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NCT00674323
|
Efficacy and Safety of Verteporfin Added to Ranibizumab in the Treatment of Symptomatic Macular Polypoidal Choroidal Vasculopathy
|
This study aims to compare the efficacy of ranibizumab and verteporfin PDT combination treatment and verteporfin PDT monotherapy vs.ranibizumab monotherapy alone in achieving complete regression of polyps in patients with symptomatic macular polypoidal choroidal vasculopathy.
|
A Multicentre, Randomized, Double Masked, Exploratory, Indocyanine Green Angiography (ICGA) Guided Study of 6 Months Duration to Compare the Safety and Effect on Polyp Regression of Verteporfin Photodynamic Therapy (PDT) Alone or Added to Ranibizumab in Patients With Symptomatic Macular Polypoidal Choroidal Vasculopathy
|
Polypoidal Choroidal Vasculopathy
|
* Drug: Verteporfin Photodynamic Therapy
* Drug: Ranibizumab
|
Inclusion Criteria:~Patients must give written informed consent before any assessment is performed.~Male or Female patients ≥18 yrs of age~Patients willing and able to comply with all study procedures~Inclusion criteria for study eye:~BCVA letter score between 73-24 (approximately 20/40 to 20/320 Snellen equivalent) using ETDRS visual acuity chart measured at 4 meters~PCV diagnosis confirmed by Central Reading Center~Greatest Linear Dimension (GLD) of the total lesion area < 5400 µm (~9 Macular Photocoagulation Study Disc Areas)~Exclusion Criteria:~Women of child-bearing potential who are not using one or more reliable contraception methods~Pregnant or nursing (lactating) women~History of hypersensitivity or allergy to fluorescein or indocyanine green (ICG), clinically significant drug allergy or known hypersensitivity to therapeutic or diagnostic protein products, or to any of the study drugs or their components~Patient with history of porphyria~Systemic medications known to be toxic to the lens, retina, or optic nerve~History of which might affect the interpretation of the results of the study, or renders the patient at high risk from treatment complications~Use of other investigational drugs within 30 days of randomization~Exclusion criteria for study eye:~Concomitant conditions/diseases:~Presence of angioid streaks, macular fibrosis, presumed ocular histoplasmosis syndrome, pathologic myopia (-8 Diopters or more)~Active ocular inflammation or infection~Uncontrolled glaucoma~Ocular disorders that may confound interpretation of study results~Prior Ocular treatment:~Prior Verteporfin PDT, external-beam radiation, laser photocoagulation, macular surgery, or transpupillary thermotherapy~Prior local treatment with Pegaptanib, Ranibizumab, Bevacizumab or other anti-angiogenic compound or any investigational treatment in both eyes or systemic use of bevacizumab within 90 days prior to randomization~History of intraocular surgery including pars plana vitrectomy and intraocular hemorrhage displacement is not allowed with the exception of uncomplicated cataract surgery that is allowed within 60 days prior to screening~Ocular conditions that required chronic concomitant therapy within 90 days prior to randomization with topical, ocular, or systemically administered corticosteroids or any herbal medication known to contain steroid-like components~Other protocol-defined inclusion/exclusion criteria may apply
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Complete Regression (CR) of Polyps Measured by Indocyanine Green Angiography (ICGA) | Indocyanine green angiography (ICGA) assessments were performed using the Heidelberg Retinal Angiography 2 (HRA2) machine to measure the Total Lesion Area and the degree of polyp regression. Complete regression was defined as no polyps seen on the imaging. | Month 6 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With at Least One Complete Polyp Regression During 6 Months Assessed by ICGA | Indocyanine green angiography (ICGA) assessments were performed using the Heidelberg Retinal Angiography 2 (HRA2) machine to measure the Total Lesion Area and the degree of polyp regression. Complete regression was defined as no polyps seen on the imaging. | Baseline through end of study (6 months) |
