
The investigators will longitudinally measure cerebrovascular reactivity (CVR) by functional near-infrared spectroscopy (fNIRS) in acute (≤3 days from injury), subacute, and chronic phases after TBI as a biomarker of TCVI as compared to healthy controls. CVR will be measured by fNIRS response to hypercapnia. The investigators hypothesize that CVR will be decreased after TBI and that these decreases will correlate with clinical outcomes. Furthermore, the investigators predict that administration of a vasodilatory medication (sildenafil) will augment CVR after TBI.
|
Cerebrovascular Reactivity Assessed With Functional Near-infrared Spectroscopy as a Biomarker of Traumatic Microvascular Injury After Moderate-severe Traumatic Brain Injury
|
TBI
|
* Drug: Sildenafil citrate
* Device: Functional Near Infared Spectroscopy
* Other: Hypercapnia Challenge
|
Inclusion Criteria:~Men and women, aged ≥18~CT evidence of TBI-linked abnormality~Traumatic subarachnoid hemorrhage~Intracerebral hemorrhage/contusion~Subdural/epidural hematoma~Ability to undergo fNIRS testing with hypercapnia challenge~Subject able to provide informed consent~Attending of record agrees to include subject in study~Exclusion Criteria:~Unstable respiratory or hemodynamic status~Evidence of penetrating brain injury~TBI requiring craniotomy or craniectomy~Evidence or risk of ICP crisis~History of disabling pre-existing neurologic disorder (e.g. dementia, uncontrolled epilepsy, multiple sclerosis, strokes, brain tumors, prior severe TBI, or other disorder that confounds interpretation of NIRS testing or neuropsychological results)~History of pre-existing disabling mental illness (e.g. major depression or schizophrenia)~Exclusion criteria for sildenafil administration:~History of melanoma~current use of organic nitrate vasodilators~current use of ritonavir (HIV-protease inhibitor)~current use of erythromycin, ketoconazole, or itraconazole; current use of cimetidine~current use of alpha-blockers such as doxazosin (Cardura), tamsulosin (Flomax), and terazosin (Hytrin) prazosin (Minipres)~resting hypotension (systolic BP <90)~severe renal insufficiency~hepatic cirrhosis~acute ischemic stroke within past 2 months~acute myocardial infarction within past 2 months~unstable angina pectoris~acute or chronic heart failure~retinitis pigmentosa~pregnant or breastfeeding female~known hypersensitivity or allergy to sildenafil~Unstable cardiac status that constitutes a contraindication to sexual activity~Inability to read and communicate in English (necessary to obtain reliable neuropsychometric data)~Nursing mothers
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CVR prior to sildenafil administration | | < 72hrs, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change CVR after sildenafil administration | | <72 hours, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years |
| Relationship of CVR with symptom reports, as measured by the Neurobehavioral Symptom Inventory (NBSI). | | < 72hrs, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years |
|
fNIRS, TBI, CVR, Hypercapnia
|
Sildenafil Citrate, Molecular Mechanisms of Pharmacological Action, Vasodilator Agents, Phosphodiesterase 5 Inhibitors, Phosphodiesterase Inhibitors, Enzyme Inhibitors, Urological Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Acute TBI<br>Subjects will be recruited from the neurointensive care unit within 72 hours of their injury. At the time of informed consent, the investigators will perform fNIRS testing with a hypercapnia challenge, fNIRS with hypercapnia challenge 60 minutes after a single oral dose of 50mg sildenafil citrate, outcome qustionaires and symptom checklists (including: Glasgow Outcomes Scale-Extended, Rivermead Post-Concussive Symptom Questionnaire, Brief Symptom Inventory, Alcohol Consumption Questionnaire, Patient Health Questionnaire, and Insomnia Severity Index). This will all be administered again at 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, and 4 years after injury. | Drug: Sildenafil citrate<br>* Sildenafil is a potent and specific PDE5 inhibitor, which was initially developed for the treatment of hypertension and angina. Its effectiveness as a treatment for male erectile dysfunction became apparent during Phase I clinical trials, and the focus of drug development shifted to this indication. In patients with cerebrovascular dysfunction, a few preliminary studies have used sildenafil to increase CVR. Participants in the pilot study had CVR tested in response to hypercapnia measured twice, at baseline and then 1 hour after administration of sildenafil citrate, 50 mg by mouth. The investigators have an IND exemption for the uses in this study.<br>* Other names: Viagra;Device: Functional Near Infared Spectroscopy<br>* Functional near-infrared spectroscopy (fNIRS) will be used to measure regional cerebral blood flow and cerebrovascular reactivity. are connected to the scalp and surrounding detectors a few cm away detect the light as it scatters through the underlying tissues. The technique is able to detect changes in the absorption spectrum of the tissue corresponding to the concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR), and indicate local perfusion changes.<br>* Other names: fNIRS;Other: Hypercapnia Challenge<br>* The study device is a Douglas Bag that traditionally is designed to measure respiratory exchange. It consists of large bag attached to a mouthpiece utilized to hold either expired air from the subject or filled with different concentrations of air to be aspired. For the purposes of this study, the Douglas Bag will be utilized to induce hypercapnia in the subject. The bag is equipped with a switch that allows rapid shifting from room air to 5% CO2 each minute over 7 minutes.<br>|
| Sub-acute/Chronic TBI<br>Subjects who suffered a TBI previously and have now entered a subacute or chronic phase of their TBI will be approached by the research team at their clinic visit with a TBI specialist. In those subjects, study timing will be based on the time of their original injury, therefore will start study visits at the next possible time point. | Drug: Sildenafil citrate<br>* Sildenafil is a potent and specific PDE5 inhibitor, which was initially developed for the treatment of hypertension and angina. Its effectiveness as a treatment for male erectile dysfunction became apparent during Phase I clinical trials, and the focus of drug development shifted to this indication. In patients with cerebrovascular dysfunction, a few preliminary studies have used sildenafil to increase CVR. Participants in the pilot study had CVR tested in response to hypercapnia measured twice, at baseline and then 1 hour after administration of sildenafil citrate, 50 mg by mouth. The investigators have an IND exemption for the uses in this study.<br>* Other names: Viagra;Device: Functional Near Infared Spectroscopy<br>* Functional near-infrared spectroscopy (fNIRS) will be used to measure regional cerebral blood flow and cerebrovascular reactivity. are connected to the scalp and surrounding detectors a few cm away detect the light as it scatters through the underlying tissues. The technique is able to detect changes in the absorption spectrum of the tissue corresponding to the concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR), and indicate local perfusion changes.<br>* Other names: fNIRS;Other: Hypercapnia Challenge<br>* The study device is a Douglas Bag that traditionally is designed to measure respiratory exchange. It consists of large bag attached to a mouthpiece utilized to hold either expired air from the subject or filled with different concentrations of air to be aspired. For the purposes of this study, the Douglas Bag will be utilized to induce hypercapnia in the subject. The bag is equipped with a switch that allows rapid shifting from room air to 5% CO2 each minute over 7 minutes.<br>|
| Healthy Controls<br>The investigators will also enroll healthy peer controls. These control subjects will be family members and friends of TBI subjects. These peer controls are likely to have similar environmental and socioeconomic exposures/support which may impact recovery after TBI and may also impact CVR. These control subjects will meet the same inclusion/exclusion criteria as TBI subjects without the requirement for an injury or acute brain imaging. These subjects will be tested in the same way as both TBI groups, but will only have one visit. | Drug: Sildenafil citrate<br>* Sildenafil is a potent and specific PDE5 inhibitor, which was initially developed for the treatment of hypertension and angina. Its effectiveness as a treatment for male erectile dysfunction became apparent during Phase I clinical trials, and the focus of drug development shifted to this indication. In patients with cerebrovascular dysfunction, a few preliminary studies have used sildenafil to increase CVR. Participants in the pilot study had CVR tested in response to hypercapnia measured twice, at baseline and then 1 hour after administration of sildenafil citrate, 50 mg by mouth. The investigators have an IND exemption for the uses in this study.<br>* Other names: Viagra;Device: Functional Near Infared Spectroscopy<br>* Functional near-infrared spectroscopy (fNIRS) will be used to measure regional cerebral blood flow and cerebrovascular reactivity. are connected to the scalp and surrounding detectors a few cm away detect the light as it scatters through the underlying tissues. The technique is able to detect changes in the absorption spectrum of the tissue corresponding to the concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR), and indicate local perfusion changes.<br>* Other names: fNIRS;Other: Hypercapnia Challenge<br>* The study device is a Douglas Bag that traditionally is designed to measure respiratory exchange. It consists of large bag attached to a mouthpiece utilized to hold either expired air from the subject or filled with different concentrations of air to be aspired. For the purposes of this study, the Douglas Bag will be utilized to induce hypercapnia in the subject. The bag is equipped with a switch that allows rapid shifting from room air to 5% CO2 each minute over 7 minutes.<br>|
|
Non-invasive Measurement of Cerebrovascular Reactivity After Traumatic Brain Injury
Study Overview
=================
Brief Summary
-----------------
The investigators will longitudinally measure cerebrovascular reactivity (CVR) by functional near-infrared spectroscopy (fNIRS) in acute (≤3 days from injury), subacute, and chronic phases after TBI as a biomarker of TCVI as compared to healthy controls. CVR will be measured by fNIRS response to hypercapnia. The investigators hypothesize that CVR will be decreased after TBI and that these decreases will correlate with clinical outcomes. Furthermore, the investigators predict that administration of a vasodilatory medication (sildenafil) will augment CVR after TBI.
Official Title
-----------------
Cerebrovascular Reactivity Assessed With Functional Near-infrared Spectroscopy as a Biomarker of Traumatic Microvascular Injury After Moderate-severe Traumatic Brain Injury
Conditions
-----------------
TBI
Intervention / Treatment
-----------------
* Drug: Sildenafil citrate
* Device: Functional Near Infared Spectroscopy
* Other: Hypercapnia Challenge
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women, aged ≥18 CT evidence of TBI-linked abnormality Traumatic subarachnoid hemorrhage Intracerebral hemorrhage/contusion Subdural/epidural hematoma Ability to undergo fNIRS testing with hypercapnia challenge Subject able to provide informed consent Attending of record agrees to include subject in study Exclusion Criteria: Unstable respiratory or hemodynamic status Evidence of penetrating brain injury TBI requiring craniotomy or craniectomy Evidence or risk of ICP crisis History of disabling pre-existing neurologic disorder (e.g. dementia, uncontrolled epilepsy, multiple sclerosis, strokes, brain tumors, prior severe TBI, or other disorder that confounds interpretation of NIRS testing or neuropsychological results) History of pre-existing disabling mental illness (e.g. major depression or schizophrenia) Exclusion criteria for sildenafil administration: History of melanoma current use of organic nitrate vasodilators current use of ritonavir (HIV-protease inhibitor) current use of erythromycin, ketoconazole, or itraconazole; current use of cimetidine current use of alpha-blockers such as doxazosin (Cardura), tamsulosin (Flomax), and terazosin (Hytrin) prazosin (Minipres) resting hypotension (systolic BP <90) severe renal insufficiency hepatic cirrhosis acute ischemic stroke within past 2 months acute myocardial infarction within past 2 months unstable angina pectoris acute or chronic heart failure retinitis pigmentosa pregnant or breastfeeding female known hypersensitivity or allergy to sildenafil Unstable cardiac status that constitutes a contraindication to sexual activity Inability to read and communicate in English (necessary to obtain reliable neuropsychometric data) Nursing mothers
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?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Acute TBI<br>Subjects will be recruited from the neurointensive care unit within 72 hours of their injury. At the time of informed consent, the investigators will perform fNIRS testing with a hypercapnia challenge, fNIRS with hypercapnia challenge 60 minutes after a single oral dose of 50mg sildenafil citrate, outcome qustionaires and symptom checklists (including: Glasgow Outcomes Scale-Extended, Rivermead Post-Concussive Symptom Questionnaire, Brief Symptom Inventory, Alcohol Consumption Questionnaire, Patient Health Questionnaire, and Insomnia Severity Index). This will all be administered again at 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, and 4 years after injury. | Drug: Sildenafil citrate<br>* Sildenafil is a potent and specific PDE5 inhibitor, which was initially developed for the treatment of hypertension and angina. Its effectiveness as a treatment for male erectile dysfunction became apparent during Phase I clinical trials, and the focus of drug development shifted to this indication. In patients with cerebrovascular dysfunction, a few preliminary studies have used sildenafil to increase CVR. Participants in the pilot study had CVR tested in response to hypercapnia measured twice, at baseline and then 1 hour after administration of sildenafil citrate, 50 mg by mouth. The investigators have an IND exemption for the uses in this study.<br>* Other names: Viagra;Device: Functional Near Infared Spectroscopy<br>* Functional near-infrared spectroscopy (fNIRS) will be used to measure regional cerebral blood flow and cerebrovascular reactivity. are connected to the scalp and surrounding detectors a few cm away detect the light as it scatters through the underlying tissues. The technique is able to detect changes in the absorption spectrum of the tissue corresponding to the concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR), and indicate local perfusion changes.<br>* Other names: fNIRS;Other: Hypercapnia Challenge<br>* The study device is a Douglas Bag that traditionally is designed to measure respiratory exchange. It consists of large bag attached to a mouthpiece utilized to hold either expired air from the subject or filled with different concentrations of air to be aspired. For the purposes of this study, the Douglas Bag will be utilized to induce hypercapnia in the subject. The bag is equipped with a switch that allows rapid shifting from room air to 5% CO2 each minute over 7 minutes.<br>|
| Sub-acute/Chronic TBI<br>Subjects who suffered a TBI previously and have now entered a subacute or chronic phase of their TBI will be approached by the research team at their clinic visit with a TBI specialist. In those subjects, study timing will be based on the time of their original injury, therefore will start study visits at the next possible time point. | Drug: Sildenafil citrate<br>* Sildenafil is a potent and specific PDE5 inhibitor, which was initially developed for the treatment of hypertension and angina. Its effectiveness as a treatment for male erectile dysfunction became apparent during Phase I clinical trials, and the focus of drug development shifted to this indication. In patients with cerebrovascular dysfunction, a few preliminary studies have used sildenafil to increase CVR. Participants in the pilot study had CVR tested in response to hypercapnia measured twice, at baseline and then 1 hour after administration of sildenafil citrate, 50 mg by mouth. The investigators have an IND exemption for the uses in this study.<br>* Other names: Viagra;Device: Functional Near Infared Spectroscopy<br>* Functional near-infrared spectroscopy (fNIRS) will be used to measure regional cerebral blood flow and cerebrovascular reactivity. are connected to the scalp and surrounding detectors a few cm away detect the light as it scatters through the underlying tissues. The technique is able to detect changes in the absorption spectrum of the tissue corresponding to the concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR), and indicate local perfusion changes.<br>* Other names: fNIRS;Other: Hypercapnia Challenge<br>* The study device is a Douglas Bag that traditionally is designed to measure respiratory exchange. It consists of large bag attached to a mouthpiece utilized to hold either expired air from the subject or filled with different concentrations of air to be aspired. For the purposes of this study, the Douglas Bag will be utilized to induce hypercapnia in the subject. The bag is equipped with a switch that allows rapid shifting from room air to 5% CO2 each minute over 7 minutes.<br>|
| Healthy Controls<br>The investigators will also enroll healthy peer controls. These control subjects will be family members and friends of TBI subjects. These peer controls are likely to have similar environmental and socioeconomic exposures/support which may impact recovery after TBI and may also impact CVR. These control subjects will meet the same inclusion/exclusion criteria as TBI subjects without the requirement for an injury or acute brain imaging. These subjects will be tested in the same way as both TBI groups, but will only have one visit. | Drug: Sildenafil citrate<br>* Sildenafil is a potent and specific PDE5 inhibitor, which was initially developed for the treatment of hypertension and angina. Its effectiveness as a treatment for male erectile dysfunction became apparent during Phase I clinical trials, and the focus of drug development shifted to this indication. In patients with cerebrovascular dysfunction, a few preliminary studies have used sildenafil to increase CVR. Participants in the pilot study had CVR tested in response to hypercapnia measured twice, at baseline and then 1 hour after administration of sildenafil citrate, 50 mg by mouth. The investigators have an IND exemption for the uses in this study.<br>* Other names: Viagra;Device: Functional Near Infared Spectroscopy<br>* Functional near-infrared spectroscopy (fNIRS) will be used to measure regional cerebral blood flow and cerebrovascular reactivity. are connected to the scalp and surrounding detectors a few cm away detect the light as it scatters through the underlying tissues. The technique is able to detect changes in the absorption spectrum of the tissue corresponding to the concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR), and indicate local perfusion changes.<br>* Other names: fNIRS;Other: Hypercapnia Challenge<br>* The study device is a Douglas Bag that traditionally is designed to measure respiratory exchange. It consists of large bag attached to a mouthpiece utilized to hold either expired air from the subject or filled with different concentrations of air to be aspired. For the purposes of this study, the Douglas Bag will be utilized to induce hypercapnia in the subject. The bag is equipped with a switch that allows rapid shifting from room air to 5% CO2 each minute over 7 minutes.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CVR prior to sildenafil administration | | < 72hrs, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change CVR after sildenafil administration | | <72 hours, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years |
| Relationship of CVR with symptom reports, as measured by the Neurobehavioral Symptom Inventory (NBSI). | | < 72hrs, 14 days, 90 days, 180 days, 1 year, 2 years, 3 years, 4 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
fNIRS, TBI, CVR, Hypercapnia
|
||
NCT01176968
|
Impact Of Eplerenone On Cardiovascular Outcomes In Patients Post Myocardial Infarction
|
Administration of eplerenone within 24 hours of onset of symptoms of myocardial infarction, in patients without heart failure, reduces cardiovascular mortality / morbidity.
|
A Double-blind, Randomized, Placebo-controlled Trial Evaluating The Safety And Efficacy Of Early Treatment With Eplerenone In Patients With Acute Myocardial Infarction
|
Myocardial Infarction
|
* Drug: Eplerenone
* Drug: Placebo
|
Inclusion Criteria:~Subjects must have experienced a myocardial infarction (STEMI) within the previous 24 hours confirmed by symptoms and ECG.~Exclusion Criteria:~Subjects with a known low ejection fraction of less than 40% or any previous history of heart failure.~Subjects treated with eplerenone or other aldosterone antagonists within the past 1 month.~The subject has uncontrolled hypotension (SBP<90mmHg).~Subjects with eGFR ≤30ml/min (based on admission serum creatinine and the MDRD formula) or serum creatinine ≥220µmol/L.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First Event of Cardiovascular Mortality, Re-hospitalization or Extended Initial Hospital Stay Due to Diagnosis of Heart Failure, Sustained Ventricular Tachycardia or Fibrillation, Ejection Fraction ≤40% or BNP Above Age Adjusted Cut Off | Cardiovascular mortality is defined as any mortality adjudicated as death due to sudden cardiac death, myocardial infarction (MI), worsening heart failure, cardiac arrhythmia, other cause (such as pulmonary embolism, peripheral arterial disease [PAD], etc.). Hospitalization due to congestive heart failure (CHF) and requires extended hospital stay or frequent visits to emergency room, observation unit or in-patient care, due to CHF as the primary or secondary diagnosis supported by a discharge report or clinical summary for hospitalization as determined by the endpoint adjudication committee (EAC). A composite of time to first event of cardiovascular mortality (CV), re-hospitalization or extended initial hospital stay due to diagnosis of heart failure, sustained ventricular tachycardia or fibrillation, ejection fraction ≤40% after 1 month or BNP >200 pg/mL or NT-proBNP >450 pg/mL (age <50 years); >900 pg/mL (age 50 to 75 years) or >1800 pg/mL (age >75 years) after 1 month. | 0-24 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular Mortality | The occurrence of cardiovascular mortality from randomization. Time-to-event analyses were measured from the date of randomization. A subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence. | 0-24 months |
| Diagnosis of Heart Failure | The occurrence of first diagnosis of heart failure from the date of randomization. Time-to-event analyses were measured from the date of randomization, and a subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence. | 0-24 months |
| First and Each Subsequent Episode (After an Event Free Interval of ≥ 48 Hours) of Sustained Ventricular Tachycardia or Ventricular Fibrillation. | The occurrence of first and each subsequent episode (after an event-free interval of ≥ 48 hours) of sustained ventricular tachycardia or ventricular fibrillation. Time-to-event analyses were measured from the date of randomization. A subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence. | 0-24 months |
| First Recorded Ejection Fraction (EF) of ≤40% (Recorded 1 Month or Later Post-randomization). | The occurrence of first recorded EF ≤40% (recorded 28 days or later post-randomization). Time-to-event analyses were measured from the date of randomization. A subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence. | 0-24 months |
| Brain (B-type) Natriuretic Peptide (BNP) >200 pg/mL or NT-proBNP >450, >900 or >1800 pg/mL for Ages <50 Years, 50-75 Years and >75 Years, Respectively (Recorded 1 Month or Later Post-randomization). | The occurrence of first occurrence of BNP >200 pg/mL or NT-proBNP >450, >900 or >1800 pg/mL for ages <50 years, 50 to 75 years and >75 years, respectively (recorded 28 days or later post-randomization). Time-to-event analyses were measured from the date of randomization. A subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence. | 0-24 months |
| Decision to Provide an Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronization Therapy (CRT). | The decision to provide an ICD or CRT. Time-to-event analyses were measured from the date of randomization. A subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence. | 0-24 months |
| Second or Subsequent Non-fatal Myocardial Infarction (MI). | The occurrence of second or subsequent nonfatal MI. Time-to-event analyses were measured from the date of randomization. A subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence. | 0-24 months |
| Electrocardiogram Q Wave to the End of the S Wave Corresponding to Ventricle Depolarization (QRS) Duration at 6 Months Post-randomization. | Electrocardiogram Q wave to the end of the S wave corresponding to ventricle depolarization (QRS) duration at 6 months post-randomization. The continuous endpoints were assessed using analysis of covariance (ANCOVA) model, fitted with corresponding baseline and treatment. These were analyzed at 6 months based on last observation carried forward (LOCF) and also using all available data up to end of study. | 6 months |
| Left Atrial Diameter (LAD) (Recorded on Each Occasion an Echocardiogram is Conducted). | LAD recorded each time an echocardiogram is conducted. The continuous endpoints were assessed using ANCOVA model, fitted with corresponding baseline and treatment. These were analyzed at 6 months based on LOCF and also using all available data up to end of study. | 0-24 months |
| Change in Serum Levels of Biomarkers (Aldosterone and Cortisol) at 6 Months Post-randomization. | Change in serum levels of aldosterone and cortisol at 6 months post-randomization. The continuous endpoints were assessed using ANCOVA model, fitted with corresponding baseline and treatment. These were analyzed at 6 months based on LOCF and also using all available data up to end of study. | 6 months |
| Change in Serum Levels of Biomarkers (PIIINP, Galectin 3, and PINP) at 6 Months Post-randomization. | Change in serum levels of PIIINP, Galectin 3, and PINP at 6 months post-randomization. The continuous endpoints were assessed using ANCOVA model, fitted with corresponding baseline and treatment. These were analyzed at 6 months based on LOCF and also using all available data up to end of study. | 6 months |
| Change in Serum Level of Biomarker (ICTP) at 6 Months Post-randomization. | Change in serum level of ICTP at 6 months post-randomization. The continuous endpoint was assessed using ANCOVA model, fitted with corresponding baseline and treatment. It was analyzed at 6 months based on LOCF and also using all available data up to end of study. | 6 months |
| Change in Serum Level of Biomarker (Interleukin-6) at 6 Months Post-randomization. | Change in serum level of Interleukin-6 at 6 months post-randomization. The continuous endpoint was assessed using ANCOVA model, fitted with corresponding baseline and treatment. It was analyzed at 6 months based on LOCF and also using all available data up to end of study. | 6 months |
|
Eplerenone, myocardial infarction, mortality, morbidity
|
Eplerenone, Mineralocorticoid Receptor Antagonists, Hormone Antagonists, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs, Diuretics, Potassium Sparing, Diuretics, Natriuretic Agents, Antihypertensive Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eplerenone plus standard of care<br> | Drug: Eplerenone<br>* Maximum dose of 2x25 mg film coated tablets per day for the duration of the study (approximately 18 months maximum). Lower doses may be administered determined by blood biochemistry data.<br>* Other names: Inspra;|
| Placebo Comparator: Placebo plus standard of care<br>Matching placebo for eplerenone 25mg film coated tablets. | Drug: Placebo<br>* Matching placebo tablets<br>|
|
Impact Of Eplerenone On Cardiovascular Outcomes In Patients Post Myocardial Infarction
Study Overview
=================
Brief Summary
-----------------
Administration of eplerenone within 24 hours of onset of symptoms of myocardial infarction, in patients without heart failure, reduces cardiovascular mortality / morbidity.
Official Title
-----------------
A Double-blind, Randomized, Placebo-controlled Trial Evaluating The Safety And Efficacy Of Early Treatment With Eplerenone In Patients With Acute Myocardial Infarction
Conditions
-----------------
Myocardial Infarction
Intervention / Treatment
-----------------
* Drug: Eplerenone
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must have experienced a myocardial infarction (STEMI) within the previous 24 hours confirmed by symptoms and ECG. Exclusion Criteria: Subjects with a known low ejection fraction of less than 40% or any previous history of heart failure. Subjects treated with eplerenone or other aldosterone antagonists within the past 1 month. The subject has uncontrolled hypotension (SBP<90mmHg). Subjects with eGFR ≤30ml/min (based on admission serum creatinine and the MDRD formula) or serum creatinine ≥220µmol/L.
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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eplerenone plus standard of care<br> | Drug: Eplerenone<br>* Maximum dose of 2x25 mg film coated tablets per day for the duration of the study (approximately 18 months maximum). Lower doses may be administered determined by blood biochemistry data.<br>* Other names: Inspra;|
| Placebo Comparator: Placebo plus standard of care<br>Matching placebo for eplerenone 25mg film coated tablets. | Drug: Placebo<br>* Matching placebo tablets<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First Event of Cardiovascular Mortality, Re-hospitalization or Extended Initial Hospital Stay Due to Diagnosis of Heart Failure, Sustained Ventricular Tachycardia or Fibrillation, Ejection Fraction ≤40% or BNP Above Age Adjusted Cut Off | Cardiovascular mortality is defined as any mortality adjudicated as death due to sudden cardiac death, myocardial infarction (MI), worsening heart failure, cardiac arrhythmia, other cause (such as pulmonary embolism, peripheral arterial disease [PAD], etc.). Hospitalization due to congestive heart failure (CHF) and requires extended hospital stay or frequent visits to emergency room, observation unit or in-patient care, due to CHF as the primary or secondary diagnosis supported by a discharge report or clinical summary for hospitalization as determined by the endpoint adjudication committee (EAC). A composite of time to first event of cardiovascular mortality (CV), re-hospitalization or extended initial hospital stay due to diagnosis of heart failure, sustained ventricular tachycardia or fibrillation, ejection fraction ≤40% after 1 month or BNP >200 pg/mL or NT-proBNP >450 pg/mL (age <50 years); >900 pg/mL (age 50 to 75 years) or >1800 pg/mL (age >75 years) after 1 month. | 0-24 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular Mortality | The occurrence of cardiovascular mortality from randomization. Time-to-event analyses were measured from the date of randomization. A subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence. | 0-24 months |
| Diagnosis of Heart Failure | The occurrence of first diagnosis of heart failure from the date of randomization. Time-to-event analyses were measured from the date of randomization, and a subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence. | 0-24 months |
| First and Each Subsequent Episode (After an Event Free Interval of ≥ 48 Hours) of Sustained Ventricular Tachycardia or Ventricular Fibrillation. | The occurrence of first and each subsequent episode (after an event-free interval of ≥ 48 hours) of sustained ventricular tachycardia or ventricular fibrillation. Time-to-event analyses were measured from the date of randomization. A subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence. | 0-24 months |
| First Recorded Ejection Fraction (EF) of ≤40% (Recorded 1 Month or Later Post-randomization). | The occurrence of first recorded EF ≤40% (recorded 28 days or later post-randomization). Time-to-event analyses were measured from the date of randomization. A subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence. | 0-24 months |
| Brain (B-type) Natriuretic Peptide (BNP) >200 pg/mL or NT-proBNP >450, >900 or >1800 pg/mL for Ages <50 Years, 50-75 Years and >75 Years, Respectively (Recorded 1 Month or Later Post-randomization). | The occurrence of first occurrence of BNP >200 pg/mL or NT-proBNP >450, >900 or >1800 pg/mL for ages <50 years, 50 to 75 years and >75 years, respectively (recorded 28 days or later post-randomization). Time-to-event analyses were measured from the date of randomization. A subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence. | 0-24 months |
| Decision to Provide an Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronization Therapy (CRT). | The decision to provide an ICD or CRT. Time-to-event analyses were measured from the date of randomization. A subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence. | 0-24 months |
| Second or Subsequent Non-fatal Myocardial Infarction (MI). | The occurrence of second or subsequent nonfatal MI. Time-to-event analyses were measured from the date of randomization. A subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence. | 0-24 months |
| Electrocardiogram Q Wave to the End of the S Wave Corresponding to Ventricle Depolarization (QRS) Duration at 6 Months Post-randomization. | Electrocardiogram Q wave to the end of the S wave corresponding to ventricle depolarization (QRS) duration at 6 months post-randomization. The continuous endpoints were assessed using analysis of covariance (ANCOVA) model, fitted with corresponding baseline and treatment. These were analyzed at 6 months based on last observation carried forward (LOCF) and also using all available data up to end of study. | 6 months |
| Left Atrial Diameter (LAD) (Recorded on Each Occasion an Echocardiogram is Conducted). | LAD recorded each time an echocardiogram is conducted. The continuous endpoints were assessed using ANCOVA model, fitted with corresponding baseline and treatment. These were analyzed at 6 months based on LOCF and also using all available data up to end of study. | 0-24 months |
| Change in Serum Levels of Biomarkers (Aldosterone and Cortisol) at 6 Months Post-randomization. | Change in serum levels of aldosterone and cortisol at 6 months post-randomization. The continuous endpoints were assessed using ANCOVA model, fitted with corresponding baseline and treatment. These were analyzed at 6 months based on LOCF and also using all available data up to end of study. | 6 months |
| Change in Serum Levels of Biomarkers (PIIINP, Galectin 3, and PINP) at 6 Months Post-randomization. | Change in serum levels of PIIINP, Galectin 3, and PINP at 6 months post-randomization. The continuous endpoints were assessed using ANCOVA model, fitted with corresponding baseline and treatment. These were analyzed at 6 months based on LOCF and also using all available data up to end of study. | 6 months |
| Change in Serum Level of Biomarker (ICTP) at 6 Months Post-randomization. | Change in serum level of ICTP at 6 months post-randomization. The continuous endpoint was assessed using ANCOVA model, fitted with corresponding baseline and treatment. It was analyzed at 6 months based on LOCF and also using all available data up to end of study. | 6 months |
| Change in Serum Level of Biomarker (Interleukin-6) at 6 Months Post-randomization. | Change in serum level of Interleukin-6 at 6 months post-randomization. The continuous endpoint was assessed using ANCOVA model, fitted with corresponding baseline and treatment. It was analyzed at 6 months based on LOCF and also using all available data up to end of study. | 6 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Eplerenone, myocardial infarction, mortality, morbidity
|
|
NCT03644511
|
Use of Sorafenib and/or Regorafenib in Liver Cancer (Hepatocellular Carcinoma) Subsequent to Another Systemic First-line Treatment
|
Researchers already did trials that showed Sorafenib and Regorafenib worked for patients with hepatocellular carcinoma (most common liver tumor type).~In this trial, they want to learn more about the same patient group in which Sorafenib or Regorafenib is given after other drugs. Patients participating in this study will be observed until 12 months after the last patient has been enrolled to collect data on how safe the drugs are and how well they are working when used as second line or beyond treatment.
|
Use of Sorafenib and/or Regorafenib in Hepatocellular Carcinoma (HCC) Subsequent to Another Systemic First-line Treatment
|
Hepatocellular Carcinoma
|
* Drug: Regorafenib (Stivarga, BAY73-4506)
* Drug: Sorafenib (Nexavar, BAY43-9006)
|
Inclusion Criteria:~Diagnosis of hepatocellular cancer in stage BCLC-B or BCLC-C~Decision to initiate treatment with Nexavar (sorafenib) and/or Stivarga (regorafenib) as 2nd-line or beyond treatment was made as per investigator's routine treatment practice. Stivarga (regorafenib) must be used according to its indication, i.e. after prior progression under Nexavar (sorafenib) treatment.~Exclusion Criteria:~Patients concurrently participating in an investigational program for the treatment of HCC with interventions outside of routine clinical practice.~Stivarga (regorafenib) treatment without prior therapy with Nexavar (sorafenib). NOTE: Nexavar (sorafenib) treatment could have been given as treatment for HCC outside of this non-interventional study. In this case Stivarga (regorafenib) would NOT constitute the second-line therapy after direct pretreatment with Nexavar (sorafenib) but e.g. 3rd-line treatment directly after a different drug.~Contra-indications according to the local marketing authorization.
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of current treatment patterns by means of individual treatment lines in the systemic HCC therapy with regards to Nexavar and Stivarga, i.e. when both drugs are used in ≥ 2nd-line under current practice conditions | | Up to 24 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) from start of Nexavar or Stivarga therapy and from start of first systemic therapy | | Up to 36 months |
| Progression free survival (PFS) | | Up to 36 months |
| Time to progression (TTP) | | Up to 36 months |
| Duration of Nexavar or Stivarga treatment | | Up to 36 months |
| Tumor response to treatment | Evaluated by the investigator according to the categories complete response, partial response, stable disease, progressive disease by clinical judgment, progressive disease measurement proven, unknown and not applicable, and will be analyzed providing absolute and relative frequencies of the tumor status categories. | Up to 36 months |
| Incidence of treatment-emergent adverse events (TEAE) | | Up to 36 months |
|
HCC, Liver cancer, Live cell carcinoma
|
Molecular Mechanisms of Pharmacological Action, Sorafenib, Antineoplastic Agents, Protein Kinase Inhibitors, Enzyme Inhibitors
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with HCC<br>Treated with Nexavar and/or Stivarga as ≥ 2nd-line systemic treatment | Drug: Regorafenib (Stivarga, BAY73-4506)<br>* Prescribed by physician.<br>Drug: Sorafenib (Nexavar, BAY43-9006)<br>* Prescribed by physician.<br>|
|
Use of Sorafenib and/or Regorafenib in Liver Cancer (Hepatocellular Carcinoma) Subsequent to Another Systemic First-line Treatment
Study Overview
=================
Brief Summary
-----------------
Researchers already did trials that showed Sorafenib and Regorafenib worked for patients with hepatocellular carcinoma (most common liver tumor type). In this trial, they want to learn more about the same patient group in which Sorafenib or Regorafenib is given after other drugs. Patients participating in this study will be observed until 12 months after the last patient has been enrolled to collect data on how safe the drugs are and how well they are working when used as second line or beyond treatment.
Official Title
-----------------
Use of Sorafenib and/or Regorafenib in Hepatocellular Carcinoma (HCC) Subsequent to Another Systemic First-line Treatment
Conditions
-----------------
Hepatocellular Carcinoma
Intervention / Treatment
-----------------
* Drug: Regorafenib (Stivarga, BAY73-4506)
* Drug: Sorafenib (Nexavar, BAY43-9006)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of hepatocellular cancer in stage BCLC-B or BCLC-C Decision to initiate treatment with Nexavar (sorafenib) and/or Stivarga (regorafenib) as 2nd-line or beyond treatment was made as per investigator's routine treatment practice. Stivarga (regorafenib) must be used according to its indication, i.e. after prior progression under Nexavar (sorafenib) treatment. Exclusion Criteria: Patients concurrently participating in an investigational program for the treatment of HCC with interventions outside of routine clinical practice. Stivarga (regorafenib) treatment without prior therapy with Nexavar (sorafenib). NOTE: Nexavar (sorafenib) treatment could have been given as treatment for HCC outside of this non-interventional study. In this case Stivarga (regorafenib) would NOT constitute the second-line therapy after direct pretreatment with Nexavar (sorafenib) but e.g. 3rd-line treatment directly after a different drug. Contra-indications according to the local marketing authorization.
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 |
| --- | --- |
| Patients with HCC<br>Treated with Nexavar and/or Stivarga as ≥ 2nd-line systemic treatment | Drug: Regorafenib (Stivarga, BAY73-4506)<br>* Prescribed by physician.<br>Drug: Sorafenib (Nexavar, BAY43-9006)<br>* Prescribed by physician.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of current treatment patterns by means of individual treatment lines in the systemic HCC therapy with regards to Nexavar and Stivarga, i.e. when both drugs are used in ≥ 2nd-line under current practice conditions | | Up to 24 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) from start of Nexavar or Stivarga therapy and from start of first systemic therapy | | Up to 36 months |
| Progression free survival (PFS) | | Up to 36 months |
| Time to progression (TTP) | | Up to 36 months |
| Duration of Nexavar or Stivarga treatment | | Up to 36 months |
| Tumor response to treatment | Evaluated by the investigator according to the categories complete response, partial response, stable disease, progressive disease by clinical judgment, progressive disease measurement proven, unknown and not applicable, and will be analyzed providing absolute and relative frequencies of the tumor status categories. | Up to 36 months |
| Incidence of treatment-emergent adverse events (TEAE) | | Up to 36 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HCC, Liver cancer, Live cell carcinoma
|
||
NCT02016469
|
Effects of Pectin on Flora Intestinal Colonization and Maintenance After Fecal Transplantation
|
The purpose of this study is to evaluate the effect and safety of pectin and fecal microbiota transplantation on patients with inflammatory bowel disease. The investigators hypothesize that patients who take pectin can promote the migration of probiotics in intestine engraftment, reduce pathogenic agents'adhesion to intestinal mucosa, cut down the inflammation, and to maintain intestinal flora diversity and steady state in a long time.
|
Inflammatory bowel disease (IBD) is a chronic relapsing disease, including ulcerative colitis (UC) and Crohn's disease (CD). Although the etiology of IBD is unknown, but more and more evidence show that the inappropriate immune response to intestinal commensal bacteria leading to dysbiosis, and pathogens further act to the mucosal lymphoid tissue, causing IBD. Has yet not to determine the specific one or more pathogens as the cause of IBD,but literatures confirm the changes of diversity of the intestine flora.Based on the current awareness of changes in the intestinal flora in IBD, fecal microbiota transplantation (FMT) proposed in recent years to rebuild the intestine flora balance to achieve therapeutic purposes. But fecal bacteria of patients can not consistent with donor's for a long term after transplantation and therefore it is not an ideal way for disease control. Maintaining the diversity of flora in a long time so that well controlled the disease become the breakthrough of fecal microbiota transplantation in the treatment of inflammatory bowel disease.~Pectin is a soluble dietary fiber (DF), produced by the gut flora after a series of fermentation with many metabolites such as short chain fatty acids (SCFA) which supply the energy for epithelial cells, regulate intestinal PH and intestinal motility and join effort in immune regulation with intestinal lymphoid tissue. Previous studies showed that: water-soluble dietary fiber with the action of intestinal flora can cut the inflammatory cytokines, prevent inflammation and induce regulatory T cells, but the type and dose of dietary fiber used were different in different studies, and no studies have confirmed whether dietary fiber could adjusted the flora colonization ability in patients with IBD. We conceive that pectin by some mechanism to promote the migration of probiotics in intestine engraftment, reduce pathogenic agents' adhesion of intestinal mucosa, cut inflammation, and to maintain intestinal flora diversity and steady state in a long time, and than achieve the goal of continue to ease IBD.
|
A Randomized, Controlled, Single-blind Study of Effects of Pectin on Flora Intestinal Colonization and Maintenance After Fecal Transplantation to Patients With Inflammatory Bowel Disease
|
Inflammatory Bowel Disease
|
* Other: co-transplantation of FMT and pectin
* Other: single fecal microbiota transplantation
* Dietary Supplement: pure give pectin 20g/d for five days
|
Inclusion Criteria:~for UC~Patients should be in the age range of 18 - 70 years;~Patients should have clinical, imaging, endoscopic and histological diagnosis of UC;~Patients should have a UCDAI score of more than 2 and less than 10 or stage at S1/S2 in Montreal Rank at enrollment;~Patients receiving a stable dose of concomitant medication (aminosalicylates, oral corticosteroids) for at least 4 weeks are eligible;~Patients are capable of providing written informed consent and obtained at the time of enrollment;~Patients are willing to adhere to the study visit schedule and other protocol requirements.~for CD:~Patients should be in the age range of 18 - 40 years;~Patients should have clinical, imaging, endoscopic and histological diagnosis of early CD*;~Patients should have a CDAI score of more than 150 and less than 400and have a C-reactive protein (CRP) level of more than10mg/L at enrollment;~Patients receiving a stable dose of concomitant medication (aminosalicylates, oral corticosteroids) for at least 4 weeks are eligible;~Patients are capable of providing written informed consent and obtained at the time of enrollment;~Patients are willing to adhere to the study visit schedule and other protocol requirements.~Exclusion Criteria:~Women who are pregnant or lactating at the time of enrollment, or who intend to be during the study period~Patients may confuse the findings or there exist any other additional risk history~Patients with end-stage disease or is expected likely to die during the study~Patients are participating in other clinical trials or participated within 3 months prior to transplantation~Outbreaks, infectious (viruses, bacteria, parasites, or other microorganisms) colitis, scheduled for abdominal surgery,take probiotics / prebiotics / synbiotics / antibiotic / PPI (past 1 month) orally, severe anemia (Hbg <6g/dl), heart cerebrovascular accident, bypass, stent implantation surgery in the last 6 months, coagulation disorders, immune suppression status (defined as: immunosuppressive drugs, a history of opportunistic infections within one year recurrent ,oral ulcers, multiple lymphadenopathy, neutropenia, etc.), major abdominal transplant surgery in the last 3 months, have took TNF-α monoclonal antibody 2 month before transplantation or planned to take within one month after transplantation, a history of megacolon -
|
18 Years
|
70 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| diversity and steady state of the stool | Change from Baseline in diversity and steady state of the stool every week within one month after the intervention and three and six months after intervention | 6 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Erythrocyte sedimentation rate | Change from Baseline in ESR 1st,3st,6st month after intervention | 6 months |
| C-reactive protein | Change from Baseline in CRP 1st,3st,6st month after intervention | 6 months |
| Fecal calcium protein | Change from Baseline in Fecal calcium protein 1st,3st,6st month after intervention | 6 months |
| Adverse reactions after fecal microbiota transplantation and/or take pectin | every day within one week after the intervention | 1 week |
| Crohn's disease activity index | Change from Baseline in CDAI two weeks,one,three and six months after intervention | 6 months |
| Ulcerative Colitis disease activity index | Change from Baseline in UCDAItwo weeks,one,three and six months after intervention | 6 months |
| the simple endoscopic score for CD | Change from Baseline in SEC-CD 3st,6st months after intervention | 6 months |
| Ulcerative Colitis endoscopic index of severity | Change from Baseline in UCDEIS 3st and 6st month after intervention | 6 months |
| diversity and steady state of the Intestinal mucosa | Change from Baseline in diversity and steady state of the intestinal mucosa three and six months after intervention | 6 months |
|
Intestinal Diseases, Inflammatory Bowel Diseases, Gastrointestinal Diseases, Digestive System Diseases, Gastroenteritis
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: co-transplantation of FMT and pectin<br>300ml Bacterial suspension (from 60g fresh stool )given for the first day and 20g pectin given from the second to the sixth day for total five days | Other: co-transplantation of FMT and pectin<br>* 300ml Bacterial suspension (from 60g fresh stool )for fecal microbiota transplantation the first day and 20g pectin given continuously for total five days<br>|
| Active Comparator: single fecal microbiota transplantation<br>300ml Bacterial suspension (from 60g fresh stool )given for the first day | Other: single fecal microbiota transplantation<br>* single fecal microbiota transplantation once the first day<br>|
| Active Comparator: give pectin 20g/d<br>pure give pectin 20g/d for five days | Dietary Supplement: pure give pectin 20g/d for five days<br>* pure give pectin 20g/d for five days<br>|
|
Effects of Pectin on Flora Intestinal Colonization and Maintenance After Fecal Transplantation
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the effect and safety of pectin and fecal microbiota transplantation on patients with inflammatory bowel disease. The investigators hypothesize that patients who take pectin can promote the migration of probiotics in intestine engraftment, reduce pathogenic agents'adhesion to intestinal mucosa, cut down the inflammation, and to maintain intestinal flora diversity and steady state in a long time.
Detailed Description
-----------------
Inflammatory bowel disease (IBD) is a chronic relapsing disease, including ulcerative colitis (UC) and Crohn's disease (CD). Although the etiology of IBD is unknown, but more and more evidence show that the inappropriate immune response to intestinal commensal bacteria leading to dysbiosis, and pathogens further act to the mucosal lymphoid tissue, causing IBD. Has yet not to determine the specific one or more pathogens as the cause of IBD,but literatures confirm the changes of diversity of the intestine flora.Based on the current awareness of changes in the intestinal flora in IBD, fecal microbiota transplantation (FMT) proposed in recent years to rebuild the intestine flora balance to achieve therapeutic purposes. But fecal bacteria of patients can not consistent with donor's for a long term after transplantation and therefore it is not an ideal way for disease control. Maintaining the diversity of flora in a long time so that well controlled the disease become the breakthrough of fecal microbiota transplantation in the treatment of inflammatory bowel disease. Pectin is a soluble dietary fiber (DF), produced by the gut flora after a series of fermentation with many metabolites such as short chain fatty acids (SCFA) which supply the energy for epithelial cells, regulate intestinal PH and intestinal motility and join effort in immune regulation with intestinal lymphoid tissue. Previous studies showed that: water-soluble dietary fiber with the action of intestinal flora can cut the inflammatory cytokines, prevent inflammation and induce regulatory T cells, but the type and dose of dietary fiber used were different in different studies, and no studies have confirmed whether dietary fiber could adjusted the flora colonization ability in patients with IBD. We conceive that pectin by some mechanism to promote the migration of probiotics in intestine engraftment, reduce pathogenic agents' adhesion of intestinal mucosa, cut inflammation, and to maintain intestinal flora diversity and steady state in a long time, and than achieve the goal of continue to ease IBD.
Official Title
-----------------
A Randomized, Controlled, Single-blind Study of Effects of Pectin on Flora Intestinal Colonization and Maintenance After Fecal Transplantation to Patients With Inflammatory Bowel Disease
Conditions
-----------------
Inflammatory Bowel Disease
Intervention / Treatment
-----------------
* Other: co-transplantation of FMT and pectin
* Other: single fecal microbiota transplantation
* Dietary Supplement: pure give pectin 20g/d for five days
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: for UC Patients should be in the age range of 18 - 70 years; Patients should have clinical, imaging, endoscopic and histological diagnosis of UC; Patients should have a UCDAI score of more than 2 and less than 10 or stage at S1/S2 in Montreal Rank at enrollment; Patients receiving a stable dose of concomitant medication (aminosalicylates, oral corticosteroids) for at least 4 weeks are eligible; Patients are capable of providing written informed consent and obtained at the time of enrollment; Patients are willing to adhere to the study visit schedule and other protocol requirements. for CD: Patients should be in the age range of 18 - 40 years; Patients should have clinical, imaging, endoscopic and histological diagnosis of early CD*; Patients should have a CDAI score of more than 150 and less than 400and have a C-reactive protein (CRP) level of more than10mg/L at enrollment; Patients receiving a stable dose of concomitant medication (aminosalicylates, oral corticosteroids) for at least 4 weeks are eligible; Patients are capable of providing written informed consent and obtained at the time of enrollment; Patients are willing to adhere to the study visit schedule and other protocol requirements. Exclusion Criteria: Women who are pregnant or lactating at the time of enrollment, or who intend to be during the study period Patients may confuse the findings or there exist any other additional risk history Patients with end-stage disease or is expected likely to die during the study Patients are participating in other clinical trials or participated within 3 months prior to transplantation Outbreaks, infectious (viruses, bacteria, parasites, or other microorganisms) colitis, scheduled for abdominal surgery,take probiotics / prebiotics / synbiotics / antibiotic / PPI (past 1 month) orally, severe anemia (Hbg <6g/dl), heart cerebrovascular accident, bypass, stent implantation surgery in the last 6 months, coagulation disorders, immune suppression status (defined as: immunosuppressive drugs, a history of opportunistic infections within one year recurrent ,oral ulcers, multiple lymphadenopathy, neutropenia, etc.), major abdominal transplant surgery in the last 3 months, have took TNF-α monoclonal antibody 2 month before transplantation or planned to take within one month after transplantation, a history of megacolon -
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 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: co-transplantation of FMT and pectin<br>300ml Bacterial suspension (from 60g fresh stool )given for the first day and 20g pectin given from the second to the sixth day for total five days | Other: co-transplantation of FMT and pectin<br>* 300ml Bacterial suspension (from 60g fresh stool )for fecal microbiota transplantation the first day and 20g pectin given continuously for total five days<br>|
| Active Comparator: single fecal microbiota transplantation<br>300ml Bacterial suspension (from 60g fresh stool )given for the first day | Other: single fecal microbiota transplantation<br>* single fecal microbiota transplantation once the first day<br>|
| Active Comparator: give pectin 20g/d<br>pure give pectin 20g/d for five days | Dietary Supplement: pure give pectin 20g/d for five days<br>* pure give pectin 20g/d for five days<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| diversity and steady state of the stool | Change from Baseline in diversity and steady state of the stool every week within one month after the intervention and three and six months after intervention | 6 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Erythrocyte sedimentation rate | Change from Baseline in ESR 1st,3st,6st month after intervention | 6 months |
| C-reactive protein | Change from Baseline in CRP 1st,3st,6st month after intervention | 6 months |
| Fecal calcium protein | Change from Baseline in Fecal calcium protein 1st,3st,6st month after intervention | 6 months |
| Adverse reactions after fecal microbiota transplantation and/or take pectin | every day within one week after the intervention | 1 week |
| Crohn's disease activity index | Change from Baseline in CDAI two weeks,one,three and six months after intervention | 6 months |
| Ulcerative Colitis disease activity index | Change from Baseline in UCDAItwo weeks,one,three and six months after intervention | 6 months |
| the simple endoscopic score for CD | Change from Baseline in SEC-CD 3st,6st months after intervention | 6 months |
| Ulcerative Colitis endoscopic index of severity | Change from Baseline in UCDEIS 3st and 6st month after intervention | 6 months |
| diversity and steady state of the Intestinal mucosa | Change from Baseline in diversity and steady state of the intestinal mucosa three and six months after intervention | 6 months |
|
|
NCT04263545
|
The Staff Stop Smoking Project
|
Participants will be randomised to either standard care or to receive our help to quit programme. The study will only be available to Portsmouth Hospital Trust staff member.
|
A randomised controlled feasibility study to trial a novel intervention to help NHS staff stop smoking compared to standard care. Participants will attend one-on-one interviews and a support group where they will undertake CO monitoring and mini-spirometry. They will complete questionnaires about their quality of life, other health problems and their general state of health. They will attend the support groups on a weekly basis and have access to support outside of these times.
|
A Randomised Feasibility Study Comparing a Novel Intervention for Smoking Cessation in NHS Staff to Standard Care
|
Smoking Cessation
|
* Behavioral: Group session with smoking cessation counsellor
* Behavioral: Standard Care
|
Inclusion Criteria:~Male or Female, aged 18 years or over~Willing and able to give informed consent for participation in the study.~Must work for PHT at QAH and be able to attend weekly meetings for the duration of the study period~Must be a current smoker~Exclusion Criteria:~-Unable to comprehend the study and provide informed consent e.g. insufficient command of English in the absence of someone to adequately interpret.
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: meeting with a smoking cessation counsellor to discuss their individual requirements for smoking cessation and be offered their choice of pharmacological intervention. They will be provided with their choice of pharmacotherapy on site.They will then be invited to attend a group session, where they will have some brief lung function tests and check carbon monoxide levels. Participants will be offered refreshments and receive a bespoke group session to address various aspects of smoking cessation.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Behavioural outcomes | Number of smokers who achieve a successful quit | 4 weeks |
| Behavioural outcomes | Number of smokers who achieve a successful quit | 12 weeks |
| Behavioural outcomes | Number of smokers who achieve a successful quit | 6 months |
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention<br> | Behavioral: Group session with smoking cessation counsellor<br>* Group session with smoking cessation counsellor<br>|
| Placebo Comparator: Standard Care<br> | Behavioral: Standard Care<br>* standard care arm will receive very brief advice (VBA) and signposting to local organisations to support a quit.<br>|
|
The Staff Stop Smoking Project
Study Overview
=================
Brief Summary
-----------------
Participants will be randomised to either standard care or to receive our help to quit programme. The study will only be available to Portsmouth Hospital Trust staff member.
Detailed Description
-----------------
A randomised controlled feasibility study to trial a novel intervention to help NHS staff stop smoking compared to standard care. Participants will attend one-on-one interviews and a support group where they will undertake CO monitoring and mini-spirometry. They will complete questionnaires about their quality of life, other health problems and their general state of health. They will attend the support groups on a weekly basis and have access to support outside of these times.
Official Title
-----------------
A Randomised Feasibility Study Comparing a Novel Intervention for Smoking Cessation in NHS Staff to Standard Care
Conditions
-----------------
Smoking Cessation
Intervention / Treatment
-----------------
* Behavioral: Group session with smoking cessation counsellor
* Behavioral: Standard Care
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or Female, aged 18 years or over Willing and able to give informed consent for participation in the study. Must work for PHT at QAH and be able to attend weekly meetings for the duration of the study period Must be a current smoker Exclusion Criteria: -Unable to comprehend the study and provide informed consent e.g. insufficient command of English in the absence of someone to adequately interpret.
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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: meeting with a smoking cessation counsellor to discuss their individual requirements for smoking cessation and be offered their choice of pharmacological intervention. They will be provided with their choice of pharmacotherapy on site.They will then be invited to attend a group session, where they will have some brief lung function tests and check carbon monoxide levels. Participants will be offered refreshments and receive a bespoke group session to address various aspects of smoking cessation.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention<br> | Behavioral: Group session with smoking cessation counsellor<br>* Group session with smoking cessation counsellor<br>|
| Placebo Comparator: Standard Care<br> | Behavioral: Standard Care<br>* standard care arm will receive very brief advice (VBA) and signposting to local organisations to support a quit.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Behavioural outcomes | Number of smokers who achieve a successful quit | 4 weeks |
| Behavioural outcomes | Number of smokers who achieve a successful quit | 12 weeks |
| Behavioural outcomes | Number of smokers who achieve a successful quit | 6 months |
|
|||
NCT00343057
|
DISCO - Influence of a Simple Information Booklet on the Evolution of Acute Low Back Pain (LBP)
|
To assess the impact of standardized written information on outcome in acute LBP.
|
A 3-month prospective, controlled study with a quasi-experimental design (i.e., a nonrandomized controlled sample with geographic stratification [30 areas]). Control and intervention areas ARE selected for their similarities in rural-to-urban distribution of the population and patients' access to GPs and to minimize risk of overlap between areas.
|
Influence of a Simple Information Booklet on the Evolution of Acute Low Back Pain (LBP): a Quasi-experimental Study in a Primary Care Setting.
|
Acute Low Back Pain
|
* Other: Patients' questionnaire
|
Inclusion Criteria:~Each GP have to enroll up to 4 patients with acute LBP.~Exclusion Criteria:~Patients are excluded if they~are less than 18 years old;~have pain for more than 4 weeks;~have pain intensity for the previous 24 hours less than 3 on a 11-point numeric scale (0= no pain, 10=maximal pain);~have sciatica;~have had a previous episode of acute LBP during the last 12 months;~have no occupational activities;~have consulted another practitioner for the same episode of back pain;~are pregnant;~have back pain related to infection, tumor, or inflammatory disease; or (j) have previously undergone back surgery.~The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
Pain, Back Pain, Low Back Pain, Neurologic Manifestations
|
| Intervention/Treatment |
| --- |
|Other: Patients' questionnaire|nan|
|
DISCO - Influence of a Simple Information Booklet on the Evolution of Acute Low Back Pain (LBP)
Study Overview
=================
Brief Summary
-----------------
To assess the impact of standardized written information on outcome in acute LBP.
Detailed Description
-----------------
A 3-month prospective, controlled study with a quasi-experimental design (i.e., a nonrandomized controlled sample with geographic stratification [30 areas]). Control and intervention areas ARE selected for their similarities in rural-to-urban distribution of the population and patients' access to GPs and to minimize risk of overlap between areas.
Official Title
-----------------
Influence of a Simple Information Booklet on the Evolution of Acute Low Back Pain (LBP): a Quasi-experimental Study in a Primary Care Setting.
Conditions
-----------------
Acute Low Back Pain
Intervention / Treatment
-----------------
* Other: Patients' questionnaire
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Each GP have to enroll up to 4 patients with acute LBP. Exclusion Criteria: Patients are excluded if they are less than 18 years old; have pain for more than 4 weeks; have pain intensity for the previous 24 hours less than 3 on a 11-point numeric scale (0= no pain, 10=maximal pain); have sciatica; have had a previous episode of acute LBP during the last 12 months; have no occupational activities; have consulted another practitioner for the same episode of back pain; are pregnant; have back pain related to infection, tumor, or inflammatory disease; or (j) have previously undergone back surgery. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
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 |
| --- |
|Other: Patients' questionnaire|nan|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
|||
NCT05524012
|
Longitudinal Multimodal Response Assessment During Neoadjuvant Treatment of Rectal Cancer
|
This pilot study aims to trial multimodal early response assessment to enable therapy adaptions in the context of non-operative therapy strategies of locally advanced rectal cancer (LARC) for development of a non-invasive response prediction model.
|
Patients with LARC, receiving neoadjuvant chemoradiotherapy (CRT) are followed by at least 4 multiparametric MRI-scans (diffusion weighted imaging and hypoxia-sensitive sequences) as well as repeated blood samples in order to analyse circulating tumour cells (CTCs). A standard pelvis radiotherapy (RT, 5040 cGy) will be performed in combination with a 5-Fluorouracil / Oxaliplatin regimen in all patients (planned: N = 50), succeeded by consolidation CTx (FOLFOX4) if feasible. Additional histologic markers, such as tumour-infiltrating lymphocytes (TILs) or PD-L1 status will be analysed before and after CRT. Resection is standard after completion of preoperative treatment. In case of complete regression and patient's request, a non-operative management (watch and wait) is offered alternatively. The primary endpoint is response, defined by tumor regression grading, secondary endpoints comprise longitudinal changes in MRI as well as in CTCs and TILs.
|
Planning Adaptive Treatment by Longitudinal Response Assessment Implementing MR Imaging, Liquid Biopsy and Analysis of Microenvironment During Neoadjuvant Treatment of Rectal Cancer (PRIMO)
|
Locally Advanced Rectal Carcinoma, Neoadjuvant Treatment, Radiotherapy, Adaptive Treatment
|
* Diagnostic Test: Blood sample
* Device: MRI scan
|
Inclusion Criteria:~locally advanced rectal cancer (LARC): UICC Stage II/III~no severe cardiac or lung disease~no severe hepatic disorders (liver enzymes <2.5 NR) or restrictions of renal function (GFR > 30ml/min)~no severe cytopenia (Neutrocytes >= 3 Gpt/l; Thrombocytes >= 100 Gpt/l; Hemoglobin >6mmol/l)~no homozygotic DPD deficiency~no other neoplasms requiring therapy~no earlier radiotherapy of the pelvis or earlier chemotherapy~no contraindications for MRI
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor regression grading (TRG) | Histological response assessment by TRG (Werner / Hoefler et al.); Response is defined as TRG 1a/b/2; | after completion of neoadjuvant treatment (up to 10 months) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI | longitudinal changes in multiparametric MRI sequences (diffusion weighted and hypoxia sensitive) | up to 10 months, until resection |
| Circulating Tumor Cells (CTC) | longitudinal changes in CTCs | 5 years |
| Tumor Infiltrating Lymphocytes (TIL) | longitudinal changes in TILs | up to 10 months, until resection |
| PFS | progression free survival | 5 years |
| OS | overall survival | 5 years |
| Surrogate marker: Interleukin 6 (IL-6) | surrogates of tumor and inflammation from routine blood draws [ng/l] | 5 years |
| Surrogate marker: Carcinoembryonic Antigen (CEA) | surrogates of tumor and inflammation from routine blood draws, [mg/l] | 5 years |
|
DWI, total neoadjuvant therapy (TNT), T2* MRI, circulating tumor cells, tumor infiltrating lymphocytes, liquid biopsy, rectal cancer, organ preservation
|
Rectal Neoplasms, Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Intestinal Diseases, Rectal Diseases
|
| Intervention/Treatment |
| --- |
|Diagnostic Test: Blood sample|longitudinal blood samples for CTC monitoring|
|Device: MRI scan|longitudinal MRI scans (non-contrast enhanced)|
|
Longitudinal Multimodal Response Assessment During Neoadjuvant Treatment of Rectal Cancer
Study Overview
=================
Brief Summary
-----------------
This pilot study aims to trial multimodal early response assessment to enable therapy adaptions in the context of non-operative therapy strategies of locally advanced rectal cancer (LARC) for development of a non-invasive response prediction model.
Detailed Description
-----------------
Patients with LARC, receiving neoadjuvant chemoradiotherapy (CRT) are followed by at least 4 multiparametric MRI-scans (diffusion weighted imaging and hypoxia-sensitive sequences) as well as repeated blood samples in order to analyse circulating tumour cells (CTCs). A standard pelvis radiotherapy (RT, 5040 cGy) will be performed in combination with a 5-Fluorouracil / Oxaliplatin regimen in all patients (planned: N = 50), succeeded by consolidation CTx (FOLFOX4) if feasible. Additional histologic markers, such as tumour-infiltrating lymphocytes (TILs) or PD-L1 status will be analysed before and after CRT. Resection is standard after completion of preoperative treatment. In case of complete regression and patient's request, a non-operative management (watch and wait) is offered alternatively. The primary endpoint is response, defined by tumor regression grading, secondary endpoints comprise longitudinal changes in MRI as well as in CTCs and TILs.
Official Title
-----------------
Planning Adaptive Treatment by Longitudinal Response Assessment Implementing MR Imaging, Liquid Biopsy and Analysis of Microenvironment During Neoadjuvant Treatment of Rectal Cancer (PRIMO)
Conditions
-----------------
Locally Advanced Rectal Carcinoma, Neoadjuvant Treatment, Radiotherapy, Adaptive Treatment
Intervention / Treatment
-----------------
* Diagnostic Test: Blood sample
* Device: MRI scan
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: locally advanced rectal cancer (LARC): UICC Stage II/III no severe cardiac or lung disease no severe hepatic disorders (liver enzymes <2.5 NR) or restrictions of renal function (GFR > 30ml/min) no severe cytopenia (Neutrocytes >= 3 Gpt/l; Thrombocytes >= 100 Gpt/l; Hemoglobin >6mmol/l) no homozygotic DPD deficiency no other neoplasms requiring therapy no earlier radiotherapy of the pelvis or earlier chemotherapy no contraindications for MRI
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 |
| --- |
|Diagnostic Test: Blood sample|longitudinal blood samples for CTC monitoring|
|Device: MRI scan|longitudinal MRI scans (non-contrast enhanced)|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor regression grading (TRG) | Histological response assessment by TRG (Werner / Hoefler et al.); Response is defined as TRG 1a/b/2; | after completion of neoadjuvant treatment (up to 10 months) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI | longitudinal changes in multiparametric MRI sequences (diffusion weighted and hypoxia sensitive) | up to 10 months, until resection |
| Circulating Tumor Cells (CTC) | longitudinal changes in CTCs | 5 years |
| Tumor Infiltrating Lymphocytes (TIL) | longitudinal changes in TILs | up to 10 months, until resection |
| PFS | progression free survival | 5 years |
| OS | overall survival | 5 years |
| Surrogate marker: Interleukin 6 (IL-6) | surrogates of tumor and inflammation from routine blood draws [ng/l] | 5 years |
| Surrogate marker: Carcinoembryonic Antigen (CEA) | surrogates of tumor and inflammation from routine blood draws, [mg/l] | 5 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
DWI, total neoadjuvant therapy (TNT), T2* MRI, circulating tumor cells, tumor infiltrating lymphocytes, liquid biopsy, rectal cancer, organ preservation
|
|
NCT02378948
|
Nutritional Route In Esophageal Resection Trial II
|
The aim of this study is to investigate the effects of early start versus delayed start of oral intake on postoperative functional recovery after an esophagectomy.
|
Early oral feeding is safe and beneficial in most types of gastro-intestinal surgery and is a crucial part of fast track or enhanced recovery protocols. Following esophagectomy, fast track programs are increasingly being applied, resulting in a reduced length of stay, perioperative morbidity and hospital charges. In a previous feasibility study (Nutrient I trial) has been shown that direct oral intake following esophagectomy was feasible and did not result in an increase of major complications. It remains unclear what the best strategy is for nutrition in the early postoperative phase following esophagectomy. The aim of this study is to investigate the effects of early start versus delayed start of oral intake on postoperative recovery and pulmonary complications following esophagectomy.~Patients will be recruited at the outpatient clinic of the Catharina Hospital Eindhoven and the Hospital Group Twente.Patients will enroll in the early oral feeding group or the delayed oral feeding group. The early oral feeding group will receive liquid oral nutrition directly after surgery. Patients in the delayed oral feeding group will receive enteral tube feeding (via a jejunostomy) for 5-7 days (standard protocol in The Netherlands). After these 5-7 days a liquid oral diet is initiated.~Patient characteristics and clinical parameters are registered in an electronic database. All surgical complications are classified using the Clavien-Dindo classification15 (Appendix II). An independent investigator will check functional recovery daily. Data is provided by local investigator via an online checklist (electronic case report form / website). Quality of life and Symptoms are scored using the European organization for research and treatment of cancer questionnaire (QLQ-C30/EORTC-OG25)16 at baseline (5 weeks after neoadjuvant treatment), 6 weeks, 3 months and 6 months postoperatively. Cost-effectiveness is scored via EQ-5D-5L, iMTA Medical Consumption Questionnaire (iMCQ) and Productivity Cost Questionnaire (iPCQ). Nutritional status will be measured using the actual caloric and protein intake versus the needed caloric and protein intake. Long-term outcome parameters such as local recurrence, overall and cancer-specific survival will be registered in a database until the end of the study.~The sample size calculation is based on functional recovery as primary outcome. Functional recovery is the time to surgical recovery according to the definition described previously. Patients in our historic cohort (1 week artificial nutrition) were at least considered functional recovered by a mean of 12 days post-surgery. Patients in the NUTRIENT I were at least functional recovered at day 10 postoperative (mean) following an esophagectomy. In this trial we consider a reduction of 2 days in functional recovery as clinically significant. Using a Power of 80%, an alpha of 5% and a standard deviation of 4 days, a total of 128 patients (64 patients in each group) is needed to show this difference. It is expected that the primary outcome will not be normally divided and therefore an extra 15% inclusion is necessary, requiring a total of 148 patients (74 patients in each group). Interim-analyses will be performed following 50 and 100 patients and will be checked by an independent physician.~All analyses will be done according to the intention-to-treat approach in which all randomized patients are included, regardless of adherence to study protocol. Occurrences of the primary and secondary endpoints are compared between the treatment groups. Results are presented as risk ratios with corresponding 95% confidence intervals. A two-tailed P < 0.05 is considered statistically significant. To compare the groups the data will be tested for normal distribution and an unpaired T-test will be performed when appropriate, otherwise the Mann-Whitney U or Chi-square tests.
|
Nutritional Route in Esophageal Resection Trial II (NUTRIENT II): a Randomized Controlled Trial
|
Esophageal Neoplasms
|
* Dietary Supplement: Liquid oral feeding
|
Inclusion Criteria:~Patients that undergo a (minimally invasive) esophagectomy with intrathoracic anastomosis.~written informed consent~age >18 years~Exclusion Criteria:~Inability for oral intake~Inability to place a surgical feeding jejunostomy~Mental retardation~Swallowing disorder~Achalasia~Malnutrition (defined as >15% weight loss just before start of the surgery)
|
18 Years
| null |
All
|
No
|
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional recovery | The primary outcome parameter is the day of functional recovery. Functional recovery is defined as postoperative patients who are free of IV fluid, have adequate pain control, restoration of mobility to an independent level, have sufficient caloric intake and no signs of active infection. | up to 4 weeks after surgery |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary complications | (Pneumonia, Acute respiratory distress syndrome, respiratory insufficiency requiring treatment) | up to 4 weeks after surgery |
| Anastomotic leakage | | up to 4 weeks after surgery |
| Nutritional status (weight loss, intake) | | postoperative day 2, 5 and 14 |
| Need for parenteral feeding/ placement of a nasojejunal feeding tube | | up to 2 weeks after surgery |
| Need for additional surgical, radiological or endoscopic interventions | | up to 4 weeks after surgery |
| 30-day surgical complications (classified according to Clavien-Dindo) | classified according to Clavien-Dindo | up to 4 weeks after surgery |
| Other complications requiring treatment | i.e. urinary tract infection | up to 4 weeks after surgery |
| Need for ICU admission and total length of ICU stay | | up to 4 weeks after surgery |
| Quality of life | | 6 weeks after neoadjuvant treatment, 6 weeks, 3 months en 6 months postoperatively |
|
Esophagectomy, Nutrition, Oral feeding, Enteral feeding, Pulmonary complications, Anastomotic leakage, Quality of life
|
Esophageal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Head and Neck Neoplasms, Digestive System Diseases, Esophageal Diseases, Gastrointestinal Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early oral feeding<br>Liquid oral feeding directly after esophagectomy. | Dietary Supplement: Liquid oral feeding<br>* Liquid oral feeding (water, soup, porridge, nutritional supplements etc.)<br>|
| No Intervention: Delayed oral feeding<br>Liquid oral feeding 5 days after esophagectomy | |
|
Nutritional Route In Esophageal Resection Trial II
Study Overview
=================
Brief Summary
-----------------
The aim of this study is to investigate the effects of early start versus delayed start of oral intake on postoperative functional recovery after an esophagectomy.
Detailed Description
-----------------
Early oral feeding is safe and beneficial in most types of gastro-intestinal surgery and is a crucial part of fast track or enhanced recovery protocols. Following esophagectomy, fast track programs are increasingly being applied, resulting in a reduced length of stay, perioperative morbidity and hospital charges. In a previous feasibility study (Nutrient I trial) has been shown that direct oral intake following esophagectomy was feasible and did not result in an increase of major complications. It remains unclear what the best strategy is for nutrition in the early postoperative phase following esophagectomy. The aim of this study is to investigate the effects of early start versus delayed start of oral intake on postoperative recovery and pulmonary complications following esophagectomy. Patients will be recruited at the outpatient clinic of the Catharina Hospital Eindhoven and the Hospital Group Twente.Patients will enroll in the early oral feeding group or the delayed oral feeding group. The early oral feeding group will receive liquid oral nutrition directly after surgery. Patients in the delayed oral feeding group will receive enteral tube feeding (via a jejunostomy) for 5-7 days (standard protocol in The Netherlands). After these 5-7 days a liquid oral diet is initiated. Patient characteristics and clinical parameters are registered in an electronic database. All surgical complications are classified using the Clavien-Dindo classification15 (Appendix II). An independent investigator will check functional recovery daily. Data is provided by local investigator via an online checklist (electronic case report form / website). Quality of life and Symptoms are scored using the European organization for research and treatment of cancer questionnaire (QLQ-C30/EORTC-OG25)16 at baseline (5 weeks after neoadjuvant treatment), 6 weeks, 3 months and 6 months postoperatively. Cost-effectiveness is scored via EQ-5D-5L, iMTA Medical Consumption Questionnaire (iMCQ) and Productivity Cost Questionnaire (iPCQ). Nutritional status will be measured using the actual caloric and protein intake versus the needed caloric and protein intake. Long-term outcome parameters such as local recurrence, overall and cancer-specific survival will be registered in a database until the end of the study. The sample size calculation is based on functional recovery as primary outcome. Functional recovery is the time to surgical recovery according to the definition described previously. Patients in our historic cohort (1 week artificial nutrition) were at least considered functional recovered by a mean of 12 days post-surgery. Patients in the NUTRIENT I were at least functional recovered at day 10 postoperative (mean) following an esophagectomy. In this trial we consider a reduction of 2 days in functional recovery as clinically significant. Using a Power of 80%, an alpha of 5% and a standard deviation of 4 days, a total of 128 patients (64 patients in each group) is needed to show this difference. It is expected that the primary outcome will not be normally divided and therefore an extra 15% inclusion is necessary, requiring a total of 148 patients (74 patients in each group). Interim-analyses will be performed following 50 and 100 patients and will be checked by an independent physician. All analyses will be done according to the intention-to-treat approach in which all randomized patients are included, regardless of adherence to study protocol. Occurrences of the primary and secondary endpoints are compared between the treatment groups. Results are presented as risk ratios with corresponding 95% confidence intervals. A two-tailed P < 0.05 is considered statistically significant. To compare the groups the data will be tested for normal distribution and an unpaired T-test will be performed when appropriate, otherwise the Mann-Whitney U or Chi-square tests.
Official Title
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Nutritional Route in Esophageal Resection Trial II (NUTRIENT II): a Randomized Controlled Trial
Conditions
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Esophageal Neoplasms
Intervention / Treatment
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* Dietary Supplement: Liquid oral feeding
Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients that undergo a (minimally invasive) esophagectomy with intrathoracic anastomosis. written informed consent age >18 years Exclusion Criteria: Inability for oral intake Inability to place a surgical feeding jejunostomy Mental retardation Swallowing disorder Achalasia Malnutrition (defined as >15% weight loss just before start of the surgery)
Ages Eligible for Study
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Minimum Age: 18 Years
Sexes Eligible for Study
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All
Accepts Healthy Volunteers
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No
Study Plan
=================
How is the study designed?
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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: Early oral feeding<br>Liquid oral feeding directly after esophagectomy. | Dietary Supplement: Liquid oral feeding<br>* Liquid oral feeding (water, soup, porridge, nutritional supplements etc.)<br>|
| No Intervention: Delayed oral feeding<br>Liquid oral feeding 5 days after esophagectomy | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional recovery | The primary outcome parameter is the day of functional recovery. Functional recovery is defined as postoperative patients who are free of IV fluid, have adequate pain control, restoration of mobility to an independent level, have sufficient caloric intake and no signs of active infection. | up to 4 weeks after surgery |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary complications | (Pneumonia, Acute respiratory distress syndrome, respiratory insufficiency requiring treatment) | up to 4 weeks after surgery |
| Anastomotic leakage | | up to 4 weeks after surgery |
| Nutritional status (weight loss, intake) | | postoperative day 2, 5 and 14 |
| Need for parenteral feeding/ placement of a nasojejunal feeding tube | | up to 2 weeks after surgery |
| Need for additional surgical, radiological or endoscopic interventions | | up to 4 weeks after surgery |
| 30-day surgical complications (classified according to Clavien-Dindo) | classified according to Clavien-Dindo | up to 4 weeks after surgery |
| Other complications requiring treatment | i.e. urinary tract infection | up to 4 weeks after surgery |
| Need for ICU admission and total length of ICU stay | | up to 4 weeks after surgery |
| Quality of life | | 6 weeks after neoadjuvant treatment, 6 weeks, 3 months en 6 months postoperatively |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
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Esophagectomy, Nutrition, Oral feeding, Enteral feeding, Pulmonary complications, Anastomotic leakage, Quality of life
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NCT01200706
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Clinical Efficacy of Amoxicillin Given Twice or Three Times a Day Among Children With Non-severe Pneumonia
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The purpose of the study is to compare the clinical efficacy of amoxicillin given twice or three times a day to children with non-severe community-acquired pneumonia.
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Clinical Efficacy of Amoxicillin Given Twice or Three Times a Day Among Children With Non-severe Community-acquired Pneumonia
|
Community-acquired Pneumonia
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* Drug: Amoxicillin
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Inclusion Criteria:~Children aged between 2 and 59 months~Report of respiratory complaints~Presence of pulmonary infiltrate on chest x-ray taken on admission and read by the pediatrician on duty~Exclusion Criteria:~lower chest indrawing~danger signs (inability to drink, convulsions, somnolence, central cyanosis, grunting in a calm child)~diagnosed underlying chronic diseases (anatomic abnormalities of the respiratory tract, chronic pulmonary illness besides asthma, immunological defects, progressing neurological disorders, psychomotor retardation, heart disease with clinical repercussion, hemoglobinopathy, liver or kidney disease)~severe malnutrition~other concurrent infection~hospitalization during the previous 7 days~amoxicillin or similar antibiotic use during the last 48 hours~allergy to amoxicillin~history of aspiration
|
2 Months
|
59 Months
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical efficacy | resolution of fever, difficulty breathing and tachypnea | 48 hours |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resolution of cough | Disappearance of cough | 96 hours |
|
children aged under 5 years, Non-severe
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Amoxicillin, Anti-Bacterial Agents, Anti-Infective Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Amoxicillin given twice a day<br> | Drug: Amoxicillin<br>* amoxicillin 50mg/kg/day given in two different administration schemes<br>* Other names: Placebo with amoxicillin,in the opposite posologic scheme;|
| Active Comparator: Amoxicillin given three times a day<br> | Drug: Amoxicillin<br>* amoxicillin 50mg/kg/day given in two different administration schemes<br>* Other names: Placebo with amoxicillin,in the opposite posologic scheme;|
|
Clinical Efficacy of Amoxicillin Given Twice or Three Times a Day Among Children With Non-severe Pneumonia
Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to compare the clinical efficacy of amoxicillin given twice or three times a day to children with non-severe community-acquired pneumonia.
Official Title
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Clinical Efficacy of Amoxicillin Given Twice or Three Times a Day Among Children With Non-severe Community-acquired Pneumonia
Conditions
-----------------
Community-acquired Pneumonia
Intervention / Treatment
-----------------
* Drug: Amoxicillin
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Children aged between 2 and 59 months Report of respiratory complaints Presence of pulmonary infiltrate on chest x-ray taken on admission and read by the pediatrician on duty Exclusion Criteria: lower chest indrawing danger signs (inability to drink, convulsions, somnolence, central cyanosis, grunting in a calm child) diagnosed underlying chronic diseases (anatomic abnormalities of the respiratory tract, chronic pulmonary illness besides asthma, immunological defects, progressing neurological disorders, psychomotor retardation, heart disease with clinical repercussion, hemoglobinopathy, liver or kidney disease) severe malnutrition other concurrent infection hospitalization during the previous 7 days amoxicillin or similar antibiotic use during the last 48 hours allergy to amoxicillin history of aspiration
Ages Eligible for Study
-----------------
Minimum Age: 2 Months
Maximum Age: 59 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 |
| --- | --- |
| Active Comparator: Amoxicillin given twice a day<br> | Drug: Amoxicillin<br>* amoxicillin 50mg/kg/day given in two different administration schemes<br>* Other names: Placebo with amoxicillin,in the opposite posologic scheme;|
| Active Comparator: Amoxicillin given three times a day<br> | Drug: Amoxicillin<br>* amoxicillin 50mg/kg/day given in two different administration schemes<br>* Other names: Placebo with amoxicillin,in the opposite posologic scheme;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical efficacy | resolution of fever, difficulty breathing and tachypnea | 48 hours |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resolution of cough | Disappearance of cough | 96 hours |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
children aged under 5 years, Non-severe
|
|
NCT04371757
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Influence of the Autonomic Nervous System in Response to Exercise in Hypertensive Individuals
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Systemic arterial hypertension (SAH) has a direct association with endothelial dysfunction and major cardiovascular events. Evidence points to possible benefits of aerobic training in the endothelial function analyzed by the flow mediated dilation technique (flow mediated dilatation - FMD) in individuals with SAH. However, little is known about the influence of the autonomic nervous system (ANS) on the results of brachial artery FMD after different types of acute exercise in individuals with SAH. Thus, the objective of the research is to analyze the influence of the ANS on the FMD of the brachial artery of individuals with SAH after a session of aerobic (EA), resistance (ER) and combined (EC) exercise. For this, thirty-nine hypertensive individuals aged 35 to 55 years will be recruited and will be randomized to 2 sessions of AS, ER or EC. Also, within each modality, they will be randomized to α1-adrenergic block (Doxazosin 0.05 mg / kg-1) or placebo. The FMD will be performed by ultrasound 10 minutes before, as well as 10, 40 and 70 minutes after the exercise sessions and the autonomic control will be monitored (Finometer) for 10 minutes before each FMD. Arterial stiffness will also be analyzed, using the pulse wave velocity (PWV) by the Complior Analyzer. It is expected to demonstrate with this research the influence of the ANS on the FMD of the brachial artery in individuals with SAH in different physical exercises. This knowledge contributes to a better training prescription in this population.
|
INTRODUCTION~Endothelial dysfunction precedes atherosclerosis. Endothelial cells play an important role in the modulation of vascular angiogenesis, inflammatory responses, homeostasis, as well as vascular tone and permeability. This vascular protection function is largely attributed to nitric oxide synthase endothelial, an enzyme responsible for the production of nitric oxide (NO).~The decrease in local NO bioavailability and/or insufficient vasomotor response characterizes endothelial dysfunction; a fact evidenced in situations such as SAH, diabetes mellitus, obesity, dyslipidemia, menopause and sedentary lifestyle. The evaluation of flow-mediated dilation (FMD) of the brachial artery, although it is an indirect method to assess endothelial function, is not invasive and a large part of its result depends on NO. The findings resulting from the acute stimulus of physical exercise can also predict long-term adaptations, therefore, it has been widely used.~Within this scenario, the change in lifestyle, including regular physical exercise, is part of the recommendations of antihypertensive therapy. The most cited factors, responsible for the potential antihypertensive effect and better endothelial response to long-term exercise include reduced sympathetic activity, balance between vasodilator and vasoconstrictor factors and reduced levels of vasoconstrictor endothelin-1.~Analyzes of a resistance exercise session in the FMD demonstrated that the knee extension exercise performed with moderate intensity, as well as, with light intensity can reduce the FMD 10-30-60 minutes after the session in individuals healthy. Interestingly, the same session, when performed at high intensity, was not able to provide changes in the FMD, leading to the idea of an inverse relationship between intensity of resistance exercise and FMD response. Recently, the investigators demonstrated that an aerobic exercise session, resisted and combined (resisted and aerobic) performed in moderate intensity for 40 minutes and exclusively with lower limbs, were not able to alter the FMD of the brachial artery of individuals with SAH when analyzed 10-40-70 minutes after the sessions. These results were accompanied by maintenance of endothelial microvesicle levels and factors involved with oxidative stress. Collectively, the investigators can raise the hypothesis that other factors, such as exacerbation of sympathetic activity in untrained members, may cause vasoconstriction and redirect blood flow to trained members, consequently, competing with endothelium-dependent vasodilating activity.~Researchers have shown that α1-adrenergic blockade with Phentolamine mitigated the reduction in blood flow in the forearm, demonstrated in a placebo condition, during a manual pressure exercise session in individuals with heart failure. Still, considering that the exacerbated activation of the sympathetic nervous system has been proposed as an important factor in the development and maintenance of SAH, the investigators can hypothesize that, after a session of acute physical exercise, there is a competition between the sympathetic activity (potentiating vasoconstriction) and endothelium-dependent vasodilation capacity, in individuals with SAH.~Whereas the acute effect of different modalities of physical exercise on FMD has conflicting results in healthy and hypertensive individuals, as well as a lack of information in the hypertensive population regarding the influence of SNA activity on vessel reactivity in response to physical exercise, the investigators developed a randomized clinical trial with the primary objective of analyzing the influence of autonomic nervous system activity on the FMD of the brachial artery of individuals with SAH after acute aerobic, resisted and combined (resisted and aerobic) exercise performed exclusively with lower limbs.~METHODS~Study setting.~The study will be carried out at the Institute of Cardiology of Rio Grande do Sul/Fundação Universitária de Cardiologia under the approval of the Ethics Committee of this Institution (UP 5678/19).~Eligibility criteria.~Men and woman with SAH, between 35-55 years old who attend the services of the Institute of Cardiology of Rio Grande do Sul and do not perform regular physical exercise (≥2 sessions per week) will be selected. The sample will exclude individuals with diabetes mellitus, chronic renal failure, body mass index (BMI) ≥35kg/m2, coronary artery disease, heart failure, not to be taking antihypertensive medication, making use of beta-blocker and/or alpha-blocker, present lesions in the lower limbs that prevent the protocol, smoking and menopause (woman).~Sample size.~Researchers have compared the FMD in healthy individuals after a session of aerobic exercise performed with the condition of placebo (SD 1.13%) and α1-adrenergic block (SD 1.91%) (difference of means: 3.1%). Thus, to find a similar difference in FMD between conditions (placebo and α1-adrenergic block) after our exercise session, the investigadors calculated a total sample of 15 individuals (α=0.05 and 80% power). For the comparison in FMD between the types of exercises, the pre-exercise (SD 1.18%) and post-exercise (SD 1.91%) of the α1-adrenergic block group. To find a difference in the FMD of 1.62% (α=0.05, power 80%), the calculated total sample was 30 individuals. Assuming a loss of 30% during the protocols, the total sample was 39 individuals.~Evaluation and interventions.~The volunteers will be selected from the information described in the medical records of the IC/FUC cardiology service. The first contact with the volunteer will be made via telephone in an attempt to check, a priori, the exclusion criteria.~Step 1. The individual's first visit to the IC/FUC will take place at the Clinical Research Laboratory (LIC) and all inclusion/exclusion criteria will be resumed. After the respective signature of the Informed Consent Form, the individuals will answer a clinical questionnaire and the International Physical Activity Questionnaire. The individual's clinical blood pressure will be checked (3 blood pressure checks on the arm with the highest value).~Anthropometry will be performed at the LIC and divided into assessment of total body mass, height and waist circumference.~The exercise test will be performed on a treadmill, with the Bruce Protocol, according to the Guidelines of the Brazilian Society of Cardiology. The test will be conducted in a specialized ICF/FUC room by a qualified professional in the presence of a cardiologist. Afterwards, the maximum oxygen consumption, respiratory equivalents and maximum heart rate will be lauded (prescription of aerobic exercises).~Step 2. The second visit will be held at the LIC, with the individual fasting for 12 hours for blood collection and biochemical analysis. After blood collection, a standardized snack will be offered and volunteers will be directed to a controlled room where they will lie for 10 minutes. The evaluation of arterial stiffness will be through the carotid-femoral pulse wave velocity (PWV), with Complior Analyze equipment®. The distance between the two points is measured by an infantometer and the data on blood pressure, height, total body mass and distance between the points of the carotid and femoral arteries are entered in the Complior Analyze software to calculate the PWV.~After analyzing the PWV, the volunteers will be tested for maximum strength of the lower limbs by testing a maximum repetition (1-RM). The test will be performed at the LIC in a specific environment for physical exercise (knee extension, knee flexion, leg pressure and plantar flexion exercises). A local warm-up will be performed with 10-12 repetitions and a load relative to 30% of the estimated weight for the 1-RM test and 2:2 cadence (concentric:eccentric), controlled by a metronome. After resting for 3-5 minutes, the 1-RM test will begin. The test will be interrupted to adjust the load when the individual performs more than 1-repetition or when he was unable to overcome the proposed load. When further attempts are required, a 5-minute rest period is allowed. The weight at which the individual performs only one repetition will be determined as 1-RM.~Step 3-4. To analyze the influence of the SNS on the FMD in response to physical exercise sessions, the α1-adrenergic blocking described in the literature will be used. Considering the interruption of the commercialization of the drug prazosin in Brazil, it will be replaced by its analogue doxazosin. Briefly, 90 minutes before starting the exercise protocol, individuals will be offered a capsule containing placebo (microcrystalline cellulose) or α1-adrenoreceptor blocker (Doxazosin 0.05 mg.kg-1 body weight) and will be instructed to lie down. A researcher collaborating in the group and blinded to the type of physical exercise, will be responsible for making the capsules available to the individual on the day of the session, according to previous randomization.~Evaluation of endothelial function: the evaluation of endothelial function will be performed by ultrasound using the FMD technique, as previously described. Initially, the speed of blood flow and the diameter of the brachial artery will be evaluated, simultaneously, in the volunteer's right arm, in a quiet, darkened room with controlled temperature (23-24°C) of the LIC, by a single qualified investigator and blinded to the condition. The initial blood pressure (left arm), resting heart rate, blood flow velocity and the diameter of the brachial artery will be evaluated after resting for 10-15 minutes in a supine position, with the subject's arm extended and positioned at an angle of ~40° of the trunk. The evaluation will take place 10 minutes before the exercise session, as well as 10-40-70 minutes after the exercise session.~To analyze the FMD of the brachial artery, individuals should be fasting for ≥6 hours, medicated for SAH. A rapid deflation cuff will be placed around the forearm 5 cm distal to the antecubital fossa and the image of the brachial artery will be obtained in the distal third of the arm in B-mode using a linear multi-frequency transducer (12MHz) connected to a high resolution Doppler Ultrasound system. The sample volume will be adjusted to cover the width of the vessel and an insonation angle of 60° will be used. Baseline diameters will be recorded for 1 minute, before the forearm cuff is inflated at 50 mmHg above the SBP, for 5 minutes. The recording of the images will be resumed 30 seconds before the deflation of the cuff and maintained for 3 minutes after deflation. The video signal of the Doppler Ultrasound will be recorded in real time by a USB video card and saved for offline analysis. The analysis of blood flow velocity and brachial artery diameter will be performed using edge detection and wall tracking software (CardiovasculareSuit™; Pisa, Italy). From the synchronized blood flow velocity data and the brachial artery diameter, the blood flow will be calculated at 30Hz. The FMD will be calculated as the percentage change in the peak diameter after deflating the cuff from the reference diameter (baseline).~Nervous system: the assessment of the ANS will be performed through the variability of heart rate and blood pressure, as already described in the literature. The data will be collected through the pressure wave acquisition system in a continuous and non-invasive way by the Finometer® system. For this, a cuffing will be installed on the middle finger (right hand) coupled to an analog-to-digital signal converter. The frequency of sampling the signals will be acquired continuously at 1000 Hz, after resting the individual (lying down for 10 minutes) and before the FMD analysis.~The collected data will be saved in the BeatsScope® and LabChart® software for analysis of blood pressure variability (BPV) histograms and pulse interval series (RR-interval) for spectral power analysis (heart rate variability, HRV). The pulse interval(PI) will be calculated as the difference between the start and end points of the cycle. The analysis of HRV and BPV in the time domain, such as the spectral composition (fast Fourier transform) will be performed using the CardioSeries® software (after removing transient and discrepant elements). The spectral bands for evaluation: very low frequency (VLF, 0.007-0.04Hz), low frequency (LF, 0.04-0.15Hz), high frequency (HF, 0.15-0.4Hz) and total power (TP, VLF+LF+HF). Spontaneous baroreflex sensitivity (SBE) will be inferred by the square root of (LF/HRV m2)/(LF/BPV m2).~The physical exercise sessions will be carried out in two visits, always in the afternoon (1:00 pm) and in random order for placebo or α1-adrenergic block. Moderate fasting (6 hours) will be required and sessions should have intervals of at least 5-7 days. The exercise sessions will be: aerobic, resistance and combined, previously published by our group.~The aerobic exercise session will be performed on a horizontal cycle ergometer. A warm-up will be performed (5 minutes), followed by 40 minutes with moderate intensity (60% HRreserve) and controlled by a heart rate monitor, as well as the subjective effort scale (Borg 6 to 20 points). Blood pressure, heart rate and the Borg scale will be assessed at the beginning of aerobic exercise and every 5 minutes until the end.~The resistance exercise session will be structured with knee extension, knee flexion, leg pressure and plantar flexion, in a station with guided weights, with 4x12 repetitions and 60% intensity of 1-RM; the cadence will be adjusted to 2:2 (concentric: eccentric) and controlled by a metronome. The rest between sets and exercises will be 90 seconds (total duration: 40 minutes). Blood pressure, heart rate and Borg scale will be recorded at the beginning and at the end of the 4th series of each exercise.~The combined exercise session will be structured with 20 minutes of resistance exercise + 20 minutes of aerobic exercise, as already described, except that the resistance exercises will have 2 sets of each exercise. As with other sessions, blood pressure, heart rate and the Borg scale will be assessed at the beginning and end of the second series of resistance exercise, as well as at the beginning and every 5 minutes of aerobic exercise up to 15 minutes after end of exercises.~Statistical analysis.~The normality of the data will be assessed by Shapiro-Wilk. Values will be presented as mean ± standard deviation or mediated and 95% CI, according to the distribution of variables. One-way ANOVA will be used for prior comparisons of baseline data between groups. The multivariate analysis of the data will be performed using the GEE for repeated measures with Bonferroni's post-hoc. The evaluation of possible correlations between variables will be performed using Pearson or Spearman tests. Statistical analysis: SPSS 24.0, p-value <0.05.
|
Influence of the Autonomic Nervous System on Endothelial Function as an Acute Response to Exercise in Hypertensive Individuals: a Randomized Double-blind Protocol Study
|
Autonomic Nervous System, Hypertension
|
* Drug: α1-adrenergic block
* Other: Placebo
|
Inclusion Criteria:~Clinical diagnosis of systemic arterial hypertension;~Must be able to reality physical exercise.~Exclusion Criteria:~Diabetes mellitus;~Chronic renal failure;~Body mass index ≥ 35kg/m2;~Coronary artery disease;~Heart failure;~Use of beta-blocker;~Uso of alpha-blocker;~Smoker;~Menopause (woman).
|
35 Years
|
55 Years
|
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomization for exercise interventions, as well as placebo or α1-adrenergic, will be performed using a computer program containing the coded distribution. The randomization of the subjects will be characterized as simple and divided into two parts; (A) directed to the three arms of exercise (aerobica exercise, resistido exercise and combinade exercise) and (B) the order in relation to the placebo or α1-adrenergic block.
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the endothelial function of hypertensive individuals after a session of aerobic exercise, resistance exercise and combined exercise in α1-adrenoreceptor blocker and placebo condition. | The method of assessing the flow-mediated dilation (FMD) of the brachial artery by ultrasonography is an indirect method to assess endothelial function. To analyze the FMD of the brachial artery a rapid deflation cuff will be placed around the forearm 5 cm distal to the antecubital fossa and the image of the brachial artery will be obtained in the distal third of the arm. Baseline diameters will be recorded for 1 minute, before the forearm cuff is inflated at 50 mmHg above the SBP, for 5 minutes. The recording of the images will be resumed 30 seconds before the deflation of the cuff and maintained for 3 minutes after deflation. The video signal of the Doppler Ultrasound will be recorded in real time by a USB video card and saved for offline analysis. The analysis of diameter will be performed using edge detection and wall tracking software. The FMD will be calculated as the percentage change in the peak diameter after deflating the cuff from the baseline diameter. | Ten minutes before the exercise session and 10, 40 and 70 minutes after the exercise session. |
|
Endothelium, Physical Exercise
|
Doxazosin, Adrenergic Agents, Antihypertensive Agents, Adrenergic alpha-1 Receptor Antagonists, Adrenergic alpha-Antagonists, Adrenergic Antagonists, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aerobic exercise session<br>The aerobic exercise session will be performed on a horizontal cycle ergometer. A warm-up will be performed (5 minutes), followed by 40 minutes with moderate intensity (60% HRreserve) and controlled by a heart rate monitor, as well as the subjective effort scale (Borg 6 to 20 points). Blood pressure, heart rate and the Borg scale will be assessed at the beginning of aerobic exercise and every 5 minutes until the end. | Drug: α1-adrenergic block<br>* Ninety minutes before starting the experimental exercise protocol, participants will be offered a capsule containing an α-1 adrenoreceptor blocker (Drozazosin; 0.05 mg / kg-1 body weight) and will be instructed to lie down. All capsules will be handled by a specialized pharmacy.<br>* Other names: Doxazosin;Other: Placebo<br>* Ninety minutes before starting the experimental exercise protocol, participants will be offered a capsule containing an placebo (microcrystalline cellulose; 0.05 mg.kg-1 body weight) and will be instructed to lie down. All capsules will be handled by a specialized pharmacy.<br>* Other names: Microcrystalline cellulose;|
| Experimental: Resistance exercise session<br>The resistance exercise session will be structured with knee extension, knee flexion, leg pressure and plantar flexion, in a station with guided weights, with 4x12 repetitions and 60% intensity of 1-RM; the cadence will be adjusted to 2:2 (concentric: eccentric) and controlled by a metronome. The rest between sets and exercises will be 90 seconds (total duration: 40 minutes). Blood pressure, heart rate and Borg scale will be recorded at the beginning and at the end of the 4th series of each exercise. | Drug: α1-adrenergic block<br>* Ninety minutes before starting the experimental exercise protocol, participants will be offered a capsule containing an α-1 adrenoreceptor blocker (Drozazosin; 0.05 mg / kg-1 body weight) and will be instructed to lie down. All capsules will be handled by a specialized pharmacy.<br>* Other names: Doxazosin;Other: Placebo<br>* Ninety minutes before starting the experimental exercise protocol, participants will be offered a capsule containing an placebo (microcrystalline cellulose; 0.05 mg.kg-1 body weight) and will be instructed to lie down. All capsules will be handled by a specialized pharmacy.<br>* Other names: Microcrystalline cellulose;|
| Experimental: Combined exercise session<br>The combined exercise session will be structured with 20 minutes of resistance exercise + 20 minutes of aerobic exercise, as already described, except that the resistance exercises will have 2 sets of each exercise. As with other sessions, blood pressure, heart rate and the Borg scale will be assessed at the beginning and end of the second series of resistance exercise, as well as at the beginning and every 5 minutes of aerobic exercise up to 15 minutes after end of exercises. | Drug: α1-adrenergic block<br>* Ninety minutes before starting the experimental exercise protocol, participants will be offered a capsule containing an α-1 adrenoreceptor blocker (Drozazosin; 0.05 mg / kg-1 body weight) and will be instructed to lie down. All capsules will be handled by a specialized pharmacy.<br>* Other names: Doxazosin;Other: Placebo<br>* Ninety minutes before starting the experimental exercise protocol, participants will be offered a capsule containing an placebo (microcrystalline cellulose; 0.05 mg.kg-1 body weight) and will be instructed to lie down. All capsules will be handled by a specialized pharmacy.<br>* Other names: Microcrystalline cellulose;|
|
Influence of the Autonomic Nervous System in Response to Exercise in Hypertensive Individuals
Study Overview
=================
Brief Summary
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Systemic arterial hypertension (SAH) has a direct association with endothelial dysfunction and major cardiovascular events. Evidence points to possible benefits of aerobic training in the endothelial function analyzed by the flow mediated dilation technique (flow mediated dilatation - FMD) in individuals with SAH. However, little is known about the influence of the autonomic nervous system (ANS) on the results of brachial artery FMD after different types of acute exercise in individuals with SAH. Thus, the objective of the research is to analyze the influence of the ANS on the FMD of the brachial artery of individuals with SAH after a session of aerobic (EA), resistance (ER) and combined (EC) exercise. For this, thirty-nine hypertensive individuals aged 35 to 55 years will be recruited and will be randomized to 2 sessions of AS, ER or EC. Also, within each modality, they will be randomized to α1-adrenergic block (Doxazosin 0.05 mg / kg-1) or placebo. The FMD will be performed by ultrasound 10 minutes before, as well as 10, 40 and 70 minutes after the exercise sessions and the autonomic control will be monitored (Finometer) for 10 minutes before each FMD. Arterial stiffness will also be analyzed, using the pulse wave velocity (PWV) by the Complior Analyzer. It is expected to demonstrate with this research the influence of the ANS on the FMD of the brachial artery in individuals with SAH in different physical exercises. This knowledge contributes to a better training prescription in this population.
Detailed Description
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INTRODUCTION Endothelial dysfunction precedes atherosclerosis. Endothelial cells play an important role in the modulation of vascular angiogenesis, inflammatory responses, homeostasis, as well as vascular tone and permeability. This vascular protection function is largely attributed to nitric oxide synthase endothelial, an enzyme responsible for the production of nitric oxide (NO). The decrease in local NO bioavailability and/or insufficient vasomotor response characterizes endothelial dysfunction; a fact evidenced in situations such as SAH, diabetes mellitus, obesity, dyslipidemia, menopause and sedentary lifestyle. The evaluation of flow-mediated dilation (FMD) of the brachial artery, although it is an indirect method to assess endothelial function, is not invasive and a large part of its result depends on NO. The findings resulting from the acute stimulus of physical exercise can also predict long-term adaptations, therefore, it has been widely used. Within this scenario, the change in lifestyle, including regular physical exercise, is part of the recommendations of antihypertensive therapy. The most cited factors, responsible for the potential antihypertensive effect and better endothelial response to long-term exercise include reduced sympathetic activity, balance between vasodilator and vasoconstrictor factors and reduced levels of vasoconstrictor endothelin-1. Analyzes of a resistance exercise session in the FMD demonstrated that the knee extension exercise performed with moderate intensity, as well as, with light intensity can reduce the FMD 10-30-60 minutes after the session in individuals healthy. Interestingly, the same session, when performed at high intensity, was not able to provide changes in the FMD, leading to the idea of an inverse relationship between intensity of resistance exercise and FMD response. Recently, the investigators demonstrated that an aerobic exercise session, resisted and combined (resisted and aerobic) performed in moderate intensity for 40 minutes and exclusively with lower limbs, were not able to alter the FMD of the brachial artery of individuals with SAH when analyzed 10-40-70 minutes after the sessions. These results were accompanied by maintenance of endothelial microvesicle levels and factors involved with oxidative stress. Collectively, the investigators can raise the hypothesis that other factors, such as exacerbation of sympathetic activity in untrained members, may cause vasoconstriction and redirect blood flow to trained members, consequently, competing with endothelium-dependent vasodilating activity. Researchers have shown that α1-adrenergic blockade with Phentolamine mitigated the reduction in blood flow in the forearm, demonstrated in a placebo condition, during a manual pressure exercise session in individuals with heart failure. Still, considering that the exacerbated activation of the sympathetic nervous system has been proposed as an important factor in the development and maintenance of SAH, the investigators can hypothesize that, after a session of acute physical exercise, there is a competition between the sympathetic activity (potentiating vasoconstriction) and endothelium-dependent vasodilation capacity, in individuals with SAH. Whereas the acute effect of different modalities of physical exercise on FMD has conflicting results in healthy and hypertensive individuals, as well as a lack of information in the hypertensive population regarding the influence of SNA activity on vessel reactivity in response to physical exercise, the investigators developed a randomized clinical trial with the primary objective of analyzing the influence of autonomic nervous system activity on the FMD of the brachial artery of individuals with SAH after acute aerobic, resisted and combined (resisted and aerobic) exercise performed exclusively with lower limbs. METHODS Study setting. The study will be carried out at the Institute of Cardiology of Rio Grande do Sul/Fundação Universitária de Cardiologia under the approval of the Ethics Committee of this Institution (UP 5678/19). Eligibility criteria. Men and woman with SAH, between 35-55 years old who attend the services of the Institute of Cardiology of Rio Grande do Sul and do not perform regular physical exercise (≥2 sessions per week) will be selected. The sample will exclude individuals with diabetes mellitus, chronic renal failure, body mass index (BMI) ≥35kg/m2, coronary artery disease, heart failure, not to be taking antihypertensive medication, making use of beta-blocker and/or alpha-blocker, present lesions in the lower limbs that prevent the protocol, smoking and menopause (woman). Sample size. Researchers have compared the FMD in healthy individuals after a session of aerobic exercise performed with the condition of placebo (SD 1.13%) and α1-adrenergic block (SD 1.91%) (difference of means: 3.1%). Thus, to find a similar difference in FMD between conditions (placebo and α1-adrenergic block) after our exercise session, the investigadors calculated a total sample of 15 individuals (α=0.05 and 80% power). For the comparison in FMD between the types of exercises, the pre-exercise (SD 1.18%) and post-exercise (SD 1.91%) of the α1-adrenergic block group. To find a difference in the FMD of 1.62% (α=0.05, power 80%), the calculated total sample was 30 individuals. Assuming a loss of 30% during the protocols, the total sample was 39 individuals. Evaluation and interventions. The volunteers will be selected from the information described in the medical records of the IC/FUC cardiology service. The first contact with the volunteer will be made via telephone in an attempt to check, a priori, the exclusion criteria. Step 1. The individual's first visit to the IC/FUC will take place at the Clinical Research Laboratory (LIC) and all inclusion/exclusion criteria will be resumed. After the respective signature of the Informed Consent Form, the individuals will answer a clinical questionnaire and the International Physical Activity Questionnaire. The individual's clinical blood pressure will be checked (3 blood pressure checks on the arm with the highest value). Anthropometry will be performed at the LIC and divided into assessment of total body mass, height and waist circumference. The exercise test will be performed on a treadmill, with the Bruce Protocol, according to the Guidelines of the Brazilian Society of Cardiology. The test will be conducted in a specialized ICF/FUC room by a qualified professional in the presence of a cardiologist. Afterwards, the maximum oxygen consumption, respiratory equivalents and maximum heart rate will be lauded (prescription of aerobic exercises). Step 2. The second visit will be held at the LIC, with the individual fasting for 12 hours for blood collection and biochemical analysis. After blood collection, a standardized snack will be offered and volunteers will be directed to a controlled room where they will lie for 10 minutes. The evaluation of arterial stiffness will be through the carotid-femoral pulse wave velocity (PWV), with Complior Analyze equipment®. The distance between the two points is measured by an infantometer and the data on blood pressure, height, total body mass and distance between the points of the carotid and femoral arteries are entered in the Complior Analyze software to calculate the PWV. After analyzing the PWV, the volunteers will be tested for maximum strength of the lower limbs by testing a maximum repetition (1-RM). The test will be performed at the LIC in a specific environment for physical exercise (knee extension, knee flexion, leg pressure and plantar flexion exercises). A local warm-up will be performed with 10-12 repetitions and a load relative to 30% of the estimated weight for the 1-RM test and 2:2 cadence (concentric:eccentric), controlled by a metronome. After resting for 3-5 minutes, the 1-RM test will begin. The test will be interrupted to adjust the load when the individual performs more than 1-repetition or when he was unable to overcome the proposed load. When further attempts are required, a 5-minute rest period is allowed. The weight at which the individual performs only one repetition will be determined as 1-RM. Step 3-4. To analyze the influence of the SNS on the FMD in response to physical exercise sessions, the α1-adrenergic blocking described in the literature will be used. Considering the interruption of the commercialization of the drug prazosin in Brazil, it will be replaced by its analogue doxazosin. Briefly, 90 minutes before starting the exercise protocol, individuals will be offered a capsule containing placebo (microcrystalline cellulose) or α1-adrenoreceptor blocker (Doxazosin 0.05 mg.kg-1 body weight) and will be instructed to lie down. A researcher collaborating in the group and blinded to the type of physical exercise, will be responsible for making the capsules available to the individual on the day of the session, according to previous randomization. Evaluation of endothelial function: the evaluation of endothelial function will be performed by ultrasound using the FMD technique, as previously described. Initially, the speed of blood flow and the diameter of the brachial artery will be evaluated, simultaneously, in the volunteer's right arm, in a quiet, darkened room with controlled temperature (23-24°C) of the LIC, by a single qualified investigator and blinded to the condition. The initial blood pressure (left arm), resting heart rate, blood flow velocity and the diameter of the brachial artery will be evaluated after resting for 10-15 minutes in a supine position, with the subject's arm extended and positioned at an angle of 40° of the trunk. The evaluation will take place 10 minutes before the exercise session, as well as 10-40-70 minutes after the exercise session. To analyze the FMD of the brachial artery, individuals should be fasting for ≥6 hours, medicated for SAH. A rapid deflation cuff will be placed around the forearm 5 cm distal to the antecubital fossa and the image of the brachial artery will be obtained in the distal third of the arm in B-mode using a linear multi-frequency transducer (12MHz) connected to a high resolution Doppler Ultrasound system. The sample volume will be adjusted to cover the width of the vessel and an insonation angle of 60° will be used. Baseline diameters will be recorded for 1 minute, before the forearm cuff is inflated at 50 mmHg above the SBP, for 5 minutes. The recording of the images will be resumed 30 seconds before the deflation of the cuff and maintained for 3 minutes after deflation. The video signal of the Doppler Ultrasound will be recorded in real time by a USB video card and saved for offline analysis. The analysis of blood flow velocity and brachial artery diameter will be performed using edge detection and wall tracking software (CardiovasculareSuit™; Pisa, Italy). From the synchronized blood flow velocity data and the brachial artery diameter, the blood flow will be calculated at 30Hz. The FMD will be calculated as the percentage change in the peak diameter after deflating the cuff from the reference diameter (baseline). Nervous system: the assessment of the ANS will be performed through the variability of heart rate and blood pressure, as already described in the literature. The data will be collected through the pressure wave acquisition system in a continuous and non-invasive way by the Finometer® system. For this, a cuffing will be installed on the middle finger (right hand) coupled to an analog-to-digital signal converter. The frequency of sampling the signals will be acquired continuously at 1000 Hz, after resting the individual (lying down for 10 minutes) and before the FMD analysis. The collected data will be saved in the BeatsScope® and LabChart® software for analysis of blood pressure variability (BPV) histograms and pulse interval series (RR-interval) for spectral power analysis (heart rate variability, HRV). The pulse interval(PI) will be calculated as the difference between the start and end points of the cycle. The analysis of HRV and BPV in the time domain, such as the spectral composition (fast Fourier transform) will be performed using the CardioSeries® software (after removing transient and discrepant elements). The spectral bands for evaluation: very low frequency (VLF, 0.007-0.04Hz), low frequency (LF, 0.04-0.15Hz), high frequency (HF, 0.15-0.4Hz) and total power (TP, VLF+LF+HF). Spontaneous baroreflex sensitivity (SBE) will be inferred by the square root of (LF/HRV m2)/(LF/BPV m2). The physical exercise sessions will be carried out in two visits, always in the afternoon (1:00 pm) and in random order for placebo or α1-adrenergic block. Moderate fasting (6 hours) will be required and sessions should have intervals of at least 5-7 days. The exercise sessions will be: aerobic, resistance and combined, previously published by our group. The aerobic exercise session will be performed on a horizontal cycle ergometer. A warm-up will be performed (5 minutes), followed by 40 minutes with moderate intensity (60% HRreserve) and controlled by a heart rate monitor, as well as the subjective effort scale (Borg 6 to 20 points). Blood pressure, heart rate and the Borg scale will be assessed at the beginning of aerobic exercise and every 5 minutes until the end. The resistance exercise session will be structured with knee extension, knee flexion, leg pressure and plantar flexion, in a station with guided weights, with 4x12 repetitions and 60% intensity of 1-RM; the cadence will be adjusted to 2:2 (concentric: eccentric) and controlled by a metronome. The rest between sets and exercises will be 90 seconds (total duration: 40 minutes). Blood pressure, heart rate and Borg scale will be recorded at the beginning and at the end of the 4th series of each exercise. The combined exercise session will be structured with 20 minutes of resistance exercise + 20 minutes of aerobic exercise, as already described, except that the resistance exercises will have 2 sets of each exercise. As with other sessions, blood pressure, heart rate and the Borg scale will be assessed at the beginning and end of the second series of resistance exercise, as well as at the beginning and every 5 minutes of aerobic exercise up to 15 minutes after end of exercises. Statistical analysis. The normality of the data will be assessed by Shapiro-Wilk. Values will be presented as mean ± standard deviation or mediated and 95% CI, according to the distribution of variables. One-way ANOVA will be used for prior comparisons of baseline data between groups. The multivariate analysis of the data will be performed using the GEE for repeated measures with Bonferroni's post-hoc. The evaluation of possible correlations between variables will be performed using Pearson or Spearman tests. Statistical analysis: SPSS 24.0, p-value <0.05.
Official Title
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Influence of the Autonomic Nervous System on Endothelial Function as an Acute Response to Exercise in Hypertensive Individuals: a Randomized Double-blind Protocol Study
Conditions
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Autonomic Nervous System, Hypertension
Intervention / Treatment
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* Drug: α1-adrenergic block
* Other: Placebo
Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of systemic arterial hypertension; Must be able to reality physical exercise. Exclusion Criteria: Diabetes mellitus; Chronic renal failure; Body mass index ≥ 35kg/m2; Coronary artery disease; Heart failure; Use of beta-blocker; Uso of alpha-blocker; Smoker; Menopause (woman).
Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 55 Years
Sexes Eligible for Study
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All
Accepts Healthy Volunteers
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No
Study Plan
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How is the study designed?
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Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomization for exercise interventions, as well as placebo or α1-adrenergic, will be performed using a computer program containing the coded distribution. The randomization of the subjects will be characterized as simple and divided into two parts; (A) directed to the three arms of exercise (aerobica exercise, resistido exercise and combinade exercise) and (B) the order in relation to the placebo or α1-adrenergic block.
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aerobic exercise session<br>The aerobic exercise session will be performed on a horizontal cycle ergometer. A warm-up will be performed (5 minutes), followed by 40 minutes with moderate intensity (60% HRreserve) and controlled by a heart rate monitor, as well as the subjective effort scale (Borg 6 to 20 points). Blood pressure, heart rate and the Borg scale will be assessed at the beginning of aerobic exercise and every 5 minutes until the end. | Drug: α1-adrenergic block<br>* Ninety minutes before starting the experimental exercise protocol, participants will be offered a capsule containing an α-1 adrenoreceptor blocker (Drozazosin; 0.05 mg / kg-1 body weight) and will be instructed to lie down. All capsules will be handled by a specialized pharmacy.<br>* Other names: Doxazosin;Other: Placebo<br>* Ninety minutes before starting the experimental exercise protocol, participants will be offered a capsule containing an placebo (microcrystalline cellulose; 0.05 mg.kg-1 body weight) and will be instructed to lie down. All capsules will be handled by a specialized pharmacy.<br>* Other names: Microcrystalline cellulose;|
| Experimental: Resistance exercise session<br>The resistance exercise session will be structured with knee extension, knee flexion, leg pressure and plantar flexion, in a station with guided weights, with 4x12 repetitions and 60% intensity of 1-RM; the cadence will be adjusted to 2:2 (concentric: eccentric) and controlled by a metronome. The rest between sets and exercises will be 90 seconds (total duration: 40 minutes). Blood pressure, heart rate and Borg scale will be recorded at the beginning and at the end of the 4th series of each exercise. | Drug: α1-adrenergic block<br>* Ninety minutes before starting the experimental exercise protocol, participants will be offered a capsule containing an α-1 adrenoreceptor blocker (Drozazosin; 0.05 mg / kg-1 body weight) and will be instructed to lie down. All capsules will be handled by a specialized pharmacy.<br>* Other names: Doxazosin;Other: Placebo<br>* Ninety minutes before starting the experimental exercise protocol, participants will be offered a capsule containing an placebo (microcrystalline cellulose; 0.05 mg.kg-1 body weight) and will be instructed to lie down. All capsules will be handled by a specialized pharmacy.<br>* Other names: Microcrystalline cellulose;|
| Experimental: Combined exercise session<br>The combined exercise session will be structured with 20 minutes of resistance exercise + 20 minutes of aerobic exercise, as already described, except that the resistance exercises will have 2 sets of each exercise. As with other sessions, blood pressure, heart rate and the Borg scale will be assessed at the beginning and end of the second series of resistance exercise, as well as at the beginning and every 5 minutes of aerobic exercise up to 15 minutes after end of exercises. | Drug: α1-adrenergic block<br>* Ninety minutes before starting the experimental exercise protocol, participants will be offered a capsule containing an α-1 adrenoreceptor blocker (Drozazosin; 0.05 mg / kg-1 body weight) and will be instructed to lie down. All capsules will be handled by a specialized pharmacy.<br>* Other names: Doxazosin;Other: Placebo<br>* Ninety minutes before starting the experimental exercise protocol, participants will be offered a capsule containing an placebo (microcrystalline cellulose; 0.05 mg.kg-1 body weight) and will be instructed to lie down. All capsules will be handled by a specialized pharmacy.<br>* Other names: Microcrystalline cellulose;|
What is the study measuring?
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Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the endothelial function of hypertensive individuals after a session of aerobic exercise, resistance exercise and combined exercise in α1-adrenoreceptor blocker and placebo condition. | The method of assessing the flow-mediated dilation (FMD) of the brachial artery by ultrasonography is an indirect method to assess endothelial function. To analyze the FMD of the brachial artery a rapid deflation cuff will be placed around the forearm 5 cm distal to the antecubital fossa and the image of the brachial artery will be obtained in the distal third of the arm. Baseline diameters will be recorded for 1 minute, before the forearm cuff is inflated at 50 mmHg above the SBP, for 5 minutes. The recording of the images will be resumed 30 seconds before the deflation of the cuff and maintained for 3 minutes after deflation. The video signal of the Doppler Ultrasound will be recorded in real time by a USB video card and saved for offline analysis. The analysis of diameter will be performed using edge detection and wall tracking software. The FMD will be calculated as the percentage change in the peak diameter after deflating the cuff from the baseline diameter. | Ten minutes before the exercise session and 10, 40 and 70 minutes after the exercise session. |
Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endothelium, Physical Exercise
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NCT02893488
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Relative Bioavailability Study of a Fixed-dose Combination Dolutegravir/Abacavir/Lamivudine Dispersible Tablet
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This is an open-label, randomized, crossover study in healthy adult subjects with 5 treatment groups over 5 dosing periods. This study will evaluate pharmacokinetic parameters and relative bioavailability of a dispersible, fixed-dose combination (FDC) tablet of TRIUMEQ™ ([abacavir, ABC]/[dolutegravir, DTG]/[lamivudine, 3TC]) when dispersed and consumed under four different dosing conditions in comparison to an oral dose of TIVICAY™ (DTG) + EPZICOM™ (ABC/3TC) non-dispersible tablets administered in the fasted state. Approximately 20 subjects will be randomized, each to one of 5 treatment groups. The total duration of participation of a subject in this study will be approximately 10-11 weeks. It will include a screening visit within 30 days prior to the first dose of study drug, five treatment periods each with a single dose of study drug per treatment period and a follow up visit within 7 10 days after the last dose. There will also be a washout of at least 7 days between doses in each treatment period. TRIUMEQ, EPZICOM, and TIVICAY are trademarks of the GlaxoSmithKline group of companies.
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A Phase I, Single Dose, Five-period Crossover Relative Bioavailability Study of a Fixed-dose Combination Dolutegravir/Abacavir/Lamivudine Dispersible Tablet as Compared to a Co-dose of TIVICAY and EPZICOM in Healthy Subjects
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Infection, Human Immunodeficiency Virus
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* Drug: DTG/ABC/3TC FDC DISPERSIBLE TABLET
* Drug: EPZICOM (ABC/3TC)
* Drug: TIVICAY (DTG)
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Inclusion Criteria~Male or female aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.~Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac evaluation (history and ECG). A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.~Body weight >=50 kilogram (kg) for males and >=45 kg for females and body mass index (BMI) within the range 18.5-31.0 kg/m^2 (inclusive).~Male or female~Females of non-reproductive potential defined as pre-menopausal females with documented tubal ligation, documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, hysterectomy, documented bilateral oophorectomy, postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone [FSH] and estradiol levels consistent with menopause). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.~Female of reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and until 2 weeks after dosing with study medication and completion of the follow-up visit. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.~Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.~Documentation that the subject is negative for the human leukocyte antigen (HLA)-B*5701 allele.~Exclusion Criteria~ALT and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).~Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).~QT interval corrected for heart rate according to Fridericia's formula (QTcF) >450 milliseconds (msec). The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial.~Unable to refrain from the use of prescription (i.e., dofetilide) or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.~History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 gram of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.~Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 1 month prior to screening.~History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.~Creatinine clearance (CrCL) <60 mL/min~Presence of HBsAg, positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.~A positive pre-study drug/alcohol screen.~A positive test for HIV antibody.~Where participation in the study would result in donation of blood or blood product in excess of 500 mL within 56 days.~The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).~Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
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18 Years
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65 Years
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All
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Accepts Healthy Volunteers
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Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
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| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating AUC [0- infinity] | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose |
| Maximum observed plasma concentration (Cmax) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post dose time points for calculating Cmax | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve from time zero (pre-dose) to 24 hours (h) AUC(0-24) of DTG, ABC, and 3TC | AUC(0-24) is defined as the area under the concentration-time curve from time zero (pre-dose) to 24 h post-dose. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24h post dose in each of the 5 treatment periods. |
| Area under the plasma concentration-time curve from time zero (pre-dose) to time of last measurable concentration (AUC[0 t]) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post dose time points for calculating AUC [0-t] | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose in each of the 5 treatment periods. |
| Time to maximum plasma concentration (Tmax) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating Tmax | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose in each of the 5 treatment periods. |
| Apparent clearance following oral dosing (CL/F) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating CL/F | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose in each of the 5 treatment periods. |
| Concentration at 24 h after dose administration (C24) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating C24 | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24h post dose in each of the 5 treatment periods. |
| Terminal phase half-time (t1/2) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating t1/2 | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose in each of the 5 treatment periods. |
| Absorption lag time (Tlag) of DTG | Absorption lag time is defined as the time taken for a drug to appear in the systemic circulation following administration | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose in each of the 5 treatment periods. |
| Number of subjects with adverse event (AE) and serious adverse event (SAE). | AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE. | Approximately 11 weeks |
| Blood pressure assessment as a safety measure | Systolic and diastolic blood pressure will be measured in supine or semi-supine position after 5 minutes rest at Day -1, pre-dose, 4h, 24h, 48 h, 72h post-dose, and at follow up | Approximately 11 weeks |
| Measurement of pulse rate as a safety measure | Heart rate will be measured at supine or semi-supine position after 5 minutes rest at Day -1, pre-dose, 4h, 24h, 48 h, 72h post-dose, and at follow up | Approximately 11 weeks |
| Body temperature assessment as a safety measure | Temperature will be recorded at supine or semi-supine position after 5 minutes rest at Day -1, pre-dose, 4h, 24h, 48 h, 72h post-dose, and at follow up | Approximately 11 weeks |
| Electrocardiogram (ECG) assessment as a measure of safety | Single 12-lead ECGs will be obtained in a supine or semi-supine position having rested in this position for at least 10 minutes beforehand at Day -1 of each of 5 treatment periods | Approximately 11 weeks |
| Number of subjects having abnormal clinical laboratory parameters as a measure of safety | Blood samples will be collected (at Day -1, and 24 h post-dose and at follow-up if needed) to analyze blood urea nitrogen, creatinine, glucose, creatine phosphokinase (CPK), sodium, potassium, calcium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, direct bilirubin, total protein, albumin | Approximately 11 weeks |
| Number of subjects having abnormal hematology laboratory parameters as a measure of safety | Blood samples will be collected (at Day -1 and 24h post-dose and at follow-up if needed) to analyze platelet count, Red Blood Cells (RBC) count, hemoglobin, hematocrit, mean corpuscular volume ( MCV), mean corpuscular hemoglobin (MCH) White Blood Cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, and basophils | Approximately 11 weeks |
| Number of subjects having abnormal urinalysis as a measure of safety | Urine samples will be collected (at Day -1, and 24 h post-dose and at follow-up if needed) to analyze specific gravity, pH, glucose, protein, blood and ketones by dipstick, and for microscopic examination | Approximately 11 weeks |
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dolutegravir, abacavir, relative bioavailability, palatability, GSK2619619, palatability questionnaire, lamivudine, pediatric, calcium, dispersible tablet
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Lamivudine, Dolutegravir, Reverse Transcriptase Inhibitors, Nucleic Acid Synthesis Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Antiviral Agents, Anti-Infective Agents, Anti-HIV Agents, Anti-Retroviral Agents, HIV Integrase Inhibitors, Integrase Inhibitors
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| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SEQUENCE ABCDE<br>Participants will receive treatment A in period 1, treatment B in period 2, treatment C in period 3, treatment D in period 4 and treatment E in period 5 (one treatment per period). Where A=EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with zero mineral content (ZMC) water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 milliliter (mL) stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 minutes(mins), re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. | Drug: DTG/ABC/3TC FDC DISPERSIBLE TABLET<br>* DTG/ABC/3TC FDC dispersible tablet<br>Drug: EPZICOM (ABC/3TC)<br>* EPZICOM will be available as orange, film coated, modified capsule shaped tablets, debossed with GS FC2 on one side.<br>Drug: TIVICAY (DTG)<br>* TIVICAY will be available as white, round, biconvex tablets<br>|
| Experimental: SEQUENCE BCDEA<br>Participants will receive treatment B in period 1, treatment C in period 2, treatment D in period 3, treatment E in period 4 and treatment A in period 5 (one treatment per period). Where A= EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with ZMC water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 mL stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 mins, re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. | Drug: DTG/ABC/3TC FDC DISPERSIBLE TABLET<br>* DTG/ABC/3TC FDC dispersible tablet<br>Drug: EPZICOM (ABC/3TC)<br>* EPZICOM will be available as orange, film coated, modified capsule shaped tablets, debossed with GS FC2 on one side.<br>Drug: TIVICAY (DTG)<br>* TIVICAY will be available as white, round, biconvex tablets<br>|
| Experimental: SEQUENCE CDEAB<br>Participants will receive treatment C in period 1, treatment D in period 2, treatment E in period 3, treatment A in period 4 and treatment B in period 5 (one treatment per period). Where A=EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with ZMC water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 mL stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 mins, re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. | Drug: DTG/ABC/3TC FDC DISPERSIBLE TABLET<br>* DTG/ABC/3TC FDC dispersible tablet<br>Drug: EPZICOM (ABC/3TC)<br>* EPZICOM will be available as orange, film coated, modified capsule shaped tablets, debossed with GS FC2 on one side.<br>Drug: TIVICAY (DTG)<br>* TIVICAY will be available as white, round, biconvex tablets<br>|
| Experimental: SEQUENCE DEABC<br>Participants will receive treatment D in period 1, treatment E in period 2, treatment A in period 3, treatment B in period 4 and treatment C in period 5 (one treatment per period). Where A=EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with ZMC water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 mL stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 mins, re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. | Drug: DTG/ABC/3TC FDC DISPERSIBLE TABLET<br>* DTG/ABC/3TC FDC dispersible tablet<br>Drug: EPZICOM (ABC/3TC)<br>* EPZICOM will be available as orange, film coated, modified capsule shaped tablets, debossed with GS FC2 on one side.<br>Drug: TIVICAY (DTG)<br>* TIVICAY will be available as white, round, biconvex tablets<br>|
| Experimental: SEQUENCE EABCD<br>Participants will receive treatment E in period 1, treatment A in period 2, treatment B in period 3, treatment C in period 4 and treatment D in period 5 (one treatment per period). Where A=EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with ZMC water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 mL stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 mins, re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. | Drug: DTG/ABC/3TC FDC DISPERSIBLE TABLET<br>* DTG/ABC/3TC FDC dispersible tablet<br>Drug: EPZICOM (ABC/3TC)<br>* EPZICOM will be available as orange, film coated, modified capsule shaped tablets, debossed with GS FC2 on one side.<br>Drug: TIVICAY (DTG)<br>* TIVICAY will be available as white, round, biconvex tablets<br>|
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Relative Bioavailability Study of a Fixed-dose Combination Dolutegravir/Abacavir/Lamivudine Dispersible Tablet
Study Overview
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Brief Summary
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This is an open-label, randomized, crossover study in healthy adult subjects with 5 treatment groups over 5 dosing periods. This study will evaluate pharmacokinetic parameters and relative bioavailability of a dispersible, fixed-dose combination (FDC) tablet of TRIUMEQ™ ([abacavir, ABC]/[dolutegravir, DTG]/[lamivudine, 3TC]) when dispersed and consumed under four different dosing conditions in comparison to an oral dose of TIVICAY™ (DTG) + EPZICOM™ (ABC/3TC) non-dispersible tablets administered in the fasted state. Approximately 20 subjects will be randomized, each to one of 5 treatment groups. The total duration of participation of a subject in this study will be approximately 10-11 weeks. It will include a screening visit within 30 days prior to the first dose of study drug, five treatment periods each with a single dose of study drug per treatment period and a follow up visit within 7 10 days after the last dose. There will also be a washout of at least 7 days between doses in each treatment period. TRIUMEQ, EPZICOM, and TIVICAY are trademarks of the GlaxoSmithKline group of companies.
Official Title
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A Phase I, Single Dose, Five-period Crossover Relative Bioavailability Study of a Fixed-dose Combination Dolutegravir/Abacavir/Lamivudine Dispersible Tablet as Compared to a Co-dose of TIVICAY and EPZICOM in Healthy Subjects
Conditions
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Infection, Human Immunodeficiency Virus
Intervention / Treatment
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* Drug: DTG/ABC/3TC FDC DISPERSIBLE TABLET
* Drug: EPZICOM (ABC/3TC)
* Drug: TIVICAY (DTG)
Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Male or female aged between 18 and 65 years of age inclusive, at the time of signing the informed consent. Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac evaluation (history and ECG). A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Body weight >=50 kilogram (kg) for males and >=45 kg for females and body mass index (BMI) within the range 18.5-31.0 kg/m^2 (inclusive). Male or female Females of non-reproductive potential defined as pre-menopausal females with documented tubal ligation, documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, hysterectomy, documented bilateral oophorectomy, postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone [FSH] and estradiol levels consistent with menopause). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. Female of reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and until 2 weeks after dosing with study medication and completion of the follow-up visit. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. Documentation that the subject is negative for the human leukocyte antigen (HLA)-B*5701 allele. Exclusion Criteria ALT and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). QT interval corrected for heart rate according to Fridericia's formula (QTcF) >450 milliseconds (msec). The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial. Unable to refrain from the use of prescription (i.e., dofetilide) or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 gram of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits. Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 1 month prior to screening. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation. Creatinine clearance (CrCL) <60 mL/min Presence of HBsAg, positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. A positive pre-study drug/alcohol screen. A positive test for HIV antibody. Where participation in the study would result in donation of blood or blood product in excess of 500 mL within 56 days. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years
Sexes Eligible for Study
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All
Accepts Healthy Volunteers
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Accepts Healthy Volunteers
Study Plan
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How is the study designed?
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Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SEQUENCE ABCDE<br>Participants will receive treatment A in period 1, treatment B in period 2, treatment C in period 3, treatment D in period 4 and treatment E in period 5 (one treatment per period). Where A=EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with zero mineral content (ZMC) water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 milliliter (mL) stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 minutes(mins), re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. | Drug: DTG/ABC/3TC FDC DISPERSIBLE TABLET<br>* DTG/ABC/3TC FDC dispersible tablet<br>Drug: EPZICOM (ABC/3TC)<br>* EPZICOM will be available as orange, film coated, modified capsule shaped tablets, debossed with GS FC2 on one side.<br>Drug: TIVICAY (DTG)<br>* TIVICAY will be available as white, round, biconvex tablets<br>|
| Experimental: SEQUENCE BCDEA<br>Participants will receive treatment B in period 1, treatment C in period 2, treatment D in period 3, treatment E in period 4 and treatment A in period 5 (one treatment per period). Where A= EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with ZMC water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 mL stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 mins, re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. | Drug: DTG/ABC/3TC FDC DISPERSIBLE TABLET<br>* DTG/ABC/3TC FDC dispersible tablet<br>Drug: EPZICOM (ABC/3TC)<br>* EPZICOM will be available as orange, film coated, modified capsule shaped tablets, debossed with GS FC2 on one side.<br>Drug: TIVICAY (DTG)<br>* TIVICAY will be available as white, round, biconvex tablets<br>|
| Experimental: SEQUENCE CDEAB<br>Participants will receive treatment C in period 1, treatment D in period 2, treatment E in period 3, treatment A in period 4 and treatment B in period 5 (one treatment per period). Where A=EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with ZMC water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 mL stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 mins, re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. | Drug: DTG/ABC/3TC FDC DISPERSIBLE TABLET<br>* DTG/ABC/3TC FDC dispersible tablet<br>Drug: EPZICOM (ABC/3TC)<br>* EPZICOM will be available as orange, film coated, modified capsule shaped tablets, debossed with GS FC2 on one side.<br>Drug: TIVICAY (DTG)<br>* TIVICAY will be available as white, round, biconvex tablets<br>|
| Experimental: SEQUENCE DEABC<br>Participants will receive treatment D in period 1, treatment E in period 2, treatment A in period 3, treatment B in period 4 and treatment C in period 5 (one treatment per period). Where A=EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with ZMC water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 mL stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 mins, re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. | Drug: DTG/ABC/3TC FDC DISPERSIBLE TABLET<br>* DTG/ABC/3TC FDC dispersible tablet<br>Drug: EPZICOM (ABC/3TC)<br>* EPZICOM will be available as orange, film coated, modified capsule shaped tablets, debossed with GS FC2 on one side.<br>Drug: TIVICAY (DTG)<br>* TIVICAY will be available as white, round, biconvex tablets<br>|
| Experimental: SEQUENCE EABCD<br>Participants will receive treatment E in period 1, treatment A in period 2, treatment B in period 3, treatment C in period 4 and treatment D in period 5 (one treatment per period). Where A=EPZICOM (ABC 600 milligrams (mg)/3TC 300 mg) plus four TIVICAY (DTG 10 mg) tablets with ZMC water. B=Four TRIUMEQ (ABC 150mg/DTG 10 mg/3TC 75 mg) tablets dispersed in 40 mL stock solution 1 and consumed immediately. C=Four TRIUMEQ tablets dispersed in 40 mL stock solution 1, held for 30 mins, re-dispersed, and then consumed. D=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2 and consumed immediately. E=Four TRIUMEQ tablets dispersed in 40 mL stock solution 2, held for 30 mins, re-dispersed, and then consumed. | Drug: DTG/ABC/3TC FDC DISPERSIBLE TABLET<br>* DTG/ABC/3TC FDC dispersible tablet<br>Drug: EPZICOM (ABC/3TC)<br>* EPZICOM will be available as orange, film coated, modified capsule shaped tablets, debossed with GS FC2 on one side.<br>Drug: TIVICAY (DTG)<br>* TIVICAY will be available as white, round, biconvex tablets<br>|
What is the study measuring?
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Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating AUC [0- infinity] | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose |
| Maximum observed plasma concentration (Cmax) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post dose time points for calculating Cmax | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve from time zero (pre-dose) to 24 hours (h) AUC(0-24) of DTG, ABC, and 3TC | AUC(0-24) is defined as the area under the concentration-time curve from time zero (pre-dose) to 24 h post-dose. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24h post dose in each of the 5 treatment periods. |
| Area under the plasma concentration-time curve from time zero (pre-dose) to time of last measurable concentration (AUC[0 t]) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post dose time points for calculating AUC [0-t] | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose in each of the 5 treatment periods. |
| Time to maximum plasma concentration (Tmax) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating Tmax | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose in each of the 5 treatment periods. |
| Apparent clearance following oral dosing (CL/F) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating CL/F | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose in each of the 5 treatment periods. |
| Concentration at 24 h after dose administration (C24) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating C24 | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24h post dose in each of the 5 treatment periods. |
| Terminal phase half-time (t1/2) of DTG, ABC, and 3TC | Blood samples will be collected at pre-dose and at specific post-dose time points for calculating t1/2 | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose in each of the 5 treatment periods. |
| Absorption lag time (Tlag) of DTG | Absorption lag time is defined as the time taken for a drug to appear in the systemic circulation following administration | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 h post dose in each of the 5 treatment periods. |
| Number of subjects with adverse event (AE) and serious adverse event (SAE). | AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE. | Approximately 11 weeks |
| Blood pressure assessment as a safety measure | Systolic and diastolic blood pressure will be measured in supine or semi-supine position after 5 minutes rest at Day -1, pre-dose, 4h, 24h, 48 h, 72h post-dose, and at follow up | Approximately 11 weeks |
| Measurement of pulse rate as a safety measure | Heart rate will be measured at supine or semi-supine position after 5 minutes rest at Day -1, pre-dose, 4h, 24h, 48 h, 72h post-dose, and at follow up | Approximately 11 weeks |
| Body temperature assessment as a safety measure | Temperature will be recorded at supine or semi-supine position after 5 minutes rest at Day -1, pre-dose, 4h, 24h, 48 h, 72h post-dose, and at follow up | Approximately 11 weeks |
| Electrocardiogram (ECG) assessment as a measure of safety | Single 12-lead ECGs will be obtained in a supine or semi-supine position having rested in this position for at least 10 minutes beforehand at Day -1 of each of 5 treatment periods | Approximately 11 weeks |
| Number of subjects having abnormal clinical laboratory parameters as a measure of safety | Blood samples will be collected (at Day -1, and 24 h post-dose and at follow-up if needed) to analyze blood urea nitrogen, creatinine, glucose, creatine phosphokinase (CPK), sodium, potassium, calcium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, direct bilirubin, total protein, albumin | Approximately 11 weeks |
| Number of subjects having abnormal hematology laboratory parameters as a measure of safety | Blood samples will be collected (at Day -1 and 24h post-dose and at follow-up if needed) to analyze platelet count, Red Blood Cells (RBC) count, hemoglobin, hematocrit, mean corpuscular volume ( MCV), mean corpuscular hemoglobin (MCH) White Blood Cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, and basophils | Approximately 11 weeks |
| Number of subjects having abnormal urinalysis as a measure of safety | Urine samples will be collected (at Day -1, and 24 h post-dose and at follow-up if needed) to analyze specific gravity, pH, glucose, protein, blood and ketones by dipstick, and for microscopic examination | Approximately 11 weeks |
Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dolutegravir, abacavir, relative bioavailability, palatability, GSK2619619, palatability questionnaire, lamivudine, pediatric, calcium, dispersible tablet
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NCT02429011
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MRI Studies of Emotion in Depression
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The purpose of this study is to research the effects of ketamine on brain function in patients with Major Depressive Disorder (MDD). This study is an ancillary MRI neuroimaging study being conducted in patients with MDD who are enrolled in a separate clinical trial. Healthy control volunteers are also enrolled. No drug or other intervention is given as part of this protocol per se.~To study brain activity related to emotion, the study team will use a technology called functional MRI (fMRI), which is a method for evaluating the flow of blood in the brain using a powerful magnet. fMRI does not involve exposure to radiation.~Patients will be shown a sample of images on a computer screen designed to bring about an emotional reaction. The MRI machine will then take a number of pictures of your head. By computer analysis, this machine is able to create a picture of your brain's activity. There are several tasks during scanning that involve looking at various images that represent different emotions, and the study team will be monitoring brain activity during these tasks.~Patients will be scanned before and 24 hours after receiving ketamine (as part of a separate study) to analyze treatments effects. These scans are compared to depressed patients who did not receive ketamine, as well as to healthy controls.
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Specific Aim 1: To characterize the function of basic neural systems involved in emotion perception and regulation in TRD.~Experiment 1.1: Neural responses to emotional faces in TRD (neutral, low and high intensity sad facial expressions).~o Hypothesis 1.1: Patients with TRD, relative to HC participants, will evidence increased activation in the amygdala/parahippocampal gyrus to sad compared to neutral faces.~Experiment 1.2: Neural responses during negative emotion regulation in TRD (cognitive reappraisal).~Hypothesis 1.2: Patients with TRD, relative to HC participants, will show enhanced activation of the amygdala during the generation of negative affect and will be impaired in their ability to recruit PFC/ACC regions during attempts to down-regulate negative affect.~Specific Aim 2: To characterize changes in emotion-processing neural networks associated with ketamine and rapid antidepressant response.~Experiment 2.1: Neural changes in response to emotional faces associated with ketamine and rapid antidepressant response.~o Hypothesis 2.1a: Ketamine, compared to midazolam, will be associated with reduced activation in the amygdala to sad compared to neutral faces. 2.1b: Antidepressant response, compared to non-response, will be specifically associated with changes in PFC/ACC function.~Experiment 2.2: Neural changes during negative emotion regulation (cognitive reappraisal) associated with ketamine and rapid antidepressant response.~Hypothesis 2.2a: Ketamine, compared to midazolam, will be associated with reduced activation in the amygdala during negative emotion generation and enhanced PFC/ACC function during down-regulation of negative affect. 2.2b: Antidepressant response, compared to non-response, will be specifically associated with enhancement of PFC/ACC function.~Specific Aim 3 (Exploratory): To investigate functional and effective connectivity between emotion perception/generation neural systems and cognitive emotional regulation systems. Hypothesis 3: TRD compared to HC will be characterized by abnormal connectivity between PFC/ACC and amygdala, which will normalize with rapid antidepressant response.~The setting of research will be MSSM. All research participants will be recruited and screened through the Mood and Anxiety Disorders Program (MAP) (Director: Dan V. Iosifescu, M.D.) at MSSM. MAP is one of the major clinical research programs of the Department of Psychiatry, with research funding from NIH, the Department of Defense, NARSAD, and industry.
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Functional MRI Studies of Emotion in Depression and Rapid Antidepressant Response
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Major Depressive Disorder
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Inclusion Criteria:~Male or female participants, 18-70 years of age;~Participants must be free of any psychiatric condition (for the healthy volunteer group) or meet DSM-IV criteria for major depressive disorder, without psychotic features, based on the Structured Clinical Interview for DSM-IV TR Axis I Disorders (SCID);~Participants have demonstrated inadequate response to a minimum of 1 adequate antidepressant treatment trial in current episode (e.g. TRD);~Participants must be willing to undergo washout of psychotropic medications that he or she is taking;~Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process.~Exclusion Criteria:~Lifetime diagnosis of schizophrenia or any psychotic disorder, bipolar disorder, pervasive developmental disorders or mental retardation;~Current diagnosis of obsessive-compulsive disorder (OCD), but not other anxiety disorders;~Diagnosis of a substance use disorder within the past six months; all participants must have a negative urine toxicology test on the day of the fMRI, prior to the scan;~Female participants who are pregnant, nursing, for may become pregnant;~Any unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease); endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;~Clinically significant abnormalities of laboratories, physical examination, or ECG;~Participants judged to be at serious suicidal risk by the PI or another study-affiliated psychiatrist;~Any contraindications to MRI, including pacemakers or metallic objects in the body.
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18 Years
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70 Years
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All
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Accepts Healthy Volunteers
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| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Montgomery-Asberg Depression Rating Scale | The Montgomery-Asberg Depression Rating Scale (74) is a well-validated 10-item instrument with good ecological validity. It is used extensively in clinical research for the evaluation of depressive symptoms in adults, and is particularly sensitive to detecting change in symptoms. This scale serves as the primary depression-related behavioral rating for correlation with our neuroimaging data. | baseline and 24hrs post fMRI scan |
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| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Clinician-Rated Inventory of Depressive Symptomatology (IDS-C30) | The 30-item Clinician-Rated Inventory of Depressive Symptomatology (IDS-C30) (75) is a clinician-rated instrument which includes all DSM-IV diagnostic criterion items for MDD as well as commonly associated symptoms such as anxiety, irritability, and melancholic and atypical symptom features. | baseline and 24hrs post fMRI scan |
| Change in Brief Psychiatric Rating Scale and the Clinician-Administered Dissociative States Scale (CADSS) | Potential dissociative or other acute behavioral changes during the KET/MID infusions will be assessed using the Brief Psychiatric Rating Scale and the Clinician-Administered Dissociative States Scale (CADSS) | baseline and 24hrs post fMRI scan |
|
depression, MRI, treatment-resistant, imaging, ketamine
|
Depression, Depressive Disorder, Depressive Disorder, Major, Behavioral Symptoms, Mood Disorders, Mental Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MDD<br>patients with current MDD | |
| Healthy Control (HC)<br>healthy control volunteers | |
|
MRI Studies of Emotion in Depression
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to research the effects of ketamine on brain function in patients with Major Depressive Disorder (MDD). This study is an ancillary MRI neuroimaging study being conducted in patients with MDD who are enrolled in a separate clinical trial. Healthy control volunteers are also enrolled. No drug or other intervention is given as part of this protocol per se. To study brain activity related to emotion, the study team will use a technology called functional MRI (fMRI), which is a method for evaluating the flow of blood in the brain using a powerful magnet. fMRI does not involve exposure to radiation. Patients will be shown a sample of images on a computer screen designed to bring about an emotional reaction. The MRI machine will then take a number of pictures of your head. By computer analysis, this machine is able to create a picture of your brain's activity. There are several tasks during scanning that involve looking at various images that represent different emotions, and the study team will be monitoring brain activity during these tasks. Patients will be scanned before and 24 hours after receiving ketamine (as part of a separate study) to analyze treatments effects. These scans are compared to depressed patients who did not receive ketamine, as well as to healthy controls.
Detailed Description
-----------------
Specific Aim 1: To characterize the function of basic neural systems involved in emotion perception and regulation in TRD. Experiment 1.1: Neural responses to emotional faces in TRD (neutral, low and high intensity sad facial expressions). o Hypothesis 1.1: Patients with TRD, relative to HC participants, will evidence increased activation in the amygdala/parahippocampal gyrus to sad compared to neutral faces. Experiment 1.2: Neural responses during negative emotion regulation in TRD (cognitive reappraisal). Hypothesis 1.2: Patients with TRD, relative to HC participants, will show enhanced activation of the amygdala during the generation of negative affect and will be impaired in their ability to recruit PFC/ACC regions during attempts to down-regulate negative affect. Specific Aim 2: To characterize changes in emotion-processing neural networks associated with ketamine and rapid antidepressant response. Experiment 2.1: Neural changes in response to emotional faces associated with ketamine and rapid antidepressant response. o Hypothesis 2.1a: Ketamine, compared to midazolam, will be associated with reduced activation in the amygdala to sad compared to neutral faces. 2.1b: Antidepressant response, compared to non-response, will be specifically associated with changes in PFC/ACC function. Experiment 2.2: Neural changes during negative emotion regulation (cognitive reappraisal) associated with ketamine and rapid antidepressant response. Hypothesis 2.2a: Ketamine, compared to midazolam, will be associated with reduced activation in the amygdala during negative emotion generation and enhanced PFC/ACC function during down-regulation of negative affect. 2.2b: Antidepressant response, compared to non-response, will be specifically associated with enhancement of PFC/ACC function. Specific Aim 3 (Exploratory): To investigate functional and effective connectivity between emotion perception/generation neural systems and cognitive emotional regulation systems. Hypothesis 3: TRD compared to HC will be characterized by abnormal connectivity between PFC/ACC and amygdala, which will normalize with rapid antidepressant response. The setting of research will be MSSM. All research participants will be recruited and screened through the Mood and Anxiety Disorders Program (MAP) (Director: Dan V. Iosifescu, M.D.) at MSSM. MAP is one of the major clinical research programs of the Department of Psychiatry, with research funding from NIH, the Department of Defense, NARSAD, and industry.
Official Title
-----------------
Functional MRI Studies of Emotion in Depression and Rapid Antidepressant Response
Conditions
-----------------
Major Depressive Disorder
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female participants, 18-70 years of age; Participants must be free of any psychiatric condition (for the healthy volunteer group) or meet DSM-IV criteria for major depressive disorder, without psychotic features, based on the Structured Clinical Interview for DSM-IV TR Axis I Disorders (SCID); Participants have demonstrated inadequate response to a minimum of 1 adequate antidepressant treatment trial in current episode (e.g. TRD); Participants must be willing to undergo washout of psychotropic medications that he or she is taking; Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process. Exclusion Criteria: Lifetime diagnosis of schizophrenia or any psychotic disorder, bipolar disorder, pervasive developmental disorders or mental retardation; Current diagnosis of obsessive-compulsive disorder (OCD), but not other anxiety disorders; Diagnosis of a substance use disorder within the past six months; all participants must have a negative urine toxicology test on the day of the fMRI, prior to the scan; Female participants who are pregnant, nursing, for may become pregnant; Any unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease); endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease; Clinically significant abnormalities of laboratories, physical examination, or ECG; Participants judged to be at serious suicidal risk by the PI or another study-affiliated psychiatrist; Any contraindications to MRI, including pacemakers or metallic objects in the body.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| MDD<br>patients with current MDD | |
| Healthy Control (HC)<br>healthy control volunteers | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Montgomery-Asberg Depression Rating Scale | The Montgomery-Asberg Depression Rating Scale (74) is a well-validated 10-item instrument with good ecological validity. It is used extensively in clinical research for the evaluation of depressive symptoms in adults, and is particularly sensitive to detecting change in symptoms. This scale serves as the primary depression-related behavioral rating for correlation with our neuroimaging data. | baseline and 24hrs post fMRI scan |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Clinician-Rated Inventory of Depressive Symptomatology (IDS-C30) | The 30-item Clinician-Rated Inventory of Depressive Symptomatology (IDS-C30) (75) is a clinician-rated instrument which includes all DSM-IV diagnostic criterion items for MDD as well as commonly associated symptoms such as anxiety, irritability, and melancholic and atypical symptom features. | baseline and 24hrs post fMRI scan |
| Change in Brief Psychiatric Rating Scale and the Clinician-Administered Dissociative States Scale (CADSS) | Potential dissociative or other acute behavioral changes during the KET/MID infusions will be assessed using the Brief Psychiatric Rating Scale and the Clinician-Administered Dissociative States Scale (CADSS) | baseline and 24hrs post fMRI scan |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
depression, MRI, treatment-resistant, imaging, ketamine
|
||
NCT02745600
|
Clinical Intervention Modelling, Planning and Proof for Ablation Cancer Treatment
|
The main objective of the project is to bring the existing radio frequency ablation (RFA) model for liver cancer treatment (Project IMPPACT, Grant No. 223877, completed in February 2012) into clinical practice. Therefore the project will pursue the following objectives:~i) to prove and refine the RFA model in a small clinical study; ii) to develop the model into a real-time patient specific RFA planning and support system for Interventional Radiologists (IR) under special consideration of their clinical workflow needs; iii) to establish a corresponding training procedure for IR's; iv) to evaluate the clinical practicality and benefit of the model for use in the routine workflow in a user survey and expert forum.
|
This ClinicIMPPACT proposal builds upon the success of the IMPPACT project (Grant No. 223877, completed in February 2012), which created a model for facilitating more accurate RFA treatment. This preliminary RFA model was tested in swine, with extensive histological workup, and in a clinical simulation study based on patient data, both of which reported relatively high correlations between estimated and actual tumor volumes. The mapping software for liver cancer RFA was developed through this project and provides a simulator for radiologists to plan, review and optimize procedures. Within IMPPACT, extensive experiments were performed on pigs and cells to develop a micro-scale cellular death model, which we used for calibrating the software. After porcine liver calibration, eight patient lesions were selected from a database of clinical procedures, and the planning software was used retrospectively to simulate interventions and predict lesion shapes. Predicted volumes were then compared against real thermal lesions, visualized and segmented in contrast-enhanced CT one month after ablation. These comparisons showed simulated and real lesion volumes to be acceptably matched after taking virtual tissue perfusion values into account. Some lesion shapes were mismatched, possibly due to inaccuracies in segmenting radiological images.~Treatment with RFA could be improved using a validated software solution to estimate lesion size and identify possible complications in advance-ideally, a solution which is adapted to real-time clinical requirements. However, the current state of the art involves long, hardware-intensive computing time (~5 hours), which is impractical for clinical use.~The main goal of this project is to develop a simulation tool, driven by a user-friendly, ergonomically optimized graphical user interface, to support the complex requirements of clinicians. Therefore, the working steps of this international project and its medical and technical partners are to accelerate simulation speed, optimize needle registration, and integrate patients' individual perfusion values into software calculations, as well as accurate validation techniques, to produce more sophisticated and reliable predictions. The software could also aid in offline planning and simulation and as an RFA teaching tool for radiologists. Its use in retrospective analysis should improve clinical follow up and scientific evaluation.
|
Clinical Intervention Modelling, Planning and Proof for Ablation Cancer Treatment (ClinicIMPPACT)
|
Hepatocellular Carcinoma, Liver Metastases
|
* Device: RFA therapy simulator
|
Inclusion Criteria:~primary or secondary tumors of the liver~consent of local tumor board stating RFA is best treatment option~Maximum tumor diameter 3cm~Maximum of 3 lesions~Stable extrahepatic tumor manifestation without growth tendency including the possibility of therapy (e.g. bone, lung metastasis are no contraindication)~If liver cirrhosis must be compensated Child-Pugh A or B~written informed consent~Exclusion Criteria:~Pregnancy and/or breastfeeding~Severe anaphylactic reaction against iodine and/ or contrast agent~Insufficient coagulation~Splenectomy~Insufficient kidney and thyroid gland function
|
18 Years
| null |
All
|
No
|
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the size and shape, using quantitative and semi-quantitative measures, of the real ablation zone one month after RFA treatment of liver tumors with the simulation results of the ClinicIMPPACT software. | For the primary endpoint, the investigators will compare lesions visualized by routine CT one month after ablation with their simulated counterparts to define the accuracy of the method itself. The coinciding volumes of the real RFA lesion and the simulated one will be determined by counting the number of matching voxels, i.e. voxels of simulation and recorded data, sharing the space coordinates, and dividing by the sum of the voxels of simulated and real lesions.~To define the accuracy of the simulation as a parameter, we introduce the following categories:~In comparison to the real ablation the simulation result would have been:~I. much smaller II. comparable III. much larger b) The spatial coordinates of the real ablation differs from the simulated one I. Strongly II. Not strongly | All patients within 1 month follow up in the trial period |
| Comparison of the spatial coordiantes of the real ablation zone one month after RFA treatment of liver tumors with the simulation results of the ClinicIMPPACT software. | To define the accuracy of the simulation as a parameter, the investigators introduce the following categories:~The spatial coordinates of the real ablation differs from the simulated one I. Strongly II. Not strongly | All patients within 1 month follow up in the trial period |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration/Efficiency of workflow steps measured in minutes | Duration of the simulation (minutes) | up to 60 minutes per lesion |
| Would the treatment protocol been influenced by the simulation results if it would have been known in advance by the treating doctor. | Influence Yes/No~• If yes, is there an expectable potential benefit for the patient due to an increase or decrease of the treatment protocol? | 12 months |
| Does the follow - up (3, 6 ,12months) imaging support the assumptions regarding local tumor control | Choice of one of the options below:~The tumor is completely treated with sufficient safety margins, healthy tissue has been largely spared by the ablation and there is no locoregional recurrence visible in the follow - up imaging (= locoregional recurrence free - survival).~The tumor (incl. safety margins) is completely treated, but lots of healthy tissue has been damaged with the risk of serious complications.~The tumor is treated incompletely or there is a visable recurrent tumor in the follow up examination. | up to 24 months due to 12m follow up |
|
RFA, Liver, Ablation Techniques, Treatment Simulation, Computer assisted therapy
|
Carcinoma, Hepatocellular, Neoplasms, Adenocarcinoma, Carcinoma, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Liver Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Digestive System Diseases, Liver Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Software assisted RFA treatment<br>Non-controlled, prospective, multicenter study arm, to evaluate RFA therapy simulation software. | Device: RFA therapy simulator<br>* Computer assisted RFA of liver tumors: Planning, simulation, and follow up,<br>|
|
Clinical Intervention Modelling, Planning and Proof for Ablation Cancer Treatment
Study Overview
=================
Brief Summary
-----------------
The main objective of the project is to bring the existing radio frequency ablation (RFA) model for liver cancer treatment (Project IMPPACT, Grant No. 223877, completed in February 2012) into clinical practice. Therefore the project will pursue the following objectives: i) to prove and refine the RFA model in a small clinical study; ii) to develop the model into a real-time patient specific RFA planning and support system for Interventional Radiologists (IR) under special consideration of their clinical workflow needs; iii) to establish a corresponding training procedure for IR's; iv) to evaluate the clinical practicality and benefit of the model for use in the routine workflow in a user survey and expert forum.
Detailed Description
-----------------
This ClinicIMPPACT proposal builds upon the success of the IMPPACT project (Grant No. 223877, completed in February 2012), which created a model for facilitating more accurate RFA treatment. This preliminary RFA model was tested in swine, with extensive histological workup, and in a clinical simulation study based on patient data, both of which reported relatively high correlations between estimated and actual tumor volumes. The mapping software for liver cancer RFA was developed through this project and provides a simulator for radiologists to plan, review and optimize procedures. Within IMPPACT, extensive experiments were performed on pigs and cells to develop a micro-scale cellular death model, which we used for calibrating the software. After porcine liver calibration, eight patient lesions were selected from a database of clinical procedures, and the planning software was used retrospectively to simulate interventions and predict lesion shapes. Predicted volumes were then compared against real thermal lesions, visualized and segmented in contrast-enhanced CT one month after ablation. These comparisons showed simulated and real lesion volumes to be acceptably matched after taking virtual tissue perfusion values into account. Some lesion shapes were mismatched, possibly due to inaccuracies in segmenting radiological images. Treatment with RFA could be improved using a validated software solution to estimate lesion size and identify possible complications in advance-ideally, a solution which is adapted to real-time clinical requirements. However, the current state of the art involves long, hardware-intensive computing time ( 5 hours), which is impractical for clinical use. The main goal of this project is to develop a simulation tool, driven by a user-friendly, ergonomically optimized graphical user interface, to support the complex requirements of clinicians. Therefore, the working steps of this international project and its medical and technical partners are to accelerate simulation speed, optimize needle registration, and integrate patients' individual perfusion values into software calculations, as well as accurate validation techniques, to produce more sophisticated and reliable predictions. The software could also aid in offline planning and simulation and as an RFA teaching tool for radiologists. Its use in retrospective analysis should improve clinical follow up and scientific evaluation.
Official Title
-----------------
Clinical Intervention Modelling, Planning and Proof for Ablation Cancer Treatment (ClinicIMPPACT)
Conditions
-----------------
Hepatocellular Carcinoma, Liver Metastases
Intervention / Treatment
-----------------
* Device: RFA therapy simulator
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: primary or secondary tumors of the liver consent of local tumor board stating RFA is best treatment option Maximum tumor diameter 3cm Maximum of 3 lesions Stable extrahepatic tumor manifestation without growth tendency including the possibility of therapy (e.g. bone, lung metastasis are no contraindication) If liver cirrhosis must be compensated Child-Pugh A or B written informed consent Exclusion Criteria: Pregnancy and/or breastfeeding Severe anaphylactic reaction against iodine and/ or contrast agent Insufficient coagulation Splenectomy Insufficient kidney and thyroid gland function
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
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Software assisted RFA treatment<br>Non-controlled, prospective, multicenter study arm, to evaluate RFA therapy simulation software. | Device: RFA therapy simulator<br>* Computer assisted RFA of liver tumors: Planning, simulation, and follow up,<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the size and shape, using quantitative and semi-quantitative measures, of the real ablation zone one month after RFA treatment of liver tumors with the simulation results of the ClinicIMPPACT software. | For the primary endpoint, the investigators will compare lesions visualized by routine CT one month after ablation with their simulated counterparts to define the accuracy of the method itself. The coinciding volumes of the real RFA lesion and the simulated one will be determined by counting the number of matching voxels, i.e. voxels of simulation and recorded data, sharing the space coordinates, and dividing by the sum of the voxels of simulated and real lesions. To define the accuracy of the simulation as a parameter, we introduce the following categories: In comparison to the real ablation the simulation result would have been: I. much smaller II. comparable III. much larger b) The spatial coordinates of the real ablation differs from the simulated one I. Strongly II. Not strongly | All patients within 1 month follow up in the trial period |
| Comparison of the spatial coordiantes of the real ablation zone one month after RFA treatment of liver tumors with the simulation results of the ClinicIMPPACT software. | To define the accuracy of the simulation as a parameter, the investigators introduce the following categories: The spatial coordinates of the real ablation differs from the simulated one I. Strongly II. Not strongly | All patients within 1 month follow up in the trial period |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration/Efficiency of workflow steps measured in minutes | Duration of the simulation (minutes) | up to 60 minutes per lesion |
| Would the treatment protocol been influenced by the simulation results if it would have been known in advance by the treating doctor. | Influence Yes/No • If yes, is there an expectable potential benefit for the patient due to an increase or decrease of the treatment protocol? | 12 months |
| Does the follow - up (3, 6 ,12months) imaging support the assumptions regarding local tumor control | Choice of one of the options below: The tumor is completely treated with sufficient safety margins, healthy tissue has been largely spared by the ablation and there is no locoregional recurrence visible in the follow - up imaging (= locoregional recurrence free - survival). The tumor (incl. safety margins) is completely treated, but lots of healthy tissue has been damaged with the risk of serious complications. The tumor is treated incompletely or there is a visable recurrent tumor in the follow up examination. | up to 24 months due to 12m follow up |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
RFA, Liver, Ablation Techniques, Treatment Simulation, Computer assisted therapy
|
NCT00279669
|
Ultrasound to Detect Evidence for Retinal Detachment in Retinopathy of Prematurity
|
Premature infants stand a risk of danger to the layer of the eye that creates sight that, if untreated, can cause severe vision problems, leading to blindness in some cases. This research study will use ultrasound to examine the eye for retinal changes of prematurity.
|
Retinopathy of prematurity requires the early detection of retinopathy in neonates with a gestational age of < 28 weeks and a birth weight <1500 g. These evaluations require pupillary dilation, diagnostic expertise, consume much time and expense and are not without morbidity.~B-scan ultrasonography using a hand-held probe is part of the current ophthalmologist's armamentarium, providing a non-invasive view of the eye and avoiding the morbidity associated with mydriatic drops used for pupillary dilation.~We will use a simple water bath enclosure for a standard 20 MHz probe currently in general ophthalmic use to determine whether this simple technique might supplant indirect ophthalmoscopy as a screening technique. We will compare, using masked observers, the clinical findings of indirect ophthalmoscopy of neonatal infants with ultrasonic findings to determine if a correlation in the stages of retinopathy of prematurity (ROP) between the two techniques existed.
|
Ultrasound to Detect Evidence for Retinal Detachment in Retinopathy of Prematurity
|
Retinopathy of Prematurity
|
* Procedure: Ultrasound examination
|
Inclusion Criteria:~premature birth~Exclusion Criteria:~none
| null | null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
Retinopathy of Prematurity, Ultrasound, Eye
|
Retinal Diseases, Retinal Detachment, Retinopathy of Prematurity, Premature Birth, Eye Diseases, Obstetric Labor, Premature, Obstetric Labor Complications, Pregnancy Complications, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Infant, Premature, Diseases, Infant, Newborn, Diseases
|
| Intervention/Treatment |
| --- |
|Procedure: Ultrasound examination|contact ultrasound examination|
|
Ultrasound to Detect Evidence for Retinal Detachment in Retinopathy of Prematurity
Study Overview
=================
Brief Summary
-----------------
Premature infants stand a risk of danger to the layer of the eye that creates sight that, if untreated, can cause severe vision problems, leading to blindness in some cases. This research study will use ultrasound to examine the eye for retinal changes of prematurity.
Detailed Description
-----------------
Retinopathy of prematurity requires the early detection of retinopathy in neonates with a gestational age of < 28 weeks and a birth weight <1500 g. These evaluations require pupillary dilation, diagnostic expertise, consume much time and expense and are not without morbidity. B-scan ultrasonography using a hand-held probe is part of the current ophthalmologist's armamentarium, providing a non-invasive view of the eye and avoiding the morbidity associated with mydriatic drops used for pupillary dilation. We will use a simple water bath enclosure for a standard 20 MHz probe currently in general ophthalmic use to determine whether this simple technique might supplant indirect ophthalmoscopy as a screening technique. We will compare, using masked observers, the clinical findings of indirect ophthalmoscopy of neonatal infants with ultrasonic findings to determine if a correlation in the stages of retinopathy of prematurity (ROP) between the two techniques existed.
Official Title
-----------------
Ultrasound to Detect Evidence for Retinal Detachment in Retinopathy of Prematurity
Conditions
-----------------
Retinopathy of Prematurity
Intervention / Treatment
-----------------
* Procedure: Ultrasound examination
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: premature birth Exclusion Criteria: none
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Intervention/Treatment |
| --- |
|Procedure: Ultrasound examination|contact ultrasound examination|
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
-----------------
Retinopathy of Prematurity, Ultrasound, Eye
|
||
NCT02345967
|
Function of Implanted Glucose Sensor 2
|
The purpose of this study is to verify safety and assess tolerance of a long-term, implanted glucose monitoring sensor. The study will also provide data to characterize the response properties and calibration of the implanted sensor and determine if such properties vary with implant duration.
|
Function of Implanted Glucose Sensor 2
|
Diabetes Mellitus
|
* Device: Model 100 Sensor
|
Inclusion Criteria:~Either: (1) male or (2) female and not pregnant, breastfeeding, or planning to become pregnant~Diabetes diagnosis of type 1, or type 2 using insulin~Under the routine care of a physician for diabetes treatment~Able to understand and follow directions~History of compliance with diabetes care regimen~Able to comply with study requirements regarding planned clinical visits and exams~In good physical condition without major medical concerns or blood chemistry abnormalities~Exclusion Criteria:~Mental disorders that might affect compliance to protocols~Diabetes diagnosis type 2 where treatment involves (1) oral medication without insulin or (2) insulin use restricted to a single daily injection of long-acting insulin or (3) control by diet/exercise regimen alone~History of intolerance or sensitivity to any of the device materials~History of any adverse reaction or allergy to any of the drugs/agents utilized in the study procedures~History of recurrent skin infections
|
21 Years
|
65 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events | Incidence of adverse events related to the Intervention | From enrollment to 2-weeks post-explant |
|
diabetes mellitus requiring insulin
|
Diabetes Mellitus, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group<br>Device: Model 100 Sensor | Device: Model 100 Sensor<br>* One Model 100 Sensor to be implanted per subject.<br>|
|
Function of Implanted Glucose Sensor 2
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to verify safety and assess tolerance of a long-term, implanted glucose monitoring sensor. The study will also provide data to characterize the response properties and calibration of the implanted sensor and determine if such properties vary with implant duration.
Official Title
-----------------
Function of Implanted Glucose Sensor 2
Conditions
-----------------
Diabetes Mellitus
Intervention / Treatment
-----------------
* Device: Model 100 Sensor
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Either: (1) male or (2) female and not pregnant, breastfeeding, or planning to become pregnant Diabetes diagnosis of type 1, or type 2 using insulin Under the routine care of a physician for diabetes treatment Able to understand and follow directions History of compliance with diabetes care regimen Able to comply with study requirements regarding planned clinical visits and exams In good physical condition without major medical concerns or blood chemistry abnormalities Exclusion Criteria: Mental disorders that might affect compliance to protocols Diabetes diagnosis type 2 where treatment involves (1) oral medication without insulin or (2) insulin use restricted to a single daily injection of long-acting insulin or (3) control by diet/exercise regimen alone History of intolerance or sensitivity to any of the device materials History of any adverse reaction or allergy to any of the drugs/agents utilized in the study procedures History of recurrent skin infections
Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 65 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: Study Group<br>Device: Model 100 Sensor | Device: Model 100 Sensor<br>* One Model 100 Sensor to be implanted per subject.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events | Incidence of adverse events related to the Intervention | From enrollment to 2-weeks post-explant |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
diabetes mellitus requiring insulin
|
||
NCT04763590
|
Cognitive Behavioral Therapy for Mechanical Ventilation Wean
|
The purpose of this study is to use CBT strategies in assisting patients hospitalized in intensive care units in ventilation wean through a case series of 2 patients.
|
Approximately a third of patients in intensive care are mechanically ventilated. The current weaning standard of care leaves much to be desired in both patient anxiety and time to wean. Cognitive behavioral therapy (CBT) is the gold standard treatment for anxiety. The purpose of this study is to use CBT strategies in assisting patients hospitalized in intensive care units in ventilation wean through a case series of 2 patients.
|
Cognitive Behavioral Therapy for Mechanical Ventilation Wean
|
Anxiety, Cognitive Behavioral Therapy, Mechanical Ventilation Complication
|
* Behavioral: Cognitive Behavioral Therapy
|
Inclusion Criteria:~Receiving mechanical ventilation and Failed 3 spontaneous breathing trials~Exclusion Criteria:~Delirium
| null |
100 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory Anxiety | The Anxiety Inventory for Respiratory Disease provides an assessment of anxiety in patient with respiratory disease which is free of the physical symptoms of respiratory disease that often overlap with and confound an accurate assessment of anxiety. A score of 14.5 discriminates between patients with and without anxiety. The measure is reliable, valid, and sensitive to change. | 6 weeks |
| Panic Symptoms | the investigators assessed whether patients experienced the panic symptoms listed in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, when weaning from the ventilator or when anticipating weaning and, if they endorsed the symptom, asked patients to rate symptom severity from 1 to 7 (7 being the worst). | 6 weeks |
| Generalized Anxiety | The investigators assessed generalized anxiety with the Generalized Anxiety Disorder 7 Scale (GAD-7). The minimum score is zero and maximum score is 21. Higher scores represent a worse outcome. A score of 10 on the Generalized Anxiety Disorder 7 represents clinically significant levels of generalized anxiety. | 6 weeks |
| Depression | The investigators assessed depression with the Patient Health Questionnaire 2 (PHQ-2). The scale ranges from zero to 6, with higher scores representing a worse outcome. A score of 3 or higher signifies likely clinical depression. | 6 weeks |
| Time spent on tracheostomy-collar (off mechanical ventilation) | Time on tracheostomy collar (TC) was assessed from the beginning of the cognitive behavioral therapy intervention until study completion. | 6 weeks |
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cognitive Behavioral Therapy<br>Cognitive Behavioral Therapy (CBT) had 3 principal components: (1) psychoeducation, (2) cognitive restructuring, and (3) exposure. In this treatment, derived from an empirically-supported treatment for panic disorder, psychoeducation consisted of teaching about the interrelationship between thoughts, feelings, and physical sensations during weaning. The cognitive component taught patients how to challenge their thoughts, with a particular focus on identifying thoughts that over-estimated the probability of negative medical events. The behavioral component consisted of reducing the need for mechanical ventilation in a step-wise, graduated, manner. | Behavioral: Cognitive Behavioral Therapy<br>* This study focuses on patients who are on a mechanical ventilator and who have been medically cleared to come off of it. The purpose of the study is to learn more about the possible influence of cognitive behavioral therapy in helping patients who are having some trouble getting off of the ventilator. Cognitive behavioral therapy is a highly effective intervention for anxiety and the investigators are evaluating whether cognitive behavioral therapy might be helpful in cases where it is difficult to come off of the ventilator.~Cognitive behavioral therapy is experimental for mechanical ventilation assistance as no research to date has evaluated whether it might be helpful.<br>|
|
Cognitive Behavioral Therapy for Mechanical Ventilation Wean
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to use CBT strategies in assisting patients hospitalized in intensive care units in ventilation wean through a case series of 2 patients.
Detailed Description
-----------------
Approximately a third of patients in intensive care are mechanically ventilated. The current weaning standard of care leaves much to be desired in both patient anxiety and time to wean. Cognitive behavioral therapy (CBT) is the gold standard treatment for anxiety. The purpose of this study is to use CBT strategies in assisting patients hospitalized in intensive care units in ventilation wean through a case series of 2 patients.
Official Title
-----------------
Cognitive Behavioral Therapy for Mechanical Ventilation Wean
Conditions
-----------------
Anxiety, Cognitive Behavioral Therapy, Mechanical Ventilation Complication
Intervention / Treatment
-----------------
* Behavioral: Cognitive Behavioral Therapy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Receiving mechanical ventilation and Failed 3 spontaneous breathing trials Exclusion Criteria: Delirium
Ages Eligible for Study
-----------------
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
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cognitive Behavioral Therapy<br>Cognitive Behavioral Therapy (CBT) had 3 principal components: (1) psychoeducation, (2) cognitive restructuring, and (3) exposure. In this treatment, derived from an empirically-supported treatment for panic disorder, psychoeducation consisted of teaching about the interrelationship between thoughts, feelings, and physical sensations during weaning. The cognitive component taught patients how to challenge their thoughts, with a particular focus on identifying thoughts that over-estimated the probability of negative medical events. The behavioral component consisted of reducing the need for mechanical ventilation in a step-wise, graduated, manner. | Behavioral: Cognitive Behavioral Therapy<br>* This study focuses on patients who are on a mechanical ventilator and who have been medically cleared to come off of it. The purpose of the study is to learn more about the possible influence of cognitive behavioral therapy in helping patients who are having some trouble getting off of the ventilator. Cognitive behavioral therapy is a highly effective intervention for anxiety and the investigators are evaluating whether cognitive behavioral therapy might be helpful in cases where it is difficult to come off of the ventilator. Cognitive behavioral therapy is experimental for mechanical ventilation assistance as no research to date has evaluated whether it might be helpful.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory Anxiety | The Anxiety Inventory for Respiratory Disease provides an assessment of anxiety in patient with respiratory disease which is free of the physical symptoms of respiratory disease that often overlap with and confound an accurate assessment of anxiety. A score of 14.5 discriminates between patients with and without anxiety. The measure is reliable, valid, and sensitive to change. | 6 weeks |
| Panic Symptoms | the investigators assessed whether patients experienced the panic symptoms listed in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, when weaning from the ventilator or when anticipating weaning and, if they endorsed the symptom, asked patients to rate symptom severity from 1 to 7 (7 being the worst). | 6 weeks |
| Generalized Anxiety | The investigators assessed generalized anxiety with the Generalized Anxiety Disorder 7 Scale (GAD-7). The minimum score is zero and maximum score is 21. Higher scores represent a worse outcome. A score of 10 on the Generalized Anxiety Disorder 7 represents clinically significant levels of generalized anxiety. | 6 weeks |
| Depression | The investigators assessed depression with the Patient Health Questionnaire 2 (PHQ-2). The scale ranges from zero to 6, with higher scores representing a worse outcome. A score of 3 or higher signifies likely clinical depression. | 6 weeks |
| Time spent on tracheostomy-collar (off mechanical ventilation) | Time on tracheostomy collar (TC) was assessed from the beginning of the cognitive behavioral therapy intervention until study completion. | 6 weeks |
|
|||
NCT05694520
|
A Pragmatic Randomized Controlled Trial of Health Impact of Pistachios on Women With Gestational Diabetes Mellitus
|
Gestational diabetes mellitus (GDM) is the hyperglycemia with first onset or recognition during pregnancy, of which prevalence has been sharply increased worldwide in the past decades. Nuts offer numerous health benefits, mainly in relation to cardiovascular diseases as well as other chronic conditions. Pistachios have a balanced nutrition profile with lower fat [polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs)], higher protein, fiber (both soluble and insoluble), potassium, phytosterols, γ-tocopherol, vitamin K, xanthophyll carotenoids and rich antioxidant phytochemical constituents (stigmasterol, campesterol, resveratrol, catechins, lutein and zeaxanthin). Recent researches have found that nutritional intervention of the Mediterranean diet with an enhanced consumption of extra virgin olive oil and pistachios lowered incidence of GDM and other adverse outcomes (urinary tract infections, emergency C-sections, perineal trauma, large-for-gestational-age and small-for gestational age newborns) for pregnant women. Another clinical trial compared the acute metabolic effect of pistachios and isocaloric whole-wheat bread in women with GDM, finding significantly improved glucose and insulin responses, higher GLP-1 and lower gastric inhibitory polypeptide (GIP) levels in those consuming pistachios. However, more compelling evidences are still in need to throw light on the long-term effects of pistachio consumption on maternal and offspring's outcomes for GDM patients. Besides, effects of pistachios on the thorough metabolic profile of GDM patients also need to be elucidated.~This study aims to further demonstrate the long-term health effects of pistachio consumption on glycemic control, lipid profile, gut hormone responses, inflammatory condition and pregnancy outcomes for women with GDM.~The clinical study is a randomized, controlled, two-arm, parallel trial from the diagnosis of gestational diabetes to delivery consisting of six study visits including screening/consent. A total of 80 singleton pregnant women with confirmed diagnosis of GDM will be consecutively recruited, all with the pregestational body mass index (BMI) greater than 24 kg/m2. All subjects will be randomly assigned to intervention group (IG) or stand care control group (CG)), in an allocation ratio of (1:1) in blocks.~According to the Chinese nutritional guidelines for GDM women, the energy intake of 1500-1800 kcal/d will be recommended for the included women with pregestational BMI≥24 kg/m2. Standard care and a balanced diet will be recommended to the women in CG incorporating the total nuts intake of less than 2.5 oz per week). While the women in the IG will be offered the otherwise same diet as their counterparts in the CG, except for the extra intake of pistachios of 1.5 oz thrice per week. All participants will be followed up in 2 weeks initially and then once every 4-6 weeks until delivery or termination of pregnancy. The effect of different interventions on the glycemic profile (the continuous glucose monitoring (CGM) plus self-monitoring), lipid profile, gut hormone responses, inflammatory factors and metabolomics profiling (multi-omics data) will be monitored and compared. The pregnant outcome of the two groups will be also followed up and compared eventually.~With all data reviewed and analyzed, this study will add evidence to the long-term health effect of pistachios on GDM women.
|
A Pragmatic Randomized Controlled Trial of Health Impact of Pistachios on Women
|
Gestational Diabetes Mellitus in Pregnancy
|
* Other: pistachios consumption of 1.5 oz thrice per week
|
Inclusion Criteria:~Chinese women at the age of 20-45 years, with Han ethnicity and singleton pregnancies~Women who are at 20-30 weeks' singleton gestation and have the first onset of hyperglycemia which fulfills at least one of the following criteria: fasting glucose ≥5.1 mmol/L, 1 h glucose ≥10 mmol/L or 2 h glucose ≥8.5 mmol/L during the 2 h 75 g OGTT.~Pregestational BMI greater than 24 kg/m2.~Willing to comply with the research requirements~Exclusion Criteria:~Gastrointestinal malabsorption and chronic diseases that alter nutrient metabolism~Allergy or intolerance to pistachios~Pre-existing diabetes, insulin resistance, impaired fasting glucose or impaired glucose tolerance~Pregnancy with more than one fetus~Current or planned corticosteroid therapy~Current or planned beta adrenergic therapy~Chronic medical conditions such as HIV/AIDS, kidney disease, or congenital heart disease~Hematologic or autoimmune disease such as sickle cell disease, other hemoglobinopathies, lupus, or antiphospholipid syndrome
|
20 Years
|
45 Years
|
Female
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All subjects will be randomly assigned to intervention group (IG) or stand care control group (CG)), in an allocation ratio of (1:1) in blocks.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline Blood glucose response at 2 months | Change from baseline of the blood glucose response (time-in-range (TIR) on CGM, Hgb A1c, area under the curve of postprandial blood glucose (CGM)) after the nutritional management over 2 months | up to 2 months |
| The incidences of adverse maternofetal outcomes | The incidences of adverse maternofetal outcomes: emergency caesarean section (C-section), perineal trauma, pregnancy-induced hypertension and preeclampsia, prematurity, large-for-gestational age, and small-for-gestational age. | From date of intervention until the date of the delivery or termination of pregnancy, up to 4 months.. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline the lipid profile at 2 months | Change from baseline of the lipid profile (TG, TC, HDL-C, LDL-C) after the nutritional management over 2 months | up to 2 months |
| Change from baseline the inflammatory factors at 2 months | Change from baseline of the inflammatory factors (IL-6, hsCRP) after the nutritional management over 2 months | up to 2 months |
|
Diabetes, Gestational, Pregnancy in Diabetics, Diabetes Mellitus, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Pregnancy Complications, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Stand care control group (CG)<br>According to the Chinese nutritional guidelines for GDM women, the energy intake of 1500-1800 kcal/d will be recommended for the included participants, who all have the pregestational BMI≥24 kg/m2. Standard care and a balanced diet will be recommended to the women in CG incorporating nuts intake of less than 2.5 oz per week. | |
| Experimental: Intervention group (IG)<br>The participants in the IG will be offered the otherwise same diet as their counterparts in the CG, except for the extra intake of pistachios of 1.5 oz thrice per week. | Other: pistachios consumption of 1.5 oz thrice per week<br>* According to the Chinese nutritional guidelines for GDM women, the energy intake of 1500-1800 kcal/d will be recommended for all the included participants with pregestational BMI≥24 kg/m2. Standard care and a balanced diet will be recommended to the women in CG incorporating the total nuts intake of less than 2.5 oz per week). While the women in the IG will be offered the otherwise same diet as their counterparts in the CG, except for the extra intake of pistachios of 1.5 oz thrice per week.<br>|
|
A Pragmatic Randomized Controlled Trial of Health Impact of Pistachios on Women With Gestational Diabetes Mellitus
Study Overview
=================
Brief Summary
-----------------
Gestational diabetes mellitus (GDM) is the hyperglycemia with first onset or recognition during pregnancy, of which prevalence has been sharply increased worldwide in the past decades. Nuts offer numerous health benefits, mainly in relation to cardiovascular diseases as well as other chronic conditions. Pistachios have a balanced nutrition profile with lower fat [polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs)], higher protein, fiber (both soluble and insoluble), potassium, phytosterols, γ-tocopherol, vitamin K, xanthophyll carotenoids and rich antioxidant phytochemical constituents (stigmasterol, campesterol, resveratrol, catechins, lutein and zeaxanthin). Recent researches have found that nutritional intervention of the Mediterranean diet with an enhanced consumption of extra virgin olive oil and pistachios lowered incidence of GDM and other adverse outcomes (urinary tract infections, emergency C-sections, perineal trauma, large-for-gestational-age and small-for gestational age newborns) for pregnant women. Another clinical trial compared the acute metabolic effect of pistachios and isocaloric whole-wheat bread in women with GDM, finding significantly improved glucose and insulin responses, higher GLP-1 and lower gastric inhibitory polypeptide (GIP) levels in those consuming pistachios. However, more compelling evidences are still in need to throw light on the long-term effects of pistachio consumption on maternal and offspring's outcomes for GDM patients. Besides, effects of pistachios on the thorough metabolic profile of GDM patients also need to be elucidated. This study aims to further demonstrate the long-term health effects of pistachio consumption on glycemic control, lipid profile, gut hormone responses, inflammatory condition and pregnancy outcomes for women with GDM. The clinical study is a randomized, controlled, two-arm, parallel trial from the diagnosis of gestational diabetes to delivery consisting of six study visits including screening/consent. A total of 80 singleton pregnant women with confirmed diagnosis of GDM will be consecutively recruited, all with the pregestational body mass index (BMI) greater than 24 kg/m2. All subjects will be randomly assigned to intervention group (IG) or stand care control group (CG)), in an allocation ratio of (1:1) in blocks. According to the Chinese nutritional guidelines for GDM women, the energy intake of 1500-1800 kcal/d will be recommended for the included women with pregestational BMI≥24 kg/m2. Standard care and a balanced diet will be recommended to the women in CG incorporating the total nuts intake of less than 2.5 oz per week). While the women in the IG will be offered the otherwise same diet as their counterparts in the CG, except for the extra intake of pistachios of 1.5 oz thrice per week. All participants will be followed up in 2 weeks initially and then once every 4-6 weeks until delivery or termination of pregnancy. The effect of different interventions on the glycemic profile (the continuous glucose monitoring (CGM) plus self-monitoring), lipid profile, gut hormone responses, inflammatory factors and metabolomics profiling (multi-omics data) will be monitored and compared. The pregnant outcome of the two groups will be also followed up and compared eventually. With all data reviewed and analyzed, this study will add evidence to the long-term health effect of pistachios on GDM women.
Official Title
-----------------
A Pragmatic Randomized Controlled Trial of Health Impact of Pistachios on Women
Conditions
-----------------
Gestational Diabetes Mellitus in Pregnancy
Intervention / Treatment
-----------------
* Other: pistachios consumption of 1.5 oz thrice per week
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Chinese women at the age of 20-45 years, with Han ethnicity and singleton pregnancies Women who are at 20-30 weeks' singleton gestation and have the first onset of hyperglycemia which fulfills at least one of the following criteria: fasting glucose ≥5.1 mmol/L, 1 h glucose ≥10 mmol/L or 2 h glucose ≥8.5 mmol/L during the 2 h 75 g OGTT. Pregestational BMI greater than 24 kg/m2. Willing to comply with the research requirements Exclusion Criteria: Gastrointestinal malabsorption and chronic diseases that alter nutrient metabolism Allergy or intolerance to pistachios Pre-existing diabetes, insulin resistance, impaired fasting glucose or impaired glucose tolerance Pregnancy with more than one fetus Current or planned corticosteroid therapy Current or planned beta adrenergic therapy Chronic medical conditions such as HIV/AIDS, kidney disease, or congenital heart disease Hematologic or autoimmune disease such as sickle cell disease, other hemoglobinopathies, lupus, or antiphospholipid syndrome
Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 45 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
Interventional Model Description: All subjects will be randomly assigned to intervention group (IG) or stand care control group (CG)), in an allocation ratio of (1:1) in blocks.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Stand care control group (CG)<br>According to the Chinese nutritional guidelines for GDM women, the energy intake of 1500-1800 kcal/d will be recommended for the included participants, who all have the pregestational BMI≥24 kg/m2. Standard care and a balanced diet will be recommended to the women in CG incorporating nuts intake of less than 2.5 oz per week. | |
| Experimental: Intervention group (IG)<br>The participants in the IG will be offered the otherwise same diet as their counterparts in the CG, except for the extra intake of pistachios of 1.5 oz thrice per week. | Other: pistachios consumption of 1.5 oz thrice per week<br>* According to the Chinese nutritional guidelines for GDM women, the energy intake of 1500-1800 kcal/d will be recommended for all the included participants with pregestational BMI≥24 kg/m2. Standard care and a balanced diet will be recommended to the women in CG incorporating the total nuts intake of less than 2.5 oz per week). While the women in the IG will be offered the otherwise same diet as their counterparts in the CG, except for the extra intake of pistachios of 1.5 oz thrice per week.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline Blood glucose response at 2 months | Change from baseline of the blood glucose response (time-in-range (TIR) on CGM, Hgb A1c, area under the curve of postprandial blood glucose (CGM)) after the nutritional management over 2 months | up to 2 months |
| The incidences of adverse maternofetal outcomes | The incidences of adverse maternofetal outcomes: emergency caesarean section (C-section), perineal trauma, pregnancy-induced hypertension and preeclampsia, prematurity, large-for-gestational age, and small-for-gestational age. | From date of intervention until the date of the delivery or termination of pregnancy, up to 4 months.. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline the lipid profile at 2 months | Change from baseline of the lipid profile (TG, TC, HDL-C, LDL-C) after the nutritional management over 2 months | up to 2 months |
| Change from baseline the inflammatory factors at 2 months | Change from baseline of the inflammatory factors (IL-6, hsCRP) after the nutritional management over 2 months | up to 2 months |
|
||
NCT00967642
|
Intravenous Insulin in Patients With Diabetes After Percutaneous Coronary Intervention (PCI)
|
The purpose of this study is to evaluate the effects of intravenous insulin/24 hours to normalize glycemia upon markers of oxidative stress (protein oxidation and total antioxidant defense) and inflammation (C-reactive protein (CRP) and sCD40L) in diabetic patients submitted to PCI with stent.
|
Intravenous Insulin for 24 Hours in Patients With Diabetes Mellitus Submitted to Percutaneous Coronary Intervention With Stent: Effects Upon Oxidative Stress and Inflammatory Markers
|
Diabetes Mellitus, Percutaneous Coronary Intervention
|
* Drug: Intravenous Insulin
|
Inclusion Criteria:~Patients with Diabetes Mellitus submitted to Percutaneous Coronary Intervention with Stent bare metal~Age: 18-80 years old~Exclusion Criteria:~Restenosis~Drug elution stent~Acute coronary syndrome at last 30 days~Use anti inflammatory, antibiotic, vitamin E~Inflammatory disease or oncologic
|
18 Years
|
80 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reintervention, Myocardial Infarction, Cardiovascular Death | | 6 months |
|
Patients with Diabetes Mellitus Submitted to Percutaneous Coronary Intervention with Stent
|
Insulin, Hypoglycemic Agents, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: standard treatment<br>glycemia before meals and subcutaneous regular insulin if higher than 200 mg/dl | |
| Other: Intravenous Insulin<br>intravenous insulin/24h guided by glycemia (Optium, Abbott) evaluated hourly, targeting values lower than 110 mg/dl | Drug: Intravenous Insulin<br>* continuous intravenous insulin/24h guided by glycemia (Optium, Abbott) evaluated hourly, targeting values lower than 110 mg/dl<br>|
|
Intravenous Insulin in Patients With Diabetes After Percutaneous Coronary Intervention (PCI)
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the effects of intravenous insulin/24 hours to normalize glycemia upon markers of oxidative stress (protein oxidation and total antioxidant defense) and inflammation (C-reactive protein (CRP) and sCD40L) in diabetic patients submitted to PCI with stent.
Official Title
-----------------
Intravenous Insulin for 24 Hours in Patients With Diabetes Mellitus Submitted to Percutaneous Coronary Intervention With Stent: Effects Upon Oxidative Stress and Inflammatory Markers
Conditions
-----------------
Diabetes Mellitus, Percutaneous Coronary Intervention
Intervention / Treatment
-----------------
* Drug: Intravenous Insulin
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with Diabetes Mellitus submitted to Percutaneous Coronary Intervention with Stent bare metal Age: 18-80 years old Exclusion Criteria: Restenosis Drug elution stent Acute coronary syndrome at last 30 days Use anti inflammatory, antibiotic, vitamin E Inflammatory disease or oncologic
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: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: standard treatment<br>glycemia before meals and subcutaneous regular insulin if higher than 200 mg/dl | |
| Other: Intravenous Insulin<br>intravenous insulin/24h guided by glycemia (Optium, Abbott) evaluated hourly, targeting values lower than 110 mg/dl | Drug: Intravenous Insulin<br>* continuous intravenous insulin/24h guided by glycemia (Optium, Abbott) evaluated hourly, targeting values lower than 110 mg/dl<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reintervention, Myocardial Infarction, Cardiovascular Death | | 6 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Patients with Diabetes Mellitus Submitted to Percutaneous Coronary Intervention with Stent
|
||
NCT03302325
|
Circulating Tumor DNA as Liquid Biopsy in Patients With Stage IV Solid Tumors, a Feasibility Study at MUSC HCC
|
To demonstrate the ability to detect specific cancer mutations in ctDNA isolated from plasma of stage IV cancer patients at HCC.~To compare, in each patient, ctDNA longitudinal samples through treatment, and when available, with those of primary tumor and metastasis.
|
The overall goal of this study is to study circulating tumor DNA (ctDNA) in the blood to determine how cancer cells in patients react to treatment. DNA is short for deoxyribonucleic acid. DNA contains information that determines in part the traits, such as eye color, height, or disease risk, that are passed on from parent to child. This reaction will be measured by studying patient blood that will be collected before and during treatment until there is disease progression.
|
Circulating Tumor DNA as Liquid Biopsy in Patients With Stage IV Solid Tumors, a Feasibility Study at MUSC HCC
|
Solid Tumor, Adult
|
* Procedure: research blood draws
|
Inclusion Criteria:~Confirmed diagnosis of stage IV malignancy, including any advanced solid tumors (including lymphoma)~Eastern Cooperative Oncology Group (ECOG) performance Status (PS) 0-3~Life expectancy ≥ 3 months~Patients must be able to provide consent~Patients can be enrolled in other interventional clinical trials~Exclusion Criteria:~- Age < 18-year-old
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detecting specific cancer mutations in ctDNA isolated from plasma of stage IV cancer patients at HCC. | | 24 months |
| Changes in patients' ctDNA longitudinal samples through treatment, and when available, of primary tumor and metastasis. | | 24 months |
|
stage IV solid tumor
|
Neoplasms
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Stage IV solid tumors<br>adult patients with stage IV cancer that are starting a new line of treatment | Procedure: research blood draws<br>* Twenty-five mL of peripheral blood (PB) will be collected for research. Blood will be collected in EDTA tubes and used to isolate ctDNA. For each subject we will request that he/she contribute 25 mL of plasma no more frequently than every 6 weeks, and at same time of standard of care blood draws and routine clinic visit, and for no more than 3 times (including baseline and end of study).<br>|
|
Circulating Tumor DNA as Liquid Biopsy in Patients With Stage IV Solid Tumors, a Feasibility Study at MUSC HCC
Study Overview
=================
Brief Summary
-----------------
To demonstrate the ability to detect specific cancer mutations in ctDNA isolated from plasma of stage IV cancer patients at HCC. To compare, in each patient, ctDNA longitudinal samples through treatment, and when available, with those of primary tumor and metastasis.
Detailed Description
-----------------
The overall goal of this study is to study circulating tumor DNA (ctDNA) in the blood to determine how cancer cells in patients react to treatment. DNA is short for deoxyribonucleic acid. DNA contains information that determines in part the traits, such as eye color, height, or disease risk, that are passed on from parent to child. This reaction will be measured by studying patient blood that will be collected before and during treatment until there is disease progression.
Official Title
-----------------
Circulating Tumor DNA as Liquid Biopsy in Patients With Stage IV Solid Tumors, a Feasibility Study at MUSC HCC
Conditions
-----------------
Solid Tumor, Adult
Intervention / Treatment
-----------------
* Procedure: research blood draws
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Confirmed diagnosis of stage IV malignancy, including any advanced solid tumors (including lymphoma) Eastern Cooperative Oncology Group (ECOG) performance Status (PS) 0-3 Life expectancy ≥ 3 months Patients must be able to provide consent Patients can be enrolled in other interventional clinical trials Exclusion Criteria: - Age < 18-year-old
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 |
| --- | --- |
| Stage IV solid tumors<br>adult patients with stage IV cancer that are starting a new line of treatment | Procedure: research blood draws<br>* Twenty-five mL of peripheral blood (PB) will be collected for research. Blood will be collected in EDTA tubes and used to isolate ctDNA. For each subject we will request that he/she contribute 25 mL of plasma no more frequently than every 6 weeks, and at same time of standard of care blood draws and routine clinic visit, and for no more than 3 times (including baseline and end of study).<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detecting specific cancer mutations in ctDNA isolated from plasma of stage IV cancer patients at HCC. | | 24 months |
| Changes in patients' ctDNA longitudinal samples through treatment, and when available, of primary tumor and metastasis. | | 24 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage IV solid tumor
|
||
NCT02900053
|
Post-traumatic Stress Disorder Treatment Using Transcranial Direct Current Stimulation (tDCS) Enhancement of Trauma-focused Therapy : a Two-arm Randomized Controlled Multicentric Study.
|
Post-Traumatic Stress Disorder (PTSD) is an anxiety disorder that can develop after exposure to a terrifying event or ordeal in which there was the potential for or actual occurrence of grave physical harm. Traumatic events that may trigger PTSD include violent personal assaults, natural or human-caused disasters, accidents, and military combat. People with PTSD have persistent frightening thoughts and memories of their ordeal, may experience sleep problems, feel detached or numb, or be easily startled. Its lifetime prevalence is quite high, with 7-8% in various studies and 4% in french studies.~The current PTSD treatment usually involves antidepressants as serotonin-specific reuptake inhibitors (SSRIs) and Cognitive Behavioral Therapies, such as exposure therapy to trauma-linked elements (memories, feelings and thoughts) so the fear associated to the traumatic event can decrease. But the therapeutic response stays partial, even combining these treatments.~To improve the PTSD treatment efficiency, innovative approaches are being explored like new drugs or cerebral stimulation. This project aims to assess the efficacy of a less known but promising therapeutic strategy for PTSD : the use of transcranial Direct-Current Stimulation (tDCS) to enhance the trauma-focused therapy results.
|
Post-traumatic Stress Disorder Treatment Using Transcranial Direct Current Stimulation (tDCS) Enhancement of Trauma-focused Therapy : a Two-arm Randomized Controlled Multicentric Study - T-TREAt
|
Post-traumatic Stress Disorder
|
* Device: tDCS
* Device: Placebo tDCS
|
Inclusion Criteria:~Having a chronic PTSD (for more than 3 months and less than 10 years) without modification of SSRI long-term treatment for more than 4 weeks~Between 18 and 65 years-old~Effective contraception for women, or inability of procreate because of medical or surgical reasons~Able to give his written informed consent~Affiliation to a social security system~Not participating to another study with psychoactive substance~Exclusion Criteria:~Partially-sighted or partially deaf person requiring equipment~Person with brain injury or neurological disease (epileptic, tumoral, vascular, degenerative), diagnoses in personal history or recognized as hereditary~Addiction to psychoactive substance for the last 6 months~Any treatment which could interact with tDCS effects on cortical reactivity (citalopram, amphetamine, L-dopa, sulpiride, pergolide, lorazepam, rivastigmine, dextromethorphan or other N-methyl-D-aspartate (NMDA) receptor antagonists, d-cycloserine, carbamazepine, flunarizine, calcium channel blockers)~Pregnancy and lactation~Any intracephalic metallic material~Person who can't conform to tests instructions~Person suffering from bipolar disorder, chronic or acute delusional disorder~Any circumstances making the person unable to understand the trial features, purposes or consequences
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of PTSD symptoms | Evolution of PTSD symptoms defined by difference of PTSD severity score measured by Clinician Administered PTSD Scale ( CAPS-5, structured interview) | between initial evaluation at J0 before beginning of treatment and follow-up evaluation at 3 month after the end of treatment |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of PTSD severity score | Evolution of PTSD severity score (measured with CAPS-5) between initial evaluation at J0 before beginning of treatment and follow-up evaluation at 1 month after the end of treatment | between initial evaluation at J0 before beginning of treatment and follow-up evaluation at 1 month after the end of treatment |
| Evolution of PTSD severity score | Evolution of PTSD severity score, measured by an auto-questionnaire (PTSD Checklist or Post-Traumatic CheckList Scale (PCL-5)), between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment | between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment |
| Evolution of severity of different PTSD under-dimensions | Evolution of severity of different PTSD under-dimensions (intrusive symptoms, evasion symptoms, mood and cognitive symptoms, reactivity and activation symptoms) as measured by CAPS-5 (structured interview) and PCL-5 (auto-questionnaire) between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment | between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment |
| Evolution of comorbid depressive symptoms | Evolution of comorbid depressive symptoms measured by Beck depression inventory (BDI), abridged version ; auto-questionnaire) between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment | between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment |
| Evolution of comorbid anxious symptoms | Evolution of comorbid anxious symptoms measured by avec la State-Trait Anxiety Inventory (STAI-A ; auto-questionnaire) between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment | between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment |
| Evolution of quality of life symptoms | Evolution of quality of life symptoms as measured by World Health Organization Quality Of Life abridged version (WHOQOL-BREF ; auto-questionnaire) between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment | between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment |
| Evolution of quality of life symptoms | Evolution of quality of life symptoms as measured by Global Functioning Evaluation scale (EGF) between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment | between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment |
| Evolution of cognitive functioning | Evolution of cognitive functioning as measured by Stroop test with emotional variant and n-back test between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment | between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment |
| Evolution of physiological response | Evolution of physiological response as measured by cutaneous conductance and cardiac and respiratory frequencies between evaluation at rest before the first session, during the first and the last session of tDCS, and 3 months after the last session of treatment | between evaluation at rest before the first session, during the first and the last session of tDCS, and 3 months after the last session of treatment |
| Evolution of clinical tolerance | Evolution of clinical tolerance to this therapeutic procedure by Brunoni questionnaire (nausea, headache, rash, skin redness, tingling, dizziness) | After each session |
|
Stress Disorders, Traumatic, Stress Disorders, Post-Traumatic, Trauma and Stressor Related Disorders, Mental Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1<br>Cerebral modulation using tDCS (transcranial Direct-Current Stimulation) associated with repetitive traumatic exposure using a personal traumatic script | Device: tDCS<br>* tDCS for transcranial Direct-Current Stimulation<br>|
| Placebo Comparator: Arm 2<br>Placebo cerebral modulation using sham-tDCS associated with repetitive traumatic exposure using a personal traumatic script | Device: Placebo tDCS<br>* Placebo tDCS for transcranial Direct-Current Stimulation<br>|
|
Post-traumatic Stress Disorder Treatment Using Transcranial Direct Current Stimulation (tDCS) Enhancement of Trauma-focused Therapy : a Two-arm Randomized Controlled Multicentric Study.
Study Overview
=================
Brief Summary
-----------------
Post-Traumatic Stress Disorder (PTSD) is an anxiety disorder that can develop after exposure to a terrifying event or ordeal in which there was the potential for or actual occurrence of grave physical harm. Traumatic events that may trigger PTSD include violent personal assaults, natural or human-caused disasters, accidents, and military combat. People with PTSD have persistent frightening thoughts and memories of their ordeal, may experience sleep problems, feel detached or numb, or be easily startled. Its lifetime prevalence is quite high, with 7-8% in various studies and 4% in french studies. The current PTSD treatment usually involves antidepressants as serotonin-specific reuptake inhibitors (SSRIs) and Cognitive Behavioral Therapies, such as exposure therapy to trauma-linked elements (memories, feelings and thoughts) so the fear associated to the traumatic event can decrease. But the therapeutic response stays partial, even combining these treatments. To improve the PTSD treatment efficiency, innovative approaches are being explored like new drugs or cerebral stimulation. This project aims to assess the efficacy of a less known but promising therapeutic strategy for PTSD : the use of transcranial Direct-Current Stimulation (tDCS) to enhance the trauma-focused therapy results.
Official Title
-----------------
Post-traumatic Stress Disorder Treatment Using Transcranial Direct Current Stimulation (tDCS) Enhancement of Trauma-focused Therapy : a Two-arm Randomized Controlled Multicentric Study - T-TREAt
Conditions
-----------------
Post-traumatic Stress Disorder
Intervention / Treatment
-----------------
* Device: tDCS
* Device: Placebo tDCS
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Having a chronic PTSD (for more than 3 months and less than 10 years) without modification of SSRI long-term treatment for more than 4 weeks Between 18 and 65 years-old Effective contraception for women, or inability of procreate because of medical or surgical reasons Able to give his written informed consent Affiliation to a social security system Not participating to another study with psychoactive substance Exclusion Criteria: Partially-sighted or partially deaf person requiring equipment Person with brain injury or neurological disease (epileptic, tumoral, vascular, degenerative), diagnoses in personal history or recognized as hereditary Addiction to psychoactive substance for the last 6 months Any treatment which could interact with tDCS effects on cortical reactivity (citalopram, amphetamine, L-dopa, sulpiride, pergolide, lorazepam, rivastigmine, dextromethorphan or other N-methyl-D-aspartate (NMDA) receptor antagonists, d-cycloserine, carbamazepine, flunarizine, calcium channel blockers) Pregnancy and lactation Any intracephalic metallic material Person who can't conform to tests instructions Person suffering from bipolar disorder, chronic or acute delusional disorder Any circumstances making the person unable to understand the trial features, purposes or consequences
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: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1<br>Cerebral modulation using tDCS (transcranial Direct-Current Stimulation) associated with repetitive traumatic exposure using a personal traumatic script | Device: tDCS<br>* tDCS for transcranial Direct-Current Stimulation<br>|
| Placebo Comparator: Arm 2<br>Placebo cerebral modulation using sham-tDCS associated with repetitive traumatic exposure using a personal traumatic script | Device: Placebo tDCS<br>* Placebo tDCS for transcranial Direct-Current Stimulation<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of PTSD symptoms | Evolution of PTSD symptoms defined by difference of PTSD severity score measured by Clinician Administered PTSD Scale ( CAPS-5, structured interview) | between initial evaluation at J0 before beginning of treatment and follow-up evaluation at 3 month after the end of treatment |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of PTSD severity score | Evolution of PTSD severity score (measured with CAPS-5) between initial evaluation at J0 before beginning of treatment and follow-up evaluation at 1 month after the end of treatment | between initial evaluation at J0 before beginning of treatment and follow-up evaluation at 1 month after the end of treatment |
| Evolution of PTSD severity score | Evolution of PTSD severity score, measured by an auto-questionnaire (PTSD Checklist or Post-Traumatic CheckList Scale (PCL-5)), between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment | between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment |
| Evolution of severity of different PTSD under-dimensions | Evolution of severity of different PTSD under-dimensions (intrusive symptoms, evasion symptoms, mood and cognitive symptoms, reactivity and activation symptoms) as measured by CAPS-5 (structured interview) and PCL-5 (auto-questionnaire) between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment | between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment |
| Evolution of comorbid depressive symptoms | Evolution of comorbid depressive symptoms measured by Beck depression inventory (BDI), abridged version ; auto-questionnaire) between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment | between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment |
| Evolution of comorbid anxious symptoms | Evolution of comorbid anxious symptoms measured by avec la State-Trait Anxiety Inventory (STAI-A ; auto-questionnaire) between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment | between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment |
| Evolution of quality of life symptoms | Evolution of quality of life symptoms as measured by World Health Organization Quality Of Life abridged version (WHOQOL-BREF ; auto-questionnaire) between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment | between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment |
| Evolution of quality of life symptoms | Evolution of quality of life symptoms as measured by Global Functioning Evaluation scale (EGF) between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment | between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment |
| Evolution of cognitive functioning | Evolution of cognitive functioning as measured by Stroop test with emotional variant and n-back test between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment | between initial evaluation at J0 before beginning of treatment, follow-up evaluation at 1 month, follow-up evaluation at 3 month after the end of treatment |
| Evolution of physiological response | Evolution of physiological response as measured by cutaneous conductance and cardiac and respiratory frequencies between evaluation at rest before the first session, during the first and the last session of tDCS, and 3 months after the last session of treatment | between evaluation at rest before the first session, during the first and the last session of tDCS, and 3 months after the last session of treatment |
| Evolution of clinical tolerance | Evolution of clinical tolerance to this therapeutic procedure by Brunoni questionnaire (nausea, headache, rash, skin redness, tingling, dizziness) | After each session |
|
||
NCT02935946
|
Cold Liquids Fed to Preterm Infants: Efficacy and Safety After 10 Minutes of Exposure
|
A previous study revealed that dysphagia preterm infants show statistically significant improvements in their swallowing mechanism when fed cold liquid barium when compared to room temperature liquid barium. The previous study was the first to identify these positive effects, although, only assessed 5 cold liquid swallows, immediately after the room temperature condition. This limited data set restricts the efficacy and safety of using cold liquids in clinical practice, emphasizing the need for further information. The present study aims to objectively assess the influence of cold liquid on the pharyngeal swallow mechanism in preterm infants with dysphagia after 10 minutes of a cold liquid feeding. The investigators will utilize videofluoroscopic swallow studies (VFSS) to analyze the frequency and severity of pharyngeal swallowing deficits during room temperature swallows and compare it to cold liquid swallows at various time points within a 10 minute feeding. Safety measures will also be obtained, such as participant axillary body temperature and gastric content temperature, to identify indicators for the development of cold stress.
|
Swallowing dysfunction, medically defined as dysphagia, commonly occurs in infants born prematurely due to inadequate timing and coordination of the sensorimotor sequences required for safe swallowing. Approximately 70% of prematurely born infants will be diagnosed with oral, pharyngeal and/or esophageal phase dysphagia with an inverse relationship between severity and gestational age at birth.(1)~Swallowing is extremely important for the infant and child to meet the nutritional requirements for growth and development. When swallowing is dysfunctional, the consequences can be devastating for the infant, possibly resulting morbidity, with complications including pneumonia, respiratory disease, growth compromise or failure to thrive.(1-6) The implications of swallowing difficulty are, therefore, of considerable medical importance to the medical team working with these infants.~A videofluoroscopic swallow study (VFSS) is a widely used assessment for the diagnosis of neonatal dysphagia. VFSS is a definitive investigation to objectively assess the adequacy of airway protection during swallowing and allows simultaneous viewing of the bolus as it passes through the oral, pharyngeal and esophageal stages of swallowing.(7) For infants feeding from a bottle, the clinician relies on the VFSS to both identify and correct the swallowing dysfunction. Several therapeutic techniques or modifications are used during a VFSS to improve swallowing safety in infants, such as various nipple flow rates,(8,9) feeding positions,(10) or pacing the infant's sucking bursts.(11) The most frequently used modification is to thicken the infant's formula or breastmilk to a thicker consistency,(12-14) however, thickening causes some difficulty making it an undesirable option for young infants treated in the neonatal intensive care unit (NICU).(15) These difficulties have resulted in clinicians using alternate therapeutic techniques to treat dysphagia neonates. One alternate technique is to feed the infant cold liquids to stimulate a safer swallow.(16-20)~Original findings obtained by these investigators was the first to indicate that cold liquid swallows reduce airway compromise in dysphagic preterm infants when compared to room temperature liquid. Specifically, the occurrence of deep penetration (p=0.029), aspiration (0.017), mild penetration (p=0.044) and nasopharyngeal reflux (p=0.006) decreased significantly in the cold swallow (CS) condition when compared to the room temperature swallow (RTS) condition during VFSS. Similar findings are documented in adults with dysphagia.(21-35) These positive effects are theorized to occur due to the cold liquid providing the sensory receptors within the pharynx increased sensory information which triggers more efficient swallowing movements.(12,13,21-23)~The original study assessed 5 cold liquid swallows, which provided important information regarding the immediate effects of cold liquids on the pharyngeal swallowing mechanism in preterm infants with dysphagia. Further information regarding the duration of these positive effects is necessary to prove its reliability as a modification to be used at bedside. This study is designed to assess the swallowing mechanism of dysphagic preterm infants after feeding cold liquids for 10 minutes to objectively identify any changes over time.~In addition to the paucity of evidence regarding improved swallowing function over time, the safety of feeding cold liquids remains questionable in the preterm infant population. The greatest concern for these infants is the development of cold stress or altered digestive functioning due to the cold temperature of the liquid. The effects of cold stress in infants are observed in all body systems, including cool skin, tachypnea, respiratory distress, desaturation, increasing episodes of apnea and bradycardia, increased gastric residuals, and emesis.(36) Several older studies have assessed the effects of cold feeds in healthy term and healthy pre term infants, however, study populations may not be representative of todays preterm infant population due to significant medical advances and increased survival rates of extremely preterm infants.~Holt and colleagues(37) found no difference in sleep pattern, vocalizations, motility, intake, feeding behavior, weight gain, temperature or regurgitation in preterm infants with a weight of >1,500gm, when fed cold formula. Gonzalez and colleagues(38) found no significant differences in axillary temperature or gastric residuals in preterm infants fed cold (0-4°C) verses room temperature (25°C) milk. Participants included 14 preterm infants with a gestational age at birth (GAB) of 28-30w, and a mean corrected gestational age of 32 weeks. Anderson and Berseth(39) found no differences in infants' antral or duodenal motor activity as assessed via manometry, as well as gastric emptying among cold (6°C), room temperature (24°C), or body temperature (37°C) feeding groups. This study included preterm infants with GAB 25-36weeks, mean birth weights 915-2,455g. Corrected gestational age of 32-36 weeks at the time of the study. Feedings were given in random order for 3 liquid temperatures. Across all temperatures they found that all infants emptied approximately one third of the bolus feeding by 20 minutes. And across all temperatures approximately 10-20% of the bolus feeding remained in their stomach 2 hours post-prandially. The authors propose that thermo-receptors within the gastrointestinal tract do not appear to be functional in this age group.~Blumenthal and colleagues(40) found no statistical differences between stomach emptying rate in cold (0-4°C), room temperature (25°C) or body temperature (37°C) formula in 20 healthy preterm infants with a mean birth weight of 2.75 ± 0-18 (range 1.49-3.38) kg, and gestation 37-7 ± 0.6 (range 34-41) weeks. They also reported that in all infants the cold feeds were well tolerated and produced no obvious clinical effects.~To assess the potential risks of cold stress, each participant's body temperature will be obtained pre and post cold liquid exposure. To assess digestive functioning, the temperature of each participant's gastric contents will be obtained pre and post cold liquid exposure by extraction of the gastric content via a naso-gastric tube (NGT). If the child does not have a naso-gastric tube in place at the time of the study, the subjects will be enrolled but no documentation of the stomach content temperature will be obtained.
|
Cold Liquids Fed to Preterm Infants: Efficacy and Safety After 10 Minutes of Exposure
|
Deglutition Disorders, Respiratory Aspiration
|
* Other: Cold Liquid Barium
|
Inclusion Criteria:~Infants born prematurely, as defined by birth at less than 37 weeks gestational age, referred for a videofluoroscopic swallow study (VFSS) due to suspected pharyngeal phase dysphagia.~Exclusion Criteria:~Infants born prematurely with a corrected gestational age of 43 weeks or greater.
|
36 Weeks
|
43 Weeks
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharyngeal Phase Dysphagia | presence of atypical or disordered movements during the pharyngeal phase of swallowing | <5 seconds post swallow trigger |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tracheal Aspiration | the occurrence of barium below the level of the true vocal cords | <5 seconds post swallow trigger |
| Laryngeal Penetration | the occurrence of barium underneath the epiglottis, in the laryngeal vestibule to the level of the vocal folds | <2 seconds post swallow trigger |
| Nasopharyngeal Reflux | the occurrence of barium detected in the nasopharynx, posterior or superior to the velum | <2 seconds post swallow trigger |
| Pharyngeal residue | the presence of residual barium coating the pharyngeal walls, pooling in the vallecula or pyriform sinuses post swallow (absent/mild/severe). | <5 seconds post swallow trigger |
|
pharyngeal swallow, NICU, intervention, thickening
|
Deglutition Disorders, Respiratory Aspiration, Esophageal Diseases, Gastrointestinal Diseases, Digestive System Diseases, Pharyngeal Diseases, Otorhinolaryngologic Diseases, Respiration Disorders, Respiratory Tract Diseases, Pathologic Processes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Room Temperature Swallows<br>Once consented, each participant underwent a video fluoroscopic swallow study (VFSS). Each participant was fed room temperature thin liquid barium (Varibar® Thin Liquid Barium Sulfate for Suspension) from a standard bottle (60ml Similac® Volu-Feeder®) with an attached Similac® Infant Nipple and Ring. The swallows were assessed in real time for any swallowing dysfunction and saved electronically. These swallows were labeled RTS for room temperature swallows. If no swallow dysfunction was observed, the participant became ineligible and the study ended. If swallow dysfunction was observed, the participant became eligible to complete the other arms of the study. | |
| Experimental: Cold Liquid Swallows- 5<br>Immediately following the RTS condition, a total of 5 swallows of Cold Liquid Barium was observed under fluoroscopy from an identical bottle and nipple. Images were saved electronically and labeled CS5 for cold swallows-5. | Other: Cold Liquid Barium<br>* Cold Liquid is defined as being between 4-9 °C. One liter bottles of Poland Spring Natural Spring Water will be kept in the radiology suite to remain at room temperature. As described by Fink and colleagues,(42) the bottled water will be used to mix the barium powder to create a thin liquid consistency, with 50% dilution, which is found to be most similar to human milk and infant formula. After the barium is prepared, 2oz will be poured into a bottle and placed in a refrigerator set to 36°F; this will allow the barium to cool to approximately 4-9°C. Before oral administration, the barium mixture will be measured with a thermometer (TP3001 Digital Thermometer from Red Lantern®) to document the exact temperature.<br>|
| Experimental: Cold Liquid Swallows- 10<br>After 10 minutes of feeding a cold liquid, a total of 10 swallows of Cold Liquid Barium was observed under fluoroscopy from an identical bottle and nipple. Images were saved electronically and labeled CS10 for cold swallows-10. | Other: Cold Liquid Barium<br>* Cold Liquid is defined as being between 4-9 °C. One liter bottles of Poland Spring Natural Spring Water will be kept in the radiology suite to remain at room temperature. As described by Fink and colleagues,(42) the bottled water will be used to mix the barium powder to create a thin liquid consistency, with 50% dilution, which is found to be most similar to human milk and infant formula. After the barium is prepared, 2oz will be poured into a bottle and placed in a refrigerator set to 36°F; this will allow the barium to cool to approximately 4-9°C. Before oral administration, the barium mixture will be measured with a thermometer (TP3001 Digital Thermometer from Red Lantern®) to document the exact temperature.<br>|
|
Cold Liquids Fed to Preterm Infants: Efficacy and Safety After 10 Minutes of Exposure
Study Overview
=================
Brief Summary
-----------------
A previous study revealed that dysphagia preterm infants show statistically significant improvements in their swallowing mechanism when fed cold liquid barium when compared to room temperature liquid barium. The previous study was the first to identify these positive effects, although, only assessed 5 cold liquid swallows, immediately after the room temperature condition. This limited data set restricts the efficacy and safety of using cold liquids in clinical practice, emphasizing the need for further information. The present study aims to objectively assess the influence of cold liquid on the pharyngeal swallow mechanism in preterm infants with dysphagia after 10 minutes of a cold liquid feeding. The investigators will utilize videofluoroscopic swallow studies (VFSS) to analyze the frequency and severity of pharyngeal swallowing deficits during room temperature swallows and compare it to cold liquid swallows at various time points within a 10 minute feeding. Safety measures will also be obtained, such as participant axillary body temperature and gastric content temperature, to identify indicators for the development of cold stress.
Detailed Description
-----------------
Swallowing dysfunction, medically defined as dysphagia, commonly occurs in infants born prematurely due to inadequate timing and coordination of the sensorimotor sequences required for safe swallowing. Approximately 70% of prematurely born infants will be diagnosed with oral, pharyngeal and/or esophageal phase dysphagia with an inverse relationship between severity and gestational age at birth.(1) Swallowing is extremely important for the infant and child to meet the nutritional requirements for growth and development. When swallowing is dysfunctional, the consequences can be devastating for the infant, possibly resulting morbidity, with complications including pneumonia, respiratory disease, growth compromise or failure to thrive.(1-6) The implications of swallowing difficulty are, therefore, of considerable medical importance to the medical team working with these infants. A videofluoroscopic swallow study (VFSS) is a widely used assessment for the diagnosis of neonatal dysphagia. VFSS is a definitive investigation to objectively assess the adequacy of airway protection during swallowing and allows simultaneous viewing of the bolus as it passes through the oral, pharyngeal and esophageal stages of swallowing.(7) For infants feeding from a bottle, the clinician relies on the VFSS to both identify and correct the swallowing dysfunction. Several therapeutic techniques or modifications are used during a VFSS to improve swallowing safety in infants, such as various nipple flow rates,(8,9) feeding positions,(10) or pacing the infant's sucking bursts.(11) The most frequently used modification is to thicken the infant's formula or breastmilk to a thicker consistency,(12-14) however, thickening causes some difficulty making it an undesirable option for young infants treated in the neonatal intensive care unit (NICU).(15) These difficulties have resulted in clinicians using alternate therapeutic techniques to treat dysphagia neonates. One alternate technique is to feed the infant cold liquids to stimulate a safer swallow.(16-20) Original findings obtained by these investigators was the first to indicate that cold liquid swallows reduce airway compromise in dysphagic preterm infants when compared to room temperature liquid. Specifically, the occurrence of deep penetration (p=0.029), aspiration (0.017), mild penetration (p=0.044) and nasopharyngeal reflux (p=0.006) decreased significantly in the cold swallow (CS) condition when compared to the room temperature swallow (RTS) condition during VFSS. Similar findings are documented in adults with dysphagia.(21-35) These positive effects are theorized to occur due to the cold liquid providing the sensory receptors within the pharynx increased sensory information which triggers more efficient swallowing movements.(12,13,21-23) The original study assessed 5 cold liquid swallows, which provided important information regarding the immediate effects of cold liquids on the pharyngeal swallowing mechanism in preterm infants with dysphagia. Further information regarding the duration of these positive effects is necessary to prove its reliability as a modification to be used at bedside. This study is designed to assess the swallowing mechanism of dysphagic preterm infants after feeding cold liquids for 10 minutes to objectively identify any changes over time. In addition to the paucity of evidence regarding improved swallowing function over time, the safety of feeding cold liquids remains questionable in the preterm infant population. The greatest concern for these infants is the development of cold stress or altered digestive functioning due to the cold temperature of the liquid. The effects of cold stress in infants are observed in all body systems, including cool skin, tachypnea, respiratory distress, desaturation, increasing episodes of apnea and bradycardia, increased gastric residuals, and emesis.(36) Several older studies have assessed the effects of cold feeds in healthy term and healthy pre term infants, however, study populations may not be representative of todays preterm infant population due to significant medical advances and increased survival rates of extremely preterm infants. Holt and colleagues(37) found no difference in sleep pattern, vocalizations, motility, intake, feeding behavior, weight gain, temperature or regurgitation in preterm infants with a weight of >1,500gm, when fed cold formula. Gonzalez and colleagues(38) found no significant differences in axillary temperature or gastric residuals in preterm infants fed cold (0-4°C) verses room temperature (25°C) milk. Participants included 14 preterm infants with a gestational age at birth (GAB) of 28-30w, and a mean corrected gestational age of 32 weeks. Anderson and Berseth(39) found no differences in infants' antral or duodenal motor activity as assessed via manometry, as well as gastric emptying among cold (6°C), room temperature (24°C), or body temperature (37°C) feeding groups. This study included preterm infants with GAB 25-36weeks, mean birth weights 915-2,455g. Corrected gestational age of 32-36 weeks at the time of the study. Feedings were given in random order for 3 liquid temperatures. Across all temperatures they found that all infants emptied approximately one third of the bolus feeding by 20 minutes. And across all temperatures approximately 10-20% of the bolus feeding remained in their stomach 2 hours post-prandially. The authors propose that thermo-receptors within the gastrointestinal tract do not appear to be functional in this age group. Blumenthal and colleagues(40) found no statistical differences between stomach emptying rate in cold (0-4°C), room temperature (25°C) or body temperature (37°C) formula in 20 healthy preterm infants with a mean birth weight of 2.75 ± 0-18 (range 1.49-3.38) kg, and gestation 37-7 ± 0.6 (range 34-41) weeks. They also reported that in all infants the cold feeds were well tolerated and produced no obvious clinical effects. To assess the potential risks of cold stress, each participant's body temperature will be obtained pre and post cold liquid exposure. To assess digestive functioning, the temperature of each participant's gastric contents will be obtained pre and post cold liquid exposure by extraction of the gastric content via a naso-gastric tube (NGT). If the child does not have a naso-gastric tube in place at the time of the study, the subjects will be enrolled but no documentation of the stomach content temperature will be obtained.
Official Title
-----------------
Cold Liquids Fed to Preterm Infants: Efficacy and Safety After 10 Minutes of Exposure
Conditions
-----------------
Deglutition Disorders, Respiratory Aspiration
Intervention / Treatment
-----------------
* Other: Cold Liquid Barium
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Infants born prematurely, as defined by birth at less than 37 weeks gestational age, referred for a videofluoroscopic swallow study (VFSS) due to suspected pharyngeal phase dysphagia. Exclusion Criteria: Infants born prematurely with a corrected gestational age of 43 weeks or greater.
Ages Eligible for Study
-----------------
Minimum Age: 36 Weeks
Maximum Age: 43 Weeks
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: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Room Temperature Swallows<br>Once consented, each participant underwent a video fluoroscopic swallow study (VFSS). Each participant was fed room temperature thin liquid barium (Varibar® Thin Liquid Barium Sulfate for Suspension) from a standard bottle (60ml Similac® Volu-Feeder®) with an attached Similac® Infant Nipple and Ring. The swallows were assessed in real time for any swallowing dysfunction and saved electronically. These swallows were labeled RTS for room temperature swallows. If no swallow dysfunction was observed, the participant became ineligible and the study ended. If swallow dysfunction was observed, the participant became eligible to complete the other arms of the study. | |
| Experimental: Cold Liquid Swallows- 5<br>Immediately following the RTS condition, a total of 5 swallows of Cold Liquid Barium was observed under fluoroscopy from an identical bottle and nipple. Images were saved electronically and labeled CS5 for cold swallows-5. | Other: Cold Liquid Barium<br>* Cold Liquid is defined as being between 4-9 °C. One liter bottles of Poland Spring Natural Spring Water will be kept in the radiology suite to remain at room temperature. As described by Fink and colleagues,(42) the bottled water will be used to mix the barium powder to create a thin liquid consistency, with 50% dilution, which is found to be most similar to human milk and infant formula. After the barium is prepared, 2oz will be poured into a bottle and placed in a refrigerator set to 36°F; this will allow the barium to cool to approximately 4-9°C. Before oral administration, the barium mixture will be measured with a thermometer (TP3001 Digital Thermometer from Red Lantern®) to document the exact temperature.<br>|
| Experimental: Cold Liquid Swallows- 10<br>After 10 minutes of feeding a cold liquid, a total of 10 swallows of Cold Liquid Barium was observed under fluoroscopy from an identical bottle and nipple. Images were saved electronically and labeled CS10 for cold swallows-10. | Other: Cold Liquid Barium<br>* Cold Liquid is defined as being between 4-9 °C. One liter bottles of Poland Spring Natural Spring Water will be kept in the radiology suite to remain at room temperature. As described by Fink and colleagues,(42) the bottled water will be used to mix the barium powder to create a thin liquid consistency, with 50% dilution, which is found to be most similar to human milk and infant formula. After the barium is prepared, 2oz will be poured into a bottle and placed in a refrigerator set to 36°F; this will allow the barium to cool to approximately 4-9°C. Before oral administration, the barium mixture will be measured with a thermometer (TP3001 Digital Thermometer from Red Lantern®) to document the exact temperature.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharyngeal Phase Dysphagia | presence of atypical or disordered movements during the pharyngeal phase of swallowing | <5 seconds post swallow trigger |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tracheal Aspiration | the occurrence of barium below the level of the true vocal cords | <5 seconds post swallow trigger |
| Laryngeal Penetration | the occurrence of barium underneath the epiglottis, in the laryngeal vestibule to the level of the vocal folds | <2 seconds post swallow trigger |
| Nasopharyngeal Reflux | the occurrence of barium detected in the nasopharynx, posterior or superior to the velum | <2 seconds post swallow trigger |
| Pharyngeal residue | the presence of residual barium coating the pharyngeal walls, pooling in the vallecula or pyriform sinuses post swallow (absent/mild/severe). | <5 seconds post swallow trigger |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pharyngeal swallow, NICU, intervention, thickening
|
NCT02176200
|
Respimat® Inhaler vs a Metered Dose Inhaler Using Berodual® in Patients With Chronic Obstructive Pulmonary Disease (COPD)
|
Study to compare the lung and oropharyngeal deposition of Berodual® (fenoterol hydrobromide 50μg + ipratropium bromide 20μg /1x puff) delivered via the Respimat® inhaler and the same dose of Berodual® delivered via an hydrofluoroalkane (HFA) - metered dose inhaler (2 x puffs ) in COPD patients at different inspiratory flow rates.
|
A Randomised Open Label, Six Way, Cross-over Scintigraphic Evaluation of the Effect of Inspiratory Flow Rate on Lung and Oropharyngeal Deposition With the Respimat® Inhaler vs a Metered Dose Inhaler (HFA-MDI) Using Berodual® in Patients With Chronic Obstructive Pulmonary Disease (COPD)
|
Pulmonary Disease, Chronic Obstructive
|
* Drug: Berodual® Respimat®, low inspiratory flow rate
* Drug: Berodual® Respimat®, medium inspiratory flow rate
* Drug: Berodual® Respimat®, high inspiratory flow rate
* Drug: Berodual® HFA-MDI, low inspiratory flow rate
* Drug: Berodual® HFA-MDI, medium inspiratory flow rate
* Drug: Berodual® HFA-MDI, high inspiratory flow rate
|
Inclusion Criteria:~All patients must have a diagnosis of COPD and must meet the following spirometric criteria:~Patients must have relatively stable, mild to severe airway obstruction with an forced expiratory volume in one second (FEV1) ≤70% of predicted normal and FEV1 ≤70% of forced vital capacity (FVC). Predicted normal values calculated according to evolutionary conserved chromosome segments (ECCS)~Male or non-pregnant/non-lactating female patients aged ≥18 years~All patients must sign an informed consent form prior to participation in the study, i.e. prior to pre-study washout of their usual pulmonary medications~Current or ex-smokers with a smoking history of >10 pack years~Exclusion Criteria:~Patients with significant diseases other than COPD will be excluded. A significant disease is defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study~Patients who have frequent exacerbations which could be expected to interfere with the patient's ability to participate in the study should be excluded. The enrolment of patients who have had an exacerbation within the six weeks prior to planned study entry has to be postponed.~Patients with clinically relevant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a disease listed as an exclusion criterion will be excluded~Patients with a recent history (i.e. six months or less) of myocardial infarction~Patients with any unstable or life-threatening cardiac arrhythmia or who have been hospitalised for heart failure within the past year~Patients who regularly use daytime oxygen therapy for more than 1 hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy~Patients with known active tuberculosis~Patients with a history of cancer within the last five years. Patients with treated basal cell carcinoma are allowed~Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis~Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion 1~Patients with any upper respiratory infection in the past 14 days prior to the screening visit or during the baseline period or lower respiratory tract infection within the last 3 months~Patients who are currently in a pulmonary rehabilitation programme or who have completed a pulmonary rehabilitation programme in the six weeks prior to the screening visit~Patients with known hypersensitivity to β2-agonists, anticholinergic drugs or any excipients of the active or placebo Berodual®~Patients with known narrow-angle glaucoma~Patients who are being treated with cromolyn sodium or nedocromil sodium~Patients who are being treated with antihistamines (H1 receptor antagonists)~Patients using oral corticosteroid medication at unstable doses (i.e. less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisolone per day or 20 mg every other day~Patients who are being treated with monamine oxidase inhibitors or tricyclic antidepressants~Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e. oral or injectable eg Depo-Provera or Noristerat contraceptives, intrauterine devices, diaphragm plus spermicide or subdermal implants eg: Norplant®)~Patients with, in the opinion of the investigator, a history of and/or active significant alcohol or drug abuse~Patients who have taken an investigational drug within four months or six half lives (whichever is the greater) prior to screening visit and/or the administration of radiolabelled dosage forms within the three months prior to the screening visit~Radiation exposure from clinical studies, including that from the present study and diagnostic X-rays but excluding background radiation, exceeding 5 millisievert (mSv) in the last 12 months or 10 mSv in the last five years. No patient whose occupational exposure is monitored will participate in the study~Precautions: As with other anticholinergic drugs, Berodual® should be used with caution in patients with prostatic hyperplasia or bladder neck obstruction.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of dose in the whole lung | disposition of aerosol via gamma scintigraphy | immediately after dosing |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of dose in the central lung zone | disposition of aerosol via gamma scintigraphy | immediately after dosing |
| Percentage of dose in the intermediate lung zone | disposition of aerosol via gamma scintigraphy | immediately after dosing |
| Percentage of dose in the peripheral lung zone | disposition of aerosol via gamma scintigraphy | immediately after dosing |
| Peripheral zone/central zone deposition ratio (lung penetration index) | disposition of aerosol via gamma scintigraphy | immediately after dosing |
| Percentate of dose in oropharyngeal deposition | disposition of aerosol via gamma scintigraphy | immediately after dosing |
|
Sympathomimetics, Fenoterol, ipratropium drug combination, Fenoterol, Ipratropium, Bronchodilator Agents, Autonomic Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anti-Asthmatic Agents, Respiratory System Agents, Tocolytic Agents, Reproductive Control Agents, Adrenergic beta-2 Receptor Agonists, Adrenergic beta-Agonists, Adrenergic Agonists, Adrenergic Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Cholinergic Antagonists, Cholinergic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Berodual® Respimat®<br> | Drug: Berodual® Respimat®, low inspiratory flow rate<br> <br> Drug: Berodual® Respimat®, medium inspiratory flow rate<br> <br> Drug: Berodual® Respimat®, high inspiratory flow rate<br> <br> Drug: Berodual® HFA-MDI, low inspiratory flow rate<br> <br> Drug: Berodual® HFA-MDI, medium inspiratory flow rate<br> <br> Drug: Berodual® HFA-MDI, high inspiratory flow rate<br> <br> |
| Active Comparator: Berodual® HFA-MDI<br> | Drug: Berodual® Respimat®, low inspiratory flow rate<br> <br> Drug: Berodual® Respimat®, medium inspiratory flow rate<br> <br> Drug: Berodual® Respimat®, high inspiratory flow rate<br> <br> Drug: Berodual® HFA-MDI, low inspiratory flow rate<br> <br> Drug: Berodual® HFA-MDI, medium inspiratory flow rate<br> <br> Drug: Berodual® HFA-MDI, high inspiratory flow rate<br> <br> |
|
Respimat® Inhaler vs a Metered Dose Inhaler Using Berodual® in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Study Overview
=================
Brief Summary
-----------------
Study to compare the lung and oropharyngeal deposition of Berodual® (fenoterol hydrobromide 50μg + ipratropium bromide 20μg /1x puff) delivered via the Respimat® inhaler and the same dose of Berodual® delivered via an hydrofluoroalkane (HFA) - metered dose inhaler (2 x puffs ) in COPD patients at different inspiratory flow rates.
Official Title
-----------------
A Randomised Open Label, Six Way, Cross-over Scintigraphic Evaluation of the Effect of Inspiratory Flow Rate on Lung and Oropharyngeal Deposition With the Respimat® Inhaler vs a Metered Dose Inhaler (HFA-MDI) Using Berodual® in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Conditions
-----------------
Pulmonary Disease, Chronic Obstructive
Intervention / Treatment
-----------------
* Drug: Berodual® Respimat®, low inspiratory flow rate
* Drug: Berodual® Respimat®, medium inspiratory flow rate
* Drug: Berodual® Respimat®, high inspiratory flow rate
* Drug: Berodual® HFA-MDI, low inspiratory flow rate
* Drug: Berodual® HFA-MDI, medium inspiratory flow rate
* Drug: Berodual® HFA-MDI, high inspiratory flow rate
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All patients must have a diagnosis of COPD and must meet the following spirometric criteria: Patients must have relatively stable, mild to severe airway obstruction with an forced expiratory volume in one second (FEV1) ≤70% of predicted normal and FEV1 ≤70% of forced vital capacity (FVC). Predicted normal values calculated according to evolutionary conserved chromosome segments (ECCS) Male or non-pregnant/non-lactating female patients aged ≥18 years All patients must sign an informed consent form prior to participation in the study, i.e. prior to pre-study washout of their usual pulmonary medications Current or ex-smokers with a smoking history of >10 pack years Exclusion Criteria: Patients with significant diseases other than COPD will be excluded. A significant disease is defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study Patients who have frequent exacerbations which could be expected to interfere with the patient's ability to participate in the study should be excluded. The enrolment of patients who have had an exacerbation within the six weeks prior to planned study entry has to be postponed. Patients with clinically relevant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a disease listed as an exclusion criterion will be excluded Patients with a recent history (i.e. six months or less) of myocardial infarction Patients with any unstable or life-threatening cardiac arrhythmia or who have been hospitalised for heart failure within the past year Patients who regularly use daytime oxygen therapy for more than 1 hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy Patients with known active tuberculosis Patients with a history of cancer within the last five years. Patients with treated basal cell carcinoma are allowed Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion 1 Patients with any upper respiratory infection in the past 14 days prior to the screening visit or during the baseline period or lower respiratory tract infection within the last 3 months Patients who are currently in a pulmonary rehabilitation programme or who have completed a pulmonary rehabilitation programme in the six weeks prior to the screening visit Patients with known hypersensitivity to β2-agonists, anticholinergic drugs or any excipients of the active or placebo Berodual® Patients with known narrow-angle glaucoma Patients who are being treated with cromolyn sodium or nedocromil sodium Patients who are being treated with antihistamines (H1 receptor antagonists) Patients using oral corticosteroid medication at unstable doses (i.e. less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisolone per day or 20 mg every other day Patients who are being treated with monamine oxidase inhibitors or tricyclic antidepressants Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e. oral or injectable eg Depo-Provera or Noristerat contraceptives, intrauterine devices, diaphragm plus spermicide or subdermal implants eg: Norplant®) Patients with, in the opinion of the investigator, a history of and/or active significant alcohol or drug abuse Patients who have taken an investigational drug within four months or six half lives (whichever is the greater) prior to screening visit and/or the administration of radiolabelled dosage forms within the three months prior to the screening visit Radiation exposure from clinical studies, including that from the present study and diagnostic X-rays but excluding background radiation, exceeding 5 millisievert (mSv) in the last 12 months or 10 mSv in the last five years. No patient whose occupational exposure is monitored will participate in the study Precautions: As with other anticholinergic drugs, Berodual® should be used with caution in patients with prostatic hyperplasia or bladder neck obstruction.