| Mean Change From Baseline in Central Retinal Thickness Measured by Optic Coherence Tomography (OCT) | High resolution 6 meridian scans were performed to measure central retinal thickness. | Baseline and Month 6 |
| Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) of the Study Eye at Month 6 | BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20. An increase in the VA score indicates improvement in visual acuity. | Baseline and Month 6 |
|
Polypoidal choroidal vasculopathy, PCV, Age-related macular degeneration (AMD) variant, vision, polyps, indocyanine green angiography, verteporfin, ranibizumab, photodynamic therapy
|
Ranibizumab, Verteporfin, Angiogenesis Inhibitors, Angiogenesis Modulating Agents, Growth Substances, Physiological Effects of Drugs, Growth Inhibitors, Antineoplastic Agents, Photosensitizing Agents, Dermatologic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Verteporfin and Ranibizumab<br>Photodynamic therapy with verteporfin in combination with ranibizumab injection. Patients received one treatment at baseline with verteporfin photodynamic therapy (PDT) in the study eye and thereafter based on re-treatment criteria at intervals of at least 90 days. Within 1-24 hours, patients also received Ranibizumab intravitreal injection on Day 1 and at Month 1 and 2 and thereafter according to the re-treatment criteria at intervals of at least 30 days through Day 150. From month 3 onward, re-treatments were determined based on study-specific re-treatment criteria that included evaluation of polyp progression on indocyanine green angiography (ICGA), and assessment of fluorescein angiograms and visual acuity. | Drug: Verteporfin Photodynamic Therapy<br>* After a 10-minute intravenous infusion of verteporfin at a dose of 6 mg/m^2 body surface area, light application of 50 J/cm^2 to the study eye was begun 15 minutes after the start of infusion.<br>* Other names: Visudyne;Drug: Ranibizumab<br>* Ranibizumab at dose of 0.5 mg administered as an intravitreal injection.<br>* Other names: Lucentis;|
| Active Comparator: Verteporfin monotherapy<br>Patients received one treatment at baseline with verteporfin photodynamic therapy in the study eye and thereafter based on re-treatment criteria at intervals of at least 90 days. Within 1-24 hours, patients also received Ranibizumab placebo (sham intravitreal injection) on Day 1 and at Month 1 and 2 and thereafter according to the re-treatment criteria at intervals of at least 30 days through Day 150. From month 3 onward, re-treatments were determined based on study-specific re-treatment criteria that included evaluation of polyp progression on indocyanine green angiography (ICGA), and assessment of fluorescein angiograms and visual acuity. | Drug: Verteporfin Photodynamic Therapy<br>* After a 10-minute intravenous infusion of verteporfin at a dose of 6 mg/m^2 body surface area, light application of 50 J/cm^2 to the study eye was begun 15 minutes after the start of infusion.<br>* Other names: Visudyne;|
| Active Comparator: Ranibizumab monotherapy<br>Patients received one treatment at baseline with verteporfin placebo (with sham photodynamic therapy) in the study eye and thereafter based on re-treatment criteria at intervals of at least 90 days. Within 1-24 hours, patients also received Ranibizumab intravitreal injection on Day 1 and at Month 1 and 2 and thereafter according to the re-treatment criteria at intervals of at least 30 days through Day 150. From month 3 onward, re-treatments were determined based on study-specific re-treatment criteria that included evaluation of polyp progression on indocyanine green angiography (ICGA), and assessment of fluorescein angiograms and visual acuity. | Drug: Ranibizumab<br>* Ranibizumab at dose of 0.5 mg administered as an intravitreal injection.<br>* Other names: Lucentis;|
|
Efficacy and Safety of Verteporfin Added to Ranibizumab in the Treatment of Symptomatic Macular Polypoidal Choroidal Vasculopathy
Study Overview
=================
Brief Summary
-----------------
This study aims to compare the efficacy of ranibizumab and verteporfin PDT combination treatment and verteporfin PDT monotherapy vs.ranibizumab monotherapy alone in achieving complete regression of polyps in patients with symptomatic macular polypoidal choroidal vasculopathy.