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: Berodual® Respimat®<br> | Drug: Berodual® Respimat®, low inspiratory flow rate<br> <br> Drug: Berodual® Respimat®, medium inspiratory flow rate<br> <br> Drug: Berodual® Respimat®, high inspiratory flow rate<br> <br> Drug: Berodual® HFA-MDI, low inspiratory flow rate<br> <br> Drug: Berodual® HFA-MDI, medium inspiratory flow rate<br> <br> Drug: Berodual® HFA-MDI, high inspiratory flow rate<br> <br> |
| Active Comparator: Berodual® HFA-MDI<br> | Drug: Berodual® Respimat®, low inspiratory flow rate<br> <br> Drug: Berodual® Respimat®, medium inspiratory flow rate<br> <br> Drug: Berodual® Respimat®, high inspiratory flow rate<br> <br> Drug: Berodual® HFA-MDI, low inspiratory flow rate<br> <br> Drug: Berodual® HFA-MDI, medium inspiratory flow rate<br> <br> Drug: Berodual® HFA-MDI, high inspiratory flow rate<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of dose in the whole lung | disposition of aerosol via gamma scintigraphy | immediately after dosing |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of dose in the central lung zone | disposition of aerosol via gamma scintigraphy | immediately after dosing |
| Percentage of dose in the intermediate lung zone | disposition of aerosol via gamma scintigraphy | immediately after dosing |
| Percentage of dose in the peripheral lung zone | disposition of aerosol via gamma scintigraphy | immediately after dosing |
| Peripheral zone/central zone deposition ratio (lung penetration index) | disposition of aerosol via gamma scintigraphy | immediately after dosing |
| Percentate of dose in oropharyngeal deposition | disposition of aerosol via gamma scintigraphy | immediately after dosing |
|
||
NCT04137978
|
Study Evaluating Patients With Cystinuria
|
This is an open label, multicentre study, evaluating the safety, tolerability, efficacy, compliance and acceptability of alkalising treatments at long-term in patients with cystinuria.
|
B14CS study is an extension study which follows the B12CS-B13CS study. Patients who have participated in B12CS-B13CS Study will have the possibility to switch to B14CS Study for a long-term treatment period (2 year-period).~The B14CS Study is an open-label long-term study and including 2 types of cohorts.~ADV7103 Cohort: Cohort of patients who will have completed either B12CS or B13CS Study. Following an optional titration period (for B12CS Study subjects), all patients will be maintained at their ADV7103 optimal dose for a 2-year-period.~SoC Cohort: Cohort of patients with cystinuria, matching-pair for age category to the patients of ADV7103 Cohort, will receive their own alkalinising treatment (SoC) taken at the usual dose and frequency and will follow their usual first intention treatment (hydration and diet) for a 2-year-period. This cohort is designed in order to contextualize the safety, tolerability and efficacy of the long-term ADV7103 treatment.~The B14CS Study will be composed of 3 periods (more detailed hereafter):~Lead-in Period: Period of 3 weeks, during which the treatment (ADV7103 or SoC) will be taken at the optimal dose as previously defined (Maintenance Phase). The Lead-in Period can include a Titration Phase, for ADV7103 B12CS Cohort only, in order to define the individual optimal dose of ADV7103 for the patients of this cohort;~Assessment Period: Period of 7 days to evaluate the effect of study products (ADV7103 and SoC) at the optimal dose;~Follow-up Period: Period of 23 months to evaluate the effects of the study products (ADV7103 and SoC) at long-term.
|
Open Label, Multicentre Study, Evaluating the Safety, Tolerability, Efficacy, Compliance and Acceptability of Alkalising Treatments at Long-term in Patients With Cystinuria
|
Cystinuria
|
* Drug: ADV7103
* Drug: Standard of Care
|
Inclusion Criteria:~For ADV7103 cohort:~Patient who has participated to and completed the previous B12CS Study or B13CS Study.~Patient for whom the safety and tolerability of ADV7103 were satisfactory during B12CS Study or B13CS Study.~Female patient of childbearing potential (defined by the Clinical Trial Facilitation Group (CTFG) as woman fertile, following menarche until becoming post-menopausal unless permanently sterile*) using an acceptable effective birth control method** and having a negative pregnancy test at the inclusion, or a woman postmenopausal*** or a woman surgically sterilized*.~Patient and/or parents or legal representative(s) who is(are) willing and able to participate in the study, to understand and to comply with study procedures for the entire length of the study.~Patient or parents or legal representative(s) who has(have) provided a signed written informed consent.~Patient of ≤17 Patient of ≤17 years of age for whom the assent has been collected or has been tried to be collected.~Patient who is affiliated to a social health insurance system and/or in compliance with the recommendations of the national law in force relating to biomedical research.~For Standard of Care cohort:~Patient who has a diagnosis of cystinuria based on medical diagnosis (at least one previous or current episode of calculus of cystine, and/or one previous or current episode of cystine crystalluria) or on genetic diagnosis (only for patients of Subset 4).~Patient treated with an alkalising treatment at a well-adapted dose (defined as a daily dose deemed by the investigator aiming to maintain overtime urinary pH value ≥ 7.0 and/or compatible with an acceptable safety profile and/or patient's constraints or compliance).~Patient male or female, including child aged between 6 months and 17 years old and adult aged ≥ 18 years old up to 70 years old.~Female patient of childbearing potential (defined by the Clinical Trial Facilitation Group (CTFG) as woman fertile, following menarche until becoming post-menopausal unless permanently sterile*) using an acceptable effective birth control method** and having a negative pregnancy test at the inclusion, or a woman postmenopausal*** or a woman surgically sterilized*.~Patient and/or parents or legal representative(s) who is(are) willing and able to participate in the study, to understand and to comply with study procedures for the entire length of the study.~Patient or parents or legal representative(s) who has/have provided a signed written informed consent.~Patient of ≤17 years of age for whom the assent has been collected or has been tried to be collected.~Patient who is affiliated to a social health insurance system and/or in compliance with the recommendations of the national law in force relating to biomedical research.~Exclusion Criteria:~For ADV7103 cohort:~Patient who has not participated to B12CS study or B13CS study~Patient for whom any safety issue could contraindicate her/his participation to the extension study~For Standard of Care cohort:~Patient that is receiving the second line therapy -- cystine chelating agents (sulfhydryl compounds).~Patient who presents kalaemia > 5.0 mmol/L.~Patient who presents a moderate or severe renal impairment (estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 according to Schwartz formula for the children and both MDRDs and CKD-EPI for adults).~Patient who presents - barring the study disease - any previous or concurrent medical condition or any laboratory or clinical findings or any other condition that in the opinion of the investigator would be negatively affected by the study product or that would affect the study product or that precludes his participation, e.g. uncontrolled diabetes mellitus, adrenal insufficiency, cardiac impairment, repeated infections, metabolic alkalosis, chronic diarrhoea.~Female patient who is pregnant or breast-feeding.~Patient who cannot stop potassium sparing diuretics (e.g. antagonists of aldosterone as such spironolactone, canrenoate and eplerenone, amiloride, triamterene), angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, tacrolimus, potassium desodic salts.~Patient who received any medication that could interfere with the study treatment within 4 weeks before the inclusion in the study, including angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, tacrolimus, potassium desodic salts, antibiotics.~Patient who received potassium sparing diuretics 6 weeks before the inclusion in the study.~Patient who is admitted to hospital in emergency settings.~Patient who participated in a clinical trial within the last 3 months before enrolment.~Patient who is at risk of non-compliance in the judgment of the investigator.~Patient who could present any other condition, which in the opinion of the investigator, would preclude participation in the study.~Patient who cannot be contacted in case of emergency.~Patient under any administrative or legal supervision.
|
6 Months
|
70 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of urinary pH values ≥ 7.0 during 24h on Day 7 (after ADV7103 treatment period) | To evaluate the safety and the tolerability of ADV7103 and standard of care (SoC) after a long-term treatment. | 7 Days |
|
Potassium Citrate, Diuretics, Natriuretic Agents, Physiological Effects of Drugs, Expectorants, Respiratory System Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ADV7103<br>Patients receive ADV7103 twice a day at optimal dose. Each dose of ADV7103 contains a fixed ratio of 1/3 of ADV7103-CK (potassium citrate) and 2/3 of ADV7103-BK (potassium bicarbonate) based on the mass of active substances.~Other Names:~• Potassium Citrate and Potassium Bicarbonate | Drug: ADV7103<br>* Patients receive ADV7103 twice a day at optimal dose.<br>* Other names: Potassium Citrate and Potassium Bicarbonate;|
| Active Comparator: Standard of care comparator<br>Alkalinising treatment (SoC) taken at the usual dose and frequency | Drug: Standard of Care<br>* Cohort of patients with cystinuria, matching-pair for age category to the patients of ADV7103 Cohort, will receive their own alkalinising treatment (SoC) taken at the usual dose and frequency and will follow their usual first intention treatment (hydration and diet) for a 2-year-period.<br>|
|
Study Evaluating Patients With Cystinuria
Study Overview
=================
Brief Summary
-----------------
This is an open label, multicentre study, evaluating the safety, tolerability, efficacy, compliance and acceptability of alkalising treatments at long-term in patients with cystinuria.
Detailed Description
-----------------
B14CS study is an extension study which follows the B12CS-B13CS study. Patients who have participated in B12CS-B13CS Study will have the possibility to switch to B14CS Study for a long-term treatment period (2 year-period). The B14CS Study is an open-label long-term study and including 2 types of cohorts. ADV7103 Cohort: Cohort of patients who will have completed either B12CS or B13CS Study. Following an optional titration period (for B12CS Study subjects), all patients will be maintained at their ADV7103 optimal dose for a 2-year-period. SoC Cohort: Cohort of patients with cystinuria, matching-pair for age category to the patients of ADV7103 Cohort, will receive their own alkalinising treatment (SoC) taken at the usual dose and frequency and will follow their usual first intention treatment (hydration and diet) for a 2-year-period. This cohort is designed in order to contextualize the safety, tolerability and efficacy of the long-term ADV7103 treatment. The B14CS Study will be composed of 3 periods (more detailed hereafter): Lead-in Period: Period of 3 weeks, during which the treatment (ADV7103 or SoC) will be taken at the optimal dose as previously defined (Maintenance Phase). The Lead-in Period can include a Titration Phase, for ADV7103 B12CS Cohort only, in order to define the individual optimal dose of ADV7103 for the patients of this cohort; Assessment Period: Period of 7 days to evaluate the effect of study products (ADV7103 and SoC) at the optimal dose; Follow-up Period: Period of 23 months to evaluate the effects of the study products (ADV7103 and SoC) at long-term.
Official Title
-----------------
Open Label, Multicentre Study, Evaluating the Safety, Tolerability, Efficacy, Compliance and Acceptability of Alkalising Treatments at Long-term in Patients With Cystinuria
Conditions
-----------------
Cystinuria
Intervention / Treatment
-----------------
* Drug: ADV7103
* Drug: Standard of Care
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: For ADV7103 cohort: Patient who has participated to and completed the previous B12CS Study or B13CS Study. Patient for whom the safety and tolerability of ADV7103 were satisfactory during B12CS Study or B13CS Study. Female patient of childbearing potential (defined by the Clinical Trial Facilitation Group (CTFG) as woman fertile, following menarche until becoming post-menopausal unless permanently sterile*) using an acceptable effective birth control method** and having a negative pregnancy test at the inclusion, or a woman postmenopausal*** or a woman surgically sterilized*. Patient and/or parents or legal representative(s) who is(are) willing and able to participate in the study, to understand and to comply with study procedures for the entire length of the study. Patient or parents or legal representative(s) who has(have) provided a signed written informed consent. Patient of ≤17 Patient of ≤17 years of age for whom the assent has been collected or has been tried to be collected. Patient who is affiliated to a social health insurance system and/or in compliance with the recommendations of the national law in force relating to biomedical research. For Standard of Care cohort: Patient who has a diagnosis of cystinuria based on medical diagnosis (at least one previous or current episode of calculus of cystine, and/or one previous or current episode of cystine crystalluria) or on genetic diagnosis (only for patients of Subset 4). Patient treated with an alkalising treatment at a well-adapted dose (defined as a daily dose deemed by the investigator aiming to maintain overtime urinary pH value ≥ 7.0 and/or compatible with an acceptable safety profile and/or patient's constraints or compliance). Patient male or female, including child aged between 6 months and 17 years old and adult aged ≥ 18 years old up to 70 years old. Female patient of childbearing potential (defined by the Clinical Trial Facilitation Group (CTFG) as woman fertile, following menarche until becoming post-menopausal unless permanently sterile*) using an acceptable effective birth control method** and having a negative pregnancy test at the inclusion, or a woman postmenopausal*** or a woman surgically sterilized*. Patient and/or parents or legal representative(s) who is(are) willing and able to participate in the study, to understand and to comply with study procedures for the entire length of the study. Patient or parents or legal representative(s) who has/have provided a signed written informed consent. Patient of ≤17 years of age for whom the assent has been collected or has been tried to be collected. Patient who is affiliated to a social health insurance system and/or in compliance with the recommendations of the national law in force relating to biomedical research. Exclusion Criteria: For ADV7103 cohort: Patient who has not participated to B12CS study or B13CS study Patient for whom any safety issue could contraindicate her/his participation to the extension study For Standard of Care cohort: Patient that is receiving the second line therapy -- cystine chelating agents (sulfhydryl compounds). Patient who presents kalaemia > 5.0 mmol/L. Patient who presents a moderate or severe renal impairment (estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 according to Schwartz formula for the children and both MDRDs and CKD-EPI for adults). Patient who presents - barring the study disease - any previous or concurrent medical condition or any laboratory or clinical findings or any other condition that in the opinion of the investigator would be negatively affected by the study product or that would affect the study product or that precludes his participation, e.g. uncontrolled diabetes mellitus, adrenal insufficiency, cardiac impairment, repeated infections, metabolic alkalosis, chronic diarrhoea. Female patient who is pregnant or breast-feeding. Patient who cannot stop potassium sparing diuretics (e.g. antagonists of aldosterone as such spironolactone, canrenoate and eplerenone, amiloride, triamterene), angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, tacrolimus, potassium desodic salts. Patient who received any medication that could interfere with the study treatment within 4 weeks before the inclusion in the study, including angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, tacrolimus, potassium desodic salts, antibiotics. Patient who received potassium sparing diuretics 6 weeks before the inclusion in the study. Patient who is admitted to hospital in emergency settings. Patient who participated in a clinical trial within the last 3 months before enrolment. Patient who is at risk of non-compliance in the judgment of the investigator. Patient who could present any other condition, which in the opinion of the investigator, would preclude participation in the study. Patient who cannot be contacted in case of emergency. Patient under any administrative or legal supervision.
Ages Eligible for Study
-----------------
Minimum Age: 6 Months
Maximum Age: 70 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 |
| --- | --- |
| Active Comparator: ADV7103<br>Patients receive ADV7103 twice a day at optimal dose. Each dose of ADV7103 contains a fixed ratio of 1/3 of ADV7103-CK (potassium citrate) and 2/3 of ADV7103-BK (potassium bicarbonate) based on the mass of active substances. Other Names: • Potassium Citrate and Potassium Bicarbonate | Drug: ADV7103<br>* Patients receive ADV7103 twice a day at optimal dose.<br>* Other names: Potassium Citrate and Potassium Bicarbonate;|
| Active Comparator: Standard of care comparator<br>Alkalinising treatment (SoC) taken at the usual dose and frequency | Drug: Standard of Care<br>* Cohort of patients with cystinuria, matching-pair for age category to the patients of ADV7103 Cohort, will receive their own alkalinising treatment (SoC) taken at the usual dose and frequency and will follow their usual first intention treatment (hydration and diet) for a 2-year-period.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of urinary pH values ≥ 7.0 during 24h on Day 7 (after ADV7103 treatment period) | To evaluate the safety and the tolerability of ADV7103 and standard of care (SoC) after a long-term treatment. | 7 Days |
|
||
NCT04736550
|
Enhancing Exercise and Psychotherapy to Treat Pain and Addiction in Opioid Use Disorders (EXPO Pilot Trial)
|
The purpose of this pilot trial is to determine the feasibility of integrating exercise and psychotherapy that is specifically targeted to reducing and managing pain into residential drug treatment programs. The investigators will evaluate the feasibility (adherence) of integrating 'assisted' rate cycling, voluntary rate cycling and psychotherapy for pain (I-STOP) in participants with an opioid use disorder (OUD) and pain enrolled in residential drug treatment programs. The investigators will also explore the potential effects of 'assisted' rate cycling, voluntary rate cycling and I-STOP on pain, cravings, depression, anxiety, weight and sleep.
|
Enhancing Exercise and Psychotherapy to Treat Pain and Addiction in Adults With an Opioid Use Disorder (EXPO): A Randomized Pilot Trial
|
Opioid-use Disorder, Pain
|
* Behavioral: Exercise
* Behavioral: Psychotherapy for Pain (I-STOP)
|
Inclusion Criteria:~18 to 65 years old~Must be enrolled in a Residential Drug Treatment Program at a collaborating drug treatment center~Must be diagnosed with an Opioid Use Disorder (OUD; ICD-10 F11.20) or a Poly-substance Drug Use that includes an opioid component (ICD-10,F19.xx) and self-reported pain or a pain condition describing a non-cancer related chronic pain disorder~Must be approved to exercise in the study by the drug treatment center Medical Director, physician or other relevant clinical staff or primary care physician (PCP)~Exclusion Criteria:~Any substantive contraindications to exercise
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: In the pilot trial (R61 Phase), the investigators will use a multi-phase optimization trial (MOST) approach to help identify which components of the exercise and psychotherapy for pain treatment program are viable and worth retaining in the planned fully powered trial (R33 Phase). In the R61 Phase/Pilot Trial, the investigators will have two intervention components: 1) exercise with 3 levels ('assisted', voluntary, none/treatment as usual (TAU); and, 2) psychotherapy for pain (I-STOP) with 2 levels (Yes/I-STOP, No/TAU). All participants will receive also receive the treatment as usual at their residential drug treatment program and any medication assisted treatment (MAT). This corresponds to a 2^1 x 3 1 full factorial with six experimental conditions.
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence (% of sessions attended) | Percentage of exercise and psychotherapy sessions attended | through study completion, an average of 8 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain | The investigators will evaluate potential changes in pain using a cold pressor pain task. Pain sensitivity is the time spent in a cold water bath until the first report of pain and pain tolerance is the total time in the cold water bath. | baseline/pre-intervention and immediately after the intervention |
| Change in weight | The investigators will evaluate potential changes in weight (lbs). | baseline/pre-intervention and immediately after the intervention |
| Change in depression | The investigators will evaluate potential changes in depression using self-report, standardized questionnaire (Depression sub-scale in Hospital Anxiety and Depression Scale, HADS). Total Score range: 0-21; Higher scores indicate higher levels of depression. | baseline/pre-intervention and immediately after the intervention |
| The investigators will evaluate potential changes in drug cravings using self-report visual analog scale (VAS) | Higher scores indicate higher levels of cravings. | baseline/pre-intervention and immediately after the intervention |
| Change in cravings assessed by standardized questionnaire (Desires for Drug Questionnaire) | Higher scores indicate higher levels of cravings. | baseline/pre-intervention and immediately after the intervention |
| Change in sleep | The investigators will evaluate potential changes in sleep using self-report, standardized questionnaire (Pittsburgh Sleep Quality Index, PSQI). Total Score range: 0-21; Higher scores indicate poorer sleep quality. | baseline/pre-intervention and immediately after the intervention |
| Change in Anxiety | The investigators will evaluate potential changes in depression using self-report, standardized questionnaire (Anxiety sub-scale in Hospital Anxiety and Depression Scale, HADS). Total Score range: 0-21; Higher scores indicate higher levels of anxiety. | baseline/pre-intervention and immediately after the intervention |
|
OUD, exercise, psychotherapy, residential drug treatment, chronic pain
|
Opioid-Related Disorders, Substance-Related Disorders, Narcotic-Related Disorders, Chemically-Induced Disorders, Mental Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Assisted Exercise and I-STOP<br>Participant will receive Assisted Exercise (stationary cycling) and psychotherapy for pain (I-STOP). Exercise (supervised) will be offered 3 days/week. I-STOP will be offered 1 day/week. | Behavioral: Exercise<br>* Participants who are randomized to exercise will be perform exercise on stationary bikes. Participants randomized to Voluntary Exercise will exercise on a standard stationary bike where they will pedal at their voluntary rates. Participants randomized to Assisted Exercise will exercise on a special bike that assists them to pedal faster than they do voluntarily on their own (assisted (exercise) bike).<br>Behavioral: Psychotherapy for Pain (I-STOP)<br>* Participants who are randomized to receive I-STOP will receive the Self-regulation Treatment for Opioid addiction and Pain (STOP) program modified for inpatients/residential drug treatment (I-STOP). I-STOP uses empirically validated pain psychotherapy approaches targeted to patients with an OUD using psycho-physiological self-regulation components and biofeedback with Bio-dots.<br>|
| Experimental: Voluntary Exercise and I-STOP<br>Participant will receive Voluntary Rate Exercise (stationary cycling) and psychotherapy for pain (I-STOP). Exercise (supervised) will be offered 3 days/week. I-STOP will be offered 1 day/week. | Behavioral: Exercise<br>* Participants who are randomized to exercise will be perform exercise on stationary bikes. Participants randomized to Voluntary Exercise will exercise on a standard stationary bike where they will pedal at their voluntary rates. Participants randomized to Assisted Exercise will exercise on a special bike that assists them to pedal faster than they do voluntarily on their own (assisted (exercise) bike).<br>Behavioral: Psychotherapy for Pain (I-STOP)<br>* Participants who are randomized to receive I-STOP will receive the Self-regulation Treatment for Opioid addiction and Pain (STOP) program modified for inpatients/residential drug treatment (I-STOP). I-STOP uses empirically validated pain psychotherapy approaches targeted to patients with an OUD using psycho-physiological self-regulation components and biofeedback with Bio-dots.<br>|
| Experimental: No Exercise (TAU) and I-STOP<br>Participant will receive psychotherapy for pain (I-STOP). I-STOP will be offered 1 day/week. | Behavioral: Psychotherapy for Pain (I-STOP)<br>* Participants who are randomized to receive I-STOP will receive the Self-regulation Treatment for Opioid addiction and Pain (STOP) program modified for inpatients/residential drug treatment (I-STOP). I-STOP uses empirically validated pain psychotherapy approaches targeted to patients with an OUD using psycho-physiological self-regulation components and biofeedback with Bio-dots.<br>|
| Experimental: Assisted Exercise and No I-STOP (TAU)<br>Participant will receive Assisted Exercise (stationary cycling). Exercise (supervised) will be offered 3 days/week. | Behavioral: Exercise<br>* Participants who are randomized to exercise will be perform exercise on stationary bikes. Participants randomized to Voluntary Exercise will exercise on a standard stationary bike where they will pedal at their voluntary rates. Participants randomized to Assisted Exercise will exercise on a special bike that assists them to pedal faster than they do voluntarily on their own (assisted (exercise) bike).<br>|
| Experimental: Voluntary Exercise and No I-STOP (TAU)<br>Participant will receive Voluntary Rate Exercise (stationary cycling). Exercise (supervised) will be offered 3 days/week. | Behavioral: Exercise<br>* Participants who are randomized to exercise will be perform exercise on stationary bikes. Participants randomized to Voluntary Exercise will exercise on a standard stationary bike where they will pedal at their voluntary rates. Participants randomized to Assisted Exercise will exercise on a special bike that assists them to pedal faster than they do voluntarily on their own (assisted (exercise) bike).<br>|
| No Intervention: No Exercise (TAU) and No I-STOP (TAU)<br>Participant will receive their usual behavioral treatment offered at the residential drug treatment center and their medicated assisted treatment (MAT) as applicable. | |
|
Enhancing Exercise and Psychotherapy to Treat Pain and Addiction in Opioid Use Disorders (EXPO Pilot Trial)
Study Overview
=================
Brief Summary
-----------------
The purpose of this pilot trial is to determine the feasibility of integrating exercise and psychotherapy that is specifically targeted to reducing and managing pain into residential drug treatment programs. The investigators will evaluate the feasibility (adherence) of integrating 'assisted' rate cycling, voluntary rate cycling and psychotherapy for pain (I-STOP) in participants with an opioid use disorder (OUD) and pain enrolled in residential drug treatment programs. The investigators will also explore the potential effects of 'assisted' rate cycling, voluntary rate cycling and I-STOP on pain, cravings, depression, anxiety, weight and sleep.
Official Title
-----------------
Enhancing Exercise and Psychotherapy to Treat Pain and Addiction in Adults With an Opioid Use Disorder (EXPO): A Randomized Pilot Trial
Conditions
-----------------
Opioid-use Disorder, Pain
Intervention / Treatment
-----------------
* Behavioral: Exercise
* Behavioral: Psychotherapy for Pain (I-STOP)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 to 65 years old Must be enrolled in a Residential Drug Treatment Program at a collaborating drug treatment center Must be diagnosed with an Opioid Use Disorder (OUD; ICD-10 F11.20) or a Poly-substance Drug Use that includes an opioid component (ICD-10,F19.xx) and self-reported pain or a pain condition describing a non-cancer related chronic pain disorder Must be approved to exercise in the study by the drug treatment center Medical Director, physician or other relevant clinical staff or primary care physician (PCP) Exclusion Criteria: Any substantive contraindications to exercise
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: Factorial Assignment
Interventional Model Description: In the pilot trial (R61 Phase), the investigators will use a multi-phase optimization trial (MOST) approach to help identify which components of the exercise and psychotherapy for pain treatment program are viable and worth retaining in the planned fully powered trial (R33 Phase). In the R61 Phase/Pilot Trial, the investigators will have two intervention components: 1) exercise with 3 levels ('assisted', voluntary, none/treatment as usual (TAU); and, 2) psychotherapy for pain (I-STOP) with 2 levels (Yes/I-STOP, No/TAU). All participants will receive also receive the treatment as usual at their residential drug treatment program and any medication assisted treatment (MAT). This corresponds to a 2^1 x 3 1 full factorial with six experimental conditions.
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Assisted Exercise and I-STOP<br>Participant will receive Assisted Exercise (stationary cycling) and psychotherapy for pain (I-STOP). Exercise (supervised) will be offered 3 days/week. I-STOP will be offered 1 day/week. | Behavioral: Exercise<br>* Participants who are randomized to exercise will be perform exercise on stationary bikes. Participants randomized to Voluntary Exercise will exercise on a standard stationary bike where they will pedal at their voluntary rates. Participants randomized to Assisted Exercise will exercise on a special bike that assists them to pedal faster than they do voluntarily on their own (assisted (exercise) bike).<br>Behavioral: Psychotherapy for Pain (I-STOP)<br>* Participants who are randomized to receive I-STOP will receive the Self-regulation Treatment for Opioid addiction and Pain (STOP) program modified for inpatients/residential drug treatment (I-STOP). I-STOP uses empirically validated pain psychotherapy approaches targeted to patients with an OUD using psycho-physiological self-regulation components and biofeedback with Bio-dots.<br>|
| Experimental: Voluntary Exercise and I-STOP<br>Participant will receive Voluntary Rate Exercise (stationary cycling) and psychotherapy for pain (I-STOP). Exercise (supervised) will be offered 3 days/week. I-STOP will be offered 1 day/week. | Behavioral: Exercise<br>* Participants who are randomized to exercise will be perform exercise on stationary bikes. Participants randomized to Voluntary Exercise will exercise on a standard stationary bike where they will pedal at their voluntary rates. Participants randomized to Assisted Exercise will exercise on a special bike that assists them to pedal faster than they do voluntarily on their own (assisted (exercise) bike).<br>Behavioral: Psychotherapy for Pain (I-STOP)<br>* Participants who are randomized to receive I-STOP will receive the Self-regulation Treatment for Opioid addiction and Pain (STOP) program modified for inpatients/residential drug treatment (I-STOP). I-STOP uses empirically validated pain psychotherapy approaches targeted to patients with an OUD using psycho-physiological self-regulation components and biofeedback with Bio-dots.<br>|
| Experimental: No Exercise (TAU) and I-STOP<br>Participant will receive psychotherapy for pain (I-STOP). I-STOP will be offered 1 day/week. | Behavioral: Psychotherapy for Pain (I-STOP)<br>* Participants who are randomized to receive I-STOP will receive the Self-regulation Treatment for Opioid addiction and Pain (STOP) program modified for inpatients/residential drug treatment (I-STOP). I-STOP uses empirically validated pain psychotherapy approaches targeted to patients with an OUD using psycho-physiological self-regulation components and biofeedback with Bio-dots.<br>|
| Experimental: Assisted Exercise and No I-STOP (TAU)<br>Participant will receive Assisted Exercise (stationary cycling). Exercise (supervised) will be offered 3 days/week. | Behavioral: Exercise<br>* Participants who are randomized to exercise will be perform exercise on stationary bikes. Participants randomized to Voluntary Exercise will exercise on a standard stationary bike where they will pedal at their voluntary rates. Participants randomized to Assisted Exercise will exercise on a special bike that assists them to pedal faster than they do voluntarily on their own (assisted (exercise) bike).<br>|
| Experimental: Voluntary Exercise and No I-STOP (TAU)<br>Participant will receive Voluntary Rate Exercise (stationary cycling). Exercise (supervised) will be offered 3 days/week. | Behavioral: Exercise<br>* Participants who are randomized to exercise will be perform exercise on stationary bikes. Participants randomized to Voluntary Exercise will exercise on a standard stationary bike where they will pedal at their voluntary rates. Participants randomized to Assisted Exercise will exercise on a special bike that assists them to pedal faster than they do voluntarily on their own (assisted (exercise) bike).<br>|
| No Intervention: No Exercise (TAU) and No I-STOP (TAU)<br>Participant will receive their usual behavioral treatment offered at the residential drug treatment center and their medicated assisted treatment (MAT) as applicable. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence (% of sessions attended) | Percentage of exercise and psychotherapy sessions attended | through study completion, an average of 8 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain | The investigators will evaluate potential changes in pain using a cold pressor pain task. Pain sensitivity is the time spent in a cold water bath until the first report of pain and pain tolerance is the total time in the cold water bath. | baseline/pre-intervention and immediately after the intervention |
| Change in weight | The investigators will evaluate potential changes in weight (lbs). | baseline/pre-intervention and immediately after the intervention |
| Change in depression | The investigators will evaluate potential changes in depression using self-report, standardized questionnaire (Depression sub-scale in Hospital Anxiety and Depression Scale, HADS). Total Score range: 0-21; Higher scores indicate higher levels of depression. | baseline/pre-intervention and immediately after the intervention |
| The investigators will evaluate potential changes in drug cravings using self-report visual analog scale (VAS) | Higher scores indicate higher levels of cravings. | baseline/pre-intervention and immediately after the intervention |
| Change in cravings assessed by standardized questionnaire (Desires for Drug Questionnaire) | Higher scores indicate higher levels of cravings. | baseline/pre-intervention and immediately after the intervention |
| Change in sleep | The investigators will evaluate potential changes in sleep using self-report, standardized questionnaire (Pittsburgh Sleep Quality Index, PSQI). Total Score range: 0-21; Higher scores indicate poorer sleep quality. | baseline/pre-intervention and immediately after the intervention |
| Change in Anxiety | The investigators will evaluate potential changes in depression using self-report, standardized questionnaire (Anxiety sub-scale in Hospital Anxiety and Depression Scale, HADS). Total Score range: 0-21; Higher scores indicate higher levels of anxiety. | baseline/pre-intervention and immediately after the intervention |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
OUD, exercise, psychotherapy, residential drug treatment, chronic pain
|
|
NCT05143229
|
Alpelisib And Sacituzumab Govitecan For Treatment Of Breast Cancer
|
This study evaluates the safety and efficacy of sacituzumab govitecan plus alpelisib for treatment of metastatic or locally recurrent HER2-negative breast cancer.
|
Phase I Trial Of Alpelisib Plus Sacituzumab Govitecan In Patients With Metastatic Or Locally Recurrent HER2-Negative Breast Cancer
|
Breast Cancer
|
* Drug: Alpelisib
* Drug: Sacituzumab govitecan
|
Inclusion criteria:~Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent~Males and females age ≥ 18 years~ECOG Performance Status 0 - 2 (See Appendix A)~Histologically proven HER2-negative breast cancer (per current ASCO-CAP guidelines); HER2-negative breast cancer includes hormone receptor-positive (estrogen receptor and/or progesterone receptor-positive) breast cancer and TNBC.~HER2-negative breast cancer that at the time of study entry is either stage III (locally advanced) disease not amenable to curative therapy, or stage IV disease. Histological confirmation of recurrent/metastatic disease is encouraged but not required if clinical evidence of stage IV disease is available.~Have measurable or evaluable disease.~Ability to swallow and retain oral medicines.~No limitations to number of prior chemotherapies or endocrine therapies for metastatic disease.~All patients should have received at least one line of chemotherapy and at least one line of hormonal therapy (where appropriate) in either the advanced or neo/adjuvant setting. Patients who are candidates for anti-PD-1 and/or anti-PD-L1 therapy should have received at least one line of anti-PD-1 and/or anti-PD-L1 therapy in either the advanced or neo/adjuvant setting.~Prior palliative radiation therapy to bony metastases is allowed. A minimum of 14 days between the end of radiation treatment and start of study treatment is required.~Participants with previously treated brain metastases must be free of central nervous system symptoms and be >21 days from treatment of brain metastases. CNS brain metastasis should be clinically stable at the time of screening, and participant is not receiving steroids and/or enzyme inducing anti-epileptic medications for brain metastases.~Participants must be >2 weeks or 5 half-lives (whichever is longer) from prior systemic chemotherapy for breast cancer AND should have recovered to Grade 1 or better (except alopecia and neuropathy) from related side effects of any prior antineoplastic therapy prior to study entry.~Women of childbearing potential must have a negative serum pregnancy test 24 hours prior to initiating treatment.~Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence or to use approved forms of contraception for the duration of study participation and for 6 months following completion of therapy.~Fasting plasma glucose ≤140 mg/dL or ≤7.8 mmol/L~HbA1c ≤6.4%~Absolute neutrophil count ≥ 1500/uL NOTE: Patients with established diagnosis of benign neutropenia are eligible to participate with ANC between 1000-1500 if in the opinion of treating physician the trial treatment does not pose excessive risk of infection to the patient.~Platelets ≥ 100,000/uL (no transfusion allowed within 2 weeks)~Hemoglobin > 9 g/dL (which may be reached by transfusion)~Total bilirubin within normal range or ≤ 1.5x institutional upper limit of normal (IULN) if liver metastases are present, or total bilirubin ≤ 3.0x IULN with direct bilirubin within normal range in patients with well-documented Gilbert's Syndrome, which is defined as presence of unconjugated hyperbilirubinemia with normal results from CBC (including normal reticulocyte count and blood smear), normal liver function test results and absence of other contributing disease processes at the time of diagnosis.~AST(SGOT)/ALT(SPGT) ≤ 2.5x IULN or ≤ 5x IULN if liver metastases are present~Serum creatinine ≤ 1.5x IULN~Creatinine clearance ≥ 35 mL/min using Cockcroft-Gault formula~Potassium within institutional normal limits~Magnesium within institutional normal limits~Calcium (corrected for serum albumin) within institutional normal limits or ≤grade 1 according to NCI-CTCAE version 4.03 if judged clinically not significant by the investigator~Serum amylase ≤ 2x IULN~Serum lipase within institutional normal limits~Albumin ≥ 2.5 g/dL~Exclusion criteria:~Simultaneously enrolled in any therapeutic clinical trial~Current or anticipating use of other anti-neoplastic or investigational agents while participating in this study~Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements~Is pregnant or breastfeeding~Has a known allergic reaction to any excipient contained in the study drug formulation Active Grade 3 (per the NCI CTCAE, Version 5.0) or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment.~Patient has previously been treated with sacituzumab govitecan or alpelisib.~Patient has a concurrent malignancy or malignancy within 3 years of study enrollment (with the exception of adequately treated basal or squamous cell carcinoma, non-melanomatous skin cancer, or curatively resected cervical cancer).~Diabetes mellitus type I, or uncontrolled type II based on fasting plasma glucose and HbA1c meeting either of the following:~Fasting plasma glucose >140 mg/dL or >7.8 mmol/L~HbA1c ≥6.5% Note: For patients with fasting plasma glucose ≥ 100 mg/dL and/or HbA1c ≥5.7% (i.e. threshold for pre-diabetes) at baseline, lifestyle changes according to American Diabetes Association guidelines were recommended~Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).~Patient is classified into Child-Pugh class B or C.~Patient has a known history of HIV infection (testing not mandatory).~Patient has active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV). In patients with a history of HBV or HCV, patients with a detectable viral load will be excluded.~Patient has symptomatic/untreated CNS disease.~Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:~Uncontrolled hypertension defined by a systolic blood pressure (SBP) ≥ 160 mmHg and/or diastolic blood pressure (DBP) ≥ 100 mm Hg, with or without anti-hypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening.~Unstable angina pectoris within 6 months prior to study entry~Symptomatic pericarditis~Documented myocardial infarction within 6 months prior to study entry~Coronary artery bypass graft within 6 months prior to study entry~History of documented congestive heart failure (New York Heart Association functional classification III-IV)~Documented cardiomyopathy~Patient has a left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)~Patient has any of the following cardiac conduction abnormalities:~Ventricular arrhythmias, except for benign premature ventricular contractions~Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medicine~Conduction abnormality requiring a pacemaker~Other cardiac arrhythmia not controlled with medication~Patient has a QTcF > 470 msec if female and >450 msec if male on the screening ECG (using the QTcF formula).~Patient is currently receiving treatment with a medication that has a known risk to prolong the QT interval or induce Torsades de Pointes and the treatment cannot be discontinued or switched to a different medication prior to start of study drug.~Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects.~Participant has received palliative radiation therapy ≤ 2 weeks prior to starting study drug, or has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia).~Patient is currently receiving or has received high-dose systemic corticosteroids (≥20mg of prednisone or its equivalent) ≤ 2 weeks prior to starting study drug or has not fully recovered from side effects of such treatment.~Note: The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular).~Patient is currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP3A. The patient must have discontinued strong inducers for at least one week before the start of treatment.~Patient is currently receiving treatment with inhibitor(s) of BCRP (see Appendix B, table with heading Prohibited BRCP inhibitors). The patient must have discontinued BCRP inhibitors for at least one week before the start of treatment.~Patient is currently receiving warfarin or other coumarin-derived anti-coagulant for treatment, prophylaxis or otherwise.~Patient has received previous treatment with a PI3K inhibitor or AKT inhibitor~Patient has a history of acute (within one year of study entry) pancreatitis or past medical history of chronic pancreatitis.~Patient has pneumonitis or interstitial lung disease.~Patient has unresolved osteonecrosis of the jaw.~Patient has inflammatory breast cancer.~Patient has a history of severe cutaneous reactions, such as Steven-Johnson Syndrome (SJS), erythema multiforme (EM), toxic epidermal necrolysis (TEM), or drug reaction with eosinophilia and systemic syndrome (DRESS).~Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation in the clinical study (including, but not limited to: severe immune disease, certain degenerative diseases, certain other acute or chronic concurrent illnesses).
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Standard 3+3 dose escalation
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended phase II dose (RP2D) of alpelisib + sacituzumab govitecan | Standard 3+3 dose escalation design (three dose levels of alpelisib plus sacituzumab govitecan) with dose-limiting toxicities (DLT) assessed during the first treatment cycle. If two or more of the six patients experienced a dose-limiting toxicity, dosing escalation would cease and maximum tolerated dose (MTD) would be reached. RP2D was the next lower dose at which <1/6 subjects experienced a DLT. | 21 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of alpelisib when administered with sacituzumab govitecan | Alpelisib area under the curve (AUC): blood sampling pre-dose and 0.5, 1, 2, 3, 4, 6, 24, and 48 hours post-sacituzumab govitecan dose | In cycle 1, from prior to sacituzumab govitecan dosing through 48 hours after sacituzumab govitecan dosing |
| Pharmacokinetics of sacituzumab govitecan when administered with alpelisib | Sacituzumab govitecan, free SN-38, and total SN-38 area under the curve (AUC): blood sampling pre-dose and 0.5, 1, 2, 3, 4, 6, 24, and 48 hours post-sacituzumab govitecan dose | In cycle 1, from prior to sacituzumab govitecan dosing through 48 hours after sacituzumab govitecan dosing |
| Overall response rate (ORR) in patients with measurable disease | ORR includes complete response (CR) plus partial response (PR). As evaluated per RECIST version 1.1. | From start of study treatment until removal from study treatment; estimated 24 months maximum. |
|
HER2-negative, Metastatic/locally advanced, Sacituzumab govitecan, Alpelisib, RP2D, Trop-2 antibody-drug conjugate, PI3K inhibitor
|
Sacituzumab govitecan, Immunoconjugates, Immunologic Factors, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose level 1: alpelisib 250 mg plus sacituzumab govitecan 8 mg/kg<br>Alpelisib: 250 mg by mouth daily Sacituzumab govitecan: 8 mg/kg intravenous on days 1 and 8 of each 21 (+/-2) day cycle | Drug: Alpelisib<br>* PI3K inhibitor<br>* Other names: Piqray;Drug: Sacituzumab govitecan<br>* Trop-2-directed antibody and topoisomerase inhibitor drug conjugate<br>* Other names: Trodelvy;|
| Experimental: Dose level 2: alpelisib 250 mg plus sacituzumab govitecan 10 mg/kg<br>Alpelisib: 250 mg by mouth daily Sacituzumab govitecan: 10 mg/kg intravenous on days 1 and 8 of each 21 (+/-2) day cycle | Drug: Alpelisib<br>* PI3K inhibitor<br>* Other names: Piqray;Drug: Sacituzumab govitecan<br>* Trop-2-directed antibody and topoisomerase inhibitor drug conjugate<br>* Other names: Trodelvy;|
| Experimental: Dose level 3: alpelisib 300 mg plus sacituzumab govitecan 10 mg/kg<br>Alpelisib: 300 mg by mouth daily Sacituzumab govitecan: 10 mg/kg intravenous on days 1 and 8 of each 21 (+/-2) day cycle | Drug: Alpelisib<br>* PI3K inhibitor<br>* Other names: Piqray;Drug: Sacituzumab govitecan<br>* Trop-2-directed antibody and topoisomerase inhibitor drug conjugate<br>* Other names: Trodelvy;|
|
Alpelisib And Sacituzumab Govitecan For Treatment Of Breast Cancer
Study Overview
=================
Brief Summary
-----------------
This study evaluates the safety and efficacy of sacituzumab govitecan plus alpelisib for treatment of metastatic or locally recurrent HER2-negative breast cancer.
Official Title
-----------------
Phase I Trial Of Alpelisib Plus Sacituzumab Govitecan In Patients With Metastatic Or Locally Recurrent HER2-Negative Breast Cancer
Conditions
-----------------
Breast Cancer
Intervention / Treatment
-----------------
* Drug: Alpelisib
* Drug: Sacituzumab govitecan
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent Males and females age ≥ 18 years ECOG Performance Status 0 - 2 (See Appendix A) Histologically proven HER2-negative breast cancer (per current ASCO-CAP guidelines); HER2-negative breast cancer includes hormone receptor-positive (estrogen receptor and/or progesterone receptor-positive) breast cancer and TNBC. HER2-negative breast cancer that at the time of study entry is either stage III (locally advanced) disease not amenable to curative therapy, or stage IV disease. Histological confirmation of recurrent/metastatic disease is encouraged but not required if clinical evidence of stage IV disease is available. Have measurable or evaluable disease. Ability to swallow and retain oral medicines. No limitations to number of prior chemotherapies or endocrine therapies for metastatic disease. All patients should have received at least one line of chemotherapy and at least one line of hormonal therapy (where appropriate) in either the advanced or neo/adjuvant setting. Patients who are candidates for anti-PD-1 and/or anti-PD-L1 therapy should have received at least one line of anti-PD-1 and/or anti-PD-L1 therapy in either the advanced or neo/adjuvant setting. Prior palliative radiation therapy to bony metastases is allowed. A minimum of 14 days between the end of radiation treatment and start of study treatment is required. Participants with previously treated brain metastases must be free of central nervous system symptoms and be >21 days from treatment of brain metastases. CNS brain metastasis should be clinically stable at the time of screening, and participant is not receiving steroids and/or enzyme inducing anti-epileptic medications for brain metastases. Participants must be >2 weeks or 5 half-lives (whichever is longer) from prior systemic chemotherapy for breast cancer AND should have recovered to Grade 1 or better (except alopecia and neuropathy) from related side effects of any prior antineoplastic therapy prior to study entry. Women of childbearing potential must have a negative serum pregnancy test 24 hours prior to initiating treatment. Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence or to use approved forms of contraception for the duration of study participation and for 6 months following completion of therapy. Fasting plasma glucose ≤140 mg/dL or ≤7.8 mmol/L HbA1c ≤6.4% Absolute neutrophil count ≥ 1500/uL NOTE: Patients with established diagnosis of benign neutropenia are eligible to participate with ANC between 1000-1500 if in the opinion of treating physician the trial treatment does not pose excessive risk of infection to the patient. Platelets ≥ 100,000/uL (no transfusion allowed within 2 weeks) Hemoglobin > 9 g/dL (which may be reached by transfusion) Total bilirubin within normal range or ≤ 1.5x institutional upper limit of normal (IULN) if liver metastases are present, or total bilirubin ≤ 3.0x IULN with direct bilirubin within normal range in patients with well-documented Gilbert's Syndrome, which is defined as presence of unconjugated hyperbilirubinemia with normal results from CBC (including normal reticulocyte count and blood smear), normal liver function test results and absence of other contributing disease processes at the time of diagnosis. AST(SGOT)/ALT(SPGT) ≤ 2.5x IULN or ≤ 5x IULN if liver metastases are present Serum creatinine ≤ 1.5x IULN Creatinine clearance ≥ 35 mL/min using Cockcroft-Gault formula Potassium within institutional normal limits Magnesium within institutional normal limits Calcium (corrected for serum albumin) within institutional normal limits or ≤grade 1 according to NCI-CTCAE version 4.03 if judged clinically not significant by the investigator Serum amylase ≤ 2x IULN Serum lipase within institutional normal limits Albumin ≥ 2.5 g/dL Exclusion criteria: Simultaneously enrolled in any therapeutic clinical trial Current or anticipating use of other anti-neoplastic or investigational agents while participating in this study Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements Is pregnant or breastfeeding Has a known allergic reaction to any excipient contained in the study drug formulation Active Grade 3 (per the NCI CTCAE, Version 5.0) or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment. Patient has previously been treated with sacituzumab govitecan or alpelisib. Patient has a concurrent malignancy or malignancy within 3 years of study enrollment (with the exception of adequately treated basal or squamous cell carcinoma, non-melanomatous skin cancer, or curatively resected cervical cancer). Diabetes mellitus type I, or uncontrolled type II based on fasting plasma glucose and HbA1c meeting either of the following: Fasting plasma glucose >140 mg/dL or >7.8 mmol/L HbA1c ≥6.5% Note: For patients with fasting plasma glucose ≥ 100 mg/dL and/or HbA1c ≥5.7% (i.e. threshold for pre-diabetes) at baseline, lifestyle changes according to American Diabetes Association guidelines were recommended Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection). Patient is classified into Child-Pugh class B or C. Patient has a known history of HIV infection (testing not mandatory). Patient has active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV). In patients with a history of HBV or HCV, patients with a detectable viral load will be excluded. Patient has symptomatic/untreated CNS disease. Patient has active cardiac disease or a history of cardiac dysfunction including any of the following: Uncontrolled hypertension defined by a systolic blood pressure (SBP) ≥ 160 mmHg and/or diastolic blood pressure (DBP) ≥ 100 mm Hg, with or without anti-hypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening. Unstable angina pectoris within 6 months prior to study entry Symptomatic pericarditis Documented myocardial infarction within 6 months prior to study entry Coronary artery bypass graft within 6 months prior to study entry History of documented congestive heart failure (New York Heart Association functional classification III-IV) Documented cardiomyopathy Patient has a left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) Patient has any of the following cardiac conduction abnormalities: Ventricular arrhythmias, except for benign premature ventricular contractions Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medicine Conduction abnormality requiring a pacemaker Other cardiac arrhythmia not controlled with medication Patient has a QTcF > 470 msec if female and >450 msec if male on the screening ECG (using the QTcF formula). Patient is currently receiving treatment with a medication that has a known risk to prolong the QT interval or induce Torsades de Pointes and the treatment cannot be discontinued or switched to a different medication prior to start of study drug. Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects. Participant has received palliative radiation therapy ≤ 2 weeks prior to starting study drug, or has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia). Patient is currently receiving or has received high-dose systemic corticosteroids (≥20mg of prednisone or its equivalent) ≤ 2 weeks prior to starting study drug or has not fully recovered from side effects of such treatment. Note: The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular). Patient is currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP3A. The patient must have discontinued strong inducers for at least one week before the start of treatment. Patient is currently receiving treatment with inhibitor(s) of BCRP (see Appendix B, table with heading Prohibited BRCP inhibitors). The patient must have discontinued BCRP inhibitors for at least one week before the start of treatment. Patient is currently receiving warfarin or other coumarin-derived anti-coagulant for treatment, prophylaxis or otherwise. Patient has received previous treatment with a PI3K inhibitor or AKT inhibitor Patient has a history of acute (within one year of study entry) pancreatitis or past medical history of chronic pancreatitis. Patient has pneumonitis or interstitial lung disease. Patient has unresolved osteonecrosis of the jaw. Patient has inflammatory breast cancer. Patient has a history of severe cutaneous reactions, such as Steven-Johnson Syndrome (SJS), erythema multiforme (EM), toxic epidermal necrolysis (TEM), or drug reaction with eosinophilia and systemic syndrome (DRESS). Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation in the clinical study (including, but not limited to: severe immune disease, certain degenerative diseases, certain other acute or chronic concurrent illnesses).
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: Sequential Assignment
Interventional Model Description: Standard 3+3 dose escalation
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose level 1: alpelisib 250 mg plus sacituzumab govitecan 8 mg/kg<br>Alpelisib: 250 mg by mouth daily Sacituzumab govitecan: 8 mg/kg intravenous on days 1 and 8 of each 21 (+/-2) day cycle | Drug: Alpelisib<br>* PI3K inhibitor<br>* Other names: Piqray;Drug: Sacituzumab govitecan<br>* Trop-2-directed antibody and topoisomerase inhibitor drug conjugate<br>* Other names: Trodelvy;|
| Experimental: Dose level 2: alpelisib 250 mg plus sacituzumab govitecan 10 mg/kg<br>Alpelisib: 250 mg by mouth daily Sacituzumab govitecan: 10 mg/kg intravenous on days 1 and 8 of each 21 (+/-2) day cycle | Drug: Alpelisib<br>* PI3K inhibitor<br>* Other names: Piqray;Drug: Sacituzumab govitecan<br>* Trop-2-directed antibody and topoisomerase inhibitor drug conjugate<br>* Other names: Trodelvy;|
| Experimental: Dose level 3: alpelisib 300 mg plus sacituzumab govitecan 10 mg/kg<br>Alpelisib: 300 mg by mouth daily Sacituzumab govitecan: 10 mg/kg intravenous on days 1 and 8 of each 21 (+/-2) day cycle | Drug: Alpelisib<br>* PI3K inhibitor<br>* Other names: Piqray;Drug: Sacituzumab govitecan<br>* Trop-2-directed antibody and topoisomerase inhibitor drug conjugate<br>* Other names: Trodelvy;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended phase II dose (RP2D) of alpelisib + sacituzumab govitecan | Standard 3+3 dose escalation design (three dose levels of alpelisib plus sacituzumab govitecan) with dose-limiting toxicities (DLT) assessed during the first treatment cycle. If two or more of the six patients experienced a dose-limiting toxicity, dosing escalation would cease and maximum tolerated dose (MTD) would be reached. RP2D was the next lower dose at which <1/6 subjects experienced a DLT. | 21 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of alpelisib when administered with sacituzumab govitecan | Alpelisib area under the curve (AUC): blood sampling pre-dose and 0.5, 1, 2, 3, 4, 6, 24, and 48 hours post-sacituzumab govitecan dose | In cycle 1, from prior to sacituzumab govitecan dosing through 48 hours after sacituzumab govitecan dosing |
| Pharmacokinetics of sacituzumab govitecan when administered with alpelisib | Sacituzumab govitecan, free SN-38, and total SN-38 area under the curve (AUC): blood sampling pre-dose and 0.5, 1, 2, 3, 4, 6, 24, and 48 hours post-sacituzumab govitecan dose | In cycle 1, from prior to sacituzumab govitecan dosing through 48 hours after sacituzumab govitecan dosing |
| Overall response rate (ORR) in patients with measurable disease | ORR includes complete response (CR) plus partial response (PR). As evaluated per RECIST version 1.1. | From start of study treatment until removal from study treatment; estimated 24 months maximum. |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HER2-negative, Metastatic/locally advanced, Sacituzumab govitecan, Alpelisib, RP2D, Trop-2 antibody-drug conjugate, PI3K inhibitor
|
|
NCT04956315
|
Accuracy and Stability of a New Automatic Knee Arthrometer in Diagnosing ACL Rupture
|
We introduced an automatic knee arthrometer (AKA) and aimed to evaluate the repeatability and effectiveness thereof in diagnosing ACL rupture compared with the KT-2000.
|
The AKA was compared to the KT-2000 at 134 N in this study, the anterior displacement and difference of both knees of every subject were measured. The first protocol was designed to evaluate examiner effect (level of experience) and contralateral-side effect (left or right knee) in a single healthy subject, ten times, on ten consecutive days. The second was to compare the stability in 20 healthy subjects, with a single experienced examiner. Third, we recruited 200 ACL rupture and 200 healthy subjects as contrast to compare the accuracy of the devices in diagnosing ACL rupture.
|
Accuracy and Stability of a New Automatic Knee Arthrometer in Diagnosing Anterior Cruciate Ligament Rupture
|
Knee Ligament; Laxity
|
* Diagnostic Test: Side-to-side difference (reproducibility)
* Diagnostic Test: Side-to-side difference (availability)
* Diagnostic Test: Side-to-side difference (Accuracy)
|
Inclusion Criteria:~patients with ACL rupture from our institution were included. All patients were diagnosed by sports medicine specialists based on clinical manifestation, combined with imaging examinations, and hospitalized for further surgery.~Exclusion Criteria:~Patients aged <18 or >45 years, with combined multiple knee ligament injury combinations, and/or limited range of motion of the knee (unable to flex to 20-30°)
|
18 Years
|
45 Years
|
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Side-to-side difference （SSD） | Side-to-side difference （SSD）at 134 N | within 3 months after ACL rupture |
|
Rupture, Wounds and Injuries
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Examiner effect group<br>Two examiners performed the test on one healthy subject with both devices for ten consecutive days. We measured the AD of both knees and calculated the ADD of every test. We evaluated the contralateral-side effect by comparing the AD standard deviations of each knee with both devices, and compared the average ADD tested by different examiners with the same device, to estimate examiner effect. | Diagnostic Test: Side-to-side difference (reproducibility)<br>* The experienced examiner performed tests on 20 healthy subjects<br>|
| Method effect group<br>The experienced examiner performed tests on 20 healthy subjects using both devices. The means and standard deviations of both knees were calculated. We examined the difference in measurements using each device to determine the method effect. | Diagnostic Test: Side-to-side difference (availability)<br>* Two examiners performed the test on one healthy subject with both devices for ten consecutive days.<br>|
| Equipment effectiveness group<br>The experienced examiner performed tests on 200 ACL ruptureand 200 healthy subjects using each device. Effectiveness was analyzed using 1.5 mm and 3 mm threshold values in ACL tears. | Diagnostic Test: Side-to-side difference (Accuracy)<br>* 200 ACL rupture and 200 healthy subjects were recruited as contrast to compare the accuracy of the devices in diagnosing ACL rupture.<br>|
|
Accuracy and Stability of a New Automatic Knee Arthrometer in Diagnosing ACL Rupture
Study Overview
=================
Brief Summary
-----------------
We introduced an automatic knee arthrometer (AKA) and aimed to evaluate the repeatability and effectiveness thereof in diagnosing ACL rupture compared with the KT-2000.
Detailed Description
-----------------
The AKA was compared to the KT-2000 at 134 N in this study, the anterior displacement and difference of both knees of every subject were measured. The first protocol was designed to evaluate examiner effect (level of experience) and contralateral-side effect (left or right knee) in a single healthy subject, ten times, on ten consecutive days. The second was to compare the stability in 20 healthy subjects, with a single experienced examiner. Third, we recruited 200 ACL rupture and 200 healthy subjects as contrast to compare the accuracy of the devices in diagnosing ACL rupture.
Official Title
-----------------
Accuracy and Stability of a New Automatic Knee Arthrometer in Diagnosing Anterior Cruciate Ligament Rupture
Conditions
-----------------
Knee Ligament; Laxity
Intervention / Treatment
-----------------
* Diagnostic Test: Side-to-side difference (reproducibility)
* Diagnostic Test: Side-to-side difference (availability)
* Diagnostic Test: Side-to-side difference (Accuracy)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patients with ACL rupture from our institution were included. All patients were diagnosed by sports medicine specialists based on clinical manifestation, combined with imaging examinations, and hospitalized for further surgery. Exclusion Criteria: Patients aged <18 or >45 years, with combined multiple knee ligament injury combinations, and/or limited range of motion of the knee (unable to flex to 20-30°)
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?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Examiner effect group<br>Two examiners performed the test on one healthy subject with both devices for ten consecutive days. We measured the AD of both knees and calculated the ADD of every test. We evaluated the contralateral-side effect by comparing the AD standard deviations of each knee with both devices, and compared the average ADD tested by different examiners with the same device, to estimate examiner effect. | Diagnostic Test: Side-to-side difference (reproducibility)<br>* The experienced examiner performed tests on 20 healthy subjects<br>|
| Method effect group<br>The experienced examiner performed tests on 20 healthy subjects using both devices. The means and standard deviations of both knees were calculated. We examined the difference in measurements using each device to determine the method effect. | Diagnostic Test: Side-to-side difference (availability)<br>* Two examiners performed the test on one healthy subject with both devices for ten consecutive days.<br>|
| Equipment effectiveness group<br>The experienced examiner performed tests on 200 ACL ruptureand 200 healthy subjects using each device. Effectiveness was analyzed using 1.5 mm and 3 mm threshold values in ACL tears. | Diagnostic Test: Side-to-side difference (Accuracy)<br>* 200 ACL rupture and 200 healthy subjects were recruited as contrast to compare the accuracy of the devices in diagnosing ACL rupture.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Side-to-side difference （SSD） | Side-to-side difference （SSD）at 134 N | within 3 months after ACL rupture |
|
|||
NCT00066716
|
Celecoxib, Paclitaxel, and Carboplatin in Treating Patients With Cancer of the Esophagus
|
RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib may increase the effectiveness of a chemotherapy drug by making tumor cells more sensitive to the drug. Celecoxib may also stop the growth of tumor cells by stopping blood flow to the tumor and/or may block the enzymes necessary for their growth. Combining celecoxib with paclitaxel and carboplatin before surgery may shrink the tumor so that it can be removed during surgery. Giving celecoxib alone after surgery may kill any remaining tumor cells.~PURPOSE: This phase II trial is studying how well giving celecoxib together with paclitaxel and carboplatin works in treating patients who are undergoing surgery for esophageal cancer.
|
OBJECTIVES:~Primary~Determine the rate of complete pathological response and/or minimal residual microscopic disease in patients with squamous cell or adenocarcinoma of the esophagus treated with preoperative celecoxib, paclitaxel, and carboplatin.~Secondary~Determine the clinical response rate of patients treated with this regimen.~Determine the chemotherapy-related toxicity of this regimen in these patients.~Determine the time to progression, disease-free survival, and overall survival of patients treated with this regimen.~OUTLINE: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on days 1, 22, and 43. Patients also receive oral celecoxib twice daily beginning 3-7 days before the first dose of chemotherapy and continuing until the morning of planned surgical resection (between days 64 and 71). Approximately 28-56 days after resection, patients may resume oral celecoxib twice daily and continue for 1 year in the absence of disease progression or unacceptable toxicity.~Patients are followed periodically for 18 months after surgery.~PROJECTED ACCRUAL: A total of 39 patients will be accrued for this study within 18 months.
|
A Phase II Study Of Preoperative Celecoxib/Paclitaxel/Carboplatin For Squamous Cell And Adenocarcinoma Of The Esophagus
|
Esophageal Cancer
|
* Drug: carboplatin
* Drug: celecoxib
* Drug: paclitaxel
* Procedure: adjuvant therapy
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy
|
DISEASE CHARACTERISTICS:~Histologically confirmed esophageal cancer of 1 of the following cellular types:~Squamous cell~Adenocarcinoma~Potentially resectable disease~No distant metastases~PATIENT CHARACTERISTICS:~Age~18 and over~Performance status~Karnofsky 80-100%~Life expectancy~Not specified~Hematopoietic~WBC at least 3,000/mm^3~Platelet count at least 100,000/mm^3~No bleeding disorder~Hepatic~Bilirubin normal~AST and ALT less than 2.5 times upper limit of normal (ULN)~Alkaline phosphatase no greater than 2.5 times ULN~Renal~Creatinine no greater than 2.0 mg/dL~Cardiovascular~No significant history of unstable cardiovascular disease~No inadequately controlled hypertension~No angina~No myocardial infarction within the past 6 months~No ventricular cardiac arrhythmias requiring medication~No congestive heart failure that would preclude study therapy~Pulmonary~Pulmonary function acceptable for surgery~No interstitial pneumonia~No interstitial fibrosis~Gastrointestinal~No history of peptic ulcer disease~No irritable bowel syndrome~No inflammatory bowel disease~No chronic diarrhea~No bowel obstruction within the past 5 years~Other~Not pregnant~Negative pregnancy test~Fertile patients must use effective contraception~No known hypersensitivity or allergic reactions to COX-2 inhibitors, sulfonamides, NSAIDs, or salicylates~No hypersensitivity to paclitaxel or carboplatin~No other serious underlying medical condition that would preclude study therapy~No significant psychiatric illness that would preclude study compliance~No uncontrolled diabetes mellitus~No uncontrolled infection~HIV negative~PRIOR CONCURRENT THERAPY:~Biologic therapy~Not specified~Chemotherapy~Not specified~Endocrine therapy~No concurrent chronic steroid use except inhaled mometasone or fluticasone~Radiotherapy~Not specified~Surgery~Not specified~Other~More than 3 weeks since other prior clinical trial therapy~At least 72 hours since prior nonsteroidal anti-inflammatory drugs (NSAIDs)~No concurrent chronic NSAID use (7 or more days of continuous therapy per month OR 3 or more days of therapy per week)~No other concurrent investigational agents~No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin or phenobarbital)~No other concurrent cyclo-oxygenase (COX)-2 inhibitors~No concurrent lithium or fluconazole~Concurrent low-dose aspirin (325 mg/day or less) allowed for cardiovascular prophylaxis
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological response rate at time of surgical resection | | At completion of pathology report. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response rate | | At the time of tumor assessment obtained prior to definitive surgery approximately 1-2 weeks prior to surgical resection. |
| Disease-free survival | | From start of treatment to time of recurrent disease measured postoperatively every 6 months for 18 months. |
| Overall survival | | 18 months after surgery |
| Toxicities and safety | | 30 days after completion of study treatment. |
|
adenocarcinoma of the esophagus, squamous cell carcinoma of the esophagus, stage I esophageal cancer, stage II esophageal cancer, stage III esophageal cancer, stage IV esophageal cancer (lymph node metastasis only)
|
Analgesics, Celecoxib, Paclitaxel, Carboplatin, Antineoplastic Agents, Phytogenic, Antineoplastic Agents, Tubulin Modulators, Antimitotic Agents, Mitosis Modulators, Molecular Mechanisms of Pharmacological Action, Anti-Inflammatory Agents, Non-Steroidal, Analgesics, Non-Narcotic, Sensory System Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anti-Inflammatory Agents, Antirheumatic Agents, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors, Enzyme Inhibitors
|
| Intervention/Treatment |
| --- |
|Drug: carboplatin|Dosed to an AUC of 6 by the Calvert formula, intravenously over 1 hour after paclitaxel on days 1, 22, and 43.|
|Drug: celecoxib|400 mg orally BID begins 3-7 days before the first dose of chemotherapy to the morning of surgery. Celecoxib 400 mg orally BID will resume post-operatively 4-8 weeks if there is adequate wound healing and will be continued for 1 year total, that is, 1 year from the date of surgery + 2 weeks unless tumor recurrence is documented.|
|Drug: paclitaxel|200 mg/m2 as a 3-hour intravenous infusion on days 1, 22, and 43.|
|Procedure: adjuvant therapy|Surgery will be performed 3-4 weeks after the third dose of paclitaxel and carboplatin.~Operation will be performed within 6-12 hours from the last dose of celecoxib.~Surgery will include an esophagectomy as well as a complete mediastinal and abdominal lymph node dissection.~Celecoxib 400 mg orally BID will resume post-operatively 4-8 weeks if there is adequate wound healing and will be continued for 1 year.|
|Procedure: conventional surgery|Surgery will be performed 3-4 weeks after the third dose of paclitaxel and carboplatin.~Operation will be performed within 6-12 hours from the last dose of celecoxib.~Surgery will include an esophagectomy as well as a complete mediastinal and abdominal lymph node dissection.|
|Procedure: neoadjuvant therapy|Surgery will be performed 3-4 weeks after the third dose of paclitaxel and carboplatin.~Operation will be performed within 6-12 hours from the last dose of celecoxib.~Surgery will include an esophagectomy as well as a complete mediastinal and abdominal lymph node dissection.|
|
Celecoxib, Paclitaxel, and Carboplatin in Treating Patients With Cancer of the Esophagus
Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib may increase the effectiveness of a chemotherapy drug by making tumor cells more sensitive to the drug. Celecoxib may also stop the growth of tumor cells by stopping blood flow to the tumor and/or may block the enzymes necessary for their growth. Combining celecoxib with paclitaxel and carboplatin before surgery may shrink the tumor so that it can be removed during surgery. Giving celecoxib alone after surgery may kill any remaining tumor cells. PURPOSE: This phase II trial is studying how well giving celecoxib together with paclitaxel and carboplatin works in treating patients who are undergoing surgery for esophageal cancer.
Detailed Description
-----------------
OBJECTIVES: Primary Determine the rate of complete pathological response and/or minimal residual microscopic disease in patients with squamous cell or adenocarcinoma of the esophagus treated with preoperative celecoxib, paclitaxel, and carboplatin. Secondary Determine the clinical response rate of patients treated with this regimen. Determine the chemotherapy-related toxicity of this regimen in these patients. Determine the time to progression, disease-free survival, and overall survival of patients treated with this regimen. OUTLINE: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on days 1, 22, and 43. Patients also receive oral celecoxib twice daily beginning 3-7 days before the first dose of chemotherapy and continuing until the morning of planned surgical resection (between days 64 and 71). Approximately 28-56 days after resection, patients may resume oral celecoxib twice daily and continue for 1 year in the absence of disease progression or unacceptable toxicity. Patients are followed periodically for 18 months after surgery. PROJECTED ACCRUAL: A total of 39 patients will be accrued for this study within 18 months.
Official Title
-----------------
A Phase II Study Of Preoperative Celecoxib/Paclitaxel/Carboplatin For Squamous Cell And Adenocarcinoma Of The Esophagus
Conditions
-----------------
Esophageal Cancer
Intervention / Treatment
-----------------
* Drug: carboplatin
* Drug: celecoxib
* Drug: paclitaxel
* Procedure: adjuvant therapy
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy
Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed esophageal cancer of 1 of the following cellular types: Squamous cell Adenocarcinoma Potentially resectable disease No distant metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 80-100% Life expectancy Not specified Hematopoietic WBC at least 3,000/mm^3 Platelet count at least 100,000/mm^3 No bleeding disorder Hepatic Bilirubin normal AST and ALT less than 2.5 times upper limit of normal (ULN) Alkaline phosphatase no greater than 2.5 times ULN Renal Creatinine no greater than 2.0 mg/dL Cardiovascular No significant history of unstable cardiovascular disease No inadequately controlled hypertension No angina No myocardial infarction within the past 6 months No ventricular cardiac arrhythmias requiring medication No congestive heart failure that would preclude study therapy Pulmonary Pulmonary function acceptable for surgery No interstitial pneumonia No interstitial fibrosis Gastrointestinal No history of peptic ulcer disease No irritable bowel syndrome No inflammatory bowel disease No chronic diarrhea No bowel obstruction within the past 5 years Other Not pregnant Negative pregnancy test Fertile patients must use effective contraception No known hypersensitivity or allergic reactions to COX-2 inhibitors, sulfonamides, NSAIDs, or salicylates No hypersensitivity to paclitaxel or carboplatin No other serious underlying medical condition that would preclude study therapy No significant psychiatric illness that would preclude study compliance No uncontrolled diabetes mellitus No uncontrolled infection HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy No concurrent chronic steroid use except inhaled mometasone or fluticasone Radiotherapy Not specified Surgery Not specified Other More than 3 weeks since other prior clinical trial therapy At least 72 hours since prior nonsteroidal anti-inflammatory drugs (NSAIDs) No concurrent chronic NSAID use (7 or more days of continuous therapy per month OR 3 or more days of therapy per week) No other concurrent investigational agents No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin or phenobarbital) No other concurrent cyclo-oxygenase (COX)-2 inhibitors No concurrent lithium or fluconazole Concurrent low-dose aspirin (325 mg/day or less) allowed for cardiovascular prophylaxis
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
| Intervention/Treatment |
| --- |
|Drug: carboplatin|Dosed to an AUC of 6 by the Calvert formula, intravenously over 1 hour after paclitaxel on days 1, 22, and 43.|
|Drug: celecoxib|400 mg orally BID begins 3-7 days before the first dose of chemotherapy to the morning of surgery. Celecoxib 400 mg orally BID will resume post-operatively 4-8 weeks if there is adequate wound healing and will be continued for 1 year total, that is, 1 year from the date of surgery + 2 weeks unless tumor recurrence is documented.|
|Drug: paclitaxel|200 mg/m2 as a 3-hour intravenous infusion on days 1, 22, and 43.|
|Procedure: adjuvant therapy|Surgery will be performed 3-4 weeks after the third dose of paclitaxel and carboplatin. Operation will be performed within 6-12 hours from the last dose of celecoxib. Surgery will include an esophagectomy as well as a complete mediastinal and abdominal lymph node dissection. Celecoxib 400 mg orally BID will resume post-operatively 4-8 weeks if there is adequate wound healing and will be continued for 1 year.|
|Procedure: conventional surgery|Surgery will be performed 3-4 weeks after the third dose of paclitaxel and carboplatin. Operation will be performed within 6-12 hours from the last dose of celecoxib. Surgery will include an esophagectomy as well as a complete mediastinal and abdominal lymph node dissection.|
|Procedure: neoadjuvant therapy|Surgery will be performed 3-4 weeks after the third dose of paclitaxel and carboplatin. Operation will be performed within 6-12 hours from the last dose of celecoxib. Surgery will include an esophagectomy as well as a complete mediastinal and abdominal lymph node dissection.|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological response rate at time of surgical resection | | At completion of pathology report. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response rate | | At the time of tumor assessment obtained prior to definitive surgery approximately 1-2 weeks prior to surgical resection. |
| Disease-free survival | | From start of treatment to time of recurrent disease measured postoperatively every 6 months for 18 months. |
| Overall survival | | 18 months after surgery |
| Toxicities and safety | | 30 days after completion of study treatment. |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adenocarcinoma of the esophagus, squamous cell carcinoma of the esophagus, stage I esophageal cancer, stage II esophageal cancer, stage III esophageal cancer, stage IV esophageal cancer (lymph node metastasis only)
|
NCT02244554
|
Comparison Study of Picosecond and Nanosecond Pulse Durations Using a Q-switched Nd:YAG Laser for Tattoo Removal
|
The purpose of this study is to evaluate the safety and efficacy of laser tattoo removal with picosecond pulse durations as compared to treatment with nanosecond pulse durations using a single novel Q-Switched (QS) Nd:YAG laser.
|
This is a randomized, split-tattoo, open-label, single-center study of up to 25 subjects with tattoos containing black or dark blue ink, alone or in combination with other colors. It will compare the safety and efficacy of nanosecond and picosecond pulse durations with the Cutera Picosecond Q-Switched Nd:YAG laser for tattoo removal.
|
Prospective, Open-Label Comparison Study of Picosecond and Nanosecond Pulse Durations Using a Q-switched Nd:YAG Laser for Tattoo Removal
|
Tattoo Removal
|
* Device: enLighten Laser
|
Inclusion Criteria:~Females or Males, 18 to 55 years of age (inclusive).~Fitzpatrick Skin Type I - VI.~Tattoos containing black/blue ink alone or in combination with other colors. No tribal, scarred, high-ink density, or highly colorful tattoos.~Target tattoos older than 1 year.~Must be able to read, understand and sign the Informed Consent Form.~Must be willing and able to adhere to the treatment and follow-up schedule and post-treatment care instructions.~Wiling to cover tattoos with a bandage or clothing; and/or have very limited sun exposure and use an approved sunscreen of SPF 50 or higher on the treated area starting 2 to 4 weeks before the treatment and/or every day for the duration of the study, including the follow-up period.~Willing to use hydroquinone approximately 4 weeks pre-treatment and post-treatment if required by Investigator.~Willingness to have digital photographs taken of the treated area.~Agree not to undergo any other procedure(s) for the tattoo removal during the study.~Post-menopausal or surgically sterilized, or using a medically acceptable form of birth control at least 3 months prior to enrollment and during the entire course of the study.~Exclusion Criteria:~Participation in a study of another device or drug within 6 months prior to enrollment or during the study.~History of allergic reaction to pigments following tattooing.~Presence of double tattoo in the treatment area or presence of tribal, scarred, high-ink density, or highly colorful single tattoos.~History of allergy to local anesthetics.~History of allergy to topical antibiotics.~History of malignant tumors in the target area.~Skin abnormalities in the target area, e.g., cuts, scrapes, wounds, scars, large moles.~Pregnant and/or breastfeeding.~Having an infection, dermatitis or a rash in the treatment area.~Significant concurrent illness, such as diabetes mellitus or cardiovascular disease, e.g., uncontrolled hypertension.~Suffering from coagulation disorders or taking prescription anticoagulation medications.~History of keloid scarring, hypertrophic scarring or of abnormal wound healing.~History of immunosuppression/immune deficiency disorders or currently using immunosuppressive medications.~History of vitiligo, eczema, or psoriasis.~History of connective tissue disease, such as systemic lupus erythematosus or scleroderma.~History of seizure disorders due to light.~Any use of medication that is known to increase sensitivity to light according to the Investigator's discretion.~History of herpes simplex and/or herpes zoster (shingles).~History of radiation to the treatment area or undergoing systemic chemotherapy for the treatment of cancer.~History of pigmentary disorders, particularly tendency for hyper- or hypo-pigmentation.~Systemic use of corticosteroid within 12 months of study participation.~Use of oral isotretinoin within 12 months of study participation and topical use of isotretinoin within 6 months on the treated area.~Anytime in life, having have used gold therapy (gold salts) for disorders such as rheumatologic disease or lupus.~Excessively tanned in areas to be treated or unable/unlikely to refrain from tanning during the study.~Current smoker or history of smoking within 6 months of study participation.~As per the Investigator's discretion, any physical or mental condition which might make it unsafe for the subject to participate in this study.
|
18 Years
|
55 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of Tattoo Clearing at 12 Weeks for Each Treatment Arm as Assessed by the Blinded Reviewers. | Physician's Global Assessment (min=0; Max=4) Higher scores indicate better outcomes | 12 weeks |
|
Nd:YAG laser, nanosecond laser, tattoo removal, Q-switched laser, picosecond laser, laser therapy, tattoo, pulsed-laser, laser treatment, remove tattoo, tattoo clearing, tattoo lightening, tattoo lighten, resistant tattoo
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: enLighten Laser Picosecond Pulse<br>Picosecond Pulse-duration with enLighten Q-switched Nd:YAG (1064 nm and 532 nm) laser treatment | Device: enLighten Laser<br>* Picosecond pulse-duration or Nanosecond pulse-duration tattoo treatment with enLighten Q-switched Laser Treatment<br>|
| Experimental: enLighten Laser Nanosecond Pulse<br>Nanosecond Pulse-duration with enLighten Q-switched Nd:YAG (1064 nm and 532 nm) laser treatment | Device: enLighten Laser<br>* Picosecond pulse-duration or Nanosecond pulse-duration tattoo treatment with enLighten Q-switched Laser Treatment<br>|
|
Comparison Study of Picosecond and Nanosecond Pulse Durations Using a Q-switched Nd:YAG Laser for Tattoo Removal
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety and efficacy of laser tattoo removal with picosecond pulse durations as compared to treatment with nanosecond pulse durations using a single novel Q-Switched (QS) Nd:YAG laser.
Detailed Description
-----------------
This is a randomized, split-tattoo, open-label, single-center study of up to 25 subjects with tattoos containing black or dark blue ink, alone or in combination with other colors. It will compare the safety and efficacy of nanosecond and picosecond pulse durations with the Cutera Picosecond Q-Switched Nd:YAG laser for tattoo removal.
Official Title
-----------------
Prospective, Open-Label Comparison Study of Picosecond and Nanosecond Pulse Durations Using a Q-switched Nd:YAG Laser for Tattoo Removal
Conditions
-----------------
Tattoo Removal
Intervention / Treatment
-----------------
* Device: enLighten Laser
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Females or Males, 18 to 55 years of age (inclusive). Fitzpatrick Skin Type I - VI. Tattoos containing black/blue ink alone or in combination with other colors. No tribal, scarred, high-ink density, or highly colorful tattoos. Target tattoos older than 1 year. Must be able to read, understand and sign the Informed Consent Form. Must be willing and able to adhere to the treatment and follow-up schedule and post-treatment care instructions. Wiling to cover tattoos with a bandage or clothing; and/or have very limited sun exposure and use an approved sunscreen of SPF 50 or higher on the treated area starting 2 to 4 weeks before the treatment and/or every day for the duration of the study, including the follow-up period. Willing to use hydroquinone approximately 4 weeks pre-treatment and post-treatment if required by Investigator. Willingness to have digital photographs taken of the treated area. Agree not to undergo any other procedure(s) for the tattoo removal during the study. Post-menopausal or surgically sterilized, or using a medically acceptable form of birth control at least 3 months prior to enrollment and during the entire course of the study. Exclusion Criteria: Participation in a study of another device or drug within 6 months prior to enrollment or during the study. History of allergic reaction to pigments following tattooing. Presence of double tattoo in the treatment area or presence of tribal, scarred, high-ink density, or highly colorful single tattoos. History of allergy to local anesthetics. History of allergy to topical antibiotics. History of malignant tumors in the target area. Skin abnormalities in the target area, e.g., cuts, scrapes, wounds, scars, large moles. Pregnant and/or breastfeeding. Having an infection, dermatitis or a rash in the treatment area. Significant concurrent illness, such as diabetes mellitus or cardiovascular disease, e.g., uncontrolled hypertension. Suffering from coagulation disorders or taking prescription anticoagulation medications. History of keloid scarring, hypertrophic scarring or of abnormal wound healing. History of immunosuppression/immune deficiency disorders or currently using immunosuppressive medications. History of vitiligo, eczema, or psoriasis. History of connective tissue disease, such as systemic lupus erythematosus or scleroderma. History of seizure disorders due to light. Any use of medication that is known to increase sensitivity to light according to the Investigator's discretion. History of herpes simplex and/or herpes zoster (shingles). History of radiation to the treatment area or undergoing systemic chemotherapy for the treatment of cancer. History of pigmentary disorders, particularly tendency for hyper- or hypo-pigmentation. Systemic use of corticosteroid within 12 months of study participation. Use of oral isotretinoin within 12 months of study participation and topical use of isotretinoin within 6 months on the treated area. Anytime in life, having have used gold therapy (gold salts) for disorders such as rheumatologic disease or lupus. Excessively tanned in areas to be treated or unable/unlikely to refrain from tanning during the study. Current smoker or history of smoking within 6 months of study participation. As per the Investigator's discretion, any physical or mental condition which might make it unsafe for the subject to participate in this study.
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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: enLighten Laser Picosecond Pulse<br>Picosecond Pulse-duration with enLighten Q-switched Nd:YAG (1064 nm and 532 nm) laser treatment | Device: enLighten Laser<br>* Picosecond pulse-duration or Nanosecond pulse-duration tattoo treatment with enLighten Q-switched Laser Treatment<br>|
| Experimental: enLighten Laser Nanosecond Pulse<br>Nanosecond Pulse-duration with enLighten Q-switched Nd:YAG (1064 nm and 532 nm) laser treatment | Device: enLighten Laser<br>* Picosecond pulse-duration or Nanosecond pulse-duration tattoo treatment with enLighten Q-switched Laser Treatment<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of Tattoo Clearing at 12 Weeks for Each Treatment Arm as Assessed by the Blinded Reviewers. | Physician's Global Assessment (min=0; Max=4) Higher scores indicate better outcomes | 12 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nd:YAG laser, nanosecond laser, tattoo removal, Q-switched laser, picosecond laser, laser therapy, tattoo, pulsed-laser, laser treatment, remove tattoo, tattoo clearing, tattoo lightening, tattoo lighten, resistant tattoo
|
||
NCT01879488
|
Effect of Ventilation Mode on Lung Deposition of a Radiolabeled Aerosol During Mechanical Ventilation: Barometric Versus Volumetric
|
Controlling the respiratory pattern of mechanically ventilated patients in volume control mode is recommended during nebulization. No studies looked into conditions of nebulization during assisted mechanical ventilation to define the optimal nebulization technique and its effect on pulmonary deposition.~The aim of this study is to analyse the effect of ventilation mode (barometric versus volumetric) on deposition by planar scintigraphy during mechanical ventilation.
| null |
Post-operative Neurosurgery
|
* Drug: technetium-99m - Diethylenetriaminepentaacetic acid
* Device: Vibrating-mesh nebulizer
* Other: Gamma scintigraphy
* Other: Preoperative spirometry
|
Inclusion Criteria:~Invasive mechanical ventilation~Healthy lungs~Exclusion Criteria:~Change of ventilation mode during nebulization
|
18 Years
|
90 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary deposition | | Immediately after nebulization by imaging assessment, an expected average of 30 minutes |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Penetration index | | Immediately after nebulization by imaging assessment, an expected average of 30 minutes |
| Mechanical ventilation settings | | During nebulisation time, an expected average of 15 minutes |
| Lung function | | Preoperative assessment, the day before inclusion |
|
Aerosol, Lung deposition, Mechanical ventilation
|
Sequestering Agents, Molecular Mechanisms of Pharmacological Action, Iron Chelating Agents, Calcium Chelating Agents, Edetic Acid, Pentetic Acid, Antidotes, Protective Agents, Physiological Effects of Drugs, Chelating Agents, Anticoagulants
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nebulization during pressure support ventilation<br>Patients ventilated in pressure support mode during nebulization | Drug: technetium-99m - Diethylenetriaminepentaacetic acid<br> <br> Device: Vibrating-mesh nebulizer<br> <br> Other: Gamma scintigraphy<br> <br> Other: Preoperative spirometry<br> <br> |
| Active Comparator: Nebulization during volume assist control mode<br>Patients ventilated in volume assist control mode during nebulization | Drug: technetium-99m - Diethylenetriaminepentaacetic acid<br> <br> Device: Vibrating-mesh nebulizer<br> <br> Other: Gamma scintigraphy<br> <br> Other: Preoperative spirometry<br> <br> |
|
Effect of Ventilation Mode on Lung Deposition of a Radiolabeled Aerosol During Mechanical Ventilation: Barometric Versus Volumetric
Study Overview
=================
Brief Summary
-----------------
Controlling the respiratory pattern of mechanically ventilated patients in volume control mode is recommended during nebulization. No studies looked into conditions of nebulization during assisted mechanical ventilation to define the optimal nebulization technique and its effect on pulmonary deposition. The aim of this study is to analyse the effect of ventilation mode (barometric versus volumetric) on deposition by planar scintigraphy during mechanical ventilation.
Conditions
-----------------
Post-operative Neurosurgery
Intervention / Treatment
-----------------
* Drug: technetium-99m - Diethylenetriaminepentaacetic acid
* Device: Vibrating-mesh nebulizer
* Other: Gamma scintigraphy
* Other: Preoperative spirometry
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Invasive mechanical ventilation Healthy lungs Exclusion Criteria: Change of ventilation mode during nebulization
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?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nebulization during pressure support ventilation<br>Patients ventilated in pressure support mode during nebulization | Drug: technetium-99m - Diethylenetriaminepentaacetic acid<br> <br> Device: Vibrating-mesh nebulizer<br> <br> Other: Gamma scintigraphy<br> <br> Other: Preoperative spirometry<br> <br> |
| Active Comparator: Nebulization during volume assist control mode<br>Patients ventilated in volume assist control mode during nebulization | Drug: technetium-99m - Diethylenetriaminepentaacetic acid<br> <br> Device: Vibrating-mesh nebulizer<br> <br> Other: Gamma scintigraphy<br> <br> Other: Preoperative spirometry<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary deposition | | Immediately after nebulization by imaging assessment, an expected average of 30 minutes |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Penetration index | | Immediately after nebulization by imaging assessment, an expected average of 30 minutes |
| Mechanical ventilation settings | | During nebulisation time, an expected average of 15 minutes |
| Lung function | | Preoperative assessment, the day before inclusion |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aerosol, Lung deposition, Mechanical ventilation
|
|
NCT00526903
|
Recurrent Abdominal Pain in Children
|
The purpose of this study is to:~To determine if fiber versus placebo improves symptoms in children with recurrent abdominal pain/irritable bowel syndrome.~To determine possible ways fiber or placebo improve(s) symptoms in children with recurrent abdominal pain/irritable bowel syndrome by carrying out gastrointestinal tests and questionnaires.~Understanding how diet and fiber affect GI function potentially will benefit the large numbers of children with irritable bowel syndrome (IBS) and provide insight into prevention of IBS in at risk children. We expect that the results from these studies can be used to lessen significantly the huge financial burden to society caused by these chronic conditions.~Consent will be obtained from the parent/guardian and assent from the child.
|
Children with recurrent abdominal pain (RAP) who meet the criteria for irritable bowel syndrome (IBS) will be recruited and studied. They will have been diagnosed by a pediatric gastroenterologist and will have had at least one healthcare visits in the past year for the complaint of abdominal pain.~Coordinators will come out to the family's home on an evening that is convenient. Both the parent and child will fill out some questionnaires. Next, the parent and child will get instructions on how to fill out a diary to record any stomach pain the child is having and what their stools look like. The child will also collect a stool sample during the regular diet and diary collection period. Once the child has completed the diary, the child will go on a special diet for eight days to remove foods that may cause stomach pain (foods and drinks containing lactose, fructose, and sorbitol will be eliminated).~Two weeks later, the coordinators will come out to the family's home again to review the pain and stool diary that the child kept while on the special diet. The coordinators will explain how to collect some samples of urine, stool, and breath. These tests will evaluate the gastrointestinal (GI) tract for inflammation and transit time. If the special diet does not make the stomach pain go away, the child will be selected at random, like the flip of a coin, to be placed in one of two groups: one group that receives fiber or one group that receives a placebo or sugar pill. Fiber has been suggested to help children with stomach pain.~After the child has been on the treatment for 6 weeks, he/she will keep another diary and collect another set of samples of urine, stool, and breath.~The children will be followed at 3 months, 6 months and 18 months after the treatment period.~Children will be asked to collect additional stools
|
Recurrent Abdominal Pain in Children
|
Abdominal Pain, Irritable Bowel Syndrome
|
* Behavioral: Elimination Diet
|
Inclusion Criteria:~Children who have had at least one physician visit in the past year for abdominal pain or IBS symptoms.~Children with recurrent abdominal pain who meet the criteria for irritable bowel syndrome.~Exclusion Criteria:~Children who have another disease that accounts for stomach pain~Current use of anti-inflammatory medication~Children taking a GI medication that makes pain go away completely~Children with other chronic conditions including chronic pain conditions (e.g. heart condition, diabetes)~Children who have decreased growth~GI blood loss~Unexplained fever~Chronic severe diarrhea~Weight loss of > or = to 5% of body weight within 3 month prior to enrollment~History of abdominal surgeries~A history of suicide~Cognitive impairment significantly below average age and/or grade level~Non-English speaking parent or child~Vomiting >2x/month~Children currently in psychotherapy for abdominal pain.
|
7 Years
|
18 Years
|
All
|
No
|
Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in pain and stooling symptoms | | The last two weeks of treatment and up to 18 months after treatment |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Child anxiety, somatization, and coping | | Four weeks prior to treatment and 6 months after treatment |
| Parental somatization, coping, and illness interaction | | Four weeks prior to treatment and 6 months after treatment |
| Changes in GI Transit time | | Prior to and after treatment |
| Changes in Breath Hydrogen production | | Prior to and after treatment |
| Changes in GI Permeability | | Prior to and after treatment |
| Changes in fecal calprotectin concentration | | Prior to and after treatment |
|
IBS, abdominal pain, recurrent abdominal pain, irritable bowel syndrome, diarrhea, constipation, bloating
|
Irritable Bowel Syndrome, Abdominal Pain, Colonic Diseases, Functional, Colonic Diseases, Intestinal Diseases, Gastrointestinal Diseases, Digestive System Diseases, Pain, Neurologic Manifestations, Signs and Symptoms, Digestive
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fiber<br>Fiber added to diet for a total of 6 weeks. | Behavioral: Elimination Diet<br>* Daily diet change for 8 days.<br>|
| Placebo Comparator: Placebo<br>Placebo powder taken for a total of 6 weeks. | Behavioral: Elimination Diet<br>* Daily diet change for 8 days.<br>|
|
Recurrent Abdominal Pain in Children
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to: To determine if fiber versus placebo improves symptoms in children with recurrent abdominal pain/irritable bowel syndrome. To determine possible ways fiber or placebo improve(s) symptoms in children with recurrent abdominal pain/irritable bowel syndrome by carrying out gastrointestinal tests and questionnaires. Understanding how diet and fiber affect GI function potentially will benefit the large numbers of children with irritable bowel syndrome (IBS) and provide insight into prevention of IBS in at risk children. We expect that the results from these studies can be used to lessen significantly the huge financial burden to society caused by these chronic conditions. Consent will be obtained from the parent/guardian and assent from the child.
Detailed Description
-----------------
Children with recurrent abdominal pain (RAP) who meet the criteria for irritable bowel syndrome (IBS) will be recruited and studied. They will have been diagnosed by a pediatric gastroenterologist and will have had at least one healthcare visits in the past year for the complaint of abdominal pain. Coordinators will come out to the family's home on an evening that is convenient. Both the parent and child will fill out some questionnaires. Next, the parent and child will get instructions on how to fill out a diary to record any stomach pain the child is having and what their stools look like. The child will also collect a stool sample during the regular diet and diary collection period. Once the child has completed the diary, the child will go on a special diet for eight days to remove foods that may cause stomach pain (foods and drinks containing lactose, fructose, and sorbitol will be eliminated). Two weeks later, the coordinators will come out to the family's home again to review the pain and stool diary that the child kept while on the special diet. The coordinators will explain how to collect some samples of urine, stool, and breath. These tests will evaluate the gastrointestinal (GI) tract for inflammation and transit time. If the special diet does not make the stomach pain go away, the child will be selected at random, like the flip of a coin, to be placed in one of two groups: one group that receives fiber or one group that receives a placebo or sugar pill. Fiber has been suggested to help children with stomach pain. After the child has been on the treatment for 6 weeks, he/she will keep another diary and collect another set of samples of urine, stool, and breath. The children will be followed at 3 months, 6 months and 18 months after the treatment period. Children will be asked to collect additional stools
Official Title
-----------------
Recurrent Abdominal Pain in Children
Conditions
-----------------
Abdominal Pain, Irritable Bowel Syndrome
Intervention / Treatment
-----------------
* Behavioral: Elimination Diet
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Children who have had at least one physician visit in the past year for abdominal pain or IBS symptoms. Children with recurrent abdominal pain who meet the criteria for irritable bowel syndrome. Exclusion Criteria: Children who have another disease that accounts for stomach pain Current use of anti-inflammatory medication Children taking a GI medication that makes pain go away completely Children with other chronic conditions including chronic pain conditions (e.g. heart condition, diabetes) Children who have decreased growth GI blood loss Unexplained fever Chronic severe diarrhea Weight loss of > or = to 5% of body weight within 3 month prior to enrollment History of abdominal surgeries A history of suicide Cognitive impairment significantly below average age and/or grade level Non-English speaking parent or child Vomiting >2x/month Children currently in psychotherapy for abdominal pain.
Ages Eligible for Study
-----------------
Minimum Age: 7 Years
Maximum 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
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fiber<br>Fiber added to diet for a total of 6 weeks. | Behavioral: Elimination Diet<br>* Daily diet change for 8 days.<br>|
| Placebo Comparator: Placebo<br>Placebo powder taken for a total of 6 weeks. | Behavioral: Elimination Diet<br>* Daily diet change for 8 days.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in pain and stooling symptoms | | The last two weeks of treatment and up to 18 months after treatment |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Child anxiety, somatization, and coping | | Four weeks prior to treatment and 6 months after treatment |
| Parental somatization, coping, and illness interaction | | Four weeks prior to treatment and 6 months after treatment |
| Changes in GI Transit time | | Prior to and after treatment |
| Changes in Breath Hydrogen production | | Prior to and after treatment |
| Changes in GI Permeability | | Prior to and after treatment |
| Changes in fecal calprotectin concentration | | Prior to and after treatment |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
IBS, abdominal pain, recurrent abdominal pain, irritable bowel syndrome, diarrhea, constipation, bloating
|
NCT02274935
|
Cognitive Motor Interference Rehabilitation in Persons With Multiple Sclerosis
|
This study examines the effect of balance and walking exercise on cognition and mobility in people with Multiple Sclerosis.
|
Walking and cognitive impairments are common in persons with multiple sclerosis (MS). Approximately 85% of persons with MS report walking as a major limitation, whereas 65% experience cognitive dysfunction. Traditionally, walking and cognition have been viewed as unrelated, but there is evidence of cognitive-motor interference (CMI). CMI is believed to stem from damage to common neural tracts. Recent evidence supports cognitive-motor interference in persons with MS. For example, there is evidence that walking performance declines when performed in conjunction with a simultaneous cognitive task (i.e., dual task cost [DTC] of walking) and this decline in walking performance is greater in persons with MS compared to healthy controls. This elevated cognitive-motor interference during walking is mainly associated with walking performance in persons with MS although cognitive function does play a role. Cognitive-motor interference during mobility tasks is of practical and clinical importance because it has been linked to decreased community mobility and a greater risk of falls in other clinical populations. Despite the adverse consequences of elevated CMI there is ambiguity concerning prevention and rehabilitation strategies for cognitive-motor interference in individuals with MS.~This study seeks to examine whether single and/or targeted dual task rehabilitation has a beneficial effect on CMI in individuals with MS. The results of this investigation will provide the foundation for future rehabilitation-based randomized control trials seeking to improve walking and cognitive function in persons with MS.
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Cognitive Motor Interference Rehabilitation in Persons With Multiple Sclerosis
|
Multiple Sclerosis
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* Other: Exercise
|
Inclusion Criteria:Physician diagnosed MS, relapse free for 30 days, self reporting problems with multitasking -~Exclusion Criteria:We will exclude all individuals with risk factors contra-indicative for undertaking strenuous exercise. Participants will verbally respond to a health history questionnaire. Those individuals who are asymptomatic and meet no more than one risk factor threshold including family history of coronary heart disease, cigarette smoking, hypertension, high cholesterol, diabetes, obesity, and sedentary lifestyle will be considered at low risk and included for participation.~-
|
18 Years
|
64 Years
|
All
|
No
|
Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive Motor interference | This will be operationalized as the percent change in walking velocity from single (walking only) to dual task (walking while thinking). Participants will complete a total of 8 walking trials over a 20' pressure sensitive (Zeno™) walkway. Four at a comfortable walking speed and four as fast as possible. Half of the trials at each speed will be conducted while reciting every other letter of the alphabet (i.e. N, P, R, etc). | 12 weeks |
|
Sclerosis, Multiple Sclerosis, Pathologic Processes, Demyelinating Autoimmune Diseases, CNS, Autoimmune Diseases of the Nervous System, Nervous System Diseases, Demyelinating Diseases, Autoimmune Diseases, Immune System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gait and balance exercise<br>Traditional exercises focusing on gait and balance | Other: Exercise<br>* Balance and gait exercise twice a week for an hour<br>* Other names: Physical Rehabilitation;|
| Experimental: Cognitive training and physical exercise<br>Gait and balance exercises done in combination with cognitive training (i.e. counting backwards by 7s from 98) | Other: Exercise<br>* Balance and gait exercise twice a week for an hour<br>* Other names: Physical Rehabilitation;|
|
Cognitive Motor Interference Rehabilitation in Persons With Multiple Sclerosis
Study Overview
=================
Brief Summary
-----------------
This study examines the effect of balance and walking exercise on cognition and mobility in people with Multiple Sclerosis.
Detailed Description
-----------------
Walking and cognitive impairments are common in persons with multiple sclerosis (MS). Approximately 85% of persons with MS report walking as a major limitation, whereas 65% experience cognitive dysfunction. Traditionally, walking and cognition have been viewed as unrelated, but there is evidence of cognitive-motor interference (CMI). CMI is believed to stem from damage to common neural tracts. Recent evidence supports cognitive-motor interference in persons with MS. For example, there is evidence that walking performance declines when performed in conjunction with a simultaneous cognitive task (i.e., dual task cost [DTC] of walking) and this decline in walking performance is greater in persons with MS compared to healthy controls. This elevated cognitive-motor interference during walking is mainly associated with walking performance in persons with MS although cognitive function does play a role. Cognitive-motor interference during mobility tasks is of practical and clinical importance because it has been linked to decreased community mobility and a greater risk of falls in other clinical populations. Despite the adverse consequences of elevated CMI there is ambiguity concerning prevention and rehabilitation strategies for cognitive-motor interference in individuals with MS. This study seeks to examine whether single and/or targeted dual task rehabilitation has a beneficial effect on CMI in individuals with MS. The results of this investigation will provide the foundation for future rehabilitation-based randomized control trials seeking to improve walking and cognitive function in persons with MS.
Official Title
-----------------
Cognitive Motor Interference Rehabilitation in Persons With Multiple Sclerosis
Conditions
-----------------
Multiple Sclerosis
Intervention / Treatment
-----------------
* Other: Exercise
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria:Physician diagnosed MS, relapse free for 30 days, self reporting problems with multitasking - Exclusion Criteria:We will exclude all individuals with risk factors contra-indicative for undertaking strenuous exercise. Participants will verbally respond to a health history questionnaire. Those individuals who are asymptomatic and meet no more than one risk factor threshold including family history of coronary heart disease, cigarette smoking, hypertension, high cholesterol, diabetes, obesity, and sedentary lifestyle will be considered at low risk and included for participation. -
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: Health Services Research
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gait and balance exercise<br>Traditional exercises focusing on gait and balance | Other: Exercise<br>* Balance and gait exercise twice a week for an hour<br>* Other names: Physical Rehabilitation;|
| Experimental: Cognitive training and physical exercise<br>Gait and balance exercises done in combination with cognitive training (i.e. counting backwards by 7s from 98) | Other: Exercise<br>* Balance and gait exercise twice a week for an hour<br>* Other names: Physical Rehabilitation;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive Motor interference | This will be operationalized as the percent change in walking velocity from single (walking only) to dual task (walking while thinking). Participants will complete a total of 8 walking trials over a 20' pressure sensitive (Zeno™) walkway. Four at a comfortable walking speed and four as fast as possible. Half of the trials at each speed will be conducted while reciting every other letter of the alphabet (i.e. N, P, R, etc). | 12 weeks |
|
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NCT01824160
|
Pulmonary Artery Repair With Covered Stents
|
The Covered Cheatham-Platinum Stent (CCPS) is being study for repair of tears that occur in the pulmonary artery during dilation (enlargement) of a conduit (passageway) connecting the right ventricle of the heart to the pulmonary arteries. Patients undergoing replacement of their pulmonary valve by transcatheter technique Melody Valve) are at risk of developing such tears in the process of preparing the conduit to accept the new valve. In order to implant such a valve, the connection between the right ventricle and the pulmonary arteries often needs to be enlarged. High pressure balloons may be needed and these balloons can sometimes cause tears in or even rupture of the connecting conduit. Such tears can allow blood to flow into the chest and rarely this can lead to a life-threatening emergency. Experience suggests that such tears can be closed by implanting into the conduit a metallic stent with an outer covering, rebuilding the wall and allowing continuation of the valve implant.
|
Recent clinical reports from multiple pediatric cardiology programs around the world indicate that the conduit can be repaired using such a stent. In the United States there are no commercially available, FDA approved, covered stents of the size required. The Covered Cheatham Platinum Stent (CCPS) manufactured by the NuMED Corporation of Hopkinton, New York has been used in Europe since 2003 and more recently in Canada. The CCPS device is not yet approved by the Food & Drug Administration (FDA). However, it has been used at many hospitals in the U.S. to repair Right Ventricle to pulmonary artery conduits under Emergency and Compassionate Use circumstances. The NuMED Covered Cheatham-Platinum Stent (CCPS) is currently being studied for use in other areas of the body. The investigators are now studying its use in RV-PA conduits. The use of the Covered Cheatham Platinum Stent in this research study is investigational.~Only patients found to have a conduit tear during a Melody Valve implant procedure will be eligible for inclusion into the trial. Implant technique is left to the catheterization physician. Clinical data obtained during the catheterization, before and after the CCPS implant will be studied in order to understand factors leading up to the tear and to evaluate how successful the CCPS is in repairing such defects. Melody valve implant patients are routinely seen for clinical and echocardiographic reevaluation 6 months after implant. Patients who have received a CCPS during their Melody valve procedure will likewise be seen. Results from their clinical evaluation will be reviewed to make sure that the presence of a CCPS does not diminish the effectiveness of the Melody valve. Finally, the catheterization angiograms and 6 month follow up echocardiograms will be reviewed by an independent expert to confirm the clinical readings.
|
Pulmonary Artery Repair With Covered Stents
|
Pulmonary Stenosis, Pulmonary Regurgitation, Tetralogy of Fallot
|
* Device: Repair of RV-PA Conduit Disruption
|
Inclusion Criteria:~Precatheterization Inclusion Criteria:~Patient meets institutional criterion for placement of Melody® TPV~Patient size adequate to receive Melody TPV® implantation via venous access using the Ensemble® Transcatheter Delivery System~RV-PA conduit original size > 16 mm diameter~Patient age between 10 and 75 years~Catheterization Inclusion Criteria:~a. Angiographic evidence for RV-PA conduit disruption including: dissection, aneurysm, pseudo-aneurysm, tears or rupture~Recognition and treatment of conduit disruption may occur before, during or after implantation of the Melody® TPV~Conduit disruption related to prior intervention, identified angiographically before conduit dilation is performed during the Melody® implant procedure, can be eligible for CCPS implantation and study inclusion~Exclusion Criteria:~Precatheterization Exclusion Criteria:~Patient size too small for transvenous placement of the Melody® TPV~Bloodstream infection, including endocarditis~Pregnancy~Prisoners and adults lacking the capacity to give consent~Catheterization Exclusion Criteria:~Conduit size is not suitable (too small or too large) for a Melody® TPV~Risk of coronary compression has been identified~Lack of angiographic evidence for RV-PA conduit disruption - Prophylactic use of study CCPS is prohibited~Vessel injury occurring in either the right or left branch pulmonary arteries -If injury to branch pulmonary arteries occurs during the catheterization and covered stent usage is indicated, Emergency Use guidelines must be employed
|
7 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful Repair of Conduit Disruption | Successfully cover a tear or disruption in a RV-PA conduit wall and prevent the development of rupture or bleeding into the mediastinum during additional enlargement of the conduit. Provide persistent conduit wall integrity.~A severity of illness scale categorizes the degree of clinical illness at baseline to be compared to the remaining level of illness after placement of the Covered CP Stent (CCPS). We assess the number of participants with minimal level of illness (level 0 to 1) after CCPS placement.~0 = No injury or conduit wall disruption~= Contained disruption~= Partially contained disruption~= Uncontained conduit disruption | Implant of Covered Stent and 6 month follow up |
|
Tetralogy of Fallot, Pulmonary Valve Stenosis, Pulmonary Valve Insufficiency, Heart Defects, Congenital, Cardiovascular Abnormalities, Cardiovascular Diseases, Heart Diseases, Congenital Abnormalities, Heart Valve Diseases, Ventricular Outflow Obstruction
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Repair of RV-PA Conduit Disruption<br>Covered stenting of RV-PA conduit injury | Device: Repair of RV-PA Conduit Disruption<br>* Repair of RV-PA Conduit Disruption<br>|
|
Pulmonary Artery Repair With Covered Stents
Study Overview
=================
Brief Summary
-----------------
The Covered Cheatham-Platinum Stent (CCPS) is being study for repair of tears that occur in the pulmonary artery during dilation (enlargement) of a conduit (passageway) connecting the right ventricle of the heart to the pulmonary arteries. Patients undergoing replacement of their pulmonary valve by transcatheter technique Melody Valve) are at risk of developing such tears in the process of preparing the conduit to accept the new valve. In order to implant such a valve, the connection between the right ventricle and the pulmonary arteries often needs to be enlarged. High pressure balloons may be needed and these balloons can sometimes cause tears in or even rupture of the connecting conduit. Such tears can allow blood to flow into the chest and rarely this can lead to a life-threatening emergency. Experience suggests that such tears can be closed by implanting into the conduit a metallic stent with an outer covering, rebuilding the wall and allowing continuation of the valve implant.
Detailed Description
-----------------
Recent clinical reports from multiple pediatric cardiology programs around the world indicate that the conduit can be repaired using such a stent. In the United States there are no commercially available, FDA approved, covered stents of the size required. The Covered Cheatham Platinum Stent (CCPS) manufactured by the NuMED Corporation of Hopkinton, New York has been used in Europe since 2003 and more recently in Canada. The CCPS device is not yet approved by the Food & Drug Administration (FDA). However, it has been used at many hospitals in the U.S. to repair Right Ventricle to pulmonary artery conduits under Emergency and Compassionate Use circumstances. The NuMED Covered Cheatham-Platinum Stent (CCPS) is currently being studied for use in other areas of the body. The investigators are now studying its use in RV-PA conduits. The use of the Covered Cheatham Platinum Stent in this research study is investigational. Only patients found to have a conduit tear during a Melody Valve implant procedure will be eligible for inclusion into the trial. Implant technique is left to the catheterization physician. Clinical data obtained during the catheterization, before and after the CCPS implant will be studied in order to understand factors leading up to the tear and to evaluate how successful the CCPS is in repairing such defects. Melody valve implant patients are routinely seen for clinical and echocardiographic reevaluation 6 months after implant. Patients who have received a CCPS during their Melody valve procedure will likewise be seen. Results from their clinical evaluation will be reviewed to make sure that the presence of a CCPS does not diminish the effectiveness of the Melody valve. Finally, the catheterization angiograms and 6 month follow up echocardiograms will be reviewed by an independent expert to confirm the clinical readings.
Official Title
-----------------
Pulmonary Artery Repair With Covered Stents
Conditions
-----------------
Pulmonary Stenosis, Pulmonary Regurgitation, Tetralogy of Fallot
Intervention / Treatment
-----------------
* Device: Repair of RV-PA Conduit Disruption
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Precatheterization Inclusion Criteria: Patient meets institutional criterion for placement of Melody® TPV Patient size adequate to receive Melody TPV® implantation via venous access using the Ensemble® Transcatheter Delivery System RV-PA conduit original size > 16 mm diameter Patient age between 10 and 75 years Catheterization Inclusion Criteria: a. Angiographic evidence for RV-PA conduit disruption including: dissection, aneurysm, pseudo-aneurysm, tears or rupture Recognition and treatment of conduit disruption may occur before, during or after implantation of the Melody® TPV Conduit disruption related to prior intervention, identified angiographically before conduit dilation is performed during the Melody® implant procedure, can be eligible for CCPS implantation and study inclusion Exclusion Criteria: Precatheterization Exclusion Criteria: Patient size too small for transvenous placement of the Melody® TPV Bloodstream infection, including endocarditis Pregnancy Prisoners and adults lacking the capacity to give consent Catheterization Exclusion Criteria: Conduit size is not suitable (too small or too large) for a Melody® TPV Risk of coronary compression has been identified Lack of angiographic evidence for RV-PA conduit disruption - Prophylactic use of study CCPS is prohibited Vessel injury occurring in either the right or left branch pulmonary arteries -If injury to branch pulmonary arteries occurs during the catheterization and covered stent usage is indicated, Emergency Use guidelines must be employed
Ages Eligible for Study
-----------------
Minimum Age: 7 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 |
| --- | --- |
| Other: Repair of RV-PA Conduit Disruption<br>Covered stenting of RV-PA conduit injury | Device: Repair of RV-PA Conduit Disruption<br>* Repair of RV-PA Conduit Disruption<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful Repair of Conduit Disruption | Successfully cover a tear or disruption in a RV-PA conduit wall and prevent the development of rupture or bleeding into the mediastinum during additional enlargement of the conduit. Provide persistent conduit wall integrity. A severity of illness scale categorizes the degree of clinical illness at baseline to be compared to the remaining level of illness after placement of the Covered CP Stent (CCPS). We assess the number of participants with minimal level of illness (level 0 to 1) after CCPS placement. 0 = No injury or conduit wall disruption = Contained disruption = Partially contained disruption = Uncontained conduit disruption | Implant of Covered Stent and 6 month follow up |
|
||
NCT05233436
|
PF-07265028 As Single Agent And In Combination With Sasanlimab in Advanced or Metastatic Solid Tumors
|
The purpose of this study is to assess the safety and effects of PF-07265028 as monotherapy and in combination with sasanlimab.~The study aims to identify the maximum tolerated dose (MTD) of PF-07265028 as monotherapy; evaluate the clinical activity of monotherapy and combination; and select the recommended dose of PF-07265028 monotherapy and in combination for potential further studies and development.~The study contains 2 parts, Dose Escalation (Part 1) to determine the recommended dose of PF-07265028 as single agent and in combination, followed by Dose Expansion (Part 2) in selected tumor types at the recommended dose.~It is expected that most participants will take part in this study for up to 1 year with six on-site visits in the first month and then at least twice every subsequent month while they are on treatment.
|
The purpose of this first-in-human study is to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of increasing doses of PF-07265028 as monotherapy and in combination with sasanlimab; identify the maximum tolerated dose (MTD) of PF-07265028 monotherapy; evaluate the clinical activity of monotherapy and combination; and select the recommended dose of PF-07265028 monotherapy and in combination for potential further studies and development. The study contains 2 parts, Dose Escalation (Part 1) to determine the recommended dose of PF-07265028 as single agent and in combination, followed by Dose Expansion (Part 2) in selected tumor types at the recommended dose.
|
A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND EXPANSION STUDY OF PF-07265028 AS A SINGLE AGENT AND IN COMBINATION WITH SASANLIMAB EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTI-TUMOR ACTIVITY OF PF-07265028 IN PARTICIPANTS WITH ADVANCED OR METASTATIC SOLID TUMORS
|
Advanced Solid Tumors, Gastric Cancer, Gastroesophageal Junction Cancer, Urothelial Cancer, Non Small Cell Lung Cancer, Head and Neck Squamous Cell Carcinomas
|
* Drug: PF-07265028
* Biological: Sasanlimab
|
Key Inclusion Criteria:~Across all cohorts:~Eastern Cooperative Oncology Group (ECOG) performance status ≤1~Adequate hematological, kidney and liver function~Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.~Resolved acute effects of any prior therapy~All participants must provide archival formalin-fixed paraffin-embedded (FFPE) tumor tissue:~Part 1: If archival sample is older than 6 months, the participant must consent to undergo a fresh biopsy during the screening.~Part 2 Fresh tumor biopsy during screening is required unless there is archival tissues less than 3 months old and subsequent to the last systemic anti-cancer therapy.~Part 1A Monotherapy:~Histologically or cytologically confirmed advanced or metastatic solid tumors which have progressed following systemic anticancer therapies, or are resistant to standard therapy or for which no standard therapy is available, or for whom standard therapy is not tolerated.~Part 1B Combination Therapy:~Histologically or cytologically confirmed advanced or metastatic solid tumor which have progressed following systemic anticancer therapies, including at least 1 checkpoint inhibitor.~Part 2 Dose Expansion:~Histologically or cytologically confirmed advanced or metastatic malignancies, including gastric/Gastroesophageal junction cancer, Head and neck squamous cell carcinoma, or urothelial cancer (non-small cell lung cancer and other solid tumors may be included) who have progressed following systemic anticancer therapies, including at least 1 checkpoint inhibitor~Key Exclusion Criteria:~Participants with any other active malignancy within 3 years prior to enrollment~Participants with active autoimmune conditions or history of autoimmune diseases that may relapse~History of interstitial lung disease, pneumonitis (non-infectious) or uncontrolled lung diseases~History of prior immune-related adverse events (irAEs) Grade ≥3~Central nervous system metastases~Significant cardiac or pulmonary conditions or events within previous 6 months~Active, uncontrolled bacterial, fungal, or viral infection~Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PF-07265028~Prior administration of HPK1 inhibitor
|
18 Years
|
99 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Dose-limiting toxicities (DLTs) in Dose Escalation (Part 1) | DLTs will be evaluated during Cycle 1 (a cycle is 28 days) in Part 1. The number of DLTs will be used to determine the optimal dose | Cycle 1 (28 days) |
| Number of participants with adverse events (AEs) | AEs characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 5.0), timing, seriousness, and relationship to study therapy. | Baseline through up to 2 years |
| Number of participants with clinically significant laboratory abnormalities | Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing. | Baseline through up to 2 years |
| Objective response rate (ORR) in Dose Expansion (Part 2) | Tumor response based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Baseline through up to 2 years or until disease progression |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through Cmax. | Maximum observed plasma concentration of PF-07265028 (Cmax) and Maximum observed steady state plasma concentration (Cmax, ss) | Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) |
| The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through Tmax. | Time to maximal observed plasma concentration of PF-07265028 (Tmax) and Time to reach Maximum Observed Steady State Plasma Concentration (Tmax,ss). | Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) |
| The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through AUC | Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-07265028 and area under the curve within one dose interval at steady state (AUCtau,ss) | Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) |
| The effect of food on the pharmacokinetic profile of PF-07265028 through Cmax. | Maximum observed plasma concentration of PF-07265028 (Cmax) under fasted and fed conditions in the subset of participants | Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) |
| The effect of food on the pharmacokinetic profile of PF-07265028 through Tmax | Time to maximal observed plasma concentration of PF-07265028 (Tmax) under fasted and fed conditions in the subset of participants | Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) |
| The effect of food on the pharmacokinetic profile of PF-07265028 through AUC | Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-07265028 under fasted and fed conditions in the subset of participants | Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) |
| The pharmacokinetic profile of sasanlimab when given in combination with PF-07265028 through Cmin | Minimum plasma concentration (Cmin) will be calculated through the measured pre-dose plasma concentration | Day 1 of cycle 1 (each cycle is 28 days), Day 1 of cycle 2, Day 1 of cycle 3, Day 1 of cycle 5 and thereafter every 6 cycles (each cycle is 28 days) |
| The immunogenicity of sasanlimab when given in combination with PF-07265028 through ADA and NAb | Incidence and titers of anti-drug antibodies (ADA) and neutralizing antibodies (NAb) against sasanlimab | Day 1 of cycle 1 (each cycle is 28 days), Day 1 of cycle 2, Day 1 of cycle 3, Day 1 of cycle 5 and thereafter every 6 cycles (each cycle is 28 days) |
| The effect of PF-07265028 alone and in combination with sasanlimab on tumor immune biomarkers modulation | Levels of intratumor T cells and PD-L1 expression in pre- and post-treatment tumor biopsies | Baseline through up to 2 years |
| ORR in Dose Escalation (Part 1) | Tumor response assessment based on RECIST 1.1 | From baseline through disease progression or study completion (approximately 2 years) |
| Time to event endpoints (DOR) in Dose Expansion (Part 2) | Duration of response (DOR) as assessed using RECIST 1.1. | From baseline through disease progression or study completion (approximately 2 years) |
| Time to event endpoints (PFS) in Dose Expansion (Part 2) | Progression free survival (PFS) as assessed using RECIST 1.1. | From baseline through disease progression or study completion (approximately 2 years) |
| Time to event endpoints (OS) in Dose Expansion (Part 2) | Overall survival (OS) assessed proportion of patients alive | From baseline through disease progression or study completion (approximately 2 years) |
|
immunotherapy, advanced solid tumor, metastatic solid tumor, first in human, Gastric cancer, Gastroesophageal junction cancer, Urothelial Cancer, Non small cell lung cancer, Head and neck squamous cell carcinomas, SCCHN, NSCLC, Lung cancer, Hematopoietic progenitor kinase 1 inhibitor, HPK1 inhibitor
|
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Stomach Neoplasms, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Neoplasms, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Neoplasms, Squamous Cell, Gastrointestinal Neoplasms, Digestive System Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Stomach Diseases, Head and Neck Neoplasms
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1A Dose Escalation Monotherapy<br>Participants will receive PF-07265028 at escalating dose levels. | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>|
| Experimental: Part 1B Dose Escalation Combination<br>Participants will receive PF-07265028 at escalating dose levels in combination with sasanlimab fixed dose | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>Biological: Sasanlimab<br>* Administered subcutaneously<br>* Other names: PF-06801591;|
| Experimental: Part 2A Dose Expansion Combination (SCCHN)<br>Participants with squamous cell carcinoma of the head and neck (SCCHN) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>Biological: Sasanlimab<br>* Administered subcutaneously<br>* Other names: PF-06801591;|
| Experimental: Part 2A Dose Expansion Combination (UC)<br>Participants with urothelial cancer (UC) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>Biological: Sasanlimab<br>* Administered subcutaneously<br>* Other names: PF-06801591;|
| Experimental: Part 2A Dose Expansion Combination (Gastric/GEJ)<br>Participants with gastric/gastroesophageal junction cancer (Gastric/GEJ) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>Biological: Sasanlimab<br>* Administered subcutaneously<br>* Other names: PF-06801591;|
| Experimental: Part 2A Dose Expansion Combination (NSCLC)<br>Participants with non small cell lung cancer (NSCLC) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>Biological: Sasanlimab<br>* Administered subcutaneously<br>* Other names: PF-06801591;|
| Experimental: Part 2A Dose Expansion Combination (selected tumor types)<br>Participants with selected tumor types will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>Biological: Sasanlimab<br>* Administered subcutaneously<br>* Other names: PF-06801591;|
| Experimental: Part 2B Dose Expansion Monotherapy (selected tumor types)<br>Participants with selected tumor types will receive PF-07265028 single agent at the recommended dose from Part 1A. | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>|
|
PF-07265028 As Single Agent And In Combination With Sasanlimab in Advanced or Metastatic Solid Tumors
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the safety and effects of PF-07265028 as monotherapy and in combination with sasanlimab. The study aims to identify the maximum tolerated dose (MTD) of PF-07265028 as monotherapy; evaluate the clinical activity of monotherapy and combination; and select the recommended dose of PF-07265028 monotherapy and in combination for potential further studies and development. The study contains 2 parts, Dose Escalation (Part 1) to determine the recommended dose of PF-07265028 as single agent and in combination, followed by Dose Expansion (Part 2) in selected tumor types at the recommended dose. It is expected that most participants will take part in this study for up to 1 year with six on-site visits in the first month and then at least twice every subsequent month while they are on treatment.