Official Title
-----------------
A Multicentre, Randomized, Double Masked, Exploratory, Indocyanine Green Angiography (ICGA) Guided Study of 6 Months Duration to Compare the Safety and Effect on Polyp Regression of Verteporfin Photodynamic Therapy (PDT) Alone or Added to Ranibizumab in Patients With Symptomatic Macular Polypoidal Choroidal Vasculopathy
Conditions
-----------------
Polypoidal Choroidal Vasculopathy
Intervention / Treatment
-----------------
* Drug: Verteporfin Photodynamic Therapy
* Drug: Ranibizumab
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must give written informed consent before any assessment is performed. Male or Female patients ≥18 yrs of age Patients willing and able to comply with all study procedures Inclusion criteria for study eye: BCVA letter score between 73-24 (approximately 20/40 to 20/320 Snellen equivalent) using ETDRS visual acuity chart measured at 4 meters PCV diagnosis confirmed by Central Reading Center Greatest Linear Dimension (GLD) of the total lesion area < 5400 µm ( 9 Macular Photocoagulation Study Disc Areas) Exclusion Criteria: Women of child-bearing potential who are not using one or more reliable contraception methods Pregnant or nursing (lactating) women History of hypersensitivity or allergy to fluorescein or indocyanine green (ICG), clinically significant drug allergy or known hypersensitivity to therapeutic or diagnostic protein products, or to any of the study drugs or their components Patient with history of porphyria Systemic medications known to be toxic to the lens, retina, or optic nerve History of which might affect the interpretation of the results of the study, or renders the patient at high risk from treatment complications Use of other investigational drugs within 30 days of randomization Exclusion criteria for study eye: Concomitant conditions/diseases: Presence of angioid streaks, macular fibrosis, presumed ocular histoplasmosis syndrome, pathologic myopia (-8 Diopters or more) Active ocular inflammation or infection Uncontrolled glaucoma Ocular disorders that may confound interpretation of study results Prior Ocular treatment: Prior Verteporfin PDT, external-beam radiation, laser photocoagulation, macular surgery, or transpupillary thermotherapy Prior local treatment with Pegaptanib, Ranibizumab, Bevacizumab or other anti-angiogenic compound or any investigational treatment in both eyes or systemic use of bevacizumab within 90 days prior to randomization History of intraocular surgery including pars plana vitrectomy and intraocular hemorrhage displacement is not allowed with the exception of uncomplicated cataract surgery that is allowed within 60 days prior to screening Ocular conditions that required chronic concomitant therapy within 90 days prior to randomization with topical, ocular, or systemically administered corticosteroids or any herbal medication known to contain steroid-like components Other protocol-defined inclusion/exclusion criteria may apply
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Verteporfin and Ranibizumab<br>Photodynamic therapy with verteporfin in combination with ranibizumab injection. Patients received one treatment at baseline with verteporfin photodynamic therapy (PDT) in the study eye and thereafter based on re-treatment criteria at intervals of at least 90 days. Within 1-24 hours, patients also received Ranibizumab intravitreal injection on Day 1 and at Month 1 and 2 and thereafter according to the re-treatment criteria at intervals of at least 30 days through Day 150. From month 3 onward, re-treatments were determined based on study-specific re-treatment criteria that included evaluation of polyp progression on indocyanine green angiography (ICGA), and assessment of fluorescein angiograms and visual acuity. | Drug: Verteporfin Photodynamic Therapy<br>* After a 10-minute intravenous infusion of verteporfin at a dose of 6 mg/m^2 body surface area, light application of 50 J/cm^2 to the study eye was begun 15 minutes after the start of infusion.<br>* Other names: Visudyne;Drug: Ranibizumab<br>* Ranibizumab at dose of 0.5 mg administered as an intravitreal injection.<br>* Other names: Lucentis;|
| Active Comparator: Verteporfin monotherapy<br>Patients received one treatment at baseline with verteporfin photodynamic therapy in the study eye and thereafter based on re-treatment criteria at intervals of at least 90 days. Within 1-24 hours, patients also received Ranibizumab placebo (sham intravitreal injection) on Day 1 and at Month 1 and 2 and thereafter according to the re-treatment criteria at intervals of at least 30 days through Day 150. From month 3 onward, re-treatments were determined based on study-specific re-treatment criteria that included evaluation of polyp progression on indocyanine green angiography (ICGA), and assessment of fluorescein angiograms and visual acuity. | Drug: Verteporfin Photodynamic Therapy<br>* After a 10-minute intravenous infusion of verteporfin at a dose of 6 mg/m^2 body surface area, light application of 50 J/cm^2 to the study eye was begun 15 minutes after the start of infusion.<br>* Other names: Visudyne;|
| Active Comparator: Ranibizumab monotherapy<br>Patients received one treatment at baseline with verteporfin placebo (with sham photodynamic therapy) in the study eye and thereafter based on re-treatment criteria at intervals of at least 90 days. Within 1-24 hours, patients also received Ranibizumab intravitreal injection on Day 1 and at Month 1 and 2 and thereafter according to the re-treatment criteria at intervals of at least 30 days through Day 150. From month 3 onward, re-treatments were determined based on study-specific re-treatment criteria that included evaluation of polyp progression on indocyanine green angiography (ICGA), and assessment of fluorescein angiograms and visual acuity. | Drug: Ranibizumab<br>* Ranibizumab at dose of 0.5 mg administered as an intravitreal injection.<br>* Other names: Lucentis;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Complete Regression (CR) of Polyps Measured by Indocyanine Green Angiography (ICGA) | Indocyanine green angiography (ICGA) assessments were performed using the Heidelberg Retinal Angiography 2 (HRA2) machine to measure the Total Lesion Area and the degree of polyp regression. Complete regression was defined as no polyps seen on the imaging. | Month 6 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With at Least One Complete Polyp Regression During 6 Months Assessed by ICGA | Indocyanine green angiography (ICGA) assessments were performed using the Heidelberg Retinal Angiography 2 (HRA2) machine to measure the Total Lesion Area and the degree of polyp regression. Complete regression was defined as no polyps seen on the imaging. | Baseline through end of study (6 months) |
| Mean Change From Baseline in Central Retinal Thickness Measured by Optic Coherence Tomography (OCT) | High resolution 6 meridian scans were performed to measure central retinal thickness. | Baseline and Month 6 |
| Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) of the Study Eye at Month 6 | BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20. An increase in the VA score indicates improvement in visual acuity. | Baseline and Month 6 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Polypoidal choroidal vasculopathy, PCV, Age-related macular degeneration (AMD) variant, vision, polyps, indocyanine green angiography, verteporfin, ranibizumab, photodynamic therapy
|
|
NCT04256434
|
A Bioavailability Study of NALDEBAIN ER Injection and Nalbuphine Injection in Healthy Volunteers.
|
This is an open-label, sequential 2 cohort, intramuscular injection study in healthy volunteers. The study will enroll approximately 24 healthy volunteers to examine the safety, pharmacokinetics, and bioavailability after intramuscular injection of NALDEBAIN ER Injection and nalbuphine injection.
|
Each subject in a cohort will be evaluated for study eligibility during the screening period, which is within 28 days prior to receiving the study drug (Day 1). Eligible subjects will be admitted into the study site on Day -1 and will be required to stay in clinical site for 5 (Cohort 1) or 2 nights (Cohort 2) for study procedures in each cohort. Eligible subjects will undergo additional eligibility assessments on Day -1 and those reconfirmed eligible will intramuscularly receive NALDEBAIN ER Injection (Cohort 1) or nalbuphine (Cohort 2) on Day 1.~The blood sampling timepoints for Cohort 1 will be at predose, 6, 12, 24, 48, 56, 64, 72, 80, 88, and 96 hours after dosing. Subjects will be discharged after the 96-hour blood sample and return to the clinical site for the sample collection at 120, 168, 216, 288 and 360 hours post dosing. The blood sampling timepoints for Cohort 2 will be predose, 5, 15, and 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose.~Subjects will return for a follow-up visit to complete safety evaluations for approximately 15 days after study drug administration in cohort 1; and 1 days after study drug administration in Cohort 2.