Detailed Description
-----------------
The purpose of this first-in-human study is to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of increasing doses of PF-07265028 as monotherapy and in combination with sasanlimab; identify the maximum tolerated dose (MTD) of PF-07265028 monotherapy; evaluate the clinical activity of monotherapy and combination; and select the recommended dose of PF-07265028 monotherapy and in combination for potential further studies and development. The study contains 2 parts, Dose Escalation (Part 1) to determine the recommended dose of PF-07265028 as single agent and in combination, followed by Dose Expansion (Part 2) in selected tumor types at the recommended dose.
Official Title
-----------------
A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND EXPANSION STUDY OF PF-07265028 AS A SINGLE AGENT AND IN COMBINATION WITH SASANLIMAB EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTI-TUMOR ACTIVITY OF PF-07265028 IN PARTICIPANTS WITH ADVANCED OR METASTATIC SOLID TUMORS
Conditions
-----------------
Advanced Solid Tumors, Gastric Cancer, Gastroesophageal Junction Cancer, Urothelial Cancer, Non Small Cell Lung Cancer, Head and Neck Squamous Cell Carcinomas
Intervention / Treatment
-----------------
* Drug: PF-07265028
* Biological: Sasanlimab
Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Across all cohorts: Eastern Cooperative Oncology Group (ECOG) performance status ≤1 Adequate hematological, kidney and liver function Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Resolved acute effects of any prior therapy All participants must provide archival formalin-fixed paraffin-embedded (FFPE) tumor tissue: Part 1: If archival sample is older than 6 months, the participant must consent to undergo a fresh biopsy during the screening. Part 2 Fresh tumor biopsy during screening is required unless there is archival tissues less than 3 months old and subsequent to the last systemic anti-cancer therapy. Part 1A Monotherapy: Histologically or cytologically confirmed advanced or metastatic solid tumors which have progressed following systemic anticancer therapies, or are resistant to standard therapy or for which no standard therapy is available, or for whom standard therapy is not tolerated. Part 1B Combination Therapy: Histologically or cytologically confirmed advanced or metastatic solid tumor which have progressed following systemic anticancer therapies, including at least 1 checkpoint inhibitor. Part 2 Dose Expansion: Histologically or cytologically confirmed advanced or metastatic malignancies, including gastric/Gastroesophageal junction cancer, Head and neck squamous cell carcinoma, or urothelial cancer (non-small cell lung cancer and other solid tumors may be included) who have progressed following systemic anticancer therapies, including at least 1 checkpoint inhibitor Key Exclusion Criteria: Participants with any other active malignancy within 3 years prior to enrollment Participants with active autoimmune conditions or history of autoimmune diseases that may relapse History of interstitial lung disease, pneumonitis (non-infectious) or uncontrolled lung diseases History of prior immune-related adverse events (irAEs) Grade ≥3 Central nervous system metastases Significant cardiac or pulmonary conditions or events within previous 6 months Active, uncontrolled bacterial, fungal, or viral infection Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PF-07265028 Prior administration of HPK1 inhibitor
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 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: Sequential Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1A Dose Escalation Monotherapy<br>Participants will receive PF-07265028 at escalating dose levels. | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>|
| Experimental: Part 1B Dose Escalation Combination<br>Participants will receive PF-07265028 at escalating dose levels in combination with sasanlimab fixed dose | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>Biological: Sasanlimab<br>* Administered subcutaneously<br>* Other names: PF-06801591;|
| Experimental: Part 2A Dose Expansion Combination (SCCHN)<br>Participants with squamous cell carcinoma of the head and neck (SCCHN) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>Biological: Sasanlimab<br>* Administered subcutaneously<br>* Other names: PF-06801591;|
| Experimental: Part 2A Dose Expansion Combination (UC)<br>Participants with urothelial cancer (UC) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>Biological: Sasanlimab<br>* Administered subcutaneously<br>* Other names: PF-06801591;|
| Experimental: Part 2A Dose Expansion Combination (Gastric/GEJ)<br>Participants with gastric/gastroesophageal junction cancer (Gastric/GEJ) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>Biological: Sasanlimab<br>* Administered subcutaneously<br>* Other names: PF-06801591;|
| Experimental: Part 2A Dose Expansion Combination (NSCLC)<br>Participants with non small cell lung cancer (NSCLC) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>Biological: Sasanlimab<br>* Administered subcutaneously<br>* Other names: PF-06801591;|
| Experimental: Part 2A Dose Expansion Combination (selected tumor types)<br>Participants with selected tumor types will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>Biological: Sasanlimab<br>* Administered subcutaneously<br>* Other names: PF-06801591;|
| Experimental: Part 2B Dose Expansion Monotherapy (selected tumor types)<br>Participants with selected tumor types will receive PF-07265028 single agent at the recommended dose from Part 1A. | Drug: PF-07265028<br>* PF-07265028 will be administered orally<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Dose-limiting toxicities (DLTs) in Dose Escalation (Part 1) | DLTs will be evaluated during Cycle 1 (a cycle is 28 days) in Part 1. The number of DLTs will be used to determine the optimal dose | Cycle 1 (28 days) |
| Number of participants with adverse events (AEs) | AEs characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 5.0), timing, seriousness, and relationship to study therapy. | Baseline through up to 2 years |
| Number of participants with clinically significant laboratory abnormalities | Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing. | Baseline through up to 2 years |
| Objective response rate (ORR) in Dose Expansion (Part 2) | Tumor response based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Baseline through up to 2 years or until disease progression |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through Cmax. | Maximum observed plasma concentration of PF-07265028 (Cmax) and Maximum observed steady state plasma concentration (Cmax, ss) | Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) |
| The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through Tmax. | Time to maximal observed plasma concentration of PF-07265028 (Tmax) and Time to reach Maximum Observed Steady State Plasma Concentration (Tmax,ss). | Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) |
| The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through AUC | Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-07265028 and area under the curve within one dose interval at steady state (AUCtau,ss) | Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) |
| The effect of food on the pharmacokinetic profile of PF-07265028 through Cmax. | Maximum observed plasma concentration of PF-07265028 (Cmax) under fasted and fed conditions in the subset of participants | Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) |
| The effect of food on the pharmacokinetic profile of PF-07265028 through Tmax | Time to maximal observed plasma concentration of PF-07265028 (Tmax) under fasted and fed conditions in the subset of participants | Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) |
| The effect of food on the pharmacokinetic profile of PF-07265028 through AUC | Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-07265028 under fasted and fed conditions in the subset of participants | Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) |
| The pharmacokinetic profile of sasanlimab when given in combination with PF-07265028 through Cmin | Minimum plasma concentration (Cmin) will be calculated through the measured pre-dose plasma concentration | Day 1 of cycle 1 (each cycle is 28 days), Day 1 of cycle 2, Day 1 of cycle 3, Day 1 of cycle 5 and thereafter every 6 cycles (each cycle is 28 days) |
| The immunogenicity of sasanlimab when given in combination with PF-07265028 through ADA and NAb | Incidence and titers of anti-drug antibodies (ADA) and neutralizing antibodies (NAb) against sasanlimab | Day 1 of cycle 1 (each cycle is 28 days), Day 1 of cycle 2, Day 1 of cycle 3, Day 1 of cycle 5 and thereafter every 6 cycles (each cycle is 28 days) |
| The effect of PF-07265028 alone and in combination with sasanlimab on tumor immune biomarkers modulation | Levels of intratumor T cells and PD-L1 expression in pre- and post-treatment tumor biopsies | Baseline through up to 2 years |
| ORR in Dose Escalation (Part 1) | Tumor response assessment based on RECIST 1.1 | From baseline through disease progression or study completion (approximately 2 years) |
| Time to event endpoints (DOR) in Dose Expansion (Part 2) | Duration of response (DOR) as assessed using RECIST 1.1. | From baseline through disease progression or study completion (approximately 2 years) |
| Time to event endpoints (PFS) in Dose Expansion (Part 2) | Progression free survival (PFS) as assessed using RECIST 1.1. | From baseline through disease progression or study completion (approximately 2 years) |
| Time to event endpoints (OS) in Dose Expansion (Part 2) | Overall survival (OS) assessed proportion of patients alive | From baseline through disease progression or study completion (approximately 2 years) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
immunotherapy, advanced solid tumor, metastatic solid tumor, first in human, Gastric cancer, Gastroesophageal junction cancer, Urothelial Cancer, Non small cell lung cancer, Head and neck squamous cell carcinomas, SCCHN, NSCLC, Lung cancer, Hematopoietic progenitor kinase 1 inhibitor, HPK1 inhibitor
|
NCT00853788
|
Skin Biopsy Specimens as Biomarkers of Systemic Sclerosis and Response to Mycophenolate Mofetil
|
The purpose of this study is to assess whether skin biopsy specimens from patients with diffuse cutaneous systemic sclerosis (dcSSc) can be used as biomarkers (measures of activity and type) of disease to predict response to various experimental treatments. There are various experimental treatments being used in the treatment of slceroderma, but there is no way to predict response to any given therapy. The investigators will use DNA microarray to analyze the changes in gene expression in skin biopsies in response to various treatments. Our hypothesis is that the investigators will see changes in gene expression in response to various treatments that will give us insight into the cause of scleroderma. The investigators predict that they will be able to use this information to predict which experimental treatments will be beneficial to individual patients
|
Systemic sclerosis (SSc) is an autoimmune connective tissue disease primarily affecting young to middle-aged women. The pathogenesis of SSc is complex involving interplay of three seemingly diverse processes: autoimmunity, vasculopathy, and fibrosis. Patients experience varying degrees of disabling skin thickening and potentially life-threatening internal organ fibrosis and vasculopathy, but there is no way to accurately predict disease subtype and risk for severity and progression. Current experimental treatments for SSc include oral and intravenous cyclophosphamide and mycophenolate mofetil that blunt the immune response, autologous stem cell transplant that may reset the immune system, and imatinib mesylate that may reduce fibrosis.~Recent exciting genomics research from our lab and our collaborator suggests that skin biopsy samples obtained from patients with SSc have robust alterations in gene expression profiles compared to controls. Changes in expression of genes known to be involved in profibrotic pathways were prominent. The present proposal describes novel experiments to evaluate genomic approaches coupled with clinical data to identify patient subsets, predict response to treatment, and to better understand the molecular basis for disease pathogenesis, and treatment response.~The Northwestern Scleroderma Program (NSP) is a novel multidisciplinary program to accelerate SSc research and provide comprehensive care to >400 SSc patients. Standardized clinical information including demographic, laboratory, and diagnostic data (echocardiography, high resolution chest computerized tomography, and pulmonary function testing) as well as DNA is currently collected on all patients and entered into a clinical database. NSP patients will be offered the option to donate dermal tissue for genomic analysis using a previously established, optimized approach to extract RNA from tissue samples.~We hypothesize that our DNA microarray technique will permit analysis of changes in gene expression from the skin of patients undergoing dermal biopsies before and after treatment and will identify unrecognized profibrotic pathways in addition to providing new, important information regarding known fibrotic pathways. The knowledge gained will not only deepen our understanding of the molecular pathways involved in fibrosis, but also provide a means to reliably predict which patients are likely to respond to various treatments.~Relevance:~SSc is a devastating orphan connective tissue disease with no known cure. There are no disease biomarkers that can accurately predict disease subtype or risk for internal organ involvement and progression at present. Using well-established genomic techniques, the current proposal will investigate if changes in gene expression of profibrotic pathways in dermal biopsies before and after various treatments correlates with clinical response. If so, genonic analysis of dermal tissue may be useful to better understand the molecular pathogenesis of SSc and as a disease biomarker.
|
Genomic and Histological Analysis of Skin Biopsy Specimens as Biomarkers of Systemic Sclerosis and Response to Mycophenolate Mofetil
|
Systemic Sclerosis
|
Inclusion Criteria:~18 years of age~systemic sclerosis~Exclusion Criteria:~pregnant~bleeding disorder~history of delayed wound healing
|
19 Years
|
90 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
systemic sclerosis, biomarkers, microarray
|
Scleroderma, Systemic, Scleroderma, Diffuse, Sclerosis, Pathologic Processes, Connective Tissue Diseases, Skin Diseases
|
Skin Biopsy Specimens as Biomarkers of Systemic Sclerosis and Response to Mycophenolate Mofetil
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess whether skin biopsy specimens from patients with diffuse cutaneous systemic sclerosis (dcSSc) can be used as biomarkers (measures of activity and type) of disease to predict response to various experimental treatments. There are various experimental treatments being used in the treatment of slceroderma, but there is no way to predict response to any given therapy. The investigators will use DNA microarray to analyze the changes in gene expression in skin biopsies in response to various treatments. Our hypothesis is that the investigators will see changes in gene expression in response to various treatments that will give us insight into the cause of scleroderma. The investigators predict that they will be able to use this information to predict which experimental treatments will be beneficial to individual patients
Detailed Description
-----------------
Systemic sclerosis (SSc) is an autoimmune connective tissue disease primarily affecting young to middle-aged women. The pathogenesis of SSc is complex involving interplay of three seemingly diverse processes: autoimmunity, vasculopathy, and fibrosis. Patients experience varying degrees of disabling skin thickening and potentially life-threatening internal organ fibrosis and vasculopathy, but there is no way to accurately predict disease subtype and risk for severity and progression. Current experimental treatments for SSc include oral and intravenous cyclophosphamide and mycophenolate mofetil that blunt the immune response, autologous stem cell transplant that may reset the immune system, and imatinib mesylate that may reduce fibrosis. Recent exciting genomics research from our lab and our collaborator suggests that skin biopsy samples obtained from patients with SSc have robust alterations in gene expression profiles compared to controls. Changes in expression of genes known to be involved in profibrotic pathways were prominent. The present proposal describes novel experiments to evaluate genomic approaches coupled with clinical data to identify patient subsets, predict response to treatment, and to better understand the molecular basis for disease pathogenesis, and treatment response. The Northwestern Scleroderma Program (NSP) is a novel multidisciplinary program to accelerate SSc research and provide comprehensive care to >400 SSc patients. Standardized clinical information including demographic, laboratory, and diagnostic data (echocardiography, high resolution chest computerized tomography, and pulmonary function testing) as well as DNA is currently collected on all patients and entered into a clinical database. NSP patients will be offered the option to donate dermal tissue for genomic analysis using a previously established, optimized approach to extract RNA from tissue samples. We hypothesize that our DNA microarray technique will permit analysis of changes in gene expression from the skin of patients undergoing dermal biopsies before and after treatment and will identify unrecognized profibrotic pathways in addition to providing new, important information regarding known fibrotic pathways. The knowledge gained will not only deepen our understanding of the molecular pathways involved in fibrosis, but also provide a means to reliably predict which patients are likely to respond to various treatments. Relevance: SSc is a devastating orphan connective tissue disease with no known cure. There are no disease biomarkers that can accurately predict disease subtype or risk for internal organ involvement and progression at present. Using well-established genomic techniques, the current proposal will investigate if changes in gene expression of profibrotic pathways in dermal biopsies before and after various treatments correlates with clinical response. If so, genonic analysis of dermal tissue may be useful to better understand the molecular pathogenesis of SSc and as a disease biomarker.
Official Title
-----------------
Genomic and Histological Analysis of Skin Biopsy Specimens as Biomarkers of Systemic Sclerosis and Response to Mycophenolate Mofetil
Conditions
-----------------
Systemic Sclerosis
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years of age systemic sclerosis Exclusion Criteria: pregnant bleeding disorder history of delayed wound healing
Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 90 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 |
| --- | --- | --- |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
systemic sclerosis, biomarkers, microarray
|
||||
NCT02570347
|
Routine Antibiotic vs. Directed Antibiotic Treatment in Snake Bite
|
Clinicians tend to overuse antibiotics in snake bite despite evidence from three previous clinical trials that failed to show a benefit. But, none of these trials was done in India. Further, the species of snake in two of these trials was quite different from that seen in the Indian setting limiting generalization of these findings. Hence, home-grown evidence is needed to persuade clinicians to use antibiotics rationally.
|
Snake bite is a common clinical problem in India and elsewhere, affecting agricultural workers and rural population, resulting in thousands of deaths every year. Apart from causing systemic manifestations such as coagulopathy, acute renal failure, and neuroparalysis, local effects of the venom manifest as swelling of the bitten limb. Despite administration of adequate antivenom, the limb swelling progresses in the first 48-72 hours accompanied by considerable pain. Often the limb swelling is accompanied by formation of blebs and gangrenous skin changes. At times, the limb swelling is severe enough to result in compartment syndrome, necessitating surgical interventions such as fasciotomy and debridement. Animal bites are typically associated with a risk of infection by the oral flora. Likewise, apart from releasing the venom, inoculation of oral flora as a result of snake bite could result in local infectious complications adding to the deleterious effects of the snake venom.~Observational studies suggest that the risk of infection following simple bites on the lower limbs is much less than what is often believed, and evidence from clinical trials also does not support routine use of antibiotics in snake bite. For this reason, clinical practice guidelines do not recommend routine prophylactic use of antibiotics in snake bite. But, in reality, many clinicians continue to use antibiotics routinely in all venomous snake bites hoping to prevent a local infection. While such a strategy may not reduce the risk of infection, it would result in overuse of antibiotics promoting antimicrobial resistance and escalating treatment costs.~The investigators hypothesize that clinically-directed use of antibiotics would be non-inferior to routine use in preventing local infectious complications of snake bite, while being superior in reducing the antibiotic consumption. Non-inferiority would be inferred if the one-sided 95% CI of the difference does not exceed 10% in favour of the routine use arm.
|
Routine vs. Clinically-Directed Antibiotic Treatment in Snake Bite With Local Envenomation: a Randomised Controlled Trial
|
Snake Bites
|
* Drug: Co-amoxiclav
* Biological: Tetanus toxoid
|
Inclusion Criteria:~Age 18-65 years~History of snake bite with features of local envenomation with/without systemic features~Less than 24 hours since bite, AND~No prior antibiotic treatment~Exclusion Criteria:~Upper limb bites~Multiple (> 1) bites~Wound manipulation~Extensive local necrosis or blebs~Seriously-ill patients with hypotension/capillary leak/life threatening bleeding.~Suspected cobra bite, OR~Pregnant/breast-feeding women
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical failure | Defined as occurrence of any one of the following on daily assessments - Abscess formation at any point of time; Surgical debridement/fasciotomy at any time; Worsening limb swelling beyond 72-96 hours or appearance of necrosis or blebs along with any one of the following: fever, persistent or worsening leucocytosis, or global deterioration on clinical assessment. | up to 4 weeks |
| Antibiotic consumption | Defined as the total amount of all antibiotics consumed regardless of clinical indication expressed in terms of defined daily doses (DDD). | up to 4 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of hospital stay | Number of days from hospital admission until discharge | up to 4 weeks |
| Anti-snake venom consumption | The total number of vials of the anti-venom administered including doses received prior to being brought to JIPMER. | up to 4 weeks |
| New-onset organ failure | This includes acute kidney injury (AKI) defined as peak serum creatinine > 2 mg/dL, shock defined as systolic blood pressure < 90 mm Hg requiring use of vasopressors; bleeding from any site necessitating transfusion of blood/blood products; and capillary leak syndrome. | up to 4 weeks |
| Death/need for surgical intervention | This would be a composite measure of death and/or need for surgical intervention. Death indicates in-hospital death due to any cause during the index hospitalisation. Surgical intervention would include need for any surgical intervention such as incision and drainage of abscess, wound debridement for necrosis or gangrene, fasciotomy for compartment syndrome, etc. | up to 4 weeks |
| Drug-related adverse events | Any suspected or confirmed adverse drug reaction | up to 4 weeks |
|
Snake Envenomation, Antibiotic Prophylaxis, Viperidae
|
Amoxicillin-Potassium Clavulanate Combination, Anti-Bacterial Agents, Anti-Infective Agents, beta-Lactamase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Routine use arm<br>All participants allocated to this arm will be given~Injection Tetanus toxoid 0.5 ml intramuscularly Stat~Antibiotic (Co-amoxiclav) will be given to all patients for a minimum duration of 5 days.~Daily clinical assessment would be done. Change of antibiotics is allowed if clinical failure occurs.~Use of antibiotics for emergent indications unrelated to the bitten limb such as nosocomial infections would be allowed at the treating physician's discretion. | Drug: Co-amoxiclav<br>* Injection Co-amoxiclav 1.2 g intravenously q8h for a minimum of 48-72 hours; switched to oral Co-amoxiclav 625 mg b.i.d. when clinically appropriate.<br>* Other names: Augmentin;Biological: Tetanus toxoid<br>* Injection Tetanus toxoid 0.5 ml intramuscularly Stat<br>|
| Experimental: Clinically-directed use arm<br>Participants allocated to this arm will be given~Injection Tetanus toxoid 0.5 ml intramuscularly Stat~Daily clinical assessment would be done. Antibiotic (Co-amoxiclav) will be started only if clinical failure occurs.~Use of antibiotics for emergent indications unrelated to the bitten limb such as nosocomial infections would be allowed at the treating physician's discretion. | Drug: Co-amoxiclav<br>* Injection Co-amoxiclav 1.2 g intravenously q8h for a minimum of 48-72 hours; switched to oral Co-amoxiclav 625 mg b.i.d. when clinically appropriate.<br>* Other names: Augmentin;Biological: Tetanus toxoid<br>* Injection Tetanus toxoid 0.5 ml intramuscularly Stat<br>|
|
Routine Antibiotic vs. Directed Antibiotic Treatment in Snake Bite
Study Overview
=================
Brief Summary
-----------------
Clinicians tend to overuse antibiotics in snake bite despite evidence from three previous clinical trials that failed to show a benefit. But, none of these trials was done in India. Further, the species of snake in two of these trials was quite different from that seen in the Indian setting limiting generalization of these findings. Hence, home-grown evidence is needed to persuade clinicians to use antibiotics rationally.
Detailed Description
-----------------
Snake bite is a common clinical problem in India and elsewhere, affecting agricultural workers and rural population, resulting in thousands of deaths every year. Apart from causing systemic manifestations such as coagulopathy, acute renal failure, and neuroparalysis, local effects of the venom manifest as swelling of the bitten limb. Despite administration of adequate antivenom, the limb swelling progresses in the first 48-72 hours accompanied by considerable pain. Often the limb swelling is accompanied by formation of blebs and gangrenous skin changes. At times, the limb swelling is severe enough to result in compartment syndrome, necessitating surgical interventions such as fasciotomy and debridement. Animal bites are typically associated with a risk of infection by the oral flora. Likewise, apart from releasing the venom, inoculation of oral flora as a result of snake bite could result in local infectious complications adding to the deleterious effects of the snake venom. Observational studies suggest that the risk of infection following simple bites on the lower limbs is much less than what is often believed, and evidence from clinical trials also does not support routine use of antibiotics in snake bite. For this reason, clinical practice guidelines do not recommend routine prophylactic use of antibiotics in snake bite. But, in reality, many clinicians continue to use antibiotics routinely in all venomous snake bites hoping to prevent a local infection. While such a strategy may not reduce the risk of infection, it would result in overuse of antibiotics promoting antimicrobial resistance and escalating treatment costs. The investigators hypothesize that clinically-directed use of antibiotics would be non-inferior to routine use in preventing local infectious complications of snake bite, while being superior in reducing the antibiotic consumption. Non-inferiority would be inferred if the one-sided 95% CI of the difference does not exceed 10% in favour of the routine use arm.
Official Title
-----------------
Routine vs. Clinically-Directed Antibiotic Treatment in Snake Bite With Local Envenomation: a Randomised Controlled Trial
Conditions
-----------------
Snake Bites
Intervention / Treatment
-----------------
* Drug: Co-amoxiclav
* Biological: Tetanus toxoid
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-65 years History of snake bite with features of local envenomation with/without systemic features Less than 24 hours since bite, AND No prior antibiotic treatment Exclusion Criteria: Upper limb bites Multiple (> 1) bites Wound manipulation Extensive local necrosis or blebs Seriously-ill patients with hypotension/capillary leak/life threatening bleeding. Suspected cobra bite, OR Pregnant/breast-feeding women
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 |
| --- | --- |
| Active Comparator: Routine use arm<br>All participants allocated to this arm will be given Injection Tetanus toxoid 0.5 ml intramuscularly Stat Antibiotic (Co-amoxiclav) will be given to all patients for a minimum duration of 5 days. Daily clinical assessment would be done. Change of antibiotics is allowed if clinical failure occurs. Use of antibiotics for emergent indications unrelated to the bitten limb such as nosocomial infections would be allowed at the treating physician's discretion. | Drug: Co-amoxiclav<br>* Injection Co-amoxiclav 1.2 g intravenously q8h for a minimum of 48-72 hours; switched to oral Co-amoxiclav 625 mg b.i.d. when clinically appropriate.<br>* Other names: Augmentin;Biological: Tetanus toxoid<br>* Injection Tetanus toxoid 0.5 ml intramuscularly Stat<br>|
| Experimental: Clinically-directed use arm<br>Participants allocated to this arm will be given Injection Tetanus toxoid 0.5 ml intramuscularly Stat Daily clinical assessment would be done. Antibiotic (Co-amoxiclav) will be started only if clinical failure occurs. Use of antibiotics for emergent indications unrelated to the bitten limb such as nosocomial infections would be allowed at the treating physician's discretion. | Drug: Co-amoxiclav<br>* Injection Co-amoxiclav 1.2 g intravenously q8h for a minimum of 48-72 hours; switched to oral Co-amoxiclav 625 mg b.i.d. when clinically appropriate.<br>* Other names: Augmentin;Biological: Tetanus toxoid<br>* Injection Tetanus toxoid 0.5 ml intramuscularly Stat<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical failure | Defined as occurrence of any one of the following on daily assessments - Abscess formation at any point of time; Surgical debridement/fasciotomy at any time; Worsening limb swelling beyond 72-96 hours or appearance of necrosis or blebs along with any one of the following: fever, persistent or worsening leucocytosis, or global deterioration on clinical assessment. | up to 4 weeks |
| Antibiotic consumption | Defined as the total amount of all antibiotics consumed regardless of clinical indication expressed in terms of defined daily doses (DDD). | up to 4 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of hospital stay | Number of days from hospital admission until discharge | up to 4 weeks |
| Anti-snake venom consumption | The total number of vials of the anti-venom administered including doses received prior to being brought to JIPMER. | up to 4 weeks |
| New-onset organ failure | This includes acute kidney injury (AKI) defined as peak serum creatinine > 2 mg/dL, shock defined as systolic blood pressure < 90 mm Hg requiring use of vasopressors; bleeding from any site necessitating transfusion of blood/blood products; and capillary leak syndrome. | up to 4 weeks |
| Death/need for surgical intervention | This would be a composite measure of death and/or need for surgical intervention. Death indicates in-hospital death due to any cause during the index hospitalisation. Surgical intervention would include need for any surgical intervention such as incision and drainage of abscess, wound debridement for necrosis or gangrene, fasciotomy for compartment syndrome, etc. | up to 4 weeks |
| Drug-related adverse events | Any suspected or confirmed adverse drug reaction | up to 4 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Snake Envenomation, Antibiotic Prophylaxis, Viperidae
|
NCT05480501
|
Clinical Trial to Evaluate the Safety and Efficacy of IM19 CAR-T Cells in Patients With Relapsed and Refractory (R/R) B-cell Acute Lymphoblastic Leukemia
|
This is a open-label to assess the efficacy and safety of IM19 CAR-T cells in R/R B-cell Acute Lymphoblastic Leukemia.
|
Clinical Trial to Evaluate the Safety and Efficacy of IM19 CAR-T Cells in Patients With Relapsed and Refractory (R/R) B-cell Acute Lymphoblastic Leukemia
|
Leukemia
|
* Biological: IM19 CAR-T cells
|
Inclusion Criteria:~Relapsed or refractory B-ALL, defined as：1）Not chieving a CR after 1 cycle of standard chemotherapy for relapsed leukemia. 2）Any relapse after HSCT and must be ≥ 6 months from HSCT at the time of IM19 CAR-T cells infusion. 3）Primary refractory as defined by not achieving a CR after 2 cycles of a standard chemotherapy regimen.~Patients with Ph+ ALL are eligible if they are intolerant to or have failed two lines of TKI ± chemotherapy ；Ph + all patients with T315I mutation are not required to receive at least two TKI ± chemotherapy in the absence of effective TKI therapy.~Morphological evidence of disease in bone marrow (at least 5% blasts).~Aged 3 to 70 years.~Estimated life expectancy >3 months.~ECOG performance status of 0 or 1(age ≥ 16 years) or Lansky (age < 16 years).~Women of childbearing age who had a negative blood pregnancy test before the start of the trial and agreed to take effective contraceptive measures during the trial period until the last follow-up; male subjects with fertility partners agreed to take effective contraceptive measures during the trial period until the last follow-up.~Adequate organ function.~Volunteer to participate in this trial and sign on the informed consent.~Exclusion Criteria:~Subjects with lsolated extramedullary disease relapse.~Subjects with Burkitt's lymphoma.~Subjects has obvious symptoms of central nervous system invasion and needs targeted treatment.~Subjects has previously received gene product therapy.~Subjects has graft-versus-host response（GVHD） and need to use immunosuppressants or GVHD ≥ grade 2 or being treated with anti GVHD or suffering from autoimmune diseases.~Subjects has received chemotherapy or radiotherapy within 3 days before leukapheresis.~Subjects received systemic steroids within 5 days prior to leukapheresis.~Subjects received drugs that stimulated the production of hematopoietic cells in the bone marrow for 5 days prior to leucapheresis.~Subjects has participated in other clinical studies within 1 month before screening or plan to participate in other drug clinical trials during this study.~Subjects received allogeneic cell therapy within 6 weeks before leukapheresis.~Subjects with History or presence of CNS disorder.~Subjects with HBV, HCV, HIV ,EBV,ECV or syphilis infection at the time of screening.~Pregnant or lactating, or planning pregnancy within 180 days after the end of CAR-T cells infusion, or male patients whose partners plan pregnancy 180 days after their CAR-T cell infusion.~Subjects with other tumors in the past 5 years.~Within 14 days before enrollment, there were active or uncontrollable infections requiring systemic treatment.
|
3 Years
|
70 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) | | Up to 28 days after CAR-T cell infusion |
| Persistence of CAR-T cells (cell counts and cell percentage in peripheral blood and bone marrow ) | | Up to 24 weeks after CAR-T cell infusion |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | | Up to 24 weeks after CAR-T cell infusion |
| Relapse free surviva（PFS） | | Up to 24 weeks after CAR-T cell infusion |
| Duration of Response (DOR) | | Up to 24 weeks after CAR-T cell infusion |
| Overall survival (OS) | | Up to 24 weeks after CAR-T cell infusion |
| Minimal residual disease（MRD） | | Up to 24 weeks after CAR-T cell infusion |
|
CAR-T, B-cell Acute Lymphoblastic Leukemia
|
Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Lymphoid, Neoplasms by Histologic Type, Neoplasms, Lymphoproliferative Disorders, Lymphatic Diseases, Immunoproliferative Disorders, Immune System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IM19 CAR-T cells<br> | Biological: IM19 CAR-T cells<br>* IM19 CAR-T cells administrated in a dosage to be selected by physician from a specific range.<br>|
|
Clinical Trial to Evaluate the Safety and Efficacy of IM19 CAR-T Cells in Patients With Relapsed and Refractory (R/R) B-cell Acute Lymphoblastic Leukemia
Study Overview
=================
Brief Summary
-----------------
This is a open-label to assess the efficacy and safety of IM19 CAR-T cells in R/R B-cell Acute Lymphoblastic Leukemia.
Official Title
-----------------
Clinical Trial to Evaluate the Safety and Efficacy of IM19 CAR-T Cells in Patients With Relapsed and Refractory (R/R) B-cell Acute Lymphoblastic Leukemia
Conditions
-----------------
Leukemia
Intervention / Treatment
-----------------
* Biological: IM19 CAR-T cells
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Relapsed or refractory B-ALL, defined as：1）Not chieving a CR after 1 cycle of standard chemotherapy for relapsed leukemia. 2）Any relapse after HSCT and must be ≥ 6 months from HSCT at the time of IM19 CAR-T cells infusion. 3）Primary refractory as defined by not achieving a CR after 2 cycles of a standard chemotherapy regimen. Patients with Ph+ ALL are eligible if they are intolerant to or have failed two lines of TKI ± chemotherapy ；Ph + all patients with T315I mutation are not required to receive at least two TKI ± chemotherapy in the absence of effective TKI therapy. Morphological evidence of disease in bone marrow (at least 5% blasts). Aged 3 to 70 years. Estimated life expectancy >3 months. ECOG performance status of 0 or 1(age ≥ 16 years) or Lansky (age < 16 years). Women of childbearing age who had a negative blood pregnancy test before the start of the trial and agreed to take effective contraceptive measures during the trial period until the last follow-up; male subjects with fertility partners agreed to take effective contraceptive measures during the trial period until the last follow-up. Adequate organ function. Volunteer to participate in this trial and sign on the informed consent. Exclusion Criteria: Subjects with lsolated extramedullary disease relapse. Subjects with Burkitt's lymphoma. Subjects has obvious symptoms of central nervous system invasion and needs targeted treatment. Subjects has previously received gene product therapy. Subjects has graft-versus-host response（GVHD） and need to use immunosuppressants or GVHD ≥ grade 2 or being treated with anti GVHD or suffering from autoimmune diseases. Subjects has received chemotherapy or radiotherapy within 3 days before leukapheresis. Subjects received systemic steroids within 5 days prior to leukapheresis. Subjects received drugs that stimulated the production of hematopoietic cells in the bone marrow for 5 days prior to leucapheresis. Subjects has participated in other clinical studies within 1 month before screening or plan to participate in other drug clinical trials during this study. Subjects received allogeneic cell therapy within 6 weeks before leukapheresis. Subjects with History or presence of CNS disorder. Subjects with HBV, HCV, HIV ,EBV,ECV or syphilis infection at the time of screening. Pregnant or lactating, or planning pregnancy within 180 days after the end of CAR-T cells infusion, or male patients whose partners plan pregnancy 180 days after their CAR-T cell infusion. Subjects with other tumors in the past 5 years. Within 14 days before enrollment, there were active or uncontrollable infections requiring systemic treatment.
Ages Eligible for Study
-----------------
Minimum Age: 3 Years
Maximum Age: 70 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: IM19 CAR-T cells<br> | Biological: IM19 CAR-T cells<br>* IM19 CAR-T cells administrated in a dosage to be selected by physician from a specific range.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) | | Up to 28 days after CAR-T cell infusion |
| Persistence of CAR-T cells (cell counts and cell percentage in peripheral blood and bone marrow ) | | Up to 24 weeks after CAR-T cell infusion |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | | Up to 24 weeks after CAR-T cell infusion |
| Relapse free surviva（PFS） | | Up to 24 weeks after CAR-T cell infusion |
| Duration of Response (DOR) | | Up to 24 weeks after CAR-T cell infusion |
| Overall survival (OS) | | Up to 24 weeks after CAR-T cell infusion |
| Minimal residual disease（MRD） | | Up to 24 weeks after CAR-T cell infusion |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CAR-T, B-cell Acute Lymphoblastic Leukemia
|
|
NCT04822792
|
Pan-canceR Early-Stage deteCtion by lIquid Biopsy tEchNique projecT
|
PRESCIENT is a multi-center, prospective observational study aimed to detect cancers early by combined assays for serum protein markers and cell-free DNA (cfDNA) methylation markers. Blood RNA markers will also be evaluated. The study will enroll approximately 11879 participants, including participants with malignancies or benign diseases, and healthy participants.
|
Pan-cancer Early-stage Detection by Liquid Biopsy in Peripheral Blood: a Multi-center, Prospective Observational Study
|
Cancer
|
* Device: Multi-cancer early detection test
|
Inclusion Criteria for All the Participants:~Ability to provide a written informed consent~40-75 years old~Exclusion Criteria for All the Participants:~Inability to comply with study procedures~Pregnancy or lactating women~Recipients of organ transplant or prior non-autologous (allogeneic) bone marrow transplant or stem cell transplant~Recipients of blood transfusion within 7 days prior to study blood draw~Recipients of any anti-cancer therapy within 30 days prior to study blood draw, due to diseases other than cancer~Inclusion Criteria for Cancer Arm Participants:~Confirmed diagnosis or suspicious cases of one of the 22 types of malignancies within 42 days prior to study blood draw~No prior or ongoing anti-cancer therapy (local or systematic) prior to study blood draw~Exclusion Criteria for Cancer Arm Participants:~Known prior diagnosis of malignancies~Other current malignant diseases or multiple primary tumors~No confirmed diagnosis of cancer by histopathological or radiological assessments within 42 days of study blood draw, or diagnosis of a benign disease by histopathological assessments, or inability to characterize whether the lesion is malignant or benign~Non-small-cell lung cancer patients with ground-class nodularity by radiological examination~Inclusion Criteria for Benign Diseases Arm Participants:~Confirmed diagnosis of benign diseases corresponding to the tumor types in the Cancer Arm by histopathological or radiological assessments within 90 days prior to study blood draw~No prior treatment of benign diseases prior to study blood draw~Exclusion Criteria for Benign Diseases Arm Participants:~History of malignancies~Current malignancies or precancerous lesions~No confirmed diagnosis of a benign disease by radiological, endoscopic or histopathological assessments within 42 days of study blood draw, or inability to characterize whether the lesion is malignant or benign~Inclusion Criteria for Non-tumor (Healthy) Arm Participants:~No cancer-related symptoms or discomfort within 30 days prior to study blood draw~No clinically significant finding by LDCT or ultrasound~No clinically significant finding by breast ultrasound or Molybdenum Target Mammography Detection, or Thinprep cytologic test (TCT) detection for female participants~No active hepatitis B or hepatitis C infection~Exclusion Criteria for Non-tumor (Healthy) Arm Participants:~Prior or ongoing treatment of cancer within 3 years prior to study blood draw~Clinically significant or uncontrolled comorbidities
|
40 Years
|
75 Years
|
All
| null |
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and specificity of early detection of 22 types of cancers and Tissue of origin (TOO) accuracy of a cfDNA methylation-based model, in combination with serum tumor markers | | 22 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and specificity of a cfDNA methylation-based model combined with serum tumor markers in participants with cancers or benign diseases | | 22 months |
| Sensitivity and specificity of serum tumor markers, cfDNA methylation-based model, and a cfDNA methylation-based model combined with serum tumor markers, in participants with cancers and healthy participants | | 22 months |
| Sensitivity and specificity of early detection of cancer in different stages | | 22 months |
|
Cancer, Liquid biopsy, Cell-free DNA (cfDNA), Early detection
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cancer Arm<br>Participants with new diagnosis of cancer, from whom blood samples will be collected | Device: Multi-cancer early detection test<br>* Blood collection and multi-cancer early detection test<br>|
| Benign Diseases Arm<br>Participants with benign diseases corresponding to the tumor types in the Cancer Arm, from whom blood samples will be collected | Device: Multi-cancer early detection test<br>* Blood collection and multi-cancer early detection test<br>|
| Healthy Arm<br>Participants without known presence of malignancies or benign disease, from whom blood samples will be collected | Device: Multi-cancer early detection test<br>* Blood collection and multi-cancer early detection test<br>|
|
Pan-canceR Early-Stage deteCtion by lIquid Biopsy tEchNique projecT
Study Overview
=================
Brief Summary
-----------------
PRESCIENT is a multi-center, prospective observational study aimed to detect cancers early by combined assays for serum protein markers and cell-free DNA (cfDNA) methylation markers. Blood RNA markers will also be evaluated. The study will enroll approximately 11879 participants, including participants with malignancies or benign diseases, and healthy participants.
Official Title
-----------------
Pan-cancer Early-stage Detection by Liquid Biopsy in Peripheral Blood: a Multi-center, Prospective Observational Study
Conditions
-----------------
Cancer
Intervention / Treatment
-----------------
* Device: Multi-cancer early detection test
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria for All the Participants: Ability to provide a written informed consent 40-75 years old Exclusion Criteria for All the Participants: Inability to comply with study procedures Pregnancy or lactating women Recipients of organ transplant or prior non-autologous (allogeneic) bone marrow transplant or stem cell transplant Recipients of blood transfusion within 7 days prior to study blood draw Recipients of any anti-cancer therapy within 30 days prior to study blood draw, due to diseases other than cancer Inclusion Criteria for Cancer Arm Participants: Confirmed diagnosis or suspicious cases of one of the 22 types of malignancies within 42 days prior to study blood draw No prior or ongoing anti-cancer therapy (local or systematic) prior to study blood draw Exclusion Criteria for Cancer Arm Participants: Known prior diagnosis of malignancies Other current malignant diseases or multiple primary tumors No confirmed diagnosis of cancer by histopathological or radiological assessments within 42 days of study blood draw, or diagnosis of a benign disease by histopathological assessments, or inability to characterize whether the lesion is malignant or benign Non-small-cell lung cancer patients with ground-class nodularity by radiological examination Inclusion Criteria for Benign Diseases Arm Participants: Confirmed diagnosis of benign diseases corresponding to the tumor types in the Cancer Arm by histopathological or radiological assessments within 90 days prior to study blood draw No prior treatment of benign diseases prior to study blood draw Exclusion Criteria for Benign Diseases Arm Participants: History of malignancies Current malignancies or precancerous lesions No confirmed diagnosis of a benign disease by radiological, endoscopic or histopathological assessments within 42 days of study blood draw, or inability to characterize whether the lesion is malignant or benign Inclusion Criteria for Non-tumor (Healthy) Arm Participants: No cancer-related symptoms or discomfort within 30 days prior to study blood draw No clinically significant finding by LDCT or ultrasound No clinically significant finding by breast ultrasound or Molybdenum Target Mammography Detection, or Thinprep cytologic test (TCT) detection for female participants No active hepatitis B or hepatitis C infection Exclusion Criteria for Non-tumor (Healthy) Arm Participants: Prior or ongoing treatment of cancer within 3 years prior to study blood draw Clinically significant or uncontrolled comorbidities
Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 75 Years
Sexes Eligible for Study
-----------------
All
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cancer Arm<br>Participants with new diagnosis of cancer, from whom blood samples will be collected | Device: Multi-cancer early detection test<br>* Blood collection and multi-cancer early detection test<br>|
| Benign Diseases Arm<br>Participants with benign diseases corresponding to the tumor types in the Cancer Arm, from whom blood samples will be collected | Device: Multi-cancer early detection test<br>* Blood collection and multi-cancer early detection test<br>|
| Healthy Arm<br>Participants without known presence of malignancies or benign disease, from whom blood samples will be collected | Device: Multi-cancer early detection test<br>* Blood collection and multi-cancer early detection test<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and specificity of early detection of 22 types of cancers and Tissue of origin (TOO) accuracy of a cfDNA methylation-based model, in combination with serum tumor markers | | 22 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and specificity of a cfDNA methylation-based model combined with serum tumor markers in participants with cancers or benign diseases | | 22 months |
| Sensitivity and specificity of serum tumor markers, cfDNA methylation-based model, and a cfDNA methylation-based model combined with serum tumor markers, in participants with cancers and healthy participants | | 22 months |
| Sensitivity and specificity of early detection of cancer in different stages | | 22 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cancer, Liquid biopsy, Cell-free DNA (cfDNA), Early detection
|
|||
NCT02932189
|
Use of a New Isokinetic Device for Inspiratory Muscle Training
|
Introduction:~It is well established that physical fitness improves muscle performance either in sedentary people or in athletes. In this regard, specific exercises for respiratory muscles can result in better functional performance in hospitalized individuals, especially in critically ill patients in prolonged weaning.~Objectives:~To compare the following variables between intervention and control patients: success in weaning, free time off ventilator on ICU after weaning, and gain of muscle strength with the use of the inspiratory muscle training (IMT).~Patients and methods:~Prospective randomized controlled clinical trial. Only individuals on prolonged weaning will be enrolled. They will undergo IMT or will be managed in a conventional manner. The primary endpoint will be successful weaning. In addition, other variables such as free time off ventilator on ICU after weaning and muscle strength will be measured. In addition, mortality in the ICU, inside the hospital and after discharge will be followed for one year after study entrance.~Expected results:~According to the working hypothesis, it is expected that the performance of patients undergoing IMT will be superior to the conventional treatment. Also, their time to mortality is expected to be longer.
|
The control group only performed inspiratory muscle training (IMT) with the use of the T-piece. From the first day of prolonged weaning, patients would remain in spontaneous breathing progressing their stay time each day, respecting the criteria already mentioned for interruption and return to mechanical ventilation in support pressure mode.~The intervention group, in addition to the protocol described above, would undergo inspiratory muscle training with the POWER breathe K-5 (UK) device. POWER breathe K-5 will be employed once a day, with an initial loading of 40% of maximal inspiratory strength in a schedule of 30 repetitions. This number of repetitions could be reached in one to 6 sessions depending on the respiratory muscle force of the patient. Most of the times more than one session were required. Typically, subjects performed two to six sessions of 5 to 15 breaths per day, with two minutes rest in ventilation pressure support mode. When the patient was unable to comply with the schedule, the training session was interrupted at a total of 3 minutes. The load was planned to be adjusted weekly with a 5 to 10% increase until 60% of the maximal inspiratory strength was reached with a total time of 10 minutes or 100 breaths. After training with POWER breathe K-5 (UK), the patient would return to mechanical ventilation in support pressure mode for 30-60 minutes, and then follow the conventional T-piece protocol. The IMT was conducted normally between 08h and 10h, Monday through Friday.~All study subjects would be under continuous surveillance through the multi-parameter DX 2010 monitor (Dixtal, São Paulo, SP, Brazil), which records the electrocardiogram, heart rate, peripheral oxygen saturation and systemic arterial pressure. At any sign of instability, the IMT was interrupted and the patient returned to the ventilatory support and/or supplemental oxygen therapy for recovery.~The trial was stopped if at least one of the following intolerance criteria was present: SaO2<90% or PaO2 <60 mm Hg with FIO2 >0.4; PaCO2 > 50 mm Hg or increased by > 8 mm Hg; arterial pH < 7.33 or decreased by 0.07 or more; breathing frequency > 35 breaths/min or increased by 50% for 5 min or longer; heart rate > 140 beats/min or a sustained increase or decrease of > 20%; mean blood pressure > 130 or < 70 mm Hg; or presence of agitation, diaphoresis, disorientation, or depressed mental status.
|
Use of a New Isokinetic Device Oriented by Software for Inspiratory Muscle Training in Prolonged Weaning
|
Respiration, Artificial
|
* Device: Inspiratory muscle training
|
Inclusion Criteria:~Individuals over the age of 18 on mechanical ventilation~Able to initiate ventilator weaning.~Exclusion Criteria:~Positive serology for HIV~Other immunesupressive conditions~Life expectancy less than 12 months~Spinal cord injury above T8~Mechanical ventilation started at another institution~Body mass index >35 kg/m2.
|
18 Years
|
86 Years
|
All
|
No
|
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful weaning | defined by 48 hours on spontaneous ventilation after ventilator withdrawal | one year |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in maximal inspiratory strength in cm H2O as measured by the digital manovacuometer MVD300 for 60 seconds | Assessment of inspiratory strength by the maximal inspiratory pressure and the timed inspiratory effort index | one year |
| Change in the timed inspiratory effort index in cm H2O/sec as calculated by the ratio of the maximal inspiratory pressure and time demanded to reach it as measured by the digital manovacuometer MVD300 for 60 seconds | Assessment of inspiratory strength by the maximal inspiratory pressure and the timed inspiratory effort index | one year |
| Time off the ventilator in the ICU in days. | Assessment of the time the patients are kept in the ICU after the successful weaning, | one year |
|
Mechanical Ventilator Weaning, Respiratory Muscle Training, Mortality Rate
|
Respiratory Aspiration, Respiration Disorders, Respiratory Tract Diseases, Pathologic Processes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Procedure: Ventilator weaning in the conventional way with a tracheal collar. | |
| Experimental: Intervention<br>Procedure: Ventilator weaning with a tracheal collar after inspiratory muscle training with an isokinetic device.~Device: K5 Power Breath | Device: Inspiratory muscle training<br>* For the inspiratory muscle training, an isokinetic device (K5 Power Breath, United Kingdom) will be attached to the artificial airway.<br>|
|
Use of a New Isokinetic Device for Inspiratory Muscle Training
Study Overview
=================
Brief Summary
-----------------
Introduction: It is well established that physical fitness improves muscle performance either in sedentary people or in athletes. In this regard, specific exercises for respiratory muscles can result in better functional performance in hospitalized individuals, especially in critically ill patients in prolonged weaning. Objectives: To compare the following variables between intervention and control patients: success in weaning, free time off ventilator on ICU after weaning, and gain of muscle strength with the use of the inspiratory muscle training (IMT). Patients and methods: Prospective randomized controlled clinical trial. Only individuals on prolonged weaning will be enrolled. They will undergo IMT or will be managed in a conventional manner. The primary endpoint will be successful weaning. In addition, other variables such as free time off ventilator on ICU after weaning and muscle strength will be measured. In addition, mortality in the ICU, inside the hospital and after discharge will be followed for one year after study entrance. Expected results: According to the working hypothesis, it is expected that the performance of patients undergoing IMT will be superior to the conventional treatment. Also, their time to mortality is expected to be longer.
Detailed Description
-----------------
The control group only performed inspiratory muscle training (IMT) with the use of the T-piece. From the first day of prolonged weaning, patients would remain in spontaneous breathing progressing their stay time each day, respecting the criteria already mentioned for interruption and return to mechanical ventilation in support pressure mode. The intervention group, in addition to the protocol described above, would undergo inspiratory muscle training with the POWER breathe K-5 (UK) device. POWER breathe K-5 will be employed once a day, with an initial loading of 40% of maximal inspiratory strength in a schedule of 30 repetitions. This number of repetitions could be reached in one to 6 sessions depending on the respiratory muscle force of the patient. Most of the times more than one session were required. Typically, subjects performed two to six sessions of 5 to 15 breaths per day, with two minutes rest in ventilation pressure support mode. When the patient was unable to comply with the schedule, the training session was interrupted at a total of 3 minutes. The load was planned to be adjusted weekly with a 5 to 10% increase until 60% of the maximal inspiratory strength was reached with a total time of 10 minutes or 100 breaths. After training with POWER breathe K-5 (UK), the patient would return to mechanical ventilation in support pressure mode for 30-60 minutes, and then follow the conventional T-piece protocol. The IMT was conducted normally between 08h and 10h, Monday through Friday. All study subjects would be under continuous surveillance through the multi-parameter DX 2010 monitor (Dixtal, São Paulo, SP, Brazil), which records the electrocardiogram, heart rate, peripheral oxygen saturation and systemic arterial pressure. At any sign of instability, the IMT was interrupted and the patient returned to the ventilatory support and/or supplemental oxygen therapy for recovery. The trial was stopped if at least one of the following intolerance criteria was present: SaO2<90% or PaO2 <60 mm Hg with FIO2 >0.4; PaCO2 > 50 mm Hg or increased by > 8 mm Hg; arterial pH < 7.33 or decreased by 0.07 or more; breathing frequency > 35 breaths/min or increased by 50% for 5 min or longer; heart rate > 140 beats/min or a sustained increase or decrease of > 20%; mean blood pressure > 130 or < 70 mm Hg; or presence of agitation, diaphoresis, disorientation, or depressed mental status.
Official Title
-----------------
Use of a New Isokinetic Device Oriented by Software for Inspiratory Muscle Training in Prolonged Weaning
Conditions
-----------------
Respiration, Artificial
Intervention / Treatment
-----------------
* Device: Inspiratory muscle training
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Individuals over the age of 18 on mechanical ventilation Able to initiate ventilator weaning. Exclusion Criteria: Positive serology for HIV Other immunesupressive conditions Life expectancy less than 12 months Spinal cord injury above T8 Mechanical ventilation started at another institution Body mass index >35 kg/m2.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 86 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Procedure: Ventilator weaning in the conventional way with a tracheal collar. | |
| Experimental: Intervention<br>Procedure: Ventilator weaning with a tracheal collar after inspiratory muscle training with an isokinetic device. Device: K5 Power Breath | Device: Inspiratory muscle training<br>* For the inspiratory muscle training, an isokinetic device (K5 Power Breath, United Kingdom) will be attached to the artificial airway.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful weaning | defined by 48 hours on spontaneous ventilation after ventilator withdrawal | one year |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in maximal inspiratory strength in cm H2O as measured by the digital manovacuometer MVD300 for 60 seconds | Assessment of inspiratory strength by the maximal inspiratory pressure and the timed inspiratory effort index | one year |
| Change in the timed inspiratory effort index in cm H2O/sec as calculated by the ratio of the maximal inspiratory pressure and time demanded to reach it as measured by the digital manovacuometer MVD300 for 60 seconds | Assessment of inspiratory strength by the maximal inspiratory pressure and the timed inspiratory effort index | one year |
| Time off the ventilator in the ICU in days. | Assessment of the time the patients are kept in the ICU after the successful weaning, | one year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Mechanical Ventilator Weaning, Respiratory Muscle Training, Mortality Rate
|
NCT01646619
|
Efficacy Study of Hypothermia Plus Magnesium Sulphate(MgSO4) in the Management of Term and Near Term Babies With Hypoxic Ischemic Encephalopathy
|
The purpose of this study is to assess whether the addition of a drug such as Magnesium sulphate while providing therapeutic hypothermia (or cooling) to babies who are asphyxiated at birth provides additional benefit to the babies' survival and outcome compared to cooling alone.
|
Perinatal Asphyxia continues to be a major cause of neonatal mortality and morbidity even in the most technologically advanced and prosperous countries of the world. The incidence remains unchanged; 1-2% of live births in developed world countries and much higher in developing world countries. Perinatal Asphyxia is a multisystem disorder. Neonatal brain is the most important organ affected by Asphyxic insult because the resulting neuronal damage is permanent. Hypoxic Ischemic Encephalopathy (HIE), the pathognomonic clinical syndrome of asphyxic neuronal insult, occurs in 50-60% of babies with Perinatal Asphyxia. Moderate and severe HIE causes significant neonatal mortality and morbidity. Among patients with moderate HIE, 10-20% die and 30-40% develop neurological deficit, whereas 50% of patients with severe HIE die and almost all survivors develop neurological deficits. Hence the toll on the society continues to be very high in spite of dramatic improvements in neonatal intact survival, particularly in developed world countries.~Until recent years, the management of HIE was limited to supportive intensive care only because there was no specific treatment available to rescue neurons during HIE. However, over the last decade, therapeutic Hypothermia, has emerged as a promising new therapy in reducing neonatal mortality and morbidity due to HIE. This is due to improved understanding of the physiology of neuronal damage during asphyxia insult. Hypoxic Ischemic Encephalopathy (HIE) is a dynamic process which evolves over a period of seventy two hours starting from the time of insult. Two distinct episodes of neuronal damage occur during this time:~The immediate (primary) hypoxic insult followed by a~latent period of recovery which lasts for almost six hours.~This is followed by a much longer and profound period of secondary neuronal damage due to the release of chemical mediators. Therapeutic modalities which can potentially reduce the release of these chemical mediators will provide neuronal rescue. Moderate controlled hypothermia (33.5-34.5 0C) offered during the first 72 hours after the asphyxic insult is one such therapeutic modality which has been the subject of animal studies as well as extensive multicenter trails in human infants over the last two decades.~The studies on animal models have not only confirmed the safety of moderate therapeutic hypothermia; they have also shown a dramatic neuronal rescue in experimental HIE model of lambs subjected to prolonged therapeutic hypothermia immediately after birth. This was followed by pilot RCT's in human infants; the outcomes of which were very encouraging. However a universal change of practice requires large well designed multicenter trails and Meta analyses.~After having established therapeutic hypothermia as a safe and effective modality for neuroprotection in HIE, the neonatologists are facing a new question. Can the investigators enhance the neuroprotective effect of therapeutic hypothermia by adding other potential neuroprotective agents? These potential therapeutic agents include Xenon, Erythropoetin, Magnisium sulphate, Allopurinol, opoids, Topiramate, Inhaled Nitric Oxide (iNO), N-Acetylcystine, Minocycline and Melatonin.13,17 Due to their different mechanisms of action, it is likely that these neuroprotective therapies may add incrementally to the proven beneficial effects of hypothermia. Indeed hypothermia may buy additional time for these neuroprotective agents to act within an expanded 'therapeutic window'.13 These Hypothermia plus therapies are going to be the subject of many new RCT's worldwide over the next few years.~Magnesium Sulphate, a potential neuroprotective agent, acts by reducing neuronal excitotoxicity. MgSO4 has long been used in Obstertrics as a tocolytic agent and has a proven neuroprotective effect in preterm babies born to mothers tocolyzed with MgSO4. A recently conducted RCT in human neonates has compared postnatal magnesium sulfate with placebo in the management of Neonatal HIE. This study, which did not use hypothermia therapy due to lack of facilities, has shown that treatment with MgSO4 improves neurologic outcomes at discharge in term neonates with severe perinatal asphyxia. The animal studies done by Knuckley's group has compared a combination of therapeutic hypothermia and MgSO4 with therapeutic hypothermia alone. In their rat model MgSO4 alone had a minimal beneficial effect. However, MgSO4 plus hypothermia had a significant beneficial effect in reducing the size of the post asphyxia infarct. This animal focal stroke model provides an intriguing suggestion that hypothermia plus MgSO4 provides an additive neuroprotection. No human studies have been done so far to test the difference between therapeutic hypothermia alone and therapeutic hypothermia plus MgSO4. Mag Cool Study (Hypothermia plus MgSO4 Vs Hypothermia plus placebo) will test this hypothesis.
|
A Multicenter Randomized Controlled Trial of Therapeutic Hypothermia Plus Magnesium Sulphate (MgSO4) Versus Therapeutic Hypothermia Plus Placebo in the Management of Term and Near Term Babies With Hypoxic Ischemic Encephalopathy
|
Severe Hypoxic Ischemic Encephalopathy, Moderate Hypoxic Ischemic Encephalopathy
|
* Drug: Magnesium Sulphate
* Drug: Placebo
|
Inclusion Criteria:~The babies will be assessed sequentially by criteria A, B and C listed below:~A. Evidence of Perinatal Asphyxia at birth: Infants ≥35 completed weeks gestation admitted to the NICU with at least one of the following:~Apgar score of <5 at 10 minutes after birth~Continued need for resuscitation, including endotracheal or mask ventilation, at 10 minutes after birth~Acidosis within 60 minutes of birth (defined as any occurrence of umbilical cord arterial or venous pH <7.00 or otherwise arterial or capillary pH <7.00)~Base Deficit (-16 mmol/L or more) in umbilical cord or any blood sample (arterial, venous or capillary) within 60 minutes of birth~Infants that meet criteria A will be assessed for whether they meet the neurological abnormality entry criteria (B) by trained personnel:~B. Clinical Evidence of Moderate to severe encephalopathy, consisting of altered state of consciousness (lethargy, stupor or coma) AND at least one of the following:~hypotonia~abnormal reflexes including oculomotor or pupillary abnormalities~absent or weak suck~clinical seizures~Infants who meet criteria A & B will be assessed by aEEG only in units where facility for Cerebral Function Monitoring (CFM) is available.~C. (Optional) At least 30 minutes duration of amplitude integrated EEG recording that shows abnormal background aEEG activity or seizures. There must be one of the following:~normal background with some seizure activity~continuous seizure activity~moderately abnormal activity: Only Lower border below 5 mV. upper border remains above 10mV~Severely Abnormal activity (suppressed activity): Both Lower border below 5 mV and upper border below 10mV~Exclusion Criteria:~Infants expected to be > 6 hours of age at the time of randomization.Every effort will be made to ensure entry to the study before 3 hours of age.~Major congenital abnormalities, such as diaphragmatic hernia requiring ventilation, or congenital abnormalities suggestive of chromosomal anomaly or other syndromes that includes brain dysgenesis.
| null |
6 Hours
|
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined outcome of Mortality and Severe Neurodevelopmental Disability | Severe Neurodevelopmental Disability will be assessed at discharge from hospital and at 18-24 months of age to assess developmental delay and cerebral palsy using the Bayley Scale of Infant Development II. | 18 - 24 months of age |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistent Hypotension | The development of persistently low blood pressure despite adequate measures to maintain normal blood pressure will be assessed and recorded throughout the hypothermia therapy. | Duration of hypothermia therapy( ie during the first 96 hours) |
| Pulmonary Hemorrhage | The development of Pulmonary hemorrhage at any stage during the patient's hospital stay will be recorded. | Duration of hospital stay, an expected average of up to 4 weeks |
| Intracranial Hemorrhage | The development of Intracranial Hemorrhage at any stage during the patient's hospital stay will be recorded by serial head ultrasounds on day 1 , day 3 and as required. | Duration of hospital stay, an expected average of up to 4 weeks |
| Pulmonary Hypertension | The development of pulmonary hypertension at any stage during the patient's hospital stay will be recorded. | Duration of Hypothermia therapy (ie during the first 96 hours) |
| Prolonged Blood Coagulation time | The development of abnormal coagulation profile during hypothermia therapy will be recorded. | Duration of hypothermia therapy ( ie during the first 96 hours) |
| Culture Proven sepsis | The development of sepsis with a positive blood culture during the patient's hospital stay will be recorded. | Duration of hospital stay, an expected average of up to 4 weeks |
| Necrotizing enterocolitis | The development of necrotizing enterocolitis during the patient's hospital stay will be recorded. | Duration of hospital stay, an expected average of up to 4 weeks |
| Cardiac Arrhythmias | The development ofcardiac arrythmia during hypothermia therapy will be recorded. | Duration of hypothermia therapy (ie during the first 96 hours) |
| Thrombocytopenia | The development of low platelet count (<20,000) during hypothermia therapy will be recorded | Duration of hypothermia therapy (ie during the first 96 hours) |
| Major venous thrombosis | The development of major venous thrombosis or a major vein thrombus during the patient's hospital stay will be recorded. | Duration of hospital stay, an expected average of up to 4 weeks |
| Renal Failure | The development of renal failure during the patient's hospital stay will be recorded | Duration of hospital stay, an expected average of up to 4 weeks |
| Abnormal liver funcion tests (elevated liver enzymes) | The devlopment of raised liver enzymes during the patient's hospital stay will be recorded. | Duration of hospital stay, an expected average of up to 4 weeks |
| Pneumonia | The development of pneumonia during the patient's hospital stay will be assessed and recorded. | Duration of hospital stay, an expected average of up to 4 weeks |
| Pulmonary air leak syndrome | The development of pulmonary air leak syndrome during the patient's hospital stay will be recorded. | Duration of hospital stay, an expected average of up to 4 weeks |
| Prolonged vs shortened hospital stay | The entire duration of hopital stay will be assessed | First day of NICU admission till the day of discharge, an expected average of up to 4 weeks |
| Neurodevelopment score | A developmental paediatrician blinded to the study groups will assess the patient's neurodevlopment on the day of his or her discharge. | On the day of discharge from hospital, an expected average of 4 weeks after admission |
| Abnormal aEEG | The aEEG is used to measure the severity of Hypoxic Ischemic Encephalopathy (moderate or severe). | Before randomization and during hypothermia therapy (0 hours till 96 hours) |
| Presence of multiple handicaps | Multiple handicaps (( defined as the presence of any two of the following in an infant at the age of 18-24 months: neuromotor disability (level 3-5 on GMF Classification), mental delay (Bayley MDI score <70),epilepsy, cortical visual impairment, sensorineural hearing loss)). | 18-24 months of age |
| Bayley Psychomotor Development Score less than 70 | | 18-24 months of age |
| Sensorineural hearing loss equal to, or more than, 40 dB | | 18-24 months of age |
| Epilepsy | Epilepsy is defined as recurrent seizures beyond the neonatal period, requiring anticonvulsant therapy at the time of assessment | 18-24 months of age |
| Microcephaly | Defined as Head circumference more than 2 standard deviations below the mean | 18-24 months of age |
| Result of EEG or MRI | To moniter any abnormal EEG patterns and any evidence of Ischemic/Hemorrhagic lesions on MRI | within the first 14 days of life |
|
Hypoxic Ischemic Encephalopathy, Therapeutic Hypothermia, Therapeutic Hypothermia plus Adjuvant Therapy, Cooling
|
Magnesium Sulfate, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anesthetics, Central Nervous System Depressants, Anti-Arrhythmia Agents, Anticonvulsants, Calcium Channel Blockers, Membrane Transport Modulators, Molecular Mechanisms of Pharmacological Action, Calcium-Regulating Hormones and Agents, Tocolytic Agents, Reproductive Control Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hypothermia + Magnesium Sulphate<br> | Drug: Magnesium Sulphate<br>* 10% MgSo4 (100mg/ml) given in a dose of 250mg/kg IV q 24 hrly for 3 doses(2.5ml/kg).~Diluent: Dextrose 5%.<br>* Other names: MgSo4;|
| Placebo Comparator: Hypothermia+ Placebo<br> | Drug: Placebo<br>* Normal Saline 0.9% Sodium Chloride is diluted in 5% Dextrose to be given as 2.5ml/kg IV q24 hrly for 3 doses.<br>* Other names: 0.9% Sodium Chloride;|
|
Efficacy Study of Hypothermia Plus Magnesium Sulphate(MgSO4) in the Management of Term and Near Term Babies With Hypoxic Ischemic Encephalopathy
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess whether the addition of a drug such as Magnesium sulphate while providing therapeutic hypothermia (or cooling) to babies who are asphyxiated at birth provides additional benefit to the babies' survival and outcome compared to cooling alone.
Detailed Description
-----------------
Perinatal Asphyxia continues to be a major cause of neonatal mortality and morbidity even in the most technologically advanced and prosperous countries of the world. The incidence remains unchanged; 1-2% of live births in developed world countries and much higher in developing world countries. Perinatal Asphyxia is a multisystem disorder. Neonatal brain is the most important organ affected by Asphyxic insult because the resulting neuronal damage is permanent. Hypoxic Ischemic Encephalopathy (HIE), the pathognomonic clinical syndrome of asphyxic neuronal insult, occurs in 50-60% of babies with Perinatal Asphyxia. Moderate and severe HIE causes significant neonatal mortality and morbidity. Among patients with moderate HIE, 10-20% die and 30-40% develop neurological deficit, whereas 50% of patients with severe HIE die and almost all survivors develop neurological deficits. Hence the toll on the society continues to be very high in spite of dramatic improvements in neonatal intact survival, particularly in developed world countries. Until recent years, the management of HIE was limited to supportive intensive care only because there was no specific treatment available to rescue neurons during HIE. However, over the last decade, therapeutic Hypothermia, has emerged as a promising new therapy in reducing neonatal mortality and morbidity due to HIE. This is due to improved understanding of the physiology of neuronal damage during asphyxia insult. Hypoxic Ischemic Encephalopathy (HIE) is a dynamic process which evolves over a period of seventy two hours starting from the time of insult. Two distinct episodes of neuronal damage occur during this time: The immediate (primary) hypoxic insult followed by a latent period of recovery which lasts for almost six hours. This is followed by a much longer and profound period of secondary neuronal damage due to the release of chemical mediators. Therapeutic modalities which can potentially reduce the release of these chemical mediators will provide neuronal rescue. Moderate controlled hypothermia (33.5-34.5 0C) offered during the first 72 hours after the asphyxic insult is one such therapeutic modality which has been the subject of animal studies as well as extensive multicenter trails in human infants over the last two decades. The studies on animal models have not only confirmed the safety of moderate therapeutic hypothermia; they have also shown a dramatic neuronal rescue in experimental HIE model of lambs subjected to prolonged therapeutic hypothermia immediately after birth. This was followed by pilot RCT's in human infants; the outcomes of which were very encouraging. However a universal change of practice requires large well designed multicenter trails and Meta analyses. After having established therapeutic hypothermia as a safe and effective modality for neuroprotection in HIE, the neonatologists are facing a new question. Can the investigators enhance the neuroprotective effect of therapeutic hypothermia by adding other potential neuroprotective agents? These potential therapeutic agents include Xenon, Erythropoetin, Magnisium sulphate, Allopurinol, opoids, Topiramate, Inhaled Nitric Oxide (iNO), N-Acetylcystine, Minocycline and Melatonin.13,17 Due to their different mechanisms of action, it is likely that these neuroprotective therapies may add incrementally to the proven beneficial effects of hypothermia. Indeed hypothermia may buy additional time for these neuroprotective agents to act within an expanded 'therapeutic window'.13 These Hypothermia plus therapies are going to be the subject of many new RCT's worldwide over the next few years. Magnesium Sulphate, a potential neuroprotective agent, acts by reducing neuronal excitotoxicity. MgSO4 has long been used in Obstertrics as a tocolytic agent and has a proven neuroprotective effect in preterm babies born to mothers tocolyzed with MgSO4. A recently conducted RCT in human neonates has compared postnatal magnesium sulfate with placebo in the management of Neonatal HIE. This study, which did not use hypothermia therapy due to lack of facilities, has shown that treatment with MgSO4 improves neurologic outcomes at discharge in term neonates with severe perinatal asphyxia. The animal studies done by Knuckley's group has compared a combination of therapeutic hypothermia and MgSO4 with therapeutic hypothermia alone. In their rat model MgSO4 alone had a minimal beneficial effect. However, MgSO4 plus hypothermia had a significant beneficial effect in reducing the size of the post asphyxia infarct. This animal focal stroke model provides an intriguing suggestion that hypothermia plus MgSO4 provides an additive neuroprotection. No human studies have been done so far to test the difference between therapeutic hypothermia alone and therapeutic hypothermia plus MgSO4. Mag Cool Study (Hypothermia plus MgSO4 Vs Hypothermia plus placebo) will test this hypothesis.
Official Title
-----------------
A Multicenter Randomized Controlled Trial of Therapeutic Hypothermia Plus Magnesium Sulphate (MgSO4) Versus Therapeutic Hypothermia Plus Placebo in the Management of Term and Near Term Babies With Hypoxic Ischemic Encephalopathy
Conditions
-----------------
Severe Hypoxic Ischemic Encephalopathy, Moderate Hypoxic Ischemic Encephalopathy
Intervention / Treatment
-----------------
* Drug: Magnesium Sulphate
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The babies will be assessed sequentially by criteria A, B and C listed below: A. Evidence of Perinatal Asphyxia at birth: Infants ≥35 completed weeks gestation admitted to the NICU with at least one of the following: Apgar score of <5 at 10 minutes after birth Continued need for resuscitation, including endotracheal or mask ventilation, at 10 minutes after birth Acidosis within 60 minutes of birth (defined as any occurrence of umbilical cord arterial or venous pH <7.00 or otherwise arterial or capillary pH <7.00) Base Deficit (-16 mmol/L or more) in umbilical cord or any blood sample (arterial, venous or capillary) within 60 minutes of birth Infants that meet criteria A will be assessed for whether they meet the neurological abnormality entry criteria (B) by trained personnel: B. Clinical Evidence of Moderate to severe encephalopathy, consisting of altered state of consciousness (lethargy, stupor or coma) AND at least one of the following: hypotonia abnormal reflexes including oculomotor or pupillary abnormalities absent or weak suck clinical seizures Infants who meet criteria A & B will be assessed by aEEG only in units where facility for Cerebral Function Monitoring (CFM) is available. C. (Optional) At least 30 minutes duration of amplitude integrated EEG recording that shows abnormal background aEEG activity or seizures. There must be one of the following: normal background with some seizure activity continuous seizure activity moderately abnormal activity: Only Lower border below 5 mV. upper border remains above 10mV Severely Abnormal activity (suppressed activity): Both Lower border below 5 mV and upper border below 10mV Exclusion Criteria: Infants expected to be > 6 hours of age at the time of randomization.Every effort will be made to ensure entry to the study before 3 hours of age. Major congenital abnormalities, such as diaphragmatic hernia requiring ventilation, or congenital abnormalities suggestive of chromosomal anomaly or other syndromes that includes brain dysgenesis.
Ages Eligible for Study
-----------------
Maximum Age: 6 Hours
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: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hypothermia + Magnesium Sulphate<br> | Drug: Magnesium Sulphate<br>* 10% MgSo4 (100mg/ml) given in a dose of 250mg/kg IV q 24 hrly for 3 doses(2.5ml/kg). Diluent: Dextrose 5%.<br>* Other names: MgSo4;|
| Placebo Comparator: Hypothermia+ Placebo<br> | Drug: Placebo<br>* Normal Saline 0.9% Sodium Chloride is diluted in 5% Dextrose to be given as 2.5ml/kg IV q24 hrly for 3 doses.<br>* Other names: 0.9% Sodium Chloride;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined outcome of Mortality and Severe Neurodevelopmental Disability | Severe Neurodevelopmental Disability will be assessed at discharge from hospital and at 18-24 months of age to assess developmental delay and cerebral palsy using the Bayley Scale of Infant Development II. | 18 - 24 months of age |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistent Hypotension | The development of persistently low blood pressure despite adequate measures to maintain normal blood pressure will be assessed and recorded throughout the hypothermia therapy. | Duration of hypothermia therapy( ie during the first 96 hours) |
| Pulmonary Hemorrhage | The development of Pulmonary hemorrhage at any stage during the patient's hospital stay will be recorded. | Duration of hospital stay, an expected average of up to 4 weeks |
| Intracranial Hemorrhage | The development of Intracranial Hemorrhage at any stage during the patient's hospital stay will be recorded by serial head ultrasounds on day 1 , day 3 and as required. | Duration of hospital stay, an expected average of up to 4 weeks |
| Pulmonary Hypertension | The development of pulmonary hypertension at any stage during the patient's hospital stay will be recorded. | Duration of Hypothermia therapy (ie during the first 96 hours) |
| Prolonged Blood Coagulation time | The development of abnormal coagulation profile during hypothermia therapy will be recorded. | Duration of hypothermia therapy ( ie during the first 96 hours) |
| Culture Proven sepsis | The development of sepsis with a positive blood culture during the patient's hospital stay will be recorded. | Duration of hospital stay, an expected average of up to 4 weeks |
| Necrotizing enterocolitis | The development of necrotizing enterocolitis during the patient's hospital stay will be recorded. | Duration of hospital stay, an expected average of up to 4 weeks |
| Cardiac Arrhythmias | The development ofcardiac arrythmia during hypothermia therapy will be recorded. | Duration of hypothermia therapy (ie during the first 96 hours) |
| Thrombocytopenia | The development of low platelet count (<20,000) during hypothermia therapy will be recorded | Duration of hypothermia therapy (ie during the first 96 hours) |
| Major venous thrombosis | The development of major venous thrombosis or a major vein thrombus during the patient's hospital stay will be recorded. | Duration of hospital stay, an expected average of up to 4 weeks |
| Renal Failure | The development of renal failure during the patient's hospital stay will be recorded | Duration of hospital stay, an expected average of up to 4 weeks |
| Abnormal liver funcion tests (elevated liver enzymes) | The devlopment of raised liver enzymes during the patient's hospital stay will be recorded. | Duration of hospital stay, an expected average of up to 4 weeks |
| Pneumonia | The development of pneumonia during the patient's hospital stay will be assessed and recorded. | Duration of hospital stay, an expected average of up to 4 weeks |
| Pulmonary air leak syndrome | The development of pulmonary air leak syndrome during the patient's hospital stay will be recorded. | Duration of hospital stay, an expected average of up to 4 weeks |
| Prolonged vs shortened hospital stay | The entire duration of hopital stay will be assessed | First day of NICU admission till the day of discharge, an expected average of up to 4 weeks |
| Neurodevelopment score | A developmental paediatrician blinded to the study groups will assess the patient's neurodevlopment on the day of his or her discharge. | On the day of discharge from hospital, an expected average of 4 weeks after admission |
| Abnormal aEEG | The aEEG is used to measure the severity of Hypoxic Ischemic Encephalopathy (moderate or severe). | Before randomization and during hypothermia therapy (0 hours till 96 hours) |
| Presence of multiple handicaps | Multiple handicaps (( defined as the presence of any two of the following in an infant at the age of 18-24 months: neuromotor disability (level 3-5 on GMF Classification), mental delay (Bayley MDI score <70),epilepsy, cortical visual impairment, sensorineural hearing loss)). | 18-24 months of age |
| Bayley Psychomotor Development Score less than 70 | | 18-24 months of age |
| Sensorineural hearing loss equal to, or more than, 40 dB | | 18-24 months of age |
| Epilepsy | Epilepsy is defined as recurrent seizures beyond the neonatal period, requiring anticonvulsant therapy at the time of assessment | 18-24 months of age |
| Microcephaly | Defined as Head circumference more than 2 standard deviations below the mean | 18-24 months of age |
| Result of EEG or MRI | To moniter any abnormal EEG patterns and any evidence of Ischemic/Hemorrhagic lesions on MRI | within the first 14 days of life |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hypoxic Ischemic Encephalopathy, Therapeutic Hypothermia, Therapeutic Hypothermia plus Adjuvant Therapy, Cooling
|
NCT01231646
|
Does Valproate Increase Levels of Folate Receptor Autoantibodies in Women?
|
Women who take folate (folic acid) before getting pregnant can lower the risk of giving birth to infant with certain birth defects. However, some medications may affect the action of folate. The purpose of this study is to compare the effect of two anti-epileptic drugs on how folate works in our body.
|
Does Valproate Increase Levels of Folate Receptor Autoantibodies in Women?
|
Epilepsy, Psychiatric or Mood Diseases or Conditions
|
* Other: No intervention
|
Inclusion Criteria:~Women ages 18-50 years inclusive who are taking valproate or lamotrigine for neurologic or psychiatric conditions~Valproate of lamotrigine must be used as monotherapy at stable doses for 6 weeks prior to the study for the neurologic or psychiatric illness; medications taken for other reasons are not excluded.~Exclusion Criteria:~Women with prior exposure to valproate or lamotrigine if they are taking lamotrigine or valproate respectively.
|
18 Years
|
50 Years
|
Female
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of Folate Receptor Autoantibodies | ELISA assays using immobilized folate receptor protein were performed to determine the titers of immunoglobulin G, immunoglobulin M, and combined immunoglobulin G and immunoglobulin M to folate receptor in serum samples collected from both groups of women. | On the same day after informed consent was obtained |
|
Folate Receptor Autoantibodies, Epilepsy, Psychiatric conditions
|
Epilepsy, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lamotrigine<br>No intervention | Other: No intervention<br>* No intervention. This is a cross-sectional study.<br>|
| Valproate<br>No intervention | Other: No intervention<br>* No intervention. This is a cross-sectional study.<br>|
|
Does Valproate Increase Levels of Folate Receptor Autoantibodies in Women?
Study Overview
=================
Brief Summary
-----------------
Women who take folate (folic acid) before getting pregnant can lower the risk of giving birth to infant with certain birth defects. However, some medications may affect the action of folate. The purpose of this study is to compare the effect of two anti-epileptic drugs on how folate works in our body.
Official Title
-----------------
Does Valproate Increase Levels of Folate Receptor Autoantibodies in Women?
Conditions
-----------------
Epilepsy, Psychiatric or Mood Diseases or Conditions
Intervention / Treatment
-----------------
* Other: No intervention
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women ages 18-50 years inclusive who are taking valproate or lamotrigine for neurologic or psychiatric conditions Valproate of lamotrigine must be used as monotherapy at stable doses for 6 weeks prior to the study for the neurologic or psychiatric illness; medications taken for other reasons are not excluded. Exclusion Criteria: Women with prior exposure to valproate or lamotrigine if they are taking lamotrigine or valproate respectively.
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?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lamotrigine<br>No intervention | Other: No intervention<br>* No intervention. This is a cross-sectional study.<br>|
| Valproate<br>No intervention | Other: No intervention<br>* No intervention. This is a cross-sectional study.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of Folate Receptor Autoantibodies | ELISA assays using immobilized folate receptor protein were performed to determine the titers of immunoglobulin G, immunoglobulin M, and combined immunoglobulin G and immunoglobulin M to folate receptor in serum samples collected from both groups of women. | On the same day after informed consent was obtained |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Folate Receptor Autoantibodies, Epilepsy, Psychiatric conditions
|
|||
NCT01658592
|
Deep Brain Stimulation of the Nucleus Accumbens and the Ventral Anterior Internal Capsule for Severe Alcohol Addiction
|
The main objective of this study is to assess the efficacy of bilateral deep brain stimulation (DBS) of the nucleus accumbens (NAc) and the ventral anterior internal capsule (VC) as a novel treatment in severe alcohol addiction. The included patients have been treated so far with drugs that inhibits alcohol, or psychological behavior training.~Our hypothesis is that bilateral NAc-VC DBS will significantly reduce the craving for alcohol and thus enable the patients to decrease their alcohol intake substantially.
|
The nucleus accumbens (NAc) is considered associating with addiction. The ventral anterior internal capsule(VC) is proved a effective target to obsessive compulsive disorder(OCD). Like other addiction behaviors most alcohol addicts contain obsessive compulsive symptom. We explored an operation method, that is, in the Leksell stereotactic positioning system take VC as the point of entry, take NAc as the point of target, then make sure that the distance between entry and target points are included in the four contacts of electrode of DBS. When stimulator is ON the investigators can adjust parameters so that the coverage of electrode contains both Vc and NAc. The investigators suppose that bilateral NAc-VC DBS will significantly reduce the craving for alcohol and thus enable the patients to decrease their alcohol intake substantially.
|
Deep Brain Stimulation of the Nucleus Accumbens and the Ventral Anterior Internal Capsule as a Novel Treatment in Severe Alcohol Addiction
|
Addiction
|
* Other: Deep brain stimulation
* Other: Placebo
|
Inclusion Criteria:~Age > 18 years~Long lasting alcohol addiction (fulfilled diagnostic-criteria according to DSM-IV,ICD-10)~At least one detoxication-treatment without a long-term period of abstinence has already taken place~Long-term inpatient treatment to support abstinence have occurred~Free patient's decision / Informed Consent (existing comprehensive ability in meaning, methodology and execution of the study and ability of acceptance)~If prior medication, stable dosage of psychopharmacological drugs over the last three months, which shall, after checking be retained during the study~Exclusion Criteria:~Hospitalization for psychotic symptoms~Clinical relevant psychiatric comorbidity (such as schizophrenic psychoses, bipolar affective diseases, severe personality disorder, and so on. And diagnosed by criteria according to DSM-IV,ICD-10)~Contraindications of a MRI-examination, e.g. implanted cardiac pacemaker/ heart defibrillator~Current and in the last six months existent paranoid-hallucinated symptomatology~Foreign aggressiveness in the last six months~Verbal IQ < 85 (evaluated with the Wechsler Adult Intelligence Scale- Chinese Revised (WAIS-CR)~Stereotactic respectively neurosurgical intervention in the past~Other neurological diseases~Contraindications of a stereotactic operation, e.g. increased bleeding-disposition, cerebrovascular diseases (e.g. arteriovenous malfunction, aneurysms, systemic vascular diseases)~Serious and instable organic diseases (e.g. instable coronal heart disease)~tested positively for HIV~pregnancy and/or lactation
|
18 Years
|
50 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of Alcohol | Reduction of the dosage of alcohol(all kinds of liquor were converted into pure alcohol) comparing baseline and the particular ward rounds during and at the end of the crossover-design. | 7 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Craving | 10-point visual analog scale (VAS) of craving | 7 months |
|
Alcohol Addiction;, Deep Brain Stimulation;, Nucleus Accumbens;, Ventral Anterior Internal capsule;
|
Alcoholism, Behavior, Addictive, Compulsive Behavior, Impulsive Behavior, Alcohol-Related Disorders, Substance-Related Disorders, Chemically-Induced Disorders, Mental Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NAC-VC Deep Brain Stimulation<br>The contractors located in NAc and VC are ON at the same time | Other: Deep brain stimulation<br>* Stimulator setting is ON<br>Other: Placebo<br>* Stimulator setting is OFF<br>|
| Sham Comparator: Placebo A<br>Stimulator setting is OFF | Other: Deep brain stimulation<br>* Stimulator setting is ON<br>Other: Placebo<br>* Stimulator setting is OFF<br>|
| Experimental: Placebo B<br>The contractor located in NAc is on | Other: Deep brain stimulation<br>* Stimulator setting is ON<br>Other: Placebo<br>* Stimulator setting is OFF<br>|
| Experimental: Placebo C<br>The contactor located in VC is on | Other: Deep brain stimulation<br>* Stimulator setting is ON<br>Other: Placebo<br>* Stimulator setting is OFF<br>|
|
Deep Brain Stimulation of the Nucleus Accumbens and the Ventral Anterior Internal Capsule for Severe Alcohol Addiction
Study Overview
=================
Brief Summary
-----------------
The main objective of this study is to assess the efficacy of bilateral deep brain stimulation (DBS) of the nucleus accumbens (NAc) and the ventral anterior internal capsule (VC) as a novel treatment in severe alcohol addiction. The included patients have been treated so far with drugs that inhibits alcohol, or psychological behavior training. Our hypothesis is that bilateral NAc-VC DBS will significantly reduce the craving for alcohol and thus enable the patients to decrease their alcohol intake substantially.
Detailed Description
-----------------
The nucleus accumbens (NAc) is considered associating with addiction. The ventral anterior internal capsule(VC) is proved a effective target to obsessive compulsive disorder(OCD). Like other addiction behaviors most alcohol addicts contain obsessive compulsive symptom. We explored an operation method, that is, in the Leksell stereotactic positioning system take VC as the point of entry, take NAc as the point of target, then make sure that the distance between entry and target points are included in the four contacts of electrode of DBS. When stimulator is ON the investigators can adjust parameters so that the coverage of electrode contains both Vc and NAc. The investigators suppose that bilateral NAc-VC DBS will significantly reduce the craving for alcohol and thus enable the patients to decrease their alcohol intake substantially.
Official Title
-----------------
Deep Brain Stimulation of the Nucleus Accumbens and the Ventral Anterior Internal Capsule as a Novel Treatment in Severe Alcohol Addiction
Conditions
-----------------
Addiction
Intervention / Treatment
-----------------
* Other: Deep brain stimulation
* Other: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age > 18 years Long lasting alcohol addiction (fulfilled diagnostic-criteria according to DSM-IV,ICD-10) At least one detoxication-treatment without a long-term period of abstinence has already taken place Long-term inpatient treatment to support abstinence have occurred Free patient's decision / Informed Consent (existing comprehensive ability in meaning, methodology and execution of the study and ability of acceptance) If prior medication, stable dosage of psychopharmacological drugs over the last three months, which shall, after checking be retained during the study Exclusion Criteria: Hospitalization for psychotic symptoms Clinical relevant psychiatric comorbidity (such as schizophrenic psychoses, bipolar affective diseases, severe personality disorder, and so on. And diagnosed by criteria according to DSM-IV,ICD-10) Contraindications of a MRI-examination, e.g. implanted cardiac pacemaker/ heart defibrillator Current and in the last six months existent paranoid-hallucinated symptomatology Foreign aggressiveness in the last six months Verbal IQ < 85 (evaluated with the Wechsler Adult Intelligence Scale- Chinese Revised (WAIS-CR) Stereotactic respectively neurosurgical intervention in the past Other neurological diseases Contraindications of a stereotactic operation, e.g. increased bleeding-disposition, cerebrovascular diseases (e.g. arteriovenous malfunction, aneurysms, systemic vascular diseases) Serious and instable organic diseases (e.g. instable coronal heart disease) tested positively for HIV pregnancy and/or lactation
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 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 |
| --- | --- |
| Experimental: NAC-VC Deep Brain Stimulation<br>The contractors located in NAc and VC are ON at the same time | Other: Deep brain stimulation<br>* Stimulator setting is ON<br>Other: Placebo<br>* Stimulator setting is OFF<br>|
| Sham Comparator: Placebo A<br>Stimulator setting is OFF | Other: Deep brain stimulation<br>* Stimulator setting is ON<br>Other: Placebo<br>* Stimulator setting is OFF<br>|
| Experimental: Placebo B<br>The contractor located in NAc is on | Other: Deep brain stimulation<br>* Stimulator setting is ON<br>Other: Placebo<br>* Stimulator setting is OFF<br>|
| Experimental: Placebo C<br>The contactor located in VC is on | Other: Deep brain stimulation<br>* Stimulator setting is ON<br>Other: Placebo<br>* Stimulator setting is OFF<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of Alcohol | Reduction of the dosage of alcohol(all kinds of liquor were converted into pure alcohol) comparing baseline and the particular ward rounds during and at the end of the crossover-design. | 7 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Craving | 10-point visual analog scale (VAS) of craving | 7 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alcohol Addiction;, Deep Brain Stimulation;, Nucleus Accumbens;, Ventral Anterior Internal capsule;
|
NCT03894189
|
The Effect of Doxapram Versus Theophylline on Diaphragmatic Function
|
Doxapram is licensed for drug-induced post-anesthesia respiratory depression , arousal effect and return airway protective reflexes caused by barbiturates, volatile anesthetics, nitrous oxide or benzodiazepines over dosage.~Value of theophylline to stimulate the respiratory neuronal network has been examined by previous studies and increases the activity of respiratory muscles, including the intercostal , transversus abdominis muscles and the diaphragm, it also has bronchodilator and anti-inflammatory effects.
|
This randomized comparative study will be conducted in the post-surgical cardio-thoracic intensive care unit in Beni -Suef University Hospital after approval of the department of anesthesiology, surgical ICU and pain management , and cardio thoracic department and the local ethics and research committee, and obtaining written informed consents from the patients to compare the effect of doxapram versus theophylline on diaphragmatic function using ultrasonography parameter: thickening fraction of the diaphragmatic muscle during respiration which defined as [(thickness at end-inspiration - thickness at end-expiration)/thickness at end-expiration] during spontaneous breathing trial as a primary outcome and its effect on weaning time and weaning success rate as secondary outcomes.
|
The Effect of Doxapram Versus Theophylline on Diaphragmatic Function and Weaning From Mechanical Ventilation After Open Heart Surgery
|
Weaning Failure
|
* Drug: Doxapram Hydrochloride
* Drug: Theophylline
|
Inclusion Criteria: Patients (males and females) in the age group 20 -60 scheduled for elective open heart surgery ( e.g. coronary artery bypass grafting, valve replacement ) under cardiopulmonary bypass .~-~Exclusion Criteria:The preoperative exclusion criteria:~Age older than 60 years~Preoperative left ventricular ejection fraction less than 30%~Chronic obstructive pulmonary disease~Significant hepatic disease (alanine aminotransferase or aspartate aminotransferase >150 U/l).~Renal failure (creatinine >200 μm).~History of seizure, or stroke.~History of diaphragmatic palsy, cervical spine injury, or neuromuscular disease (eg, myasthenia gravis, Guillain-Barré syndrome).~Lesion adjacent to the diaphragm~Intra-abdominal hypertension (intra-abdominal pressure ≥12 mm Hg )~Known allergy to the study drugs.~The Post enrollment exclusion criteria:~Postoperative hemorrhage (chest tube drainage ≥ 200 ml/h).~Surgical complications necessitating reoperation.~Postoperative cardiac failure necessitating high-dose inotropes or intra -aortic balloon pump.~Refractory hypoxemia (ratio of arterial oxygen tension [PaO2] to fraction of inspired oxygen [FIO2] <150 mmHg).~Occurrence of neurologic deficit.~-Myocardial ischemia (ST-segment depression) lasting more than 30 min~Failure of spontaneous breathing trial.~-
|
20 Years
|
60 Years
|
All
|
No
|
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the effect of doxapram versus theophylline on diaphragmatic function | : thickening fraction of the diaphragmatic muscle during respiration which defined as [(thickness at end-inspiration - thickness at end-expiration)/thickness at end-expiration](18) (19) during spontaneous breathing trial as a primary outcome and its effect on weaning time and weaning success rate as secondary outcomes. | the study drugs will be infused for 1 hour,At the end of 60 min of SBT, the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound. |
|
Theophylline, Doxapram, Bronchodilator Agents, Autonomic Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anti-Asthmatic Agents, Respiratory System Agents, Phosphodiesterase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Vasodilator Agents, Purinergic P1 Receptor Antagonists, Purinergic Antagonists, Purinergic Agents, Neurotransmitter Agents, Central Nervous System Stimulants
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: doxapram group (GROUP D)<br>The patients in this group will receive loading dose of (1 mg/kg) followed by an infusion of (1mg/kg/h) | Drug: Doxapram Hydrochloride<br>* the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound. following the administration of the selected drug<br>* Other names: Doxapram;Drug: Theophylline<br>* the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound. following the administration of the selected drug<br>|
| Active Comparator: theophylline group (GROUP T)<br>the therapeutic loading dose (5mg/kg) followed by an infusion of (0.5 mg/kg/h) | Drug: Doxapram Hydrochloride<br>* the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound. following the administration of the selected drug<br>* Other names: Doxapram;Drug: Theophylline<br>* the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound. following the administration of the selected drug<br>|
|
The Effect of Doxapram Versus Theophylline on Diaphragmatic Function
Study Overview
=================
Brief Summary
-----------------
Doxapram is licensed for drug-induced post-anesthesia respiratory depression , arousal effect and return airway protective reflexes caused by barbiturates, volatile anesthetics, nitrous oxide or benzodiazepines over dosage. Value of theophylline to stimulate the respiratory neuronal network has been examined by previous studies and increases the activity of respiratory muscles, including the intercostal , transversus abdominis muscles and the diaphragm, it also has bronchodilator and anti-inflammatory effects.
Detailed Description
-----------------
This randomized comparative study will be conducted in the post-surgical cardio-thoracic intensive care unit in Beni -Suef University Hospital after approval of the department of anesthesiology, surgical ICU and pain management , and cardio thoracic department and the local ethics and research committee, and obtaining written informed consents from the patients to compare the effect of doxapram versus theophylline on diaphragmatic function using ultrasonography parameter: thickening fraction of the diaphragmatic muscle during respiration which defined as [(thickness at end-inspiration - thickness at end-expiration)/thickness at end-expiration] during spontaneous breathing trial as a primary outcome and its effect on weaning time and weaning success rate as secondary outcomes.
Official Title
-----------------
The Effect of Doxapram Versus Theophylline on Diaphragmatic Function and Weaning From Mechanical Ventilation After Open Heart Surgery
Conditions
-----------------
Weaning Failure
Intervention / Treatment
-----------------
* Drug: Doxapram Hydrochloride
* Drug: Theophylline
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients (males and females) in the age group 20 -60 scheduled for elective open heart surgery ( e.g. coronary artery bypass grafting, valve replacement ) under cardiopulmonary bypass . - Exclusion Criteria:The preoperative exclusion criteria: Age older than 60 years Preoperative left ventricular ejection fraction less than 30% Chronic obstructive pulmonary disease Significant hepatic disease (alanine aminotransferase or aspartate aminotransferase >150 U/l). Renal failure (creatinine >200 μm). History of seizure, or stroke. History of diaphragmatic palsy, cervical spine injury, or neuromuscular disease (eg, myasthenia gravis, Guillain-Barré syndrome). Lesion adjacent to the diaphragm Intra-abdominal hypertension (intra-abdominal pressure ≥12 mm Hg ) Known allergy to the study drugs. The Post enrollment exclusion criteria: Postoperative hemorrhage (chest tube drainage ≥ 200 ml/h). Surgical complications necessitating reoperation. Postoperative cardiac failure necessitating high-dose inotropes or intra -aortic balloon pump. Refractory hypoxemia (ratio of arterial oxygen tension [PaO2] to fraction of inspired oxygen [FIO2] <150 mmHg). Occurrence of neurologic deficit. -Myocardial ischemia (ST-segment depression) lasting more than 30 min Failure of spontaneous breathing trial. -
Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 60 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
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 |
| --- | --- |
| Active Comparator: doxapram group (GROUP D)<br>The patients in this group will receive loading dose of (1 mg/kg) followed by an infusion of (1mg/kg/h) | Drug: Doxapram Hydrochloride<br>* the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound. following the administration of the selected drug<br>* Other names: Doxapram;Drug: Theophylline<br>* the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound. following the administration of the selected drug<br>|
| Active Comparator: theophylline group (GROUP T)<br>the therapeutic loading dose (5mg/kg) followed by an infusion of (0.5 mg/kg/h) | Drug: Doxapram Hydrochloride<br>* the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound. following the administration of the selected drug<br>* Other names: Doxapram;Drug: Theophylline<br>* the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound. following the administration of the selected drug<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the effect of doxapram versus theophylline on diaphragmatic function | : thickening fraction of the diaphragmatic muscle during respiration which defined as [(thickness at end-inspiration - thickness at end-expiration)/thickness at end-expiration](18) (19) during spontaneous breathing trial as a primary outcome and its effect on weaning time and weaning success rate as secondary outcomes. | the study drugs will be infused for 1 hour,At the end of 60 min of SBT, the diaphragmatic function will be assessed measuring right and left diaphragmatic thickening fraction in the two groups to be compared as a primary outcome using ultrasound. |
|
||
NCT04719234
|
Lung Ultrasonography in COVID-19 Pneumonia
|
Lung ultrasonography has been used for diagnosis and treatment in many departments including intensive care before the pandemic. The gold standard method for the diagnosis of pneumonia is still chest tomography. Ultrasonography, which has advantages over tomography, has also been tried to be used in covid 19 pneumonia.
|
In this study, it was aimed to investigate the efficiency of lung ultrasonography in diagnosis of covid 19 pneumonia.
|
Comparison of Lung Ultrasonography Findings With Chest Computerized Tomography Results in Corona virüs (COVID-19) Pneumonia
|
Lung Ultrasound, Pneumonia, Covid19
|
* Device: lung ultrasonography
|
Inclusion Criteria:~18 and 85 years old~Hospitalized in intensive care unit~PCR tested~Thoracic CT applied~Exclusion Criteria:~Previous lung and thoracic wall surgery~Anatomically with thoracic wall disorder~Patients who did not consent to participate in the study
|
18 Years
|
85 Years
|
All
|
No
|
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship between Thoracic CT imaging results and LUS results | Lung ultrasonography will be performed within 6 hours of the Thoracic CT. | 6 hours |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characteristics of lesions | İdentifying the characteristics of the abnormal findings detected in Thoracic CT and LUS | 6 hours |
|
COVID-19, Pneumonia, Pneumonia, Viral, Respiratory Tract Infections, Infections, Virus Diseases, Coronavirus Infections, Coronaviridae Infections, Nidovirales Infections, RNA Virus Infections, Lung Diseases, Respiratory Tract Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: lung ultrasound<br>lung ultrasonography protocol will be applied. | Device: lung ultrasonography<br>* Application of 12 zone lung ultrasonography protocol using the konvex ultrasound probe (2-6 MHz)<br>|
|
Lung Ultrasonography in COVID-19 Pneumonia
Study Overview
=================
Brief Summary
-----------------
Lung ultrasonography has been used for diagnosis and treatment in many departments including intensive care before the pandemic. The gold standard method for the diagnosis of pneumonia is still chest tomography. Ultrasonography, which has advantages over tomography, has also been tried to be used in covid 19 pneumonia.
Detailed Description
-----------------
In this study, it was aimed to investigate the efficiency of lung ultrasonography in diagnosis of covid 19 pneumonia.
Official Title
-----------------
Comparison of Lung Ultrasonography Findings With Chest Computerized Tomography Results in Corona virüs (COVID-19) Pneumonia
Conditions
-----------------
Lung Ultrasound, Pneumonia, Covid19
Intervention / Treatment
-----------------
* Device: lung ultrasonography
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 and 85 years old Hospitalized in intensive care unit PCR tested Thoracic CT applied Exclusion Criteria: Previous lung and thoracic wall surgery Anatomically with thoracic wall disorder Patients who did not consent to participate in the study
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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: lung ultrasound<br>lung ultrasonography protocol will be applied. | Device: lung ultrasonography<br>* Application of 12 zone lung ultrasonography protocol using the konvex ultrasound probe (2-6 MHz)<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship between Thoracic CT imaging results and LUS results | Lung ultrasonography will be performed within 6 hours of the Thoracic CT. | 6 hours |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characteristics of lesions | İdentifying the characteristics of the abnormal findings detected in Thoracic CT and LUS | 6 hours |
|
|
NCT04769778
|
Renin Angiotensin System Blockade in Renal Transplant Patients With Presence of PECs in Urine
|
By means of a personalized medicine strategy, investigators are going to evaluate if the treatment with an angiotensin II receptor antagonist (ARAII) in renal transplant patients with the presence of renal progenitor cells (PECs) in the urine is able to prevent the expected loss of glomerular filtration (GFR) observed in this subgroup of patients. In addition, investigators intend to deepen the mechanisms of glomerular damage and glomerular repair involved in the process of chronic allograft damage.
|
A randomized, double-blind clinical trial will be performed in renal transplant patients in month 6 post-transplant, at the time of protocol renal biopsy. After verifying the inclusion and exclusion criteria, informed consent will be obtained. Patients with urinary PECs will be randomized to 80 mg of valsartan vs. placebo (sample size calculated for a superiority study, 45 patients per group). Patients without PECs in urine will be followed according to usual clinical practice. The follow-up will be up to 2 years post-transplant. At baseline (6 m post-transplant) and at 2 years the GFR will be measured by means of iohexol clearance (main variable) and, in addition, we will analyze safety variables such as patient and graft survival and RAGIs. By means of morphometry techniques on renal biopsy and by measuring the renal cortical volume by high resolution CT, the number of glomeruli will be determined, which in turn, will allow to calculate the SN-GFR. Finally, in 5 patients per study group and in 5 controls, PECs of renal tissue will be isolated by means of laser microdissection techniques to perform single-cell RNA sequencing techniques to assess the molecular pathways involved in the glomerular damage and repair process and how the RAAS blockade modifies such molecular pathways.
|
Renin Angiotensin System Blockade in Renal Transplant Patients With Presence of PECs in Urine
|
Chronic Kidney Allograft Nephropathy
|
* Drug: Valsartan 80Mg Oral Tablet
|
Inclusion Criteria:~Written informed consent~Stable renal function understood as a variation of eGFR of less than 15% in the last 3 months~Immunosuppression maintenance based on tacrolimus and MMF / MPA~Exclusion Criteria:~Chronic active infection by HCV, HBV, HIV.~Treatment with inhibitors of the renin angiotensin system.~Double kidney transplant or combined with another organ.~Immunosuppression of maintenance other than tacrolimus and MMF / MPA.~eGFR <20 ml / min / 1.73m2.~History of allergy or intolerance to inhibitors of the renin angiotensin system.~Physically fertile women who plan to become pregnant, are pregnant and~/ or breast-feeding, or who do not want to use effective contraception during their participation in the study.~Any other medical condition that, in the opinion of the investigator, based on the counting or review of clinical records, could affect the completion of the study, including, but not limited to, visual problems or cognitive impairment.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Treatment with valsartan versus no treatment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| prevention of fall of glomerular filtration rate | To assess whether treatment with an angiotensin II receptor antagonist (AIIRA) prevents the fall of glomerular filtration in the subgroup of kidney transplant patients with presence of PECs in urine. | 12 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SN-GFR | Compare the SN-GFR (nephron glomerular filtration rate) | 12 months |
| Single cell RNA sequencing | Carry out single cell RNA sequencing studies using cell microdissection techniques of PEC cells isolated from renal biopsies performed at 6 and 24 m after transplantation in patients without uPECs and in patients with uPECs included in the therapeutic intervention study. These studies will allow us to know the changes of gene expression in PECS cells that can be associated with the favorable response in treated or untreated patients. | 12 months |
| podocyturia | To determine the influence of the treatment on podocyturia and the preservation of the number of podocytes at 2 years post transplant. | 12 months |
| graft survival | Evaluate the influence of treatment on graft survival | 12 months |
| patient survival | Evaluate the influence of treatment on patient survival and proteinuria. | 12 months |
| Chronic Glomerular Lessions | Evaluate the influence of treatment on number of participants with chronic glomerular lesions. | 12 months |
| Suspected Unexpected Serious Adverse Reaction (SUSAR) reporting unexpected serious adverse reactions) | Evaluate the safety of the treatment on the number of patients with Suspected Unexpected Serious Adverse Reaction (SUSAR) reporting unexpected serious adverse reactions) unexpected adverse reactions) and rate of treatment discontinuations. | 12 months |
| Proteinuria | Evaluate the influence of treatment on measure of proteinuria | 12 months |
|
renin angiotensin, kidney transplant, PEC's
|
Valsartan, Antihypertensive Agents, Angiotensin II Type 1 Receptor Blockers, Angiotensin Receptor Antagonists, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Valsartan<br>Treatment with valsartan | Drug: Valsartan 80Mg Oral Tablet<br>* treatment with 80mg /day of valsartan<br>|
| No Intervention: no treatment<br>no treatment received | |
|
Renin Angiotensin System Blockade in Renal Transplant Patients With Presence of PECs in Urine
Study Overview
=================
Brief Summary
-----------------
By means of a personalized medicine strategy, investigators are going to evaluate if the treatment with an angiotensin II receptor antagonist (ARAII) in renal transplant patients with the presence of renal progenitor cells (PECs) in the urine is able to prevent the expected loss of glomerular filtration (GFR) observed in this subgroup of patients. In addition, investigators intend to deepen the mechanisms of glomerular damage and glomerular repair involved in the process of chronic allograft damage.
Detailed Description
-----------------
A randomized, double-blind clinical trial will be performed in renal transplant patients in month 6 post-transplant, at the time of protocol renal biopsy. After verifying the inclusion and exclusion criteria, informed consent will be obtained. Patients with urinary PECs will be randomized to 80 mg of valsartan vs. placebo (sample size calculated for a superiority study, 45 patients per group). Patients without PECs in urine will be followed according to usual clinical practice. The follow-up will be up to 2 years post-transplant. At baseline (6 m post-transplant) and at 2 years the GFR will be measured by means of iohexol clearance (main variable) and, in addition, we will analyze safety variables such as patient and graft survival and RAGIs. By means of morphometry techniques on renal biopsy and by measuring the renal cortical volume by high resolution CT, the number of glomeruli will be determined, which in turn, will allow to calculate the SN-GFR. Finally, in 5 patients per study group and in 5 controls, PECs of renal tissue will be isolated by means of laser microdissection techniques to perform single-cell RNA sequencing techniques to assess the molecular pathways involved in the glomerular damage and repair process and how the RAAS blockade modifies such molecular pathways.
Official Title
-----------------
Renin Angiotensin System Blockade in Renal Transplant Patients With Presence of PECs in Urine
Conditions
-----------------
Chronic Kidney Allograft Nephropathy
Intervention / Treatment
-----------------
* Drug: Valsartan 80Mg Oral Tablet
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent Stable renal function understood as a variation of eGFR of less than 15% in the last 3 months Immunosuppression maintenance based on tacrolimus and MMF / MPA Exclusion Criteria: Chronic active infection by HCV, HBV, HIV. Treatment with inhibitors of the renin angiotensin system. Double kidney transplant or combined with another organ. Immunosuppression of maintenance other than tacrolimus and MMF / MPA. eGFR <20 ml / min / 1.73m2. History of allergy or intolerance to inhibitors of the renin angiotensin system. Physically fertile women who plan to become pregnant, are pregnant and / or breast-feeding, or who do not want to use effective contraception during their participation in the study. Any other medical condition that, in the opinion of the investigator, based on the counting or review of clinical records, could affect the completion of the study, including, but not limited to, visual problems or cognitive impairment.
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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Treatment with valsartan versus no treatment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Valsartan<br>Treatment with valsartan | Drug: Valsartan 80Mg Oral Tablet<br>* treatment with 80mg /day of valsartan<br>|
| No Intervention: no treatment<br>no treatment received | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| prevention of fall of glomerular filtration rate | To assess whether treatment with an angiotensin II receptor antagonist (AIIRA) prevents the fall of glomerular filtration in the subgroup of kidney transplant patients with presence of PECs in urine. | 12 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SN-GFR | Compare the SN-GFR (nephron glomerular filtration rate) | 12 months |
| Single cell RNA sequencing | Carry out single cell RNA sequencing studies using cell microdissection techniques of PEC cells isolated from renal biopsies performed at 6 and 24 m after transplantation in patients without uPECs and in patients with uPECs included in the therapeutic intervention study. These studies will allow us to know the changes of gene expression in PECS cells that can be associated with the favorable response in treated or untreated patients. | 12 months |
| podocyturia | To determine the influence of the treatment on podocyturia and the preservation of the number of podocytes at 2 years post transplant. | 12 months |
| graft survival | Evaluate the influence of treatment on graft survival | 12 months |
| patient survival | Evaluate the influence of treatment on patient survival and proteinuria. | 12 months |
| Chronic Glomerular Lessions | Evaluate the influence of treatment on number of participants with chronic glomerular lesions. | 12 months |
| Suspected Unexpected Serious Adverse Reaction (SUSAR) reporting unexpected serious adverse reactions) | Evaluate the safety of the treatment on the number of patients with Suspected Unexpected Serious Adverse Reaction (SUSAR) reporting unexpected serious adverse reactions) unexpected adverse reactions) and rate of treatment discontinuations. | 12 months |
| Proteinuria | Evaluate the influence of treatment on measure of proteinuria | 12 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
renin angiotensin, kidney transplant, PEC's
|
NCT01165931
|
Coronary Vasomotor Response After Riociguat Exposure
|
The aim of the study is to assess the effects of intracoronary Riociguat on coronary blood flow in subjects with coronary artery disease and to compare this effect with the intracoronary nitroglycerin, a coronary vasodilator widly used to treat patients with coronary artery disease.
|
A Study to Compare the Acute Coronary Vasodilating Effects of the sGC Stimulator Riociguat (BAY 63-2521) With the Nitric Oxide Donor Nitroglycerin in Patients With Coronary Artery Disease
|
Coronary Artery Disease
|
* Drug: Riociguat (BAY63-2521)
|
Inclusion Criteria:~Male and female patients with coronary artery disease~Exclusion Criteria:~Patents with coronary artery disease with >/= 70% luminal stenosis by coronary angiography in one of the 3 major epicardial coronary arteries (left anterior descending artery [LAD], left circumflex coronary artery [LCX] or right coronary artery [RCA]) undergoing cardiac catheterization
|
18 Years
|
90 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The ratio of the coronary blood flow after Riociguat to the corresponding flow observed after adenosine, compared to that after nitroglycerin administration | | Within 5 min after completion of the intracoronary Riociguat infusion |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event collection | | Until 30 days after study drug treatment |
|
Coronary artery disease
|
Riociguat, Enzyme Activators, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: Riociguat (BAY63-2521)<br>* 0.1 mg intracoronary infusion through coronary guide catheter. Single dose. Sequential application after initial vasoactive bolus of Adenosine (non-study drug) and Nitroglycerin (non-study drug).<br>|
|
Coronary Vasomotor Response After Riociguat Exposure
Study Overview
=================
Brief Summary
-----------------
The aim of the study is to assess the effects of intracoronary Riociguat on coronary blood flow in subjects with coronary artery disease and to compare this effect with the intracoronary nitroglycerin, a coronary vasodilator widly used to treat patients with coronary artery disease.
Official Title
-----------------
A Study to Compare the Acute Coronary Vasodilating Effects of the sGC Stimulator Riociguat (BAY 63-2521) With the Nitric Oxide Donor Nitroglycerin in Patients With Coronary Artery Disease
Conditions
-----------------
Coronary Artery Disease
Intervention / Treatment
-----------------
* Drug: Riociguat (BAY63-2521)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female patients with coronary artery disease Exclusion Criteria: Patents with coronary artery disease with >/= 70% luminal stenosis by coronary angiography in one of the 3 major epicardial coronary arteries (left anterior descending artery [LAD], left circumflex coronary artery [LCX] or right coronary artery [RCA]) undergoing cardiac catheterization
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?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: Riociguat (BAY63-2521)<br>* 0.1 mg intracoronary infusion through coronary guide catheter. Single dose. Sequential application after initial vasoactive bolus of Adenosine (non-study drug) and Nitroglycerin (non-study drug).<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The ratio of the coronary blood flow after Riociguat to the corresponding flow observed after adenosine, compared to that after nitroglycerin administration | | Within 5 min after completion of the intracoronary Riociguat infusion |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event collection | | Until 30 days after study drug treatment |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Coronary artery disease
|
|
NCT05754476
|
Multi-center Study of Artificial Intelligence Model for Gadolinium-based Contrast Agent Reduction in Brain MRI (MAGNET)
|
MAGNET is a multi-center and prospective study to minimize Gadolinium-based Contrast Agent (GBCA) combining novel artificial intelligence (AI) methods with pre-contrast images and/or low-dose images to synthesize virtual contrast-enhanced T1 (vir-T1c) images, based on a large clinical and MRI database and subsequently validated for its clinical value. MRI examinations for patients included T1-weighted images (T1WI) before and after contrast agent administration and at two dose levels: low-dose (10% or 25%) and full-dose (100%), T2-weighted images (T2WI), fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging sequences (DWI) and the computed apparent diffusion coefficient (ADC), all either acquired three dimensional [3D] or two dimensional [2D]). The standard dose of intravenous gadolinium contrast agent was 0.1mmol/kg(body weight) by manual injection or automatic injection with a high-pressure syringe at a flow rate of 4mL/s.The sequence parameters used for the 3DT1WI scans must be consistent, and the standard for intravenous injection of gadolinium contrast agent is 0.1mmol/kg (body weight), administered either manually or automatically with a high-pressure syringe at a rate of 4mL/s.~Additionally, arterial spin labeling (ASL), amide-proton transfer chemical exchange saturation transfer (APT-CEST), susceptibility-weighted imaging (SWI), or quantitative susceptibility mapping (QSM) can be acquired at the same time if the conditions permit.
|
MRI with GBCA is an indispensable part of imaging exams for brain disease diagnosis. Generally, GBCA is safe, with a few mild side effects since GBCAs received FDA approval in 1989. There are numerous issues that challenge the current practice of widespread use of GBCA. GBCA can trigger nephrogenic systemic fibrosis(NSF) under particular circumstances, cause allergic reactions, may increase the risk of fetal death, and accumulate in the brain such as the dentate nucleus and globus pallidus. Efforts need to be made to reduce dose while still maintaining diagnostic capabilities. Artificial intelligence (AI) techniques have shown great potential in medical fields. Deep learning (DL), a branch of AI, has been applied to image segmentation, computer-aided diagnosis, and reduce GBCA dose.~This study intends to build a prospective brain MRI dataset including patients with suspected or known brain abnormalities to minimize the use of GBCA. Then train DL models to process pre-contrast images and/or low-dose T1 images to predict virtual contrast-enhanced T1 (vir-T1c) images, taking the full-dose images as the reference standard. Later quantitatively and qualitatively evaluating and comparing vir-T1c images from DL models about clinical diagnostic performance, focusing on lesion detection, diagnosis, and therapy, to explore a DL model universal, provide enhanced images faster and more convenient in clinical practice. To minimize the use of GBCA, we will:~Use novel artificial intelligence (AI) methods with pre-contrast images including conventional (T1WI, T2WI, FLAIR, DWI/ADC), new physiological MRI techniques (ASL, APT-CEST, SWI/QSM) by adding physiological information from perfusion as well as metabolic and susceptibility imaging, and/or low-dose images (10% or 25%) to synthesize vir-T1c images;~Quantify when (in which patients and at what follow-up times) GBCA can be omitted or minimized without influencing brain disease diagnosis and treatment evaluation for doctor raters and therefore patient prognosis.~This study does not limit manufacturers including 1.5T and 3.0T scanners， or kinds of GBCAs.
|
Multi-center and Prospective Cohort Study of Artificial Intelligence Model for Gadolinium-based Contrast Agent Reduction in Brain MRI (MAGNET)
|
Brain Diseases
|
* Other: Low-dose GBCA levels
|
Inclusion Criteria:~Patients with suspected or known brain diseases including tumors, vascular disorders, inflammatory diseases, neurodegenerative diseases and trauma, follow-up, routine brain, and others requiring MRI exams with GBCAs.~Informed written consent obtained from the patient, and/or patient's parent(s), and/or legal representative.~Exclusion Criteria:~Patients with contraindications to MR examination.~Patients with incomplete MRI data and obvious image artifacts.
| null | null |
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| quantitative metrics | To quantitatively describe the discrepancies between the vir-T1c and the full-dose images by measuring the peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM). The PSNR measures the voxelwise difference and the PSNR range is between -1 and 1. The SSIM compares nonlocal structural similarity and the minimum value of PSNR is 0. The metrics will be reported in separate(e.g.,SSIM, 0.90; PSNR,42 in vir-T1c, SSIM, 0.94; PSNR,45 in full-dose images). | after training and applying of the proposed deep learning model, an average of 1 year |
| qualitative assessments | To qualitatively describe discrepancies between the vir-T1c and full-dose images by evaluating enhancement degree, homogeneity, and pattern.~Firstly, zero indicates no intracranial or non-enhancing lesion. For enhancement degree, 1 indicates mild enhancement, 2 indicates moderate enhancement, and 3 indicates clear enhancement.~For enhancement homogeneity, 1 indicates heterogeneous enhancement, 2 indicates mildly heterogeneous enhancement, and 3 indicates homogeneous enhancement.~For enhancement pattern, 1 indicates mass enhancement（proportion enhancement more than 50%）, 2 indicates nodular enhancement (proportion enhancement less than or equal to 50%）, 3 indicates ring enhancement, 4 indicates linear enhancement, and 5 indicates other enhancement. | after training and applying of the proposed deep learning model, an average of 15 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical effects | To describe whether vir-T1c images combing other sequences affect diagnosis or treatment according to evaluation of neuroradiologist and neurologist from 1 to 5 scores.~Zero indicates enhancement error and can not be used. 1 indicates non-diagnostic. 2 indicates affecting diagnosis or treatment significantly. 3 indicates affecting diagnosis or treatment moderately. 4 indicates no affecting diagnosis or treatment almost. 5 indicates no affecting diagnosis or treatment completely. | after training and applying of the proposed deep learning model, an average of 18 month |
|
Brain Diseases, Central Nervous System Diseases, Nervous System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Brain Diseases<br>This study does not limit the kinds of brain diseases. The cohort includes patients with suspected or known brain diseases including tumors, vascular disorder, inflammatory disease, neurodegenerative diseases and trauma, follow-up, routine brain, and others requiring MRI exams with GBCAs. | Other: Low-dose GBCA levels<br>* MRI examinations for patients at two dose levels: low-dose (10% or 25%）can be chosen.<br>|
|
Multi-center Study of Artificial Intelligence Model for Gadolinium-based Contrast Agent Reduction in Brain MRI (MAGNET)
Study Overview
=================
Brief Summary
-----------------
MAGNET is a multi-center and prospective study to minimize Gadolinium-based Contrast Agent (GBCA) combining novel artificial intelligence (AI) methods with pre-contrast images and/or low-dose images to synthesize virtual contrast-enhanced T1 (vir-T1c) images, based on a large clinical and MRI database and subsequently validated for its clinical value. MRI examinations for patients included T1-weighted images (T1WI) before and after contrast agent administration and at two dose levels: low-dose (10% or 25%) and full-dose (100%), T2-weighted images (T2WI), fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging sequences (DWI) and the computed apparent diffusion coefficient (ADC), all either acquired three dimensional [3D] or two dimensional [2D]). The standard dose of intravenous gadolinium contrast agent was 0.1mmol/kg(body weight) by manual injection or automatic injection with a high-pressure syringe at a flow rate of 4mL/s.The sequence parameters used for the 3DT1WI scans must be consistent, and the standard for intravenous injection of gadolinium contrast agent is 0.1mmol/kg (body weight), administered either manually or automatically with a high-pressure syringe at a rate of 4mL/s. Additionally, arterial spin labeling (ASL), amide-proton transfer chemical exchange saturation transfer (APT-CEST), susceptibility-weighted imaging (SWI), or quantitative susceptibility mapping (QSM) can be acquired at the same time if the conditions permit.