|
A Bioavailability Study of NALDEBAIN ER Injection and Nalbuphine Injection in Healthy Volunteers.
|
Health
|
* Drug: Dinalbuphine sebacate
* Drug: Nalbuphine HCl
|
Inclusion Criteria:~Male or female, 18 to 55 years of age inclusive at the time of signing the informed consent form~Body weight must be above 60 kg.~Body Mass Index (BMI) 18 to 40 kg/m2~In good health on the basis of medical history, physical examination, electrocardiogram, chest X-ray, and routine laboratory evaluations.~If male, must agree to use contraception as detailed in Appendix 5 of this protocol during the treatment period until the final PK sample, and refrain from donating sperm for 90 days after the dosing.~If female, is not pregnant (see Appendix 5), not breastfeeding, and at least one of the following conditions applies:~Not a woman of childbearing potential (WOCBP) as defined in Appendix 5 OR A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 during the treatment period until the last PK sample.~Vital signs (after 3 minutes resting in a semi-supine position) which are within the following ranges:~Oral temperature between 35.0-37.5°C.~Systolic blood pressure, 90-140 mm Hg.~Diastolic blood pressure, 50-90 mm Hg.~Pulse rate, 50-90 bpm.~Respiratory rate, 12-20 bpm~Oxyhemoglobin saturation, ≥95%~Fasting blood glucose, <110 mg/dL.~Able to communicate well with the investigator and comply with the requirements of the study.~Exclusion Criteria:~Use of any prescription medications or over-the-counter, non-prescription preparations (including herbal preparations) within 2 weeks prior to study entry unless deemed acceptable by the Investigator (except up to 5 doses of ≤ 1000 mg of acetaminophen or ≤ 400 mg ibuprofen within this 2 weeks period).~Alcohol or caffeine ingested within 72 hours prior to dosing.~Significant illness within 2 weeks prior to dosing.~Participation in any clinical investigation within 2 months prior to dosing or longer as required by local regulation.~Donation or loss of more than 500 mL of blood within 3 months prior to dosing. Donation or loss of more than 250 mL of blood within 2 months prior to dosing.~Documented history of cardiovascular disease.~Documented history of gastrointestinal disease.~Documented history of asthma or lung disease.~Presence of liver disease or liver injury as indicated by an abnormal liver function profile such as aspartate aminotransaminase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (gamma-GT), Alkaline Phosphatase, or Total Bilirubin at Screening. (value of AST or ALT above 3 times of the upper limit of the normal range; other items clinically significant abnormality judged by investigator).~Presence of impaired renal function as indicated by abnormal creatinine or BUN values or abnormal urinary constituents at Screening. (value of creatinine or BUN beyond the range from -20% of the lower limit of the normal range to +20% of the upper limit of the normal range; other items clinically significant abnormality judged by investigator)~Documented history of neurological disease.~Documented history of psychiatric disease.~Has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV; has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or tests positive for HBsAg or anti-HCV at Screening.~A known hypersensitivity to nalbuphine or its analogs.~History of drug or alcohol abuse within 12 months prior to dosing or positive test results for alcohol or drugs of abuse at Screening and admission.~Permanent confinement to an institution.~Pregnant or lactating women.~Subject has received any investigational product within 30 days or 5 half-lives (whichever is longer) prior to the dosing day or is planning to participate in a clinical trial during the study period.~Has preplanned surgery or procedures that would interfere with the conduct of the study~Individuals are judged by the investigator to be undesirable subjects for other reasons.~Is an employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the Investigator.