Detailed Description
-----------------
MRI with GBCA is an indispensable part of imaging exams for brain disease diagnosis. Generally, GBCA is safe, with a few mild side effects since GBCAs received FDA approval in 1989. There are numerous issues that challenge the current practice of widespread use of GBCA. GBCA can trigger nephrogenic systemic fibrosis(NSF) under particular circumstances, cause allergic reactions, may increase the risk of fetal death, and accumulate in the brain such as the dentate nucleus and globus pallidus. Efforts need to be made to reduce dose while still maintaining diagnostic capabilities. Artificial intelligence (AI) techniques have shown great potential in medical fields. Deep learning (DL), a branch of AI, has been applied to image segmentation, computer-aided diagnosis, and reduce GBCA dose. This study intends to build a prospective brain MRI dataset including patients with suspected or known brain abnormalities to minimize the use of GBCA. Then train DL models to process pre-contrast images and/or low-dose T1 images to predict virtual contrast-enhanced T1 (vir-T1c) images, taking the full-dose images as the reference standard. Later quantitatively and qualitatively evaluating and comparing vir-T1c images from DL models about clinical diagnostic performance, focusing on lesion detection, diagnosis, and therapy, to explore a DL model universal, provide enhanced images faster and more convenient in clinical practice. To minimize the use of GBCA, we will: Use novel artificial intelligence (AI) methods with pre-contrast images including conventional (T1WI, T2WI, FLAIR, DWI/ADC), new physiological MRI techniques (ASL, APT-CEST, SWI/QSM) by adding physiological information from perfusion as well as metabolic and susceptibility imaging, and/or low-dose images (10% or 25%) to synthesize vir-T1c images; Quantify when (in which patients and at what follow-up times) GBCA can be omitted or minimized without influencing brain disease diagnosis and treatment evaluation for doctor raters and therefore patient prognosis. This study does not limit manufacturers including 1.5T and 3.0T scanners， or kinds of GBCAs.
Official Title
-----------------
Multi-center and Prospective Cohort Study of Artificial Intelligence Model for Gadolinium-based Contrast Agent Reduction in Brain MRI (MAGNET)
Conditions
-----------------
Brain Diseases
Intervention / Treatment
-----------------
* Other: Low-dose GBCA levels
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with suspected or known brain diseases including tumors, vascular disorders, inflammatory diseases, neurodegenerative diseases and trauma, follow-up, routine brain, and others requiring MRI exams with GBCAs. Informed written consent obtained from the patient, and/or patient's parent(s), and/or legal representative. Exclusion Criteria: Patients with contraindications to MR examination. Patients with incomplete MRI data and obvious image artifacts.
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 |
| --- | --- |
| Brain Diseases<br>This study does not limit the kinds of brain diseases. The cohort includes patients with suspected or known brain diseases including tumors, vascular disorder, inflammatory disease, neurodegenerative diseases and trauma, follow-up, routine brain, and others requiring MRI exams with GBCAs. | Other: Low-dose GBCA levels<br>* MRI examinations for patients at two dose levels: low-dose (10% or 25%）can be chosen.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| quantitative metrics | To quantitatively describe the discrepancies between the vir-T1c and the full-dose images by measuring the peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM). The PSNR measures the voxelwise difference and the PSNR range is between -1 and 1. The SSIM compares nonlocal structural similarity and the minimum value of PSNR is 0. The metrics will be reported in separate(e.g.,SSIM, 0.90; PSNR,42 in vir-T1c, SSIM, 0.94; PSNR,45 in full-dose images). | after training and applying of the proposed deep learning model, an average of 1 year |
| qualitative assessments | To qualitatively describe discrepancies between the vir-T1c and full-dose images by evaluating enhancement degree, homogeneity, and pattern. Firstly, zero indicates no intracranial or non-enhancing lesion. For enhancement degree, 1 indicates mild enhancement, 2 indicates moderate enhancement, and 3 indicates clear enhancement. For enhancement homogeneity, 1 indicates heterogeneous enhancement, 2 indicates mildly heterogeneous enhancement, and 3 indicates homogeneous enhancement. For enhancement pattern, 1 indicates mass enhancement（proportion enhancement more than 50%）, 2 indicates nodular enhancement (proportion enhancement less than or equal to 50%）, 3 indicates ring enhancement, 4 indicates linear enhancement, and 5 indicates other enhancement. | after training and applying of the proposed deep learning model, an average of 15 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical effects | To describe whether vir-T1c images combing other sequences affect diagnosis or treatment according to evaluation of neuroradiologist and neurologist from 1 to 5 scores. Zero indicates enhancement error and can not be used. 1 indicates non-diagnostic. 2 indicates affecting diagnosis or treatment significantly. 3 indicates affecting diagnosis or treatment moderately. 4 indicates no affecting diagnosis or treatment almost. 5 indicates no affecting diagnosis or treatment completely. | after training and applying of the proposed deep learning model, an average of 18 month |
|
||
NCT05502159
|
M-Tapa Block vs External Oblique Intercostal Block for Laparoscopic Cholesistectomy
|
Ultrasound (US)-guided Modified Perichondral Approach Thoracoabdominal Nerve (M-TAPA) block is a novel block that provides effective analgesia in the anterior and lateral abdominal walls after laparoscopic surgery, and local anesthetic is applied only to the lower side of the perichondral surface. M-TAPA block is a good alternative for analgesia of the upper dermatome levels and the abdominal lateral wall and may be an opioid-sparing strategy with good quality recovery in patients undergoing laparoscopic surgery.~US-guided External oblique intercostal block (EOB) is a block performed by injection of local anesthetic between the external and internal oblique muscles. This block provides abdominal analgesia between T6-T10 levels. There are studies in the literature showing that it provides effective analgesia. However, there is no study comparing M-TAPA and EOB yet.~In this study, our aim is to compare the effectiveness of US-guided M-TAPA block and EOB for postoperative analgesia management after laparoscopic cholecystectomy surgery. Our primary aim is to compare patient recovery scores (QoR15 Turkish version), our secondary aim is to compare postoperative pain scores (24-hour NRS), postoperative rescue analgesic use (opioid), and opioid-related side effects (allergic reaction, nausea, vomiting).
|
Cholecystectomy is the most common of the abdominal surgical procedures performed in developed countries and is usually performed laparoscopically. Many factors play a role in the pain that develops after laparoscopic cholecystectomy and is generally considered to be visceral pain. Phrenic nerve irritation as a result of CO2 insufflation into the peritoneal cavity, abdominal distention, tissue trauma, trauma due to the removal of the gallbladder, sociocultural status, and individual factors are the factors that play a role in the emergence of this pain.~Postoperative pain is acute pain that is accompanied by an inflammatory process due to surgical trauma and gradually decreases with tissue healing. Postoperative pain in patients undergoing laparoscopic cholecystectomy is a serious problem that reduces patient comfort and delays the patient's return to work after surgery. Successful postoperative analgesia, occurs in the patient due to pain; It is a known fact that it prevents many of the effects such as not being able to breathe easily and delayed mobilization.~Modified Perichondral Approach Thoracoabdominal Nerve (M-TAPA) block performed with ultrasound (US) is a new block that provides effective analgesia in the anterior and lateral abdominal walls after laparoscopic surgery in which local anesthetic is applied only to the lower side of the perichondral surface. M-TAPA block is a good alternative for analgesia of the upper dermatome levels and the abdominal lateral wall and may be an opioid-sparing strategy with good quality recovery in patients undergoing laparoscopic surgery.~M-TAPA block provides analgesia in the T5-T11 abdominal region. Sonoanatomy is easy to visualize on US and the spread of local anesthetic can be easily seen. With the cephalo-caudal spread of the local anesthetic solution, analgesia occurs in several dermatomes. In the literature, there are studies investigating the effectiveness of M-TAPA block for post-operative pain management in bariatric surgery. In the literature, there is no randomized study evaluating the effectiveness of M-TAPA block for postoperative analgesia management after laparoscopic cholecystectomy operation.~US-guided External oblique intercostal block (EOB) is a block performed by injection of local anesthetic between the external and internal oblique muscles. This block provides abdominal analgesia between T6-T10 levels. There are studies in the literature showing that it provides effective analgesia. However, there is no study comparing M-TAPA and EOB yet.
|
Comparison of Ultrasound-Guided M-TAPA Block and External Oblique Intercostal Block for Postoperative Analgesia Management in Patients Undergoing Laparoscopic Cholecystectomy
|
Cholecystitis, Cholecystitis, Acute
|
* Drug: M-TAPA
* Drug: EOB
|
Inclusion Criteria:~American Society of Anesthesiologists (ASA) classification I-II~Scheduled for laparoscopic inguinal hernia repair surgery under general anesthesia~Exclusion Criteria:~Bleeding diathesis~anticoagulant treatment~local anesthetics and opioid allergy~Infection at the site of block~Patients who do not accept the procedure
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Sixty patients aged 18-65 years old with American Society of Anesthesiologists (ASA) classification I-II and scheduled for laparoscopic cholesistectomy surgery will be included in the study. Patients will be randomly divided into two groups (Group M = M-TAPA group, Group EOB = EOB group) including 30 patients each, before entering the operating room.
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global recovery scoring system (patient satisfaction scale) | We will use the Turkish version of Quality of Recovery / QoR-15 questionairre | Change from baseline score at postoperative 24 hour |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative pain scores (Numerical rating scale) (0-meaning no pain to 10-meaning worst pain imaginable) | Change from Baseline Pain Scores at Postoperative 24 hours. | Postoperative 24 hours period (0, 2, 4, 8, 16 ve 24 h) |
| The use of rescue analgesia | Meperidin using (Number of Participants and Concentration of Meperidin) | Postoperative 24 hours period |
|
Laparoscopic Cholesistectomy, Postoperative pain management, M-TAPA block, External oblique intercostal block
|
Cholecystitis, Acalculous Cholecystitis, Cholecystitis, Acute, Gallbladder Diseases, Biliary Tract Diseases, Digestive System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group M-TAPA = M-TAPA group<br>Patients will be administered ibuprofen 400 mgr IV every 8 hours in the postoperative period. Postoperative patient evaluation will be performed by a pain nurse blinded to the procedure. 0,5 mg/kg meperidin will be performed for rescue analgesia. | Drug: M-TAPA<br>* Under aseptic conditions, a high-frequency linear probe will be placed on the costochondral angle in the sagittal plane. Then the probe will be slightly angled deeply to visualize the lower view of the perichondrium. We will perform M-TAPA with total of 40 ml (20 ml for each side) of %0,25 bupivacaine.<br>|
| Active Comparator: Group EOB = EOB group<br>Patients will be administered ibuprofen 400 mgr IV every 8 hours in the postoperative period. Postoperative patient evaluation will be performed by a pain nurse blinded to the procedure. 0,5 mg/kg meperidin will be performed for rescue analgesia. | Drug: EOB<br>* In the supine position, a high-frequency linear US probe (11-12 MHz, Vivid Q) will be covered with a sterile sheath, and an 80 mm block needle (Braun 360°) will be used. The US probe will be placed on the midaxillary line between the spina iliaca anterior superior and the umbilicus. Using the In-Plane technique, 5 ml of saline will be injected under the external oblique muscle of the block needle and the block location will be confirmed. After the block location is confirmed, 20 ml of 0.25% bupivacaine will be administered. The same procedure will be applied to the other side (40 ml of 0.25% bupivacaine in total).<br>|
|
M-Tapa Block vs External Oblique Intercostal Block for Laparoscopic Cholesistectomy
Study Overview
=================
Brief Summary
-----------------
Ultrasound (US)-guided Modified Perichondral Approach Thoracoabdominal Nerve (M-TAPA) block is a novel block that provides effective analgesia in the anterior and lateral abdominal walls after laparoscopic surgery, and local anesthetic is applied only to the lower side of the perichondral surface. M-TAPA block is a good alternative for analgesia of the upper dermatome levels and the abdominal lateral wall and may be an opioid-sparing strategy with good quality recovery in patients undergoing laparoscopic surgery. US-guided External oblique intercostal block (EOB) is a block performed by injection of local anesthetic between the external and internal oblique muscles. This block provides abdominal analgesia between T6-T10 levels. There are studies in the literature showing that it provides effective analgesia. However, there is no study comparing M-TAPA and EOB yet. In this study, our aim is to compare the effectiveness of US-guided M-TAPA block and EOB for postoperative analgesia management after laparoscopic cholecystectomy surgery. Our primary aim is to compare patient recovery scores (QoR15 Turkish version), our secondary aim is to compare postoperative pain scores (24-hour NRS), postoperative rescue analgesic use (opioid), and opioid-related side effects (allergic reaction, nausea, vomiting).
Detailed Description
-----------------
Cholecystectomy is the most common of the abdominal surgical procedures performed in developed countries and is usually performed laparoscopically. Many factors play a role in the pain that develops after laparoscopic cholecystectomy and is generally considered to be visceral pain. Phrenic nerve irritation as a result of CO2 insufflation into the peritoneal cavity, abdominal distention, tissue trauma, trauma due to the removal of the gallbladder, sociocultural status, and individual factors are the factors that play a role in the emergence of this pain. Postoperative pain is acute pain that is accompanied by an inflammatory process due to surgical trauma and gradually decreases with tissue healing. Postoperative pain in patients undergoing laparoscopic cholecystectomy is a serious problem that reduces patient comfort and delays the patient's return to work after surgery. Successful postoperative analgesia, occurs in the patient due to pain; It is a known fact that it prevents many of the effects such as not being able to breathe easily and delayed mobilization. Modified Perichondral Approach Thoracoabdominal Nerve (M-TAPA) block performed with ultrasound (US) is a new block that provides effective analgesia in the anterior and lateral abdominal walls after laparoscopic surgery in which local anesthetic is applied only to the lower side of the perichondral surface. M-TAPA block is a good alternative for analgesia of the upper dermatome levels and the abdominal lateral wall and may be an opioid-sparing strategy with good quality recovery in patients undergoing laparoscopic surgery. M-TAPA block provides analgesia in the T5-T11 abdominal region. Sonoanatomy is easy to visualize on US and the spread of local anesthetic can be easily seen. With the cephalo-caudal spread of the local anesthetic solution, analgesia occurs in several dermatomes. In the literature, there are studies investigating the effectiveness of M-TAPA block for post-operative pain management in bariatric surgery. In the literature, there is no randomized study evaluating the effectiveness of M-TAPA block for postoperative analgesia management after laparoscopic cholecystectomy operation. US-guided External oblique intercostal block (EOB) is a block performed by injection of local anesthetic between the external and internal oblique muscles. This block provides abdominal analgesia between T6-T10 levels. There are studies in the literature showing that it provides effective analgesia. However, there is no study comparing M-TAPA and EOB yet.
Official Title
-----------------
Comparison of Ultrasound-Guided M-TAPA Block and External Oblique Intercostal Block for Postoperative Analgesia Management in Patients Undergoing Laparoscopic Cholecystectomy
Conditions
-----------------
Cholecystitis, Cholecystitis, Acute
Intervention / Treatment
-----------------
* Drug: M-TAPA
* Drug: EOB
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: American Society of Anesthesiologists (ASA) classification I-II Scheduled for laparoscopic inguinal hernia repair surgery under general anesthesia Exclusion Criteria: Bleeding diathesis anticoagulant treatment local anesthetics and opioid allergy Infection at the site of block Patients who do not accept the procedure
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: Sixty patients aged 18-65 years old with American Society of Anesthesiologists (ASA) classification I-II and scheduled for laparoscopic cholesistectomy surgery will be included in the study. Patients will be randomly divided into two groups (Group M = M-TAPA group, Group EOB = EOB group) including 30 patients each, before entering the operating room.
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group M-TAPA = M-TAPA group<br>Patients will be administered ibuprofen 400 mgr IV every 8 hours in the postoperative period. Postoperative patient evaluation will be performed by a pain nurse blinded to the procedure. 0,5 mg/kg meperidin will be performed for rescue analgesia. | Drug: M-TAPA<br>* Under aseptic conditions, a high-frequency linear probe will be placed on the costochondral angle in the sagittal plane. Then the probe will be slightly angled deeply to visualize the lower view of the perichondrium. We will perform M-TAPA with total of 40 ml (20 ml for each side) of %0,25 bupivacaine.<br>|
| Active Comparator: Group EOB = EOB group<br>Patients will be administered ibuprofen 400 mgr IV every 8 hours in the postoperative period. Postoperative patient evaluation will be performed by a pain nurse blinded to the procedure. 0,5 mg/kg meperidin will be performed for rescue analgesia. | Drug: EOB<br>* In the supine position, a high-frequency linear US probe (11-12 MHz, Vivid Q) will be covered with a sterile sheath, and an 80 mm block needle (Braun 360°) will be used. The US probe will be placed on the midaxillary line between the spina iliaca anterior superior and the umbilicus. Using the In-Plane technique, 5 ml of saline will be injected under the external oblique muscle of the block needle and the block location will be confirmed. After the block location is confirmed, 20 ml of 0.25% bupivacaine will be administered. The same procedure will be applied to the other side (40 ml of 0.25% bupivacaine in total).<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global recovery scoring system (patient satisfaction scale) | We will use the Turkish version of Quality of Recovery / QoR-15 questionairre | Change from baseline score at postoperative 24 hour |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative pain scores (Numerical rating scale) (0-meaning no pain to 10-meaning worst pain imaginable) | Change from Baseline Pain Scores at Postoperative 24 hours. | Postoperative 24 hours period (0, 2, 4, 8, 16 ve 24 h) |
| The use of rescue analgesia | Meperidin using (Number of Participants and Concentration of Meperidin) | Postoperative 24 hours period |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Laparoscopic Cholesistectomy, Postoperative pain management, M-TAPA block, External oblique intercostal block
|
NCT01253616
|
Proof-of-Concept Study Assessing VNS Paired With Tones for Tinnitus
|
This is a proof-of-concept study designed to provide feasibility information on the clinical use of vagus nerve stimulation (VNS) paired with tones for the treatment of severe tinnitus. The study is expected to give preliminary efficacy and safety information.
|
A Proof-of-Concept Pilot Study Assessing Vagus Nerve Stimulation (VNS) Paired With Tones for Tinnitus
|
Severe Tinnitus
|
* Device: vagus nerve stimulation (VNS)
|
Key Inclusion Criteria:~18 to 65 years of age~Diagnosed with subjective tinnitus due to hearing loss with at least some tonal quality of the tinnitus.~Diagnosis of tinnitus for at least one year~Tinnitus severity of 18 or greater on TRQ cross checked with TQ severity of Grade 3 or worse~Key Exclusion Criteria:~Acute or intermittent tinnitus~Severe hearing loss~History of significant ear disease such as Meniere's disease, ear tumors, or evidence of active middle ear disease.~Any other implanted device
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Audiometric measurements | | weekly through one month |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tinnitus questionaires | | weekly through one month |
| adverse events | | as they occur |
|
Tinnitus, Hearing Disorders, Ear Diseases, Otorhinolaryngologic Diseases, Sensation Disorders, Neurologic Manifestations, Nervous System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VNS plus tones<br> | Device: vagus nerve stimulation (VNS)<br>* Daily stimulation synchronized with tones at the study assigned dose (amplitude, frequency, on/off cycle and treatment period).<br>|
|
Proof-of-Concept Study Assessing VNS Paired With Tones for Tinnitus
Study Overview
=================
Brief Summary
-----------------
This is a proof-of-concept study designed to provide feasibility information on the clinical use of vagus nerve stimulation (VNS) paired with tones for the treatment of severe tinnitus. The study is expected to give preliminary efficacy and safety information.
Official Title
-----------------
A Proof-of-Concept Pilot Study Assessing Vagus Nerve Stimulation (VNS) Paired With Tones for Tinnitus
Conditions
-----------------
Severe Tinnitus
Intervention / Treatment
-----------------
* Device: vagus nerve stimulation (VNS)
Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: 18 to 65 years of age Diagnosed with subjective tinnitus due to hearing loss with at least some tonal quality of the tinnitus. Diagnosis of tinnitus for at least one year Tinnitus severity of 18 or greater on TRQ cross checked with TQ severity of Grade 3 or worse Key Exclusion Criteria: Acute or intermittent tinnitus Severe hearing loss History of significant ear disease such as Meniere's disease, ear tumors, or evidence of active middle ear disease. Any other implanted device
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
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VNS plus tones<br> | Device: vagus nerve stimulation (VNS)<br>* Daily stimulation synchronized with tones at the study assigned dose (amplitude, frequency, on/off cycle and treatment period).<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Audiometric measurements | | weekly through one month |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tinnitus questionaires | | weekly through one month |
| adverse events | | as they occur |
|
||
NCT04715152
|
ACB Versus IA Analgesia in Knee Arthroscopy
|
Reconstruction of the anterior cruciate ligament (ACL) of the knee is a painful procedure, and effective postoperative analgesia is important for early return of patient activity.
|
Reconstruction of the anterior cruciate ligament (ACL) of the knee is a painful procedure, with postoperative analgesia providing patient comfort, early mobilization, and discharge within 24 hours.~Various methods for postoperative analgesia management are available, such as systemic opioids, epidural local anesthetic, peripheral nerve block and local anesthetic infiltration analgesia. Use of systemic opioids can cause adverse effects that may affect functional rehabilitation, such as nausea, vomiting, pruritus, sedation and respiratory depression. Hypotension, urinary retention, and pruritus are more common in patients with epidural analgesia. In addition, use of long-acting intrathecal opioids causes adverse effects such as bilateral motor block, tremor and hypotension. Systemic and intrathecal methods for postoperative analgesia are gradually being abandoned because of these negative effects.~The saphenous nerve is the largest contributor to sensory perception around the knee, while the adductor canal contains the nerve to the vastus medialis, the medial femoral cutaneous nerve, the medial retinacular nerve, articular branches from the posterior division of the obturator nerve and occasionally the anterior branch of the obturator nerve. Although adductor canal block (ACB) can contribute towards motor blockade of the periarticular musculature, its effect on functional weakness of the quadriceps has been reported to be minimal, compared with femoral nerve block (FNB).~Intra-articular (IA) local anesthetic agents have been used either alone or in combination with other agent. However, it was observed that use of combination of drug is better than single drug for prevention of postoperative pain, providing synergistic effect and reducing side effects compared to high dose of single drug.~Levobupivacaine, the S-enantiomer of bupivacaine is a comparatively newer local anesthetic agent introduced into clinical practice and it also possesses less cardiac and neural toxicity. Levobupivacaine has been shown to be safe and effective for epidural and spinal anesthesia and blockade of the brachial plexus.~Dexamethasone is a potent and highly selective glucocorticoid with minimal mineralocorticoid effect. It blocks the nociceptive impulse transmission along the myelinated C fibers. Dexamethasone prolongs the duration of regional blocks, when combined with local anesthetics.
|
Adductor Canal Block Versus Intra-articular Analgesia for Postoperative Pain After Arthroscopic Anterior Cruciate Ligament Reconstruction: a Randomized Trial
|
Postoperative Pain
|
* Drug: ACB with levobupivacaine and dexamethasone
* Drug: IA analgesia with levobupivacaine and dexamethasone
|
Inclusion Criteria:~Patients undergoing elective arthroscopic reconstruction of the anterior cruciate ligament (ACL) under spinal anesthesia, aged from 18 to 65 years old~Exclusion Criteria:~Contraindications to peripheral nerve block (e.g. allergy to local anesthetics, coagulopathy, infection in the area)~History of cardiovascular, cerebrovascular, and respiratory diseases~Preexisting neuropathies~Chronic pain syndrome~Opioid dependence~Patients with diabetes mellitus, sever hypertension, hepatic or renal dysfunction~Pregnancy~Preoperative inability to perform the mobilization test (TUG test)~Not willingness to participate.
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pain free time after surgery | Assessed using the visual analogue scale of pain graded from 0 = no pain to 10 = maximum pain | 24 hours after surgery |
|
Dexamethasone, Dexamethasone acetate, Levobupivacaine, BB 1101, Anti-Inflammatory Agents, Antiemetics, Autonomic Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Gastrointestinal Agents, Glucocorticoids, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Antineoplastic Agents, Hormonal, Antineoplastic Agents, Protease Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Anesthetics, Local, Anesthetics, Central Nervous System Depressants, Sensory System Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ACB group<br>Patients will receive ultrasound-guided (USG) ACB with levobupivacaine and dexamethasone 30 minutes before spinal anesthesia and sham intra-articular normal saline. | Drug: ACB with levobupivacaine and dexamethasone<br>* Patients will receive ultrasound-guided (USG) ACB with levobupivacaine and dexamethasone 30 minutes before spinal anesthesia and sham intra-articular normal saline<br>|
| Placebo Comparator: IA group<br>Patients will receive intra-articular levobupivacaine and dexamethasone at the end of surgery and sham USG-ACB with normal saline. | Drug: IA analgesia with levobupivacaine and dexamethasone<br>* Patients will receive intra-articular levobupivacaine and dexamethasone at the end of surgery and sham USG-ACB with normal saline<br>|
|
ACB Versus IA Analgesia in Knee Arthroscopy
Study Overview
=================
Brief Summary
-----------------
Reconstruction of the anterior cruciate ligament (ACL) of the knee is a painful procedure, and effective postoperative analgesia is important for early return of patient activity.
Detailed Description
-----------------
Reconstruction of the anterior cruciate ligament (ACL) of the knee is a painful procedure, with postoperative analgesia providing patient comfort, early mobilization, and discharge within 24 hours. Various methods for postoperative analgesia management are available, such as systemic opioids, epidural local anesthetic, peripheral nerve block and local anesthetic infiltration analgesia. Use of systemic opioids can cause adverse effects that may affect functional rehabilitation, such as nausea, vomiting, pruritus, sedation and respiratory depression. Hypotension, urinary retention, and pruritus are more common in patients with epidural analgesia. In addition, use of long-acting intrathecal opioids causes adverse effects such as bilateral motor block, tremor and hypotension. Systemic and intrathecal methods for postoperative analgesia are gradually being abandoned because of these negative effects. The saphenous nerve is the largest contributor to sensory perception around the knee, while the adductor canal contains the nerve to the vastus medialis, the medial femoral cutaneous nerve, the medial retinacular nerve, articular branches from the posterior division of the obturator nerve and occasionally the anterior branch of the obturator nerve. Although adductor canal block (ACB) can contribute towards motor blockade of the periarticular musculature, its effect on functional weakness of the quadriceps has been reported to be minimal, compared with femoral nerve block (FNB). Intra-articular (IA) local anesthetic agents have been used either alone or in combination with other agent. However, it was observed that use of combination of drug is better than single drug for prevention of postoperative pain, providing synergistic effect and reducing side effects compared to high dose of single drug. Levobupivacaine, the S-enantiomer of bupivacaine is a comparatively newer local anesthetic agent introduced into clinical practice and it also possesses less cardiac and neural toxicity. Levobupivacaine has been shown to be safe and effective for epidural and spinal anesthesia and blockade of the brachial plexus. Dexamethasone is a potent and highly selective glucocorticoid with minimal mineralocorticoid effect. It blocks the nociceptive impulse transmission along the myelinated C fibers. Dexamethasone prolongs the duration of regional blocks, when combined with local anesthetics.
Official Title
-----------------
Adductor Canal Block Versus Intra-articular Analgesia for Postoperative Pain After Arthroscopic Anterior Cruciate Ligament Reconstruction: a Randomized Trial
Conditions
-----------------
Postoperative Pain
Intervention / Treatment
-----------------
* Drug: ACB with levobupivacaine and dexamethasone
* Drug: IA analgesia with levobupivacaine and dexamethasone
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients undergoing elective arthroscopic reconstruction of the anterior cruciate ligament (ACL) under spinal anesthesia, aged from 18 to 65 years old Exclusion Criteria: Contraindications to peripheral nerve block (e.g. allergy to local anesthetics, coagulopathy, infection in the area) History of cardiovascular, cerebrovascular, and respiratory diseases Preexisting neuropathies Chronic pain syndrome Opioid dependence Patients with diabetes mellitus, sever hypertension, hepatic or renal dysfunction Pregnancy Preoperative inability to perform the mobilization test (TUG test) Not willingness to participate.
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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ACB group<br>Patients will receive ultrasound-guided (USG) ACB with levobupivacaine and dexamethasone 30 minutes before spinal anesthesia and sham intra-articular normal saline. | Drug: ACB with levobupivacaine and dexamethasone<br>* Patients will receive ultrasound-guided (USG) ACB with levobupivacaine and dexamethasone 30 minutes before spinal anesthesia and sham intra-articular normal saline<br>|
| Placebo Comparator: IA group<br>Patients will receive intra-articular levobupivacaine and dexamethasone at the end of surgery and sham USG-ACB with normal saline. | Drug: IA analgesia with levobupivacaine and dexamethasone<br>* Patients will receive intra-articular levobupivacaine and dexamethasone at the end of surgery and sham USG-ACB with normal saline<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pain free time after surgery | Assessed using the visual analogue scale of pain graded from 0 = no pain to 10 = maximum pain | 24 hours after surgery |
|
||
NCT05042999
|
The Use of Virtual Reality During Breast Ultrasound-Guided Biopsy Procedures
|
To determine if a virtual reality simulation will reduce pain and anxiety in patients undergoing an ultrasound guided breast biopsy procedure.
|
Breast biopsies for patients with abnormal mammograms are required to identify cancerous tissue. Currently this procedure is done with or without a local anesthetic. Patients report anxiety regarding potentially having cancer and the possibility of cancer-related procedures. Different types of biopsies may have different pain and anxiety based on their duration and complexity. This research is designed to determine if VR simulated environment can reduce pain and anxiety.~The aim is to study the efficacy of a virtual environment in reducing pain and procedural anxiety. It is intended for patients undergoing an ultrasound guided breast biopsy procedure that have had an abnormal mammogram. The overall aim is to discover an efficacious nonpharmacologic method to lower pain and anxiety during a standard of care procedure.
|
The Use of Virtual Reality During Breast Ultrasound-Guided Biopsy Procedures
|
Breast Neoplasm Female
|
* Device: Oculus Go Virtual Reality Goggles
|
Inclusion Criteria:~Informed consent is obtained from the patient~Females who are 18 years of age~Patient is scheduled for preoperative ultrasound guided breast biopsy procedure~Exclusion Criteria:~Patient is scheduled for a stereotactic biopsy procedure~The patient has motion sickness~The patient has severe cognitive disabilities or language barriers that inhibit study form completion in English~The patient has a history of seizures or epilepsy~Refusal of patient to sign consent
|
18 Years
| null |
Female
|
No
|
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective Pain Assessment: Visual Analog Scale | Pain Measured with the Visual Analog Scale. Visual Analogue Scale (VAS) is a measurement instrument that tries to measure a characteristic or attitude that is believed to range across a continuum of values and cannot easily be directly measured. The individual will score their pain level by circling a number 0 - 10 both pre-operative and post-operatively. The scale range includes 0-10 scales, with < 2 =well controlled, 2 - 5: partly controlled, > 5: uncontrolled. | Immediate post-procedure |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| State-Trait Anxiety Inventory (STAI: Y-6 item) | The State-Trait Anxiety Inventory uses a 4 point Likert scale to assess how much worry, tension or apprehension the subject experiences in his or her present circumstances (state anxiety) and how much anxiety represent a personality characteristic (trait anxiety). Items emphasize the frequency of particular symptoms (ranging from 1 = not at all to 4 = very much). The range of possible scores for form Y of the STAI varies from a minimum score of 20 to a maximum score of 80 on both the STAI-T and STAI-S subscales. STAI scores are commonly classified as no or low anxiety (20-37), moderate anxiety (38-44), and high anxiety (45-80). | Immediate post-procedure |
| Patient Satisfaction | Patients in both groups will be asked to rate their satisfaction with their procedures using a five point likert scale (ranging from 1 = definitely disagree to 5 = definitely agree). | Immediate post-procedure |
|
Virtual Reality, Pain, Anxiety, Ultrasound Guided Biopsy
|
Breast Neoplasms, Neoplasms by Site, Neoplasms, Breast Diseases, Skin Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Virtual Reality Goggles<br>Patients randomized to the intervention group will undergo their procedure as standard of care but will wear the Oculus Go Goggles and experience a virtual reality simulation. The simulation is a non-interactive polar theme video. | Device: Oculus Go Virtual Reality Goggles<br>* Oculus Go is a standalone portable Virtual Reality device that enables the user to immerse in different virtual environments. Non pharmacological technique to reduce pain and anxiety during a procedure.<br>|
| No Intervention: Control<br>Patients randomized to the control group will undergo their procedure as standard of care without the use of virtual reality goggles. | |
|
The Use of Virtual Reality During Breast Ultrasound-Guided Biopsy Procedures
Study Overview
=================
Brief Summary
-----------------
To determine if a virtual reality simulation will reduce pain and anxiety in patients undergoing an ultrasound guided breast biopsy procedure.
Detailed Description
-----------------
Breast biopsies for patients with abnormal mammograms are required to identify cancerous tissue. Currently this procedure is done with or without a local anesthetic. Patients report anxiety regarding potentially having cancer and the possibility of cancer-related procedures. Different types of biopsies may have different pain and anxiety based on their duration and complexity. This research is designed to determine if VR simulated environment can reduce pain and anxiety. The aim is to study the efficacy of a virtual environment in reducing pain and procedural anxiety. It is intended for patients undergoing an ultrasound guided breast biopsy procedure that have had an abnormal mammogram. The overall aim is to discover an efficacious nonpharmacologic method to lower pain and anxiety during a standard of care procedure.
Official Title
-----------------
The Use of Virtual Reality During Breast Ultrasound-Guided Biopsy Procedures
Conditions
-----------------
Breast Neoplasm Female
Intervention / Treatment
-----------------
* Device: Oculus Go Virtual Reality Goggles
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Informed consent is obtained from the patient Females who are 18 years of age Patient is scheduled for preoperative ultrasound guided breast biopsy procedure Exclusion Criteria: Patient is scheduled for a stereotactic biopsy procedure The patient has motion sickness The patient has severe cognitive disabilities or language barriers that inhibit study form completion in English The patient has a history of seizures or epilepsy Refusal of patient to sign consent
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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Virtual Reality Goggles<br>Patients randomized to the intervention group will undergo their procedure as standard of care but will wear the Oculus Go Goggles and experience a virtual reality simulation. The simulation is a non-interactive polar theme video. | Device: Oculus Go Virtual Reality Goggles<br>* Oculus Go is a standalone portable Virtual Reality device that enables the user to immerse in different virtual environments. Non pharmacological technique to reduce pain and anxiety during a procedure.<br>|
| No Intervention: Control<br>Patients randomized to the control group will undergo their procedure as standard of care without the use of virtual reality goggles. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective Pain Assessment: Visual Analog Scale | Pain Measured with the Visual Analog Scale. Visual Analogue Scale (VAS) is a measurement instrument that tries to measure a characteristic or attitude that is believed to range across a continuum of values and cannot easily be directly measured. The individual will score their pain level by circling a number 0 - 10 both pre-operative and post-operatively. The scale range includes 0-10 scales, with < 2 =well controlled, 2 - 5: partly controlled, > 5: uncontrolled. | Immediate post-procedure |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| State-Trait Anxiety Inventory (STAI: Y-6 item) | The State-Trait Anxiety Inventory uses a 4 point Likert scale to assess how much worry, tension or apprehension the subject experiences in his or her present circumstances (state anxiety) and how much anxiety represent a personality characteristic (trait anxiety). Items emphasize the frequency of particular symptoms (ranging from 1 = not at all to 4 = very much). The range of possible scores for form Y of the STAI varies from a minimum score of 20 to a maximum score of 80 on both the STAI-T and STAI-S subscales. STAI scores are commonly classified as no or low anxiety (20-37), moderate anxiety (38-44), and high anxiety (45-80). | Immediate post-procedure |
| Patient Satisfaction | Patients in both groups will be asked to rate their satisfaction with their procedures using a five point likert scale (ranging from 1 = definitely disagree to 5 = definitely agree). | Immediate post-procedure |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Virtual Reality, Pain, Anxiety, Ultrasound Guided Biopsy
|
NCT05428566
|
A Comparison of a PULSE Diet and the TLC Diet on Reproductive, Metabolic Parameters in Women With PCOS
|
The main objective of the study is to evaluate the effectiveness of a lifestyle program for women with Polycystic Ovary Syndrome (PCOS). The investigators want to assess the efficacy of a pulse-based diet (i.e. a diet that contains lentils, chick-peas, and beans) on the clinical features, biochemical, and hormonal parameters of PCOS compared to the healthy therapeutic lifestyle changes diet.
|
The main objective of the study is to identify the effect of pulses on a range of PCOS and metabolic syndrome features. In this parallel clinical trial, 110 (18-35 years old) women with PCOS will be recruited. Participants will be randomly assigned to either a pulse-based diet or a therapeutic lifestyle changes-based diet. The effect of a pulse-based diet on a range of reproductive and metabolic parameters will be evaluated. The results of this study are anticipated to evaluate the therapeutic merits of a pulse-based diet for women with PCOS which would influence dietary guidelines.
|
A Comparison of a Pulse-Based Diet and the Therapeutic Lifestyle Changes Diet on Reproductive and Metabolic Parameters in Women With Polycystic Ovary Syndrome
|
Polycystic Ovary Syndrome, Metabolic Syndrome
|
* Dietary Supplement: Pulse-based diet
* Dietary Supplement: TLC diet
|
Inclusion Criteria:~Female~Diagnosis of PCOS in addition to insulin resistance (Homeostasis model assessment (HOMA)-insulin resistance index ≥ 2).~Aged 18-35 years~Exclusion Criteria:~Individuals that are Keto diet, vegetarian, pregnant, lactating, class 2 obese (body mass index (BMI) ≥35) current smoker, or if they have diabetes, cardiovascular, kidney, liver, or hormonal disease.~Individuals taking any medication or supplementation known to affect lipid, glucose, or hormone levels, and/or body weight for at least the last 3 months.~Any individual who has an allergy or intolerance to pulses.
|
18 Years
|
35 Years
|
Female
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood concentration of androgen hormone | Androgen hormone; testosterone will be evaluated for all participants across the 2 study arms | Change from Baseline sample at 3 months |
| Ovarian volume | An experienced ultrasonographer will evaluate the ovarian volume for each ovary. | Change from Baseline ovarian morphology at 3 months |
| Ovulatory dysfunction | Assessed by measuring the duration of the menstrual cycle | During nine months |
| Lipid profile | Blood Cholesterol will be evaluated for all participants across the 2 study arms | Change from Baseline sample at 3 months |
| Change in fat mass | Body composition scan using InBody 120 (the body composition analyzer) will be evaluated for all participants across the 2 study arms | Change from Baseline measurements at 3 months |
| Physical activity | The validated Arabic short form of the International Physical Activity Questionnaire (IPAQ) will be used to evaluate physical activity of all participants. And an overall total physical activity MET-minutes/week score can be computed as: Total physical activity MET-minutes/week = sum of Total (Walking + Moderate + Vigorous) MET- minutes/week scores.~( < 4 : Low), (4-6 Moderate) and ( >6: Vigorous) | Change from Baseline point at 3 months |
| Blood pressure | In mmHg.(Systolic and Diastolic) | Change from Baseline Systolic Blood Pressure at 3 months |
|
Polycystic Ovary Syndrome, Metabolic Syndrome, Therapeutic Lifestyle Changes Diet, Pulse-Based Diet, Aerobic Exercise
|
Syndrome, Hyperinsulinism, Glucose Metabolism Disorders, Metabolic Diseases, Ovarian Cysts, Cysts, Polycystic Ovary Syndrome, Metabolic Syndrome, Disease, Pathologic Processes, Insulin Resistance, Neoplasms, Ovarian Diseases, Adnexal Diseases, Genital Diseases, Female, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Genital Diseases, Gonadal Disorders, Endocrine System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pulse-based diet<br>The pulse diet will include two pulse-based meals; each pulse meal will be consisted of about one cup of non-oil seed pulses, different varieties of pulses (dried beans, peas, lentils, lupine, and chickpeas) will be used. Varieties of pulses will be included and the participants will be provided with recipes and preparation ideas, which would enhance the palatability of pulses, give different taste choices, and ease the follow of the prescribed diet and encourage the participants to consume it for the target duration.~The diet is isocaloric and balanced with a fixed macronutrient composition of 28% fat, 55% carbohydrate, and 17% protein. | Dietary Supplement: Pulse-based diet<br>* An isocaloric, balanced diet with a fixed macronutrient composition of 28% fat, 55% carbohydrate, and 17% protein.~The pulse diet will include two pulse-based meals; each pulse meal will be consisted of about one cup of non-oil seed pulses, different varieties of pulses (dried beans, peas, lentils, lupine and chickpeas) will be used.<br>|
| Placebo Comparator: TLC diet<br>TLC group will be provided with instructions to follow the TLC guidelines and a sample diet plan will be individualized for each participant. The healthy TLC diet will be tailored for each participant according to their energy levels in order to achieve the following amount of nutrients: less than 7% of total calories of saturated fatty acids, up to 10% of total calories of polyunsaturated fat, up to 20% of total calories of monounsaturated fat, less than 200 mg a day of cholesterol, at least 5 to 10 grams a day of soluble fiber.~The diet is isocaloric and balanced with a fixed macronutrient composition of 28% fat, 55% carbohydrate, and 17% protein. | Dietary Supplement: TLC diet<br>* An isocaloric, balanced diet with a fixed macronutrient composition of 28% fat, 55% carbohydrate, and 17% protein.~The healthy TLC diet will be tailored for each participant according to their energy levels in order to achieve the following amount of nutrients: less than 7% of total calories of saturated fatty acids, up to 10% of total calories of polyunsaturated fat, up to 20% of total calories of monounsaturated fat, less than 200 mg a day of cholesterol, at least 5 to 10 grams a day of soluble fiber.<br>|
|
A Comparison of a PULSE Diet and the TLC Diet on Reproductive, Metabolic Parameters in Women With PCOS
Study Overview
=================
Brief Summary
-----------------
The main objective of the study is to evaluate the effectiveness of a lifestyle program for women with Polycystic Ovary Syndrome (PCOS). The investigators want to assess the efficacy of a pulse-based diet (i.e. a diet that contains lentils, chick-peas, and beans) on the clinical features, biochemical, and hormonal parameters of PCOS compared to the healthy therapeutic lifestyle changes diet.
Detailed Description
-----------------
The main objective of the study is to identify the effect of pulses on a range of PCOS and metabolic syndrome features. In this parallel clinical trial, 110 (18-35 years old) women with PCOS will be recruited. Participants will be randomly assigned to either a pulse-based diet or a therapeutic lifestyle changes-based diet. The effect of a pulse-based diet on a range of reproductive and metabolic parameters will be evaluated. The results of this study are anticipated to evaluate the therapeutic merits of a pulse-based diet for women with PCOS which would influence dietary guidelines.
Official Title
-----------------
A Comparison of a Pulse-Based Diet and the Therapeutic Lifestyle Changes Diet on Reproductive and Metabolic Parameters in Women With Polycystic Ovary Syndrome
Conditions
-----------------
Polycystic Ovary Syndrome, Metabolic Syndrome
Intervention / Treatment
-----------------
* Dietary Supplement: Pulse-based diet
* Dietary Supplement: TLC diet
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female Diagnosis of PCOS in addition to insulin resistance (Homeostasis model assessment (HOMA)-insulin resistance index ≥ 2). Aged 18-35 years Exclusion Criteria: Individuals that are Keto diet, vegetarian, pregnant, lactating, class 2 obese (body mass index (BMI) ≥35) current smoker, or if they have diabetes, cardiovascular, kidney, liver, or hormonal disease. Individuals taking any medication or supplementation known to affect lipid, glucose, or hormone levels, and/or body weight for at least the last 3 months. Any individual who has an allergy or intolerance to pulses.
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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pulse-based diet<br>The pulse diet will include two pulse-based meals; each pulse meal will be consisted of about one cup of non-oil seed pulses, different varieties of pulses (dried beans, peas, lentils, lupine, and chickpeas) will be used. Varieties of pulses will be included and the participants will be provided with recipes and preparation ideas, which would enhance the palatability of pulses, give different taste choices, and ease the follow of the prescribed diet and encourage the participants to consume it for the target duration. The diet is isocaloric and balanced with a fixed macronutrient composition of 28% fat, 55% carbohydrate, and 17% protein. | Dietary Supplement: Pulse-based diet<br>* An isocaloric, balanced diet with a fixed macronutrient composition of 28% fat, 55% carbohydrate, and 17% protein. The pulse diet will include two pulse-based meals; each pulse meal will be consisted of about one cup of non-oil seed pulses, different varieties of pulses (dried beans, peas, lentils, lupine and chickpeas) will be used.<br>|
| Placebo Comparator: TLC diet<br>TLC group will be provided with instructions to follow the TLC guidelines and a sample diet plan will be individualized for each participant. The healthy TLC diet will be tailored for each participant according to their energy levels in order to achieve the following amount of nutrients: less than 7% of total calories of saturated fatty acids, up to 10% of total calories of polyunsaturated fat, up to 20% of total calories of monounsaturated fat, less than 200 mg a day of cholesterol, at least 5 to 10 grams a day of soluble fiber. The diet is isocaloric and balanced with a fixed macronutrient composition of 28% fat, 55% carbohydrate, and 17% protein. | Dietary Supplement: TLC diet<br>* An isocaloric, balanced diet with a fixed macronutrient composition of 28% fat, 55% carbohydrate, and 17% protein. The healthy TLC diet will be tailored for each participant according to their energy levels in order to achieve the following amount of nutrients: less than 7% of total calories of saturated fatty acids, up to 10% of total calories of polyunsaturated fat, up to 20% of total calories of monounsaturated fat, less than 200 mg a day of cholesterol, at least 5 to 10 grams a day of soluble fiber.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood concentration of androgen hormone | Androgen hormone; testosterone will be evaluated for all participants across the 2 study arms | Change from Baseline sample at 3 months |
| Ovarian volume | An experienced ultrasonographer will evaluate the ovarian volume for each ovary. | Change from Baseline ovarian morphology at 3 months |
| Ovulatory dysfunction | Assessed by measuring the duration of the menstrual cycle | During nine months |
| Lipid profile | Blood Cholesterol will be evaluated for all participants across the 2 study arms | Change from Baseline sample at 3 months |
| Change in fat mass | Body composition scan using InBody 120 (the body composition analyzer) will be evaluated for all participants across the 2 study arms | Change from Baseline measurements at 3 months |
| Physical activity | The validated Arabic short form of the International Physical Activity Questionnaire (IPAQ) will be used to evaluate physical activity of all participants. And an overall total physical activity MET-minutes/week score can be computed as: Total physical activity MET-minutes/week = sum of Total (Walking + Moderate + Vigorous) MET- minutes/week scores. ( < 4 : Low), (4-6 Moderate) and ( >6: Vigorous) | Change from Baseline point at 3 months |
| Blood pressure | In mmHg.(Systolic and Diastolic) | Change from Baseline Systolic Blood Pressure at 3 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Polycystic Ovary Syndrome, Metabolic Syndrome, Therapeutic Lifestyle Changes Diet, Pulse-Based Diet, Aerobic Exercise
|
|
NCT02872714
|
A Study to Evaluate the Efficacy and Safety of Pemigatinib (INCB054828) in Subjects With Urothelial Carcinoma - (FIGHT-201)
|
The purpose of this study is to evaluate the overall response rate (ORR) of pemigatinib as a monotherapy in the treatment of metastatic or surgically unresectable urothelial carcinoma harboring FGF/FGFR alterations.
|
A Phase 2, Open-Label, Single-Agent, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib (INCB054828) in Subjects With Metastatic or Surgically Unresectable Urothelial Carcinoma Harboring FGF/FGFR Alterations - (FIGHT-201)
|
UC (Urothelial Cancer)
|
* Drug: pemigatinib
* Drug: pemigatinib
|
Inclusion Criteria:~20 years and older in Japan~Histologically documented metastatic or surgically unresectable urothelial carcinoma; may include primary site from urethra, ureters, upper tract, renal pelvis, and bladder.~Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.~Life expectancy ≥ 12 weeks.~Radiographically measurable per RECIST v1.1.~Documented FGF/FGFR alteration and have either 1a) failed at least 1 previous treatment for their metastatic or surgically unresectable urothelial carcinoma (ie, chemotherapy, immunotherapy) or 1b) have not received chemotherapy due to poor ECOG status or 2) have insufficient renal function.~Exclusion Criteria:~Prior receipt of a selective FGFR inhibitor.~Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug.~Inability or unwillingness to swallow pemigatinib or significant gastrointestinal disorder(s) that could interfere with the absorption, metabolism, or excretion of pemigatinib.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) in Participants With FGFR3 Mutations or Fusions on a CD Regimen | ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) at any post-Baseline visit prior to first progressive disease (PD), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Response was based on review of scans by an independent centralized radiological review committee. Response was confirmed. | up to 1138 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR in Participants With FGFR3 Mutations or Fusions on an ID Regimen | ORR was defined as the percentage of participants with a best overall response of CR or PR at any post-Baseline visit prior to first PD, per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Response was based on review of scans by an independent centralized radiological review committee. Response was confirmed. | up to 817 days |
| ORR in Participants With All Other FGF/FGFR Alterations | ORR was defined as the percentage of participants with a best overall response of CR or PR at any post-Baseline visit prior to first PD, per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Response was based on review of scans by an independent centralized radiological review committee. Response was confirmed. | up to 1198 days |
| ORR in All Participants on an ID or CD Regimen in Combined Cohorts | ORR was defined as the percentage of participants with a best overall response of CR or PR at any post-Baseline visit prior to first PD, per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Response was based on review of scans by an independent centralized radiological review committee. Response was confirmed. | up to 1198 days |
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and within 30 days of the last dose of study drug. | up to approximately 25 weeks |
| Progression-free Survival (PFS) | PFS was defined as the length of time from the start of the study drug (Day 1) to the earlier of death or disease progression by RECIST v1.1, as assessed by the independent centralized radiological review committee. | up to 1138 days |
| Duration of Response (DOR) | DOR was defined as the time from the first overall response contributing to an objective response (CR or PR) to the earlier of death or first overall response of PD occurring after the first overall response contributing to the objective response. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Response was based on review of scans by an independent centralized radiological review committee. Response was confirmed | up to 1075 days |
| Overall Survival | Overall survival was defined as the length of time from the start of the study drug (Day 1) until the date of death due to any cause. | up to 1610 days |
|
Urothelial carcinoma, fibroblast growth factor receptor (FGFR), FGF/FGFR alterations, fibroblast growth factor (FGF)
|
Carcinoma, Carcinoma, Transitional Cell, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Neoplasms
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A-ID (Intermittent Dose) Pemigatinib<br>Pemigatinib in subjects with FGFR3 mutations or fusions. | Drug: pemigatinib<br>* Pemigatinib once a day by mouth for 2 consecutive weeks and 1 week off therapy.<br>* Other names: INCB054828;|
| Experimental: Cohort A-CD (Continuous Dose) Pemigatinib<br>Pemigatinib in subjects with FGFR3 mutations or fusions. | Drug: pemigatinib<br>* Pemigatinib once a day by mouth continuously.<br>* Other names: INCB054828;|
| Experimental: Cohort B Pemigatinib<br>Pemigatinib in subjects with other FGF/FGFR alterations. | Drug: pemigatinib<br>* Pemigatinib once a day by mouth for 2 consecutive weeks and 1 week off therapy.<br>* Other names: INCB054828;|
|
A Study to Evaluate the Efficacy and Safety of Pemigatinib (INCB054828) in Subjects With Urothelial Carcinoma - (FIGHT-201)
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the overall response rate (ORR) of pemigatinib as a monotherapy in the treatment of metastatic or surgically unresectable urothelial carcinoma harboring FGF/FGFR alterations.
Official Title
-----------------
A Phase 2, Open-Label, Single-Agent, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib (INCB054828) in Subjects With Metastatic or Surgically Unresectable Urothelial Carcinoma Harboring FGF/FGFR Alterations - (FIGHT-201)
Conditions
-----------------
UC (Urothelial Cancer)
Intervention / Treatment
-----------------
* Drug: pemigatinib
* Drug: pemigatinib
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 20 years and older in Japan Histologically documented metastatic or surgically unresectable urothelial carcinoma; may include primary site from urethra, ureters, upper tract, renal pelvis, and bladder. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Life expectancy ≥ 12 weeks. Radiographically measurable per RECIST v1.1. Documented FGF/FGFR alteration and have either 1a) failed at least 1 previous treatment for their metastatic or surgically unresectable urothelial carcinoma (ie, chemotherapy, immunotherapy) or 1b) have not received chemotherapy due to poor ECOG status or 2) have insufficient renal function. Exclusion Criteria: Prior receipt of a selective FGFR inhibitor. Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug. Inability or unwillingness to swallow pemigatinib or significant gastrointestinal disorder(s) that could interfere with the absorption, metabolism, or excretion of pemigatinib.
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: Cohort A-ID (Intermittent Dose) Pemigatinib<br>Pemigatinib in subjects with FGFR3 mutations or fusions. | Drug: pemigatinib<br>* Pemigatinib once a day by mouth for 2 consecutive weeks and 1 week off therapy.<br>* Other names: INCB054828;|
| Experimental: Cohort A-CD (Continuous Dose) Pemigatinib<br>Pemigatinib in subjects with FGFR3 mutations or fusions. | Drug: pemigatinib<br>* Pemigatinib once a day by mouth continuously.<br>* Other names: INCB054828;|
| Experimental: Cohort B Pemigatinib<br>Pemigatinib in subjects with other FGF/FGFR alterations. | Drug: pemigatinib<br>* Pemigatinib once a day by mouth for 2 consecutive weeks and 1 week off therapy.<br>* Other names: INCB054828;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) in Participants With FGFR3 Mutations or Fusions on a CD Regimen | ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) at any post-Baseline visit prior to first progressive disease (PD), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Response was based on review of scans by an independent centralized radiological review committee. Response was confirmed. | up to 1138 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR in Participants With FGFR3 Mutations or Fusions on an ID Regimen | ORR was defined as the percentage of participants with a best overall response of CR or PR at any post-Baseline visit prior to first PD, per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Response was based on review of scans by an independent centralized radiological review committee. Response was confirmed. | up to 817 days |
| ORR in Participants With All Other FGF/FGFR Alterations | ORR was defined as the percentage of participants with a best overall response of CR or PR at any post-Baseline visit prior to first PD, per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Response was based on review of scans by an independent centralized radiological review committee. Response was confirmed. | up to 1198 days |
| ORR in All Participants on an ID or CD Regimen in Combined Cohorts | ORR was defined as the percentage of participants with a best overall response of CR or PR at any post-Baseline visit prior to first PD, per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Response was based on review of scans by an independent centralized radiological review committee. Response was confirmed. | up to 1198 days |
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and within 30 days of the last dose of study drug. | up to approximately 25 weeks |
| Progression-free Survival (PFS) | PFS was defined as the length of time from the start of the study drug (Day 1) to the earlier of death or disease progression by RECIST v1.1, as assessed by the independent centralized radiological review committee. | up to 1138 days |
| Duration of Response (DOR) | DOR was defined as the time from the first overall response contributing to an objective response (CR or PR) to the earlier of death or first overall response of PD occurring after the first overall response contributing to the objective response. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Response was based on review of scans by an independent centralized radiological review committee. Response was confirmed | up to 1075 days |
| Overall Survival | Overall survival was defined as the length of time from the start of the study drug (Day 1) until the date of death due to any cause. | up to 1610 days |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Urothelial carcinoma, fibroblast growth factor receptor (FGFR), FGF/FGFR alterations, fibroblast growth factor (FGF)
|
|
NCT01303380
|
Canakinumab in Patients With Active Hyper-IgD Syndrome
|
This pilot study is designed to evaluate the efficacy, the safety, and the pharmacokinetics (PK) / pharmacodynamics (PD) of canakinumab treatment in patients with HIDS.
|
An Open-label, Multicenter, Efficacy and Safety Pilot Study of 6-month Canakinumab Treatment With up to 6-month Follow-up in Patients With Active Hyper-IgD Syndrome (HIDS)
|
Mevalonate Kinase Deficiency
|
* Drug: Canakinumab
|
Inclusion Criteria:~Patients with a diagnosis of HIDS proven by DNA analysis and/or enzymatic studies.~At time of start of drug treatment: active HIDS as evidenced by a physician global assessment of HIDS flare severity ≥ 2 and CRP values >10 mg/L (normal CRP < or = 10 mg/L).~Patients who have a history of > or = 3 febrile acute HIDS flares in a 6-month period when not receiving prophylaxis treatment (e.g. anakinra daily treatment) with a duration of each flare lasting > or = 4 days and limiting the normal daily activities.~Exclusion Criteria:~Pregnant or nursing (lactating) women.~History of being immunocompromised, including a positive HIV at screening (ELISA and Western blot) test result.~Positive Hepatitis B or Hepatitis C.~Live vaccinations within 3 months prior to the start of the trial~Positive tuberculosis screening test.~Other protocol-defined inclusion/exclusion criteria may apply
|
24 Months
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Flares Per Participant During Historical Period and Treatment Period | A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a C-reactive protein (CRP) value > 10 mg/L. Flares during a historical period were defined as most recent 6-months in which the participant has not received treatment for their HIDS other than symptomatic treatment with NSAIDs and/or corticosteroids. | Historical period, Month 6 (End of treatment period) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Flares Per Participant at During Treatment Period and 24 Month Extension Period | A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L. | Month 6 (End of treatment period), Month 36 (End of Long term treatment Period 2) |
| Number of Participants Who Flared at Month 6, Month 24 and Month 36 | A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L. | Baseline, Month 6 (End of treatment period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Physician global assessment of severity of HIDS after each flare was based on HIDS flare severity score, a 5- point scale: 0 = Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3= Moderate; 4 = Severe. | Any flare event [Baseline up to Month 36 (End of long term treatment period 2)] |
| Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Participant's global assessment of severity of HIDS after each flare was based on HIDS flare severity score, a 5-point scale: 0 = Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3= Moderate; 4 = Severe. Same investigator assessed the same participant throughout the study to ensure consistency between assessments. Investigators reviewed every participant's diary at each visit after their own clinical assessment. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Participants were assessed by participants/parent (participants aged 6-18 years) for control of signs and symptoms associated with HIDS based on 5-point scale: 0 = No control; 1 = Poor control; 2 = Somewhat control; 3 = Good control; and 4= Excellent control. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Participants were assessed by physician for control of signs and symptoms associated with HIDS based on 5-point scale: 0 = No control; 1 = Poor control; 2 = Somewhat control; 3 = Good control; and 4= Excellent control. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Fever severity was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Apthus ulcers were assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Lymphadenopathy severity was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Abdominal pain was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Time to Resolution of the Initial Flare After First Canakinumab Treatment | Time to resolution of the initial flare after first dose of canakinumab was determined. | Day 1 (Baseline), Day 28 |
| Change From Baseline in Inflammation Markers Over Time up to Month 24 | The C-reactive Protein (CRP) and/or Serum amyloid A protein (SAA) were used as inflammatory markers. The normal range of CRP was 0-10 mg/L. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Health Assessment Questionnaire (HAQ) Global Score in Adults Over Time | Participants were assessed for health-related quality of life (HRQoL) based on Health Assessment Questionnaire (HAQ). HAQ was an eight 8 categories questionnaire representing all activities related to physical function. Each category has various sub-categories, which were rated by the participants on a 4- point difficulty scale: 0 = any difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. The total score was the mean of the 8 scores, and ranged from 0 (no disability) to 3 (completely disabled). | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Childhood Health Assessment Questionnaire (CHAQ) Global Score in Children Over Time | Participants or their parents (participants aged 6 to 17 years) were assessed for HRQoL based on Childhood Health Assessment Questionnaire (CHAQ). CHAQ was an eight domain questionnaire representing functional capacity and independence, evaluated for previous week. Each domain was rated on a 4-point difficulty scale: 0 = any difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do.The total score is the mean from the 8 scores, and ranges from 0 (no disability) to 3 (completely disabled). | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants Who Received Dose Up-titration During 6-month Treatment Period | Participants who experienced a new HIDS flare between baseline and Week 4 and received an escalated dose of 450 mg of canakinumab every 6 weeks thereafter starting at Week 6 were determined. | Day 1 up to Month 6 (End of follow up) |
| Duration of Flares Experienced During the Study | Flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L. The change in post canakinumab treatment flare duration during the study were assessed as compared to historical period. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Time to Flare After the Last Dose of Canakinumab During the Follow-up Period | The median time to flare by the participants after administration of the last dose of canakinumab during the follow-up period was analysed using Kaplan-Meier method. | Last dose of canakinumab treatment in follow-up period to end of follow-up period (Day 337) |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalisation, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards. | Day 1 (Start of study treatment) up to Month 36 (End of study) |
| Participants Who Received Rescue Treatment | Participants who experienced flares were treated with corticosteroids and NSAIDs as rescue medication. | Baseline up to Month 36 (End of study) |
| Serum Concentration-time Profile of Canakinumab | Canakinumab concentrations in serum were assessed for evaluating pharmacokinetics (PK) of the drug. | Day 1 (Pre-dose), Day 4, Day 15, Day 43, Day 85, Day 127, Day 169 (End of treatment period), Day 197, Day 225, Day 253, Day 281, Day 309, and Day 337 (End of follow-up period) (Post-dose) |
| Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Pharmacodynamics of canakinumab was assessed by total IL-1β (sum of free and bound canakinumab) concentration, determined in serum by means of sandwich ELISA assay with limit of detection at 0.1 picogram/millilitre. | Day 1 (Pre-dose), Day 4, Day 15, Day 43, Day 85, Day 127, Day 169 (End of treatment period), Day 197, Day 225, Day 253, Day 281, Day 309, and Day 337 (End of follow-up period) (Post-dose) |
| Number of Participants Exhibiting Anti-canakinumab Antibodies at Any Visit | Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using bridging ECLIA assay. | Baseline up to Month 36 (End of study) |
|
Hyper IgD syndrome, canakinumab, HIDS, mevalonate kinase deficiency, MKD
|
Mevalonate Kinase Deficiency, Brain Diseases, Metabolic, Inborn, Brain Diseases, Metabolic, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Hypergammaglobulinemia, Blood Protein Disorders, Hematologic Diseases, Hereditary Autoinflammatory Diseases, Genetic Diseases, Inborn, Metabolism, Inborn Errors, Peroxisomal Disorders, Metabolic Diseases, Immunoproliferative Disorders, Immune System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Canakinumab<br> | Drug: Canakinumab<br> <br> |
|
Canakinumab in Patients With Active Hyper-IgD Syndrome
Study Overview
=================
Brief Summary
-----------------
This pilot study is designed to evaluate the efficacy, the safety, and the pharmacokinetics (PK) / pharmacodynamics (PD) of canakinumab treatment in patients with HIDS.
Official Title
-----------------
An Open-label, Multicenter, Efficacy and Safety Pilot Study of 6-month Canakinumab Treatment With up to 6-month Follow-up in Patients With Active Hyper-IgD Syndrome (HIDS)
Conditions
-----------------
Mevalonate Kinase Deficiency
Intervention / Treatment
-----------------
* Drug: Canakinumab
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with a diagnosis of HIDS proven by DNA analysis and/or enzymatic studies. At time of start of drug treatment: active HIDS as evidenced by a physician global assessment of HIDS flare severity ≥ 2 and CRP values >10 mg/L (normal CRP < or = 10 mg/L). Patients who have a history of > or = 3 febrile acute HIDS flares in a 6-month period when not receiving prophylaxis treatment (e.g. anakinra daily treatment) with a duration of each flare lasting > or = 4 days and limiting the normal daily activities. Exclusion Criteria: Pregnant or nursing (lactating) women. History of being immunocompromised, including a positive HIV at screening (ELISA and Western blot) test result. Positive Hepatitis B or Hepatitis C. Live vaccinations within 3 months prior to the start of the trial Positive tuberculosis screening test. Other protocol-defined inclusion/exclusion criteria may apply
Ages Eligible for Study
-----------------
Minimum Age: 24 Months
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: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Canakinumab<br> | Drug: Canakinumab<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Flares Per Participant During Historical Period and Treatment Period | A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a C-reactive protein (CRP) value > 10 mg/L. Flares during a historical period were defined as most recent 6-months in which the participant has not received treatment for their HIDS other than symptomatic treatment with NSAIDs and/or corticosteroids. | Historical period, Month 6 (End of treatment period) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Flares Per Participant at During Treatment Period and 24 Month Extension Period | A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L. | Month 6 (End of treatment period), Month 36 (End of Long term treatment Period 2) |
| Number of Participants Who Flared at Month 6, Month 24 and Month 36 | A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L. | Baseline, Month 6 (End of treatment period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Physician global assessment of severity of HIDS after each flare was based on HIDS flare severity score, a 5- point scale: 0 = Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3= Moderate; 4 = Severe. | Any flare event [Baseline up to Month 36 (End of long term treatment period 2)] |
| Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Participant's global assessment of severity of HIDS after each flare was based on HIDS flare severity score, a 5-point scale: 0 = Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3= Moderate; 4 = Severe. Same investigator assessed the same participant throughout the study to ensure consistency between assessments. Investigators reviewed every participant's diary at each visit after their own clinical assessment. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Participants were assessed by participants/parent (participants aged 6-18 years) for control of signs and symptoms associated with HIDS based on 5-point scale: 0 = No control; 1 = Poor control; 2 = Somewhat control; 3 = Good control; and 4= Excellent control. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Participants were assessed by physician for control of signs and symptoms associated with HIDS based on 5-point scale: 0 = No control; 1 = Poor control; 2 = Somewhat control; 3 = Good control; and 4= Excellent control. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Fever severity was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Apthus ulcers were assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Lymphadenopathy severity was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Abdominal pain was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Time to Resolution of the Initial Flare After First Canakinumab Treatment | Time to resolution of the initial flare after first dose of canakinumab was determined. | Day 1 (Baseline), Day 28 |
| Change From Baseline in Inflammation Markers Over Time up to Month 24 | The C-reactive Protein (CRP) and/or Serum amyloid A protein (SAA) were used as inflammatory markers. The normal range of CRP was 0-10 mg/L. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Health Assessment Questionnaire (HAQ) Global Score in Adults Over Time | Participants were assessed for health-related quality of life (HRQoL) based on Health Assessment Questionnaire (HAQ). HAQ was an eight 8 categories questionnaire representing all activities related to physical function. Each category has various sub-categories, which were rated by the participants on a 4- point difficulty scale: 0 = any difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. The total score was the mean of the 8 scores, and ranged from 0 (no disability) to 3 (completely disabled). | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Childhood Health Assessment Questionnaire (CHAQ) Global Score in Children Over Time | Participants or their parents (participants aged 6 to 17 years) were assessed for HRQoL based on Childhood Health Assessment Questionnaire (CHAQ). CHAQ was an eight domain questionnaire representing functional capacity and independence, evaluated for previous week. Each domain was rated on a 4-point difficulty scale: 0 = any difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do.The total score is the mean from the 8 scores, and ranges from 0 (no disability) to 3 (completely disabled). | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants Who Received Dose Up-titration During 6-month Treatment Period | Participants who experienced a new HIDS flare between baseline and Week 4 and received an escalated dose of 450 mg of canakinumab every 6 weeks thereafter starting at Week 6 were determined. | Day 1 up to Month 6 (End of follow up) |
| Duration of Flares Experienced During the Study | Flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L. The change in post canakinumab treatment flare duration during the study were assessed as compared to historical period. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Time to Flare After the Last Dose of Canakinumab During the Follow-up Period | The median time to flare by the participants after administration of the last dose of canakinumab during the follow-up period was analysed using Kaplan-Meier method. | Last dose of canakinumab treatment in follow-up period to end of follow-up period (Day 337) |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalisation, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards. | Day 1 (Start of study treatment) up to Month 36 (End of study) |
| Participants Who Received Rescue Treatment | Participants who experienced flares were treated with corticosteroids and NSAIDs as rescue medication. | Baseline up to Month 36 (End of study) |
| Serum Concentration-time Profile of Canakinumab | Canakinumab concentrations in serum were assessed for evaluating pharmacokinetics (PK) of the drug. | Day 1 (Pre-dose), Day 4, Day 15, Day 43, Day 85, Day 127, Day 169 (End of treatment period), Day 197, Day 225, Day 253, Day 281, Day 309, and Day 337 (End of follow-up period) (Post-dose) |
| Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Pharmacodynamics of canakinumab was assessed by total IL-1β (sum of free and bound canakinumab) concentration, determined in serum by means of sandwich ELISA assay with limit of detection at 0.1 picogram/millilitre. | Day 1 (Pre-dose), Day 4, Day 15, Day 43, Day 85, Day 127, Day 169 (End of treatment period), Day 197, Day 225, Day 253, Day 281, Day 309, and Day 337 (End of follow-up period) (Post-dose) |
| Number of Participants Exhibiting Anti-canakinumab Antibodies at Any Visit | Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using bridging ECLIA assay. | Baseline up to Month 36 (End of study) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hyper IgD syndrome, canakinumab, HIDS, mevalonate kinase deficiency, MKD
|
|
NCT03689257
|
Study to Evaluate the Epidemiology and the Characteristics Omics in Patients Recently Diagnosed of Inflammatory Bowel Disease in Spain
|
This is a prospective, observational, multicenter, population-based incidence cohort study which will enroll cases of inflammatory bowel disease IBD (Crohn´s disease CD, ulcerative colitis UC, or indeterminate colitis) diagnosed in adults over 18 months in Spain.~In addition, each incident case that gave his/her informed consent, will be followed up for 12 months to determine changes in phenotype or disease location, the need for immunosuppressive and biologic treatments, and the need for hospital admissions and surgery during the first year after diagnosis.~Also, samples of of blood, urine and stool will be collected during the first year after diagnosis
|
STUDY DESIGN This is a prospective, observational, multicenter, population-based incidence cohort study which will enroll cases of IBD (CD, UC, or indeterminate colitis) diagnosed in adults over 18 months in Spain.~In addition, each incident case that gave his/her informed consent, will be followed up for 12 months to determine changes in phenotype or disease location, the need for immunosuppressive and biologic treatments, and the need for hospital admissions and surgery during the first year after diagnosis.~Samples of blood, urine and stool will be collected during the study visits.~To achieve the aims this study will be Split in two studies.~Epidemiology study to achieve aims 1 and 2.~Characterization omics study to achieve aims 3, 4 and 5.~CASES DETECION~Case detection In Spain, health care is performed mostly by the public health services. According to recent data, approximately 15% of the Spanish population has private health insurance (Informe Sanidad Privada: Aportando Valor. Análisis de situación 2014 (Report on Private Health Care: Providing Value. 2014 Situation Analysis); available at: https://www.fundacionidis.com/wp-content/informes/informe_analisis situac_2014_0.pdf). In addition, of those persons having private health insurance, only about 15% make exclusive use of it. For these reasons and taking into account the specific characteristics of IBD, the risk of underestimating the incidence of IBD considering only cases seen in public health centers would be of little relevance. Therefore, this study will be conducted at centers providing public health care within the National Health System.~To conduct this research project, an IBD specialist who is a member of GETECCU has been selected from each Autonomous Community, who will include patients from their health area.~Each participating investigator will confirm the diagnosis at the time of entering patients in the study and 3 months later to assure this diagnosis and the phenotypic characteristics of the disease, and thereby have greater diagnostic accuracy. External monitoring of incident cases included in the registry will also be performed by review of cases selected at random by the research team of Hospital Universitario de la Princesa.~DEFINITIONS~Disease location and phenotype: IBD location and phenotype will be defined according to the Montreal classification.~Time to diagnosis: It will be defined as the time from the first medical consultation made by the patient after onset of symptoms to the diagnosis of IBD.~Population center: The type of population center at the patient's birth and at diagnosis of IBD will be recorded. Whether the population center of origin of the patient is considered rural or urban will be based on the classification of the National Statistics Institute (INE) of each municipality.~Socioeconomic level: Socioeconomic level will be assessed through different variables, such as the patient's educational level (primary education or lower, secondary education, higher education or equivalent), occupational status (self-employed, employee, unemployed, retired), professional status (nonsalaried or salaried) and type of working hours (full time or part time).~Number of cohabitants: The number of cohabitants in the patient's home during childhood (up to 16 years) and at diagnosis of IBD will be recorded.~Smoking: Smoking status will be categorized as nonsmoker, smoker, or ex-smoker, and will be considered at the time of diagnosis of IBD. Patients will be considered smokers if they have a smoked more than 7 cigarettes per week for at least 6 months or smoked at least 1 cigarette in the 6 months prior to diagnosis. Patients will be considered ex-smokers l if they quit smoking at least 6 months before diagnosis. Patients will be considered nonsmokers if they never smoked or did so in a very small amount or occasionally.~Treatments: Treatments received by the patient in the 12 months since diagnosis of the disease will be included, provided they were received for IBD. Only the first prescription of each therapeutic group will be recorded.~Changes in phenotype: Changes in phenotype will be considered as the appearance of new lesions not present at diagnosis subsequent to the initial tests performed to determine disease extent and severity. In these cases, the phenotype, the complication leading to classification of the patient in a different phenotype and date of occurrence of the complication will be recorded.~Hospital admission Hospital admission occurring during the first year from diagnosis of the disease will be included. The date of admission, date of discharge, if related or not to IBD and the cause of admission.~Surgical procedures: The surgical procedures performed on the patient since diagnosis of IBD (including those performed before knowing the patient had IBD and which led to its diagnosis), the indication for surgery and the date of surgery will be recorded. An emergency surgical procedure will be considered as any surgery performed within 24 from admission of the patient to the emergency department. An elective surgical procedure will be considered as any procedure performed subsequent to the first day of admission and by the usual surgical team.~DATA COLLECTION~Epidemiology study:~Demographic data (age, sex, smoking), family history of IBD, socioeconomic characteristics, IBD type, pattern, and location and presence of extraintestinal manifestations at diagnosis will collected from each patient. The occurrence of complications (fistulas, stenosis, abscesses), changes in disease location, treatments for IBD, surgeries for IBD, and hospital admission during the first year since diagnosis will also be recorded.~Characterization omics study Samples of blood, urine and stool. Date of collection and number of samples.~STUDY VISITS~Visit 0 (baseline): inclusion of patient in the study and collection of socioeconomic data and on diagnosis of IBD. Collection samples of blood, urine and stool.~Visit 1 (month 3): confirmation of IBD diagnosis and updating of data related to treatment, changes in phenotype, hospital admissions, and surgery. Collection samples of blood, urine and stool.~Visit 2 (month 12): confirmation of IBD diagnosis and updating of data related to treatment, changes in phenotype, hospital admissions, and surgery. Collection samples of blood, urine and stool. End of study.
|
Prospective and Multicenter Study About the Epidemiology and the Characteristics Omics in Patients Recently Diagnosed of Inflammatory Bowel Disease in Spain
|
Inflammatory Bowel Diseases
|
Inclusion Criteria:~Male or female ≥18 years of age diagnosed of inflammatory bowel disease~Diagnosis of IBD according to European Crohns and Colitis Organisation (ECCO) criteria.~The patient must belong to the health area of one of the participating center~Patients who have accepted to participate in the epidemiology study~< 1 month since the date of the diagnosis colonoscopy~Exclusion Criteria:~Patients who do not belong to the health area of the participating centers~Patients who do not accept to participate in the study~Patients who have initiated a treatment to IBD~Patients who received a immunomodulators to treat other disease~Patients with a immune-mediates systemic disease~Patients with a active infection or a malignancy in the baseline~Pregnant patients or breastfeeding
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of IBD in Spain | Measure the incidence of IBD in Spain | 1 year |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characteristics of patients at diagnosis of inflammatory bowel disease and resources used in the first year after diagnosis | Type of IBD, extension of the IBD, severity of the IBD at diagnosis. Immunosuppressive treatments, biologic drugs, surgery, and hospital | 1 year |
| Create a wide collection of samples | Blood simple, urine simple, stool sample | 1 year |
| Identify the molecular and cellular pathways involved with IBD development and pathogenesis. | To describe the serum proteomic profile and to characterize the density and composition of serum extracellular vesicles in newly diagnosed IBD patients, aiming to identify the molecular and cellular pathways involved with IBD development and pathogenesis. | 1 year |
| Correlate the serum proteomic profile and the density | To correlate the serum proteomic profile and the density and composition of serum extracellular vesicles with IBD phenotype at diagnose and its subsequent evolution during the first year. | 1 year |
|
omics, inflammatory bowel disease, Ulcerative colitis, Crohn´s disease, epidemiology, incidence
|
Intestinal Diseases, Inflammatory Bowel Diseases, Gastrointestinal Diseases, Digestive System Diseases, Gastroenteritis
|
Study to Evaluate the Epidemiology and the Characteristics Omics in Patients Recently Diagnosed of Inflammatory Bowel Disease in Spain
Study Overview
=================
Brief Summary
-----------------
This is a prospective, observational, multicenter, population-based incidence cohort study which will enroll cases of inflammatory bowel disease IBD (Crohn´s disease CD, ulcerative colitis UC, or indeterminate colitis) diagnosed in adults over 18 months in Spain. In addition, each incident case that gave his/her informed consent, will be followed up for 12 months to determine changes in phenotype or disease location, the need for immunosuppressive and biologic treatments, and the need for hospital admissions and surgery during the first year after diagnosis. Also, samples of of blood, urine and stool will be collected during the first year after diagnosis
Detailed Description
-----------------
STUDY DESIGN This is a prospective, observational, multicenter, population-based incidence cohort study which will enroll cases of IBD (CD, UC, or indeterminate colitis) diagnosed in adults over 18 months in Spain. In addition, each incident case that gave his/her informed consent, will be followed up for 12 months to determine changes in phenotype or disease location, the need for immunosuppressive and biologic treatments, and the need for hospital admissions and surgery during the first year after diagnosis. Samples of blood, urine and stool will be collected during the study visits. To achieve the aims this study will be Split in two studies. Epidemiology study to achieve aims 1 and 2. Characterization omics study to achieve aims 3, 4 and 5. CASES DETECION Case detection In Spain, health care is performed mostly by the public health services. According to recent data, approximately 15% of the Spanish population has private health insurance (Informe Sanidad Privada: Aportando Valor. Análisis de situación 2014 (Report on Private Health Care: Providing Value. 2014 Situation Analysis); available at: https://www.fundacionidis.com/wp-content/informes/informe_analisis situac_2014_0.pdf). In addition, of those persons having private health insurance, only about 15% make exclusive use of it. For these reasons and taking into account the specific characteristics of IBD, the risk of underestimating the incidence of IBD considering only cases seen in public health centers would be of little relevance. Therefore, this study will be conducted at centers providing public health care within the National Health System. To conduct this research project, an IBD specialist who is a member of GETECCU has been selected from each Autonomous Community, who will include patients from their health area. Each participating investigator will confirm the diagnosis at the time of entering patients in the study and 3 months later to assure this diagnosis and the phenotypic characteristics of the disease, and thereby have greater diagnostic accuracy. External monitoring of incident cases included in the registry will also be performed by review of cases selected at random by the research team of Hospital Universitario de la Princesa. DEFINITIONS Disease location and phenotype: IBD location and phenotype will be defined according to the Montreal classification. Time to diagnosis: It will be defined as the time from the first medical consultation made by the patient after onset of symptoms to the diagnosis of IBD. Population center: The type of population center at the patient's birth and at diagnosis of IBD will be recorded. Whether the population center of origin of the patient is considered rural or urban will be based on the classification of the National Statistics Institute (INE) of each municipality. Socioeconomic level: Socioeconomic level will be assessed through different variables, such as the patient's educational level (primary education or lower, secondary education, higher education or equivalent), occupational status (self-employed, employee, unemployed, retired), professional status (nonsalaried or salaried) and type of working hours (full time or part time). Number of cohabitants: The number of cohabitants in the patient's home during childhood (up to 16 years) and at diagnosis of IBD will be recorded. Smoking: Smoking status will be categorized as nonsmoker, smoker, or ex-smoker, and will be considered at the time of diagnosis of IBD. Patients will be considered smokers if they have a smoked more than 7 cigarettes per week for at least 6 months or smoked at least 1 cigarette in the 6 months prior to diagnosis. Patients will be considered ex-smokers l if they quit smoking at least 6 months before diagnosis. Patients will be considered nonsmokers if they never smoked or did so in a very small amount or occasionally. Treatments: Treatments received by the patient in the 12 months since diagnosis of the disease will be included, provided they were received for IBD. Only the first prescription of each therapeutic group will be recorded. Changes in phenotype: Changes in phenotype will be considered as the appearance of new lesions not present at diagnosis subsequent to the initial tests performed to determine disease extent and severity. In these cases, the phenotype, the complication leading to classification of the patient in a different phenotype and date of occurrence of the complication will be recorded. Hospital admission Hospital admission occurring during the first year from diagnosis of the disease will be included. The date of admission, date of discharge, if related or not to IBD and the cause of admission. Surgical procedures: The surgical procedures performed on the patient since diagnosis of IBD (including those performed before knowing the patient had IBD and which led to its diagnosis), the indication for surgery and the date of surgery will be recorded. An emergency surgical procedure will be considered as any surgery performed within 24 from admission of the patient to the emergency department. An elective surgical procedure will be considered as any procedure performed subsequent to the first day of admission and by the usual surgical team. DATA COLLECTION Epidemiology study: Demographic data (age, sex, smoking), family history of IBD, socioeconomic characteristics, IBD type, pattern, and location and presence of extraintestinal manifestations at diagnosis will collected from each patient. The occurrence of complications (fistulas, stenosis, abscesses), changes in disease location, treatments for IBD, surgeries for IBD, and hospital admission during the first year since diagnosis will also be recorded. Characterization omics study Samples of blood, urine and stool. Date of collection and number of samples. STUDY VISITS Visit 0 (baseline): inclusion of patient in the study and collection of socioeconomic data and on diagnosis of IBD. Collection samples of blood, urine and stool. Visit 1 (month 3): confirmation of IBD diagnosis and updating of data related to treatment, changes in phenotype, hospital admissions, and surgery. Collection samples of blood, urine and stool. Visit 2 (month 12): confirmation of IBD diagnosis and updating of data related to treatment, changes in phenotype, hospital admissions, and surgery. Collection samples of blood, urine and stool. End of study.
Official Title
-----------------
Prospective and Multicenter Study About the Epidemiology and the Characteristics Omics in Patients Recently Diagnosed of Inflammatory Bowel Disease in Spain
Conditions
-----------------
Inflammatory Bowel Diseases
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female ≥18 years of age diagnosed of inflammatory bowel disease Diagnosis of IBD according to European Crohns and Colitis Organisation (ECCO) criteria. The patient must belong to the health area of one of the participating center Patients who have accepted to participate in the epidemiology study < 1 month since the date of the diagnosis colonoscopy Exclusion Criteria: Patients who do not belong to the health area of the participating centers Patients who do not accept to participate in the study Patients who have initiated a treatment to IBD Patients who received a immunomodulators to treat other disease Patients with a immune-mediates systemic disease Patients with a active infection or a malignancy in the baseline Pregnant patients 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?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of IBD in Spain | Measure the incidence of IBD in Spain | 1 year |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characteristics of patients at diagnosis of inflammatory bowel disease and resources used in the first year after diagnosis | Type of IBD, extension of the IBD, severity of the IBD at diagnosis. Immunosuppressive treatments, biologic drugs, surgery, and hospital | 1 year |
| Create a wide collection of samples | Blood simple, urine simple, stool sample | 1 year |
| Identify the molecular and cellular pathways involved with IBD development and pathogenesis. | To describe the serum proteomic profile and to characterize the density and composition of serum extracellular vesicles in newly diagnosed IBD patients, aiming to identify the molecular and cellular pathways involved with IBD development and pathogenesis. | 1 year |
| Correlate the serum proteomic profile and the density | To correlate the serum proteomic profile and the density and composition of serum extracellular vesicles with IBD phenotype at diagnose and its subsequent evolution during the first year. | 1 year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
omics, inflammatory bowel disease, Ulcerative colitis, Crohn´s disease, epidemiology, incidence
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NCT02595177
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Multifocal Intraocular Lens x Monovision x Hybrid Monovision After Bilateral Cataract Surgery
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To compare refractive outcomes and patient's visual quality after bilateral cataract surgery when implanting multifocal intraocular lens, monofocal with monovision or hybrid monovision.
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The purpose of this study is to evaluate the results in randomized patients that receive bilateral multifocal IOLs, monofocal IOLs with monovision with emmetropia in one eye and 1.50 D of myopia in the other eye, or monofocal IOL in the dominant eye and multifocal IOL in the non-dominant eye, then evaluate visual and refractive outcomes, as well as independence for glasses after bilateral surgery with 1 year of follow up.
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Multifocal Intraocular Lens vs. Monovision vs. Hybrid Monovision After Bilateral Cataract Surgery
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Cataract, Presbyopia
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* Procedure: Cataract surgery with intraocular lens implantation.
|
Inclusion Criteria:~Bilateral senile cataracts.~Implantation of IOL in the capsular bag;~Implants from 10-30 diopter;~Potential Visual Acuity in ≥ 0.2 logMAR (20/32, metric scale) after surgery;~Exclusion Criteria:~Amblyopia;~Single Eye;~History of intraocular surgery in the previous year;~Sequel to prior ocular trauma;~Important Microphthalmia or aniridia;~History of damage to the corneal endothelium (chemical burns, herpetic keratitis, corneal guttata);~Corneal astigmatism > 1.0 D;~IOP ≥ 21 mmHg in standard caliper;~Ocular pathology that affects visual function (uveitis, diabetic retinopathy, age-related macular degeneration, macular dystrophy, retinal detachment, glaucoma, optic neuropathy);~Pupil > 5 mm or < 2 mm under photopic conditions;~Asymmetrical pupils in the eye or between the eyes;~Binocular vision absence;~Any situation that endangers the implant position in the capsular bag (post-traumatic zonular weakness, pseudoexfoliation, for example);~Patient probably need to laser treatment of the retina;~Patients whose expectations are unrealistic;~Patients whose lifestyle involves high expectations of visual acuity (writer, driver, for example);~Patients at risk of not meeting the clinical follow-up requirements (distance of travel difficulties, for example);
|
50 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual acuity | Binocular visual acuity in a semi-darkened room without correction to far, intermediate and near using a typical Snellen chart that is frequently used for visual acuity testing. | 1 year |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Speed reading measure | Assessment is performed to measure the speed reading in each group and compare them. Then using a timer to measure how long does it take to read the page. The speed reading is measured in words per minute (WPM). | 1 year |
| Near stereopsis measure | Calculate stereopsis in each group and compare them. Stereoacuity is measured using a stereogram in which separate panels are shown to each eye. | 1 year |
| Contrast sensitivity measure | Comparison between groups of the contrast sensitivity. Contrast sensitivity function at five spatial frequencies is measured with the validated instrument (Functional Vision Analyzer® (Stereo Optical, Chicago, IL, USA) with best refraction. | 1 year |
| National Eye Institute Visual Functioning Questionnaire - 25 (VFQ-25) questionnaire | | 1 year |
|
multifocal IOL, monovision, hybrid monovision, spectacles independence
|
Cataract, Presbyopia, Lens Diseases, Eye Diseases, Refractive Errors
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multifocal IOL<br>Cataract removal with topical anesthesia and phacoemulsification is performed. At the end, multifocal intraocular lens implantation in both eyes planning for emmetropia complete the intervention. | Procedure: Cataract surgery with intraocular lens implantation.<br>* Phacoemulsification under topical anesthesia with intraocular lens implantation.<br>|
| Experimental: Monovision<br>Cataract removal with topical anesthesia and phacoemulsification is performed. At the end, a monofocal intraocular lens implantation planning for emmetropia in one eye (dominant) and a monofocal IOL planning for 1.50 D of myopia in the other eye (non-dominant) complete the intervention. | Procedure: Cataract surgery with intraocular lens implantation.<br>* Phacoemulsification under topical anesthesia with intraocular lens implantation.<br>|
| Experimental: Hybrid Monovision<br>Cataract removal with topical anesthesia and phacoemulsification is performed. At the end, a monofocal intraocular lens implantation in the dominant eye and a multifocal IOL in the non-dominant eye complete the intervention. | Procedure: Cataract surgery with intraocular lens implantation.<br>* Phacoemulsification under topical anesthesia with intraocular lens implantation.<br>|
|
Multifocal Intraocular Lens x Monovision x Hybrid Monovision After Bilateral Cataract Surgery
Study Overview
=================
Brief Summary
-----------------
To compare refractive outcomes and patient's visual quality after bilateral cataract surgery when implanting multifocal intraocular lens, monofocal with monovision or hybrid monovision.
Detailed Description
-----------------
The purpose of this study is to evaluate the results in randomized patients that receive bilateral multifocal IOLs, monofocal IOLs with monovision with emmetropia in one eye and 1.50 D of myopia in the other eye, or monofocal IOL in the dominant eye and multifocal IOL in the non-dominant eye, then evaluate visual and refractive outcomes, as well as independence for glasses after bilateral surgery with 1 year of follow up.
Official Title
-----------------
Multifocal Intraocular Lens vs. Monovision vs. Hybrid Monovision After Bilateral Cataract Surgery
Conditions
-----------------
Cataract, Presbyopia
Intervention / Treatment
-----------------
* Procedure: Cataract surgery with intraocular lens implantation.
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Bilateral senile cataracts. Implantation of IOL in the capsular bag; Implants from 10-30 diopter; Potential Visual Acuity in ≥ 0.2 logMAR (20/32, metric scale) after surgery; Exclusion Criteria: Amblyopia; Single Eye; History of intraocular surgery in the previous year; Sequel to prior ocular trauma; Important Microphthalmia or aniridia; History of damage to the corneal endothelium (chemical burns, herpetic keratitis, corneal guttata); Corneal astigmatism > 1.0 D; IOP ≥ 21 mmHg in standard caliper; Ocular pathology that affects visual function (uveitis, diabetic retinopathy, age-related macular degeneration, macular dystrophy, retinal detachment, glaucoma, optic neuropathy); Pupil > 5 mm or < 2 mm under photopic conditions; Asymmetrical pupils in the eye or between the eyes; Binocular vision absence; Any situation that endangers the implant position in the capsular bag (post-traumatic zonular weakness, pseudoexfoliation, for example); Patient probably need to laser treatment of the retina; Patients whose expectations are unrealistic; Patients whose lifestyle involves high expectations of visual acuity (writer, driver, for example); Patients at risk of not meeting the clinical follow-up requirements (distance of travel difficulties, for example);
Ages Eligible for Study
-----------------
Minimum 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: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multifocal IOL<br>Cataract removal with topical anesthesia and phacoemulsification is performed. At the end, multifocal intraocular lens implantation in both eyes planning for emmetropia complete the intervention. | Procedure: Cataract surgery with intraocular lens implantation.<br>* Phacoemulsification under topical anesthesia with intraocular lens implantation.<br>|
| Experimental: Monovision<br>Cataract removal with topical anesthesia and phacoemulsification is performed. At the end, a monofocal intraocular lens implantation planning for emmetropia in one eye (dominant) and a monofocal IOL planning for 1.50 D of myopia in the other eye (non-dominant) complete the intervention. | Procedure: Cataract surgery with intraocular lens implantation.<br>* Phacoemulsification under topical anesthesia with intraocular lens implantation.<br>|
| Experimental: Hybrid Monovision<br>Cataract removal with topical anesthesia and phacoemulsification is performed. At the end, a monofocal intraocular lens implantation in the dominant eye and a multifocal IOL in the non-dominant eye complete the intervention. | Procedure: Cataract surgery with intraocular lens implantation.<br>* Phacoemulsification under topical anesthesia with intraocular lens implantation.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual acuity | Binocular visual acuity in a semi-darkened room without correction to far, intermediate and near using a typical Snellen chart that is frequently used for visual acuity testing. | 1 year |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Speed reading measure | Assessment is performed to measure the speed reading in each group and compare them. Then using a timer to measure how long does it take to read the page. The speed reading is measured in words per minute (WPM). | 1 year |
| Near stereopsis measure | Calculate stereopsis in each group and compare them. Stereoacuity is measured using a stereogram in which separate panels are shown to each eye. | 1 year |
| Contrast sensitivity measure | Comparison between groups of the contrast sensitivity. Contrast sensitivity function at five spatial frequencies is measured with the validated instrument (Functional Vision Analyzer® (Stereo Optical, Chicago, IL, USA) with best refraction. | 1 year |
| National Eye Institute Visual Functioning Questionnaire - 25 (VFQ-25) questionnaire | | 1 year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
multifocal IOL, monovision, hybrid monovision, spectacles independence
|
NCT01074515
|
Chronic Obstructive Pulmonary Disease (COPD) Activity: Serotonin Transporter (SERT), Cytokines and Depression (CASCADE Study)
|
The goal of the study is to look at how genes and certain chemicals in the body are related to depression and chronic obstructive pulmonary disease.
|
Depression is highly prevalent among patients with chronic obstructive pulmonary disease (COPD) and is associated with adverse clinical outcomes. The overall goal of this proposal is to examine the impact of inflammation and genetic risk factors on depression in patients with severe COPD, and to assess the combined effects of inflammation, genetics, and depression on changes in functional outcomes. There is increasing evidence that COPD is associated with systemic inflammation that impacts other organ systems. High levels of systemic inflammatory markers have also been linked to increased risk of depression in both healthy and chronically ill populations. The neurotransmitter serotonin which is involved in the pathophysiology of affective disorders is regulated by the serotonin transporter (SERT) that controls reuptake of serotonin at brain synapses. Recent studies report that SERT polymorphisms are associated with depression, suggesting that variants of this gene may be important in determining whether patients with COPD will develop depression during the course of their disease. The preliminary data linking SERT polymorphisms with depression and data suggesting a relationship between inflammation, depression and COPD strongly argue for a large scale prospective study to critically test these relationships. Therefore, the aims of this prospective study of patients with moderate to very severe COPD are to: 1) Examine the relationship between SERT polymorphisms with depression; 2) Examine the bi-directional longitudinal relationship between markers of systemic inflammation (CRP, IL-1ra, IL-6, IL-12, TNF-α, and IFN-γ) and depressive symptoms in COPD, and explore the role of exacerbations and SERT genotype in this relationship; and 3) Determine the relationship of depression, inflammation, and SERT genotype with decline in functional outcomes (six minute walk test distance, physical activity measured with accelerometers, dyspnea severity, and health related quality of life) in COPD over 2 years. Patients with COPD GOLD Stages II-IV (n=350) will be recruited from two clinical sites over 30 months. Assessments at baseline, year 1 and year 2 will include: blood samples for genotyping (5-HTTLPR, STin2 VNTR, and rs25331) and cytokine assays (CRP, IL-1ra, IL-6, IL-12, TNF-α, and IFN-γ), spirometry, assessment of depression, functional capacity (six minute walk test), performance (physical activity derived from accelerometry), dyspnea, and health related quality of life (HRQL). We will use advanced longitudinal statistical techniques, structural equations modeling and latent growth models, to assess the dynamics of change in depression, inflammation, and functional status as posited by our models as these processes unfold over time.
|
Depression and Functional Outcomes in COPD: Impact of Genetics and Inflammation
|
Chronic Obstructive Pulmonary Disease
|
Inclusion Criteria:~Diagnosis of COPD confirmed by the following: 1) FEV1/FVC < 70%; 2) Moderate to very severe disease by GOLD criteria (FEV1 <65%); 2) Age > 40 years; and 3) A significant history of current or past cigarette smoking (> 10 pack-years);~Stable disease with no acute exacerbations of COPD in the past 4 weeks;~Ability to speak, read and write English~Exclusion Criteria:~Acute COPD exacerbation within the past 4 weeks (temp exclusion)~Chronic obstructive lung disorders unrelated to COPD: asthma, bronchiectasis, cystic fibrosis~Idiopathic Pulmonary Fibrosis~Congestive Heart Failure~Chronic renal failure requiring dialysis~Primary pulmonary vascular disease~Chronic inflammatory, infectious or auto-immune disease, e.g. osteomyelitis, crohn's disease or rheumatoid arthritis~Chronic liver disease~Metastatic cancer~Chronic antibiotic use or ongoing infection~Chronic oral prednisone use~Moderate to severe dementia~Severe primary mental illness, e.g. schizophrenia, bipolar disease, severe obsessive compulsive disorder~<2 years life expectancy~History of fainting with spirometry
|
40 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depression | | 1 year & 2 year |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical activity by accelerometry | | 1 year & 2 year |
| Dyspnea | | 1 year & 2 year |
| Health related quality of life | | 1 year & 2 year |
| Six Minute Walk Distance | | 1 year & 2 year |
|
COPD, Depression, Inflammation, Genetics, Functioning, Dyspnea, Physical activity
|
Lung Diseases, Lung Diseases, Obstructive, Pulmonary Disease, Chronic Obstructive, Depression, Behavioral Symptoms, Respiratory Tract Diseases, Chronic Disease, Disease Attributes, Pathologic Processes
|
Chronic Obstructive Pulmonary Disease (COPD) Activity: Serotonin Transporter (SERT), Cytokines and Depression (CASCADE Study)
Study Overview
=================
Brief Summary
-----------------
The goal of the study is to look at how genes and certain chemicals in the body are related to depression and chronic obstructive pulmonary disease.
Detailed Description
-----------------
Depression is highly prevalent among patients with chronic obstructive pulmonary disease (COPD) and is associated with adverse clinical outcomes. The overall goal of this proposal is to examine the impact of inflammation and genetic risk factors on depression in patients with severe COPD, and to assess the combined effects of inflammation, genetics, and depression on changes in functional outcomes. There is increasing evidence that COPD is associated with systemic inflammation that impacts other organ systems. High levels of systemic inflammatory markers have also been linked to increased risk of depression in both healthy and chronically ill populations. The neurotransmitter serotonin which is involved in the pathophysiology of affective disorders is regulated by the serotonin transporter (SERT) that controls reuptake of serotonin at brain synapses. Recent studies report that SERT polymorphisms are associated with depression, suggesting that variants of this gene may be important in determining whether patients with COPD will develop depression during the course of their disease. The preliminary data linking SERT polymorphisms with depression and data suggesting a relationship between inflammation, depression and COPD strongly argue for a large scale prospective study to critically test these relationships. Therefore, the aims of this prospective study of patients with moderate to very severe COPD are to: 1) Examine the relationship between SERT polymorphisms with depression; 2) Examine the bi-directional longitudinal relationship between markers of systemic inflammation (CRP, IL-1ra, IL-6, IL-12, TNF-α, and IFN-γ) and depressive symptoms in COPD, and explore the role of exacerbations and SERT genotype in this relationship; and 3) Determine the relationship of depression, inflammation, and SERT genotype with decline in functional outcomes (six minute walk test distance, physical activity measured with accelerometers, dyspnea severity, and health related quality of life) in COPD over 2 years. Patients with COPD GOLD Stages II-IV (n=350) will be recruited from two clinical sites over 30 months. Assessments at baseline, year 1 and year 2 will include: blood samples for genotyping (5-HTTLPR, STin2 VNTR, and rs25331) and cytokine assays (CRP, IL-1ra, IL-6, IL-12, TNF-α, and IFN-γ), spirometry, assessment of depression, functional capacity (six minute walk test), performance (physical activity derived from accelerometry), dyspnea, and health related quality of life (HRQL). We will use advanced longitudinal statistical techniques, structural equations modeling and latent growth models, to assess the dynamics of change in depression, inflammation, and functional status as posited by our models as these processes unfold over time.
Official Title
-----------------
Depression and Functional Outcomes in COPD: Impact of Genetics and Inflammation
Conditions
-----------------
Chronic Obstructive Pulmonary Disease
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of COPD confirmed by the following: 1) FEV1/FVC < 70%; 2) Moderate to very severe disease by GOLD criteria (FEV1 <65%); 2) Age > 40 years; and 3) A significant history of current or past cigarette smoking (> 10 pack-years); Stable disease with no acute exacerbations of COPD in the past 4 weeks; Ability to speak, read and write English Exclusion Criteria: Acute COPD exacerbation within the past 4 weeks (temp exclusion) Chronic obstructive lung disorders unrelated to COPD: asthma, bronchiectasis, cystic fibrosis Idiopathic Pulmonary Fibrosis Congestive Heart Failure Chronic renal failure requiring dialysis Primary pulmonary vascular disease Chronic inflammatory, infectious or auto-immune disease, e.g. osteomyelitis, crohn's disease or rheumatoid arthritis Chronic liver disease Metastatic cancer Chronic antibiotic use or ongoing infection Chronic oral prednisone use Moderate to severe dementia Severe primary mental illness, e.g. schizophrenia, bipolar disease, severe obsessive compulsive disorder <2 years life expectancy History of fainting with spirometry
Ages Eligible for Study
-----------------
Minimum Age: 40 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 |
| --- | --- | --- |
| Depression | | 1 year & 2 year |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical activity by accelerometry | | 1 year & 2 year |
| Dyspnea | | 1 year & 2 year |
| Health related quality of life | | 1 year & 2 year |
| Six Minute Walk Distance | | 1 year & 2 year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COPD, Depression, Inflammation, Genetics, Functioning, Dyspnea, Physical activity
|
|||
NCT04543201
|
Telehealth Visits to Discuss Advanced Directives for Patients Newly Diagnosed With High Grade Glioma
|
High grade gliomas (HGGs) are rapidly progressive brain tumors resulting in death for most patients between 6 months and 2 years after diagnosis. It is important for patients with HGG to discuss and document their wishes at the end of life. However, many of these patients experience early changes in cognition which impede their decision-making. For this reason, these patients should have early discussions with their providers. However, implementation of this remains challenging in clinical practice.~In this study, we will create an Early STructured Advanced care Referrals by Telehealth (Early START) visit for patients soon after their initial oncology visit. A checklist and pre-visit guide were developed to help guide the visit for both the provider and patient. Providers will receive special training in running these visits. Caregivers and/or family members will be encouraged to participate. Visits will be done using video or telephone and recorded. For patients who do not have access to technology for these visits, it will be provided. After the visit, patients, caregivers and/or family who participated, and providers will fill out surveys to address feasibility of having these extra visits and improve the visits for future. Patients will be followed until death. Caregivers and/or family who participated will be asked about whether end of life was in line with the patient's wishes. We will also use the patient's medical record to assess other aspects of end of life. We will compare end of life outcomes with other similar patients treated at our center.
|
High grade gliomas (HGGs) are rapidly progressive brain tumors resulting in death for most patients between 6 months and 2 years after diagnosis. Discussion and documentation of an advance care plan are needed to achieve end of life goals that are concordant with a patient's wishes. Early cognitive dysfunction in brain tumor patients can impede patients from making decisions about their own care. Patients with HGG, therefore require discussion and documentation of end of life goals early in their disease course, but implementation of this has been elusive.~In this study, we will integrate an Early STructured Advanced care Referrals by Telehealth (Early START) visit into standard neuro-oncologic care prior to initiation of adjuvant chemotherapy in patients with HGG. Multi-disciplinary providers including physicians, advanced practice providers, and nurses will undergo an in-service by palliative care experts to perform Early START with a standardized checklist followed by periodic training sessions. Fifty patients with HGG will be enrolled over a 12-month period. They will receive a pre-visit educational guide to increase literacy regarding advance directives (AD) followed by a provider-led Early START visit that will be recorded. Post-visit assessments will address patient and caregiver perspectives on the intervention, patient and caregiver knowledge, patient satisfaction and patient-reported anxiety measures. A provider questionnaire will assess length of visit, adherence to the checklist and AD outcomes of the visit. Patients will be followed until death. End of life quality measures and concordance of death with goals of care will be assessed using a combination of caregiver surveys and the electronic medical record. These outcomes will be compared to historical controls treated at our center from 2010-2015.~Specific Aims:~Aim 1a. To determine the effectiveness of Early START as measured by AD documentation.~Aim 1b. To determine the utility of Early START as measured by timing of hospice enrollment at the end of life and place of death concordant with the patient's goals.~Hypothesis: As our primary aim, we hypothesize that Early START will increase the percentage of AD documentation by the 3rd oncology visit from 51% to 80%. As secondary outcomes, we hypothesize that it will decrease the percentage of AD that are completed by proxy from 45% to 25%, will improve end of life quality measures as compared to our published historical controls and that the majority of patients who undergo Early START will die in a setting of their choosing.~Aim 2a. To demonstrate the feasibility of Early START as measured by the percent of visits completed prior to the third oncology visit, adherence to a pre-specified checklist, and length of time to complete the visit.~Aim 2b. To optimize the Early START intervention by incorporating patient/caregiver and provider feedback.~Hypothesis: We hypothesize that 80% of visits will be completed using telehealth by the 3rd oncology visit, 80% of providers will utilize the pre-specified checklist and that average visit duration will be less than one hour.
|
Early Telehealth Visits for Discussion of Advanced Directives for Patients Newly Diagnosed With High Grade Glioma: Impact on Patient Care and Satisfaction
|
Glioma
|
* Behavioral: Early START visit using checklist over telephone or zoom
|
Inclusion Criteria:~New pathologic diagnosis of WHO grade III or IV glioma within four months of consent~English speaking~Exclusion Criteria:~Severe cognitive dysfunction or aphasia precluding discussion of advanced care planning issues
|
18 Years
| null |
All
|
No
|
Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Advanced Directive Completion Rate | Percentage of patients who complete an advanced directive by the third oncology visit | Time of diagnosis to 3rd oncology visit at an average of 4 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early START visit completion | Percentage of Early START (Early STructured Advanced care Referrals by Telehealth) visits completed by the third oncology visit | Time of diagnosis to 3rd oncology visit at an average of 4 months |
| Checklist use | Percentage of providers who use the checklist | Time of Early START visit [on average between 3-4 months after diagnosis] |
| Duration of visit | Duration of time in minutes | Duration of visit [average 60 min] |
| Advanced Care Directive Completion by patient vs proxy | Percentage of completed Advanced Care Directives completed by proxy (rather than by the patient) | Time of diagnosis to death up to 5 years after registration |
| Chemotherapy use at end of life | Percentage of patients that were treated with chemotherapy within 14 days of death | Time of diagnosis to death up to 5 years after registration |
| Hospice enrollment | Percentage of patients who were enrolled in hospice >7 days prior to death | Time of diagnosis to death up to 5 years after registration |
| Palliative care and/or hospice involvement at end of life | Percentage of patients who received a palliative care or hospice consult prior to death | Time of diagnosis to death up to 5 years after registration |
| Setting of end of life | Percentage of patients for whom setting of death was consistent with their wishes | Time of diagnosis to death up to 5 years after registration |
|
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: Early STructured Advanced care Referrals by Telehealth<br>Early START visit using checklist over telephone or zoom:~A telehealth visit conducted within 4 months of patient diagnosis, with the goal of encouraging patients to discuss and document their end-of-life wishes prior to the onset of cognitive impediments common among patients with late-stage high grade glioma. | Behavioral: Early START visit using checklist over telephone or zoom<br>* Prior to visit subject receives pre-visit educational guide and copy of advance directive form~Follow up surveys:~Immediate: provider feedback survey~2-4 weeks after visit: subject feedback survey and caregiver/family feedback survey~After subject death: caregiver/family survey<br>|
|
Telehealth Visits to Discuss Advanced Directives for Patients Newly Diagnosed With High Grade Glioma
Study Overview
=================
Brief Summary
-----------------
High grade gliomas (HGGs) are rapidly progressive brain tumors resulting in death for most patients between 6 months and 2 years after diagnosis. It is important for patients with HGG to discuss and document their wishes at the end of life. However, many of these patients experience early changes in cognition which impede their decision-making. For this reason, these patients should have early discussions with their providers. However, implementation of this remains challenging in clinical practice. In this study, we will create an Early STructured Advanced care Referrals by Telehealth (Early START) visit for patients soon after their initial oncology visit. A checklist and pre-visit guide were developed to help guide the visit for both the provider and patient. Providers will receive special training in running these visits. Caregivers and/or family members will be encouraged to participate. Visits will be done using video or telephone and recorded. For patients who do not have access to technology for these visits, it will be provided. After the visit, patients, caregivers and/or family who participated, and providers will fill out surveys to address feasibility of having these extra visits and improve the visits for future. Patients will be followed until death. Caregivers and/or family who participated will be asked about whether end of life was in line with the patient's wishes. We will also use the patient's medical record to assess other aspects of end of life. We will compare end of life outcomes with other similar patients treated at our center.
Detailed Description
-----------------
High grade gliomas (HGGs) are rapidly progressive brain tumors resulting in death for most patients between 6 months and 2 years after diagnosis. Discussion and documentation of an advance care plan are needed to achieve end of life goals that are concordant with a patient's wishes. Early cognitive dysfunction in brain tumor patients can impede patients from making decisions about their own care. Patients with HGG, therefore require discussion and documentation of end of life goals early in their disease course, but implementation of this has been elusive. In this study, we will integrate an Early STructured Advanced care Referrals by Telehealth (Early START) visit into standard neuro-oncologic care prior to initiation of adjuvant chemotherapy in patients with HGG. Multi-disciplinary providers including physicians, advanced practice providers, and nurses will undergo an in-service by palliative care experts to perform Early START with a standardized checklist followed by periodic training sessions. Fifty patients with HGG will be enrolled over a 12-month period. They will receive a pre-visit educational guide to increase literacy regarding advance directives (AD) followed by a provider-led Early START visit that will be recorded. Post-visit assessments will address patient and caregiver perspectives on the intervention, patient and caregiver knowledge, patient satisfaction and patient-reported anxiety measures. A provider questionnaire will assess length of visit, adherence to the checklist and AD outcomes of the visit. Patients will be followed until death. End of life quality measures and concordance of death with goals of care will be assessed using a combination of caregiver surveys and the electronic medical record. These outcomes will be compared to historical controls treated at our center from 2010-2015. Specific Aims: Aim 1a. To determine the effectiveness of Early START as measured by AD documentation. Aim 1b. To determine the utility of Early START as measured by timing of hospice enrollment at the end of life and place of death concordant with the patient's goals. Hypothesis: As our primary aim, we hypothesize that Early START will increase the percentage of AD documentation by the 3rd oncology visit from 51% to 80%. As secondary outcomes, we hypothesize that it will decrease the percentage of AD that are completed by proxy from 45% to 25%, will improve end of life quality measures as compared to our published historical controls and that the majority of patients who undergo Early START will die in a setting of their choosing. Aim 2a. To demonstrate the feasibility of Early START as measured by the percent of visits completed prior to the third oncology visit, adherence to a pre-specified checklist, and length of time to complete the visit. Aim 2b. To optimize the Early START intervention by incorporating patient/caregiver and provider feedback. Hypothesis: We hypothesize that 80% of visits will be completed using telehealth by the 3rd oncology visit, 80% of providers will utilize the pre-specified checklist and that average visit duration will be less than one hour.
Official Title
-----------------
Early Telehealth Visits for Discussion of Advanced Directives for Patients Newly Diagnosed With High Grade Glioma: Impact on Patient Care and Satisfaction
Conditions
-----------------
Glioma
Intervention / Treatment
-----------------
* Behavioral: Early START visit using checklist over telephone or zoom
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: New pathologic diagnosis of WHO grade III or IV glioma within four months of consent English speaking Exclusion Criteria: Severe cognitive dysfunction or aphasia precluding discussion of advanced care planning issues
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: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early STructured Advanced care Referrals by Telehealth<br>Early START visit using checklist over telephone or zoom: A telehealth visit conducted within 4 months of patient diagnosis, with the goal of encouraging patients to discuss and document their end-of-life wishes prior to the onset of cognitive impediments common among patients with late-stage high grade glioma. | Behavioral: Early START visit using checklist over telephone or zoom<br>* Prior to visit subject receives pre-visit educational guide and copy of advance directive form Follow up surveys: Immediate: provider feedback survey 2-4 weeks after visit: subject feedback survey and caregiver/family feedback survey After subject death: caregiver/family survey<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Advanced Directive Completion Rate | Percentage of patients who complete an advanced directive by the third oncology visit | Time of diagnosis to 3rd oncology visit at an average of 4 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early START visit completion | Percentage of Early START (Early STructured Advanced care Referrals by Telehealth) visits completed by the third oncology visit | Time of diagnosis to 3rd oncology visit at an average of 4 months |
| Checklist use | Percentage of providers who use the checklist | Time of Early START visit [on average between 3-4 months after diagnosis] |
| Duration of visit | Duration of time in minutes | Duration of visit [average 60 min] |
| Advanced Care Directive Completion by patient vs proxy | Percentage of completed Advanced Care Directives completed by proxy (rather than by the patient) | Time of diagnosis to death up to 5 years after registration |
| Chemotherapy use at end of life | Percentage of patients that were treated with chemotherapy within 14 days of death | Time of diagnosis to death up to 5 years after registration |
| Hospice enrollment | Percentage of patients who were enrolled in hospice >7 days prior to death | Time of diagnosis to death up to 5 years after registration |
| Palliative care and/or hospice involvement at end of life | Percentage of patients who received a palliative care or hospice consult prior to death | Time of diagnosis to death up to 5 years after registration |
| Setting of end of life | Percentage of patients for whom setting of death was consistent with their wishes | Time of diagnosis to death up to 5 years after registration |
|
|
NCT02178449
|
Prolongation of Pain Free Time by the Use of Dexamethasone in Peripheral Nerve Blockade
|
The main aim of the study is to investigate the proven effect of dexamethsone on the duration of the interscalene block. The investigators try to define optimal dose and volume for ropivacaine, when used together with dexamethsone. The current literature uses often very high volumes of ropivacain when used together with dexamethasone. The investigators try to research the effect of using dexamethsone together with low volume, high concentration ropivacaine for interscalene blockade. The investigators' hypothesis is that dexamethasone has an positive effect on the pain free after used together with ropivacaine at the scalene block.
|
The Effect of Dexamethasone Used Together With Low Volume Ropivacaine in a Single Shot Interscalene Block on the Pain Free Time Experienced by the Patient
|
Interscalene Block, Shoulder Arthroscopy, Dexamethasone, Low Volume Regional Anesthesia
|
* Drug: Dexamethasone acetate
* Drug: Placebo
* Drug: Ropivacaine
|
Inclusion Criteria:~atroscopy of the shoulder~repair of the RM~Exclusion Criteria:~patient under 18 years~patient is fertile~chronic opiat use more than 30mg oxycodone per day~operations at the shoulder that involves the bone~usage of cortisone for more than 2 weeks~risk greater as asa III~damage to nerves~neuropathy at the target arm
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain free time measured by the duration between block and the point at which the patient is asking for painkillers | | Patients will be followed during their stay at the hospital, which will be normally around 24 to 48 hours. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Rating Scale for Pain at Movement and Rest | | Measured 10 hours after the intervention |
|
Dexamethasone acetate, Physiological Effects of Drugs, Dexamethasone, Ropivacaine, BB 1101, Anti-Inflammatory Agents, Antiemetics, Autonomic Agents, Peripheral Nervous System Agents, Gastrointestinal Agents, Glucocorticoids, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Antineoplastic Agents, Hormonal, Antineoplastic Agents, Anesthetics, Local, Anesthetics, Central Nervous System Depressants, Sensory System Agents, Protease Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Verum<br>Dexamethasone and Ropivacaine | Drug: Dexamethasone acetate<br> <br> Drug: Ropivacaine<br> <br> |
| Active Comparator: Placebo<br>Ropivacaine and Saline | Drug: Placebo<br> <br> Drug: Ropivacaine<br> <br> |
|
Prolongation of Pain Free Time by the Use of Dexamethasone in Peripheral Nerve Blockade
Study Overview
=================
Brief Summary
-----------------
The main aim of the study is to investigate the proven effect of dexamethsone on the duration of the interscalene block. The investigators try to define optimal dose and volume for ropivacaine, when used together with dexamethsone. The current literature uses often very high volumes of ropivacain when used together with dexamethasone. The investigators try to research the effect of using dexamethsone together with low volume, high concentration ropivacaine for interscalene blockade. The investigators' hypothesis is that dexamethasone has an positive effect on the pain free after used together with ropivacaine at the scalene block.
Official Title
-----------------
The Effect of Dexamethasone Used Together With Low Volume Ropivacaine in a Single Shot Interscalene Block on the Pain Free Time Experienced by the Patient
Conditions
-----------------
Interscalene Block, Shoulder Arthroscopy, Dexamethasone, Low Volume Regional Anesthesia
Intervention / Treatment
-----------------
* Drug: Dexamethasone acetate
* Drug: Placebo
* Drug: Ropivacaine
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: atroscopy of the shoulder repair of the RM Exclusion Criteria: patient under 18 years patient is fertile chronic opiat use more than 30mg oxycodone per day operations at the shoulder that involves the bone usage of cortisone for more than 2 weeks risk greater as asa III damage to nerves neuropathy at the target arm
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 |
| --- | --- |
| Experimental: Verum<br>Dexamethasone and Ropivacaine | Drug: Dexamethasone acetate<br> <br> Drug: Ropivacaine<br> <br> |
| Active Comparator: Placebo<br>Ropivacaine and Saline | Drug: Placebo<br> <br> Drug: Ropivacaine<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain free time measured by the duration between block and the point at which the patient is asking for painkillers | | Patients will be followed during their stay at the hospital, which will be normally around 24 to 48 hours. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Rating Scale for Pain at Movement and Rest | | Measured 10 hours after the intervention |
|
||
NCT05448521
|
Postoperative Lactate and Atrial Fibrillation After CABG
|
Postoperative atrial fibrillation (POAF) is associated with increased mortality and morbidity in patients undergoing isolated coronary artery bypass grafting (CABG). It has been estimated that 5-40% of CABG patients experience POAF. Advanced age, P wave abnormalities, left atrial dilation, emergency surgery, low left ventricle ejection fraction, low glomerular filtration rate and chronic obstructive pulmonary disease have been reported in the etiology. Predicting which patients would experience POAF following CABG is important since it would allow physicians to apply more focused prophylactic measures. Lactate is the final product of anaerobic glycolysis. Serum lactate level are increased in case of inadequate oxygen delivery to tissues. The investigators aim to assess whether serum lactate levels measured early in the postoperative period could be used as a predictive marker of POAF in adults undergoing isolated CABG.
|
Association of Postoperative Lactate Levels With Postoperative Atrial Fibrillation in Patients Undergoing Isolated Coronary Artery Bypass Graft Surgery
|
Coronary Artery Disease, Atrial Fibrillation
|
Inclusion Criteria:~Undergoing isolated CABG~Age >18 years~Exclusion Criteria:~Age <18 years~Pregnancy~History of paroxysmal atrial fibrillation prior to surgery~Undergoing concomitant procedures (e.g., CABG + valve surgery)~Any preoperative cardiac rhythm other than normal sinus rhythm~More than mild cardiac valve stenosis or insufficiency
|
18 Years
| null |
All
| null |
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative atrial fibrillation | New-onset atrial fibrillation occurring in the immediate period after CABG | 30 days |
|
Atrial Fibrillation, Coronary Artery Disease, Arrhythmias, Cardiac, Heart Diseases, Cardiovascular Diseases, Pathologic Processes, Coronary Disease, Myocardial Ischemia, Arteriosclerosis, Arterial Occlusive Diseases, Vascular Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Low lactate<br>Patients with a low lactate level defined by logistic regression analysis. | |
| High lactate<br>Patients with a high lactate level defined by logistic regression analysis. | |
|
Postoperative Lactate and Atrial Fibrillation After CABG
Study Overview
=================
Brief Summary
-----------------
Postoperative atrial fibrillation (POAF) is associated with increased mortality and morbidity in patients undergoing isolated coronary artery bypass grafting (CABG). It has been estimated that 5-40% of CABG patients experience POAF. Advanced age, P wave abnormalities, left atrial dilation, emergency surgery, low left ventricle ejection fraction, low glomerular filtration rate and chronic obstructive pulmonary disease have been reported in the etiology. Predicting which patients would experience POAF following CABG is important since it would allow physicians to apply more focused prophylactic measures. Lactate is the final product of anaerobic glycolysis. Serum lactate level are increased in case of inadequate oxygen delivery to tissues. The investigators aim to assess whether serum lactate levels measured early in the postoperative period could be used as a predictive marker of POAF in adults undergoing isolated CABG.
Official Title
-----------------
Association of Postoperative Lactate Levels With Postoperative Atrial Fibrillation in Patients Undergoing Isolated Coronary Artery Bypass Graft Surgery
Conditions
-----------------
Coronary Artery Disease, Atrial Fibrillation
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Undergoing isolated CABG Age >18 years Exclusion Criteria: Age <18 years Pregnancy History of paroxysmal atrial fibrillation prior to surgery Undergoing concomitant procedures (e.g., CABG + valve surgery) Any preoperative cardiac rhythm other than normal sinus rhythm More than mild cardiac valve stenosis or insufficiency
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Low lactate<br>Patients with a low lactate level defined by logistic regression analysis. | |
| High lactate<br>Patients with a high lactate level defined by logistic regression analysis. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative atrial fibrillation | New-onset atrial fibrillation occurring in the immediate period after CABG | 30 days |
|
|||||
NCT02922387
|
Smoking Cessation Intervention in Respiratory Inpatients
|
Prospective, open-label, parallel-group, 52-week trial comparing varenicline in combination with behavioral support with one session of behavioral support alone.~Eligible patients were smokers hospitalized due to a) acute exacerbation of chronic obstructive pulmonary disease (COPD), or b) bronchial asthma attack, or c) community-acquired pneumonia (CAP).~The primary outcome was the success rate (%) at week 52. Secondary outcomes were quality of life (QoL) alterations on the domains of the 36-Item Short Form Health Survey (SF36) and investigation of possible predictors for smoking abstinence.
|
Patients screened for eligibility were all the smokers who were hospitalized in the First Pulmonology Clinic of Kavala General Hospital from May 2012 to May 2014.~Patients had an initial private consultation session and motivational interview while still in the hospital. Following this interview, patients chose the smoking cessation intervention they preferred: either the standard regimen for varenicline and behavioral support or behavioral support without pharmacotherapy.~All patients quit smoking while still hospitalized.Follow-up phone calls with a minimum duration of 10 minutes were scheduled in weeks 1, 2, 4, and months 3,6 and 9 following smoking cessation.~Patients in both groups were asked to return to hospital in month 12 (week 52) for a final assessment. At this last visit, the SF36 was again completed and exhaled CO was (re) measured.
|
Varenicline and Advanced Behavioral Support on Smoking Cessation and Quality of Life in Inpatients With Acute Exacerbation of COPD, Bronchial Asthma Attack, or Community-acquired Pneumonia: a Prospective Open-label 52-week Follow-up Trial
|
Pulmonary Disease, Chronic Obstructive, Asthma, Community Acquired Pneumonia
|
* Drug: Varenicline
* Behavioral: Behavioral support
|
Inclusion criteria:~Adult smokers (> 100 cigarettes in their lifetime)~Patients hospitalized due to either a) acute exacerbation of COPD, or b) acute exacerbation of bronchial asthma, or c) community acquired pneumonia.~Patients who agreed to participate and provided written informed consent were recruited.~Exclusion criteria:~Inpatients younger than 18~adult smokers hospitalized for any reason other than acute exacerbation of COPD / bronchial asthma or community acquired pneumonia.
|
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 |
| --- | --- | --- |
| Smoking Cessation Rate at week 52 | | 12 months follow up |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life changes following smoking cessation | Quality of life (QoL) was assessed, in both groups, with the Short Form SF36 questionnaire at baseline and at the end of the followup period, week 52. | 12 months follow up |
|
varenicline, COPD, asthma, pneumonia, smoking cessation
|
Varenicline, Nicotinic Agonists, Cholinergic Agonists, Cholinergic Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Varenicline + Behavioral support<br>varenicline and behavioral support | Drug: Varenicline<br>* Varenicline was given for 12 weeks to all patients in group A. The initial dose was 0.5 mg/day for days 1-3, and was then up-titrated to 0.5mg on days 4-7, and finally to 1 mg twice daily from day 8 until the end of treatment<br>* Other names: Chantix;Behavioral: Behavioral support<br>* An initial private consultation session and motivational interview while still in the hospital that lasted for at least 60 minutes. Follow-up phone calls with a minimum duration of 10 minutes were scheduled in weeks 1, 2, 4, and months 3,6 and 9 following smoking cessation.<br>* Other names: consultation session;|
| Active Comparator: Behavioral support<br>behavioral support | Behavioral: Behavioral support<br>* An initial private consultation session and motivational interview while still in the hospital that lasted for at least 60 minutes. Follow-up phone calls with a minimum duration of 10 minutes were scheduled in weeks 1, 2, 4, and months 3,6 and 9 following smoking cessation.<br>* Other names: consultation session;|
|
Smoking Cessation Intervention in Respiratory Inpatients
Study Overview
=================
Brief Summary
-----------------
Prospective, open-label, parallel-group, 52-week trial comparing varenicline in combination with behavioral support with one session of behavioral support alone. Eligible patients were smokers hospitalized due to a) acute exacerbation of chronic obstructive pulmonary disease (COPD), or b) bronchial asthma attack, or c) community-acquired pneumonia (CAP). The primary outcome was the success rate (%) at week 52. Secondary outcomes were quality of life (QoL) alterations on the domains of the 36-Item Short Form Health Survey (SF36) and investigation of possible predictors for smoking abstinence.
Detailed Description
-----------------
Patients screened for eligibility were all the smokers who were hospitalized in the First Pulmonology Clinic of Kavala General Hospital from May 2012 to May 2014. Patients had an initial private consultation session and motivational interview while still in the hospital. Following this interview, patients chose the smoking cessation intervention they preferred: either the standard regimen for varenicline and behavioral support or behavioral support without pharmacotherapy. All patients quit smoking while still hospitalized.Follow-up phone calls with a minimum duration of 10 minutes were scheduled in weeks 1, 2, 4, and months 3,6 and 9 following smoking cessation. Patients in both groups were asked to return to hospital in month 12 (week 52) for a final assessment. At this last visit, the SF36 was again completed and exhaled CO was (re) measured.
Official Title
-----------------
Varenicline and Advanced Behavioral Support on Smoking Cessation and Quality of Life in Inpatients With Acute Exacerbation of COPD, Bronchial Asthma Attack, or Community-acquired Pneumonia: a Prospective Open-label 52-week Follow-up Trial
Conditions
-----------------
Pulmonary Disease, Chronic Obstructive, Asthma, Community Acquired Pneumonia
Intervention / Treatment
-----------------
* Drug: Varenicline
* Behavioral: Behavioral support
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Adult smokers (> 100 cigarettes in their lifetime) Patients hospitalized due to either a) acute exacerbation of COPD, or b) acute exacerbation of bronchial asthma, or c) community acquired pneumonia. Patients who agreed to participate and provided written informed consent were recruited. Exclusion criteria: Inpatients younger than 18 adult smokers hospitalized for any reason other than acute exacerbation of COPD / bronchial asthma or community acquired pneumonia.
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: Varenicline + Behavioral support<br>varenicline and behavioral support | Drug: Varenicline<br>* Varenicline was given for 12 weeks to all patients in group A. The initial dose was 0.5 mg/day for days 1-3, and was then up-titrated to 0.5mg on days 4-7, and finally to 1 mg twice daily from day 8 until the end of treatment<br>* Other names: Chantix;Behavioral: Behavioral support<br>* An initial private consultation session and motivational interview while still in the hospital that lasted for at least 60 minutes. Follow-up phone calls with a minimum duration of 10 minutes were scheduled in weeks 1, 2, 4, and months 3,6 and 9 following smoking cessation.<br>* Other names: consultation session;|
| Active Comparator: Behavioral support<br>behavioral support | Behavioral: Behavioral support<br>* An initial private consultation session and motivational interview while still in the hospital that lasted for at least 60 minutes. Follow-up phone calls with a minimum duration of 10 minutes were scheduled in weeks 1, 2, 4, and months 3,6 and 9 following smoking cessation.<br>* Other names: consultation session;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Smoking Cessation Rate at week 52 | | 12 months follow up |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life changes following smoking cessation | Quality of life (QoL) was assessed, in both groups, with the Short Form SF36 questionnaire at baseline and at the end of the followup period, week 52. | 12 months follow up |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
varenicline, COPD, asthma, pneumonia, smoking cessation
|
NCT03914521
|
Pre-surgical CT Scan Assessment of Bone Mineral Density Before Resection of NHO of the Hip
|
Neurogenic heterotopic ossification (NHO) is defined as an ectopic ossification around proximal joints usually seen after traumatic brain injury, spinal cord injury or polytrauma.~NHO causes pain, partial or total joint ankylosis and vascular or nerve complications.~The osteopenia (low bone density) induced by ankylose increases the fracture risk of femoral neck during the hip surgery performed to remove the NHO.~The analyse of femoral head bone mineral density from hip pre-surgical CT scan could anticipate this kind of complication establishing a presurgical prognostic.~If as it turns out the bone density measured from hip pre-surgical CT scan is relevant fracture risk marker, a preventive osteosynthesis or femoral head and neck resection could be performed in the same time of NHO resection.
|
Pre-surgical CT Scan Assessment of Femoral Head Bone Mineral Density Before Resection of Neurogenic Heterotopic Ossification (NHO) of the Hip
|
Paraosteoarthropathies
|
Inclusion Criteria:~Patients aged 18 years and over~Patients having surgery resection of surgery resection of Neurogenic heterotopic ossification of hip.~Patients with pre-surgery CT-scan and surgery report available~Exclusion criteria:~Minor patients~Patients didn't have surgery surgery resection of Neurogenic heterotopic ossification of hip.~Pre-surgery CT-scan and surgery report not available~Exclusion Criteria:~-
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| femoral head bone mineral density | femoral head bone mineral density | 1 year |
|
hip surgery, bone mineral density, femoral head, Pre-surgical prognostic
|
Pre-surgical CT Scan Assessment of Bone Mineral Density Before Resection of NHO of the Hip
Study Overview
=================
Brief Summary
-----------------
Neurogenic heterotopic ossification (NHO) is defined as an ectopic ossification around proximal joints usually seen after traumatic brain injury, spinal cord injury or polytrauma. NHO causes pain, partial or total joint ankylosis and vascular or nerve complications. The osteopenia (low bone density) induced by ankylose increases the fracture risk of femoral neck during the hip surgery performed to remove the NHO. The analyse of femoral head bone mineral density from hip pre-surgical CT scan could anticipate this kind of complication establishing a presurgical prognostic. If as it turns out the bone density measured from hip pre-surgical CT scan is relevant fracture risk marker, a preventive osteosynthesis or femoral head and neck resection could be performed in the same time of NHO resection.
Official Title
-----------------
Pre-surgical CT Scan Assessment of Femoral Head Bone Mineral Density Before Resection of Neurogenic Heterotopic Ossification (NHO) of the Hip
Conditions
-----------------
Paraosteoarthropathies
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients aged 18 years and over Patients having surgery resection of surgery resection of Neurogenic heterotopic ossification of hip. Patients with pre-surgery CT-scan and surgery report available Exclusion criteria: Minor patients Patients didn't have surgery surgery resection of Neurogenic heterotopic ossification of hip. Pre-surgery CT-scan and surgery report not available Exclusion Criteria: -
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 |
| --- | --- | --- |
| femoral head bone mineral density | femoral head bone mineral density | 1 year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hip surgery, bone mineral density, femoral head, Pre-surgical prognostic
|
||||||
NCT00983892
|
Care Partners: Web-based Support for Caregivers of Veterans Undergoing Chemotherapy
|
Given the growing strain on the Veterans Administration resulting from increasing caseloads of cancer patients, interventions are badly needed that assist patients in managing their illness, improve quality of life and avoid acute episodes that result in urgent care use and increased mortality. Previous studies have found that cancer patients undergoing chemotherapy can effectively manage their own symptoms when monitored using automated telephone calls. Such technology, however, may challenge the number of Veterans who lack social support and/or independence. The goal was to develop and test a technology that not only monitors patients automatically by telephone, but also gives them self management advice and engages a friend or family member to serve as a CarePartner willing to play a limited role in identifying patient symptoms and psychosocial needs to reinforce self management and provide social support. The investigators found that this technology indeed helped patients better control their symptoms, especially when a caregiver participated in the program along with them.
|
Cancer is a prevalent problem that causes much suffering among Veterans and their families. Most interventions to improve symptom control require Veterans to engage in activities such as managing medications, altering diets, or accessing outside resources that may be beyond their reach due to limitations in physical and mental functioning. Friends and family inside and outside of the Veteran's household can help, but often lack the skills and resources they need to do so.~Cancer CarePartners was designed to address these needs by providing cancer-stricken Veterans and their informal caregivers with the information they need to make effective management decisions, decrease symptom burden, and improve outcomes. Cancer CarePartners is a Web-enabled program that alerts caregivers of patients' symptoms and provides them with a framework for identifying problems, receiving structured advice, formulating a 'task list,' and following up with their patients as they receive chemotherapy. Specifically, Cancer CarePartners includes weekly, automated telephonic symptom assessment (ATSA) with self-management (SM) support to the Veteran paired with Web-based alerts to the caregiver pointing them to a website where s/he can obtain customized advice. A randomized control trial was conducted to test the efficacy of this program in controlling symptoms as well as improving adherence to chemotherapy.~Objectives~1) To determine if Veterans undergoing chemotherapy who receive Cancer CarePartners report significant improvement in the summed severity of symptoms (the sum of 0-10 severity across 8 core symptoms) compared to Veterans receiving symptom monitoring and self-management advice; secondarily, to determine if they experience better adherence to chemotherapy and utilization. (2) To determine if caregivers participating in the intervention provide significantly more social support to patients than do controls; secondarily, to determine if they experience more caregiver burden and distress than do controls. (3) To determine whether impacts on patients are mediated by mastery. (4) To determine whether impacts on caregivers are mediated by mastery.~Methods Consenting Veterans with solid tumors undergoing chemotherapy at one of three VAMCs (Ann Arbor, Loma Linda and Fargo) who reported at least one core symptom at a moderate level or higher and had a caregiver willing to enroll in the study were randomly assigned to either 10 weeks of Cancer CarePartners or 10 weeks of automated, telephonic symptom assessment (ATSA) with self management support. Arms were balanced for non-small cell lung cancer status and caregiver type. Patients and caregivers were surveyed at intake, 10, and 14 weeks. In addition, the investigators tracked patient participation with ATSA and (in the experimental arm) caregiver use of the Cancer CarePartners Website. The investigators reviewed all medical records for content of care received during the 14 weeks on study.
|
Web-based Support for Caregivers of Veterans Undergoing Chemotherapy
|
Cancer
|
* Behavioral: Caregiver website
|
Inclusion Criteria:~Patients must be 18 years or older, cognitively intact, English-speaking, able to hear, and own a telephone.~Patients can have any solid tumor.~Patients must be initiating IV cytotoxic chemotherapy and, if recurrent, have experienced a 1 month treatment free interval.~Caregivers must be 18 years or older, cognitively intact, English-speaking, and able to hear/speak for interviews.~Caregivers must have access to a telephone and computer with high speed internet access.~Exclusion Criteria:~Patients will be excluded if they have a hematologic malignancy or are receiving bone marrow transplantation.~Patients and caregivers will be excluded if they have an untreated serious mental illness or cognitive impairment, are institutionalized or enrolled in hospice (prior to trial), or plan on not receiving all care from VA
|
18 Years
| null |
All
|
No
|
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summed Symptom Severity | Summed severity across 8 symptoms of interest, as measured using the MD Anderson Symptom Inventory. 8 core symptoms rated by the patient on a scale of 0 to 10. These 8 symptoms were chosen based on their prevalence of 50% or greater in the population of interest. Higher scores mean WORSE or GREATER SYMPTOM BURDEN. | 3 months |
|
Cancer, caregiver, pain, symptom, information technology, palliative care
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CarePartners+<br>Patients receive automated telephonic symptom assessment and symptom management advice; caregivers receive the intervention (Intervention = access to a caregiver Web site that updates them on patient's symptoms and provides tailored problem solving advice). | Behavioral: Caregiver website<br>* Website receives patient symptom assessment data from IVR and provides caregivers with weekly updates on patient status, allowing caregivers to access tailored symptom management advice and formulate an action plan.<br>* Other names: Care Partners;|
| No Intervention: CarePartners-<br>Patients receive automated telephonic symptom assessment and symptom management advice; caregivers receive nothing (i.e. no access to the caregiver website, or 'intervention'). | |
|
Care Partners: Web-based Support for Caregivers of Veterans Undergoing Chemotherapy
Study Overview
=================
Brief Summary
-----------------
Given the growing strain on the Veterans Administration resulting from increasing caseloads of cancer patients, interventions are badly needed that assist patients in managing their illness, improve quality of life and avoid acute episodes that result in urgent care use and increased mortality. Previous studies have found that cancer patients undergoing chemotherapy can effectively manage their own symptoms when monitored using automated telephone calls. Such technology, however, may challenge the number of Veterans who lack social support and/or independence. The goal was to develop and test a technology that not only monitors patients automatically by telephone, but also gives them self management advice and engages a friend or family member to serve as a CarePartner willing to play a limited role in identifying patient symptoms and psychosocial needs to reinforce self management and provide social support. The investigators found that this technology indeed helped patients better control their symptoms, especially when a caregiver participated in the program along with them.
Detailed Description
-----------------
Cancer is a prevalent problem that causes much suffering among Veterans and their families. Most interventions to improve symptom control require Veterans to engage in activities such as managing medications, altering diets, or accessing outside resources that may be beyond their reach due to limitations in physical and mental functioning. Friends and family inside and outside of the Veteran's household can help, but often lack the skills and resources they need to do so. Cancer CarePartners was designed to address these needs by providing cancer-stricken Veterans and their informal caregivers with the information they need to make effective management decisions, decrease symptom burden, and improve outcomes. Cancer CarePartners is a Web-enabled program that alerts caregivers of patients' symptoms and provides them with a framework for identifying problems, receiving structured advice, formulating a 'task list,' and following up with their patients as they receive chemotherapy. Specifically, Cancer CarePartners includes weekly, automated telephonic symptom assessment (ATSA) with self-management (SM) support to the Veteran paired with Web-based alerts to the caregiver pointing them to a website where s/he can obtain customized advice. A randomized control trial was conducted to test the efficacy of this program in controlling symptoms as well as improving adherence to chemotherapy. Objectives 1) To determine if Veterans undergoing chemotherapy who receive Cancer CarePartners report significant improvement in the summed severity of symptoms (the sum of 0-10 severity across 8 core symptoms) compared to Veterans receiving symptom monitoring and self-management advice; secondarily, to determine if they experience better adherence to chemotherapy and utilization. (2) To determine if caregivers participating in the intervention provide significantly more social support to patients than do controls; secondarily, to determine if they experience more caregiver burden and distress than do controls. (3) To determine whether impacts on patients are mediated by mastery. (4) To determine whether impacts on caregivers are mediated by mastery. Methods Consenting Veterans with solid tumors undergoing chemotherapy at one of three VAMCs (Ann Arbor, Loma Linda and Fargo) who reported at least one core symptom at a moderate level or higher and had a caregiver willing to enroll in the study were randomly assigned to either 10 weeks of Cancer CarePartners or 10 weeks of automated, telephonic symptom assessment (ATSA) with self management support. Arms were balanced for non-small cell lung cancer status and caregiver type. Patients and caregivers were surveyed at intake, 10, and 14 weeks. In addition, the investigators tracked patient participation with ATSA and (in the experimental arm) caregiver use of the Cancer CarePartners Website. The investigators reviewed all medical records for content of care received during the 14 weeks on study.
Official Title
-----------------
Web-based Support for Caregivers of Veterans Undergoing Chemotherapy
Conditions
-----------------
Cancer
Intervention / Treatment
-----------------
* Behavioral: Caregiver website
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must be 18 years or older, cognitively intact, English-speaking, able to hear, and own a telephone. Patients can have any solid tumor. Patients must be initiating IV cytotoxic chemotherapy and, if recurrent, have experienced a 1 month treatment free interval. Caregivers must be 18 years or older, cognitively intact, English-speaking, and able to hear/speak for interviews. Caregivers must have access to a telephone and computer with high speed internet access. Exclusion Criteria: Patients will be excluded if they have a hematologic malignancy or are receiving bone marrow transplantation. Patients and caregivers will be excluded if they have an untreated serious mental illness or cognitive impairment, are institutionalized or enrolled in hospice (prior to trial), or plan on not receiving all care from VA
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: Supportive Care
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CarePartners+<br>Patients receive automated telephonic symptom assessment and symptom management advice; caregivers receive the intervention (Intervention = access to a caregiver Web site that updates them on patient's symptoms and provides tailored problem solving advice). | Behavioral: Caregiver website<br>* Website receives patient symptom assessment data from IVR and provides caregivers with weekly updates on patient status, allowing caregivers to access tailored symptom management advice and formulate an action plan.<br>* Other names: Care Partners;|
| No Intervention: CarePartners-<br>Patients receive automated telephonic symptom assessment and symptom management advice; caregivers receive nothing (i.e. no access to the caregiver website, or 'intervention'). | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summed Symptom Severity | Summed severity across 8 symptoms of interest, as measured using the MD Anderson Symptom Inventory. 8 core symptoms rated by the patient on a scale of 0 to 10. These 8 symptoms were chosen based on their prevalence of 50% or greater in the population of interest. Higher scores mean WORSE or GREATER SYMPTOM BURDEN. | 3 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cancer, caregiver, pain, symptom, information technology, palliative care
|
||
NCT03510962
|
Comparison of 5 Buffering Agents on Changes in Salivary pH in Individuals Previously Exposed to a Test Fruit Juice
|
The diurnal variation in the flow of saliva and hence the composition of saliva is an established fact. Consumption of most types of acidic and sweetened foods and beverages are known to reduce the pH of saliva and some of them even reduce it to critical pH levels and result in structural damage to the hard tissues of the tooth.~The purpose of this study is to ascertain the effect of the selected commercially available test fruit-juice drink on the salivary pH and assess the buffering capacity of the saliva with or without various intervention measures following the exposure to the test fruit-juice drink at different time intervals.
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There are substantial existing evidences that there is diurnal variation in the flow of saliva and hence the composition of saliva. The average of normal pH of saliva is reported to be 6.8. Consumption of most types of acidic and sweetened foods and beverages are known to reduce the pH of saliva and some of them even reduce it to critical pH levels and result in structural damage to the hard tissues of the tooth.~Such damages can be prevented by maintaining the pH of saliva within optimal range by using oral hygiene measures.~The purpose of this study is to ascertain the effect of the selected commercially available test fruit-juice drink containing sugar on the pH of saliva and assess the buffering capacity of the saliva with or without various intervention measures following the exposure to the commercially available test fruit-juice drink at different time intervals.~Aims and Objectives:~To measure the pH of saliva post-exposure to commercially available test fruit-juice drink after 5, 15, 30, 45 and 60 minutes.~To measure the pH of saliva at 15, 30 and 45 minutes after using a tap water gargle as a buffering agent in those subjects who had prior exposure to commercially available test fruit-juice drink 15 minutes ago.~To measure the pH of saliva at 15, 30 and 45 minutes after using a 0.2%Chlorhexidine mouth rinse as a buffering agent in those subjects who had prior exposure to commercially available test fruit-juice drink 15 minutes ago.~To measure the pH of saliva at 15, 30 and 45 minutes after chewing Orbit® gum as a buffering agent in those subjects who had prior exposure to commercially available test fruit-juice drink 15 minutes ago~To measure the pH of saliva at 15, 30 and 45 minutes after brushing with commercially available fluoridated tooth paste and soft brush as a buffering agent in those subjects who had prior exposure to test fruit-juice drink 15 minutes ago~To measure the pH of saliva at 15, 30 and 45 minutes after gargling with 1% solution of baking soda as a buffering agent in those subjects who had prior exposure to commercially available test fruit-juice drink 15 minutes ago~To compare the efficacy of buffering agents on the pH of saliva at 15, 30, 45 minutes post intervention in subjects who have had the commercially available test fruit-juice drink 15 min prior to the a specific intervention, with the pH of saliva recorded in the same subjects at the same time periods when no intervention with any buffering agent was carried out after having the commercially available test fruit-juice drink.~To compare the pH of saliva recorded in the subjects at 15, 30, 45 minutes time periods when they used an intervention of gargle with tap water, with that recorded when they used mouth rinse of 0.2% Chlorhexidine, with that recorded when they brushed with soft brush and fluoridated tooth paste, with that recorded when they gargled with 1% baking soda solution and with that recorded when they chewed Orbit® chewing gum (15 minutes after using the test fruit-juice drink)~Materials and Methods:~30 volunteers in the age group of 18- 30 year with healthy oral cavities will be selected. Subjects with a history of any chronic medical illness, history of allergy, intake of drugs in the last 8 weeks, history of gastritis, bulimia will be excluded. Subjects with a DMFT score of more than 2 and Loe and Sillness Index of more than 0 will be excluded. Individuals who have and are currently undergoing orthodontic treatment will not be included in the study. Individuals who smoke or chew tobacco will not be included in the study sample. An informed consent for the research will be obtained from all the subjects who have volunteered for the study. The trial will be conducted as per the guidelines in the WHO-Handbook for Good Clinical Practice and the research protocol is approved by the Institutional Ethics Committee of the college.~The test fruit-juice drink that will be selected is Tropicana® Mixed Fruit Juice®.~The various buffering agents that will be used are:~0.2% Chlorhexidine mouth wash (Rexidine®, Indoco Remidies Ltd, Mumbai, India)- 10 ml solution swish for 60 sec and spit~Tap water- 10ml swish for 60 sec and spit~Brushing with fluoridated (Colgate Total®, Colgate-Palmolive Company, Mumbai, India) tooth paste- 2min using soft brush~Chewing polyol containing gum (Orbit®, Wrigley Company)- chew for 5 minutes and spit~Freshly prepared Sodium bicarbonate (baking soda) 1% w/v solution swish for 60 sec and spit.~The observer who will be measuring the salivary pH will remain blinded about the samples and buffering agent used.~The select individuals will be instructed to not use any mouth wash as part of oral hygiene regimen on test day and not consume any food or beverage for 2 hours prior to the collection of baseline sample of saliva at 10 AM on the test day. The select group of 30 individuals will be given a sample of 100 ml of Tropicana® mixed fruit-juice after recording their baseline salivary pH (0 min). They will be asked to sip, swish and swallow the drink within 2 minutes. After the exposure, salivary samples will be collected at 5 min and 15 min intervals for assessment of pH. Fifteen minutes after the exposure (consumption of test drink), the individuals will be asked to use one of the intervention methods included in this study. The salivary samples will be collected after 15, 30 and 45 minutes interval after the intervention. (i.e. 30, 45 and 60 minutes post exposure to the test drink respectively) The same protocol will be repeated using each intervention methods included in this study after a wash out period of minimum of 3 days. The protocol will be repeated on the study sample without any intervention following the exposure to the test fruit juice as a control.~Measurement of salivary pH will be done using a portable PH-035 Digital pH meter with automatic temperature compensation, to the accuracy of 0.1 and the machine will be calibrated on the morning of every test day and after 60 uses during the test day using Aquasol® pH calibration solutions with pH 4, 7 and 10.
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Comparison of Five Different Salivary Buffering Agents on the Changes in Salivary pH in a Cohort Previously Exposed to a Test Fruit Juice: A Randomized Controlled Crossover Trial.
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pH, Saliva Altered, Oral Hygiene, Tooth Structure; Disorder
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* Other: Group 1: no intervention
* Other: Group 2: tap water gargle
* Drug: Group 3: 0.2% Chlorhexidine
* Other: Group 4: Fluoridated tooth paste
* Other: Group 5: Polyol containing gum
* Other: Group 6: 1% sodium bicarbonate solution
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Inclusion Criteria:~subjects in the age group of 18 to 30 years.~subjects with a DMFT index score of less than 2.~subjects with Loe and Silness index score of 0.~subjects willing to volunteer for the study.~subjects who are available for the whole study period of 4 months~Exclusion Criteria:~subjects with history of gastritis and bulimia.~subjects with chronic medical illness.~subjects with history of allergy.~subjects with history of drug intake for last 8 weeks.~subjects who smoke or chew tobacco.
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18 Years
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30 Years
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All
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Accepts Healthy Volunteers
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Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single
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| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pH of saliva at baseline | All subjects in all groups collects the unstimulated saliva in a sterile glass dish for the measurement of baseline pH of the saliva. The subject will give the saliva sample just before being exposed to the test mixed fruit juice by swishing 100ml of Tropicana® Mixed Fruit Juice in mouth for 2 minutes and then drinking it The outcome accessor is blinded to origin of sample (from which group). | 0 minute |
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| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pH of Saliva 5 minutes after exposure to test mixed fruit juice | All subjects will be given 100 ml of test mixed fruit juice, Tropicana® Mixed Fruit Juice to drink. The subject will sip, swish and swallow the drink within 2 minutes. Five minutes after this, each subject will give unstimulated saliva in a sterile dish for measurement of saliva - 5minutes after exposure to test mixed fruit juice. The outcome accessor is blinded to the origin of sample (from which group). | 5 minutes |
| pH of Saliva 15 minutes after exposure to test mixed fruit juice | All subjects will give unstimulated saliva in a sterile dish for measurement of saliva -15minutes after exposure to test mixed fruit juice. The outcome accessor is blinded to the origin of sample (from which group). | 15 minutes |
| pH of Saliva 30 minutes after exposure to test mixed fruit juice | All subjects from all six (5 test and 1 comparator) groups will perform the assigned intervention as per schedule at time 15minutes post exposure to mixed fruit juice and shall give unstimulated saliva in a sterile dish for measurement of saliva -30minutes after exposure to test mixed fruit juice or in other words 15minutes after assigned intervention. The outcome accessor is blinded to the origin of sample (from which group). | 30 minutes |
| pH of Saliva 45 minutes after exposure to test mixed fruit juice | All subjects from all six (5 test and 1 comparator) groups will perform the assigned intervention as per given schedule at time 15minutes post exposure to mixed fruit juice and shall give unstimulated saliva in a sterile dish for measurement of saliva -45minutes after exposure to test mixed fruit juice or in other words 30minutes after assigned intervention. The outcome accessor is blinded to the origin of sample (from which group). | 45 minutes |
| pH of Saliva 60 minutes after exposure to test mixed fruit juice | All subjects from all six (5 test and 1 comparator) groups will perform the assigned intervention as per given schedule at time 15 minutes post exposure to mixed fruit juice and shall give unstimulated saliva in a sterile dish for measurement of saliva -60minutes after exposure to test mixed fruit juice or in other words 45minutes after assigned intervention. The outcome accessor is blinded to the origin of sample (from which group). | 60 minutes |
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pH of saliva, Fruit juice, buffering agent, oral hygiene
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Chlorhexidine, Anti-Infective Agents, Local, Anti-Infective Agents, Disinfectants
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| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1: no intervention<br>The subject collects the unstimulated saliva in a sterile glass dish for the measurement of baseline pH of the saliva.The subject is then given 100 ml of test mixed fruit juice,Tropicana® Mixed Fruit Juice, (PepsiCo, Inc) to drink. The subject will sip, swish and swallow the drink within 2 minutes.~Unstimulated saliva samples are collected from the subject to measure the pH of saliva after 5, 15, 30, 45 and 60 minutes of consumption of the test mixed fruit juice. | Other: Group 1: no intervention<br>* Unstimulated saliva samples are collected from the subject to measure the pH of saliva after 5, 15, 30, 45 and 60 minutes of consumption of the test mixed fruit juice without any intervention.<br>|
| Experimental: Group 2: tap water gargle<br>The subject collects the unstimulated saliva in a sterile glass dish for the measurement of baseline pH of the saliva.The subject is then given 100 ml of test mixed fruit juice,Tropicana® Mixed Fruit Juice, (PepsiCo, Inc) to drink. The subject will sip, swish and swallow the drink within 2 minutes.~Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva after 5 and 15 minutes of consumption of the test mixed fruit juice.~The subject will use 10 ml of tap water as mouth rinse to swish for 60 seconds and spit. Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes the gargle as an intervention. | Other: Group 2: tap water gargle<br>* The subject will use 10 ml of tap water as mouth rinse to swish for 60 seconds and spit. Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes the gargle as an intervention.<br>|
| Experimental: Group 3: 0.2% chlorhexidine<br>The subject collects the unstimulated saliva in a sterile glass dish for the measurement of baseline pH of the saliva. The subject is then given 100 ml of test mixed fruit juice, Tropicana® Mixed Fruit Juice, (PepsiCo, Inc) to drink. The subject will sip, swish and swallow the drink within 2 minutes.~Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva after 5 and 15 minutes of consumption of the test mixed fruit juice.~The subject will use 10 ml of 0.2% Chlorhexidine mouth rinse (Rexidine®, Indoco Remidies Ltd, Mumbai, India) to swish for 60 seconds and spit. Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes the gargle as an intervention. | Drug: Group 3: 0.2% Chlorhexidine<br>* The subject will use 10 ml of 0.2% Chlorhexidine mouth rinse (Rexidine®, Indoco Remidies Ltd, Mumbai, India) to swish for 60 seconds and spit. Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes the gargle as an intervention.<br>* Other names: Rexidine®;|
| Experimental: Group 4: fluoridated tooth paste<br>The subject collects the unstimulated saliva in a sterile glass dish for the measurement of baseline pH of the saliva. The subject is then given 100 ml of test mixed fruit juice, Tropicana® Mixed Fruit Juice, (PepsiCo, Inc) to drink. The subject will sip, swish and swallow the drink within 2 minutes.~Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva after 5 and 15 minutes of consumption of the test mixed fruit juice.~The subject will Brush with fluoridated toothpaste (Colgate Total®, Colgate-Palmolive Company, Mumbai, India) for 2 minutes using soft brush.~Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes the brushing as an intervention. | Other: Group 4: Fluoridated tooth paste<br>* The subject will Brush with fluoridated toothpaste-(Colgate Total®, Colgate-Palmolive Company, Mumbai, India) for 2 minutes using soft brush.~Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes using tooth paste as an intervention.<br>* Other names: Colgate Total®;|
| Experimental: Group 5: Polyol containing gum<br>The subject collects the unstimulated saliva in a sterile glass dish for the measurement of baseline pH of the saliva. The subject is then given 100 ml of test mixed fruit juice, Tropicana® Mixed Fruit Juice, (PepsiCo, Inc) to drink. The subject will sip, swish and swallow the drink within 2 minutes.~Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva after 5 and 15 minutes of consumption of the test mixed fruit juice.~The subject will chew polyol containing gum (Orbit®, Wrigley Company) for 5 minutes and spit.~Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes the chewing gum as an intervention. | Other: Group 5: Polyol containing gum<br>* The subject will chew polyol containing gum (Orbit®, WrigleyCompany) for 5 minutes and spit.~Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes chewing as an intervention.<br>* Other names: Orbit®;|
| Experimental: Group 6: 1% sodium bicarbonate solution<br>The subject collects the unstimulated saliva in a sterile glass dish for the measurement of baseline pH of the saliva. The subject is then given 100 ml of test mixed fruit juice, Tropicana® Mixed Fruit Juice, (PepsiCo, Inc) to drink. The subject will sip, swish and swallow the drink within 2 minutes.~Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva after 5 and 15 minutes of consumption of the test mixed fruit juice.~The subject will use 10 ml freshly prepared 1% sodium bicarbonate w/v solution to swish for 60 seconds and spit.~Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes the gargle as an intervention. | Other: Group 6: 1% sodium bicarbonate solution<br>* The subject will use 10 ml freshly prepared 1% sodium bicarbonate w/v solution to swish for 60 seconds and spit.~Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes the gargle as an intervention.<br>|
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Comparison of 5 Buffering Agents on Changes in Salivary pH in Individuals Previously Exposed to a Test Fruit Juice
Study Overview
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Brief Summary
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The diurnal variation in the flow of saliva and hence the composition of saliva is an established fact. Consumption of most types of acidic and sweetened foods and beverages are known to reduce the pH of saliva and some of them even reduce it to critical pH levels and result in structural damage to the hard tissues of the tooth. The purpose of this study is to ascertain the effect of the selected commercially available test fruit-juice drink on the salivary pH and assess the buffering capacity of the saliva with or without various intervention measures following the exposure to the test fruit-juice drink at different time intervals.
Detailed Description
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There are substantial existing evidences that there is diurnal variation in the flow of saliva and hence the composition of saliva. The average of normal pH of saliva is reported to be 6.8. Consumption of most types of acidic and sweetened foods and beverages are known to reduce the pH of saliva and some of them even reduce it to critical pH levels and result in structural damage to the hard tissues of the tooth. Such damages can be prevented by maintaining the pH of saliva within optimal range by using oral hygiene measures. The purpose of this study is to ascertain the effect of the selected commercially available test fruit-juice drink containing sugar on the pH of saliva and assess the buffering capacity of the saliva with or without various intervention measures following the exposure to the commercially available test fruit-juice drink at different time intervals. Aims and Objectives: To measure the pH of saliva post-exposure to commercially available test fruit-juice drink after 5, 15, 30, 45 and 60 minutes. To measure the pH of saliva at 15, 30 and 45 minutes after using a tap water gargle as a buffering agent in those subjects who had prior exposure to commercially available test fruit-juice drink 15 minutes ago. To measure the pH of saliva at 15, 30 and 45 minutes after using a 0.2%Chlorhexidine mouth rinse as a buffering agent in those subjects who had prior exposure to commercially available test fruit-juice drink 15 minutes ago. To measure the pH of saliva at 15, 30 and 45 minutes after chewing Orbit® gum as a buffering agent in those subjects who had prior exposure to commercially available test fruit-juice drink 15 minutes ago To measure the pH of saliva at 15, 30 and 45 minutes after brushing with commercially available fluoridated tooth paste and soft brush as a buffering agent in those subjects who had prior exposure to test fruit-juice drink 15 minutes ago To measure the pH of saliva at 15, 30 and 45 minutes after gargling with 1% solution of baking soda as a buffering agent in those subjects who had prior exposure to commercially available test fruit-juice drink 15 minutes ago To compare the efficacy of buffering agents on the pH of saliva at 15, 30, 45 minutes post intervention in subjects who have had the commercially available test fruit-juice drink 15 min prior to the a specific intervention, with the pH of saliva recorded in the same subjects at the same time periods when no intervention with any buffering agent was carried out after having the commercially available test fruit-juice drink. To compare the pH of saliva recorded in the subjects at 15, 30, 45 minutes time periods when they used an intervention of gargle with tap water, with that recorded when they used mouth rinse of 0.2% Chlorhexidine, with that recorded when they brushed with soft brush and fluoridated tooth paste, with that recorded when they gargled with 1% baking soda solution and with that recorded when they chewed Orbit® chewing gum (15 minutes after using the test fruit-juice drink) Materials and Methods: 30 volunteers in the age group of 18- 30 year with healthy oral cavities will be selected. Subjects with a history of any chronic medical illness, history of allergy, intake of drugs in the last 8 weeks, history of gastritis, bulimia will be excluded. Subjects with a DMFT score of more than 2 and Loe and Sillness Index of more than 0 will be excluded. Individuals who have and are currently undergoing orthodontic treatment will not be included in the study. Individuals who smoke or chew tobacco will not be included in the study sample. An informed consent for the research will be obtained from all the subjects who have volunteered for the study. The trial will be conducted as per the guidelines in the WHO-Handbook for Good Clinical Practice and the research protocol is approved by the Institutional Ethics Committee of the college. The test fruit-juice drink that will be selected is Tropicana® Mixed Fruit Juice®. The various buffering agents that will be used are: 0.2% Chlorhexidine mouth wash (Rexidine®, Indoco Remidies Ltd, Mumbai, India)- 10 ml solution swish for 60 sec and spit Tap water- 10ml swish for 60 sec and spit Brushing with fluoridated (Colgate Total®, Colgate-Palmolive Company, Mumbai, India) tooth paste- 2min using soft brush Chewing polyol containing gum (Orbit®, Wrigley Company)- chew for 5 minutes and spit Freshly prepared Sodium bicarbonate (baking soda) 1% w/v solution swish for 60 sec and spit. The observer who will be measuring the salivary pH will remain blinded about the samples and buffering agent used. The select individuals will be instructed to not use any mouth wash as part of oral hygiene regimen on test day and not consume any food or beverage for 2 hours prior to the collection of baseline sample of saliva at 10 AM on the test day. The select group of 30 individuals will be given a sample of 100 ml of Tropicana® mixed fruit-juice after recording their baseline salivary pH (0 min). They will be asked to sip, swish and swallow the drink within 2 minutes. After the exposure, salivary samples will be collected at 5 min and 15 min intervals for assessment of pH. Fifteen minutes after the exposure (consumption of test drink), the individuals will be asked to use one of the intervention methods included in this study. The salivary samples will be collected after 15, 30 and 45 minutes interval after the intervention. (i.e. 30, 45 and 60 minutes post exposure to the test drink respectively) The same protocol will be repeated using each intervention methods included in this study after a wash out period of minimum of 3 days. The protocol will be repeated on the study sample without any intervention following the exposure to the test fruit juice as a control. Measurement of salivary pH will be done using a portable PH-035 Digital pH meter with automatic temperature compensation, to the accuracy of 0.1 and the machine will be calibrated on the morning of every test day and after 60 uses during the test day using Aquasol® pH calibration solutions with pH 4, 7 and 10.
Official Title
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Comparison of Five Different Salivary Buffering Agents on the Changes in Salivary pH in a Cohort Previously Exposed to a Test Fruit Juice: A Randomized Controlled Crossover Trial.
Conditions
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pH, Saliva Altered, Oral Hygiene, Tooth Structure; Disorder
Intervention / Treatment
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* Other: Group 1: no intervention
* Other: Group 2: tap water gargle
* Drug: Group 3: 0.2% Chlorhexidine
* Other: Group 4: Fluoridated tooth paste
* Other: Group 5: Polyol containing gum
* Other: Group 6: 1% sodium bicarbonate solution
Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: subjects in the age group of 18 to 30 years. subjects with a DMFT index score of less than 2. subjects with Loe and Silness index score of 0. subjects willing to volunteer for the study. subjects who are available for the whole study period of 4 months Exclusion Criteria: subjects with history of gastritis and bulimia. subjects with chronic medical illness. subjects with history of allergy. subjects with history of drug intake for last 8 weeks. subjects who smoke or chew tobacco.
Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years
Sexes Eligible for Study
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All
Accepts Healthy Volunteers
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Accepts Healthy Volunteers
Study Plan
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How is the study designed?
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Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1: no intervention<br>The subject collects the unstimulated saliva in a sterile glass dish for the measurement of baseline pH of the saliva.The subject is then given 100 ml of test mixed fruit juice,Tropicana® Mixed Fruit Juice, (PepsiCo, Inc) to drink. The subject will sip, swish and swallow the drink within 2 minutes. Unstimulated saliva samples are collected from the subject to measure the pH of saliva after 5, 15, 30, 45 and 60 minutes of consumption of the test mixed fruit juice. | Other: Group 1: no intervention<br>* Unstimulated saliva samples are collected from the subject to measure the pH of saliva after 5, 15, 30, 45 and 60 minutes of consumption of the test mixed fruit juice without any intervention.<br>|
| Experimental: Group 2: tap water gargle<br>The subject collects the unstimulated saliva in a sterile glass dish for the measurement of baseline pH of the saliva.The subject is then given 100 ml of test mixed fruit juice,Tropicana® Mixed Fruit Juice, (PepsiCo, Inc) to drink. The subject will sip, swish and swallow the drink within 2 minutes. Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva after 5 and 15 minutes of consumption of the test mixed fruit juice. The subject will use 10 ml of tap water as mouth rinse to swish for 60 seconds and spit. Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes the gargle as an intervention. | Other: Group 2: tap water gargle<br>* The subject will use 10 ml of tap water as mouth rinse to swish for 60 seconds and spit. Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes the gargle as an intervention.<br>|
| Experimental: Group 3: 0.2% chlorhexidine<br>The subject collects the unstimulated saliva in a sterile glass dish for the measurement of baseline pH of the saliva. The subject is then given 100 ml of test mixed fruit juice, Tropicana® Mixed Fruit Juice, (PepsiCo, Inc) to drink. The subject will sip, swish and swallow the drink within 2 minutes. Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva after 5 and 15 minutes of consumption of the test mixed fruit juice. The subject will use 10 ml of 0.2% Chlorhexidine mouth rinse (Rexidine®, Indoco Remidies Ltd, Mumbai, India) to swish for 60 seconds and spit. Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes the gargle as an intervention. | Drug: Group 3: 0.2% Chlorhexidine<br>* The subject will use 10 ml of 0.2% Chlorhexidine mouth rinse (Rexidine®, Indoco Remidies Ltd, Mumbai, India) to swish for 60 seconds and spit. Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes the gargle as an intervention.<br>* Other names: Rexidine®;|
| Experimental: Group 4: fluoridated tooth paste<br>The subject collects the unstimulated saliva in a sterile glass dish for the measurement of baseline pH of the saliva. The subject is then given 100 ml of test mixed fruit juice, Tropicana® Mixed Fruit Juice, (PepsiCo, Inc) to drink. The subject will sip, swish and swallow the drink within 2 minutes. Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva after 5 and 15 minutes of consumption of the test mixed fruit juice. The subject will Brush with fluoridated toothpaste (Colgate Total®, Colgate-Palmolive Company, Mumbai, India) for 2 minutes using soft brush. Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes the brushing as an intervention. | Other: Group 4: Fluoridated tooth paste<br>* The subject will Brush with fluoridated toothpaste-(Colgate Total®, Colgate-Palmolive Company, Mumbai, India) for 2 minutes using soft brush. Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes using tooth paste as an intervention.<br>* Other names: Colgate Total®;|
| Experimental: Group 5: Polyol containing gum<br>The subject collects the unstimulated saliva in a sterile glass dish for the measurement of baseline pH of the saliva. The subject is then given 100 ml of test mixed fruit juice, Tropicana® Mixed Fruit Juice, (PepsiCo, Inc) to drink. The subject will sip, swish and swallow the drink within 2 minutes. Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva after 5 and 15 minutes of consumption of the test mixed fruit juice. The subject will chew polyol containing gum (Orbit®, Wrigley Company) for 5 minutes and spit. Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes the chewing gum as an intervention. | Other: Group 5: Polyol containing gum<br>* The subject will chew polyol containing gum (Orbit®, WrigleyCompany) for 5 minutes and spit. Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes chewing as an intervention.<br>* Other names: Orbit®;|
| Experimental: Group 6: 1% sodium bicarbonate solution<br>The subject collects the unstimulated saliva in a sterile glass dish for the measurement of baseline pH of the saliva. The subject is then given 100 ml of test mixed fruit juice, Tropicana® Mixed Fruit Juice, (PepsiCo, Inc) to drink. The subject will sip, swish and swallow the drink within 2 minutes. Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva after 5 and 15 minutes of consumption of the test mixed fruit juice. The subject will use 10 ml freshly prepared 1% sodium bicarbonate w/v solution to swish for 60 seconds and spit. Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes the gargle as an intervention. | Other: Group 6: 1% sodium bicarbonate solution<br>* The subject will use 10 ml freshly prepared 1% sodium bicarbonate w/v solution to swish for 60 seconds and spit. Unstimulated saliva samples are collected from the subject to measure and record the pH of saliva at 15, 30 and 45 minutes after the subject completes the gargle as an intervention.<br>|
What is the study measuring?
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Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pH of saliva at baseline | All subjects in all groups collects the unstimulated saliva in a sterile glass dish for the measurement of baseline pH of the saliva. The subject will give the saliva sample just before being exposed to the test mixed fruit juice by swishing 100ml of Tropicana® Mixed Fruit Juice in mouth for 2 minutes and then drinking it The outcome accessor is blinded to origin of sample (from which group). | 0 minute |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pH of Saliva 5 minutes after exposure to test mixed fruit juice | All subjects will be given 100 ml of test mixed fruit juice, Tropicana® Mixed Fruit Juice to drink. The subject will sip, swish and swallow the drink within 2 minutes. Five minutes after this, each subject will give unstimulated saliva in a sterile dish for measurement of saliva - 5minutes after exposure to test mixed fruit juice. The outcome accessor is blinded to the origin of sample (from which group). | 5 minutes |
| pH of Saliva 15 minutes after exposure to test mixed fruit juice | All subjects will give unstimulated saliva in a sterile dish for measurement of saliva -15minutes after exposure to test mixed fruit juice. The outcome accessor is blinded to the origin of sample (from which group). | 15 minutes |
| pH of Saliva 30 minutes after exposure to test mixed fruit juice | All subjects from all six (5 test and 1 comparator) groups will perform the assigned intervention as per schedule at time 15minutes post exposure to mixed fruit juice and shall give unstimulated saliva in a sterile dish for measurement of saliva -30minutes after exposure to test mixed fruit juice or in other words 15minutes after assigned intervention. The outcome accessor is blinded to the origin of sample (from which group). | 30 minutes |
| pH of Saliva 45 minutes after exposure to test mixed fruit juice | All subjects from all six (5 test and 1 comparator) groups will perform the assigned intervention as per given schedule at time 15minutes post exposure to mixed fruit juice and shall give unstimulated saliva in a sterile dish for measurement of saliva -45minutes after exposure to test mixed fruit juice or in other words 30minutes after assigned intervention. The outcome accessor is blinded to the origin of sample (from which group). | 45 minutes |
| pH of Saliva 60 minutes after exposure to test mixed fruit juice | All subjects from all six (5 test and 1 comparator) groups will perform the assigned intervention as per given schedule at time 15 minutes post exposure to mixed fruit juice and shall give unstimulated saliva in a sterile dish for measurement of saliva -60minutes after exposure to test mixed fruit juice or in other words 45minutes after assigned intervention. The outcome accessor is blinded to the origin of sample (from which group). | 60 minutes |
Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pH of saliva, Fruit juice, buffering agent, oral hygiene
|
NCT00379184
|
Sensitization in Osteoarthritic Knees
|
Musculoskeletal pains represent a major part of pain complaints in patients. Moreover, the treatment of musculoskeletal pain conditions by currently available drugs is not optimal (Curatolo and Bogduk 2001). Thus, deep pain is a diagnostic and therapeutic problem, and further insights into the peripheral and central neurophysiologic mechanisms are necessary to improve diagnosis and therapy and to implement a mechanism-based approach. Peripheral sensitization and central hyper excitability are, most likely the important factors for chronic musculoskeletal pain and in particular osteoarthritis (OA).~The focus of this project is to study the involvement of peripheral and central sensitization underlying deep tissue hyperalgesia and referred pain in male and female OA patients.~Adequate quantitative sensory testing assessment techniques for measuring hyper excitability are needed to investigate, in more detail the mechanisms involved in generating the sensitization in OA patients.
|
Methods~General procedure:~In the Outpatient Department of Clinic Farsoe, Northern Orthopaedic Division patients eligible for participating in the study will be informed and asked to participate. Those who agree and sign the informed consent will be scheduled for the investigational procedures to be performed at the SMI as soon as possible.~At the SMI all patients are interviewed and assessed with the following three procedures with at least 10 minutes between procedures. Duration of visit will be approximately 3 hours in one session.~Procedure 1:~Pressure pain sensitivity and temporal summation of pressure pain~Equipment: computer controlled pressure algometer.~Sites: knee, tibialis anterior, forearm~Stimulus intensity: pressure pain threshold~Stimuli number: 10~Frequency: ISI 1s~Pain rating: pain intensity, pressure pain threshold, unpleasantness and after-sensations will be collected.~General:~Pressure pain sensitivity and temporal summation of pressure are tested on bilateral knee, tibialis anterior muscle and forearm. Test sites are located and marked according to the landmark stated below. Pressure pain threshold of these test sites are measured first. Sequential stimulations are applied to these test sites respectively to test the pain perception for each press stimulus. Unpleasantness and after-sensations are collected after cessation of sequential stimulation to evaluate the affective aspect of pain.~Specific:~Seven test sites (2 cm proximal to the superior lateral edge of patella, 2 cm proximal to the superior edge of patella, 2 cm proximal to the superior medial edge of patella, 2 cm distal to the inferior lateral edge of patella, 2 cm distal to the inferior medial edge of patella, 5 cm lateral to the superior lateral edge of patella and 5 cm medial to the superior medial edge of patella) are marked around the knee. The site for measuring temporal summation of pain is the most sensitive site among these five sites.~The test site on the arm is 7 cm distal to the lateral humeral epicondyle on the line connecting the lateral epicondyle and the styloid process of the radius, located on the extensor carpi radialis longus muscle.~The test site on the leg is at the tibialis anterior (TA) muscle 14 cm distal to the inferior lateral edge of the patella.~Pressure pain threshold on these test sites are measured. A mechanical pressure stimulus with gradient of 0.3 kg/s will be applied until the subject reports pain and presses a stop button. The PPT measurements start from the contralateral knee of the affected knee.~Sequential stimulation consists of 10 pressure stimuli (1 sec duration) at the pressure pain threshold level. Inter-stimulus interval (ISI) is set to 1 sec. Skin contact between the individual pressure stimuli will be ensured by keeping a constant force of 0.1 kg; i.e. during the series of sequential stimulation the probe has skin contact and is first withdrawn after 10 stimulations. The subjects rate the pain intensity continuously during the sequential stimulation on an electronic visual analogue scale (VAS) on which 0 indicates no pain and 10 cm indicates maximal pain. Sequential stimulation is to be applied on each test site with at least a 1 min interval. The sequence of test sites is chosen in a randomized way to minimize order effects.~Unpleasantness and after-sensations are collected 15 sec after cessation of sequential stimulation.~Procedure 2:~Referred pain~Equipment: computer controlled pressure algometer, computer-controlled auto-infusion syringe pump.~Site: tibialis anterior~Concentration: 6% hypertonic saline.~Method: continuous infusion.~Pain rating: pain intensity, pain area drawing (primary and secondary pain area), pressure pain threshold, unpleasantness and after-sensations will be collected.~General:~Hypertonic saline is infused into the tibialis anterior (TA) muscle to elicit local and referred pain. The experiment will be conducted in one leg at a time, by giving a single bolus infusion of hypertonic saline with a time interval of approximately 20 min between each leg. Test sites are located and marked on the TA. Pressure pain thresholds on injection site and front side of ankle are measured before infusion. Hypertonic saline is infused by using a computer-controlled syringe pump. Subjects report pain intensity and draw the pain area induced by infusion. Pressure pain thresholds on injection site and front side of ankle are measured 10 min after infusion- evoked-pain disappears. Unpleasantness and after-sensations for the evoked pain are collected as well.~Specific:~Injection site is placed at the belly of the TA 14 cm distal to the inferior lateral edge of the patella on both legs. At the marked site in the TA a 24G - 40 mm needle will be inserted vertically until a piercing of the muscle fascia is felt, at a depth of approximately 20 mm from the skin surface. Then the plunger of the syringe will be withdrawn to ensure that the needle is deep in the muscle and not in a blood vessel. The needle will then be connected through a polyethylene extension tube (Vygon, France, No. 1155.70) to a 10 ml syringe fitted in a computer-controlled auto-infusion syringe pump (Terumo Terufusion syringe pump, model STC-S27, Type CG). A total volume of 0.5 ml sterile 6% hypertonic saline (58.5 mg/ml, Sygehus Apotekerne, Denmark) will be infused over 20 s into the TA muscle (infusion-rate 90 ml/h).~The pain intensity response is scored on a visual analogue scale (VAS) after the infusion. The subjects mark the painful region(s) on pain maps after the infusion. Local pain is defined as the pain area drawn at the infusion site, referred pain is defined as the pain areas drawn away from the infusion site and radiating pain is defined as the pain areas drawn radiating from the local site into the other regions of the leg.~Pressure pain thresholds on injection site and front side of ankle are measured before and 10 min after infusion when infusion evoked pain disappears.~Unpleasantness and after-sensations for the evoked pain are collected afterwards.~Procedure 3:~Cuff pressure pain and DNIC~Equipment: computer controlled cuff algometer.~Site: upper arms~Pain rating: pain intensity, cuff pressure pain threshold, pressure pain threshold, unpleasantness and after-sensations collected.~General:~Continuous cuff pressure stimulation is applied to measure the inhibitory control of the pain sensory system. Cuff stimulation is applied to bilateral upper arms and tibialis anterior (location see procedure 1). Pressure pain threshold on the test sites around knee, on the ipsilateral and contralateral arm (on the belly of biceps brachii) are measured before, during and after cuff pressure stimulation. Cuff pressure stimulation is applied by computer-controlled cuff algometer to induce continuous pain perception for 10 min. Pain intensity of ongoing pain in the stimulated limb and affected knee are rated on electrical VAS.~Specific:~The cuff is wrapped around the middle of both arms. The lower rim of the tourniquet cuff (7.5 cm wide) is at least 3 cm proximal to the cubital fossa. The setup of the cuff algometer is programmed to stop the pressure increase at a preset pain intensity of 4 cm on the VAS and to automatically adjust the pressure to maintain the obtained pain within ±0.5 cm VAS for 10 min or until the subject presses the stop button. If the pain increases over the upper pain limit, the system decreases the pressure until the pain returns into the 'target' zone and vice versa.~When the VAS rise up to 4 cm and keep constant for 1 min, we will measure PPTs on the same test sites except tested arm. Pain intensity of ongoing pain in affected knee and arm which is not stimulated is rated on another electrical VAS during cuff pressure stimulation. Five minutes following deflation, pain intensity of ongoing pain in affected knee and arms is rated. Fifteen minutes following deflation, PPTs are measured on the test sites.~The sequence of test limb is chosen at random to minimize order effects.
|
Quantitative Assessment of Central Sensitization in Osteoarthritis Patients
|
Arthritis
|
Inclusion Criteria:~Osteoarthritis in the knee~Exclusion Criteria:~No other painful conditions
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
arthritis
|
Arthritis, Joint Diseases, Musculoskeletal Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| A<br>Osteoarthritis patients scheduled for Total Knee Arthroplasty. | |
| B<br>Osteoarthritis patients not scheduled for Total Knee Arthroplasty. | |
| C<br>Healthy volunteers | |
|
Sensitization in Osteoarthritic Knees
Study Overview
=================
Brief Summary
-----------------
Musculoskeletal pains represent a major part of pain complaints in patients. Moreover, the treatment of musculoskeletal pain conditions by currently available drugs is not optimal (Curatolo and Bogduk 2001). Thus, deep pain is a diagnostic and therapeutic problem, and further insights into the peripheral and central neurophysiologic mechanisms are necessary to improve diagnosis and therapy and to implement a mechanism-based approach. Peripheral sensitization and central hyper excitability are, most likely the important factors for chronic musculoskeletal pain and in particular osteoarthritis (OA). The focus of this project is to study the involvement of peripheral and central sensitization underlying deep tissue hyperalgesia and referred pain in male and female OA patients. Adequate quantitative sensory testing assessment techniques for measuring hyper excitability are needed to investigate, in more detail the mechanisms involved in generating the sensitization in OA patients.
Detailed Description
-----------------
Methods General procedure: In the Outpatient Department of Clinic Farsoe, Northern Orthopaedic Division patients eligible for participating in the study will be informed and asked to participate. Those who agree and sign the informed consent will be scheduled for the investigational procedures to be performed at the SMI as soon as possible. At the SMI all patients are interviewed and assessed with the following three procedures with at least 10 minutes between procedures. Duration of visit will be approximately 3 hours in one session. Procedure 1: Pressure pain sensitivity and temporal summation of pressure pain Equipment: computer controlled pressure algometer. Sites: knee, tibialis anterior, forearm Stimulus intensity: pressure pain threshold Stimuli number: 10 Frequency: ISI 1s Pain rating: pain intensity, pressure pain threshold, unpleasantness and after-sensations will be collected. General: Pressure pain sensitivity and temporal summation of pressure are tested on bilateral knee, tibialis anterior muscle and forearm. Test sites are located and marked according to the landmark stated below. Pressure pain threshold of these test sites are measured first. Sequential stimulations are applied to these test sites respectively to test the pain perception for each press stimulus. Unpleasantness and after-sensations are collected after cessation of sequential stimulation to evaluate the affective aspect of pain. Specific: Seven test sites (2 cm proximal to the superior lateral edge of patella, 2 cm proximal to the superior edge of patella, 2 cm proximal to the superior medial edge of patella, 2 cm distal to the inferior lateral edge of patella, 2 cm distal to the inferior medial edge of patella, 5 cm lateral to the superior lateral edge of patella and 5 cm medial to the superior medial edge of patella) are marked around the knee. The site for measuring temporal summation of pain is the most sensitive site among these five sites. The test site on the arm is 7 cm distal to the lateral humeral epicondyle on the line connecting the lateral epicondyle and the styloid process of the radius, located on the extensor carpi radialis longus muscle. The test site on the leg is at the tibialis anterior (TA) muscle 14 cm distal to the inferior lateral edge of the patella. Pressure pain threshold on these test sites are measured. A mechanical pressure stimulus with gradient of 0.3 kg/s will be applied until the subject reports pain and presses a stop button. The PPT measurements start from the contralateral knee of the affected knee. Sequential stimulation consists of 10 pressure stimuli (1 sec duration) at the pressure pain threshold level. Inter-stimulus interval (ISI) is set to 1 sec. Skin contact between the individual pressure stimuli will be ensured by keeping a constant force of 0.1 kg; i.e. during the series of sequential stimulation the probe has skin contact and is first withdrawn after 10 stimulations. The subjects rate the pain intensity continuously during the sequential stimulation on an electronic visual analogue scale (VAS) on which 0 indicates no pain and 10 cm indicates maximal pain. Sequential stimulation is to be applied on each test site with at least a 1 min interval. The sequence of test sites is chosen in a randomized way to minimize order effects. Unpleasantness and after-sensations are collected 15 sec after cessation of sequential stimulation. Procedure 2: Referred pain Equipment: computer controlled pressure algometer, computer-controlled auto-infusion syringe pump. Site: tibialis anterior Concentration: 6% hypertonic saline. Method: continuous infusion. Pain rating: pain intensity, pain area drawing (primary and secondary pain area), pressure pain threshold, unpleasantness and after-sensations will be collected. General: Hypertonic saline is infused into the tibialis anterior (TA) muscle to elicit local and referred pain. The experiment will be conducted in one leg at a time, by giving a single bolus infusion of hypertonic saline with a time interval of approximately 20 min between each leg. Test sites are located and marked on the TA. Pressure pain thresholds on injection site and front side of ankle are measured before infusion. Hypertonic saline is infused by using a computer-controlled syringe pump. Subjects report pain intensity and draw the pain area induced by infusion. Pressure pain thresholds on injection site and front side of ankle are measured 10 min after infusion- evoked-pain disappears. Unpleasantness and after-sensations for the evoked pain are collected as well. Specific: Injection site is placed at the belly of the TA 14 cm distal to the inferior lateral edge of the patella on both legs. At the marked site in the TA a 24G - 40 mm needle will be inserted vertically until a piercing of the muscle fascia is felt, at a depth of approximately 20 mm from the skin surface. Then the plunger of the syringe will be withdrawn to ensure that the needle is deep in the muscle and not in a blood vessel. The needle will then be connected through a polyethylene extension tube (Vygon, France, No. 1155.70) to a 10 ml syringe fitted in a computer-controlled auto-infusion syringe pump (Terumo Terufusion syringe pump, model STC-S27, Type CG). A total volume of 0.5 ml sterile 6% hypertonic saline (58.5 mg/ml, Sygehus Apotekerne, Denmark) will be infused over 20 s into the TA muscle (infusion-rate 90 ml/h). The pain intensity response is scored on a visual analogue scale (VAS) after the infusion. The subjects mark the painful region(s) on pain maps after the infusion. Local pain is defined as the pain area drawn at the infusion site, referred pain is defined as the pain areas drawn away from the infusion site and radiating pain is defined as the pain areas drawn radiating from the local site into the other regions of the leg. Pressure pain thresholds on injection site and front side of ankle are measured before and 10 min after infusion when infusion evoked pain disappears. Unpleasantness and after-sensations for the evoked pain are collected afterwards. Procedure 3: Cuff pressure pain and DNIC Equipment: computer controlled cuff algometer. Site: upper arms Pain rating: pain intensity, cuff pressure pain threshold, pressure pain threshold, unpleasantness and after-sensations collected. General: Continuous cuff pressure stimulation is applied to measure the inhibitory control of the pain sensory system. Cuff stimulation is applied to bilateral upper arms and tibialis anterior (location see procedure 1). Pressure pain threshold on the test sites around knee, on the ipsilateral and contralateral arm (on the belly of biceps brachii) are measured before, during and after cuff pressure stimulation. Cuff pressure stimulation is applied by computer-controlled cuff algometer to induce continuous pain perception for 10 min. Pain intensity of ongoing pain in the stimulated limb and affected knee are rated on electrical VAS. Specific: The cuff is wrapped around the middle of both arms. The lower rim of the tourniquet cuff (7.5 cm wide) is at least 3 cm proximal to the cubital fossa. The setup of the cuff algometer is programmed to stop the pressure increase at a preset pain intensity of 4 cm on the VAS and to automatically adjust the pressure to maintain the obtained pain within ±0.5 cm VAS for 10 min or until the subject presses the stop button. If the pain increases over the upper pain limit, the system decreases the pressure until the pain returns into the 'target' zone and vice versa. When the VAS rise up to 4 cm and keep constant for 1 min, we will measure PPTs on the same test sites except tested arm. Pain intensity of ongoing pain in affected knee and arm which is not stimulated is rated on another electrical VAS during cuff pressure stimulation. Five minutes following deflation, pain intensity of ongoing pain in affected knee and arms is rated. Fifteen minutes following deflation, PPTs are measured on the test sites. The sequence of test limb is chosen at random to minimize order effects.
Official Title
-----------------
Quantitative Assessment of Central Sensitization in Osteoarthritis Patients
Conditions
-----------------
Arthritis
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Osteoarthritis in the knee Exclusion Criteria: No other painful conditions
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?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| A<br>Osteoarthritis patients scheduled for Total Knee Arthroplasty. | |
| B<br>Osteoarthritis patients not scheduled for Total Knee Arthroplasty. | |
| C<br>Healthy volunteers | |
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
-----------------
arthritis
|
|||
NCT05085418
|
A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Immune Nephritis
|
A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Immune Nephritis
|
Immune nephritis is a chronic glomerular disease originating in the kidney caused by various etiologies.Clinically, secondary chronic kidney damage caused by systemic diseases such as diabetes, systemic lupus erythematosus and gout is named after its primary disease, such as diabetic nephropathy and lupus nephritis. Autoimmune diseases only show local pathological damage, but more often systemic lesions. If not diagnosed and treated in time or poorly controlled, a risk of disability or even death as the course of the disease progresses. Studies have shown that B cells can present their own antigens to autoimmune T cells to promote the release of inflammatory factors, or they can differentiate into plasma cells to release autoantibodies, and play an important role in the occurrence and progression of autoimmune diseases. In recent years, it has become a major research focus to deplete B cells in patients or inhibit B cell function. This research focuses on CAR-T cells killing B cells.~Based on the current research progress, our center intends to conduct research on the safety and effectiveness of CD19/BCMA CAR-T cells in the treatment of refractory systemic lupus erythematosus.
|
A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Immune Nephritis
|
Immune Nephritis, Autoimmune Diseases, Lupus Nephritis
|
* Biological: Assigned Interventions CD19/BCMA CAR T-cells
|
Inclusion Criteria:~1. Immune Nephritis with positive CD19/BCMA expression , and the conventional treatment is not effective and (or) no effective treatment 2. Estimated survival time> 12 weeks; 3. Patients had a negative urine pregnancy test before the start of administration and agreed to take effective contraceptive measures during the test period until the last follow-up; 4. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.~Exclusion Criteria:~Subjects with any of the following exclusion criteria were not eligible for this trial:~History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases;~Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;~Pregnant (or lactating) women;~Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);~Active infection of hepatitis B virus or hepatitis C virus;~Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving in haled steroids;~Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl;~Other uncontrolled diseases that were not suitable for this trial;~Patients with HIV infection;~Any situations that the investigator believes may increase the risk of patients or interfere with the results of study~Platelets ≥30×10E9/L, and absolute lymphocyte count ≥1.0×10E9/L~Methylprednisolone (maximum dose 1mg/kg) or prednisone (maximum dose 1.25mg/kg) instead of immunosuppressive agents to control the disease.
| null | null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | Adverse events assessed according to NCI-CTCAE v5.0 criteria | Baseline up to 28 days after CD19/BCMA CAR T-cells infusion |
| Incidence of treatment-emergent adverse events (TEAEs) | Incidence of treatment-emergent adverse events [Safety and Tolerability] | Up to 90 days after CD19/BCMA CAR T-cells infusion |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of CAR-T cells | In peripheral blood and bone marrow | From admission to the end of the follow-up, up to 2 years |
| Objective Response Rate, ORR | Proportion of subjects with complete or partial remission | In 3 months of CD19/BCMA CAR-T cell infusion |
| Disease control rate, DCR | The percentage of patients with remission and stable disease after treatment in the total evaluable cases. | From Day 28 CD19/BCMA CAR-T infusion up to 2 years |
| Duration of remission, DOR | The time from the first assessment of remission or partial remission of the disease to the first assessment of disease progression or death from any cause | 24 months post CD19/BCMA CAR-T cells infusion |
| Progression-free survival, PFS | The time from cell reinfusion to the first assessment of disease progression or death from any cause | 24 months post CD19/BCMA CAR-Tcells infusion |
| Overall survival, OS | The time from the cell reinfusion to death due to any cause | From CD19/BCMA CAR-T infusion to death，up to 2 years |
|
Immune Nephritis, CD19 CAR T-cell therapy, BCMA CAR T-cell therapy
|
Kidney Diseases, Urologic Diseases, Nephritis, Lupus Nephritis, Autoimmune Diseases, Immune System Diseases, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Male Urogenital Diseases, Glomerulonephritis, Lupus Erythematosus, Systemic, Connective Tissue Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment of Immune Nephritis<br>Administration of CD19/BCMA CAR T-cells A dose levels of 1-4*10E6/kg are administrated for each subject. | Biological: Assigned Interventions CD19/BCMA CAR T-cells<br>* Drug: CD19/BCMA CAR T-cells Each subject receive CD19/BCMA CAR T-cells by intravenous infusion Other Name: CD19/BCMA CAR T-cells injection<br>|
|
A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Immune Nephritis
Study Overview
=================
Brief Summary
-----------------
A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Immune Nephritis
Detailed Description
-----------------
Immune nephritis is a chronic glomerular disease originating in the kidney caused by various etiologies.Clinically, secondary chronic kidney damage caused by systemic diseases such as diabetes, systemic lupus erythematosus and gout is named after its primary disease, such as diabetic nephropathy and lupus nephritis. Autoimmune diseases only show local pathological damage, but more often systemic lesions. If not diagnosed and treated in time or poorly controlled, a risk of disability or even death as the course of the disease progresses. Studies have shown that B cells can present their own antigens to autoimmune T cells to promote the release of inflammatory factors, or they can differentiate into plasma cells to release autoantibodies, and play an important role in the occurrence and progression of autoimmune diseases. In recent years, it has become a major research focus to deplete B cells in patients or inhibit B cell function. This research focuses on CAR-T cells killing B cells. Based on the current research progress, our center intends to conduct research on the safety and effectiveness of CD19/BCMA CAR-T cells in the treatment of refractory systemic lupus erythematosus.
Official Title
-----------------
A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Immune Nephritis
Conditions
-----------------
Immune Nephritis, Autoimmune Diseases, Lupus Nephritis
Intervention / Treatment
-----------------
* Biological: Assigned Interventions CD19/BCMA CAR T-cells
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Immune Nephritis with positive CD19/BCMA expression , and the conventional treatment is not effective and (or) no effective treatment 2. Estimated survival time> 12 weeks; 3. Patients had a negative urine pregnancy test before the start of administration and agreed to take effective contraceptive measures during the test period until the last follow-up; 4. Patients or their legal guardians volunteer to participate in the study and sign the informed consent. Exclusion Criteria: Subjects with any of the following exclusion criteria were not eligible for this trial: History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases; Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past; Pregnant (or lactating) women; Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis); Active infection of hepatitis B virus or hepatitis C virus; Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving in haled steroids; Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl; Other uncontrolled diseases that were not suitable for this trial; Patients with HIV infection; Any situations that the investigator believes may increase the risk of patients or interfere with the results of study Platelets ≥30×10E9/L, and absolute lymphocyte count ≥1.0×10E9/L Methylprednisolone (maximum dose 1mg/kg) or prednisone (maximum dose 1.25mg/kg) instead of immunosuppressive agents to control the disease.
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: Treatment of Immune Nephritis<br>Administration of CD19/BCMA CAR T-cells A dose levels of 1-4*10E6/kg are administrated for each subject. | Biological: Assigned Interventions CD19/BCMA CAR T-cells<br>* Drug: CD19/BCMA CAR T-cells Each subject receive CD19/BCMA CAR T-cells by intravenous infusion Other Name: CD19/BCMA CAR T-cells injection<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | Adverse events assessed according to NCI-CTCAE v5.0 criteria | Baseline up to 28 days after CD19/BCMA CAR T-cells infusion |
| Incidence of treatment-emergent adverse events (TEAEs) | Incidence of treatment-emergent adverse events [Safety and Tolerability] | Up to 90 days after CD19/BCMA CAR T-cells infusion |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of CAR-T cells | In peripheral blood and bone marrow | From admission to the end of the follow-up, up to 2 years |
| Objective Response Rate, ORR | Proportion of subjects with complete or partial remission | In 3 months of CD19/BCMA CAR-T cell infusion |
| Disease control rate, DCR | The percentage of patients with remission and stable disease after treatment in the total evaluable cases. | From Day 28 CD19/BCMA CAR-T infusion up to 2 years |
| Duration of remission, DOR | The time from the first assessment of remission or partial remission of the disease to the first assessment of disease progression or death from any cause | 24 months post CD19/BCMA CAR-T cells infusion |
| Progression-free survival, PFS | The time from cell reinfusion to the first assessment of disease progression or death from any cause | 24 months post CD19/BCMA CAR-Tcells infusion |
| Overall survival, OS | The time from the cell reinfusion to death due to any cause | From CD19/BCMA CAR-T infusion to death，up to 2 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immune Nephritis, CD19 CAR T-cell therapy, BCMA CAR T-cell therapy
|
NCT04192539
|
The Prospect of Using Serum Taurine Level as a Potential Biomarker for Early Detection of Colorectal Carcinoma and Its Correlation With Other Prognostic Markers
|
Serum taurine results in this study showed that, besides CRC biomarkers; it is most attractive, more precious and more accurate early biomarker for early detecting of any malignant change which may led to CRC by other mean it is the most sensitive and more specific tumor marker for CRC. As a result, we can recommend measuring its level regularly with other prognostic tumor biomarkers and screening examination for all people with abdominal and gastrointestinal problems and for precancerous patients as a pre-early biomarker for colorectal carcinoma. So, it needs further studies to confirm that observations on large scale of population as it obvious the small sample size in early stage and lack data due to limited financial resources and it needs more efforts to collect first and precancerous stages patients.
|
Two-hundred and fifty Egyptian patients (males and females) who attended National Cancer Institute, Cairo university; most of them were referred from private clinics and non-specialized hospitals, complain with abdominal troubles and gastrointestinal problems and bleeding per rectum, after full investigation, clinical examination, biochemical analysis, screening examination according to their cases (Ultra sound, CT or endoscopy either rectal or colonoscopy) and histopathological examination, we choose 'after their approval' one-hundred patients and six which diagnosed as CRC patients aged (19-69 years old) and excluded the others from participated in these studies because they diagnosed as non-colonic diseases like; Irritable colon, Gastroenteritis, Pancreatitis, Liver flexure or Chronic cholecystitis. According to Histopathological architecture, we divided patients to:~Inflammatory group number=7.~Benign tumor group number=8 which was assessed preoperatively and postoperatively.~Malignant tumor group number=91 Lastly, ten health volunteers were enrolled as a frank control. For all included subjects, the measured biochemical analysis were CBC, ALT, AST, Albumin, Total Bilirubin, Creatinine, Blood urea, Sodium, Potassium, CEA, CA19.9 and Taurine.
|
The Prospect of Using Serum Taurine Level as a Potential Biomarker for Early Detection of Colorectal Carcinoma and Its Correlation With Other Prognostic Markers
|
Taurine in Cancer Colon
|
* Diagnostic Test: Taurine
|
Inclusion Criteria:~Patients complain of abdominal troubles and gastrointestinal problems and bleeding per rectum~Exclusion Criteria:~Patients refusal,non-colonic diseases like; Irritable colon, Gastroenteritis, Pancreatitis, Chronic cholecystitis
|
19 Years
|
69 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum taurine levels | | 8 months |
|
Colorectal Neoplasms, Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Digestive System Diseases, Gastrointestinal Diseases, Colonic Diseases, Intestinal Diseases, Rectal Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br> | Diagnostic Test: Taurine<br>* Serum taurine was determined by High Performance Liquid Chromatography (HPLC) according to the pre-column extraction and derivatization methodology of McMahon et al. In the present work, we use Shimadzu HPLC model LC-10AT<br>|
| Active Comparator: Inflammation<br> | Diagnostic Test: Taurine<br>* Serum taurine was determined by High Performance Liquid Chromatography (HPLC) according to the pre-column extraction and derivatization methodology of McMahon et al. In the present work, we use Shimadzu HPLC model LC-10AT<br>|
| Active Comparator: Benign group<br> | Diagnostic Test: Taurine<br>* Serum taurine was determined by High Performance Liquid Chromatography (HPLC) according to the pre-column extraction and derivatization methodology of McMahon et al. In the present work, we use Shimadzu HPLC model LC-10AT<br>|
| Active Comparator: Malignant group<br> | Diagnostic Test: Taurine<br>* Serum taurine was determined by High Performance Liquid Chromatography (HPLC) according to the pre-column extraction and derivatization methodology of McMahon et al. In the present work, we use Shimadzu HPLC model LC-10AT<br>|
|
The Prospect of Using Serum Taurine Level as a Potential Biomarker for Early Detection of Colorectal Carcinoma and Its Correlation With Other Prognostic Markers
Study Overview
=================
Brief Summary
-----------------
Serum taurine results in this study showed that, besides CRC biomarkers; it is most attractive, more precious and more accurate early biomarker for early detecting of any malignant change which may led to CRC by other mean it is the most sensitive and more specific tumor marker for CRC. As a result, we can recommend measuring its level regularly with other prognostic tumor biomarkers and screening examination for all people with abdominal and gastrointestinal problems and for precancerous patients as a pre-early biomarker for colorectal carcinoma. So, it needs further studies to confirm that observations on large scale of population as it obvious the small sample size in early stage and lack data due to limited financial resources and it needs more efforts to collect first and precancerous stages patients.
Detailed Description
-----------------
Two-hundred and fifty Egyptian patients (males and females) who attended National Cancer Institute, Cairo university; most of them were referred from private clinics and non-specialized hospitals, complain with abdominal troubles and gastrointestinal problems and bleeding per rectum, after full investigation, clinical examination, biochemical analysis, screening examination according to their cases (Ultra sound, CT or endoscopy either rectal or colonoscopy) and histopathological examination, we choose 'after their approval' one-hundred patients and six which diagnosed as CRC patients aged (19-69 years old) and excluded the others from participated in these studies because they diagnosed as non-colonic diseases like; Irritable colon, Gastroenteritis, Pancreatitis, Liver flexure or Chronic cholecystitis. According to Histopathological architecture, we divided patients to: Inflammatory group number=7. Benign tumor group number=8 which was assessed preoperatively and postoperatively. Malignant tumor group number=91 Lastly, ten health volunteers were enrolled as a frank control. For all included subjects, the measured biochemical analysis were CBC, ALT, AST, Albumin, Total Bilirubin, Creatinine, Blood urea, Sodium, Potassium, CEA, CA19.9 and Taurine.
Official Title
-----------------
The Prospect of Using Serum Taurine Level as a Potential Biomarker for Early Detection of Colorectal Carcinoma and Its Correlation With Other Prognostic Markers
Conditions
-----------------
Taurine in Cancer Colon
Intervention / Treatment
-----------------
* Diagnostic Test: Taurine
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients complain of abdominal troubles and gastrointestinal problems and bleeding per rectum Exclusion Criteria: Patients refusal,non-colonic diseases like; Irritable colon, Gastroenteritis, Pancreatitis, Chronic cholecystitis
Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 69 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br> | Diagnostic Test: Taurine<br>* Serum taurine was determined by High Performance Liquid Chromatography (HPLC) according to the pre-column extraction and derivatization methodology of McMahon et al. In the present work, we use Shimadzu HPLC model LC-10AT<br>|
| Active Comparator: Inflammation<br> | Diagnostic Test: Taurine<br>* Serum taurine was determined by High Performance Liquid Chromatography (HPLC) according to the pre-column extraction and derivatization methodology of McMahon et al. In the present work, we use Shimadzu HPLC model LC-10AT<br>|
| Active Comparator: Benign group<br> | Diagnostic Test: Taurine<br>* Serum taurine was determined by High Performance Liquid Chromatography (HPLC) according to the pre-column extraction and derivatization methodology of McMahon et al. In the present work, we use Shimadzu HPLC model LC-10AT<br>|
| Active Comparator: Malignant group<br> | Diagnostic Test: Taurine<br>* Serum taurine was determined by High Performance Liquid Chromatography (HPLC) according to the pre-column extraction and derivatization methodology of McMahon et al. In the present work, we use Shimadzu HPLC model LC-10AT<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum taurine levels | | 8 months |
|
||
NCT02996214
|
Paclitaxel Liposome for Squamous Non-Small-cell Lung Cancer Study(LIPUSU)
|
The purpose of this study is to investigate the efficacy and the safety of paclitaxel liposome and cisplatin compared with gemcitabine and cisplatin as first-line therapy in advanced squamous non-small-cell lung cancer .
|
The purpose of this study is to investigate the efficacy and safety of paclitaxel liposome and cisplatin compared with gemcitabine and cisplatin as first-line therapy in advanced squamous non-small-cell lung cancer .
|
A Multicenter, Randomized, Open-label, Parallel-group Study of Paclitaxel Liposome and Cisplatin Compared With Gemcitabine and Cisplatin as First-line Therapy in Advanced Squamous Non-Small-Cell Lung Cancer
|
Squamous Non-small-cell Lung Cancer
|
* Drug: Paclitaxel Liposome
* Drug: Gemcitabine
* Drug: Cisplatin
|
Inclusion Criteria:~Aged 18-75 years old, both gender;~ECOG: 0-1;~Squamous non-small-cell lung cancer (stage IIIB or IV) confirmed by histologically or cytologically ;~No prior chemotherapy, biological therapy or immunotherapy; or subjects have recurrence and metastasis more than 6 months after the end of chemotherapy, but not gemcitabine or paclitaxel;~At least one radiographically measurable or assessable lesion on chest CG according to RECIST1.1 (response evaluation criteria of solid tumors); regional lymph node metastases may also be measured or assessed by imaging (mediastinal lymph nodes);~Life expectancy of at least 12 weeks;~Before treatment, blood tests or biochemical measurements must meet the following criteria:~White blood cell count (WBC)≥ 4.0*10^9/L;~Neutrophil count (ANC)≥ 2.0*10^9/L;~Platelet count (PLT)≥ 100*10^9/L;~Hemoglobin (Hb)≥ 100g/L;~Hepatic function: serum bilirubin ≤ 1.5 times the upper normal limit,aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper normal limit;~Renal function: creatinine ≤ 1.5 times the upper normal limit;~Signed informed consent.~Exclusion Criteria:~Hypersensitivity reaction to the interventional drugs;~Pregnant or breastfeeding;~Women or men of childbearing age who disagree with the use of effective contraceptive measures during the study period;~Brain metastase ;~Uncontrolled pleural effusion in patients with squamous non-small-cell lung cancer
|
18 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression free survival will be calculated from study entry to documented disease progression using RECISTv1.1 or death from any cause, whichever occurs first. | From study entry to measured progressive disease, up to 2 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Objective response rate is the percentage of participants who achieve best overall tumor response of complete response or partial response . | From study entry to measured progressive disease, up to 2 years |
| Overall Survival | Overall survival is defined from study entry to the date of death from any cause. | From study entry to death from any cause, up to 2 years |
| Adverse events | Adverse events is evaluated according to Common Terminology Criteria for Adverse Events Version 4.0 | From baseline until 21 days after the last dose |
| Quality of Life questionnaire | The quality of life is assessed using the European Organization for the Research and Treatment of Cancer Questionnaire Core-30 (EORTC QLQ-C30) and Quality of Life Questionnaire Lung Cancer 13(QLQ-LC13). | From study entry to measured progressive disease, up to 2 years |
| Correlation between gene sequence or expression level and therapeutic effect | Correlation between gene sequence or expression level and therapeutic effect is assessed using the blood or tumor tissue of subjects by genetic testing | From study entry untill radiological disease progression, up to 2 years |
|
Paclitaxel, Gemcitabine, Antineoplastic Agents, Phytogenic, Antineoplastic Agents, Tubulin Modulators, Antimitotic Agents, Mitosis Modulators, Molecular Mechanisms of Pharmacological Action, Antimetabolites, Antineoplastic, Antimetabolites
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LP group<br>Liposome paclitaxel(Lipusu®) plus cisplatin. Paclitaxel liposome Sterile injection powder 175 mg/m^2, given on day 1 of a 21-day cycle, for 4-6 cycles. Cisplatin 75 mg/m^2, given on day 1 of a 21-day cycle, for 4-6 cycles. | Drug: Paclitaxel Liposome<br>* Paclitaxel liposome injection 175 mg/m^2, given on day 1 of a 21-day cycle, for 4-6 cycles.<br>* Other names: Lipusu®;Drug: Cisplatin<br>* Cisplatin 75 mg/m^2, given on day 1 of a 21-day cycle, for 4-6 cycles.<br>* Other names: Nuoxin®;|
| Active Comparator: GP group<br>Gemcitabine (Gemzar®) plus cisplatin. Gemcitabine hydrochloride for injection 1000 mg/m^2, given on days 1 and 8 of a 21-day cycle, for 4-6 cycles. Cisplatin 75 mg/m^2, given on day 1 of a 21-day cycle, for 4-6 cycles. | Drug: Gemcitabine<br>* Gemcitabine 1000 mg/m^2, given on days 1 and 8 of a 21-day cycle, for 4-6 cycles.<br>* Other names: Gemzar®;Drug: Cisplatin<br>* Cisplatin 75 mg/m^2, given on day 1 of a 21-day cycle, for 4-6 cycles.<br>* Other names: Nuoxin®;|
|
Paclitaxel Liposome for Squamous Non-Small-cell Lung Cancer Study(LIPUSU)
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the efficacy and the safety of paclitaxel liposome and cisplatin compared with gemcitabine and cisplatin as first-line therapy in advanced squamous non-small-cell lung cancer .
Detailed Description
-----------------
The purpose of this study is to investigate the efficacy and safety of paclitaxel liposome and cisplatin compared with gemcitabine and cisplatin as first-line therapy in advanced squamous non-small-cell lung cancer .
Official Title
-----------------
A Multicenter, Randomized, Open-label, Parallel-group Study of Paclitaxel Liposome and Cisplatin Compared With Gemcitabine and Cisplatin as First-line Therapy in Advanced Squamous Non-Small-Cell Lung Cancer
Conditions
-----------------
Squamous Non-small-cell Lung Cancer
Intervention / Treatment
-----------------
* Drug: Paclitaxel Liposome
* Drug: Gemcitabine
* Drug: Cisplatin
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 18-75 years old, both gender; ECOG: 0-1; Squamous non-small-cell lung cancer (stage IIIB or IV) confirmed by histologically or cytologically ; No prior chemotherapy, biological therapy or immunotherapy; or subjects have recurrence and metastasis more than 6 months after the end of chemotherapy, but not gemcitabine or paclitaxel; At least one radiographically measurable or assessable lesion on chest CG according to RECIST1.1 (response evaluation criteria of solid tumors); regional lymph node metastases may also be measured or assessed by imaging (mediastinal lymph nodes); Life expectancy of at least 12 weeks; Before treatment, blood tests or biochemical measurements must meet the following criteria: White blood cell count (WBC)≥ 4.0*10^9/L; Neutrophil count (ANC)≥ 2.0*10^9/L; Platelet count (PLT)≥ 100*10^9/L; Hemoglobin (Hb)≥ 100g/L; Hepatic function: serum bilirubin ≤ 1.5 times the upper normal limit,aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper normal limit; Renal function: creatinine ≤ 1.5 times the upper normal limit; Signed informed consent. Exclusion Criteria: Hypersensitivity reaction to the interventional drugs; Pregnant or breastfeeding; Women or men of childbearing age who disagree with the use of effective contraceptive measures during the study period; Brain metastase ; Uncontrolled pleural effusion in patients with squamous non-small-cell lung cancer
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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LP group<br>Liposome paclitaxel(Lipusu®) plus cisplatin. Paclitaxel liposome Sterile injection powder 175 mg/m^2, given on day 1 of a 21-day cycle, for 4-6 cycles. Cisplatin 75 mg/m^2, given on day 1 of a 21-day cycle, for 4-6 cycles. | Drug: Paclitaxel Liposome<br>* Paclitaxel liposome injection 175 mg/m^2, given on day 1 of a 21-day cycle, for 4-6 cycles.<br>* Other names: Lipusu®;Drug: Cisplatin<br>* Cisplatin 75 mg/m^2, given on day 1 of a 21-day cycle, for 4-6 cycles.<br>* Other names: Nuoxin®;|
| Active Comparator: GP group<br>Gemcitabine (Gemzar®) plus cisplatin. Gemcitabine hydrochloride for injection 1000 mg/m^2, given on days 1 and 8 of a 21-day cycle, for 4-6 cycles. Cisplatin 75 mg/m^2, given on day 1 of a 21-day cycle, for 4-6 cycles. | Drug: Gemcitabine<br>* Gemcitabine 1000 mg/m^2, given on days 1 and 8 of a 21-day cycle, for 4-6 cycles.<br>* Other names: Gemzar®;Drug: Cisplatin<br>* Cisplatin 75 mg/m^2, given on day 1 of a 21-day cycle, for 4-6 cycles.<br>* Other names: Nuoxin®;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression free survival will be calculated from study entry to documented disease progression using RECISTv1.1 or death from any cause, whichever occurs first. | From study entry to measured progressive disease, up to 2 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Objective response rate is the percentage of participants who achieve best overall tumor response of complete response or partial response . | From study entry to measured progressive disease, up to 2 years |
| Overall Survival | Overall survival is defined from study entry to the date of death from any cause. | From study entry to death from any cause, up to 2 years |
| Adverse events | Adverse events is evaluated according to Common Terminology Criteria for Adverse Events Version 4.0 | From baseline until 21 days after the last dose |
| Quality of Life questionnaire | The quality of life is assessed using the European Organization for the Research and Treatment of Cancer Questionnaire Core-30 (EORTC QLQ-C30) and Quality of Life Questionnaire Lung Cancer 13(QLQ-LC13). | From study entry to measured progressive disease, up to 2 years |
| Correlation between gene sequence or expression level and therapeutic effect | Correlation between gene sequence or expression level and therapeutic effect is assessed using the blood or tumor tissue of subjects by genetic testing | From study entry untill radiological disease progression, up to 2 years |
|
|
NCT00315302
|
Trial Comparing Atropine to Atropine Plus a Plano Lens for the Sound Eye for Amblyopia in Children 3 to <7 Years Old
|
The purpose of the study is:~To compare the effectiveness and safety of weekend atropine augmented with a plano lens for the sound eye versus weekend atropine alone for moderate amblyopia (20/40 to 20/100) in children 3 to less than 7 years old.~To provide data on the response of severe amblyopia (20/125 to 20/400) to atropine treatment with and without a plano lens.
|
Atropine is an effective treatment of moderate amblyopia. Reduction of the plus sphere for the sound eye is an accepted method of enhancing and possibly accelerating the treatment effect. Demonstrating additional value of the plano lens in terms of speed of improvement will shorten the treatment period, possibly improving child and parental compliance, leading to improved overall outcomes for patients with amblyopia. If the plano lens leads to greater improvement, then there will be less permanent visual impairment in patients with a history of amblyopia. It also is important to determine if the use of a plano lens in conjunction with atropine has a deleterious effect on the sound eye, and if yes, how often this occurs.~Little is known about the pharmacologic treatment of severe amblyopia. This study will provide important prospectively determined outcome data at little additional expense.~In a study conducted by the Pediatric Eye Disease Investigator Group, A Randomized Trial Comparing Daily Atropine Versus Weekend Atropine for Moderate Amblyopia, the use of weekend atropine for moderate amblyopia was as effective as daily treatment. Intermittent atropine use (such as using it only on the weekends) has the theoretical potential benefit of the sound eye having some time each week during which cycloplegia is only partial. It is possible that allowing some loss of the cycloplegic effect over the course of each week may be safer for the sound eye.~The study has been designed as a simple trial that, other than the type of amblyopia therapy being determined through the randomization process, approximates standard clinical practice. The two treatment regimes for the 18 week primary treatment period are: 1) Atropine 1% once each weekend day in the sound eye and 2) Atropine 1% once each weekend day in the sound eye plus a plano lens for the sound eye.
|
A Randomized Trial Comparing Atropine to Atropine Plus a Plano Lens for the Sound Eye As Prescribed Treatments for Amblyopia in Children 3 to <7 Years Old
|
Amblyopia
|
* Drug: Atropine
* Device: Plano Lens
|
Inclusion Criteria:~Patients must be 3 to less than 7 years old with amblyopia associated with strabismus, anisometropia, or both.~Visual acuity in the amblyopic eye must be between 20/40 and 20/400 inclusive, visual acuity in the sound eye 20/40 or better and inter-eye acuity difference > 3 logMAR lines.~Spectacles, if needed, must be worn for at least 16 weeks or until visual acuity documented to be stable.~Exclusion Criteria:~Atropine treatment within 6 months of enrollment and other amblyopia treatment of any type (other than normal spectacle lenses) used within one month of enrollment~No myopia in amblyopic eye
|
3 Years
|
6 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Acuity Mean Score in the Amblyopic Eye | Visual acuity is measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol at 18 weeks resulting in an Snellen equivalent acuity score that can range from 20/16 to 20/800. This visual acuity score is converted to logMAR (log of min angle of resolution) for statistical analysis.~20/16=-0.1 logMAR; best 20/20=0.0 logMAR; 20/25=0.1; 20/32=0.2; 20/40=0.3; 20/50=0.4; 20/63=0.5; 20/80=0.6; 20/100=0.7; 20/125=0.8; 20/160=0.9; 20/200=1.0; 20/250=1.1; 20/320=1.2; 20/400=1.3; 20/500=1.4; 20/640=1.5; 20/800=1.6; worst | 18 weeks |
| Visual Acuity Distribution in the Amblyopic Eye | Visual acuity is measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol at 18 weeks resulting in a Snellen acuity score that can range from 20/16 to 20/800. This visual acuity score is converted to logMAR (log of min angle of resolution) for statistical analysis.~20/16=-0.1 logMAR; best 20/20=0.0 logMAR; 20/25=0.1; 20/32=0.2; 20/40=0.3; 20/50=0.4; 20/63=0.5; 20/80=0.6; 20/100=0.7; 20/125=0.8; 20/160=0.9; 20/200=1.0; 20/250=1.1; 20/320=1.2; 20/400=1.3; 20/500=1.4; 20/640=1.5; 20/800=1.6; worst | 18 weeks |
| Mean Change in Visual Acuity in the Amblyopic Eye | Acuity is measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol at baseline and at 18wks resulting in a Snellen acuity score that can range from 20/16 to 20/800. The score is converted to logMAR (log of min angle of resolution) for statistical analysis, and a difference between the scores is calculated.~A positive difference indicates acuity was better at 18wks than at baseline; a negative difference indicates acuity was worse at 18wks than at baseline. | baseline to 18 weeks |
| Distribution of Change in Visual Acuity in the Amblyopic Eye | Acuity is measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol at baseline and at 18wks resulting in a Snellen acuity score that can range from 20/16 to 20/800. The score is converted to logMAR (log of min angle of resolution) for statistical analysis, and a difference between the scores is calculated.~A positive difference indicates acuity was better at 18wks than at baseline; a negative difference indicates acuity was worse at 18wks than at baseline. | baseline to 18 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Randot Preschool Stereoacuity at 18 Weeks- Participants With All Causes of Amblyopia | The Randot Preschool Stereotest measures stereopsis from 800 to 40 seconds of arc on patients as young as 2 years of age. This Stereotest is designed as a matching game in which the patient matches pictures in a test booklet wearing special glasses. A subject can fail the pretest (not see any pictures) or can score >800 (the worst), 800, 400, 200, 100, 60, or 40 (the best) seconds of arc. If two shapes are identified correctly the patient progresses to the next lower stereoacuity level. A failed test occurs when the patient cannot identify any shapes. | 18 weeks |
| Randot Preschool Stereoacuity at 18 Weeks- Anisometropic Participants Only | The Randot Preschool Stereotest measures stereopsis from 800 to 40 seconds of arc on patients as young as 2 years of age. This Stereotest is designed as a matching game in which the patient matches pictures in a test booklet wearing special glasses. A subject can fail the pretest (not see any pictures) or can score >800 (the worst), 800, 400, 200, 100, 60, or 40 (the best) seconds of arc. If two shapes are identified correctly the patient progresses to the next lower stereoacuity level. A failed test occurs when the patient cannot identify any shapes. | 18 weeks |
| Mean Change in Visual Acuity in the Sound Eye | Acuity is measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol at baseline and at 18wks resulting in a Snellen acuity score that can range from 20/16 to 20/800. The score is converted to logMAR (log of min angle of resolution) for statistical analysis, and a difference between the scores is calculated.~A positive difference indicates acuity was better at 18wks than at baseline; a negative difference indicates acuity was worse at 18wks than at baseline. | baseline to 18 weeks |
| Distribution of Change in Visual Acuity in the Sound Eye | Acuity is measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol at baseline and at 18wks resulting in a Snellen acuity score that can range from 20/16 to 20/800. The score is converted to logMAR (log of min angle of resolution) for statistical analysis, and a difference between the scores is calculated.~A positive difference indicates acuity was better at 18wks than at baseline; a negative difference indicates acuity was worse at 18wks than at baseline. | baseline to 18 weeks |
| Visual Acuity Distribution in the Sound Eye | Acuity is measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol at baseline and at 18 wks resulting in a Snellen acuity score that can range from 20/16 to 20/800. This acuity score is converted to logMAR (log of min angle of resolution) for statistical analysis.~20/16=-0.1 logMAR; best 20/20=0.0 logMAR; 20/25=0.1; 20/32=0.2; 20/40=0.3; 20/50=0.4; 20/63=0.5; 20/80=0.6; 20/100=0.7; 20/125=0.8; 20/160=0.9; 20/200=1.0; 20/250=1.1; 20/320=1.2; 20/400=1.3; 20/500=1.4; 20/640=1.5; 20/800=1.6; worst | 18 weeks |
|
Amblyopia, Atropine, Plano lens
|
Atropine, Adjuvants, Anesthesia, Anti-Arrhythmia Agents, Bronchodilator Agents, Autonomic Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anti-Asthmatic Agents, Respiratory System Agents, Mydriatics, Parasympatholytics, Muscarinic Antagonists, Cholinergic Antagonists, Cholinergic Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Atropine<br>Atropine 1% once each weekend day in the sound eye | Drug: Atropine<br>* Atropine 1% once each weekend day<br>|
| Active Comparator: Atropine plus plano<br>Atropine 1% once each weekend day in the sound eye plus a plano lens for the sound eye | Drug: Atropine<br>* Atropine 1% once each weekend day<br>Device: Plano Lens<br>* Plano lens for the sound eye<br>|
|
Trial Comparing Atropine to Atropine Plus a Plano Lens for the Sound Eye for Amblyopia in Children 3 to <7 Years Old
Study Overview
=================
Brief Summary
-----------------
The purpose of the study is: To compare the effectiveness and safety of weekend atropine augmented with a plano lens for the sound eye versus weekend atropine alone for moderate amblyopia (20/40 to 20/100) in children 3 to less than 7 years old. To provide data on the response of severe amblyopia (20/125 to 20/400) to atropine treatment with and without a plano lens.
Detailed Description
-----------------
Atropine is an effective treatment of moderate amblyopia. Reduction of the plus sphere for the sound eye is an accepted method of enhancing and possibly accelerating the treatment effect. Demonstrating additional value of the plano lens in terms of speed of improvement will shorten the treatment period, possibly improving child and parental compliance, leading to improved overall outcomes for patients with amblyopia. If the plano lens leads to greater improvement, then there will be less permanent visual impairment in patients with a history of amblyopia. It also is important to determine if the use of a plano lens in conjunction with atropine has a deleterious effect on the sound eye, and if yes, how often this occurs. Little is known about the pharmacologic treatment of severe amblyopia. This study will provide important prospectively determined outcome data at little additional expense. In a study conducted by the Pediatric Eye Disease Investigator Group, A Randomized Trial Comparing Daily Atropine Versus Weekend Atropine for Moderate Amblyopia, the use of weekend atropine for moderate amblyopia was as effective as daily treatment. Intermittent atropine use (such as using it only on the weekends) has the theoretical potential benefit of the sound eye having some time each week during which cycloplegia is only partial. It is possible that allowing some loss of the cycloplegic effect over the course of each week may be safer for the sound eye. The study has been designed as a simple trial that, other than the type of amblyopia therapy being determined through the randomization process, approximates standard clinical practice. The two treatment regimes for the 18 week primary treatment period are: 1) Atropine 1% once each weekend day in the sound eye and 2) Atropine 1% once each weekend day in the sound eye plus a plano lens for the sound eye.
Official Title
-----------------
A Randomized Trial Comparing Atropine to Atropine Plus a Plano Lens for the Sound Eye As Prescribed Treatments for Amblyopia in Children 3 to <7 Years Old
Conditions
-----------------
Amblyopia
Intervention / Treatment
-----------------
* Drug: Atropine
* Device: Plano Lens
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must be 3 to less than 7 years old with amblyopia associated with strabismus, anisometropia, or both. Visual acuity in the amblyopic eye must be between 20/40 and 20/400 inclusive, visual acuity in the sound eye 20/40 or better and inter-eye acuity difference > 3 logMAR lines. Spectacles, if needed, must be worn for at least 16 weeks or until visual acuity documented to be stable. Exclusion Criteria: Atropine treatment within 6 months of enrollment and other amblyopia treatment of any type (other than normal spectacle lenses) used within one month of enrollment No myopia in amblyopic eye
Ages Eligible for Study
-----------------
Minimum Age: 3 Years
Maximum Age: 6 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: Atropine<br>Atropine 1% once each weekend day in the sound eye | Drug: Atropine<br>* Atropine 1% once each weekend day<br>|
| Active Comparator: Atropine plus plano<br>Atropine 1% once each weekend day in the sound eye plus a plano lens for the sound eye | Drug: Atropine<br>* Atropine 1% once each weekend day<br>Device: Plano Lens<br>* Plano lens for the sound eye<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Acuity Mean Score in the Amblyopic Eye | Visual acuity is measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol at 18 weeks resulting in an Snellen equivalent acuity score that can range from 20/16 to 20/800. This visual acuity score is converted to logMAR (log of min angle of resolution) for statistical analysis. 20/16=-0.1 logMAR; best 20/20=0.0 logMAR; 20/25=0.1; 20/32=0.2; 20/40=0.3; 20/50=0.4; 20/63=0.5; 20/80=0.6; 20/100=0.7; 20/125=0.8; 20/160=0.9; 20/200=1.0; 20/250=1.1; 20/320=1.2; 20/400=1.3; 20/500=1.4; 20/640=1.5; 20/800=1.6; worst | 18 weeks |
| Visual Acuity Distribution in the Amblyopic Eye | Visual acuity is measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol at 18 weeks resulting in a Snellen acuity score that can range from 20/16 to 20/800. This visual acuity score is converted to logMAR (log of min angle of resolution) for statistical analysis. 20/16=-0.1 logMAR; best 20/20=0.0 logMAR; 20/25=0.1; 20/32=0.2; 20/40=0.3; 20/50=0.4; 20/63=0.5; 20/80=0.6; 20/100=0.7; 20/125=0.8; 20/160=0.9; 20/200=1.0; 20/250=1.1; 20/320=1.2; 20/400=1.3; 20/500=1.4; 20/640=1.5; 20/800=1.6; worst | 18 weeks |
| Mean Change in Visual Acuity in the Amblyopic Eye | Acuity is measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol at baseline and at 18wks resulting in a Snellen acuity score that can range from 20/16 to 20/800. The score is converted to logMAR (log of min angle of resolution) for statistical analysis, and a difference between the scores is calculated. A positive difference indicates acuity was better at 18wks than at baseline; a negative difference indicates acuity was worse at 18wks than at baseline. | baseline to 18 weeks |
| Distribution of Change in Visual Acuity in the Amblyopic Eye | Acuity is measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol at baseline and at 18wks resulting in a Snellen acuity score that can range from 20/16 to 20/800. The score is converted to logMAR (log of min angle of resolution) for statistical analysis, and a difference between the scores is calculated. A positive difference indicates acuity was better at 18wks than at baseline; a negative difference indicates acuity was worse at 18wks than at baseline. | baseline to 18 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Randot Preschool Stereoacuity at 18 Weeks- Participants With All Causes of Amblyopia | The Randot Preschool Stereotest measures stereopsis from 800 to 40 seconds of arc on patients as young as 2 years of age. This Stereotest is designed as a matching game in which the patient matches pictures in a test booklet wearing special glasses. A subject can fail the pretest (not see any pictures) or can score >800 (the worst), 800, 400, 200, 100, 60, or 40 (the best) seconds of arc. If two shapes are identified correctly the patient progresses to the next lower stereoacuity level. A failed test occurs when the patient cannot identify any shapes. | 18 weeks |
| Randot Preschool Stereoacuity at 18 Weeks- Anisometropic Participants Only | The Randot Preschool Stereotest measures stereopsis from 800 to 40 seconds of arc on patients as young as 2 years of age. This Stereotest is designed as a matching game in which the patient matches pictures in a test booklet wearing special glasses. A subject can fail the pretest (not see any pictures) or can score >800 (the worst), 800, 400, 200, 100, 60, or 40 (the best) seconds of arc. If two shapes are identified correctly the patient progresses to the next lower stereoacuity level. A failed test occurs when the patient cannot identify any shapes. | 18 weeks |
| Mean Change in Visual Acuity in the Sound Eye | Acuity is measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol at baseline and at 18wks resulting in a Snellen acuity score that can range from 20/16 to 20/800. The score is converted to logMAR (log of min angle of resolution) for statistical analysis, and a difference between the scores is calculated. A positive difference indicates acuity was better at 18wks than at baseline; a negative difference indicates acuity was worse at 18wks than at baseline. | baseline to 18 weeks |
| Distribution of Change in Visual Acuity in the Sound Eye | Acuity is measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol at baseline and at 18wks resulting in a Snellen acuity score that can range from 20/16 to 20/800. The score is converted to logMAR (log of min angle of resolution) for statistical analysis, and a difference between the scores is calculated. A positive difference indicates acuity was better at 18wks than at baseline; a negative difference indicates acuity was worse at 18wks than at baseline. | baseline to 18 weeks |
| Visual Acuity Distribution in the Sound Eye | Acuity is measured in each eye using the Amblyopia Treatment Study (ATS) visual acuity testing protocol at baseline and at 18 wks resulting in a Snellen acuity score that can range from 20/16 to 20/800. This acuity score is converted to logMAR (log of min angle of resolution) for statistical analysis. 20/16=-0.1 logMAR; best 20/20=0.0 logMAR; 20/25=0.1; 20/32=0.2; 20/40=0.3; 20/50=0.4; 20/63=0.5; 20/80=0.6; 20/100=0.7; 20/125=0.8; 20/160=0.9; 20/200=1.0; 20/250=1.1; 20/320=1.2; 20/400=1.3; 20/500=1.4; 20/640=1.5; 20/800=1.6; worst | 18 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Amblyopia, Atropine, Plano lens
|
NCT00291811
|
Access Program for Use of AMD3100 to Increase Peripheral Blood Stem Cells for Transplantation in Patients Who Have Failed Standard Therapy Stem Cell Mobilization
|
The purpose of this program is to provide access to AMD3100 for patients who would benefit from an autologous stem cell transplant but who have either previously failed to collect enough cells for transplant following standard therapy or are not considered by their physician to have a reasonable chance of collecting enough cells for transplant.
|
The purpose of this program is to provide access to AMD3100 for patients who would benefit from an autologous stem cell transplant but who have either previously failed to collect enough cells for transplant following standard therapy or are not considered by their physician to have a reasonable chance of collecting enough cells for transplant.~Compassionate use is a way to provide experimental treatment to a patient who is not eligible to receive that therapy in a clinical trial, but who has a serious or life-threatening illness for which other treatments are not available.~Peripheral blood stem cells are obtained by apheresis following a stem cell mobilization regimen. The standard of care regimen for stem cell mobilization includes a growth factor, G-CSF. AMD3100 is given in addition to G-CSF prior to each apheresis session. If enough peripheral blood stem cells for transplant are collected, the patient is treated with high dose chemotherapy in preparation for transplant and is transplanted with cells obtained from the AMD3100 and G-CSF regimen. Patients are followed for safety and transplant outcomes for up to 12 months after transplant.
|
Compassionate Use Protocol for the Use of AMD3100 to Mobilize Peripheral Blood Stem Cells for Collection and Transplantation
|
Autologous Stem Cell Transplant
|
* Drug: AMD3100 + G-CSF
|
Inclusion Criteria:~Patient is eligible for autologous transplant~Patient has failed previous conventional therapies for stem cell collection, or is not considered by the physician to have a reasonable chance of collecting enough cells for transplant~Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.~Patient has recovered from all acute toxic effects of prior chemotherapy~Patient has white blood cell count greater than 2.5 x 10^9 cells/L~Patient has absolute neutrophil count (ANC) greater than 1.5 x 10^9 cells/L~Patient has platelet count greater than 85 x 10^9 cells/L~Patient has serum creatinine less than or equal to 1.5 mg/dL~Patient has creatinine clearance greater than 60 mL/min~Patient has liver function tests less than 2x upper limit of normal~Patient has left ventricle ejection fraction greater than 45%~Patient has forced expiratory volume in 1 second (FEV1) greater than 60% of predicted or diffusing capacity of lung carbon monoxide (DLCO) and greater than or equal to 45% of predicted~Patient has no active infection of hepatitis B or C~Patient is negative for HIV~Patient has signed informed consent~Women of child bearing potential agree to use an approved form of contraception~Exclusion Criteria:~Patients with leukemia (Note: Patients with multiple myeloma must be evaluated for plasma cells or blasts within 24 hours prior to the first dose of AMD3100)~Patient has an existing condition which, in the view of the Investigator, renders the patient at high risk from treatment complications~Patient has a residual acute medical condition resulting from prior chemotherapy~Patient has brain metastases or carcinomatous meningitis~Patient has an acute infection~Patient has a fever (temperature greater than 38 degrees C/100.4 degrees F)~Patient has hypercalcaemia greater than 1 mg/dL above the upper limit of normal~Female patient has positive pregnancy test~Female patient is lactating~Patient is of child-bearing potential and is unwilling to use adequate birth control~Patients with actual body weight exceeding 175% of their ideal body weight~Patients who previously received experimental therapy within 4 weeks of enrolling in this protocol or who are currently enrolled in another experimental protocol~Patients who experience a deterioration in health between the time of enrollment and transplant (such that they no longer meet entry criteria) may be removed from study at the discretion of the treating physician, principal Investigator, or Sponsor
|
18 Years
|
78 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
AMD3100, G-CSF
|
Plerixafor, Anti-HIV Agents, Anti-Retroviral Agents, Antiviral Agents, Anti-Infective Agents
|
| Intervention/Treatment |
| --- |
|Drug: AMD3100 + G-CSF|Subcutaneous injection of 240 mcg/kg on the evening prior to each apheresis session|
|
Access Program for Use of AMD3100 to Increase Peripheral Blood Stem Cells for Transplantation in Patients Who Have Failed Standard Therapy Stem Cell Mobilization
Study Overview
=================
Brief Summary
-----------------
The purpose of this program is to provide access to AMD3100 for patients who would benefit from an autologous stem cell transplant but who have either previously failed to collect enough cells for transplant following standard therapy or are not considered by their physician to have a reasonable chance of collecting enough cells for transplant.
Detailed Description
-----------------
The purpose of this program is to provide access to AMD3100 for patients who would benefit from an autologous stem cell transplant but who have either previously failed to collect enough cells for transplant following standard therapy or are not considered by their physician to have a reasonable chance of collecting enough cells for transplant. Compassionate use is a way to provide experimental treatment to a patient who is not eligible to receive that therapy in a clinical trial, but who has a serious or life-threatening illness for which other treatments are not available. Peripheral blood stem cells are obtained by apheresis following a stem cell mobilization regimen. The standard of care regimen for stem cell mobilization includes a growth factor, G-CSF. AMD3100 is given in addition to G-CSF prior to each apheresis session. If enough peripheral blood stem cells for transplant are collected, the patient is treated with high dose chemotherapy in preparation for transplant and is transplanted with cells obtained from the AMD3100 and G-CSF regimen. Patients are followed for safety and transplant outcomes for up to 12 months after transplant.