|
18 Years
|
55 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This is an open-label, sequential 2 cohort, intramuscular injection study in healthy volunteers.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioavailability of nalbuphine after intramuscular injection of NALDEBAIN and Nalbuphine. | To evaluate the relative bioavailability of nalbuphine after intramuscular injection of NALDEBAIN and Nalbuphine. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) of nalbuphine, sebacoyl mononalbuphine ester (SME) and dinalbuphine sebacate. | Cmax for NALDEBAIN and Nalbuphine. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
| Tmax of nalbuphine, sebacoyl mononalbuphine ester (SME) and dinalbuphine sebacate. | Tmax for NALDEBAIN and Nalbuphine. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
| AUCinf of nalbuphine, sebacoyl mononalbuphine ester (SME) and dinalbuphine sebacate. | AUCinf for NALDEBAIN and Nalbuphine. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
| AUClast of nalbuphine, sebacoyl mononalbuphine ester (SME) and dinalbuphine sebacate. | AUClast for NALDEBAIN and Nalbuphine. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
| Elimination half-life (t1/2) of nalbuphine, sebacoyl mononalbuphine ester (SME) and dinalbuphine sebacate. | Elimination half-life for NALDEBAIN and Nalbuphine. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
| Total body clearance of the drug from plasma (CL) of nalbuphine, sebacoyl mononalbuphine ester (SME) and dinalbuphine sebacate. | Total body clearance for NALDEBAIN and Nalbuphine. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
| Volume of distribution (Vd) of nalbuphine, sebacoyl mononalbuphine ester (SME) and dinalbuphine sebacate. | Volume of distribution for NALDEBAIN and Nalbuphine. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
| Incidence and severity of adverse events (AEs) | To evaluate the systemic and local safety and tolerance. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
| Number of subjects with AEs | To evaluate number of subjects with adverse events. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
|
Analgesics, Sensory System Agents, Nalbuphine, Analgesics, Opioid, Narcotics, Central Nervous System Depressants, Physiological Effects of Drugs, Peripheral Nervous System Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dinabuphine sebacate<br>Each subject in cohort 1 will receive 150 mg Dinalbuphine sebacate (75 mg/mL x 2 mL) intramuscularly. | Drug: Dinalbuphine sebacate<br>* 150 mg Dinalbuphine sebacate<br>* Other names: LT1001;|
| Active Comparator: Nalbuphine HCl<br>Each subject in cohort 2 will receive 20 mg Nalbuphine (20 mg x 1 mL) intramuscularly. | Drug: Nalbuphine HCl<br>* 20 mg Nalbuphine<br>* Other names: Nalbuphine HCl Injection;|
|
A Bioavailability Study of NALDEBAIN ER Injection and Nalbuphine Injection in Healthy Volunteers.
Study Overview
=================
Brief Summary
-----------------
This is an open-label, sequential 2 cohort, intramuscular injection study in healthy volunteers. The study will enroll approximately 24 healthy volunteers to examine the safety, pharmacokinetics, and bioavailability after intramuscular injection of NALDEBAIN ER Injection and nalbuphine injection.
Detailed Description
-----------------
Each subject in a cohort will be evaluated for study eligibility during the screening period, which is within 28 days prior to receiving the study drug (Day 1). Eligible subjects will be admitted into the study site on Day -1 and will be required to stay in clinical site for 5 (Cohort 1) or 2 nights (Cohort 2) for study procedures in each cohort. Eligible subjects will undergo additional eligibility assessments on Day -1 and those reconfirmed eligible will intramuscularly receive NALDEBAIN ER Injection (Cohort 1) or nalbuphine (Cohort 2) on Day 1. The blood sampling timepoints for Cohort 1 will be at predose, 6, 12, 24, 48, 56, 64, 72, 80, 88, and 96 hours after dosing. Subjects will be discharged after the 96-hour blood sample and return to the clinical site for the sample collection at 120, 168, 216, 288 and 360 hours post dosing. The blood sampling timepoints for Cohort 2 will be predose, 5, 15, and 30 minutes postdose, and 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose. Subjects will return for a follow-up visit to complete safety evaluations for approximately 15 days after study drug administration in cohort 1; and 1 days after study drug administration in Cohort 2.
Official Title
-----------------
A Bioavailability Study of NALDEBAIN ER Injection and Nalbuphine Injection in Healthy Volunteers.
Conditions
-----------------
Health
Intervention / Treatment
-----------------
* Drug: Dinalbuphine sebacate
* Drug: Nalbuphine HCl
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, 18 to 55 years of age inclusive at the time of signing the informed consent form Body weight must be above 60 kg. Body Mass Index (BMI) 18 to 40 kg/m2 In good health on the basis of medical history, physical examination, electrocardiogram, chest X-ray, and routine laboratory evaluations. If male, must agree to use contraception as detailed in Appendix 5 of this protocol during the treatment period until the final PK sample, and refrain from donating sperm for 90 days after the dosing. If female, is not pregnant (see Appendix 5), not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) as defined in Appendix 5 OR A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 during the treatment period until the last PK sample. Vital signs (after 3 minutes resting in a semi-supine position) which are within the following ranges: Oral temperature between 35.0-37.5°C. Systolic blood pressure, 90-140 mm Hg. Diastolic blood pressure, 50-90 mm Hg. Pulse rate, 50-90 bpm. Respiratory rate, 12-20 bpm Oxyhemoglobin saturation, ≥95% Fasting blood glucose, <110 mg/dL. Able to communicate well with the investigator and comply with the requirements of the study. Exclusion Criteria: Use of any prescription medications or over-the-counter, non-prescription preparations (including herbal preparations) within 2 weeks prior to study entry unless deemed acceptable by the Investigator (except up to 5 doses of ≤ 1000 mg of acetaminophen or ≤ 400 mg ibuprofen within this 2 weeks period). Alcohol or caffeine ingested within 72 hours prior to dosing. Significant illness within 2 weeks prior to dosing. Participation in any clinical investigation within 2 months prior to dosing or longer as required by local regulation. Donation or loss of more than 500 mL of blood within 3 months prior to dosing. Donation or loss of more than 250 mL of blood within 2 months prior to dosing. Documented history of cardiovascular disease. Documented history of gastrointestinal disease. Documented history of asthma or lung disease. Presence of liver disease or liver injury as indicated by an abnormal liver function profile such as aspartate aminotransaminase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (gamma-GT), Alkaline Phosphatase, or Total Bilirubin at Screening. (value of AST or ALT above 3 times of the upper limit of the normal range; other items clinically significant abnormality judged by investigator). Presence of impaired renal function as indicated by abnormal creatinine or BUN values or abnormal urinary constituents at Screening. (value of creatinine or BUN beyond the range from -20% of the lower limit of the normal range to +20% of the upper limit of the normal range; other items clinically significant abnormality judged by investigator) Documented history of neurological disease. Documented history of psychiatric disease. Has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV; has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or tests positive for HBsAg or anti-HCV at Screening. A known hypersensitivity to nalbuphine or its analogs. History of drug or alcohol abuse within 12 months prior to dosing or positive test results for alcohol or drugs of abuse at Screening and admission. Permanent confinement to an institution. Pregnant or lactating women. Subject has received any investigational product within 30 days or 5 half-lives (whichever is longer) prior to the dosing day or is planning to participate in a clinical trial during the study period. Has preplanned surgery or procedures that would interfere with the conduct of the study Individuals are judged by the investigator to be undesirable subjects for other reasons. Is an employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the Investigator.