Official Title
-----------------
Compassionate Use Protocol for the Use of AMD3100 to Mobilize Peripheral Blood Stem Cells for Collection and Transplantation
Conditions
-----------------
Autologous Stem Cell Transplant
Intervention / Treatment
-----------------
* Drug: AMD3100 + G-CSF
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient is eligible for autologous transplant Patient has failed previous conventional therapies for stem cell collection, or is not considered by the physician to have a reasonable chance of collecting enough cells for transplant Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patient has recovered from all acute toxic effects of prior chemotherapy Patient has white blood cell count greater than 2.5 x 10^9 cells/L Patient has absolute neutrophil count (ANC) greater than 1.5 x 10^9 cells/L Patient has platelet count greater than 85 x 10^9 cells/L Patient has serum creatinine less than or equal to 1.5 mg/dL Patient has creatinine clearance greater than 60 mL/min Patient has liver function tests less than 2x upper limit of normal Patient has left ventricle ejection fraction greater than 45% Patient has forced expiratory volume in 1 second (FEV1) greater than 60% of predicted or diffusing capacity of lung carbon monoxide (DLCO) and greater than or equal to 45% of predicted Patient has no active infection of hepatitis B or C Patient is negative for HIV Patient has signed informed consent Women of child bearing potential agree to use an approved form of contraception Exclusion Criteria: Patients with leukemia (Note: Patients with multiple myeloma must be evaluated for plasma cells or blasts within 24 hours prior to the first dose of AMD3100) Patient has an existing condition which, in the view of the Investigator, renders the patient at high risk from treatment complications Patient has a residual acute medical condition resulting from prior chemotherapy Patient has brain metastases or carcinomatous meningitis Patient has an acute infection Patient has a fever (temperature greater than 38 degrees C/100.4 degrees F) Patient has hypercalcaemia greater than 1 mg/dL above the upper limit of normal Female patient has positive pregnancy test Female patient is lactating Patient is of child-bearing potential and is unwilling to use adequate birth control Patients with actual body weight exceeding 175% of their ideal body weight Patients who previously received experimental therapy within 4 weeks of enrolling in this protocol or who are currently enrolled in another experimental protocol Patients who experience a deterioration in health between the time of enrollment and transplant (such that they no longer meet entry criteria) may be removed from study at the discretion of the treating physician, principal Investigator, or Sponsor
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 78 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Intervention/Treatment |
| --- |
|Drug: AMD3100 + G-CSF|Subcutaneous injection of 240 mcg/kg on the evening prior to each apheresis session|
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
-----------------
AMD3100, G-CSF
|
||
NCT04223882
|
Stress Management in Patients With Coronary Artery Disease
|
Introduction: Stress can cause hemodynamic and metabolic changes that contribute to endothelial dysfunction and there is a significant association between high stress and cardiovascular events. Objective: To evaluate the influence of stress management on endothelial function in patients undergoing percutaneous coronary intervention (PCI). Methods: Randomized, controlled, parallel, intention-to-treat clinical trial. Will be considered eligible patients who underwent percutaneous coronary intervention and who have high stress (above average for the Brazilian population) in the Perceived Stress Scale (PSS-10). Patients will be evaluated on PCI admission and stress management with cognitive behavioral techniques will be implemented one month after hospital discharge in the intervention group. Group sessions will be held between 6-9 people. There will be 4 1-hour meetings for 8 weeks. The primary outcome will be the difference in the variation of brachial artery flow-mediated dilatation (FMD) between the groups and at 3 months of baseline evaluation and at 6-month follow-up after the intervention and the secondary outcome will be the difference in the variation of the velocity of brachial artery. Pulse wave evaluated at the same time periods as DMF. Outcomes will be evaluated by Generalized Estimation Equations (GEE). Expected Results: In patients undergoing high-stress percutaneous coronary intervention, the use of cognitive behavioral techniques for stress management will improve endothelial function and vascular stiffness.
|
Stress Management in Patients With Coronary Artery Disease: a Randomized Clinical Trial
|
Stress, Psychological
|
* Behavioral: Management of Stress
* Other: Usual care
|
Inclusion Criteria:~Age ≥ 18 years;~Patients with CAD - obstruction of one or more epicardial arteries with at least 70% stenosis and / or Left Coronary Trunk (TBI) with at least 50% - measured by catheterization (CATE) and having performed elective PCI~High stress: above average score for the Brazilian population in the Perceived Stress Scale (PSS-10)~Signing of the Informed Consent.~Exclusion Criteria:~Age ≥ 80 years~Patients with inpatient events (AMI, CABG, stroke)~Indication of catheterization for valvulopathies or congenital heart disease~Severe aortic stenosis / Ejection fraction <30%, cardiomyopathy, severe congestive heart disease~Severe diseases with life expectancy <6 months~Cognitive or mental difficulties to understand the instrument~Inability to follow up visits
|
18 Years
|
79 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in Flow-mediated Dilation in the Brachial Artery in the Base and After the Treatment. | Inter group difference in flow-mediated dilation in the brachial artery in the baseline and after the treatment (about Three months after the first).~Vasodilatation of the endothelium-dependent brachial artery was evaluated by ultrasound using a 3-12 MHz linear transducer. Three images of the basal diameter (BD) of the brachial artery at the end of the diastole were acquired, as well as the mean velocity of the baseline arterial flow, with the linear transducer positioned 5 cm above the antecubital fossa. Subsequently, the sphygmomanometer was placed in the arm and inflated 50 mmHg above baseline systolic blood pressure for five minutes. After that, 3 images of the arterial diameter were acquired up to 80 seconds of the deflation of the cuff (post-occlusion diameter- PD), as well as the average of the arterial flow velocity. Flow-dependent vasodilation responses were expressed as a percentage variation from the baseline brachial diameter (PD-BD/ BD x 100). | Three months after the first evaluation |
|
Stress, Psychological;, Coronary Artery Disease;, Percutaneous Coronary Intervention;, Endothelium;
|
Coronary Artery Disease, Myocardial Ischemia, Coronary Disease, Stress, Psychological, Heart Diseases, Cardiovascular Diseases, Arteriosclerosis, Arterial Occlusive Diseases, Vascular Diseases, Behavioral Symptoms
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group Intervention- Management of stress<br>Patients in the intervention group will receive usual medical care and more stress management intervention. Stress management with cognitive behavioral techniques will be implemented one month after hospital discharge in the intervention group. Group sessions will be held between 6-9 people. There will be 3 1-hour meetings for 3 weeks. The intervention will be performed by psychologist. | Behavioral: Management of Stress<br>* Psychoeducation:~Coronary artery disease, Percutaneous Coronary Intervention, traditional risk factors and emotional stress.~Stress: physiology, triggers, triad (thinking, emotion, action).~Skills training:~Identify warning signs - signs and symptoms; Monitoring of irrational automatic thoughts generating alternative interpretations of situations or unrealistic thinking patterns (Dysfunctional Thinking Records Sheet).~Self-control for stress management:~Assertiveness training, problem solving. Thought-stopping technique, designed for dysfunctional thoughts, such as, I won't do it, It won't work.~Stress Relief / Control Techniques:~Diaphragmatic Breathing: Expansion of the abdomen rather than the chest when breathing.~Progressive Muscle Relaxation: Maximize tension and alternately relax the muscles (legs, abdomen, chest, arms and face).<br>|
| Active Comparator: Group Control<br>Patients in the control group will receive usual medical care. | Other: Usual care<br>* outpatient medical appointments<br>* Other names: Patients in the control group will receive usual medical care;|
|
Stress Management in Patients With Coronary Artery Disease
Study Overview
=================
Brief Summary
-----------------
Introduction: Stress can cause hemodynamic and metabolic changes that contribute to endothelial dysfunction and there is a significant association between high stress and cardiovascular events. Objective: To evaluate the influence of stress management on endothelial function in patients undergoing percutaneous coronary intervention (PCI). Methods: Randomized, controlled, parallel, intention-to-treat clinical trial. Will be considered eligible patients who underwent percutaneous coronary intervention and who have high stress (above average for the Brazilian population) in the Perceived Stress Scale (PSS-10). Patients will be evaluated on PCI admission and stress management with cognitive behavioral techniques will be implemented one month after hospital discharge in the intervention group. Group sessions will be held between 6-9 people. There will be 4 1-hour meetings for 8 weeks. The primary outcome will be the difference in the variation of brachial artery flow-mediated dilatation (FMD) between the groups and at 3 months of baseline evaluation and at 6-month follow-up after the intervention and the secondary outcome will be the difference in the variation of the velocity of brachial artery. Pulse wave evaluated at the same time periods as DMF. Outcomes will be evaluated by Generalized Estimation Equations (GEE). Expected Results: In patients undergoing high-stress percutaneous coronary intervention, the use of cognitive behavioral techniques for stress management will improve endothelial function and vascular stiffness.
Official Title
-----------------
Stress Management in Patients With Coronary Artery Disease: a Randomized Clinical Trial
Conditions
-----------------
Stress, Psychological
Intervention / Treatment
-----------------
* Behavioral: Management of Stress
* Other: Usual care
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years; Patients with CAD - obstruction of one or more epicardial arteries with at least 70% stenosis and / or Left Coronary Trunk (TBI) with at least 50% - measured by catheterization (CATE) and having performed elective PCI High stress: above average score for the Brazilian population in the Perceived Stress Scale (PSS-10) Signing of the Informed Consent. Exclusion Criteria: Age ≥ 80 years Patients with inpatient events (AMI, CABG, stroke) Indication of catheterization for valvulopathies or congenital heart disease Severe aortic stenosis / Ejection fraction <30%, cardiomyopathy, severe congestive heart disease Severe diseases with life expectancy <6 months Cognitive or mental difficulties to understand the instrument Inability to follow up visits
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 79 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: Group Intervention- Management of stress<br>Patients in the intervention group will receive usual medical care and more stress management intervention. Stress management with cognitive behavioral techniques will be implemented one month after hospital discharge in the intervention group. Group sessions will be held between 6-9 people. There will be 3 1-hour meetings for 3 weeks. The intervention will be performed by psychologist. | Behavioral: Management of Stress<br>* Psychoeducation: Coronary artery disease, Percutaneous Coronary Intervention, traditional risk factors and emotional stress. Stress: physiology, triggers, triad (thinking, emotion, action). Skills training: Identify warning signs - signs and symptoms; Monitoring of irrational automatic thoughts generating alternative interpretations of situations or unrealistic thinking patterns (Dysfunctional Thinking Records Sheet). Self-control for stress management: Assertiveness training, problem solving. Thought-stopping technique, designed for dysfunctional thoughts, such as, I won't do it, It won't work. Stress Relief / Control Techniques: Diaphragmatic Breathing: Expansion of the abdomen rather than the chest when breathing. Progressive Muscle Relaxation: Maximize tension and alternately relax the muscles (legs, abdomen, chest, arms and face).<br>|
| Active Comparator: Group Control<br>Patients in the control group will receive usual medical care. | Other: Usual care<br>* outpatient medical appointments<br>* Other names: Patients in the control group will receive usual medical care;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in Flow-mediated Dilation in the Brachial Artery in the Base and After the Treatment. | Inter group difference in flow-mediated dilation in the brachial artery in the baseline and after the treatment (about Three months after the first). Vasodilatation of the endothelium-dependent brachial artery was evaluated by ultrasound using a 3-12 MHz linear transducer. Three images of the basal diameter (BD) of the brachial artery at the end of the diastole were acquired, as well as the mean velocity of the baseline arterial flow, with the linear transducer positioned 5 cm above the antecubital fossa. Subsequently, the sphygmomanometer was placed in the arm and inflated 50 mmHg above baseline systolic blood pressure for five minutes. After that, 3 images of the arterial diameter were acquired up to 80 seconds of the deflation of the cuff (post-occlusion diameter- PD), as well as the average of the arterial flow velocity. Flow-dependent vasodilation responses were expressed as a percentage variation from the baseline brachial diameter (PD-BD/ BD x 100). | Three months after the first evaluation |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Stress, Psychological;, Coronary Artery Disease;, Percutaneous Coronary Intervention;, Endothelium;
|
||
NCT05470777
|
CD22/CD19 CAR-T and Auto-HSCT Sandwich Strategy as Consolidation Therapy for B-ALL
|
Chimeric antigen receptor T-cell (CAR-T) therapy has achieved remarkable efficacy in B-cell acute lymphoblastic leukemia (B-ALL). However, relapse after CAR-T has been a major issue. Multi-antigen CAR T and combination with other regimens may reduce the relapse rate. The investigators first conducted CD22/CD19 CAR T-cells and auto-HSCT sandwich strategy as consolidation therapy in patients with B-ALL. The main Purpose of this study was to observe the safety and efficacy of this new strategy.
|
The patients received sequential infusion of CD22 and CD19 CAR-T cells (co-stimulatory molecule was 4-1BB and infusion dose was 5*10^6/kg respectively) after standard induction and consolidation chemotherapy. Autologous stem cells mobilization and collection were performed 6-8 weeks after CAR-T infusion. Standard BuCy as conditioning regimen for Auto-HSCT was used 4 weeks after successful stem cell collection. CD22 and CD19 CAR-T cells were re-infused 2 days after Auto-HSCT. Patients were followed up and minimal residual diseases (MRD) was monitored by flow cytometry and second-generation gene sequencing of IgH rearrangement.
|
Safety and Efficacy of CD22/CD19 CAR T-cells and Autologous HSCT Sandwich Strategy as Consolidation Therapy for B-cell Acute Lymphoblastic Leukemia
|
B-cell Acute Lymphoblastic Leukemia
|
* Combination Product: CD22/CD19 CAR T and auto-HSCT sandwich strategy
|
Inclusion Criteria:~subjects with a primary diagnosis of B-ALL who have any of the following: (a) no suitable allogeneic HSCT donor. (b) refusal of allogeneic HSCT.~positive expression of CD19 and CD22 in peripheral blood or bone marrow primary cells detected by flow cytometry.~cardiac ultrasound left ventricular ejection fraction ≥ 50%; Creatinine ≤ 1.6 mg/dl; alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the normal range and total bilirubin ≤ 2.0 mg/dl; Pulmonary function ≤ grade 1 dyspnea (CTCAE v5.0) with oxygen saturation > 91% without oxygenation.~subjects aged 15-65 years (including 15 and 65 years), regardless of gender.~T-cell amplification test pass.~expected survival > 3 months.~Exclusion Criteria:~patients with recurrence of only isolated extramedullary lesions.~combination of other malignant tumors.~previously treated with anti-CD19 or/and CD22 or/and CD3 therapies.~immunosuppressants use within 2 weeks prior to signing informed consent or plan to immunosuppressants after signing informed consent.~uncontrolled active infections.~HIV infection.~active hepatitis B or hepatitis C infection.~history of severe tachyphylaxis to aminoglycoside antibiotics.~history or presence of clinically relevant Central Nervous System (CNS) pathology, such as epilepsy, generalized seizure disorder, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
|
15 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events | Adverse events are evaluated with CTCAE V5.0 from the date of entry into this trial. | 2 years |
| Overall response rate (ORR） | The percentage of participants achieving CR or CRi after the whole treatment strategy; patients not known to have any of these events are censored on the date they were last examined. | 1 month after auto-HSCT |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival（OS） | It is measured from the date of entry into this trial to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive. | 2 years |
| leukemia free survival（LFS） | It is measured from the date of achievement of a remission until the date of relapse from CR, or CRi, or death from any cause; patients not known to have any of these events are censored on the date they were last examined. | 2 years |
|
CD22/CD19 CAR-T, auto-HSCT
|
Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Lymphoid, Neoplasms by Histologic Type, Neoplasms, Lymphoproliferative Disorders, Lymphatic Diseases, Immunoproliferative Disorders, Immune System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD22/CD19 CAR T and auto-HSCT sandwich strategy as consolidation therapy for B-ALL<br> | Combination Product: CD22/CD19 CAR T and auto-HSCT sandwich strategy<br>* The patients received sequential infusion of CD22 and CD19 CAR-T cells (co-stimulatory molecule was 4-1BB and infusion dose was 5*10^6/kg respectively) after standard induction and consolidation chemotherapy. Autologous stem cells mobilization and collection were performed 6-8 weeks after CAR-T infusion. Standard BuCy as conditioning regimen for Auto-HSCT was used 4 weeks after successful stem cell collection. CD22 and CD19 CAR-T cells were re-infused 2 days after Auto-HSCT. Patients were followed up and minimal residual diseases (MRD) was monitored by flow cytometry and second-generation gene sequencing of IgH rearrangement.<br>|
|
CD22/CD19 CAR-T and Auto-HSCT Sandwich Strategy as Consolidation Therapy for B-ALL
Study Overview
=================
Brief Summary
-----------------
Chimeric antigen receptor T-cell (CAR-T) therapy has achieved remarkable efficacy in B-cell acute lymphoblastic leukemia (B-ALL). However, relapse after CAR-T has been a major issue. Multi-antigen CAR T and combination with other regimens may reduce the relapse rate. The investigators first conducted CD22/CD19 CAR T-cells and auto-HSCT sandwich strategy as consolidation therapy in patients with B-ALL. The main Purpose of this study was to observe the safety and efficacy of this new strategy.
Detailed Description
-----------------
The patients received sequential infusion of CD22 and CD19 CAR-T cells (co-stimulatory molecule was 4-1BB and infusion dose was 5*10^6/kg respectively) after standard induction and consolidation chemotherapy. Autologous stem cells mobilization and collection were performed 6-8 weeks after CAR-T infusion. Standard BuCy as conditioning regimen for Auto-HSCT was used 4 weeks after successful stem cell collection. CD22 and CD19 CAR-T cells were re-infused 2 days after Auto-HSCT. Patients were followed up and minimal residual diseases (MRD) was monitored by flow cytometry and second-generation gene sequencing of IgH rearrangement.
Official Title
-----------------
Safety and Efficacy of CD22/CD19 CAR T-cells and Autologous HSCT Sandwich Strategy as Consolidation Therapy for B-cell Acute Lymphoblastic Leukemia
Conditions
-----------------
B-cell Acute Lymphoblastic Leukemia
Intervention / Treatment
-----------------
* Combination Product: CD22/CD19 CAR T and auto-HSCT sandwich strategy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: subjects with a primary diagnosis of B-ALL who have any of the following: (a) no suitable allogeneic HSCT donor. (b) refusal of allogeneic HSCT. positive expression of CD19 and CD22 in peripheral blood or bone marrow primary cells detected by flow cytometry. cardiac ultrasound left ventricular ejection fraction ≥ 50%; Creatinine ≤ 1.6 mg/dl; alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the normal range and total bilirubin ≤ 2.0 mg/dl; Pulmonary function ≤ grade 1 dyspnea (CTCAE v5.0) with oxygen saturation > 91% without oxygenation. subjects aged 15-65 years (including 15 and 65 years), regardless of gender. T-cell amplification test pass. expected survival > 3 months. Exclusion Criteria: patients with recurrence of only isolated extramedullary lesions. combination of other malignant tumors. previously treated with anti-CD19 or/and CD22 or/and CD3 therapies. immunosuppressants use within 2 weeks prior to signing informed consent or plan to immunosuppressants after signing informed consent. uncontrolled active infections. HIV infection. active hepatitis B or hepatitis C infection. history of severe tachyphylaxis to aminoglycoside antibiotics. history or presence of clinically relevant Central Nervous System (CNS) pathology, such as epilepsy, generalized seizure disorder, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
Ages Eligible for Study
-----------------
Minimum Age: 15 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD22/CD19 CAR T and auto-HSCT sandwich strategy as consolidation therapy for B-ALL<br> | Combination Product: CD22/CD19 CAR T and auto-HSCT sandwich strategy<br>* The patients received sequential infusion of CD22 and CD19 CAR-T cells (co-stimulatory molecule was 4-1BB and infusion dose was 5*10^6/kg respectively) after standard induction and consolidation chemotherapy. Autologous stem cells mobilization and collection were performed 6-8 weeks after CAR-T infusion. Standard BuCy as conditioning regimen for Auto-HSCT was used 4 weeks after successful stem cell collection. CD22 and CD19 CAR-T cells were re-infused 2 days after Auto-HSCT. Patients were followed up and minimal residual diseases (MRD) was monitored by flow cytometry and second-generation gene sequencing of IgH rearrangement.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events | Adverse events are evaluated with CTCAE V5.0 from the date of entry into this trial. | 2 years |
| Overall response rate (ORR） | The percentage of participants achieving CR or CRi after the whole treatment strategy; patients not known to have any of these events are censored on the date they were last examined. | 1 month after auto-HSCT |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival（OS） | It is measured from the date of entry into this trial to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive. | 2 years |
| leukemia free survival（LFS） | It is measured from the date of achievement of a remission until the date of relapse from CR, or CRi, or death from any cause; patients not known to have any of these events are censored on the date they were last examined. | 2 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CD22/CD19 CAR-T, auto-HSCT
|
NCT01247909
|
Infant Severe Sepsis and Bacterial Meningitis in Malawi
|
This study aims to improve the outcome of infants (<2 months) with severe sepsis and meningitis at the Queen Elizabeth Central Hospital, Blantyre, Malawi.~Currently WHO recommends the treatment of infant severe sepsis and bacterial meningitis with 14 to 21 day course of penicillin and gentamicin as first line. The second line treatment is cefotaxime or ceftriaxone.~Severe bacterial infections are common in infants under 2 months of age and the mortality is very high (~50%). There are several reasons for this; one is that the first line antibiotics used are no longer as effective as they used to be. Bacterial resistance to the first line antibiotics has increased and some infections especially of the central nervous system may only be partly treated and not eradicated by present therapy. First line treatment is cheap and available but requires 4 injections a day, for at least 14 days, a total of 58 injections. Many mothers find this number too much and abscond. The investigators second line therapy is ceftriaxone which is also available and cheap and the advantage of being given as a daily injection. The disadvantage is that it can cause (reversible) jaundice particularly in premature babies and it must not be given with calcium products. The investigators do not give calcium to the investigators infants as the investigators cannot routinely check electrolytes. All the most common causes of bacterial meningitis in this age group in the investigators setting are sensitive to ceftriaxone.~The investigators wish to undertake an open randomized trial of penicillin and gentamicin v ceftriaxone as first line treatment for infant meningitis. The investigators are able to monitor for side effects.~The investigators hypothesise that the ceftriaxone arm will have 20% less deaths that the penicillin and gentamicin group.
|
An Open Randomised Trial of Ceftriaxone v Penicillin and Gentamicin in Infant Severe Sepsis and Bacterial Meningitis in Malawi
|
Infant Bacterial Meningitis
|
* Drug: Ceftriaxone v penicillin and gentamicin
|
Inclusion Criteria:~Children less than 2 months~Suspicion of bacterial meningitis~Parental/guardian informed consent~Exclusion Criteria:~Infant with hyperbilirubinaemia~Infant requiring calcium~Infant know to be hypersensitive to any of the three drugs~Infant who has been an inpatient for more than 72 hours~Infant with congenital central nervous system abnormalities
| null |
2 Months
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recovery v death or severe residual neurological sequelae at hospital discharge, 1 month and 6 months post discharge. | | 3 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Outcome by causative bacterial agent, recovery v death or severe residual neurological sequelae at hospital discharge, 1 month and 6 months post discharge. | | 3 years |
|
Gentamicins, Ceftriaxone, Penicillins, Anti-Bacterial Agents, Anti-Infective Agents, Protein Synthesis Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ceftriaxone<br>Ceftriaxone in infants with sepsis and bacterial meningitis | Drug: Ceftriaxone v penicillin and gentamicin<br>* Ceftriaxone v the standard treatment of infant meningitis (penicillin and gentamicin). Ceftriaxone will be given at a dose of 80mg/kg once a day for at least 14 days.<br>|
| Active Comparator: Penicillin and gentamicin<br>Penicillin and Gentamicin in infants with sepsis and bacterial meningitis | Drug: Ceftriaxone v penicillin and gentamicin<br>* Ceftriaxone v the standard treatment of infant meningitis (penicillin and gentamicin). Ceftriaxone will be given at a dose of 80mg/kg once a day for at least 14 days.<br>|
|
Infant Severe Sepsis and Bacterial Meningitis in Malawi
Study Overview
=================
Brief Summary
-----------------
This study aims to improve the outcome of infants (<2 months) with severe sepsis and meningitis at the Queen Elizabeth Central Hospital, Blantyre, Malawi. Currently WHO recommends the treatment of infant severe sepsis and bacterial meningitis with 14 to 21 day course of penicillin and gentamicin as first line. The second line treatment is cefotaxime or ceftriaxone. Severe bacterial infections are common in infants under 2 months of age and the mortality is very high ( 50%). There are several reasons for this; one is that the first line antibiotics used are no longer as effective as they used to be. Bacterial resistance to the first line antibiotics has increased and some infections especially of the central nervous system may only be partly treated and not eradicated by present therapy. First line treatment is cheap and available but requires 4 injections a day, for at least 14 days, a total of 58 injections. Many mothers find this number too much and abscond. The investigators second line therapy is ceftriaxone which is also available and cheap and the advantage of being given as a daily injection. The disadvantage is that it can cause (reversible) jaundice particularly in premature babies and it must not be given with calcium products. The investigators do not give calcium to the investigators infants as the investigators cannot routinely check electrolytes. All the most common causes of bacterial meningitis in this age group in the investigators setting are sensitive to ceftriaxone. The investigators wish to undertake an open randomized trial of penicillin and gentamicin v ceftriaxone as first line treatment for infant meningitis. The investigators are able to monitor for side effects. The investigators hypothesise that the ceftriaxone arm will have 20% less deaths that the penicillin and gentamicin group.
Official Title
-----------------
An Open Randomised Trial of Ceftriaxone v Penicillin and Gentamicin in Infant Severe Sepsis and Bacterial Meningitis in Malawi
Conditions
-----------------
Infant Bacterial Meningitis
Intervention / Treatment
-----------------
* Drug: Ceftriaxone v penicillin and gentamicin
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Children less than 2 months Suspicion of bacterial meningitis Parental/guardian informed consent Exclusion Criteria: Infant with hyperbilirubinaemia Infant requiring calcium Infant know to be hypersensitive to any of the three drugs Infant who has been an inpatient for more than 72 hours Infant with congenital central nervous system abnormalities
Ages Eligible for Study
-----------------
Maximum Age: 2 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: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ceftriaxone<br>Ceftriaxone in infants with sepsis and bacterial meningitis | Drug: Ceftriaxone v penicillin and gentamicin<br>* Ceftriaxone v the standard treatment of infant meningitis (penicillin and gentamicin). Ceftriaxone will be given at a dose of 80mg/kg once a day for at least 14 days.<br>|
| Active Comparator: Penicillin and gentamicin<br>Penicillin and Gentamicin in infants with sepsis and bacterial meningitis | Drug: Ceftriaxone v penicillin and gentamicin<br>* Ceftriaxone v the standard treatment of infant meningitis (penicillin and gentamicin). Ceftriaxone will be given at a dose of 80mg/kg once a day for at least 14 days.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recovery v death or severe residual neurological sequelae at hospital discharge, 1 month and 6 months post discharge. | | 3 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Outcome by causative bacterial agent, recovery v death or severe residual neurological sequelae at hospital discharge, 1 month and 6 months post discharge. | | 3 years |
|
||
NCT02546791
|
Frequency and Severity of Pleural Effusion Associated With the Use of Dasatinib in Patients With Chronic Myeloid Leukemia. A Descriptive, Mexican Multicenter Study
|
This is a retrospective, multicenter, descriptive analysis of patients with a diagnosis of chronic myeloid leukemia, treated with dasatinib for at least 45 days. The study will include 100 patients treated in different public centers in the Mexican Republic.
|
Frequency and Severity of Pleural Effusion Associated With the Use of Dasatinib in Patients With Chronic Myeloid Leukemia. A Descriptive, Mexican Multicenter Study
|
Leukemia
|
* Drug: Dasatinib
|
Inclusion Criteria:~Men and women ≥15 years of age~Diagnosis of chronic myeloid leukemia in any phase that used dasatinib at any time between January 2008 and November 2014~Have received dasatinib as part of their first-line or second-line treatment for at least 45 days~Exclusion Criteria:~Patients who received dasatinib as part of any clinical trial~Patients who do not have complete data on the data collection sheet~Patients who do not have medical records available at the moment of the data verification
|
15 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detect the absence and presence of pleural effusion in Mexican patients measured from the medical records and databases of each of the participating medical centers | | 1 year and 4 month of data collection |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establish the factors associated with response of the patients who develop pleural effusion | Factors:~Hematological Response~Standardization of counts in peripheral blood with leukocytes <10 × 10^9 and platelets <450 ×10^9~Absence of immature elements in the smear~Basophils <5%~Absence of palpable splenomegaly~Complete Molecular Response (CMR)~Undetectable BCR-ABL mRNA transcripts by real time quantitative and/or nested Partial Cytogenetic Response (PCR) in two consecutive blood samples of adequate quality (sensitivity >104) Major Molecular Response (MMR)~Ratio of BCR-ABL to ABL (or other housekeeping genes) ≤0.1% on the international scale | 1 year and 4 month of data collection |
| Main characteristics of the patients who develop pleural effusion | Characteristics: Age, gender, comorbidity | 1 year and 4 month of data collection |
|
Dasatinib, Antineoplastic Agents, Protein Kinase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Chronic myeloid leukemia patients treated with Dasatinib<br>patients with a diagnosis of chronic myeloid leukemia treated with Dasatinib for at least 45 days | Drug: Dasatinib<br> <br> |
|
Frequency and Severity of Pleural Effusion Associated With the Use of Dasatinib in Patients With Chronic Myeloid Leukemia. A Descriptive, Mexican Multicenter Study
Study Overview
=================
Brief Summary
-----------------
This is a retrospective, multicenter, descriptive analysis of patients with a diagnosis of chronic myeloid leukemia, treated with dasatinib for at least 45 days. The study will include 100 patients treated in different public centers in the Mexican Republic.
Official Title
-----------------
Frequency and Severity of Pleural Effusion Associated With the Use of Dasatinib in Patients With Chronic Myeloid Leukemia. A Descriptive, Mexican Multicenter Study
Conditions
-----------------
Leukemia
Intervention / Treatment
-----------------
* Drug: Dasatinib
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women ≥15 years of age Diagnosis of chronic myeloid leukemia in any phase that used dasatinib at any time between January 2008 and November 2014 Have received dasatinib as part of their first-line or second-line treatment for at least 45 days Exclusion Criteria: Patients who received dasatinib as part of any clinical trial Patients who do not have complete data on the data collection sheet Patients who do not have medical records available at the moment of the data verification
Ages Eligible for Study
-----------------
Minimum Age: 15 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 |
| --- | --- |
| Chronic myeloid leukemia patients treated with Dasatinib<br>patients with a diagnosis of chronic myeloid leukemia treated with Dasatinib for at least 45 days | Drug: Dasatinib<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detect the absence and presence of pleural effusion in Mexican patients measured from the medical records and databases of each of the participating medical centers | | 1 year and 4 month of data collection |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establish the factors associated with response of the patients who develop pleural effusion | Factors: Hematological Response Standardization of counts in peripheral blood with leukocytes <10 × 10^9 and platelets <450 ×10^9 Absence of immature elements in the smear Basophils <5% Absence of palpable splenomegaly Complete Molecular Response (CMR) Undetectable BCR-ABL mRNA transcripts by real time quantitative and/or nested Partial Cytogenetic Response (PCR) in two consecutive blood samples of adequate quality (sensitivity >104) Major Molecular Response (MMR) Ratio of BCR-ABL to ABL (or other housekeeping genes) ≤0.1% on the international scale | 1 year and 4 month of data collection |
| Main characteristics of the patients who develop pleural effusion | Characteristics: Age, gender, comorbidity | 1 year and 4 month of data collection |
|
|||
NCT00251979
|
A Study to Prevent Rebleeding After Initial Successful Primary Endoscopic Haemostasis of a Bleeding Peptic Ulcer
|
This study is being carried out to see if constant 3 days infusion of Nexium is effective in preventing rebleeding after an endoscopic treatment.
|
A Randomised, Double-blind, Parallel-group, Placebo Controlled Study of Esomeprazole i.v. (Bolus Infusion of 80 mg Followed by a Continuous Infusion of 8 mg Per Hour) Administered for 72 Hours to Assess Prevention of Rebleeding in Subjects That Have Undergone Successful Primary Endoscopic Haemostasis of a Bleeding Peptic Ulcer - the PUB Study.
|
Gastrointestinal Hemorrhage
|
* Drug: Esomeprazole
|
Inclusion Criteria:~Signs of a bleeding in the stomach~One endoscopically confirmed bleeding ulcer in the stomach or duodenum~Exclusion Criteria:~Malignancy or other advanced disease.~Major cardiovascular event.~Severe hepatic disease
|
18 Years
| null |
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically Significant Rebleeding Within 72 Hours of Continous Infusion of Esomeprazole or Placebo | | Within 72 hours |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically Significant Rebleeding Within 7 Days | | Within 7 days |
| Clinically Significant Rebleeding Within 30 Days | | Within 30 days |
| Death Within 72 Hours | | Within 72 hours |
| Death Within 30 Days | | Within 30 days |
| Death Related to Rebleeding Within 30 Days as Judged by the EpC | | Within 30 days |
| Requirement for Surgery Within 72 Hours | | Within 72 hours |
| Requirement for Surgery Within 30 Days | | Within 30 days |
| Requirement for Endoscopic Re-treatment Within 72 Hours | | Within 72 hours |
| Requirement for Endoscopic Re-treatment Within 30 Days | | Within 30 days |
| Number of Blood Units Transfused Within 72 Hours | | Within 72 hours |
| Number of Blood Units Transfused Within 30 Days | | within 30 days |
| Number of Days Hospitalized Due to Rebleeding During the 30-day Treatment Period | | Within 30 days |
|
Esomeprazole, Anti-Ulcer Agents, Gastrointestinal Agents, Proton Pump Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
|
| Intervention/Treatment |
| --- |
|Drug: Esomeprazole|nan|
|
A Study to Prevent Rebleeding After Initial Successful Primary Endoscopic Haemostasis of a Bleeding Peptic Ulcer
Study Overview
=================
Brief Summary
-----------------
This study is being carried out to see if constant 3 days infusion of Nexium is effective in preventing rebleeding after an endoscopic treatment.
Official Title
-----------------
A Randomised, Double-blind, Parallel-group, Placebo Controlled Study of Esomeprazole i.v. (Bolus Infusion of 80 mg Followed by a Continuous Infusion of 8 mg Per Hour) Administered for 72 Hours to Assess Prevention of Rebleeding in Subjects That Have Undergone Successful Primary Endoscopic Haemostasis of a Bleeding Peptic Ulcer - the PUB Study.
Conditions
-----------------
Gastrointestinal Hemorrhage
Intervention / Treatment
-----------------
* Drug: Esomeprazole
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signs of a bleeding in the stomach One endoscopically confirmed bleeding ulcer in the stomach or duodenum Exclusion Criteria: Malignancy or other advanced disease. Major cardiovascular event. Severe hepatic 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Intervention/Treatment |
| --- |
|Drug: Esomeprazole|nan|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically Significant Rebleeding Within 72 Hours of Continous Infusion of Esomeprazole or Placebo | | Within 72 hours |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically Significant Rebleeding Within 7 Days | | Within 7 days |
| Clinically Significant Rebleeding Within 30 Days | | Within 30 days |
| Death Within 72 Hours | | Within 72 hours |
| Death Within 30 Days | | Within 30 days |
| Death Related to Rebleeding Within 30 Days as Judged by the EpC | | Within 30 days |
| Requirement for Surgery Within 72 Hours | | Within 72 hours |
| Requirement for Surgery Within 30 Days | | Within 30 days |
| Requirement for Endoscopic Re-treatment Within 72 Hours | | Within 72 hours |
| Requirement for Endoscopic Re-treatment Within 30 Days | | Within 30 days |
| Number of Blood Units Transfused Within 72 Hours | | Within 72 hours |
| Number of Blood Units Transfused Within 30 Days | | within 30 days |
| Number of Days Hospitalized Due to Rebleeding During the 30-day Treatment Period | | Within 30 days |
|
||
NCT02161796
|
A Study to Evaluate the Dose-proportionality and Effects of FG-4592 in Healthy Young and Elderly Male and Female Subjects
|
This study evaluates the concentration of FG-4592 in the blood over a certain period after the intake of different doses, and assesses the effects, the safety and the tolerability of the study drug in healthy young and elderly male and female subjects.~On Day 1 of each of 4 periods subjects receive different single doses of FG-4592 or a placebo, depending on the treatment sequence to which they are randomized. For each period the subjects remain in the clinic for 6 days (Days -2 to 4). They are discharged after all assessments are completed on Day 4 of each period, and return for an End of Study visit (ESV) between 5 and 9 days after the last assessment of Period 4.
|
In this study eligible subjects reside in the clinic for 4 periods of 6 days (Day -2 through Day 4). Screening takes place from Day -23 through Day -3. Subjects are admitted to the clinic on Day -2 of Period 1. Within each cohort (young and elderly subjects), subjects are randomized to one of 24 treatment sequences of 4 treatment options (3 different doses of FG-4592 and placebo) and 4 periods.~On Day 1 of each period, subjects receive a single oral dose of FG-4592 or placebo followed by a 72-hour evaluation period. Subjects are discharged on Day 4, if there are no medical reasons for a prolonged stay. Each period is separated by a wash-out period of at least 10 days between dosing on Day 1 of the previous period and dosing on Day 1 of the following period. The subjects return for an end-of-study visit (ESV) 5-9 days after the last assessment of Period 4 (or after early withdrawal).~Plasma and urine samples are collected for pharmacokinetic (PK) and pharmacodynamic (PD) assessments. Safety assessments are performed throughout the study.
|
A Phase 1, Double-blind, Randomized, Placebo-controlled, 4-way Crossover Study to Evaluate the Dose-proportionality and Pharmacokinetics of FG-4592 in Healthy Young and Elderly Male and Female Subjects
|
PK for FG-4592, Healthy Subjects
|
* Drug: FG-4592
* Drug: Placebo
|
Inclusion Criteria:~YOUNG: Subject is a healthy young male or a healthy female subject aged 18 to 45 years of age inclusive~ELDERLY: Subject is a healthy elderly male or female subject aged 65 or above~Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control~Male subject must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration~Female subject must be either of non-childbearing potential or, if of childbearing potential, must have a negative pregnancy test at screening and Day -2 and must use 2 forms of birth control~Female subject must not be breastfeeding at screening or during the study period and for 28 days after the final study drug administration~Female subject must not donate ova starting at screening and throughout the study period and for 28 days after the final study drug administration~Exclusion Criteria:~Female subject who has been pregnant within 6 months before screening or breastfeeding within 3 months before screening~Subject used grapefruit, grapefruit juice (more than 3 x 200 mL) or orange marmalade (more than 3 times) in the week prior to admission to the clinic until ESV~The subject is a vulnerable subject
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK after a single dose of FG-4592 measured by area under the concentration-time curve from the time of dosing extrapolated to time infinity (AUCinf), | | Days 1- 4 (all periods) |
| PK after a single dose of FG-4592 measured by maximum concentration (Cmax) | | Days 1- 4 (all periods) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK of FG-4592 in plasma | area under the concentration-time curve (AUC) from time point 0 to time point 24 hours (AUC0-24h), unbound AUC from time point 0 to time point 24 hours (AUC0-24h,u), AUC from the time of dosing to the last measurable concentration (Clast) (AUClast), unbound AUC from the time of dosing to Clast (AUClast,u), unbound AUC extrapolated to infinity (AUCinf,u), maximum unbound plasma concentration (Cmax,u), apparent total body clearance after extra-vascular dosing (CL/F), unbound CL/F (CLu/F), fraction unbound (fu), time interval between the time of dosing and the first measurable concentration above LOQ in Plasma (tlag), time of the maximum concentration (tmax), terminal elimination half-life (t1/2), apparent volume of distribution during the terminal elimination phase after single extravascular dosing (Vz/F), unbound Vz/F (Vz,u/F) | Days 1 - 4 (all periods) |
| PK of FG-4592 in urine | renal clearance (CLR), unbound CLR (CLR,u), CLR from time point 0 to 24 hours (CLR,0-24h), unbound CLR,0-24h (CLR,0-24h,u), cumulative amount of drug excreted unchanged into urine, from time of dosing extrapolated to time infinity (Aeinf), percent of drug excreted unchanged into urine from time of dosing extrapolated to time infinity in percent of dose (Aeinf%), cumulative amount of drug excreted unchanged into urine, from time of dosing up to the collection time of the last measurable concentration (Aelast), percent of drug excreted into urine (Aelast) from time of dosing up to the collection time of the last measurable concentration in percent of dose (Aelast%), cumulative amount of drug excreted unchanged into urine, from time of dosing up to the collection time of 24 hours (Ae0-24h), Ae0-24h in percent of dose (Ae0-24h%) | Days 1 - 4 (all periods) |
| Plasma concentration of EPO, VEGF, reticulocytes and hepcidin | EPO(erythropoietin), VEGF(vascular endothelial growth factor) | Days 1 - 4 (all periods) |
| Safety and tolerability of a single dose FG-4592 | AEs, resting vital signs, safety laboratory tests, 12-lead safety ECG, mean heart rate per hour for 24-hours | Screening to ESV (5-9 days after the last assessment of Period 4 (or after early withdrawal)) |
|
Phase 1, FG-4592, Age/gender comparison
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1: young male subjects<br>3x single dose of FG-4592 and a placebo | Drug: FG-4592<br>* Oral<br>* Other names: roxadustat;Drug: Placebo<br>* Oral<br>|
| Experimental: 2: young female subjects<br>3x single dose of FG-4592 and a placebo | Drug: FG-4592<br>* Oral<br>* Other names: roxadustat;Drug: Placebo<br>* Oral<br>|
| Experimental: 3: elderly male subjects<br>3x single dose of FG-4592 and a placebo | Drug: FG-4592<br>* Oral<br>* Other names: roxadustat;Drug: Placebo<br>* Oral<br>|
| Experimental: 4: elderly female subjects<br>3x single dose of FG-4592 and a placebo | Drug: FG-4592<br>* Oral<br>* Other names: roxadustat;Drug: Placebo<br>* Oral<br>|
|
A Study to Evaluate the Dose-proportionality and Effects of FG-4592 in Healthy Young and Elderly Male and Female Subjects
Study Overview
=================
Brief Summary
-----------------
This study evaluates the concentration of FG-4592 in the blood over a certain period after the intake of different doses, and assesses the effects, the safety and the tolerability of the study drug in healthy young and elderly male and female subjects. On Day 1 of each of 4 periods subjects receive different single doses of FG-4592 or a placebo, depending on the treatment sequence to which they are randomized. For each period the subjects remain in the clinic for 6 days (Days -2 to 4). They are discharged after all assessments are completed on Day 4 of each period, and return for an End of Study visit (ESV) between 5 and 9 days after the last assessment of Period 4.
Detailed Description
-----------------
In this study eligible subjects reside in the clinic for 4 periods of 6 days (Day -2 through Day 4). Screening takes place from Day -23 through Day -3. Subjects are admitted to the clinic on Day -2 of Period 1. Within each cohort (young and elderly subjects), subjects are randomized to one of 24 treatment sequences of 4 treatment options (3 different doses of FG-4592 and placebo) and 4 periods. On Day 1 of each period, subjects receive a single oral dose of FG-4592 or placebo followed by a 72-hour evaluation period. Subjects are discharged on Day 4, if there are no medical reasons for a prolonged stay. Each period is separated by a wash-out period of at least 10 days between dosing on Day 1 of the previous period and dosing on Day 1 of the following period. The subjects return for an end-of-study visit (ESV) 5-9 days after the last assessment of Period 4 (or after early withdrawal). Plasma and urine samples are collected for pharmacokinetic (PK) and pharmacodynamic (PD) assessments. Safety assessments are performed throughout the study.
Official Title
-----------------
A Phase 1, Double-blind, Randomized, Placebo-controlled, 4-way Crossover Study to Evaluate the Dose-proportionality and Pharmacokinetics of FG-4592 in Healthy Young and Elderly Male and Female Subjects
Conditions
-----------------
PK for FG-4592, Healthy Subjects
Intervention / Treatment
-----------------
* Drug: FG-4592
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: YOUNG: Subject is a healthy young male or a healthy female subject aged 18 to 45 years of age inclusive ELDERLY: Subject is a healthy elderly male or female subject aged 65 or above Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control Male subject must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration Female subject must be either of non-childbearing potential or, if of childbearing potential, must have a negative pregnancy test at screening and Day -2 and must use 2 forms of birth control Female subject must not be breastfeeding at screening or during the study period and for 28 days after the final study drug administration Female subject must not donate ova starting at screening and throughout the study period and for 28 days after the final study drug administration Exclusion Criteria: Female subject who has been pregnant within 6 months before screening or breastfeeding within 3 months before screening Subject used grapefruit, grapefruit juice (more than 3 x 200 mL) or orange marmalade (more than 3 times) in the week prior to admission to the clinic until ESV The subject is a vulnerable subject
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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1: young male subjects<br>3x single dose of FG-4592 and a placebo | Drug: FG-4592<br>* Oral<br>* Other names: roxadustat;Drug: Placebo<br>* Oral<br>|
| Experimental: 2: young female subjects<br>3x single dose of FG-4592 and a placebo | Drug: FG-4592<br>* Oral<br>* Other names: roxadustat;Drug: Placebo<br>* Oral<br>|
| Experimental: 3: elderly male subjects<br>3x single dose of FG-4592 and a placebo | Drug: FG-4592<br>* Oral<br>* Other names: roxadustat;Drug: Placebo<br>* Oral<br>|
| Experimental: 4: elderly female subjects<br>3x single dose of FG-4592 and a placebo | Drug: FG-4592<br>* Oral<br>* Other names: roxadustat;Drug: Placebo<br>* Oral<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK after a single dose of FG-4592 measured by area under the concentration-time curve from the time of dosing extrapolated to time infinity (AUCinf), | | Days 1- 4 (all periods) |
| PK after a single dose of FG-4592 measured by maximum concentration (Cmax) | | Days 1- 4 (all periods) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK of FG-4592 in plasma | area under the concentration-time curve (AUC) from time point 0 to time point 24 hours (AUC0-24h), unbound AUC from time point 0 to time point 24 hours (AUC0-24h,u), AUC from the time of dosing to the last measurable concentration (Clast) (AUClast), unbound AUC from the time of dosing to Clast (AUClast,u), unbound AUC extrapolated to infinity (AUCinf,u), maximum unbound plasma concentration (Cmax,u), apparent total body clearance after extra-vascular dosing (CL/F), unbound CL/F (CLu/F), fraction unbound (fu), time interval between the time of dosing and the first measurable concentration above LOQ in Plasma (tlag), time of the maximum concentration (tmax), terminal elimination half-life (t1/2), apparent volume of distribution during the terminal elimination phase after single extravascular dosing (Vz/F), unbound Vz/F (Vz,u/F) | Days 1 - 4 (all periods) |
| PK of FG-4592 in urine | renal clearance (CLR), unbound CLR (CLR,u), CLR from time point 0 to 24 hours (CLR,0-24h), unbound CLR,0-24h (CLR,0-24h,u), cumulative amount of drug excreted unchanged into urine, from time of dosing extrapolated to time infinity (Aeinf), percent of drug excreted unchanged into urine from time of dosing extrapolated to time infinity in percent of dose (Aeinf%), cumulative amount of drug excreted unchanged into urine, from time of dosing up to the collection time of the last measurable concentration (Aelast), percent of drug excreted into urine (Aelast) from time of dosing up to the collection time of the last measurable concentration in percent of dose (Aelast%), cumulative amount of drug excreted unchanged into urine, from time of dosing up to the collection time of 24 hours (Ae0-24h), Ae0-24h in percent of dose (Ae0-24h%) | Days 1 - 4 (all periods) |
| Plasma concentration of EPO, VEGF, reticulocytes and hepcidin | EPO(erythropoietin), VEGF(vascular endothelial growth factor) | Days 1 - 4 (all periods) |
| Safety and tolerability of a single dose FG-4592 | AEs, resting vital signs, safety laboratory tests, 12-lead safety ECG, mean heart rate per hour for 24-hours | Screening to ESV (5-9 days after the last assessment of Period 4 (or after early withdrawal)) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Phase 1, FG-4592, Age/gender comparison
|
|
NCT03529201
|
QLB After Nephrectomy
|
Oxycodone consumption and postoperative pain intensity in patients undergoing nephrectomy procedures. Of all study participants, 50% will obtain quadratus lumborum block (QLB).
|
Patients undergoing nephrectomy procedures will be allocated to one of the study arms. At the end of an operation, still under general anesthesia, 50% patients will obtain QLB with ropivacaine.~Ultrasound-guided QLB will be performed on the side of surgery with 0.375% ropivacaine solution (0.2 mL per kg).~Every patient will get patient-controlled analgesia pump with oxycodone in the postoperative period.~Postoperative pain will be measured with VAS (visual-analogue scale) 2, 4, 8, 12 and 24 hours after the end of the operation. 24 -hours period.~At the 1, 3, 6 months patients will be interviewed by phone to assess neuropathic pain. Neuropathic Pain Symptom Inventory (NPSI) will be used.
|
Effectiveness of Quadratus Lumborum Block After Nephrectomy
|
Pain, Postoperative, Chronic Postoperative Pain
|
* Procedure: QLB
* Device: PCA
* Procedure: GA
* Drug: Oxycodone
* Drug: Sevoflurane
* Drug: Fentanyl
* Drug: Rocuronium
|
Inclusion Criteria:~obtained consent~nephrectomy procedure~Exclusion Criteria:~coagulopathy allergy to local anesthetics depression, antidepressant drugs treatment epilepsy usage of painkiller before surgery addiction to alcohol or recreational drugs
|
18 Years
|
80 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomly allocated to one of the study arms: QLB or control group.
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total consumption of oxycodone | Overall use of oxycodone administered by PCA pump will be assessed. | 24 hours after the end of surgery. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity | Pain intensity measured on VAS scale at the 2, 4, 8, 12, 24 hours. VAS in milimmeters. Minimum value 0, maximum 100. Less better - less severe pain. 0 no pain at all. | 24 hours after the end of surgery |
| Chronic pain | Chronic pain occurrence assessed with Neuropathic Pain Symptom Inventory (NPSI) 10 descriptive variables, each one from 0 to 10. 0 means no pain. 10 very high chance of occurrence of neuropathic pain. | 6 months after the surgery |
|
Fentanyl, Oxycodone, Sevoflurane, Rocuronium, Analgesics, Opioid, Narcotics, Central Nervous System Depressants, Physiological Effects of Drugs, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Adjuvants, Anesthesia, Anesthetics, Intravenous, Anesthetics, General, Anesthetics, Platelet Aggregation Inhibitors, Anesthetics, Inhalation, Neuromuscular Nondepolarizing Agents, Neuromuscular Blocking Agents, Neuromuscular Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QLB<br>At the end of surgery, QLB with ropivacaine will be done on the side of the operation. | Procedure: QLB<br>* On the side of the surgery, QLB with 0.375% ropivacaine (0.2 mL/kg)<br>Device: PCA<br>* Patient-controlled analgesia<br>Procedure: GA<br>* General anesthesia<br>Drug: Oxycodone<br>* administered by PCA<br>Drug: Sevoflurane<br>* Inhalational anesthetic during GA<br>Drug: Fentanyl<br>* painkiller during GA<br>Drug: Rocuronium<br>* muscle relaxant during GA<br>|
| Experimental: Control<br>Standard care. No regional blocks. | Device: PCA<br>* Patient-controlled analgesia<br>Procedure: GA<br>* General anesthesia<br>Drug: Oxycodone<br>* administered by PCA<br>Drug: Sevoflurane<br>* Inhalational anesthetic during GA<br>Drug: Fentanyl<br>* painkiller during GA<br>Drug: Rocuronium<br>* muscle relaxant during GA<br>|
|
QLB After Nephrectomy
Study Overview
=================
Brief Summary
-----------------
Oxycodone consumption and postoperative pain intensity in patients undergoing nephrectomy procedures. Of all study participants, 50% will obtain quadratus lumborum block (QLB).
Detailed Description
-----------------
Patients undergoing nephrectomy procedures will be allocated to one of the study arms. At the end of an operation, still under general anesthesia, 50% patients will obtain QLB with ropivacaine. Ultrasound-guided QLB will be performed on the side of surgery with 0.375% ropivacaine solution (0.2 mL per kg). Every patient will get patient-controlled analgesia pump with oxycodone in the postoperative period. Postoperative pain will be measured with VAS (visual-analogue scale) 2, 4, 8, 12 and 24 hours after the end of the operation. 24 -hours period. At the 1, 3, 6 months patients will be interviewed by phone to assess neuropathic pain. Neuropathic Pain Symptom Inventory (NPSI) will be used.
Official Title
-----------------
Effectiveness of Quadratus Lumborum Block After Nephrectomy
Conditions
-----------------
Pain, Postoperative, Chronic Postoperative Pain
Intervention / Treatment
-----------------
* Procedure: QLB
* Device: PCA
* Procedure: GA
* Drug: Oxycodone
* Drug: Sevoflurane
* Drug: Fentanyl
* Drug: Rocuronium
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: obtained consent nephrectomy procedure Exclusion Criteria: coagulopathy allergy to local anesthetics depression, antidepressant drugs treatment epilepsy usage of painkiller before surgery addiction to alcohol or recreational drugs
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: Patients will be randomly allocated to one of the study arms: QLB or control group.
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QLB<br>At the end of surgery, QLB with ropivacaine will be done on the side of the operation. | Procedure: QLB<br>* On the side of the surgery, QLB with 0.375% ropivacaine (0.2 mL/kg)<br>Device: PCA<br>* Patient-controlled analgesia<br>Procedure: GA<br>* General anesthesia<br>Drug: Oxycodone<br>* administered by PCA<br>Drug: Sevoflurane<br>* Inhalational anesthetic during GA<br>Drug: Fentanyl<br>* painkiller during GA<br>Drug: Rocuronium<br>* muscle relaxant during GA<br>|
| Experimental: Control<br>Standard care. No regional blocks. | Device: PCA<br>* Patient-controlled analgesia<br>Procedure: GA<br>* General anesthesia<br>Drug: Oxycodone<br>* administered by PCA<br>Drug: Sevoflurane<br>* Inhalational anesthetic during GA<br>Drug: Fentanyl<br>* painkiller during GA<br>Drug: Rocuronium<br>* muscle relaxant during GA<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total consumption of oxycodone | Overall use of oxycodone administered by PCA pump will be assessed. | 24 hours after the end of surgery. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity | Pain intensity measured on VAS scale at the 2, 4, 8, 12, 24 hours. VAS in milimmeters. Minimum value 0, maximum 100. Less better - less severe pain. 0 no pain at all. | 24 hours after the end of surgery |
| Chronic pain | Chronic pain occurrence assessed with Neuropathic Pain Symptom Inventory (NPSI) 10 descriptive variables, each one from 0 to 10. 0 means no pain. 10 very high chance of occurrence of neuropathic pain. | 6 months after the surgery |
|
|
NCT04432259
|
Oral Dexamethasone as an Intervention for Postoperative Pain and Nausea Management in Total Knee Arthroplasty
|
This study aims to determine if oral dexamethasone provides clinically significant improvement in postoperative outcomes, specifically nausea and pain scores.
|
Protocols in perioperative pain management during total joint arthroplasty (TJA) have contributed to early discharge after surgery. As practices move to favor ambulatory surgery in total joint arthroplasty changes must be made to postoperative pain and nausea management. Spinal anesthesia has been essential in managing associated ambulatory TJA, however, nausea and vomiting are known detrimental side effects. The use of systemic steroids has also been shown in the literature to reduce pain scores, length of stay, the need for antiemetics, and increase the distance of ambulation without increasing the rate of surgical site infection or prosthetic joint infection. As more same-day total joint replacement is incorporated into practice, an oral alternative may prove beneficial.
|
Oral Dexamethasone as an Intervention for Postoperative Pain and Nausea Management in Total Knee Arthroplasty
|
Arthritis Knee, Postoperative Nausea, Postoperative Pain
|
* Drug: Dexamethasone
* Drug: Placebo
|
Inclusion Criteria:~adult patients age 18 and older who will be undergoing joint replacement~Exclusion Criteria:~Patients with uncontrolled diabetes ( HbA1C, >7.5%), impaired hepatic function (Child class, >B), impaired renal failure (Glomerular filtration rate <60 mL/min/1.73 m2), chronic narcotic use, alcohol and/or opioid dependence, patients with a known adverse reaction to corticosteroids, and patients unable to give informed consent.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomly assigned to one of two groups, treatment or no treatment. Randomizations will be balanced at random accrual points.
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative Pain | Postoperative pain will be collected via visual analog scores | 3 weeks following surgery |
| Postoperative Nausea | Postoperative Nausea will be collected via visual analog scores | 3 weeks following surgery |
| Opioid Consumption | Opioid consumption will be recorded by participant in assigned journal, morphine equivalence will be recorded | 6 months |
| Antiemetic Consumption | | 6 months |
| Episodes of Nausea | | 3 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative complications | Incidence of surgical site infection, acute prosthetic joint infection | 6 months |
| Patient-reported outcome scores (PROMS) | | 6 months |
| Knee Injury and Osteoarthritis Outcome Score (KOOS) | | 6 months |
|
Dexamethasone, Anti-Inflammatory Agents, Antiemetics, Autonomic Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Gastrointestinal Agents, Glucocorticoids, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Antineoplastic Agents, Hormonal, Antineoplastic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm B: Oral Dexamethasone<br>Participants will be randomly assigned to receive 4 mg Oral Dexamethasone taken twice daily for 4 days | Drug: Dexamethasone<br>* 4 mg bid for 4 days<br>|
| Placebo Comparator: Arm A: Placebo<br>Participants will be randomly assigned to receive 4 mg placebo taken twice daily for 4 days | Drug: Placebo<br>* oral placebo<br>|
|
Oral Dexamethasone as an Intervention for Postoperative Pain and Nausea Management in Total Knee Arthroplasty
Study Overview
=================
Brief Summary
-----------------
This study aims to determine if oral dexamethasone provides clinically significant improvement in postoperative outcomes, specifically nausea and pain scores.
Detailed Description
-----------------
Protocols in perioperative pain management during total joint arthroplasty (TJA) have contributed to early discharge after surgery. As practices move to favor ambulatory surgery in total joint arthroplasty changes must be made to postoperative pain and nausea management. Spinal anesthesia has been essential in managing associated ambulatory TJA, however, nausea and vomiting are known detrimental side effects. The use of systemic steroids has also been shown in the literature to reduce pain scores, length of stay, the need for antiemetics, and increase the distance of ambulation without increasing the rate of surgical site infection or prosthetic joint infection. As more same-day total joint replacement is incorporated into practice, an oral alternative may prove beneficial.
Official Title
-----------------
Oral Dexamethasone as an Intervention for Postoperative Pain and Nausea Management in Total Knee Arthroplasty
Conditions
-----------------
Arthritis Knee, Postoperative Nausea, Postoperative Pain
Intervention / Treatment
-----------------
* Drug: Dexamethasone
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: adult patients age 18 and older who will be undergoing joint replacement Exclusion Criteria: Patients with uncontrolled diabetes ( HbA1C, >7.5%), impaired hepatic function (Child class, >B), impaired renal failure (Glomerular filtration rate <60 mL/min/1.73 m2), chronic narcotic use, alcohol and/or opioid dependence, patients with a known adverse reaction to corticosteroids, and patients unable to give informed consent.
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: Participants will be randomly assigned to one of two groups, treatment or no treatment. Randomizations will be balanced at random accrual points.
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm B: Oral Dexamethasone<br>Participants will be randomly assigned to receive 4 mg Oral Dexamethasone taken twice daily for 4 days | Drug: Dexamethasone<br>* 4 mg bid for 4 days<br>|
| Placebo Comparator: Arm A: Placebo<br>Participants will be randomly assigned to receive 4 mg placebo taken twice daily for 4 days | Drug: Placebo<br>* oral placebo<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative Pain | Postoperative pain will be collected via visual analog scores | 3 weeks following surgery |
| Postoperative Nausea | Postoperative Nausea will be collected via visual analog scores | 3 weeks following surgery |
| Opioid Consumption | Opioid consumption will be recorded by participant in assigned journal, morphine equivalence will be recorded | 6 months |
| Antiemetic Consumption | | 6 months |
| Episodes of Nausea | | 3 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative complications | Incidence of surgical site infection, acute prosthetic joint infection | 6 months |
| Patient-reported outcome scores (PROMS) | | 6 months |
| Knee Injury and Osteoarthritis Outcome Score (KOOS) | | 6 months |
|
|
NCT01074489
|
Challenging the Gold Standard: Pilot Study Comparing Continuous Glucose Monitoring System (CGMS), Capillary Glucose Monitors and 3 Hour Glucose Tolerance Test (GTT) to Diagnose Gestational Diabetes Mellitus (GDM)
|
The purpose of this research study is to compare 3 methods of measuring blood glucose (blood sugar) levels to see if the finger-stick method or the continuous glucose monitoring system is better than or as good as the 3 hour glucose tolerance test (GTT) for the diagnosis of gestational diabetes.
|
The rate of gestational diabetes and fetal macrosomia is increasing. Moreover, it appears that many macrosomic infants are born to non-diabetic mothers. However, this presents the question of whether our current accepted means of diagnosis is reflecting the true prevalence of GDM. The 3-hour GTT measures glycemic control over a limited period of time. A more prolonged period of monitoring makes more physiologic sense, as it would paint a picture of a patient's overall trend before a diagnosis can be confirmed or excluded. Given the ability of the CGMS and capillary glucose monitor to follow glycemic trends over an extended time period, these methods may prove more effective at identifying patients with abnormal glucose tolerance. As these modalities test the patients in their native environments, the effect of dietary changes prior to the testing period may be minimized, potentially providing an more accurate assessment of abnormal glucose utilization. Furthermore, both modalities should be more cost-effective than the 3- hour GTT.
|
Challenging the Gold Standard: A Pilot Study Comparing CGMS and Capillary Glucose Monitors Versus 3 Hour GTT to Diagnose Gestational Diabetes Mellitus
|
Diabetes, Gestational
|
Inclusion Criteria:~Pregnant patients seen in the Center for Women's Health at University Hospital in Cincinnati, Ohio between 24-28 weeks gestation~One hour 50-g Glucose Challenge Test (GCT) value greater than 130 mg/dL.~Exclusion Criteria:~Patients with known diabetes mellitus~Patients receiving steroids or oral terbutaline therapy~Patients entering prenatal care later than 20 weeks gestation
|
18 Years
|
50 Years
|
Female
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood glucose levels | | Over 1 week |
|
GDM, Gestational Diabetes, GTT, CGMS
|
Diabetes, Gestational, Diabetes Mellitus, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Pregnancy Complications, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases
|
Challenging the Gold Standard: Pilot Study Comparing Continuous Glucose Monitoring System (CGMS), Capillary Glucose Monitors and 3 Hour Glucose Tolerance Test (GTT) to Diagnose Gestational Diabetes Mellitus (GDM)
Study Overview
=================
Brief Summary
-----------------
The purpose of this research study is to compare 3 methods of measuring blood glucose (blood sugar) levels to see if the finger-stick method or the continuous glucose monitoring system is better than or as good as the 3 hour glucose tolerance test (GTT) for the diagnosis of gestational diabetes.
Detailed Description
-----------------
The rate of gestational diabetes and fetal macrosomia is increasing. Moreover, it appears that many macrosomic infants are born to non-diabetic mothers. However, this presents the question of whether our current accepted means of diagnosis is reflecting the true prevalence of GDM. The 3-hour GTT measures glycemic control over a limited period of time. A more prolonged period of monitoring makes more physiologic sense, as it would paint a picture of a patient's overall trend before a diagnosis can be confirmed or excluded. Given the ability of the CGMS and capillary glucose monitor to follow glycemic trends over an extended time period, these methods may prove more effective at identifying patients with abnormal glucose tolerance. As these modalities test the patients in their native environments, the effect of dietary changes prior to the testing period may be minimized, potentially providing an more accurate assessment of abnormal glucose utilization. Furthermore, both modalities should be more cost-effective than the 3- hour GTT.
Official Title
-----------------
Challenging the Gold Standard: A Pilot Study Comparing CGMS and Capillary Glucose Monitors Versus 3 Hour GTT to Diagnose Gestational Diabetes Mellitus
Conditions
-----------------
Diabetes, Gestational
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pregnant patients seen in the Center for Women's Health at University Hospital in Cincinnati, Ohio between 24-28 weeks gestation One hour 50-g Glucose Challenge Test (GCT) value greater than 130 mg/dL. Exclusion Criteria: Patients with known diabetes mellitus Patients receiving steroids or oral terbutaline therapy Patients entering prenatal care later than 20 weeks gestation
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?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood glucose levels | | Over 1 week |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
GDM, Gestational Diabetes, GTT, CGMS
|
||||
NCT05251272
|
A Combined Model Based on Spleen Stiffness, Liver Stiffness and Platelets for Assessing Portal Hypertension in Compensated Cirrhosis (CHESS2202)
|
Portal hypertension contributed to the main complications of liver cirrhosis. Currently, hepatic venous pressure gradient (HVPG) was the reference standard for evaluating portal pressure in patients with cirrhosis. However, the practice of HVPG is limited to require the extensive experience and highly specialized centers. In recent years, non-invasive methods were proposed to predict the degree of cirrhotic portal hypertension. Of them, liver stiffness measured by transient elastography had shown good performance for predicting clinically significant portal hypertension. However, liver stiffness only has a good correlation with portal pressure in the early stage of portal hypertension (HVPG<10 mmHg), because liver fibrosis is the main cause of portal hypertension in this period. In the stage of clinically significant portal hypertension (CSPH) (HVPG≥10 mmHg), increased portal vein inflow due to splanchnic vasodilation and hyperdynamic circulation, spleen stiffness may have a better correlation with HVPG than that of liver stiffness. Several studies have explored the combination of liver stiffness, platelet count and spleen stiffness for varices screening. However, there are few studies to report the above parameters for assessing CSPH and unneeded HVPG avoiding.~Since the spleen was stiffer than the liver, the current vibration-controlled transient elastography examination is dedicated to the liver, rather than the spleen. Very recently, a novel spleen-dedicated stiffness measured by transient elastography was proposed. The prospective, multicenter study aims to add spleen stiffness as a supplementary parameter to establish new criteria for identify CSPH in patients with compensated cirrhosis, with a dedicated probe on transient elastography equipment to assess spleen stiffness and liver stiffness, and further develop a novel model based on spleen stiffness for predicting the liver decompensation in patients with compensated cirrhosis.
|
Portal hypertension contributed to the main complications of liver cirrhosis. Currently, hepatic venous pressure gradient (HVPG) was the reference standard for evaluating portal pressure in patients with cirrhosis. However, the practice of HVPG is limited to require the extensive experience and highly specialized centers. In recent years, non-invasive methods were proposed to predict the degree of cirrhotic portal hypertension. Of them, liver stiffness measured by transient elastography had shown good performance for predicting clinically significant portal hypertension. However, liver stiffness only has a good correlation with portal pressure in the early stage of portal hypertension (HVPG<10 mmHg), because liver fibrosis is the main cause of portal hypertension in this period. In the stage of clinically significant portal hypertension (CSPH) (HVPG≥10 mmHg), increased portal vein inflow due to splanchnic vasodilation and hyperdynamic circulation, spleen stiffness may have a better correlation with HVPG than that of liver stiffness. Several studies have explored the combination of liver stiffness, platelet count and spleen stiffness for varices screening. However, there are few studies to report the above parameters for assessing CSPH and unneeded HVPG avoiding.~Since the spleen was stiffer than the liver, the current vibration-controlled transient elastography examination is dedicated to the liver, rather than the spleen. Very recently, a novel spleen-dedicated stiffness measured by transient elastography was proposed. The prospective, multicenter study (leaded by The First Hospital of Lanzhou University and Shulan (Hangzhou) Hospital) aims to add spleen stiffness as a supplementary parameter to establish new criteria for identify CSPH in patients with compensated cirrhosis, with a dedicated probe on transient elastography equipment to assess spleen stiffness and liver stiffness, and further develop a novel model based on spleen stiffness for predicting the liver decompensation in patients with compensated cirrhosis.
|
A Combined Model Based on Spleen Stiffness, Liver Stiffness and Platelets for Assessing Portal Hypertension in Compensated Cirrhosis: A Prospective, Multicenter Study (CHESS2202)
|
Portal Hypertension
|
* Diagnostic Test: Hepatic venous pressure gradient
|
Inclusion Criteria:~age above or equal to 18-year-old~fulfilled diagnosis of compensated cirrhosis based on radiological, histological features of liver cirrhosis and clinical manifestations~without decompensated events (e.g. ascites, bleeding, or overt encephalopathy)~with spleen stiffness and liver stiffness by a dedicated probe on transient elastography examination and platelet count measurement~with HVPG measurement~signed informed consent~Exclusion Criteria:~non-cirrhotic portal hypertension~accepted primary prevention (non-selective beta blockers or endoscopic variceal ligation)~lactation or pregnancy~suspicious or confirmed hepatocellular carcinoma~asplenia or splenectomy~incomplete clinical information
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy of a new model based on spleen stiffness (kPa), liver stiffness (kPa) or platelets (/L) for assessing portal hypertension in compensated cirrhosis. | In HVPG (mmHg) as reference method in evaluating portal pressure measured by intervention specialist, to develop a new model based on spleen stiffness (kPa), liver stiffness (kPa) or platelets (/L) and evaluate the accuracy in diagnosing portal hypertension.~Spleen stiffness (kPa) and liver stiffness (kPa) are measured by transient elastography with a dedicated probe. | 1 years |
|
compensated cirrhosis, spleen stiffness, liver stiffness, portal hypertension, hepatic venous pressure gradient
|
Vascular Diseases, Fibrosis, Hypertension, Hypertension, Portal, Cardiovascular Diseases, Pathologic Processes, Liver Diseases, Digestive System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Training cohort<br>Patients were fulfilled diagnosis of compensated cirrhosis based on radiological, histological features of liver cirrhosis and clinical manifestations. | Diagnostic Test: Hepatic venous pressure gradient<br>* All patients underwent measurement of HVPG under local anesthesia.<br>|
| Validation cohort<br>Patients were fulfilled diagnosis of compensated cirrhosis based on radiological, histological features of liver cirrhosis and clinical manifestations. | Diagnostic Test: Hepatic venous pressure gradient<br>* All patients underwent measurement of HVPG under local anesthesia.<br>|
|
A Combined Model Based on Spleen Stiffness, Liver Stiffness and Platelets for Assessing Portal Hypertension in Compensated Cirrhosis (CHESS2202)
Study Overview
=================
Brief Summary
-----------------
Portal hypertension contributed to the main complications of liver cirrhosis. Currently, hepatic venous pressure gradient (HVPG) was the reference standard for evaluating portal pressure in patients with cirrhosis. However, the practice of HVPG is limited to require the extensive experience and highly specialized centers. In recent years, non-invasive methods were proposed to predict the degree of cirrhotic portal hypertension. Of them, liver stiffness measured by transient elastography had shown good performance for predicting clinically significant portal hypertension. However, liver stiffness only has a good correlation with portal pressure in the early stage of portal hypertension (HVPG<10 mmHg), because liver fibrosis is the main cause of portal hypertension in this period. In the stage of clinically significant portal hypertension (CSPH) (HVPG≥10 mmHg), increased portal vein inflow due to splanchnic vasodilation and hyperdynamic circulation, spleen stiffness may have a better correlation with HVPG than that of liver stiffness. Several studies have explored the combination of liver stiffness, platelet count and spleen stiffness for varices screening. However, there are few studies to report the above parameters for assessing CSPH and unneeded HVPG avoiding. Since the spleen was stiffer than the liver, the current vibration-controlled transient elastography examination is dedicated to the liver, rather than the spleen. Very recently, a novel spleen-dedicated stiffness measured by transient elastography was proposed. The prospective, multicenter study aims to add spleen stiffness as a supplementary parameter to establish new criteria for identify CSPH in patients with compensated cirrhosis, with a dedicated probe on transient elastography equipment to assess spleen stiffness and liver stiffness, and further develop a novel model based on spleen stiffness for predicting the liver decompensation in patients with compensated cirrhosis.
Detailed Description
-----------------
Portal hypertension contributed to the main complications of liver cirrhosis. Currently, hepatic venous pressure gradient (HVPG) was the reference standard for evaluating portal pressure in patients with cirrhosis. However, the practice of HVPG is limited to require the extensive experience and highly specialized centers. In recent years, non-invasive methods were proposed to predict the degree of cirrhotic portal hypertension. Of them, liver stiffness measured by transient elastography had shown good performance for predicting clinically significant portal hypertension. However, liver stiffness only has a good correlation with portal pressure in the early stage of portal hypertension (HVPG<10 mmHg), because liver fibrosis is the main cause of portal hypertension in this period. In the stage of clinically significant portal hypertension (CSPH) (HVPG≥10 mmHg), increased portal vein inflow due to splanchnic vasodilation and hyperdynamic circulation, spleen stiffness may have a better correlation with HVPG than that of liver stiffness. Several studies have explored the combination of liver stiffness, platelet count and spleen stiffness for varices screening. However, there are few studies to report the above parameters for assessing CSPH and unneeded HVPG avoiding. Since the spleen was stiffer than the liver, the current vibration-controlled transient elastography examination is dedicated to the liver, rather than the spleen. Very recently, a novel spleen-dedicated stiffness measured by transient elastography was proposed. The prospective, multicenter study (leaded by The First Hospital of Lanzhou University and Shulan (Hangzhou) Hospital) aims to add spleen stiffness as a supplementary parameter to establish new criteria for identify CSPH in patients with compensated cirrhosis, with a dedicated probe on transient elastography equipment to assess spleen stiffness and liver stiffness, and further develop a novel model based on spleen stiffness for predicting the liver decompensation in patients with compensated cirrhosis.
Official Title
-----------------
A Combined Model Based on Spleen Stiffness, Liver Stiffness and Platelets for Assessing Portal Hypertension in Compensated Cirrhosis: A Prospective, Multicenter Study (CHESS2202)
Conditions
-----------------
Portal Hypertension
Intervention / Treatment
-----------------
* Diagnostic Test: Hepatic venous pressure gradient
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: age above or equal to 18-year-old fulfilled diagnosis of compensated cirrhosis based on radiological, histological features of liver cirrhosis and clinical manifestations without decompensated events (e.g. ascites, bleeding, or overt encephalopathy) with spleen stiffness and liver stiffness by a dedicated probe on transient elastography examination and platelet count measurement with HVPG measurement signed informed consent Exclusion Criteria: non-cirrhotic portal hypertension accepted primary prevention (non-selective beta blockers or endoscopic variceal ligation) lactation or pregnancy suspicious or confirmed hepatocellular carcinoma asplenia or splenectomy incomplete clinical information
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 |
| --- | --- |
| Training cohort<br>Patients were fulfilled diagnosis of compensated cirrhosis based on radiological, histological features of liver cirrhosis and clinical manifestations. | Diagnostic Test: Hepatic venous pressure gradient<br>* All patients underwent measurement of HVPG under local anesthesia.<br>|
| Validation cohort<br>Patients were fulfilled diagnosis of compensated cirrhosis based on radiological, histological features of liver cirrhosis and clinical manifestations. | Diagnostic Test: Hepatic venous pressure gradient<br>* All patients underwent measurement of HVPG under local anesthesia.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy of a new model based on spleen stiffness (kPa), liver stiffness (kPa) or platelets (/L) for assessing portal hypertension in compensated cirrhosis. | In HVPG (mmHg) as reference method in evaluating portal pressure measured by intervention specialist, to develop a new model based on spleen stiffness (kPa), liver stiffness (kPa) or platelets (/L) and evaluate the accuracy in diagnosing portal hypertension. Spleen stiffness (kPa) and liver stiffness (kPa) are measured by transient elastography with a dedicated probe. | 1 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
compensated cirrhosis, spleen stiffness, liver stiffness, portal hypertension, hepatic venous pressure gradient
|
||
NCT05641155
|
A Feasibility Study Evaluating the Performance of Focused Multipolar Stimulation and Sound Coding in Adults.
|
The purpose of this early feasibility study is to explore several facets of hearing performance that may show improvements for alternative modes of stimulation compared to Monopolar (MP stimulation) in cochlear implant recipients. This study will iteratively evaluate different parameter sets that intend to maximize hearing performance benefits within technical requirements. This study is exploratory in nature and will achieve its objectives through ongoing review and adjustment of device parameters and fitting
|
Alternative modes of stimulation will be investigated that may improve spectral resolution through reduced cochlear spread of excitation and in turn provide enhanced speech perception and real-world clinical benefits over MP stimulation. The purpose of this study is to balance the clinical improvements of alternative modes of stimulation with technical and usability requirements for power usage. By iteratively evaluating different sets of stimulation and sound coding parameters, this study will determine device settings and fitting techniques. Measures of speech recognition, listening effort, neural responses, electrode placement, battery life, and usability acceptance will be obtained to evaluate clinical benefits
|
An Early Feasibility, Prospective, Exploratory Study Evaluating the Performance of Focused Multipolar Stimulation and Sound Coding Enhancements in Adult Cochlear Implant Recipients (SASC).
|
Hearing Impairment, Sensorineural
|
* Device: Focused Multipolar Stimulation (FMS) strategy
|
Inclusion Criteria:~1) Candidate for unilateral cochlear implantation according to bilateral sensorineural hearing loss criteria, who has decided to proceed with implantation through routine processes.~a) Bilateral sensorineural hearing loss criteria for clinics in the United States: i) Ear to be implanted:~Moderate to profound sensorineural hearing loss, defined as a pure-tone average (PTA) (250 - 1000 Hz) ≥ 40 dB HL and a PTA (2000 - 8000 Hz) ≥ 65 dB HL~Aided word score ≤ 40% ii) Contralateral ear:~(1) PTA (500, 1000, 2000, and 4000 Hz) > 30 dB HL (2) Aided word score ≤ 80% b) Bilateral sensorineural hearing loss criteria for clinics in Belgium: i) Both ears:~PTA (500, 1000, 2000, and 4000 Hz) ≥ 70 dB HL for average of 3 out of 4 frequencies~Unaided phoneme score ≤ 50% on CVC in quiet at 70 dB SPL in free field~ABR peak ≥ 75 dB nHL~2) 18 years of age or older.~3) Fluent in the language used for speech testing.~4) Willing to comply with all investigational requirements.~5) Willing and able to provide written informed consent~-~Exclusion Criteria:~Previous or existing cochlear-implant recipient.~Severe or greater sensorineural hearing loss in the ear to be implanted prior to five years of age.~Duration of severe to profound hearing loss > 20 years in the ear to be implanted.~Ossification or other cochlear anomaly that might prevent complete insertion of the electrode array.~Diagnosis of auditory neuropathy.~Deafness due to lesions of the acoustic nerve or central auditory pathway.~Pregnant at the time of surgery.~Additional handicaps that would prevent or restrict participation in the audiological evaluations.~Unrealistic expectations on the part of the subject regarding the possible benefits, risks, and limitations that are inherent to the surgical procedure and prosthetic device.~Unable or unwilling to comply with the requirements of the clinical investigation as determined by the Investigator.~Investigator site personnel directly affiliated with this study and/or their immediate families; immediate family is defined as a spouse, parent, child, or sibling.~Cochlear employees or employees of Contract Research Organisations or contractors engaged by Cochlear for the purposes of this investigation.~Currently participating, or participated within the last 30 days, in another interventional clinical investigation/trial involving an investigational drug or device
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean difference across maximum map stimulation (C) levels | Mean difference across maps using alternative modes and sound coding parameters for the highest and average comfortable loudness level (clinical unit) (C-level). | 10 weeks |
| Mean difference across Spectral resolution (QSMD) | Mean difference across maps using alternative modes and sound coding parameters for spectral resolution (% correct) (QSMD - Quick spectral modulation detection) | 10 weeks |
| Mean difference across phoneme discrimination (LIT- Language independent test) | Mean difference across maps using alternative modes and sound coding parameters for phoneme discrimination (% correct) (LIT - Language independent test) | 10 weeks |
|
Hearing Loss, Deafness, Hearing Loss, Sensorineural, Hearing Disorders, Ear Diseases, Otorhinolaryngologic Diseases, Sensation Disorders, Neurologic Manifestations, Nervous System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adult Cochlear implant<br>Adult cochlear implant recipients receiving different combinations of alternative modes and, sound coding parameters | Device: Focused Multipolar Stimulation (FMS) strategy<br>* Adult cochlear implant recipients receiving different combinations of alternative modes and, sound coding parameters.<br>|
|
A Feasibility Study Evaluating the Performance of Focused Multipolar Stimulation and Sound Coding in Adults.
Study Overview
=================
Brief Summary
-----------------
The purpose of this early feasibility study is to explore several facets of hearing performance that may show improvements for alternative modes of stimulation compared to Monopolar (MP stimulation) in cochlear implant recipients. This study will iteratively evaluate different parameter sets that intend to maximize hearing performance benefits within technical requirements. This study is exploratory in nature and will achieve its objectives through ongoing review and adjustment of device parameters and fitting
Detailed Description
-----------------
Alternative modes of stimulation will be investigated that may improve spectral resolution through reduced cochlear spread of excitation and in turn provide enhanced speech perception and real-world clinical benefits over MP stimulation. The purpose of this study is to balance the clinical improvements of alternative modes of stimulation with technical and usability requirements for power usage. By iteratively evaluating different sets of stimulation and sound coding parameters, this study will determine device settings and fitting techniques. Measures of speech recognition, listening effort, neural responses, electrode placement, battery life, and usability acceptance will be obtained to evaluate clinical benefits
Official Title
-----------------
An Early Feasibility, Prospective, Exploratory Study Evaluating the Performance of Focused Multipolar Stimulation and Sound Coding Enhancements in Adult Cochlear Implant Recipients (SASC).
Conditions
-----------------
Hearing Impairment, Sensorineural
Intervention / Treatment
-----------------
* Device: Focused Multipolar Stimulation (FMS) strategy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1) Candidate for unilateral cochlear implantation according to bilateral sensorineural hearing loss criteria, who has decided to proceed with implantation through routine processes. a) Bilateral sensorineural hearing loss criteria for clinics in the United States: i) Ear to be implanted: Moderate to profound sensorineural hearing loss, defined as a pure-tone average (PTA) (250 - 1000 Hz) ≥ 40 dB HL and a PTA (2000 - 8000 Hz) ≥ 65 dB HL Aided word score ≤ 40% ii) Contralateral ear: (1) PTA (500, 1000, 2000, and 4000 Hz) > 30 dB HL (2) Aided word score ≤ 80% b) Bilateral sensorineural hearing loss criteria for clinics in Belgium: i) Both ears: PTA (500, 1000, 2000, and 4000 Hz) ≥ 70 dB HL for average of 3 out of 4 frequencies Unaided phoneme score ≤ 50% on CVC in quiet at 70 dB SPL in free field ABR peak ≥ 75 dB nHL 2) 18 years of age or older. 3) Fluent in the language used for speech testing. 4) Willing to comply with all investigational requirements. 5) Willing and able to provide written informed consent - Exclusion Criteria: Previous or existing cochlear-implant recipient. Severe or greater sensorineural hearing loss in the ear to be implanted prior to five years of age. Duration of severe to profound hearing loss > 20 years in the ear to be implanted. Ossification or other cochlear anomaly that might prevent complete insertion of the electrode array. Diagnosis of auditory neuropathy. Deafness due to lesions of the acoustic nerve or central auditory pathway. Pregnant at the time of surgery. Additional handicaps that would prevent or restrict participation in the audiological evaluations. Unrealistic expectations on the part of the subject regarding the possible benefits, risks, and limitations that are inherent to the surgical procedure and prosthetic device. Unable or unwilling to comply with the requirements of the clinical investigation as determined by the Investigator. Investigator site personnel directly affiliated with this study and/or their immediate families; immediate family is defined as a spouse, parent, child, or sibling. Cochlear employees or employees of Contract Research Organisations or contractors engaged by Cochlear for the purposes of this investigation. Currently participating, or participated within the last 30 days, in another interventional clinical investigation/trial involving an investigational drug or device
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: Adult Cochlear implant<br>Adult cochlear implant recipients receiving different combinations of alternative modes and, sound coding parameters | Device: Focused Multipolar Stimulation (FMS) strategy<br>* Adult cochlear implant recipients receiving different combinations of alternative modes and, sound coding parameters.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean difference across maximum map stimulation (C) levels | Mean difference across maps using alternative modes and sound coding parameters for the highest and average comfortable loudness level (clinical unit) (C-level). | 10 weeks |
| Mean difference across Spectral resolution (QSMD) | Mean difference across maps using alternative modes and sound coding parameters for spectral resolution (% correct) (QSMD - Quick spectral modulation detection) | 10 weeks |
| Mean difference across phoneme discrimination (LIT- Language independent test) | Mean difference across maps using alternative modes and sound coding parameters for phoneme discrimination (% correct) (LIT - Language independent test) | 10 weeks |
|
||
NCT02410161
|
Effect of an Alpha-linolenic Acid-rich Supplement on Ketogenesis and Plasma Fatty Acids
|
Background: As the main alternative fuel to glucose for the brain, increased plasma ketones could potentially help compensate for brain glucose hypometabolism occurring during aging. The precursor long-chain n-3 polyunsaturated fatty acid (PUFA), α-linolenic acid (ALA), is normally mostly β-oxidized and so could potentially be used to stimulate ketogenesis in humans.~Objective: To compare the impact of an ALA-rich supplement on the ketogenic response in young and older healthy adults.~Design: Ten young and ten older adults will consume a flaxseed oil supplement providing 2 g/d of ALA for 4 weeks. Plasma ketones, free fatty acids, triglycerides, glucose and insulin will be measured over 6 h during two metabolic study days, one before and one at the end of the supplementation.~Hypothesis: ALA-rich supplement for 4 weeks will increase ketone production in both groups.
|
Effect of an Alpha-linolenic Acid-rich Supplement on Ketogenesis and Plasma n-3 Polyunsaturated Fatty Acids in Young Compared to Older Adults
|
Healthy
|
* Dietary Supplement: alpha-linolenic acid-rich supplement
|
Inclusion Criteria:~aged between 18 and 30 or 65 years and more~Exclusion Criteria:~non smoker~pregnancy or breastfeeding~diabetes or insulin resistance~uncontrolled thyroid disease, hepatic or renal disease~uncontrolled high blood pressure~medical treatment influencing lipid or glucide metabolism~ongoing or past severe drug or alcohol abuse~dementia or psychiatric difficulties or depression~chronic immune condition or inflammation
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Dietary Supplement: alpha-linolenic acid-rich supplement
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ketone Production | Total Ketone (acetoacetate + beta-hydroxybutyrate) concentration in plasma in average during the metabolic study day, measured hourly between 1 and 6h after breakfast | After 4 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Glucose | Glucose measured in plasma in average during the metabolic study day, measure hourly between 0 and 6 h after breakfast | After 4 weeks |
| Plasma Triglycerides | Triglycerides measured in plasma in average during the metabolic study day, measured hourly between 1 to 6h after breakfast | After 4 weeks |
| Plasma Free Fatty Acids | Free fatty acids measured in plasma in average during the metabolic study day, measured hourly between 1 to 6h after breakfast | 4 weeks |
| Insulin Concentration in Plasma | Insulin measured in plasma in average during the metabolic study day, measured hourly between 0 ans 6 h after breakfast | after 4 weeks |
|
ketone, α-linolenic acid, flaxseed, aging, β-hydroxybutyrate, acetoacetate, omega-3 fatty acids, ketogenesis
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 4 week ALA treatment<br>Participants will receive the alpha-linolenic acid-rich supplement (1000mg 4 times par day) for 4 weeks | Dietary Supplement: alpha-linolenic acid-rich supplement<br>* each participant consumed one 1000 mg capsule of flaxseed oil four times per day for 4 weeks, providing a total of 2 g/d of ALA. The capsules used were a commercially available flaxseed oil supplement containing ALA at 56% of total fatty acids (Jamieson, Toronto, ON, Canada). The other main fatty acids present in flaxseed oil include linoleic acid (18%), oleic acid (16%), palmitic and stearic acid (10% combined).<br>|
|
Effect of an Alpha-linolenic Acid-rich Supplement on Ketogenesis and Plasma Fatty Acids
Study Overview
=================
Brief Summary
-----------------
Background: As the main alternative fuel to glucose for the brain, increased plasma ketones could potentially help compensate for brain glucose hypometabolism occurring during aging. The precursor long-chain n-3 polyunsaturated fatty acid (PUFA), α-linolenic acid (ALA), is normally mostly β-oxidized and so could potentially be used to stimulate ketogenesis in humans. Objective: To compare the impact of an ALA-rich supplement on the ketogenic response in young and older healthy adults. Design: Ten young and ten older adults will consume a flaxseed oil supplement providing 2 g/d of ALA for 4 weeks. Plasma ketones, free fatty acids, triglycerides, glucose and insulin will be measured over 6 h during two metabolic study days, one before and one at the end of the supplementation. Hypothesis: ALA-rich supplement for 4 weeks will increase ketone production in both groups.
Official Title
-----------------
Effect of an Alpha-linolenic Acid-rich Supplement on Ketogenesis and Plasma n-3 Polyunsaturated Fatty Acids in Young Compared to Older Adults
Conditions
-----------------
Healthy
Intervention / Treatment
-----------------
* Dietary Supplement: alpha-linolenic acid-rich supplement
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: aged between 18 and 30 or 65 years and more Exclusion Criteria: non smoker pregnancy or breastfeeding diabetes or insulin resistance uncontrolled thyroid disease, hepatic or renal disease uncontrolled high blood pressure medical treatment influencing lipid or glucide metabolism ongoing or past severe drug or alcohol abuse dementia or psychiatric difficulties or depression chronic immune condition or inflammation
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: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Dietary Supplement: alpha-linolenic acid-rich supplement
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 4 week ALA treatment<br>Participants will receive the alpha-linolenic acid-rich supplement (1000mg 4 times par day) for 4 weeks | Dietary Supplement: alpha-linolenic acid-rich supplement<br>* each participant consumed one 1000 mg capsule of flaxseed oil four times per day for 4 weeks, providing a total of 2 g/d of ALA. The capsules used were a commercially available flaxseed oil supplement containing ALA at 56% of total fatty acids (Jamieson, Toronto, ON, Canada). The other main fatty acids present in flaxseed oil include linoleic acid (18%), oleic acid (16%), palmitic and stearic acid (10% combined).<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ketone Production | Total Ketone (acetoacetate + beta-hydroxybutyrate) concentration in plasma in average during the metabolic study day, measured hourly between 1 and 6h after breakfast | After 4 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Glucose | Glucose measured in plasma in average during the metabolic study day, measure hourly between 0 and 6 h after breakfast | After 4 weeks |
| Plasma Triglycerides | Triglycerides measured in plasma in average during the metabolic study day, measured hourly between 1 to 6h after breakfast | After 4 weeks |
| Plasma Free Fatty Acids | Free fatty acids measured in plasma in average during the metabolic study day, measured hourly between 1 to 6h after breakfast | 4 weeks |
| Insulin Concentration in Plasma | Insulin measured in plasma in average during the metabolic study day, measured hourly between 0 ans 6 h after breakfast | after 4 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ketone, α-linolenic acid, flaxseed, aging, β-hydroxybutyrate, acetoacetate, omega-3 fatty acids, ketogenesis
|
||
NCT01479036
|
Trial of Neoadjuvant Endostar, Docetaxel and Epirubicin for Patients With Breast Cancer
|
This study was designed to determine the efficacy and safety of neoadjuvant docetaxel and epirubicin (DE) with or without human recombinant endostatin (endostar) for breast cancer patients. The hypothesis of this protocol is that a combined angiogenesis inhibiting therapy to chemotherapy could further benefit breast cancer patients.
|
This is a multicenter, prospective, randomized, controlled phase Ⅲ clinical trial. A total of 800 patients with core-biopsy confirmed breast cancer, stage ⅡA to ⅢC, and to be treated with neoadjuvant systemic therapy are eligible for entry into this study. Patients will be allocated randomly to two groups to receive either 3 cycles of neoadjuvant DE and endostar or 3 cycles of neoadjuvant DE. All cases receive mammography, contrast-enhanced ultrasound (CEUS), magnetic resonance angiography (MRA), and positron emission tomography (PET) scanning pre- and post-neoadjuvant therapy, and then undergo surgical resection. The primary endpoint is clinical/pathological response. The clinical response will be evaluated according to RECIST criteria. The parameters of tumor metabolism and blood supply, as demonstrated by PET, MRA and CEUS, will be collected and analysed. The secondary endpoint is (1) the number of participants with adverse events, (2) quality of life scores, and (3) the number of adverse events reported during neoadjuvant therapy. In addition, the role of mammography, CEUS, MRA and PET for response evaluation, as well as the angiogenic profile and biological information involved in tumor response will be investigated.
|
Phase Ⅲ Trial of Neoadjuvant Recombinant Human Endostatin, Docetaxel and Epirubicin as First-Line Therapy in Patients With Breast Cancer
|
Breast Cancer
|
* Drug: docetaxel and epirubicin
* Drug: docetaxel and epirubicin plus endostatin
|
Inclusion Criteria:~Histologically confirmed invasive breast cancer (core needle biopsy for breast cancer diagnosis and fine needle aspiration for lymph node metastasis diagnosis)~Stage ⅡA-ⅢC~Age 18-70~ECOG performance status 0-2~No evidence of distant metastasis~No previous therapy~Normal hematologic function~left ventricular ejection fraction greater than 50 percent~No abnormality of renal or liver function~Written informed consent~Exclusion Criteria:~With allergic constitution or possible allergic reflection to drugs to be used in this study~Any concurrent uncontrolled medical or psychiatric disorder~History of severe heart diseases, including congestive heart failure, unstable angina, uncontrolled arrhythmia, myocardial infarction, uncontrolled high blood pressure, or heart valve disease.~History of bleeding diathesis~Being pregnant or nursing
|
18 Years
|
70 Years
|
Female
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical/pathological response | The clincial response will be evaluated according to RECIST criteria. The parameters of tumor metabolism and blood supply, as demonstrated by PET, MRA and CEUS, will be collected and analysed. | 3 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | The number of participants with adverse events will be recorded and analysed. | 3 years |
| Quality of life | Quality of life is scored using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life of Questionnaire (QLQ30) at study entry and prior to surgery. | 3 years |
| Number of adverse events reported during neoadjuvant therapy | The adverse events during neoadjuvant therapy will be graded using the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 2.0. | 3 years |
|
breast cancer, neoadjuvant chemotherapy, recombinant human endostatin (endostar), docetaxel, epirubicin
|
Topoisomerase Inhibitors, Enzyme Inhibitors, Angiogenesis Inhibitors, Angiogenesis Modulating Agents, Growth Substances, Physiological Effects of Drugs, Growth Inhibitors, Docetaxel, Epirubicin, Endostatins, Antineoplastic Agents, Tubulin Modulators, Antimitotic Agents, Mitosis Modulators, Molecular Mechanisms of Pharmacological Action, Antibiotics, Antineoplastic, Topoisomerase II Inhibitors
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: docetaxel and epirubicin<br>DE chemotherapy alone | Drug: docetaxel and epirubicin<br>* docetaxel 75mg/m2, IV (in the vein) on day 1 of each 21 day cycle; epirubicin 75 mg/m2, IV (in the vein) on day 1 of each 21 day cycle, totally 3 cycles<br>* Other names: Epirubicin, Pfizer;|
| Experimental: docetaxel and epirubicin plus endostatin<br>chemotherapy plus endostatin | Drug: docetaxel and epirubicin plus endostatin<br>* docetaxel 75mg/m2, IV (in the vein) on day 1 of each 21 day cycle; epirubicin 75 mg/m2, IV (in the vein) on day 1 of each 21 day cycle; endostatin 7.5mg/m2, IV (in the vein) on 1st to 14th days of each 21 day cycle; every 3 weeks, totally 3 cycles<br>* Other names: Endostatin, Simcere-Medgenn (No. S20050088);|
|
Trial of Neoadjuvant Endostar, Docetaxel and Epirubicin for Patients With Breast Cancer
Study Overview
=================
Brief Summary
-----------------
This study was designed to determine the efficacy and safety of neoadjuvant docetaxel and epirubicin (DE) with or without human recombinant endostatin (endostar) for breast cancer patients. The hypothesis of this protocol is that a combined angiogenesis inhibiting therapy to chemotherapy could further benefit breast cancer patients.
Detailed Description
-----------------
This is a multicenter, prospective, randomized, controlled phase Ⅲ clinical trial. A total of 800 patients with core-biopsy confirmed breast cancer, stage ⅡA to ⅢC, and to be treated with neoadjuvant systemic therapy are eligible for entry into this study. Patients will be allocated randomly to two groups to receive either 3 cycles of neoadjuvant DE and endostar or 3 cycles of neoadjuvant DE. All cases receive mammography, contrast-enhanced ultrasound (CEUS), magnetic resonance angiography (MRA), and positron emission tomography (PET) scanning pre- and post-neoadjuvant therapy, and then undergo surgical resection. The primary endpoint is clinical/pathological response. The clinical response will be evaluated according to RECIST criteria. The parameters of tumor metabolism and blood supply, as demonstrated by PET, MRA and CEUS, will be collected and analysed. The secondary endpoint is (1) the number of participants with adverse events, (2) quality of life scores, and (3) the number of adverse events reported during neoadjuvant therapy. In addition, the role of mammography, CEUS, MRA and PET for response evaluation, as well as the angiogenic profile and biological information involved in tumor response will be investigated.
Official Title
-----------------
Phase Ⅲ Trial of Neoadjuvant Recombinant Human Endostatin, Docetaxel and Epirubicin as First-Line Therapy in Patients With Breast Cancer
Conditions
-----------------
Breast Cancer
Intervention / Treatment
-----------------
* Drug: docetaxel and epirubicin
* Drug: docetaxel and epirubicin plus endostatin
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed invasive breast cancer (core needle biopsy for breast cancer diagnosis and fine needle aspiration for lymph node metastasis diagnosis) Stage ⅡA-ⅢC Age 18-70 ECOG performance status 0-2 No evidence of distant metastasis No previous therapy Normal hematologic function left ventricular ejection fraction greater than 50 percent No abnormality of renal or liver function Written informed consent Exclusion Criteria: With allergic constitution or possible allergic reflection to drugs to be used in this study Any concurrent uncontrolled medical or psychiatric disorder History of severe heart diseases, including congestive heart failure, unstable angina, uncontrolled arrhythmia, myocardial infarction, uncontrolled high blood pressure, or heart valve disease. History of bleeding diathesis Being pregnant or nursing
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 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: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: docetaxel and epirubicin<br>DE chemotherapy alone | Drug: docetaxel and epirubicin<br>* docetaxel 75mg/m2, IV (in the vein) on day 1 of each 21 day cycle; epirubicin 75 mg/m2, IV (in the vein) on day 1 of each 21 day cycle, totally 3 cycles<br>* Other names: Epirubicin, Pfizer;|
| Experimental: docetaxel and epirubicin plus endostatin<br>chemotherapy plus endostatin | Drug: docetaxel and epirubicin plus endostatin<br>* docetaxel 75mg/m2, IV (in the vein) on day 1 of each 21 day cycle; epirubicin 75 mg/m2, IV (in the vein) on day 1 of each 21 day cycle; endostatin 7.5mg/m2, IV (in the vein) on 1st to 14th days of each 21 day cycle; every 3 weeks, totally 3 cycles<br>* Other names: Endostatin, Simcere-Medgenn (No. S20050088);|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical/pathological response | The clincial response will be evaluated according to RECIST criteria. The parameters of tumor metabolism and blood supply, as demonstrated by PET, MRA and CEUS, will be collected and analysed. | 3 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | The number of participants with adverse events will be recorded and analysed. | 3 years |
| Quality of life | Quality of life is scored using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life of Questionnaire (QLQ30) at study entry and prior to surgery. | 3 years |
| Number of adverse events reported during neoadjuvant therapy | The adverse events during neoadjuvant therapy will be graded using the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 2.0. | 3 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
breast cancer, neoadjuvant chemotherapy, recombinant human endostatin (endostar), docetaxel, epirubicin
|
NCT04042090
|
The Efficacy, Acceptability, Tolerability and Feasibility of a Therapeutic Virtual Reality Application
|
This study evaluates the effect of therapeutic Virtual Reality (VR) on quality of life of 60 patients with non-specific chronic low-back pain. 30 patients will be included in the intervention group. These patients will use Reducept, a therapeutic virtual reality application based on diverse cognitive therapies (ACT, mindfulness, EMDR, hypnotherapy), at home over a period of 28 days, for at least 10 minutes each day. This will be an add-on intervention next to standard care, while the patient is waiting to receive actual treatment for chronic pain. 30 patients in the control group will only receive standard care, whilst waiting to receive actual treatment for their chronic pain. Intervention and control group will be compared on a number of outcome measures related to quality of life before using VR, during VR use, just after use and 4 months after final use. This explorative study is necessary to get first insights as a basis for a confirmative study.
|
Rationale:~21,2% of the Dutch population is suffering from chronic low-back pain. 90% of these patients suffers from chronic low-back pain not attributable to a recognisable, specific pathology (non-specific low-back pain). 30-40% of all patients suffering from chronic pain visit their GP for treatment. Treatment includes mostly analgesics, in particular NSAIDs and opioids.~Adequate treatment of chronic pain is important as chronic pain negatively impacts, amongst others, quality of life, activities of daily living and feelings of helplessness. A systematic review by Bala et al. however shows that chronic pain treatment is often inadequate. Moreover, each different type of analgesic has its own associated side effects. NSAIDs increase the risk of cardiovascular and gastrointestinal complications. Common side effects of opioid analgesics include sedation, dizziness, nausea, vomiting, constipation, physical dependence, and even cases of hyperalgesia.~Recently, more attention has been given to psychological interventions for relieving chronic pain. A systematic review by Castelnuovo et al. shows the efficacy of a range of psychological interventions, including acceptance and commitment therapy (ACT), mindfulness-based interventions, hypnotherapy, eye movement and desensitization and reprocessing (EMDR) therapies and virtual reality based interventions. All of these psychological interventions focus on changing people's attitudes, feelings and behaviors on chronic pain, to improve their quality of life.~The first psychological intervention is the commonly used acceptance and commitment therapy (ACT). ACT is a cognitive behavioral therapy for treating chronic pain that uses exposure-based and experiential methods aiming at improving patients' abilities to cope with their chronic pain. Several systematic reviews indicate that ACT is effective in improving health outcomes of chronic pain patients. Mindfulness-based interventions seem to work as well for chronic pain relief. This set of interventions aims at learning strategies for pain awareness and acceptance. Furthermore, hypnotherapy is a mind-body based intervention that uses hypnoses to learn patients to cope with their pain. It focuses attention away from pain, thereby blocking its experience. Hypnotherapy seems effective in reducing pain experience. Then, eye movement desensitization and reprocessing (EMDR) is another psychotherapeutic approach in treating chronic pain. EMDR has already shown to be effective in treating posttraumatic stress disorder, and has recently as well been introduced as a treatment for chronic pain. Early research findings indicate EMDR to be effective in treating chronic pain.~Finally, one of the most recent fields of inquiry in treating chronic pain by means of psychological interventions is Virtual Reality. VR consists of a Head Mounted Device (HMD) and a sound system which immerses the user in a three-dimensional (3D) virtual world. There are multiple mechanisms behind the efficacy of VR in treating chronic pain. The most commonly studied mechanism is distraction. VR seems to be effective in reducing pain via distraction as it diverts attention away from pain. As both the VR application and the pain require attention and the brain has only limited attentional capacity, less attention is available for pain processing. In this manner, it reduces current feelings of pain, anxiety and stress. Though, the distraction mechanism only diverts attention away from pain shortly. To actually treat chronic pain by means of VR, it seems that other strategies, apart from distraction, are required.~Several studies aimed to find alternative mechanisms behind pain reduction by VR. The use of psychological interventions in VR, such as ACT or hypnosis, appears to be effective. Although the context of VR is different from traditional psychotherapy, the idea of how change occurs is not. Moreover, the immersiveness of VR provides opportunities to even better influence cognitions and emotions of patients suffering from chronic pain. Multiple virtual reality interventions have been designed with this knowledge in mind. A proof-of-concept study by Gromala et al., for example, looked into the application Virtual Meditative Walk (VMW). VNW focuses on mindfulness-based stress reduction via VR. The user study shows VNW's efficacy compared to non-VR interventions. Likewise, Guarino et al. proved that using virtual mindfulness therapy eight times over a period of a month is effective in chronic pain reduction. Therapeutic hypnosis has as well been tested in several case report studies. All conclude that virtual reality hypnosis seems to be effective in dealing with chronic pain.~The VR serious game Reducept is a novel psychological VR intervention for treating chronic pain. It incorporates several psychological therapies into one application: hypnotherapy, mindfulness, ACT and EMDR. Reducept has been made in co-creation with patients, researchers, psychologists and developers and can be installed and played on a VR goggles. It consists of an education module and three games.~Education: Reducept provides its players with information about the biological mechanisms underlying chronic pain. Learning about chronic pain helps to cope with it in daily life.~Control: Reducept's first game has been based on the mechanisms of hypnotherapy. The patient should shoot away painful stimuli in the nervous system. By visualizing their pain, they learn to control and cope with it.~Relaxation: the second game within Reducept is a mindfulness-based intervention. It takes place in the spinal cord. Players should collect positive neurotransmitters and focus on their respiration rate.~Processing: game three has been based on the mechanisms of ACT and EMDR. It asks players to recover negative patterns in the brain. Players have to switch attention between the pain and the game, helping them to decrease their experience of pain.~This study aims to gain a first understanding in the ability of the therapeutic VR intervention Reducept to treat chronic low-back pain. It will define a wide range of outcome measures, including quality of life indicators, pain, stress and anxiety measures and measures on ability to execute daily activities. What outcome measures does it affect? What outcome measures will be left unaffected? Moreover, tolerability, feasibility and acceptability of Reducept in relation to different patient characteristics (age, gender, Motivaction profiling) will be measured to understand which patients might benefit most from virtual reality based psychological interventions. The study focuses on patients with non-specific chronic low-back pain as this group represents a large part of all chronic pain patients. This explorative study is necessary as an input for future studies on the actual effects of therapeutic virtual reality interventions on quality of life of patients.~Objective:~To investigate whether a therapeutic virtual reality application can improve the quality of life of people suffering from non-specific chronic low-back pain, compared to a control condition.~Study design:~This explorative study uses a randomised controlled parallel design (1:1). Participants will be randomly assigned to either the control group or the intervention group. In the control group, participants are placed on the waiting list to receive the common treatment to handle their chronic pain. As they are placed on the waiting list, they will receive no therapeutic treatment yet (apart from the during intake prescribed physiotherapy and medication). Participants placed in the intervention group, who are also placed on the waiting list and only receive, when prescribed, physiotherapy and medication, will use the therapeutic virtual reality intervention meanwhile at home during a period of 28 days for at least ten minutes each day and in addition the education module at least during day 1 (which lasts 25 minutes). The randomisation is not blinded: both researchers and participants know which participants are part of the intervention and control group.~Study population:~Adult patients, males and females, suffering from daily non-specific chronic low-back pain are eligible for this study. Patients' pain should have last for at least three months. Patients should report a pain score of ≥4 during the intake questionnaires filled in before intake at the Rijnstate Pijncentrum.~Intervention (if applicable):~Participants will be randomly assigned to either the intervention group or the control group. Participants assigned to the intervention group will receive virtual reality glasses with the Reducept application. They are asked to use the therapeutic virtual reality intervention at home over a period of 28 days starting the day after collecting the virtual reality goggles. Participants are asked to use the therapeutic virtual reality intervention at least once a day for ten minutes. In addition, they should, on the first day, and preferably during more days, watch the whole education program which lasts 25 minutes. Participants can decide themselves to use the application more often. Participants assigned to the control group will receive no intervention, they are, just as the intervention group, placed on the waiting list to receive normal treatment.~Unfortunately, it is not possible to provide all patients with the opportunity to use the virtual reality application, as the design requires a control group that does not use it over the study period.~The investigators will study the possibility of continuing the virtual reality treatment for all participants want-ing to after finishing this study. At least they will be able to buy themselves the virtual reality glasses for using the therapeutic virtual reality.~Nature and extent of the burden and risks associated with participation, benefit and group relatedness:~There is no risk involved in exposure to the therapeutic virtual reality application. Participants can leave the study at any time for any reason if they wish to do so without any consequences. As mentioned before, the burden for participants associated with this study is mainly related to measurements of endpoints, which will take approximately 30-45 minutes three times over a period of five months. The intervention group will spend at least ten minutes a day on the therapeutic virtual reality application and in addition on day 1 25 minutes.. As explained in the rationale, no or only minimal adverse effects from this intervention are expected.
|
A Pilot Study on the Efficacy, Acceptability, Tolerability and Feasibility of a Therapeutic Virtual Reality Application on Improving the Quality of Life in Non-specific Chronic Low-back Pain Patients
|
Back Pain Lower Back Chronic, Quality of Life
|
* Device: Reducept, virtual reality
|
Inclusion Criteria:~Patient suffers from chronic non-specific low-back pain (LBP) not attributable to a recognisable, known specific pathology (e.g. infection, tumour, osteoporosis, lumbar spine fracture, structural deformity, inflammatory disorder, radicular syndrome, or cauda equina syndrome).~Patient reports a pain score related to chronic low-back pain ≥4.~Patient is placed on the waiting list to receive intervention and receives no treatment yet, apart from medication or physiotherapy.~At the day of recruitment, the estimated length of the waiting list for intervention is at least six weeks.~Patient did not receive any invasive treatment for his chronic non-specific low-back pain in the last year.~Patient is willing and able to comply with the trial protocol.~Patient is at least 18 years old on the day the oral informed consent will be given.~Patient can read and understand the Dutch language.~Exclusion Criteria:~Patient is included in another trial to evaluate new ways of treating pain.~Patients suffers from severe anxiety or depression (HADS≥16).~Patient has difficulties to handle virtual reality:~Patient suffers from delirium or acute confusional state.~Patient has (a history of) dementia, seizure, or epilepsy.~Patient has severe hearing/visual impairment not corrected.~The skin of the patient's head or face is not intact (for example head wounds, psoriasis, eczema).
|
18 Years
|
110 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomly assigned (1:1) to either the intervention group or the control group. Both intervention and control group are placed on the waiting list (approximate time of waiting is 6 weeks) to receive treatment. Meanwhile, our study will be executed. Intervention group: use of virtual reality intervention at home over a period of 28 days (with a maximum of 35 days) at least ten minutes a day (excluding day 1, in which the participants should do the entire education module of 25 minutes) and in addition, when participants feel the need. The control group: no intervention, patient is waiting to receive normal chronic pain treatment. Randomisation is not blinded: both researchers and participants know which participants are part of the intervention and control group. Randomisation will take place using a computerised randomisation list with variably sized blocks, directly after providing oral informed consent.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in SF12: short form health survey | Measurement of changes in quality of life of patient before intervention, just after intervention period and 4 months after intervention period. SF12 measures via different scaled questions eight concepts: physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health. The first four items together form the physical health scale. The latter four items form the mental health scale. The higher the scores, the better the physical and mental health. Highest possible score: 56. Lowest possible score: 12. | Day 0, day 28, day 148 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in positive health questionnaire | Measurement of changes in the positive health framework (a questionnaire and conversation tool for understanding health in a larger context) before intervention period, just after the intervention period and four months after the intervention period. Positive health consists out of 42 statements separated in 6 categories: bodily functioning, mental functioning, spiritual dimension, quality of life, social participation, daily functioning. Each question should be rated with a 0 (worst) to a 10 (best). The higher the scores, the better the quality of life. | Day 0, day 28, day 148 |
| Change in pain via numeric rating score | Measurement of changes in pain scores of patient before intervention period, just after intervention period and 4 months after intervention period. Pain scores are measured via a numeric rating score from 0 (no pain at all)-10 (worst pain ever). Questionnaire consists out of 4 questions, with a maximum score of 40. | Day 0, day 28, day 148 |
| Change in BPI: brief pain inventory, numeric rating score | Measurement of changes in pain inventory of patient before intervention period, just after intervention period and 4 months after intervention period. Questionnaire consists out of 7 questions to be answered with 0 (no obstruction) to 10 (full obstruction). A total of 70 points is the maximum score. | Day 0, day 28, day 148 |
| Change in PCS: Pain Catastrophizing Scale | Measurement of changes in pain catastrophizing of patient before intervention period, just after intervention period and 4 months after intervention period. Questionnaire consists out of 13 questions to be answered with 0 (not at all) to 4 (always). Questionnaire has 3 subscales (rumination, magnification, helplessness) and a total score of maximum 52. | Day 0, day 28, day 148 |
| Change in PCCL: Pain Coping and Cognition list | Measurement of changes in pain coping strategies (PCCL) of patient before intervention, just after intervention period and 4 months after intervention period. Questionnaire consists out of 42 questions to be answered with 0 (don't agree) to 5 (totally agree). 4 subscales: catastrophizing, pain coping, internal pain control, external pain control. Per subscale is the total sum calculated and divided by the number of questions. A score of 1-6 is assigned per subscale. | Day 0, day 28, day 148 |
| Change in HADS: Hospital Anxiety and Depression Scale | Measurement of changes in anxiety (HADS) of patient before intervention period, just after intervention period and 4 months after intervention period. Questionnaire consists out of 14 questions with answers ranging from 0 (often) to 3 (almost never). All questions are summed up to a total of 42 points. | Day 0, day 28, day 148 |
| Change in OLBPDQ: Oswestry Low Back Pain Disability Questionnaire | Measurement of changes in activities of daily life as a consequence of experienced pain of patient before intervention period, just after intervention period and 4 months after intervention period. Questionnaire consists out of 10 questions to be answered with 0 (no disability) to 6 (full disability). All questions are to be summed up to a total of 60 points. | Day 0, day 28, day 148 |
| Change in ADL: Activities of Daily Life | Measurement of changes in activities of daily life (ADL) of patient before intervention, just after intervention period and 4 months after intervention period. Questionnaire consists of 22 questions ranging from 0 (not at all) to 3 (easily autonomous). Maximum score is 63. | Day 0, day 28, day 148 |
| Change in pain questionnaire via numeric pain rating scale | Changes in pain intensity during the intervention period measured via 4 questions on scales ranging from 0 (pain doesn't influence me) to 10 (pain hinders me a lot). And two visual analogue scales of 10 centimeters (I don't have pain at all - I am in full pain). | Questionnaires will be filled in at the end of each intervention day during the intervention period of 28 days |
| Medication use questionnaire | Use of medication during the intervention period. | Questionnaires will be filled in at the end of each intervention day during the intervention period of 28 days |
|
Virtual reality, Quality of life, Back pain
|
Back Pain, Pain, Neurologic Manifestations
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group: use of therapeutic virtual reality<br>Intervention group: use of virtual reality intervention at home over a period of 28 days (with a maximum of 35 days) at least ten minutes a day (excluding day 1, in which the participants should do the entire education module of 25 minutes) and in addition, when participants feel the need. Meanwhile, participant is placed on the waiting list to receive normal chronic pain treatment. | Device: Reducept, virtual reality<br>* The VR serious game Reducept is a novel psychological VR intervention for treating chronic pain. It incorporates several psychological therapies into one application: hypnotherapy, mindfulness, ACT and EMDR. Reducept has been made in co-creation with patients, researchers, psychologists and developers and can be installed and played on a VR goggles. It consists of an education module and three games.<br>|
| No Intervention: Control group: no use of therapeutic virtual reality<br>Control group: no intervention, patient is waiting to receive normal chronic pain treatment. | |
|
The Efficacy, Acceptability, Tolerability and Feasibility of a Therapeutic Virtual Reality Application
Study Overview
=================
Brief Summary
-----------------
This study evaluates the effect of therapeutic Virtual Reality (VR) on quality of life of 60 patients with non-specific chronic low-back pain. 30 patients will be included in the intervention group. These patients will use Reducept, a therapeutic virtual reality application based on diverse cognitive therapies (ACT, mindfulness, EMDR, hypnotherapy), at home over a period of 28 days, for at least 10 minutes each day. This will be an add-on intervention next to standard care, while the patient is waiting to receive actual treatment for chronic pain. 30 patients in the control group will only receive standard care, whilst waiting to receive actual treatment for their chronic pain. Intervention and control group will be compared on a number of outcome measures related to quality of life before using VR, during VR use, just after use and 4 months after final use. This explorative study is necessary to get first insights as a basis for a confirmative study.
Detailed Description
-----------------
Rationale: 21,2% of the Dutch population is suffering from chronic low-back pain. 90% of these patients suffers from chronic low-back pain not attributable to a recognisable, specific pathology (non-specific low-back pain). 30-40% of all patients suffering from chronic pain visit their GP for treatment. Treatment includes mostly analgesics, in particular NSAIDs and opioids. Adequate treatment of chronic pain is important as chronic pain negatively impacts, amongst others, quality of life, activities of daily living and feelings of helplessness. A systematic review by Bala et al. however shows that chronic pain treatment is often inadequate. Moreover, each different type of analgesic has its own associated side effects. NSAIDs increase the risk of cardiovascular and gastrointestinal complications. Common side effects of opioid analgesics include sedation, dizziness, nausea, vomiting, constipation, physical dependence, and even cases of hyperalgesia. Recently, more attention has been given to psychological interventions for relieving chronic pain. A systematic review by Castelnuovo et al. shows the efficacy of a range of psychological interventions, including acceptance and commitment therapy (ACT), mindfulness-based interventions, hypnotherapy, eye movement and desensitization and reprocessing (EMDR) therapies and virtual reality based interventions. All of these psychological interventions focus on changing people's attitudes, feelings and behaviors on chronic pain, to improve their quality of life. The first psychological intervention is the commonly used acceptance and commitment therapy (ACT). ACT is a cognitive behavioral therapy for treating chronic pain that uses exposure-based and experiential methods aiming at improving patients' abilities to cope with their chronic pain. Several systematic reviews indicate that ACT is effective in improving health outcomes of chronic pain patients. Mindfulness-based interventions seem to work as well for chronic pain relief. This set of interventions aims at learning strategies for pain awareness and acceptance. Furthermore, hypnotherapy is a mind-body based intervention that uses hypnoses to learn patients to cope with their pain. It focuses attention away from pain, thereby blocking its experience. Hypnotherapy seems effective in reducing pain experience. Then, eye movement desensitization and reprocessing (EMDR) is another psychotherapeutic approach in treating chronic pain. EMDR has already shown to be effective in treating posttraumatic stress disorder, and has recently as well been introduced as a treatment for chronic pain. Early research findings indicate EMDR to be effective in treating chronic pain. Finally, one of the most recent fields of inquiry in treating chronic pain by means of psychological interventions is Virtual Reality. VR consists of a Head Mounted Device (HMD) and a sound system which immerses the user in a three-dimensional (3D) virtual world. There are multiple mechanisms behind the efficacy of VR in treating chronic pain. The most commonly studied mechanism is distraction. VR seems to be effective in reducing pain via distraction as it diverts attention away from pain. As both the VR application and the pain require attention and the brain has only limited attentional capacity, less attention is available for pain processing. In this manner, it reduces current feelings of pain, anxiety and stress. Though, the distraction mechanism only diverts attention away from pain shortly. To actually treat chronic pain by means of VR, it seems that other strategies, apart from distraction, are required. Several studies aimed to find alternative mechanisms behind pain reduction by VR. The use of psychological interventions in VR, such as ACT or hypnosis, appears to be effective. Although the context of VR is different from traditional psychotherapy, the idea of how change occurs is not. Moreover, the immersiveness of VR provides opportunities to even better influence cognitions and emotions of patients suffering from chronic pain. Multiple virtual reality interventions have been designed with this knowledge in mind. A proof-of-concept study by Gromala et al., for example, looked into the application Virtual Meditative Walk (VMW). VNW focuses on mindfulness-based stress reduction via VR. The user study shows VNW's efficacy compared to non-VR interventions. Likewise, Guarino et al. proved that using virtual mindfulness therapy eight times over a period of a month is effective in chronic pain reduction. Therapeutic hypnosis has as well been tested in several case report studies. All conclude that virtual reality hypnosis seems to be effective in dealing with chronic pain. The VR serious game Reducept is a novel psychological VR intervention for treating chronic pain. It incorporates several psychological therapies into one application: hypnotherapy, mindfulness, ACT and EMDR. Reducept has been made in co-creation with patients, researchers, psychologists and developers and can be installed and played on a VR goggles. It consists of an education module and three games. Education: Reducept provides its players with information about the biological mechanisms underlying chronic pain. Learning about chronic pain helps to cope with it in daily life. Control: Reducept's first game has been based on the mechanisms of hypnotherapy. The patient should shoot away painful stimuli in the nervous system. By visualizing their pain, they learn to control and cope with it. Relaxation: the second game within Reducept is a mindfulness-based intervention. It takes place in the spinal cord. Players should collect positive neurotransmitters and focus on their respiration rate. Processing: game three has been based on the mechanisms of ACT and EMDR. It asks players to recover negative patterns in the brain. Players have to switch attention between the pain and the game, helping them to decrease their experience of pain. This study aims to gain a first understanding in the ability of the therapeutic VR intervention Reducept to treat chronic low-back pain. It will define a wide range of outcome measures, including quality of life indicators, pain, stress and anxiety measures and measures on ability to execute daily activities. What outcome measures does it affect? What outcome measures will be left unaffected? Moreover, tolerability, feasibility and acceptability of Reducept in relation to different patient characteristics (age, gender, Motivaction profiling) will be measured to understand which patients might benefit most from virtual reality based psychological interventions. The study focuses on patients with non-specific chronic low-back pain as this group represents a large part of all chronic pain patients. This explorative study is necessary as an input for future studies on the actual effects of therapeutic virtual reality interventions on quality of life of patients. Objective: To investigate whether a therapeutic virtual reality application can improve the quality of life of people suffering from non-specific chronic low-back pain, compared to a control condition. Study design: This explorative study uses a randomised controlled parallel design (1:1). Participants will be randomly assigned to either the control group or the intervention group. In the control group, participants are placed on the waiting list to receive the common treatment to handle their chronic pain. As they are placed on the waiting list, they will receive no therapeutic treatment yet (apart from the during intake prescribed physiotherapy and medication). Participants placed in the intervention group, who are also placed on the waiting list and only receive, when prescribed, physiotherapy and medication, will use the therapeutic virtual reality intervention meanwhile at home during a period of 28 days for at least ten minutes each day and in addition the education module at least during day 1 (which lasts 25 minutes). The randomisation is not blinded: both researchers and participants know which participants are part of the intervention and control group. Study population: Adult patients, males and females, suffering from daily non-specific chronic low-back pain are eligible for this study. Patients' pain should have last for at least three months. Patients should report a pain score of ≥4 during the intake questionnaires filled in before intake at the Rijnstate Pijncentrum. Intervention (if applicable): Participants will be randomly assigned to either the intervention group or the control group. Participants assigned to the intervention group will receive virtual reality glasses with the Reducept application. They are asked to use the therapeutic virtual reality intervention at home over a period of 28 days starting the day after collecting the virtual reality goggles. Participants are asked to use the therapeutic virtual reality intervention at least once a day for ten minutes. In addition, they should, on the first day, and preferably during more days, watch the whole education program which lasts 25 minutes. Participants can decide themselves to use the application more often. Participants assigned to the control group will receive no intervention, they are, just as the intervention group, placed on the waiting list to receive normal treatment. Unfortunately, it is not possible to provide all patients with the opportunity to use the virtual reality application, as the design requires a control group that does not use it over the study period. The investigators will study the possibility of continuing the virtual reality treatment for all participants want-ing to after finishing this study. At least they will be able to buy themselves the virtual reality glasses for using the therapeutic virtual reality. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: There is no risk involved in exposure to the therapeutic virtual reality application. Participants can leave the study at any time for any reason if they wish to do so without any consequences. As mentioned before, the burden for participants associated with this study is mainly related to measurements of endpoints, which will take approximately 30-45 minutes three times over a period of five months. The intervention group will spend at least ten minutes a day on the therapeutic virtual reality application and in addition on day 1 25 minutes.. As explained in the rationale, no or only minimal adverse effects from this intervention are expected.
Official Title
-----------------
A Pilot Study on the Efficacy, Acceptability, Tolerability and Feasibility of a Therapeutic Virtual Reality Application on Improving the Quality of Life in Non-specific Chronic Low-back Pain Patients
Conditions
-----------------
Back Pain Lower Back Chronic, Quality of Life
Intervention / Treatment
-----------------
* Device: Reducept, virtual reality
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient suffers from chronic non-specific low-back pain (LBP) not attributable to a recognisable, known specific pathology (e.g. infection, tumour, osteoporosis, lumbar spine fracture, structural deformity, inflammatory disorder, radicular syndrome, or cauda equina syndrome). Patient reports a pain score related to chronic low-back pain ≥4. Patient is placed on the waiting list to receive intervention and receives no treatment yet, apart from medication or physiotherapy. At the day of recruitment, the estimated length of the waiting list for intervention is at least six weeks. Patient did not receive any invasive treatment for his chronic non-specific low-back pain in the last year. Patient is willing and able to comply with the trial protocol. Patient is at least 18 years old on the day the oral informed consent will be given. Patient can read and understand the Dutch language. Exclusion Criteria: Patient is included in another trial to evaluate new ways of treating pain. Patients suffers from severe anxiety or depression (HADS≥16). Patient has difficulties to handle virtual reality: Patient suffers from delirium or acute confusional state. Patient has (a history of) dementia, seizure, or epilepsy. Patient has severe hearing/visual impairment not corrected. The skin of the patient's head or face is not intact (for example head wounds, psoriasis, eczema).
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 110 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: Participants will be randomly assigned (1:1) to either the intervention group or the control group. Both intervention and control group are placed on the waiting list (approximate time of waiting is 6 weeks) to receive treatment. Meanwhile, our study will be executed. Intervention group: use of virtual reality intervention at home over a period of 28 days (with a maximum of 35 days) at least ten minutes a day (excluding day 1, in which the participants should do the entire education module of 25 minutes) and in addition, when participants feel the need. The control group: no intervention, patient is waiting to receive normal chronic pain treatment. Randomisation is not blinded: both researchers and participants know which participants are part of the intervention and control group. Randomisation will take place using a computerised randomisation list with variably sized blocks, directly after providing oral informed consent.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group: use of therapeutic virtual reality<br>Intervention group: use of virtual reality intervention at home over a period of 28 days (with a maximum of 35 days) at least ten minutes a day (excluding day 1, in which the participants should do the entire education module of 25 minutes) and in addition, when participants feel the need. Meanwhile, participant is placed on the waiting list to receive normal chronic pain treatment. | Device: Reducept, virtual reality<br>* The VR serious game Reducept is a novel psychological VR intervention for treating chronic pain. It incorporates several psychological therapies into one application: hypnotherapy, mindfulness, ACT and EMDR. Reducept has been made in co-creation with patients, researchers, psychologists and developers and can be installed and played on a VR goggles. It consists of an education module and three games.<br>|
| No Intervention: Control group: no use of therapeutic virtual reality<br>Control group: no intervention, patient is waiting to receive normal chronic pain treatment. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in SF12: short form health survey | Measurement of changes in quality of life of patient before intervention, just after intervention period and 4 months after intervention period. SF12 measures via different scaled questions eight concepts: physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health. The first four items together form the physical health scale. The latter four items form the mental health scale. The higher the scores, the better the physical and mental health. Highest possible score: 56. Lowest possible score: 12. | Day 0, day 28, day 148 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in positive health questionnaire | Measurement of changes in the positive health framework (a questionnaire and conversation tool for understanding health in a larger context) before intervention period, just after the intervention period and four months after the intervention period. Positive health consists out of 42 statements separated in 6 categories: bodily functioning, mental functioning, spiritual dimension, quality of life, social participation, daily functioning. Each question should be rated with a 0 (worst) to a 10 (best). The higher the scores, the better the quality of life. | Day 0, day 28, day 148 |
| Change in pain via numeric rating score | Measurement of changes in pain scores of patient before intervention period, just after intervention period and 4 months after intervention period. Pain scores are measured via a numeric rating score from 0 (no pain at all)-10 (worst pain ever). Questionnaire consists out of 4 questions, with a maximum score of 40. | Day 0, day 28, day 148 |
| Change in BPI: brief pain inventory, numeric rating score | Measurement of changes in pain inventory of patient before intervention period, just after intervention period and 4 months after intervention period. Questionnaire consists out of 7 questions to be answered with 0 (no obstruction) to 10 (full obstruction). A total of 70 points is the maximum score. | Day 0, day 28, day 148 |
| Change in PCS: Pain Catastrophizing Scale | Measurement of changes in pain catastrophizing of patient before intervention period, just after intervention period and 4 months after intervention period. Questionnaire consists out of 13 questions to be answered with 0 (not at all) to 4 (always). Questionnaire has 3 subscales (rumination, magnification, helplessness) and a total score of maximum 52. | Day 0, day 28, day 148 |
| Change in PCCL: Pain Coping and Cognition list | Measurement of changes in pain coping strategies (PCCL) of patient before intervention, just after intervention period and 4 months after intervention period. Questionnaire consists out of 42 questions to be answered with 0 (don't agree) to 5 (totally agree). 4 subscales: catastrophizing, pain coping, internal pain control, external pain control. Per subscale is the total sum calculated and divided by the number of questions. A score of 1-6 is assigned per subscale. | Day 0, day 28, day 148 |
| Change in HADS: Hospital Anxiety and Depression Scale | Measurement of changes in anxiety (HADS) of patient before intervention period, just after intervention period and 4 months after intervention period. Questionnaire consists out of 14 questions with answers ranging from 0 (often) to 3 (almost never). All questions are summed up to a total of 42 points. | Day 0, day 28, day 148 |
| Change in OLBPDQ: Oswestry Low Back Pain Disability Questionnaire | Measurement of changes in activities of daily life as a consequence of experienced pain of patient before intervention period, just after intervention period and 4 months after intervention period. Questionnaire consists out of 10 questions to be answered with 0 (no disability) to 6 (full disability). All questions are to be summed up to a total of 60 points. | Day 0, day 28, day 148 |
| Change in ADL: Activities of Daily Life | Measurement of changes in activities of daily life (ADL) of patient before intervention, just after intervention period and 4 months after intervention period. Questionnaire consists of 22 questions ranging from 0 (not at all) to 3 (easily autonomous). Maximum score is 63. | Day 0, day 28, day 148 |
| Change in pain questionnaire via numeric pain rating scale | Changes in pain intensity during the intervention period measured via 4 questions on scales ranging from 0 (pain doesn't influence me) to 10 (pain hinders me a lot). And two visual analogue scales of 10 centimeters (I don't have pain at all - I am in full pain). | Questionnaires will be filled in at the end of each intervention day during the intervention period of 28 days |
| Medication use questionnaire | Use of medication during the intervention period. | Questionnaires will be filled in at the end of each intervention day during the intervention period of 28 days |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Virtual reality, Quality of life, Back pain
|
NCT03865446
|
Evaluate Severe Hepatic Impairment on Dacomitinib PK
|
This is a post approval requirement to study the effect of severe hepatic impairment on the pharmacokinetics of dacomitinib.
|
This is a Phase 1, open label, parallel group study to investigate the effect of severe hepatic impairment on the plasma PK, safety and tolerability after a single oral 30 mg dose of dacomitinib under fasted conditions.~Approximately 18 participants will be enrolled into the study to ensure at least 6 PK evaluable (having data for estimating primary PK parameters for dacomitinib) participants in each cohort.
|
A PHASE 1, OPEN-LABEL, SINGLE-DOSE, PARALLEL-GROUP STUDY TO EVALUATE THE PLASMA PHARMACOKINETICS AND SAFETY OF DACOMITINIB IN PARTICIPANTS WITH SEVERELY IMPAIRED HEPATIC FUNCTION RELATIVE TO PARTICIPANTS WITH NORMAL HEPATIC FUNCTION
|
Severe Hepatic Impairment
|
* Drug: Dacomitinib
|
Inclusion Criteria~Participants are eligible to be included in the study only if all of the following criteria apply:~Male and/or female participants of non childbearing potential must be 18 to 75 years of age, inclusive, at the time of signing the informed consent document (ICD).~Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.~Weight:~Body mass index (BMI) of 17.5 to 40 kg/m2; and a total body weight >50 kg (110 lb).~Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.~Exclusion Criteria:~Participants are excluded from the study if any of the following criteria apply:~Any condition possibly affecting drug absorption (eg, gastrectomy).~Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or IP administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.~History of or current positive results for human immunodeficiency virus (HIV).~Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of IP used in this study (whichever is longer).~Hypersensitivity to dacomitinib or its excipients.~A positive urine drug test. Participants with severe hepatic impairment (Cohort 1) will be eligible to participate if their urine drug test is positive with a drug for a prescribed condition that is not expected to interfere with the PK of dacomitinib.~Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.~History of sensitivity to heparin or heparin induced thrombocytopenia.~Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.~Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Sponsor employees, including their family members, directly involved in the conduct of the study.
|
18 Years
|
75 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of Dacomitinib | Cmax of Dacomitinib was analyzed. | Pre-dose and 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 264 hours post dose on Day 1 |
| Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of Dacomitinib | AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). | Pre-dose and 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 264 hours post dose on Day 1 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Laboratory Abnormalities | Laboratory abnormalities included hematology- Erythrocyte mean corpuscular hemoglobin: less than (<) 0.9 *lower limit of normal (LLN), platelets: < 0.5* LLN, leukocytes: < 0.6* LLN, lymphocytes: < 0.8* LLN, eosinophils: greater than (>) 1.2* lower limit of normal (ULN), partial thromboplastin time (PTT): > 1.1* ULN, prothrombin time: > 1.1* ULN, Prothrombin Intl. normalized ratio: > 1.1* ULN, clinical chemistry- bilirubin: > 1.5* ULN, protein: < 0.8* LLN, albumin: < 0.8* LLN, urinalysis- urine protein: greater than or equal to (>=) 1, urine hemoglobin: >= 1, urobilinogen: >= 1, urine erythrocytes: >= 20. | Baseline up to Day 7 |
| Number of Participants With Physical Examination Abnormalities | Height and weight were measured to calculate body mass index abnormality. | Baseline up to Day 7 |
| Number of Participants With Vital Sign Parameters Meeting Criteria of Potential Clinical Concern | Systolic blood pressure, diastolic blood pressure and pulse rate were evaluated for examination of vital signs. Criteria for potential concern in absolute values of vital sign: pulse rate: <40 beats per minute (bpm), >120 beats per minute; supine diastolic blood pressure: <50 millimeter of mercury (mm Hg); supine systolic blood pressure: <90 mm Hg. Criteria for potential concern in change from baseline in vital sign values: supine diastolic blood pressure: greater than or equal to >= 30 mm Hg increase or decrease from baseline; supine diastolic blood pressure: >=20 mm Hg increase or decrease from baseline. Only participants with vital sign parameters meeting criteria of potential clinical concern are reported. | Baseline up to Day 7 |
| Number of Participants With ECG Parameters Meeting Criteria of Potential Clinical Concern | ECG parameters RR interval, PR interval, QRS interval, QT interval, QTC interval, QTCB, QTCF and heart rate were measured. Criteria of potential concern for absolute values: PR interval: >=300 milliseconds; QRS interval >=140 milliseconds; QT interval: >=500 milliseconds; QTCF (Fridericia's correction formula) : >= 450 to < 480 milliseconds, >=480 to <500 milliseconds, >=500 milliseconds. Criteria of potential concern for change from baseline values: PR interval: when baseline is >200 millisecond- change >=25%, when baseline <200 milliseconds- change >=50%; QRS interval: change >= 50%; QTCF: change >=30 to <60, change >=60. In this outcome measure, participants meeting the criteria of potential concern for any of the ECG parameters are reported. | Baseline up to Day 7 |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. 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; medically important events. A treatment emergent AE was defined as an event that emerged during the treatment period (Up to Day 35) that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. | Baseline up to Day 35 |
|
Pharmacokinetics, Dacomitinib, Hepatic Impairment
|
Liver Diseases, Digestive System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (Dacomitinib)<br>severe hepatic impairment group | Drug: Dacomitinib<br>* anti-cancer agent<br>* Other names: PF-00299804; VIZIMPRO;|
| Experimental: Cohort 2 (Dacomitinib)<br>normal hepatic function | Drug: Dacomitinib<br>* anti-cancer agent<br>* Other names: PF-00299804; VIZIMPRO;|
|
Evaluate Severe Hepatic Impairment on Dacomitinib PK
Study Overview
=================
Brief Summary
-----------------
This is a post approval requirement to study the effect of severe hepatic impairment on the pharmacokinetics of dacomitinib.
Detailed Description
-----------------
This is a Phase 1, open label, parallel group study to investigate the effect of severe hepatic impairment on the plasma PK, safety and tolerability after a single oral 30 mg dose of dacomitinib under fasted conditions. Approximately 18 participants will be enrolled into the study to ensure at least 6 PK evaluable (having data for estimating primary PK parameters for dacomitinib) participants in each cohort.
Official Title
-----------------
A PHASE 1, OPEN-LABEL, SINGLE-DOSE, PARALLEL-GROUP STUDY TO EVALUATE THE PLASMA PHARMACOKINETICS AND SAFETY OF DACOMITINIB IN PARTICIPANTS WITH SEVERELY IMPAIRED HEPATIC FUNCTION RELATIVE TO PARTICIPANTS WITH NORMAL HEPATIC FUNCTION
Conditions
-----------------
Severe Hepatic Impairment
Intervention / Treatment
-----------------
* Drug: Dacomitinib
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Participants are eligible to be included in the study only if all of the following criteria apply: Male and/or female participants of non childbearing potential must be 18 to 75 years of age, inclusive, at the time of signing the informed consent document (ICD). Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. Weight: Body mass index (BMI) of 17.5 to 40 kg/m2; and a total body weight >50 kg (110 lb). Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: Any condition possibly affecting drug absorption (eg, gastrectomy). Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or IP administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. History of or current positive results for human immunodeficiency virus (HIV). Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of IP used in this study (whichever is longer). Hypersensitivity to dacomitinib or its excipients. A positive urine drug test. Participants with severe hepatic impairment (Cohort 1) will be eligible to participate if their urine drug test is positive with a drug for a prescribed condition that is not expected to interfere with the PK of dacomitinib. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing. History of sensitivity to heparin or heparin induced thrombocytopenia. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Sponsor employees, including their family members, directly involved in the conduct of the study.
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: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (Dacomitinib)<br>severe hepatic impairment group | Drug: Dacomitinib<br>* anti-cancer agent<br>* Other names: PF-00299804; VIZIMPRO;|
| Experimental: Cohort 2 (Dacomitinib)<br>normal hepatic function | Drug: Dacomitinib<br>* anti-cancer agent<br>* Other names: PF-00299804; VIZIMPRO;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of Dacomitinib | Cmax of Dacomitinib was analyzed. | Pre-dose and 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 264 hours post dose on Day 1 |
| Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of Dacomitinib | AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). | Pre-dose and 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 264 hours post dose on Day 1 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Laboratory Abnormalities | Laboratory abnormalities included hematology- Erythrocyte mean corpuscular hemoglobin: less than (<) 0.9 *lower limit of normal (LLN), platelets: < 0.5* LLN, leukocytes: < 0.6* LLN, lymphocytes: < 0.8* LLN, eosinophils: greater than (>) 1.2* lower limit of normal (ULN), partial thromboplastin time (PTT): > 1.1* ULN, prothrombin time: > 1.1* ULN, Prothrombin Intl. normalized ratio: > 1.1* ULN, clinical chemistry- bilirubin: > 1.5* ULN, protein: < 0.8* LLN, albumin: < 0.8* LLN, urinalysis- urine protein: greater than or equal to (>=) 1, urine hemoglobin: >= 1, urobilinogen: >= 1, urine erythrocytes: >= 20. | Baseline up to Day 7 |
| Number of Participants With Physical Examination Abnormalities | Height and weight were measured to calculate body mass index abnormality. | Baseline up to Day 7 |
| Number of Participants With Vital Sign Parameters Meeting Criteria of Potential Clinical Concern | Systolic blood pressure, diastolic blood pressure and pulse rate were evaluated for examination of vital signs. Criteria for potential concern in absolute values of vital sign: pulse rate: <40 beats per minute (bpm), >120 beats per minute; supine diastolic blood pressure: <50 millimeter of mercury (mm Hg); supine systolic blood pressure: <90 mm Hg. Criteria for potential concern in change from baseline in vital sign values: supine diastolic blood pressure: greater than or equal to >= 30 mm Hg increase or decrease from baseline; supine diastolic blood pressure: >=20 mm Hg increase or decrease from baseline. Only participants with vital sign parameters meeting criteria of potential clinical concern are reported. | Baseline up to Day 7 |
| Number of Participants With ECG Parameters Meeting Criteria of Potential Clinical Concern | ECG parameters RR interval, PR interval, QRS interval, QT interval, QTC interval, QTCB, QTCF and heart rate were measured. Criteria of potential concern for absolute values: PR interval: >=300 milliseconds; QRS interval >=140 milliseconds; QT interval: >=500 milliseconds; QTCF (Fridericia's correction formula) : >= 450 to < 480 milliseconds, >=480 to <500 milliseconds, >=500 milliseconds. Criteria of potential concern for change from baseline values: PR interval: when baseline is >200 millisecond- change >=25%, when baseline <200 milliseconds- change >=50%; QRS interval: change >= 50%; QTCF: change >=30 to <60, change >=60. In this outcome measure, participants meeting the criteria of potential concern for any of the ECG parameters are reported. | Baseline up to Day 7 |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. 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; medically important events. A treatment emergent AE was defined as an event that emerged during the treatment period (Up to Day 35) that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. | Baseline up to Day 35 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pharmacokinetics, Dacomitinib, Hepatic Impairment
|
NCT00913913
|
Bevacizumab, Autologous Tumor/DC Vaccine, IL-2 and IFNα-2b in Metastatic Renal Cell Carcinoma (RCC) Patients
|
Immune therapies, such as a IL-2, for metastatic renal cell carcinoma (mRCC) are designed to mobilize immune effector cells that recognize and destroy cancer. The investigators have recently observed a 50% objective response rate (16% CR) in mRCC patients treated with autologous tumor lysate -dendritic cell (DC)-vaccine, IL-2 and interferon alfa (IFN). New agents inhibiting vascular endothelial growth factor (VEGF) pathways have demonstrated significant benefit in mRCC patients as well, but rarely induce CRs. High blood VEGF is associated with poor response to IL-2 and can cause tumor specific immune dysregulation. To test whether complementary mechanisms of immune activation and disruption of regulatory pathways enhance outcome the investigators plan to treat 24 mRCC patients in a phase II trial using bevacizumab, DC vaccine, IL-2, and IFN. Observations from this project will be used in the development of novel cancer therapies which, if successful, will decrease the burden of cancer on the public.~The investigators propose to determine 1) the objective clinical response rate to treatment and progression free survival, 2) the clinical and autoimmune related toxicity profile of therapy, and 3) the treatment related tumor-specific immune response and the relationship of tumor-specific immune response and objective clinical response.
|
All eligible patients will receive a total of five treatment weeks, each consisting of approximately 5 days. Prior to therapy, patients will undergo apheresis for DC preparation. DC-Tumor vaccines will be frozen in 90% pooled human AB serum/ 10% DMSO to be used for treatment Patients will be dosed with bevacizumab (10mg/kg, Genentech) intravenously every two weeks beginning four weeks prior to the first vaccine. Each treatment week includes ultrasound guided intranodal DC-vaccine injection (1 X 107 cells/1mL), followed by 5 days of continuous intravenous infusion of IL-2 (18 MiU/m2, Novartis), and three subcutaneous injections of IFNa-2b (6 MiU, Schering -Plough Corp.) (every other day). The first two treatment weeks, the induction phase, will be separated by a 9 day rest. Three additional treatment weeks, the maintenance phase, will be separated by 23 rest days.
|
A Phase II Study of VEGF Blockade With Bevacizumab Combined With Autologous Tumor/Dendritic Cell Vaccine (DC Vaccine), Interleukin-2 (IL-2) and Interferon-α-2b (IFNα-2b) in Patients With Metastatic Renal Cell Carcinoma (RCC)
|
Metastatic Renal Cell Carcinoma
|
* Biological: DC vaccine
* Drug: Bevacizumab
* Biological: IL-2
* Biological: IFN
|
Inclusion Criteria:~Histologically confirmed metastatic renal cell carcinoma with measurable disease.~Adequate tumor tissue properly stored and available to produce lysate for a minimum of three vaccine preparations.~Patients must be at least 4 weeks from their last therapy (tyrosine kinase inhibitors, immunotherapy, radiation, surgery or chemotherapy (6 weeks for nitrosureas) and recovered from all ill effects.~Have measurable disease.~Patients must be at least 4 weeks from major surgery, 1 week from minor surgery, and recovered from all ill effects.~Karnofsky Performance Status ≥80%.~Adequate end organ function:~Women should not be lactating and, if of childbearing age, have a negative pregnancy test within two weeks of entry to the study.~Appropriate contraception in both genders.~The patient must be competent and have signed informed consent.~Patients may have received one prior therapy with targeted therapies (e.g. sorafenib and sunitinib).~Exclusion Criteria:~Patients who have previously received bevacizumab or IL-2 are not eligible.~Concomitant second malignancy except for non-melanoma skin cancer, and non-invasive cancer such as cervical CIS, superficial bladder cancer without local recurrence or breast CIS.~In patients with a prior history of invasive malignancy, less than five years in complete remission.~Positive serology for HIV, hepatitis B or hepatitis C which should be confirmed with antigenemia.~Significant co-morbid illness such as uncontrolled diabetes or active infection that would preclude treatment on this regimen.~Use of corticosteroids or other immunosuppression (if patient had been taking steroids, at least 2 weeks must have passed since the last dose). Inhaled steroids > 1000mcg beclomethasone per day or its equivalent.~History of inflammatory bowel disease or other serious autoimmune disease. (Not including thyroiditis and rheumatoid arthritis).~Patients with organ allografts.~Uncontrolled hypertension (BP >150/100 mmHg).~Proteinuria dipstick > 3+ or > 2gm/24 hours, or a urine protein:creatinine ratio > 1.0 at screening.~Major surgery, open biopsy, significant traumatic injury within 28 days of starting treatment or anticipation of need for major surgical procedure during the course of the study.~Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to starting treatment. Central venous catheter placements are permitted.~History of abdominal fistula, gastrointestinal perforation, or intrabdominal abscess within 6 months prior to starting treatment.~Serious, non-healing wound, ulcer, or bone fracture.~History of tumor-related or other serious hemorrhage, bleeding diathesis, or underlying coagulopathy.~History of deep venous thrombosis, or other thrombotic event within the past six months or clinically significant peripheral vascular disease.~Inability to comply with study and/or follow-up procedures.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | median progression free survival | 5 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Characterize the Number of Participants With Clinical and Autoimune Related Toxicity of Treatment | To characterize the clinical and autoimmune related toxicity profile of the combined treatment regimen using CTCAE 3. Toxicity reported are those expected from high dose IL-2 and were not considered adverse events. | 5 years |
|
Renal Cell Carcinoma
|
Bevacizumab, Antineoplastic Agents, Immunological, Antineoplastic Agents, Angiogenesis Inhibitors, Angiogenesis Modulating Agents, Growth Substances, Physiological Effects of Drugs, Growth Inhibitors
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bevacizumab,IL-2, IFN, DC vaccine<br>Patients will be dosed with bevacizumab (10mg/kg) intravenously every two weeks beginning four weeks prior to the first vaccine. Each treatment week includes ultrasound guided intranodal DC-vaccine injection (1 X 107 cells/1mL), followed by 5 days of continuous intravenous infusion of IL-2 (18 MiU/m2), and three subcutaneous injections of IFNa-2b (6 MiU) (every other day) | Biological: DC vaccine<br>* DC Vaccine therapy 10E7 intranodally every cycle<br>Drug: Bevacizumab<br>* Bevacizumab 10mg/kg iv every 2 weeks<br>* Other names: Avastin;Biological: IL-2<br>* IL-2 18 MiU/m2 CI 5 days<br>Biological: IFN<br>* IFN 6 MiU subc TIW<br>|
|
Bevacizumab, Autologous Tumor/DC Vaccine, IL-2 and IFNα-2b in Metastatic Renal Cell Carcinoma (RCC) Patients
Study Overview
=================
Brief Summary
-----------------
Immune therapies, such as a IL-2, for metastatic renal cell carcinoma (mRCC) are designed to mobilize immune effector cells that recognize and destroy cancer. The investigators have recently observed a 50% objective response rate (16% CR) in mRCC patients treated with autologous tumor lysate -dendritic cell (DC)-vaccine, IL-2 and interferon alfa (IFN). New agents inhibiting vascular endothelial growth factor (VEGF) pathways have demonstrated significant benefit in mRCC patients as well, but rarely induce CRs. High blood VEGF is associated with poor response to IL-2 and can cause tumor specific immune dysregulation. To test whether complementary mechanisms of immune activation and disruption of regulatory pathways enhance outcome the investigators plan to treat 24 mRCC patients in a phase II trial using bevacizumab, DC vaccine, IL-2, and IFN. Observations from this project will be used in the development of novel cancer therapies which, if successful, will decrease the burden of cancer on the public. The investigators propose to determine 1) the objective clinical response rate to treatment and progression free survival, 2) the clinical and autoimmune related toxicity profile of therapy, and 3) the treatment related tumor-specific immune response and the relationship of tumor-specific immune response and objective clinical response.
Detailed Description
-----------------
All eligible patients will receive a total of five treatment weeks, each consisting of approximately 5 days. Prior to therapy, patients will undergo apheresis for DC preparation. DC-Tumor vaccines will be frozen in 90% pooled human AB serum/ 10% DMSO to be used for treatment Patients will be dosed with bevacizumab (10mg/kg, Genentech) intravenously every two weeks beginning four weeks prior to the first vaccine. Each treatment week includes ultrasound guided intranodal DC-vaccine injection (1 X 107 cells/1mL), followed by 5 days of continuous intravenous infusion of IL-2 (18 MiU/m2, Novartis), and three subcutaneous injections of IFNa-2b (6 MiU, Schering -Plough Corp.) (every other day). The first two treatment weeks, the induction phase, will be separated by a 9 day rest. Three additional treatment weeks, the maintenance phase, will be separated by 23 rest days.
Official Title
-----------------
A Phase II Study of VEGF Blockade With Bevacizumab Combined With Autologous Tumor/Dendritic Cell Vaccine (DC Vaccine), Interleukin-2 (IL-2) and Interferon-α-2b (IFNα-2b) in Patients With Metastatic Renal Cell Carcinoma (RCC)
Conditions
-----------------
Metastatic Renal Cell Carcinoma
Intervention / Treatment
-----------------
* Biological: DC vaccine
* Drug: Bevacizumab
* Biological: IL-2
* Biological: IFN
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed metastatic renal cell carcinoma with measurable disease. Adequate tumor tissue properly stored and available to produce lysate for a minimum of three vaccine preparations. Patients must be at least 4 weeks from their last therapy (tyrosine kinase inhibitors, immunotherapy, radiation, surgery or chemotherapy (6 weeks for nitrosureas) and recovered from all ill effects. Have measurable disease. Patients must be at least 4 weeks from major surgery, 1 week from minor surgery, and recovered from all ill effects. Karnofsky Performance Status ≥80%. Adequate end organ function: Women should not be lactating and, if of childbearing age, have a negative pregnancy test within two weeks of entry to the study. Appropriate contraception in both genders. The patient must be competent and have signed informed consent. Patients may have received one prior therapy with targeted therapies (e.g. sorafenib and sunitinib). Exclusion Criteria: Patients who have previously received bevacizumab or IL-2 are not eligible. Concomitant second malignancy except for non-melanoma skin cancer, and non-invasive cancer such as cervical CIS, superficial bladder cancer without local recurrence or breast CIS. In patients with a prior history of invasive malignancy, less than five years in complete remission. Positive serology for HIV, hepatitis B or hepatitis C which should be confirmed with antigenemia. Significant co-morbid illness such as uncontrolled diabetes or active infection that would preclude treatment on this regimen. Use of corticosteroids or other immunosuppression (if patient had been taking steroids, at least 2 weeks must have passed since the last dose). Inhaled steroids > 1000mcg beclomethasone per day or its equivalent. History of inflammatory bowel disease or other serious autoimmune disease. (Not including thyroiditis and rheumatoid arthritis). Patients with organ allografts. Uncontrolled hypertension (BP >150/100 mmHg). Proteinuria dipstick > 3+ or > 2gm/24 hours, or a urine protein:creatinine ratio > 1.0 at screening. Major surgery, open biopsy, significant traumatic injury within 28 days of starting treatment or anticipation of need for major surgical procedure during the course of the study. Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to starting treatment. Central venous catheter placements are permitted. History of abdominal fistula, gastrointestinal perforation, or intrabdominal abscess within 6 months prior to starting treatment. Serious, non-healing wound, ulcer, or bone fracture. History of tumor-related or other serious hemorrhage, bleeding diathesis, or underlying coagulopathy. History of deep venous thrombosis, or other thrombotic event within the past six months or clinically significant peripheral vascular disease. Inability to comply with study and/or follow-up procedures.
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: bevacizumab,IL-2, IFN, DC vaccine<br>Patients will be dosed with bevacizumab (10mg/kg) intravenously every two weeks beginning four weeks prior to the first vaccine. Each treatment week includes ultrasound guided intranodal DC-vaccine injection (1 X 107 cells/1mL), followed by 5 days of continuous intravenous infusion of IL-2 (18 MiU/m2), and three subcutaneous injections of IFNa-2b (6 MiU) (every other day) | Biological: DC vaccine<br>* DC Vaccine therapy 10E7 intranodally every cycle<br>Drug: Bevacizumab<br>* Bevacizumab 10mg/kg iv every 2 weeks<br>* Other names: Avastin;Biological: IL-2<br>* IL-2 18 MiU/m2 CI 5 days<br>Biological: IFN<br>* IFN 6 MiU subc TIW<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | median progression free survival | 5 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Characterize the Number of Participants With Clinical and Autoimune Related Toxicity of Treatment | To characterize the clinical and autoimmune related toxicity profile of the combined treatment regimen using CTCAE 3. Toxicity reported are those expected from high dose IL-2 and were not considered adverse events. | 5 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Renal Cell Carcinoma
|
NCT01027793
|
Trial Comparing Treatment of Tretinoin or Superficial Dermabrasion for Stretch Marks
|
This study aims to evaluate head-to-head the effectiveness of tretinoin 0.5% and superficial dermabrasion in subjects that have recent stretch marks.
|
Healthy female subjects, from 11 t0 25 years old, that have thin (1-5mm) recent(less than 6 months of evolution),reddish or purple line stretch marks. The striae should be symmetrical and it could be located in the abdomen,breasts, upper arms, thighs (both inner and outer), hips, and buttocks.~Thirty subjects will be randomly divided in two groups:~Group 1 will receive tretinoin cream that should be applied daily in areas affected by stretch marks.~Group 2 will receive 16 sessions of dermabrasion that would be held in the research center.~Subjects will be evaluated by pictures, measurement of width and length of stretch marks, using Mirror System(Canfield).~Biopsy to quantify alterations of epidermis and dermis of treated area, will be held pre-treatment and 2 weeks after the conclusion of treatment. For biopsy will be used a punch of 3mm.~The results will be evaluated two weeks after the conclusion of the interventions. An independent dermatologist, blinded for intervention, will analyse pictures pre and post treatment. This subjective evaluation will be performed using Global Aesthetic Improvement Scale.~Safety and adverse events will be assessed each visit.
|
Randomized Clinical Trial Comparing Treatment of Tretinoin or Superficial Dermabrasion for Recent Stretch Marks
|
Stretch Marks, Striae, Treatment
|
* Drug: Tretinoin cream 0.005%
* Device: Superficial Dermabrasion
|
Inclusion Criteria:~Female subjects, aged between 11 and 25 years~Female subjects of childbearing age that present a negative urine pregnancy test and are using an effective contraceptive method for at least 3 months prior the study~Subjects that have thin (1-5mm) recent(less than 6 months of evolution),reddish or purple line stretch marks. The striae should be symmetrical and it could be located in the abdomen,breasts, upper arms, thighs (both inner and outer), hips, and buttocks~Subjects agreeing to take part of the study, after being fully informed of the purpose and the nature of the investigation and after having signed the informed consent form~Subjects with sufficient schooling and awareness to enable them to cooperate to the degree required by this protocol~Subjects who had never received treatment for striae in the studied area~Exclusion Criteria:~Subjects whose medical history and physical examination present clinical pathology, as marfan Syndrome, cushing, systemic autoimmune or neurological diseases~Pregnant or women in breastfeeding, or women planning to become pregnant~Previous treatment for striae in the local area of the study.~Subjects that are in use of tretinoin or glycolic acid in the local area of the study.~Presence of white striae in the local area of the study~History of Connective Tissue Disease~History of keloid development or skin healing problems~Subjects that are taking medications associated with striae development, as systemic corticosteroids, indinavir, hormonal replacement therapy~Hypersensibility to retinoic acid~Subjects who intend to get tan in the area of the study, through exposure of sun or tanning machines during the study~Subjects that have a variation in their weight of more than 2 kg in a period of four months prior the study~Predisposition for chronic inflammatory process~Subjects with chronic diseases as diabetes, cardiopathy, neoplasm, HIV and autoimmune diseases (vitiligo, lupus)
|
11 Years
|
25 Years
|
Female
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Width of Stretch Marks | Striae width was measured with Mirror Medical Imaging Software (Canfield Scientific, Inc., Parsippany, NJ) | Baseline and 16 weeks |
| Length of Stretch Marks | Striae length was measured with Mirror Medical Imaging Software (Canfield Scientific, Inc., Parsippany, NJ) | Baseline and 16 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Aesthetic Improvement Scale | Very much improved: Optimal cosmetic result for the implant in this patient~Much improved: Marked improvement in appearance from the initial condition but not completely optimal for this patient; touch-up would slightly improve the result 3 - Improved: Obvious improvement in appearance from the initial condition, but touch-up or retreatment is indicated 4 - No change: Appearance essentially the same as the original condition 5 - Worse: Appearance worse than the original condition | 16 weeks |
| Patient Satisfaction | Patient satisfaction measured with Lickert scale (Very satisfied, Satisfied, Neither satisfied nor unsatisfied, unsatisfied, very unsatisfied) | 16 weeks |
|
Stretch marks, Striae, Tretinoin, Superficial dermabrasion
|
Tretinoin, Antineoplastic Agents, Keratolytic Agents, Dermatologic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tretinoin<br>Group 1 will receive tretinoin cream 0.05%(Vitanol A, Stiefel) that should be applied daily in areas affected by stretch marks, in both sides, for a period of 16 weeks. | Drug: Tretinoin cream 0.005%<br>* Group 1 will receive tretinoin cream 0.05%(Vitanol A, Stiefel) that should be applied daily in areas affected by stretch marks, in both sides, for a period of 16 weeks.<br>* Other names: (Vitanol A, Stiefel);|
| Active Comparator: Superficial Dermabrasion<br>Group 2 will receive 16 sessions of dermabrasion that would be held in the research center. | Device: Superficial Dermabrasion<br>* Group 2 will receive 16 sessions of dermabrasion that would be held in the research center<br>|
|
Trial Comparing Treatment of Tretinoin or Superficial Dermabrasion for Stretch Marks
Study Overview
=================
Brief Summary
-----------------
This study aims to evaluate head-to-head the effectiveness of tretinoin 0.5% and superficial dermabrasion in subjects that have recent stretch marks.
Detailed Description
-----------------
Healthy female subjects, from 11 t0 25 years old, that have thin (1-5mm) recent(less than 6 months of evolution),reddish or purple line stretch marks. The striae should be symmetrical and it could be located in the abdomen,breasts, upper arms, thighs (both inner and outer), hips, and buttocks. Thirty subjects will be randomly divided in two groups: Group 1 will receive tretinoin cream that should be applied daily in areas affected by stretch marks. Group 2 will receive 16 sessions of dermabrasion that would be held in the research center. Subjects will be evaluated by pictures, measurement of width and length of stretch marks, using Mirror System(Canfield). Biopsy to quantify alterations of epidermis and dermis of treated area, will be held pre-treatment and 2 weeks after the conclusion of treatment. For biopsy will be used a punch of 3mm. The results will be evaluated two weeks after the conclusion of the interventions. An independent dermatologist, blinded for intervention, will analyse pictures pre and post treatment. This subjective evaluation will be performed using Global Aesthetic Improvement Scale. Safety and adverse events will be assessed each visit.
Official Title
-----------------
Randomized Clinical Trial Comparing Treatment of Tretinoin or Superficial Dermabrasion for Recent Stretch Marks
Conditions
-----------------
Stretch Marks, Striae, Treatment
Intervention / Treatment
-----------------
* Drug: Tretinoin cream 0.005%
* Device: Superficial Dermabrasion
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female subjects, aged between 11 and 25 years Female subjects of childbearing age that present a negative urine pregnancy test and are using an effective contraceptive method for at least 3 months prior the study Subjects that have thin (1-5mm) recent(less than 6 months of evolution),reddish or purple line stretch marks. The striae should be symmetrical and it could be located in the abdomen,breasts, upper arms, thighs (both inner and outer), hips, and buttocks Subjects agreeing to take part of the study, after being fully informed of the purpose and the nature of the investigation and after having signed the informed consent form Subjects with sufficient schooling and awareness to enable them to cooperate to the degree required by this protocol Subjects who had never received treatment for striae in the studied area Exclusion Criteria: Subjects whose medical history and physical examination present clinical pathology, as marfan Syndrome, cushing, systemic autoimmune or neurological diseases Pregnant or women in breastfeeding, or women planning to become pregnant Previous treatment for striae in the local area of the study. Subjects that are in use of tretinoin or glycolic acid in the local area of the study. Presence of white striae in the local area of the study History of Connective Tissue Disease History of keloid development or skin healing problems Subjects that are taking medications associated with striae development, as systemic corticosteroids, indinavir, hormonal replacement therapy Hypersensibility to retinoic acid Subjects who intend to get tan in the area of the study, through exposure of sun or tanning machines during the study Subjects that have a variation in their weight of more than 2 kg in a period of four months prior the study Predisposition for chronic inflammatory process Subjects with chronic diseases as diabetes, cardiopathy, neoplasm, HIV and autoimmune diseases (vitiligo, lupus)
Ages Eligible for Study
-----------------
Minimum Age: 11 Years
Maximum Age: 25 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: Tretinoin<br>Group 1 will receive tretinoin cream 0.05%(Vitanol A, Stiefel) that should be applied daily in areas affected by stretch marks, in both sides, for a period of 16 weeks. | Drug: Tretinoin cream 0.005%<br>* Group 1 will receive tretinoin cream 0.05%(Vitanol A, Stiefel) that should be applied daily in areas affected by stretch marks, in both sides, for a period of 16 weeks.<br>* Other names: (Vitanol A, Stiefel);|
| Active Comparator: Superficial Dermabrasion<br>Group 2 will receive 16 sessions of dermabrasion that would be held in the research center. | Device: Superficial Dermabrasion<br>* Group 2 will receive 16 sessions of dermabrasion that would be held in the research center<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Width of Stretch Marks | Striae width was measured with Mirror Medical Imaging Software (Canfield Scientific, Inc., Parsippany, NJ) | Baseline and 16 weeks |
| Length of Stretch Marks | Striae length was measured with Mirror Medical Imaging Software (Canfield Scientific, Inc., Parsippany, NJ) | Baseline and 16 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Aesthetic Improvement Scale | Very much improved: Optimal cosmetic result for the implant in this patient Much improved: Marked improvement in appearance from the initial condition but not completely optimal for this patient; touch-up would slightly improve the result 3 - Improved: Obvious improvement in appearance from the initial condition, but touch-up or retreatment is indicated 4 - No change: Appearance essentially the same as the original condition 5 - Worse: Appearance worse than the original condition | 16 weeks |
| Patient Satisfaction | Patient satisfaction measured with Lickert scale (Very satisfied, Satisfied, Neither satisfied nor unsatisfied, unsatisfied, very unsatisfied) | 16 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Stretch marks, Striae, Tretinoin, Superficial dermabrasion
|
NCT00004727
|
Antiplatelet Therapy to Prevent Stroke in African Americans
|
The African-American Antiplatelet Stroke Prevention Study is designed to prevent recurrent strokes by administration of aspirin or ticlopidine. The study also provides community information on reducing risk of stroke and recognizing the symptoms of stroke. The study involves more than 50 participating hospitals located throughout the United States. Study medication is provided free of charge, and a transportation stipend is available for those in need.
|
Stroke is one of the important diseases that disproportionately affects African-Americans. African-American men and women are about 2 times more likely than whites to die of cerebrovascular disease or experience stroke. Scientific information about the efficacy and safety of stroke preventatives in this group is much needed, yet African-Americans and other minorities have been underrepresented in biomedical research studies. Preliminary data collected from nonwhite, predominantly African-American patients, suggest that ticlopidine is more effective than aspirin in the secondary prevention of stroke and death for these patients and that the risk of serious adverse events is lower. This is a multicenter, randomized, double-blind clinical trial of ticlopidine hydrochloride (500mg/day) and aspirin (650mg/day) in African-American patients with recent non-cardioembolic ischemic stroke. The primary purpose of the study is to compare the efficacy of ticlopidine and aspirin in the prevention of the outcome endpoints recurrent stroke, vascular death, and myocardial infarction in these African-American patients. Adverse experiences will be studied to further our understanding of the safety of these medications in this group. The study is being conducted at 50 sites experienced in the diagnosis and treatment of stroke. 1800 patients are being enrolled over 3-5 years, and each will be in the study for at least 2 years. Patients will be randomly assigned to treatment at least 7 days, but no more than 90 days after cerebral infarction. The trial promises to provide much needed information about secondary stroke prevention in African-Americans and has the support of established African-American physician, church-based, and community organizations. Enrollment of a substantial number of African-American women is anticipated. Data from these patients will significantly add to our understanding of cerebrovascular disease among black women. Furthermore, the study could also serve as an organizational framework for future studies of stroke prevention or hyperacute treatment in the African-American population.
|
African American Antiplatelet Stroke Prevention Study
|
Stroke, Cerebral Infarction
|
* Drug: aspirin
* Drug: ticlopidine
|
Inclusion Criteria:~African Americans are eligible if they had a non-cardioembolic ischemic stroke at lease 7 days, but no more than 90 days before entering the trial.~African American~29-85 years of age~Non-cardioembolic cerebral infarct~Onset of entry stroke at least 7 days but no more than 90 days~CT or MRI following entry stroke and consistent with occurrence of entry stroke (i.e., shows entry infarct, shows old infarct, or shows no infarct) Measurable neurologic deficit that correlates with onset of entry stroke.~Informed consent~Able to follow outpatient treatment program~Exclusion Criteria:~Volunteers with transient ischemic attack (TIA) as the potentially qualifying event, intracranial hemorrhage, nonatherosclerotic stroke, sensitivity or major allergy to the study drugs, Modified Barthel Index < 10 or childbearing potential are not eligible.~Non-qualifying entry events: TIA, subarachnoid hemorrhage, cardiac embolism, iatrogenic stroke, postoperative stroke within 30 days of operation, and carotid endarterectomy as preventive treatment of entry stroke.~Mean arterial blood pressure > 130mmHg on 3 consecutive days~Modified Barthel Index < 10~History of dementia or neurodegenerative disease~Severe comorbid condition such as cancer that would limit survival during 2 year follow-up period~Concurrent enrollment in another clinical trial~Sensitivity or allergy to aspirin or ticlopidine~Women of childbearing potential~Peptic ulcer disease, active bleeding diathesis, lower gastrointestinal bleeding, platelet or other hematologic abnormality currently active or clinically active in the past year, hematuria, positive stool guaiac, prolonged PT or PTT, BUN > 40mg%, serum creatinine > 2.0mg%, thrombocytopenia or neutropenia as defined by the lower limit of normal for the platelet count or white blood cell count, respectively (absolute neutrophil count of > 1800/mm3 required for participation), or > 2 times the upper range of normal on liver function tests (SGOT, SGPT, total bilirubin)
|
29 Years
|
85 Years
|
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
acetylsalicylic acid, ticlopidine, prevention, stroke, cerebral infarction, Chicago, non-cardioembolic ischemic stroke, African American, antiplatelet, aspirin, ASA
|
Antipyretics, Aspirin, Ticlopidine, Analgesics, Anti-Inflammatory Agents, Non-Steroidal, Analgesics, Non-Narcotic, 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, Purinergic P2Y Receptor Antagonists, Purinergic P2 Receptor Antagonists, Purinergic Antagonists, Purinergic Agents, Neurotransmitter Agents, Cytochrome P-450 CYP2C19 Inhibitors, Cytochrome P-450 Enzyme Inhibitors
|
| Intervention/Treatment |
| --- |
|Drug: aspirin|nan|
|Drug: ticlopidine|nan|
|
Antiplatelet Therapy to Prevent Stroke in African Americans
Study Overview
=================
Brief Summary
-----------------
The African-American Antiplatelet Stroke Prevention Study is designed to prevent recurrent strokes by administration of aspirin or ticlopidine. The study also provides community information on reducing risk of stroke and recognizing the symptoms of stroke. The study involves more than 50 participating hospitals located throughout the United States. Study medication is provided free of charge, and a transportation stipend is available for those in need.
Detailed Description
-----------------
Stroke is one of the important diseases that disproportionately affects African-Americans. African-American men and women are about 2 times more likely than whites to die of cerebrovascular disease or experience stroke. Scientific information about the efficacy and safety of stroke preventatives in this group is much needed, yet African-Americans and other minorities have been underrepresented in biomedical research studies. Preliminary data collected from nonwhite, predominantly African-American patients, suggest that ticlopidine is more effective than aspirin in the secondary prevention of stroke and death for these patients and that the risk of serious adverse events is lower. This is a multicenter, randomized, double-blind clinical trial of ticlopidine hydrochloride (500mg/day) and aspirin (650mg/day) in African-American patients with recent non-cardioembolic ischemic stroke. The primary purpose of the study is to compare the efficacy of ticlopidine and aspirin in the prevention of the outcome endpoints recurrent stroke, vascular death, and myocardial infarction in these African-American patients. Adverse experiences will be studied to further our understanding of the safety of these medications in this group. The study is being conducted at 50 sites experienced in the diagnosis and treatment of stroke. 1800 patients are being enrolled over 3-5 years, and each will be in the study for at least 2 years. Patients will be randomly assigned to treatment at least 7 days, but no more than 90 days after cerebral infarction. The trial promises to provide much needed information about secondary stroke prevention in African-Americans and has the support of established African-American physician, church-based, and community organizations. Enrollment of a substantial number of African-American women is anticipated. Data from these patients will significantly add to our understanding of cerebrovascular disease among black women. Furthermore, the study could also serve as an organizational framework for future studies of stroke prevention or hyperacute treatment in the African-American population.
Official Title
-----------------
African American Antiplatelet Stroke Prevention Study
Conditions
-----------------
Stroke, Cerebral Infarction
Intervention / Treatment
-----------------
* Drug: aspirin
* Drug: ticlopidine
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: African Americans are eligible if they had a non-cardioembolic ischemic stroke at lease 7 days, but no more than 90 days before entering the trial. African American 29-85 years of age Non-cardioembolic cerebral infarct Onset of entry stroke at least 7 days but no more than 90 days CT or MRI following entry stroke and consistent with occurrence of entry stroke (i.e., shows entry infarct, shows old infarct, or shows no infarct) Measurable neurologic deficit that correlates with onset of entry stroke. Informed consent Able to follow outpatient treatment program Exclusion Criteria: Volunteers with transient ischemic attack (TIA) as the potentially qualifying event, intracranial hemorrhage, nonatherosclerotic stroke, sensitivity or major allergy to the study drugs, Modified Barthel Index < 10 or childbearing potential are not eligible. Non-qualifying entry events: TIA, subarachnoid hemorrhage, cardiac embolism, iatrogenic stroke, postoperative stroke within 30 days of operation, and carotid endarterectomy as preventive treatment of entry stroke. Mean arterial blood pressure > 130mmHg on 3 consecutive days Modified Barthel Index < 10 History of dementia or neurodegenerative disease Severe comorbid condition such as cancer that would limit survival during 2 year follow-up period Concurrent enrollment in another clinical trial Sensitivity or allergy to aspirin or ticlopidine Women of childbearing potential Peptic ulcer disease, active bleeding diathesis, lower gastrointestinal bleeding, platelet or other hematologic abnormality currently active or clinically active in the past year, hematuria, positive stool guaiac, prolonged PT or PTT, BUN > 40mg%, serum creatinine > 2.0mg%, thrombocytopenia or neutropenia as defined by the lower limit of normal for the platelet count or white blood cell count, respectively (absolute neutrophil count of > 1800/mm3 required for participation), or > 2 times the upper range of normal on liver function tests (SGOT, SGPT, total bilirubin)
Ages Eligible for Study
-----------------
Minimum Age: 29 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: Prevention
Allocation: Randomized
Masking: Double
Arms and Interventions
| Intervention/Treatment |
| --- |
|Drug: aspirin|nan|
|Drug: ticlopidine|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
-----------------
acetylsalicylic acid, ticlopidine, prevention, stroke, cerebral infarction, Chicago, non-cardioembolic ischemic stroke, African American, antiplatelet, aspirin, ASA
|
|
NCT04329091
|
Implications of Anesthetics on Sleep Consolidation
|
Sleep leads to consolidation of learning in humans, restoring memories that were forgotten over a waking day and protecting memories against future forgetting. Although theories of consolidation have linked sleep spindles seen on electroencephalography to consolidation due to their putative role in hippocampal transfer to the neocortex (Antony et al, 2019; Antony & Paller, 2017), spindles have not yet been linked to consolidation of perceptual learning or generalized learning. Prior research by a collaborator on this project has shown that sleep specifically aids in the consolidation of generalized perceptual learning of speech (Fenn, Nusbaum, & Margoliash, 2003). Subjects show a 10-point reduction in performance after a waking retention period, while no loss is found after a retention period containing sleep (Fenn et al., 2003).~Various measurable activities in the brain are associated with memory consolidation during sleep. This project intends study the effect of dexmedetomidine on memory consolidation during sleep~Hypothesis 1 The gain in perceptual learning after a 90 minute natural sleep nap will also occur after 90 minutes of a sufficient dose of IV dexmedetomidine to replicate sleep. This result would suggest that consolidation can occur under this anesthetic state of consciousness.~Hypothesis 2 The number and quality of sleep spindles seen on EEG in subjects administered dexmedetomidine will correlate with this gain in perceptual learning. This result would suggest that biomimetic sleep spindles are sufficient for producing memory consolidation.~Only those subjects capable of giving their own consent will be considered for this study.~The study will enroll 20 healthy subjects for this study between the ages of 18 and 35.~All volunteers will be fit and healthy, meeting the American Society of Anesthesiologists (ASA) physical status classification ASA 1 (normal healthy subjects) and ASA 2 (stable chronic condition) and of normal body habitus. Prior to the study enrollment, each volunteer will sign an informed consent form. A standard anesthetic medical history will be taken in addition to performing a focused standard pre-anesthetic physical examination in order to rule out active and chronic medical problems.
|
Implications of Anesthetics on Sleep Consolidation
|
Sleep
|
* Drug: Dexmedetomidine
|
Primary Inclusion Criteria for Healthy volunteers~Age between 18-35~Native English speaking~No hearing or speech difficulties~No psychiatric, neurologic, or sleep disorders~No chronic medical conditions, as reflected below under Primary Exclusion Criteria and above in 'Medical History'~Non-smokers (within 3 months)~Non-users of recreational or illicit drugs (including marijuana)~Must be willing and able to pass the drug tests (no psychoactive substances), no ingestion of alcohol or sleep-altering drugs for the 48 hours prior to the study session.~Normal weight~Primary Exclusion Criteria for Healthy volunteers~Speech difficulties/disorders~Hearing difficulties (including occluded or infected ear canals)~Current hairstyles that do not allow the high-density EEG cap to make contact with the scalp (e.g., individuals with hair extensions, braids, dreadlocks or hairstyles that restrict the ability of electrodes to touch the scalp)~Metal on/in/near their heads (including jewelry) that cannot be removed for the duration of the study~Metal implants~Serious abusers of alcohol or caffeine.~Existing or suspected psychological or neurological disorders~Pregnancy or suspected pregnancy (urine pregnancy test at visit 2)~Chronic or transient (e.g., jet lag) problems with sleep; suspected sleep disorder~Abnormal sleep habits, such as:~Sleeping less than 5 hours each night~Going to sleep before 8:00 PM or after 2:00 AM on a regular basis~Waking up before 5:00 AM or after 10:00 AM on a regular basis.~Currently taking medications that regulate blood pressure; a history of high blood pressure, diabetes or stroke~Chronic smokers~Current use of aspirin, or other medications which increase bleeding, prior to the study session.~Known drug allergies to anesthetics or a history of an adverse reaction to anesthesia.~Known allergy to adhesives or electrode gel~Medication that alters sleep, cognitive function, or both
|
18 Years
|
35 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perceptual Learning Protocol | Subjects are tested in the morning for word recognition on hard-to-understand speech, then trained on this speech (never hearing the same words twice) which produces about 20 percentage points of improvement. After sedation subjects are re-tested. During the morning, afternoon and evening post-tests, subjects will be tested on new spoken words. At each time point where the perceptual learning protocol is administered the number of words correctly perceived out of 50 will be measured. | 1 day |
|
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 Arm<br>Dexmedetomidine: Administration of a 0.5 mcg/kg bolus followed by an infusion of 0.5-0.7 mcg/kg/hr, titrated up by 0.1 mcg every 1 minute until the subject spontaneously closes his or her eyes. When the subject spontaneously closes his or her eyes the infusion continues for 90 minutes from that point. | Drug: Dexmedetomidine<br>* All subjects will receive Dexmedetomidine to induce sedation between their pre-sedation and post-sedation perceptual learning tests.<br>* Other names: Precedex;|
|
Implications of Anesthetics on Sleep Consolidation
Study Overview
=================
Brief Summary
-----------------
Sleep leads to consolidation of learning in humans, restoring memories that were forgotten over a waking day and protecting memories against future forgetting. Although theories of consolidation have linked sleep spindles seen on electroencephalography to consolidation due to their putative role in hippocampal transfer to the neocortex (Antony et al, 2019; Antony & Paller, 2017), spindles have not yet been linked to consolidation of perceptual learning or generalized learning. Prior research by a collaborator on this project has shown that sleep specifically aids in the consolidation of generalized perceptual learning of speech (Fenn, Nusbaum, & Margoliash, 2003). Subjects show a 10-point reduction in performance after a waking retention period, while no loss is found after a retention period containing sleep (Fenn et al., 2003). Various measurable activities in the brain are associated with memory consolidation during sleep. This project intends study the effect of dexmedetomidine on memory consolidation during sleep Hypothesis 1 The gain in perceptual learning after a 90 minute natural sleep nap will also occur after 90 minutes of a sufficient dose of IV dexmedetomidine to replicate sleep. This result would suggest that consolidation can occur under this anesthetic state of consciousness. Hypothesis 2 The number and quality of sleep spindles seen on EEG in subjects administered dexmedetomidine will correlate with this gain in perceptual learning. This result would suggest that biomimetic sleep spindles are sufficient for producing memory consolidation. Only those subjects capable of giving their own consent will be considered for this study. The study will enroll 20 healthy subjects for this study between the ages of 18 and 35. All volunteers will be fit and healthy, meeting the American Society of Anesthesiologists (ASA) physical status classification ASA 1 (normal healthy subjects) and ASA 2 (stable chronic condition) and of normal body habitus. Prior to the study enrollment, each volunteer will sign an informed consent form. A standard anesthetic medical history will be taken in addition to performing a focused standard pre-anesthetic physical examination in order to rule out active and chronic medical problems.
Official Title
-----------------
Implications of Anesthetics on Sleep Consolidation
Conditions
-----------------
Sleep
Intervention / Treatment
-----------------
* Drug: Dexmedetomidine
Participation Criteria
=================
Eligibility Criteria
-----------------
Primary Inclusion Criteria for Healthy volunteers Age between 18-35 Native English speaking No hearing or speech difficulties No psychiatric, neurologic, or sleep disorders No chronic medical conditions, as reflected below under Primary Exclusion Criteria and above in 'Medical History' Non-smokers (within 3 months) Non-users of recreational or illicit drugs (including marijuana) Must be willing and able to pass the drug tests (no psychoactive substances), no ingestion of alcohol or sleep-altering drugs for the 48 hours prior to the study session. Normal weight Primary Exclusion Criteria for Healthy volunteers Speech difficulties/disorders Hearing difficulties (including occluded or infected ear canals) Current hairstyles that do not allow the high-density EEG cap to make contact with the scalp (e.g., individuals with hair extensions, braids, dreadlocks or hairstyles that restrict the ability of electrodes to touch the scalp) Metal on/in/near their heads (including jewelry) that cannot be removed for the duration of the study Metal implants Serious abusers of alcohol or caffeine. Existing or suspected psychological or neurological disorders Pregnancy or suspected pregnancy (urine pregnancy test at visit 2) Chronic or transient (e.g., jet lag) problems with sleep; suspected sleep disorder Abnormal sleep habits, such as: Sleeping less than 5 hours each night Going to sleep before 8:00 PM or after 2:00 AM on a regular basis Waking up before 5:00 AM or after 10:00 AM on a regular basis. Currently taking medications that regulate blood pressure; a history of high blood pressure, diabetes or stroke Chronic smokers Current use of aspirin, or other medications which increase bleeding, prior to the study session. Known drug allergies to anesthetics or a history of an adverse reaction to anesthesia. Known allergy to adhesives or electrode gel Medication that alters sleep, cognitive function, or both
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 35 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: Dexmedetomidine Arm<br>Dexmedetomidine: Administration of a 0.5 mcg/kg bolus followed by an infusion of 0.5-0.7 mcg/kg/hr, titrated up by 0.1 mcg every 1 minute until the subject spontaneously closes his or her eyes. When the subject spontaneously closes his or her eyes the infusion continues for 90 minutes from that point. | Drug: Dexmedetomidine<br>* All subjects will receive Dexmedetomidine to induce sedation between their pre-sedation and post-sedation perceptual learning tests.<br>* Other names: Precedex;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perceptual Learning Protocol | Subjects are tested in the morning for word recognition on hard-to-understand speech, then trained on this speech (never hearing the same words twice) which produces about 20 percentage points of improvement. After sedation subjects are re-tested. During the morning, afternoon and evening post-tests, subjects will be tested on new spoken words. At each time point where the perceptual learning protocol is administered the number of words correctly perceived out of 50 will be measured. | 1 day |
|
|||
NCT01304485
|
PET Imaging Characteristics of C11-Acetate in Patients With Recurrent Prostate Carcinoma
|
Positron emission tomography (PET) imaging evaluation in men with recurrent prostate cancer to select patients who may benefit from directed therapy
|
The goal of this project is improved imaging of prostate cancer by positron emission tomography (PET) with use of the radiopharmaceutical C-11 Acetate, utilizing state-of-the-art PET/CT camera technology and processing algorithms.~A successful effort will lead to more accurate diagnosis of recurrence in patients with prostate cancer to allow for early directed therapy. This study is designed to generate data to add to the understanding of the effectiveness of C-11 Acetate, focusing on patients with recurrent or persistent disease after prostatectomy or radiation therapy.~The study is designed to expand on the database of C11-Acetate PET imaging in patients with prior definitive therapy for prostate cancer and evidence of biochemical recurrence (post therapy rise in PSA), and to evaluate the relationship between detection on C11-Acetate PET imaging, PSA (Trigger, Velocity and Doubling Time) and FDG PET imaging.~Specific questions to be addressed:~What is the yield of current state-of-the-art PET/CT with C-11 Acetate in detecting recurrent disease in this patient population?~How does the performance of PET with C-11 Acetate compare with that of PET using F-18 fluorodeoxyglucose (FDG-PET), Sodium F18 PET bone scans and with that of CT?~What is the optimal imaging protocol in terms of imaging time after injection?
|
Phase 2 Study: PET Imaging Characteristics of C11-Acetate in Patients With Prostate Carcinoma, Detection of Recurrent Disease With PSA Relapse
|
Prostate Cancer
|
* Drug: Sodium Acetate C11
|
Inclusion Criteria:~recurrent prostate cancer (detectable PSA following radical prostatectomy or rising PSA in patients with radiation therapy as the primary treatment)~Exclusion Criteria:~< 18 years old~claustrophobic patients
|
18 Years
| null |
Male
|
No
|
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SUV (Standardized Uptake Value) | Imaging studies will be evaluated both qualitatively and quantitatively using SUV (standardized uptake values): a measure of metabolism based on injected dose, patient weight and region of interest. | Day1 - Assessed at time of PET imaging - i.e. at the time of primary investigation/PET agent administration |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA (prostate specific antigen) | PSA will be monitored per routine clinical follow-up. | Every 3 - 6 months for 24 months after PET imaging |
|
Recurrent Prostate Carcinoma, sodium acetate c11, PET, prostate cancer, rising PSA, PSA recurrence, biochemical recurrence
|
Carcinoma, Prostatic Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Neoplasms, Genital Neoplasms, Male, Urogenital Neoplasms, Neoplasms by Site, Genital Diseases, Male, Genital Diseases, Urogenital Diseases, Prostatic Diseases, Male Urogenital Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium Acetate C11 PET Imaging<br> | Drug: Sodium Acetate C11<br>* PET Imaging with Sodium Acetate C11<br>* Other names: AC-PET;|
|
PET Imaging Characteristics of C11-Acetate in Patients With Recurrent Prostate Carcinoma
Study Overview
=================
Brief Summary
-----------------
Positron emission tomography (PET) imaging evaluation in men with recurrent prostate cancer to select patients who may benefit from directed therapy
Detailed Description
-----------------
The goal of this project is improved imaging of prostate cancer by positron emission tomography (PET) with use of the radiopharmaceutical C-11 Acetate, utilizing state-of-the-art PET/CT camera technology and processing algorithms. A successful effort will lead to more accurate diagnosis of recurrence in patients with prostate cancer to allow for early directed therapy. This study is designed to generate data to add to the understanding of the effectiveness of C-11 Acetate, focusing on patients with recurrent or persistent disease after prostatectomy or radiation therapy. The study is designed to expand on the database of C11-Acetate PET imaging in patients with prior definitive therapy for prostate cancer and evidence of biochemical recurrence (post therapy rise in PSA), and to evaluate the relationship between detection on C11-Acetate PET imaging, PSA (Trigger, Velocity and Doubling Time) and FDG PET imaging. Specific questions to be addressed: What is the yield of current state-of-the-art PET/CT with C-11 Acetate in detecting recurrent disease in this patient population? How does the performance of PET with C-11 Acetate compare with that of PET using F-18 fluorodeoxyglucose (FDG-PET), Sodium F18 PET bone scans and with that of CT? What is the optimal imaging protocol in terms of imaging time after injection?
Official Title
-----------------
Phase 2 Study: PET Imaging Characteristics of C11-Acetate in Patients With Prostate Carcinoma, Detection of Recurrent Disease With PSA Relapse
Conditions
-----------------
Prostate Cancer
Intervention / Treatment
-----------------
* Drug: Sodium Acetate C11
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: recurrent prostate cancer (detectable PSA following radical prostatectomy or rising PSA in patients with radiation therapy as the primary treatment) Exclusion Criteria: < 18 years old claustrophobic patients
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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium Acetate C11 PET Imaging<br> | Drug: Sodium Acetate C11<br>* PET Imaging with Sodium Acetate C11<br>* Other names: AC-PET;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SUV (Standardized Uptake Value) | Imaging studies will be evaluated both qualitatively and quantitatively using SUV (standardized uptake values): a measure of metabolism based on injected dose, patient weight and region of interest. | Day1 - Assessed at time of PET imaging - i.e. at the time of primary investigation/PET agent administration |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA (prostate specific antigen) | PSA will be monitored per routine clinical follow-up. | Every 3 - 6 months for 24 months after PET imaging |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Recurrent Prostate Carcinoma, sodium acetate c11, PET, prostate cancer, rising PSA, PSA recurrence, biochemical recurrence
|
NCT00874146
|
Level of HER2-neu Gene Amplification an Response to Trastuzumab
|
Primary objective of the study is to evaluate the correlation between level of HER2-neu gene amplification evalued by dual-color Fluorescent in-situ hybridization (FISH) test and time to progression (TTP) in patients with HER2-positive advanced breast cancer treated with trastuzumab-containing regimens.
|
Retrospective Study of the Level of HER2-neu Gene Amplification as Predictive Factor of Response in Patients With HER2-positive Advanced Breast Cancer Treated With Trastuzumab Containing Regimens.
|
Advanced Breast Cancer
|
* Genetic: Fluorescent in-situ hybridization (FISH)
|
Inclusion Criteria:~HER2-positive breast cancer Trastuzumab-containing regimen delivered for advanced disease Tumor sample available at Pathology Archive~Exclusion Criteria:~HER2-negative advanced breast cancer Pretreatment with trastuzumab
|
18 Years
| null |
Female
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association of tumor cytogenetic paremeters with TTP and OS. | | one year |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association of cytogenetic parameters evalued by FISH test and patients' characteristics. | | one year |
|
Breast Neoplasms, Neoplasms by Site, Neoplasms, Breast Diseases, Skin Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>HER2-positive advanced breast cancer | Genetic: Fluorescent in-situ hybridization (FISH)<br>* Dual color FISH test to assess ratio of HER2/neu amplification<br>|
|
Level of HER2-neu Gene Amplification an Response to Trastuzumab
Study Overview
=================
Brief Summary
-----------------
Primary objective of the study is to evaluate the correlation between level of HER2-neu gene amplification evalued by dual-color Fluorescent in-situ hybridization (FISH) test and time to progression (TTP) in patients with HER2-positive advanced breast cancer treated with trastuzumab-containing regimens.
Official Title
-----------------
Retrospective Study of the Level of HER2-neu Gene Amplification as Predictive Factor of Response in Patients With HER2-positive Advanced Breast Cancer Treated With Trastuzumab Containing Regimens.
Conditions
-----------------
Advanced Breast Cancer
Intervention / Treatment
-----------------
* Genetic: Fluorescent in-situ hybridization (FISH)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: HER2-positive breast cancer Trastuzumab-containing regimen delivered for advanced disease Tumor sample available at Pathology Archive Exclusion Criteria: HER2-negative advanced breast cancer Pretreatment with trastuzumab
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>HER2-positive advanced breast cancer | Genetic: Fluorescent in-situ hybridization (FISH)<br>* Dual color FISH test to assess ratio of HER2/neu amplification<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association of tumor cytogenetic paremeters with TTP and OS. | | one year |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association of cytogenetic parameters evalued by FISH test and patients' characteristics. | | one year |
|
|||
NCT04246255
|
Pain Relief During Intravenous Cannulation in Pediatric Patients
|
Performing intravenous (IV) cannulation to pediatric patients might be much harder than adult ones according to their anxiety levels. However, managing adult patients during intravenous cannulation is also challenging if he or she had a noxious memory about the situation or has a low pain threshold. Therefore, it is essential to relieve the pain of an IV needle or an IV cannula insertion in the pediatric patient population. Lidocaine Hcl spray (Xylocaine 10% Oral ) will be utilized to the research group, and Serum Physiologic (Serum Fizyolojik %0,9 10 ml ampule, Biofarma İlaç San. ve Tic A.Ş., İstanbul, Turkey) will be utilized to the control group of the study. Both medications will be administrated by spraying the formula three times to an adhesive bandage and placing it to the skin that IV cannulation will be performed. After waiting for a minimum of 5 to a maximum of 15 minutes ( waiting time is closely associated with the patient's anxiety level), IV cannulation will be performed from the same area by an experienced pediatric nurse. The investigator hypothesizes that utilizing the spray form of the Lidocaine Hcl formula to the skin with an adhesive bandage before IV cannulation might lower the pain of the manipulation in pediatric patients, which might cause lower anxiety levels with stable vital signs.
|
The G-Power 3.0.10. Computed required sample size (alpha:0.05, effect size:0.3 and power 0.8) related to t-test of the difference between two dependent means(matched pairs) according to the 5% change of before and after heartbeat outcome parameters with Standard derivations of ( -/+12 to +/-15). The total sample size of ninety participants is evaluated to be enough for the study. However, fifty participants are planned to be enrolled in each group (a total of 100 participants) to compensate for possible losses in this prospective, randomized clinical study. Six parameters will be evaluated, and three scales will be performed in each group. The six parameters are Heart Rate-1, Spo2-1, Body Temperature-1, Heart Rate-2, Spo2-2, Body Temperature-2. The three scales are 11 point Verbal Numeric Rating Scale-1, 11 point Verbal Numeric Rating Scale-2, and Visual Analog Scale. Those parameters will be measured non-invasively, without causing any pain.~The randomization is planned to be done with the sealed envelope modeling. One of the envelopes is planned to be chosen by each participant after the written consent form approval from the child and his/her parents. The envelopes have either a C letter or L letter inside representing C as {Group C: The Control Group}, representing L as {Group L: The Lidocaine Group} will be opened by the principal investigator. The bottle 1(Serum Physiologic inside) or bottle 2( Lidocaine inside) will be given to the ward nurse according to the letters in the envelope. The ward nurse will be blinded according to the ingredients in the bottles. The outcome parameters and the scales will be recorded by the nurse in the investigation. The nurse in the investigation will be blinded about the groups, the envelopes and the ingredients performed to the participants.~The study is planned to last in 4 months (16 weeks) time. However, in the middle of the study( 25 participants undertaken within each group), post-doc tests are planned to be done. If the power of the study according to the post-Hoc tests are more than 80%, the study will be stopped.
|
A New Method for Pain Relief, Intravenous Cannulation in Pediatric Patients; A Randomized Prospective Clinical Trial.
|
Cannula Site Pain, Local Anesthesia
|
* Drug: Xylocaine 10% Oral
* Drug: Placebo- Serum Fizyolojik Izotonik 0,9% 10 ml ampul
|
Inclusion Criteria:~The subject has to be treated with any drug submitted via intravenous cannula.~The subject weighted more than 10 kg.~The subject has a maximum ASA-2 score.~Exclusion Criteria:~Allergic to amide group local anesthetics.~The subject has a dermatological disease.
|
72 Months
|
215 Months
|
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart Rate-1 | Heart Beat per minute, data obtained from SpO2 pediatric probe, before IV cannula insertion | It is going to be measured in the first minute(1st min) of the total 15 mins. study, for each participant, through study completion up to 16 weeks. |
| SpO2-1 | Peripheral Oxygen concentration, data obtained from SpO2 pediatric probe, before IV cannula insertion. | It is going to be measured in the first minute(1st min) of the total 15 mins. study, for each participant, through study completion up to 16 weeks. |
| Body Temperature-1 | Body temperature, data obtained from tympanic temperature, before IV cannula insertion | It is going to be measured in the second minute(2nd min) of the total 15 mins. study, for each participant, through study completion up to 16 weeks. |
| Heart Rate-2 | Heart Beat per minute, data obtained from SpO2 pediatric probe, after IV cannula insertion | It is going to be measured in the last 5 minutes period of the study(approximately in the 12th minute) of the total 15 mins. study, for each participant, through study completion up to 16 weeks. |
| SpO2-2 | Peripheral Oxygen concentration, data obtained from SpO2 pediatric probe, after IV cannula insertion. | It is going to be measured in the last 5 minutes period of the study(approximately in the 12th minute) of the total 15 mins. study, for each participant, through study completion up to 16 weeks. |
| Body Temperature-2 | Body temperature, data obtained from tympanic temperature, after IV cannula insertion | It is going to be measured in the last 5 minutes period of the study(approximately in the 13th minute) of the total 15 mins. study, for each participant, through study completion up to 16 weeks. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 11-point Verbal Numeric Rating Scale-1 (VNS-1) | The subject is going to be asked to rate the cannula insertion pain, which the subject had experienced before the study ( if they had no experience Outcome 7 would stay empty), verbally according to the intensity from 0-10 with 0 representing no pain and 10 representing the most intense pain imaginable. | It is going to be measured in the third minute(3rd min) of the total 15 mins. study, for each participant, through study completion up to 16 weeks. |
| Visual Analog Scales | The subject will be asked to rate the cannula insertion pain after insertion by placing a vertical mark on a 100 mm horizontal VAS. The left and right extremes of the VAS are labeled as; least possible pain and worst possible pain respectively. 100mm VAS is devided into 5 categorical descriptors: much less pain, a little less pain, about the same pain, a little more pain, or much more pain. | It is going to be measured in the in the last 5 minutes period of the study(approximately in the 14th minute) of the total 15 mins. study, for each participant, through study completion up to 16 weeks. |
| 11-point Verbal Numeric Rating Scale-2 (VNS-2) | The subject is going to be asked to rate the cannula insertion pain after insertion verbally according to the intensity from 0-10 with 0 representing no pain and 10 representing the most intense pain imaginable. | It is going to be measured in the in the last 5 minutes period of the study(approximately in the 15th minute) of the total 15 mins. study, for each participant, through study completion up to 16 weeks. |
|
Local Anesthesia, Cannula Site Pain, Lidocaine Hydrocloride
|
Lidocaine, Anesthetics, Local, Anesthetics, Central Nervous System Depressants, Physiological Effects of Drugs, Sensory System Agents, Peripheral Nervous System Agents, Anti-Arrhythmia Agents, Voltage-Gated Sodium Channel Blockers, Sodium Channel Blockers, Membrane Transport Modulators, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group C<br>Serum Physiologic %0,9 ampules ; 0,3ml {spraying three times from a pump spray bottle that sprays 0,1 ml each time to Tegaderm + (2,5 cm x 4 cm) Non-Adherent Pad} 10 minutes before the IV cannula application | Drug: Placebo- Serum Fizyolojik Izotonik 0,9% 10 ml ampul<br>* 50 ml of Serum physiologic in a bottle with a spray pump which pumps 0,1ml for each pump will be used for placebo.~3 pumps of placebo will be administrated to 3M TegadermTM +Pad Film Dressing with Non-Adherent Pad and put onto the skin for 10 minutes that IV cannula planned to be inserted.<br>* Other names: Serum Fizyolojik Biofarma % 0,9, 10 Ml 100 Ampul;|
| Experimental: Group L<br>xylocaine %10 pump spray ; 30mg lidocaine {spraying three times from a pump spray bottle that sprays 0,1 ml each time to Tegaderm + (2,5 cm x 4 cm) Non-Adherent Pad} 10 minutes before the IV cannula application | Drug: Xylocaine 10% Oral<br>* 50 ml of lidocaine solution maintained from xylocaine 10% oral that transferred to a bottle with a spray pump which pumps 0,1ml for each pump will be used for the experiment.~3 pumps of lidocaine will be administrated to 3M TegadermTM +Pad Film Dressing with Non-Adherent Pad and put onto the skin for 10 minutes that IV cannula planned to be inserted.<br>* Other names: VEMCAINE pump sprey %10;|
|
Pain Relief During Intravenous Cannulation in Pediatric Patients
Study Overview
=================
Brief Summary
-----------------
Performing intravenous (IV) cannulation to pediatric patients might be much harder than adult ones according to their anxiety levels. However, managing adult patients during intravenous cannulation is also challenging if he or she had a noxious memory about the situation or has a low pain threshold. Therefore, it is essential to relieve the pain of an IV needle or an IV cannula insertion in the pediatric patient population. Lidocaine Hcl spray (Xylocaine 10% Oral ) will be utilized to the research group, and Serum Physiologic (Serum Fizyolojik %0,9 10 ml ampule, Biofarma İlaç San. ve Tic A.Ş., İstanbul, Turkey) will be utilized to the control group of the study. Both medications will be administrated by spraying the formula three times to an adhesive bandage and placing it to the skin that IV cannulation will be performed. After waiting for a minimum of 5 to a maximum of 15 minutes ( waiting time is closely associated with the patient's anxiety level), IV cannulation will be performed from the same area by an experienced pediatric nurse. The investigator hypothesizes that utilizing the spray form of the Lidocaine Hcl formula to the skin with an adhesive bandage before IV cannulation might lower the pain of the manipulation in pediatric patients, which might cause lower anxiety levels with stable vital signs.
Detailed Description
-----------------
The G-Power 3.0.10. Computed required sample size (alpha:0.05, effect size:0.3 and power 0.8) related to t-test of the difference between two dependent means(matched pairs) according to the 5% change of before and after heartbeat outcome parameters with Standard derivations of ( -/+12 to +/-15). The total sample size of ninety participants is evaluated to be enough for the study. However, fifty participants are planned to be enrolled in each group (a total of 100 participants) to compensate for possible losses in this prospective, randomized clinical study. Six parameters will be evaluated, and three scales will be performed in each group. The six parameters are Heart Rate-1, Spo2-1, Body Temperature-1, Heart Rate-2, Spo2-2, Body Temperature-2. The three scales are 11 point Verbal Numeric Rating Scale-1, 11 point Verbal Numeric Rating Scale-2, and Visual Analog Scale. Those parameters will be measured non-invasively, without causing any pain. The randomization is planned to be done with the sealed envelope modeling. One of the envelopes is planned to be chosen by each participant after the written consent form approval from the child and his/her parents. The envelopes have either a C letter or L letter inside representing C as {Group C: The Control Group}, representing L as {Group L: The Lidocaine Group} will be opened by the principal investigator. The bottle 1(Serum Physiologic inside) or bottle 2( Lidocaine inside) will be given to the ward nurse according to the letters in the envelope. The ward nurse will be blinded according to the ingredients in the bottles. The outcome parameters and the scales will be recorded by the nurse in the investigation. The nurse in the investigation will be blinded about the groups, the envelopes and the ingredients performed to the participants. The study is planned to last in 4 months (16 weeks) time. However, in the middle of the study( 25 participants undertaken within each group), post-doc tests are planned to be done. If the power of the study according to the post-Hoc tests are more than 80%, the study will be stopped.
Official Title
-----------------
A New Method for Pain Relief, Intravenous Cannulation in Pediatric Patients; A Randomized Prospective Clinical Trial.
Conditions
-----------------
Cannula Site Pain, Local Anesthesia
Intervention / Treatment
-----------------
* Drug: Xylocaine 10% Oral
* Drug: Placebo- Serum Fizyolojik Izotonik 0,9% 10 ml ampul
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The subject has to be treated with any drug submitted via intravenous cannula. The subject weighted more than 10 kg. The subject has a maximum ASA-2 score. Exclusion Criteria: Allergic to amide group local anesthetics. The subject has a dermatological disease.
Ages Eligible for Study
-----------------
Minimum Age: 72 Months
Maximum Age: 215 Months
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: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group C<br>Serum Physiologic %0,9 ampules ; 0,3ml {spraying three times from a pump spray bottle that sprays 0,1 ml each time to Tegaderm + (2,5 cm x 4 cm) Non-Adherent Pad} 10 minutes before the IV cannula application | Drug: Placebo- Serum Fizyolojik Izotonik 0,9% 10 ml ampul<br>* 50 ml of Serum physiologic in a bottle with a spray pump which pumps 0,1ml for each pump will be used for placebo. 3 pumps of placebo will be administrated to 3M TegadermTM +Pad Film Dressing with Non-Adherent Pad and put onto the skin for 10 minutes that IV cannula planned to be inserted.<br>* Other names: Serum Fizyolojik Biofarma % 0,9, 10 Ml 100 Ampul;|
| Experimental: Group L<br>xylocaine %10 pump spray ; 30mg lidocaine {spraying three times from a pump spray bottle that sprays 0,1 ml each time to Tegaderm + (2,5 cm x 4 cm) Non-Adherent Pad} 10 minutes before the IV cannula application | Drug: Xylocaine 10% Oral<br>* 50 ml of lidocaine solution maintained from xylocaine 10% oral that transferred to a bottle with a spray pump which pumps 0,1ml for each pump will be used for the experiment. 3 pumps of lidocaine will be administrated to 3M TegadermTM +Pad Film Dressing with Non-Adherent Pad and put onto the skin for 10 minutes that IV cannula planned to be inserted.<br>* Other names: VEMCAINE pump sprey %10;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart Rate-1 | Heart Beat per minute, data obtained from SpO2 pediatric probe, before IV cannula insertion | It is going to be measured in the first minute(1st min) of the total 15 mins. study, for each participant, through study completion up to 16 weeks. |
| SpO2-1 | Peripheral Oxygen concentration, data obtained from SpO2 pediatric probe, before IV cannula insertion. | It is going to be measured in the first minute(1st min) of the total 15 mins. study, for each participant, through study completion up to 16 weeks. |
| Body Temperature-1 | Body temperature, data obtained from tympanic temperature, before IV cannula insertion | It is going to be measured in the second minute(2nd min) of the total 15 mins. study, for each participant, through study completion up to 16 weeks. |
| Heart Rate-2 | Heart Beat per minute, data obtained from SpO2 pediatric probe, after IV cannula insertion | It is going to be measured in the last 5 minutes period of the study(approximately in the 12th minute) of the total 15 mins. study, for each participant, through study completion up to 16 weeks. |
| SpO2-2 | Peripheral Oxygen concentration, data obtained from SpO2 pediatric probe, after IV cannula insertion. | It is going to be measured in the last 5 minutes period of the study(approximately in the 12th minute) of the total 15 mins. study, for each participant, through study completion up to 16 weeks. |
| Body Temperature-2 | Body temperature, data obtained from tympanic temperature, after IV cannula insertion | It is going to be measured in the last 5 minutes period of the study(approximately in the 13th minute) of the total 15 mins. study, for each participant, through study completion up to 16 weeks. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 11-point Verbal Numeric Rating Scale-1 (VNS-1) | The subject is going to be asked to rate the cannula insertion pain, which the subject had experienced before the study ( if they had no experience Outcome 7 would stay empty), verbally according to the intensity from 0-10 with 0 representing no pain and 10 representing the most intense pain imaginable. | It is going to be measured in the third minute(3rd min) of the total 15 mins. study, for each participant, through study completion up to 16 weeks. |
| Visual Analog Scales | The subject will be asked to rate the cannula insertion pain after insertion by placing a vertical mark on a 100 mm horizontal VAS. The left and right extremes of the VAS are labeled as; least possible pain and worst possible pain respectively. 100mm VAS is devided into 5 categorical descriptors: much less pain, a little less pain, about the same pain, a little more pain, or much more pain. | It is going to be measured in the in the last 5 minutes period of the study(approximately in the 14th minute) of the total 15 mins. study, for each participant, through study completion up to 16 weeks. |
| 11-point Verbal Numeric Rating Scale-2 (VNS-2) | The subject is going to be asked to rate the cannula insertion pain after insertion verbally according to the intensity from 0-10 with 0 representing no pain and 10 representing the most intense pain imaginable. | It is going to be measured in the in the last 5 minutes period of the study(approximately in the 15th minute) of the total 15 mins. study, for each participant, through study completion up to 16 weeks. |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Local Anesthesia, Cannula Site Pain, Lidocaine Hydrocloride
|
NCT01593592
|
Lactobacillus Reuteri in Management of Helicobacter Pylori Infection in Dyspeptic Patients
|
Addition of L. reuteri to the standard triple therapy improves H. Pylori treatment outcomes.
|
Helicobacter pylori (H. Pylori) infection is a wide spread disease and is endemic in many countries including Egypt with a wide range of morbidity; that requires appropriate antimicrobial therapy . However, worldwide the eradication rate following the standard triple therapy is declining and this may necessitates introduction of new antimicrobial agents . On the sight of bearing in vivo and in vitro activity against H. Pylori, the use of different strains of probiotics in treatment of H. Pylori may be thus justifiable, Lactobacillus reuteri (L. reuteri) which through different mechanisms including production of reuterin have anti H.pylori activity have been tried in improving the eradication rates of H.pylori with contradictory results . This study is conducted to test the assumption that addition of L. reuteri to the standard triple therapy in treatment of H. Pylori improves the eradication rates and clinical aspects in H. Pylori infection.
|
Lactobacillus Reuteri in Management of Helicobacter Pylori Infection in Dyspeptic Patients: a Double Blind Placebo Controlled Randomized Clinical Trial
|
Helicobacter Pylori Infection
|
* Dietary Supplement: Lactobacillus reuteri
* Dietary Supplement: Placebo
* Drug: Omeprazole
* Drug: Amoxicillin
* Drug: Clarithromycin
|
Inclusion Criteria:~Inclusion of patients with these criteria~Age: 18-60 years~Any sex~Confirmed H. Pylori infection defined by pathological lesions and either histopathological confirmation of the organism, rapid urease test or H. Pylori antigen in stool~Good mentality to understand aim, benefits and steps of the study~Assumed availability during the study period~Written informed consent~Exclusion Criteria:~Exclusion of~Patients with chronic diseases e.g. diabetes, renal failure, cirrhosis…etc.~Patients with malignancy.~Patients with gall bladder disorders.~Patients with peptic ulcer.~Patients with prior upper GIT surgery.~Patients with probiotics therapy in the last one month.~Patients with triple therapy, antibiotics, proton pump inhibitors and H2 receptor blockers therapy within one month.~Patients with known allergy to the used medications~-
|
18 Years
|
60 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eradication of H Pylori Infection 4 Weeks After Completion of Therapy | H. pylori eradication is defined in this study as concomitant negativity to all previously positive tests (H. pylori antigen in stool; histopathological confirmation of H. pylori bacilli; and rapid urease test.) 4 weeks after the end of therapy. | 4 weeks therapy |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe Adverse Effects to the Used Medications and Dietary Supplements. | | 4 weeks |
| The Secondary End Point Was the Development of Severe Adverse Effects to the Used Medications and Dietary Supplements. | Severe adverse effects to the used medications and dietary supplements, these may expose the participants to major morbidity and may change the outcomes in them. | 8 weeks |
|
Helicobacter pylori, Lactobacillus reuteri, dyspeptic patients, eradication
|
Omeprazole, Amoxicillin, Clarithromycin, Anti-Bacterial Agents, Anti-Infective Agents, Anti-Ulcer Agents, Gastrointestinal Agents, Proton Pump Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Protein Synthesis Inhibitors, Cytochrome P-450 CYP3A Inhibitors, Cytochrome P-450 Enzyme Inhibitors
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lactobacillus reuteri group<br>The active group that will receive the standard triple therapy and Lactobacillus reuteri | Dietary Supplement: Lactobacillus reuteri<br>* Will receive triple therapy (omeprazole 20 mg b.i.d., amoxicillin 1000 mg b.i.d, clarithromycin 500mg b.i.d) and L. reuteri (is a mixture of L. reuteri DSM 17938 and L. reuteri ATCC PTA 6475, will be delivered a dose of 1x108 CFU each strain, means giving daily chewable tablet containing 2x108 CFU/day) for 2 weeks followed by L. reuteri for another 2 weeks.<br>Drug: Omeprazole<br>* All patients will receive omeprazole 20 mg b.i.d for 2 week<br>Drug: Amoxicillin<br>* amoxicillin 1000 mg b.i.d for 2 weeks<br>Drug: Clarithromycin<br>* clarithromycin 500mg b.i.d for 2 weeks<br>|
| Placebo Comparator: Control group<br>The control group that will receive the standard triple therapy and placebo | Dietary Supplement: Placebo<br>* Will receive triple therapy (omeprazole 20 mg b.i.d., amoxicillin 1000 mg b.i.d, clarithromycin 500mg b.i.d) and a placebo (1.5 mg per dose as chewable tablets) for 2 weeks followed by placebo for another 2 weeks.<br>Drug: Omeprazole<br>* All patients will receive omeprazole 20 mg b.i.d for 2 week<br>Drug: Amoxicillin<br>* amoxicillin 1000 mg b.i.d for 2 weeks<br>Drug: Clarithromycin<br>* clarithromycin 500mg b.i.d for 2 weeks<br>|
|
Lactobacillus Reuteri in Management of Helicobacter Pylori Infection in Dyspeptic Patients
Study Overview
=================
Brief Summary
-----------------
Addition of L. reuteri to the standard triple therapy improves H. Pylori treatment outcomes.
Detailed Description
-----------------
Helicobacter pylori (H. Pylori) infection is a wide spread disease and is endemic in many countries including Egypt with a wide range of morbidity; that requires appropriate antimicrobial therapy . However, worldwide the eradication rate following the standard triple therapy is declining and this may necessitates introduction of new antimicrobial agents . On the sight of bearing in vivo and in vitro activity against H. Pylori, the use of different strains of probiotics in treatment of H. Pylori may be thus justifiable, Lactobacillus reuteri (L. reuteri) which through different mechanisms including production of reuterin have anti H.pylori activity have been tried in improving the eradication rates of H.pylori with contradictory results . This study is conducted to test the assumption that addition of L. reuteri to the standard triple therapy in treatment of H. Pylori improves the eradication rates and clinical aspects in H. Pylori infection.
Official Title
-----------------
Lactobacillus Reuteri in Management of Helicobacter Pylori Infection in Dyspeptic Patients: a Double Blind Placebo Controlled Randomized Clinical Trial
Conditions
-----------------
Helicobacter Pylori Infection
Intervention / Treatment
-----------------
* Dietary Supplement: Lactobacillus reuteri
* Dietary Supplement: Placebo
* Drug: Omeprazole
* Drug: Amoxicillin
* Drug: Clarithromycin
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Inclusion of patients with these criteria Age: 18-60 years Any sex Confirmed H. Pylori infection defined by pathological lesions and either histopathological confirmation of the organism, rapid urease test or H. Pylori antigen in stool Good mentality to understand aim, benefits and steps of the study Assumed availability during the study period Written informed consent Exclusion Criteria: Exclusion of Patients with chronic diseases e.g. diabetes, renal failure, cirrhosis…etc. Patients with malignancy. Patients with gall bladder disorders. Patients with peptic ulcer. Patients with prior upper GIT surgery. Patients with probiotics therapy in the last one month. Patients with triple therapy, antibiotics, proton pump inhibitors and H2 receptor blockers therapy within one month. Patients with known allergy to the used medications -
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 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: Lactobacillus reuteri group<br>The active group that will receive the standard triple therapy and Lactobacillus reuteri | Dietary Supplement: Lactobacillus reuteri<br>* Will receive triple therapy (omeprazole 20 mg b.i.d., amoxicillin 1000 mg b.i.d, clarithromycin 500mg b.i.d) and L. reuteri (is a mixture of L. reuteri DSM 17938 and L. reuteri ATCC PTA 6475, will be delivered a dose of 1x108 CFU each strain, means giving daily chewable tablet containing 2x108 CFU/day) for 2 weeks followed by L. reuteri for another 2 weeks.<br>Drug: Omeprazole<br>* All patients will receive omeprazole 20 mg b.i.d for 2 week<br>Drug: Amoxicillin<br>* amoxicillin 1000 mg b.i.d for 2 weeks<br>Drug: Clarithromycin<br>* clarithromycin 500mg b.i.d for 2 weeks<br>|
| Placebo Comparator: Control group<br>The control group that will receive the standard triple therapy and placebo | Dietary Supplement: Placebo<br>* Will receive triple therapy (omeprazole 20 mg b.i.d., amoxicillin 1000 mg b.i.d, clarithromycin 500mg b.i.d) and a placebo (1.5 mg per dose as chewable tablets) for 2 weeks followed by placebo for another 2 weeks.<br>Drug: Omeprazole<br>* All patients will receive omeprazole 20 mg b.i.d for 2 week<br>Drug: Amoxicillin<br>* amoxicillin 1000 mg b.i.d for 2 weeks<br>Drug: Clarithromycin<br>* clarithromycin 500mg b.i.d for 2 weeks<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eradication of H Pylori Infection 4 Weeks After Completion of Therapy | H. pylori eradication is defined in this study as concomitant negativity to all previously positive tests (H. pylori antigen in stool; histopathological confirmation of H. pylori bacilli; and rapid urease test.) 4 weeks after the end of therapy. | 4 weeks therapy |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe Adverse Effects to the Used Medications and Dietary Supplements. | | 4 weeks |
| The Secondary End Point Was the Development of Severe Adverse Effects to the Used Medications and Dietary Supplements. | Severe adverse effects to the used medications and dietary supplements, these may expose the participants to major morbidity and may change the outcomes in them. | 8 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Helicobacter pylori, Lactobacillus reuteri, dyspeptic patients, eradication
|
NCT03218891
|
Cardiac Rehabilitation in Patients With Refractory Angina
|
The purpose of this study is to evaluate the safety and feasibility of cardiovascular rehabilitation in Patients with refractory angina, evaluate the effect of cardiovascular rehabilitation in patients with angina Refractory, by maximal oxygen consumption (VO2max) and global myocardial ischemic load by Stress Echocardiography; To evaluate the presence of myocardial injury, caused by physical stress, through ultra-sensitive troponin after sessions of aerobic physical activity, evaluating the behavior during the training period; To evaluate the effect of rehabilitation on the modulation of sympathetic activity and inflammation, muscular blood flow and lipid metabolism; To evaluate of the effect of rehabilitation on ventricular function through Stress echocardiography; Detection of ischemic episodes and arrhythmias identified during the Rehabilitation sessions through external cardiac monitoring (telemetry); Evaluate the quality of life assessment through the SF-36 questionnaire, Canadian Cardiovascular Society, the number of symptomatic episodes of ischemia, daily sublingual nitrate intake.
|
After signing the informed consent form, patients will be randomized into 4 groups: 1. Optimized clinical treatment group + physical training for 12 weeks (TF); 2. optimized clinical treatment group (CT); 3. Group with coronary insufficiency without angina (CD); Group 4: normal healthy subjects All patients will be submitted to the following procedures in 2 moments * (times 0 and 3): -Routine laboratory tests including study of total cholesterol, LDL-cholesterol, -HDL-cholesterol, including study of the functionality of HDL-c, triglycerides, complete blood count, renal function, fasting glycemia, glycosylated hemoglobin (HbA1C); - Dosage of biomarkers of myocardial ischemia (ultra-sensitive troponin); - Dosage of inflammatory markers: Tumor necrosis factor (TNFn), interleukins 1 and 6 (IL-1 and IL-6), ultra-sensitive C-reactive protein (CRP); - Vascular endothelial growth factor (VEGF) dosage; - ergospirometric test in cycloergometer; - Echocardiogram with physical stress with evaluation of myocardial perfusion and function; - Evaluation of sympathetic activity through microneurography; - Evaluation of vascular reactivity through ultrasound of the brachial artery. - Evaluation of muscular blood flow through plethysmography; - Isometric exercise protocols; - Mental stress protocol - Quality of Life Questionnaire; - Diary of angina. After the initial examinations, the candidates of the TF group will be evaluated by cardiovascular rehabilitation team, for training prescription, which will be performed in a hospital environment, supervised by a qualified doctor. The rehabilitation may be interrupted in any patient, for safety measure, if the investigator deems it appropriate. All patients in both groups will receive clinical follow-up during the protocol, with monthly consultations during the 12-week protocol period (time 0 to 3), in which clinical evaluations of symptoms and quality of life of the patients will be performed . Any clinical intercurrence will be promptly annotated and evaluated according to the need of the moment. After this period, routine outpatient follow-up is scheduled at the outpatient clinic, and counseling for unsupervised physical training, according to the results of the study. All laboratory, clinical, imaging, and functional parameters will be evaluated before and at the end of the protocol.
|
Cardiac Rehabilitation in Patients With Refractory Angina
|
Refractory Angina
|
* Behavioral: Cardiac Rehabilitation
|
Group 1 and 2~Inclusion Criteria:~Stable angina functional class II to IV according to the classification of Canadian Cardiovascular Society (CCS) 39, or limiting angina in Perception of the patient;~Documented myocardial ischemia by imaging method;~Patients not eligible for myocardial revascularization procedures surgical conventional, due to the unfavorable anatomy;~Signature of the Free and Informed Consent Form.~Exclusion Criteria:~Patients with definitive pacemaker or implantable cardioverter defibrillator (ICD);~Patients with non-sinus heart rhythm;~Patients with complete intraventricular block;~Acute coronary syndrome (myocardial infarction or unstable angina) or previous procedures for myocardial revascularization (angioplasty / surgery) less than 3 months;~Functional impossibility (orthopedic, rheumatic, neurological, or otherwise) or social for participation in the Rehabilitation Program;~Classification of risk for American Heart Association class D physical training (unstable ischemia, stenosis or severe or symptomatic valve insufficiency, congenital heart disease, decompensated heart failure, uncontrolled arrhythmias and other conditions that may be aggravated by exercise).~Group 3~Inclusion Criteria:~Patients with coronary insufficiency without angina;~Signature of the Free and Informed Consent Form.~Group 4~Inclusion Criteria:~Signature of the Free and Informed Consent Form;~Healthy;~Non-smokers;~Sedentary
|
45 Years
|
75 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Optimized clinical treatment group + physical training for 12 weeks (TF);~optimized clinical treatment group (CT);~Group with coronary insufficiency without angina (CD);~Group normal healthy subjects
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular rehabilitation in patients with refractory angina is safe; | Evaluated number of patients who have any kind of cardiovascular event during rehabilitation, as well as number of sore throat during the sessions. | 3 months of rehabilitation |
| Cardiovascular rehabilitation in patients with refractory angina is efficient; | Evaluated number of sore throat during the sessions. | 3 months of rehabilitation |
| Improve the maximal oxygen consumption | Improvement of Maximal oxygen uptake (VO2max) | 3 months of rehabilitation |
| Improve the global myocardial ischemic load | Reduction of myocardial ischemia, evidenced by improvement of the standard by effort echocardiography | 3 months of rehabilitation |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of myocardial injury caused by physical stress | Improves levels of Troponin-T after 1 exercise session at the initial moment of the Protocol and after 3 months. | 3 months of rehabilitation |
| Rehabilitation will modulate sympathetic activity | Decreased sympathetic nerve activity measured by the amount of shots in his microneurography | 3 months of rehabilitation |
| Improvement of ventricular function | Improvement of ventricular function through stress echocardiography in patients undergoing rehabilitation | 3 months of rehabilitation |
| Improvement of the quality of life | Improvement of the quality of life measured through the SF-36 questionnaire. | 3 months of rehabilitation |
| Rehabilitation will increase muscle blood flow | Increase peripheral muscle blood flow measured by plethysmography. | 3 months of rehabilitation |
| Reduction in the number of symptomatic episodes of ischemia | Reduction in the number of episodes of ischemia, reduction of daily sublingual nitrate intake. | 3 months of rehabilitation |
| Reduction of the daily consumption of sublingual nitrate | Reduction of daily sublingual nitrate intake. | 3 months of rehabilitation |
| Improve the functional class of Refractory Angina | Improve the functional class decrease of angina (according to Canadian Cardiovascular Society classification) | 3 months of rehabilitation |
|
Refractory Angina, Rehabilitation
|
Angina Pectoris, Myocardial Ischemia, Heart Diseases, Cardiovascular Diseases, Vascular Diseases, Chest Pain, Pain, Neurologic Manifestations
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clinical treatment physical training<br>Patients with optimized clinical treatment group that will do physical training for 12 weeks. They will do the tests in moment 1 and after 3 mounths.~The intervention is the Cardiac Rehabilitation. | Behavioral: Cardiac Rehabilitation<br>* The physical training program will start shortly after the initial exams have been completed. The physical training protocol will consist of a 12-week duration, with a frequency of 3 weekly sessions of 60 minutes duration each. The intensity will be prescribed from the echocardiogram with effort and cardiopulmonary test. All sessions will be monitored by telemetry and will be distributed as follows:~5 minutes warm up~30 to 40 minutes of aerobic exercise (treadmill). The training intensity will be prescribed individually, based on the results of the test results;~10 minutes of localized exercises;~5 minutes of relaxation.<br>|
| No Intervention: Optimized clinical treatment<br>Patients with optimized clinical treatment group that will not do physical training.They will do the tests in moment 1 and after 3 mounths. | |
| No Intervention: Coronary insufficiency without angina<br>Group with coronary insufficiency without angina and will not do physical training. They will do the tests only one moment. | |
| No Intervention: Normal healthy subjects<br>Group normal healthy subjects, without coronary injuries, diabetes, hypertension and another chronic disease. These group have be sedentary and will not do physical training. They will do the tests only one moment. | |
|
Cardiac Rehabilitation in Patients With Refractory Angina
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety and feasibility of cardiovascular rehabilitation in Patients with refractory angina, evaluate the effect of cardiovascular rehabilitation in patients with angina Refractory, by maximal oxygen consumption (VO2max) and global myocardial ischemic load by Stress Echocardiography; To evaluate the presence of myocardial injury, caused by physical stress, through ultra-sensitive troponin after sessions of aerobic physical activity, evaluating the behavior during the training period; To evaluate the effect of rehabilitation on the modulation of sympathetic activity and inflammation, muscular blood flow and lipid metabolism; To evaluate of the effect of rehabilitation on ventricular function through Stress echocardiography; Detection of ischemic episodes and arrhythmias identified during the Rehabilitation sessions through external cardiac monitoring (telemetry); Evaluate the quality of life assessment through the SF-36 questionnaire, Canadian Cardiovascular Society, the number of symptomatic episodes of ischemia, daily sublingual nitrate intake.
Detailed Description
-----------------
After signing the informed consent form, patients will be randomized into 4 groups: 1. Optimized clinical treatment group + physical training for 12 weeks (TF); 2. optimized clinical treatment group (CT); 3. Group with coronary insufficiency without angina (CD); Group 4: normal healthy subjects All patients will be submitted to the following procedures in 2 moments * (times 0 and 3): -Routine laboratory tests including study of total cholesterol, LDL-cholesterol, -HDL-cholesterol, including study of the functionality of HDL-c, triglycerides, complete blood count, renal function, fasting glycemia, glycosylated hemoglobin (HbA1C); - Dosage of biomarkers of myocardial ischemia (ultra-sensitive troponin); - Dosage of inflammatory markers: Tumor necrosis factor (TNFn), interleukins 1 and 6 (IL-1 and IL-6), ultra-sensitive C-reactive protein (CRP); - Vascular endothelial growth factor (VEGF) dosage; - ergospirometric test in cycloergometer; - Echocardiogram with physical stress with evaluation of myocardial perfusion and function; - Evaluation of sympathetic activity through microneurography; - Evaluation of vascular reactivity through ultrasound of the brachial artery. - Evaluation of muscular blood flow through plethysmography; - Isometric exercise protocols; - Mental stress protocol - Quality of Life Questionnaire; - Diary of angina. After the initial examinations, the candidates of the TF group will be evaluated by cardiovascular rehabilitation team, for training prescription, which will be performed in a hospital environment, supervised by a qualified doctor. The rehabilitation may be interrupted in any patient, for safety measure, if the investigator deems it appropriate. All patients in both groups will receive clinical follow-up during the protocol, with monthly consultations during the 12-week protocol period (time 0 to 3), in which clinical evaluations of symptoms and quality of life of the patients will be performed . Any clinical intercurrence will be promptly annotated and evaluated according to the need of the moment. After this period, routine outpatient follow-up is scheduled at the outpatient clinic, and counseling for unsupervised physical training, according to the results of the study. All laboratory, clinical, imaging, and functional parameters will be evaluated before and at the end of the protocol.
Official Title
-----------------
Cardiac Rehabilitation in Patients With Refractory Angina
Conditions
-----------------
Refractory Angina
Intervention / Treatment
-----------------
* Behavioral: Cardiac Rehabilitation
Participation Criteria
=================
Eligibility Criteria
-----------------
Group 1 and 2 Inclusion Criteria: Stable angina functional class II to IV according to the classification of Canadian Cardiovascular Society (CCS) 39, or limiting angina in Perception of the patient; Documented myocardial ischemia by imaging method; Patients not eligible for myocardial revascularization procedures surgical conventional, due to the unfavorable anatomy; Signature of the Free and Informed Consent Form. Exclusion Criteria: Patients with definitive pacemaker or implantable cardioverter defibrillator (ICD); Patients with non-sinus heart rhythm; Patients with complete intraventricular block; Acute coronary syndrome (myocardial infarction or unstable angina) or previous procedures for myocardial revascularization (angioplasty / surgery) less than 3 months; Functional impossibility (orthopedic, rheumatic, neurological, or otherwise) or social for participation in the Rehabilitation Program; Classification of risk for American Heart Association class D physical training (unstable ischemia, stenosis or severe or symptomatic valve insufficiency, congenital heart disease, decompensated heart failure, uncontrolled arrhythmias and other conditions that may be aggravated by exercise). Group 3 Inclusion Criteria: Patients with coronary insufficiency without angina; Signature of the Free and Informed Consent Form. Group 4 Inclusion Criteria: Signature of the Free and Informed Consent Form; Healthy; Non-smokers; Sedentary
Ages Eligible for Study
-----------------
Minimum Age: 45 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: Parallel Assignment
Interventional Model Description: Optimized clinical treatment group + physical training for 12 weeks (TF); optimized clinical treatment group (CT); Group with coronary insufficiency without angina (CD); Group normal healthy subjects
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clinical treatment physical training<br>Patients with optimized clinical treatment group that will do physical training for 12 weeks. They will do the tests in moment 1 and after 3 mounths. The intervention is the Cardiac Rehabilitation. | Behavioral: Cardiac Rehabilitation<br>* The physical training program will start shortly after the initial exams have been completed. The physical training protocol will consist of a 12-week duration, with a frequency of 3 weekly sessions of 60 minutes duration each. The intensity will be prescribed from the echocardiogram with effort and cardiopulmonary test. All sessions will be monitored by telemetry and will be distributed as follows: 5 minutes warm up 30 to 40 minutes of aerobic exercise (treadmill). The training intensity will be prescribed individually, based on the results of the test results; 10 minutes of localized exercises; 5 minutes of relaxation.<br>|
| No Intervention: Optimized clinical treatment<br>Patients with optimized clinical treatment group that will not do physical training.They will do the tests in moment 1 and after 3 mounths. | |
| No Intervention: Coronary insufficiency without angina<br>Group with coronary insufficiency without angina and will not do physical training. They will do the tests only one moment. | |
| No Intervention: Normal healthy subjects<br>Group normal healthy subjects, without coronary injuries, diabetes, hypertension and another chronic disease. These group have be sedentary and will not do physical training. They will do the tests only one moment. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular rehabilitation in patients with refractory angina is safe; | Evaluated number of patients who have any kind of cardiovascular event during rehabilitation, as well as number of sore throat during the sessions. | 3 months of rehabilitation |
| Cardiovascular rehabilitation in patients with refractory angina is efficient; | Evaluated number of sore throat during the sessions. | 3 months of rehabilitation |
| Improve the maximal oxygen consumption | Improvement of Maximal oxygen uptake (VO2max) | 3 months of rehabilitation |
| Improve the global myocardial ischemic load | Reduction of myocardial ischemia, evidenced by improvement of the standard by effort echocardiography | 3 months of rehabilitation |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of myocardial injury caused by physical stress | Improves levels of Troponin-T after 1 exercise session at the initial moment of the Protocol and after 3 months. | 3 months of rehabilitation |
| Rehabilitation will modulate sympathetic activity | Decreased sympathetic nerve activity measured by the amount of shots in his microneurography | 3 months of rehabilitation |
| Improvement of ventricular function | Improvement of ventricular function through stress echocardiography in patients undergoing rehabilitation | 3 months of rehabilitation |
| Improvement of the quality of life | Improvement of the quality of life measured through the SF-36 questionnaire. | 3 months of rehabilitation |
| Rehabilitation will increase muscle blood flow | Increase peripheral muscle blood flow measured by plethysmography. | 3 months of rehabilitation |
| Reduction in the number of symptomatic episodes of ischemia | Reduction in the number of episodes of ischemia, reduction of daily sublingual nitrate intake. | 3 months of rehabilitation |
| Reduction of the daily consumption of sublingual nitrate | Reduction of daily sublingual nitrate intake. | 3 months of rehabilitation |
| Improve the functional class of Refractory Angina | Improve the functional class decrease of angina (according to Canadian Cardiovascular Society classification) | 3 months of rehabilitation |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Refractory Angina, Rehabilitation
|
NCT05374980
|
The Effects of Yogurt on Gut Microbiome and Metabolism in H. Pylori.
|
Helicobacter pylori is a common pathogen causing upper gastrointestinal diseases including gastric ulcer and gastric cancer. Recent epidemiological findings have also shown that it is also related to colon cancer, metabolic syndrome, gut dysbiosis, glycemic control and insulin resistance.~The aim of this study is to investigate whether the gut microbiota and insulin resistance of patients with H. pylori infection are abnormal. In addition, whether drinking fermented milk product with probiotic reduces Helicobacter pylori, improves gut microbiota, and increases butyrate-producing bacteria and insulin resistance.
|
The Effects of Fermented Milk Product With Probiotic on Helicobacter Pylori Infection, Gut Microbiome and Metabolism.
|
Probiotic, Gut Microbiota, Helicobacter Pylori Infection, Insulin Resistance
|
* Dietary Supplement: Yogurt
* Dietary Supplement: Placebo
|
Inclusion Criteria:~Age between 20 to 70 years old with positive Helicobacter pylori gastric C13 urea breath test (ΔUBT>10%).~Negative gastric Helicobacter (ΔUBT<2%) matching age, gender, and body mass index.~Exclusion Criteria:~Unhealthy habits or poor health status, including habitual smoking, alcoholism, polypharmacy or drug abuses.~Patients with acute diseases, such as respiratory tract infection, acute gastroenteritis.~In the past three months, those who have had dyspepsia but have not undergone gastroscopy, or have a history of active gastrointestinal ulcers and gastrointestinal bleeding.~Those who have had gastrointestinal cancer or have undergone gastrointestinal surgery.~Those who are unwilling to delay receiving Anti-H. pylori therapy.~Newly diagnosed cancer (except basal cell carcinoma) or cancer treatment in the past 5 years.~People who have had cardiovascular disease, respiratory disease, autoimmune disease, mental disease or other chronic diseases that are not well controlled, such as myocardial infarction or stroke, chronic obstructive pulmonary disease, inflammatory bowel disease, Schizophrenia.~Diabetes and those who are or need to take drugs.~Those who have used the following drugs in the past month: antibiotics, NSAIDs, obesity drugs, steroid therapy, proton pump inhibitors, bismuth agents.~In the past month, regularly consume the following foods (at least 2 times a week): probiotics, prebiotics, or any foods containing probiotics, dairy products (yogurt, cheese), Chinese medicine, kimchi, miso, honey, cranberry, spicy food.~Fecal occult blood positive, unexplained iron-deficiency anemia, weight increase or decrease by more than 5% within six months.~Abnormal liver function index (AST, ALT or ALP greater than 2 times the upper limit of normal), abnormal renal function index (eGFR less than 45 ml/min).~Pregnant or breast-feeding women.
|
20 Years
|
70 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of gut Microbiome | uses high-throughput sequencing to sequence the 16S rRNA | Baseline to day 28 and day 56 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of C13 urea breath test | Delta urea breath test | Baseline to day 28 and day 56 |
|
Infections, Helicobacter Infections, Insulin Resistance, Hyperinsulinism, Glucose Metabolism Disorders, Metabolic Diseases, Gram-Negative Bacterial Infections, Bacterial Infections, Bacterial Infections and Mycoses
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Yogurt<br>Drink a bottle of 200ml yogurt every morning and evening for 8 weeks | Dietary Supplement: Yogurt<br>* Drink a bottle of 200ml yogurt every morning and evening for 8 weeks<br>|
| Placebo Comparator: Placebo<br>Drink a bottle of 200ml placebo every morning and evening for 8 weeks | Dietary Supplement: Placebo<br>* Drink a bottle of 200ml placebo every morning and evening for 8 weeks<br>|
| No Intervention: Healthy volunteer<br>Patients with Helicobacter pylori negative (ΔUBT<2%) need blood test and collect stool samples at first, and collect stool samples again after 2 months. | |
|
The Effects of Yogurt on Gut Microbiome and Metabolism in H. Pylori.
Study Overview
=================
Brief Summary
-----------------
Helicobacter pylori is a common pathogen causing upper gastrointestinal diseases including gastric ulcer and gastric cancer. Recent epidemiological findings have also shown that it is also related to colon cancer, metabolic syndrome, gut dysbiosis, glycemic control and insulin resistance. The aim of this study is to investigate whether the gut microbiota and insulin resistance of patients with H. pylori infection are abnormal. In addition, whether drinking fermented milk product with probiotic reduces Helicobacter pylori, improves gut microbiota, and increases butyrate-producing bacteria and insulin resistance.
Official Title
-----------------
The Effects of Fermented Milk Product With Probiotic on Helicobacter Pylori Infection, Gut Microbiome and Metabolism.
Conditions
-----------------
Probiotic, Gut Microbiota, Helicobacter Pylori Infection, Insulin Resistance
Intervention / Treatment
-----------------
* Dietary Supplement: Yogurt
* Dietary Supplement: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 20 to 70 years old with positive Helicobacter pylori gastric C13 urea breath test (ΔUBT>10%). Negative gastric Helicobacter (ΔUBT<2%) matching age, gender, and body mass index. Exclusion Criteria: Unhealthy habits or poor health status, including habitual smoking, alcoholism, polypharmacy or drug abuses. Patients with acute diseases, such as respiratory tract infection, acute gastroenteritis. In the past three months, those who have had dyspepsia but have not undergone gastroscopy, or have a history of active gastrointestinal ulcers and gastrointestinal bleeding. Those who have had gastrointestinal cancer or have undergone gastrointestinal surgery. Those who are unwilling to delay receiving Anti-H. pylori therapy. Newly diagnosed cancer (except basal cell carcinoma) or cancer treatment in the past 5 years. People who have had cardiovascular disease, respiratory disease, autoimmune disease, mental disease or other chronic diseases that are not well controlled, such as myocardial infarction or stroke, chronic obstructive pulmonary disease, inflammatory bowel disease, Schizophrenia. Diabetes and those who are or need to take drugs. Those who have used the following drugs in the past month: antibiotics, NSAIDs, obesity drugs, steroid therapy, proton pump inhibitors, bismuth agents. In the past month, regularly consume the following foods (at least 2 times a week): probiotics, prebiotics, or any foods containing probiotics, dairy products (yogurt, cheese), Chinese medicine, kimchi, miso, honey, cranberry, spicy food. Fecal occult blood positive, unexplained iron-deficiency anemia, weight increase or decrease by more than 5% within six months. Abnormal liver function index (AST, ALT or ALP greater than 2 times the upper limit of normal), abnormal renal function index (eGFR less than 45 ml/min). Pregnant or breast-feeding women.
Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 70 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: Yogurt<br>Drink a bottle of 200ml yogurt every morning and evening for 8 weeks | Dietary Supplement: Yogurt<br>* Drink a bottle of 200ml yogurt every morning and evening for 8 weeks<br>|
| Placebo Comparator: Placebo<br>Drink a bottle of 200ml placebo every morning and evening for 8 weeks | Dietary Supplement: Placebo<br>* Drink a bottle of 200ml placebo every morning and evening for 8 weeks<br>|
| No Intervention: Healthy volunteer<br>Patients with Helicobacter pylori negative (ΔUBT<2%) need blood test and collect stool samples at first, and collect stool samples again after 2 months. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of gut Microbiome | uses high-throughput sequencing to sequence the 16S rRNA | Baseline to day 28 and day 56 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of C13 urea breath test | Delta urea breath test | Baseline to day 28 and day 56 |
|
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