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: Sequential Assignment
Interventional Model Description: This is an open-label, sequential 2 cohort, intramuscular injection study in healthy volunteers.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dinabuphine sebacate<br>Each subject in cohort 1 will receive 150 mg Dinalbuphine sebacate (75 mg/mL x 2 mL) intramuscularly. | Drug: Dinalbuphine sebacate<br>* 150 mg Dinalbuphine sebacate<br>* Other names: LT1001;|
| Active Comparator: Nalbuphine HCl<br>Each subject in cohort 2 will receive 20 mg Nalbuphine (20 mg x 1 mL) intramuscularly. | Drug: Nalbuphine HCl<br>* 20 mg Nalbuphine<br>* Other names: Nalbuphine HCl Injection;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioavailability of nalbuphine after intramuscular injection of NALDEBAIN and Nalbuphine. | To evaluate the relative bioavailability of nalbuphine after intramuscular injection of NALDEBAIN and Nalbuphine. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) of nalbuphine, sebacoyl mononalbuphine ester (SME) and dinalbuphine sebacate. | Cmax for NALDEBAIN and Nalbuphine. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
| Tmax of nalbuphine, sebacoyl mononalbuphine ester (SME) and dinalbuphine sebacate. | Tmax for NALDEBAIN and Nalbuphine. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
| AUCinf of nalbuphine, sebacoyl mononalbuphine ester (SME) and dinalbuphine sebacate. | AUCinf for NALDEBAIN and Nalbuphine. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
| AUClast of nalbuphine, sebacoyl mononalbuphine ester (SME) and dinalbuphine sebacate. | AUClast for NALDEBAIN and Nalbuphine. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
| Elimination half-life (t1/2) of nalbuphine, sebacoyl mononalbuphine ester (SME) and dinalbuphine sebacate. | Elimination half-life for NALDEBAIN and Nalbuphine. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
| Total body clearance of the drug from plasma (CL) of nalbuphine, sebacoyl mononalbuphine ester (SME) and dinalbuphine sebacate. | Total body clearance for NALDEBAIN and Nalbuphine. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
| Volume of distribution (Vd) of nalbuphine, sebacoyl mononalbuphine ester (SME) and dinalbuphine sebacate. | Volume of distribution for NALDEBAIN and Nalbuphine. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
| Incidence and severity of adverse events (AEs) | To evaluate the systemic and local safety and tolerance. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
| Number of subjects with AEs | To evaluate number of subjects with adverse events. | Cohort 1: From predose to 360 hours post dosing. Cohort 2 : From predose to 24 hours post dosing. |
|
|
NCT04609293
|
Observational Study of Camrelizumab Combined With Apatinib and Hyperfractionated Radiotherapy for Renal Cell Carcinoma
|
This trial will explore effectiveness and safety using the combination therapy of camrelizumab，apatinib and hyperfractionated radiotherapy in patients with renal cell carcinoma(RCC). Hypofractionation is a technique that delivers higher daily doses of radiation over a shorter period of time.immunotherapy. hyperfractionated radiotherapy, represented by stereotactic body radiation therapy (SBRT), can significantly improve the radiotherapy sensitivity of RCC. This trial will also observe whether SBRT can bring about immune effects and explore the group and individual indicators that affect the treatment effect of RCC.
|
This trial is a prospective, single-center, observational clinical trial evaluating the combination therapy of camrelizumab，apatinib and hyperfractionated radiotherapy in patients with renal cell carcinoma(RCC). All enrolled patients will receive the following treatments: camrelizumab 200mg every 2 weeks for 1 years combined with apatinib 250mg everyday until disease progression (as determined by RECIST 1.1), intolerance, or patient/physician decision to stop treatment. One week following completion of the second immunotherapy, hypofractionated radiotherapy with marginal dose of 50Gy/2Gy/25f and tumor center dose of local hyperfraction increase 24-32Gy/8-12Gy/3-4f will be performed 3-5 times. The routine radiotherapy will be started at the same time as the third immunotherapy and 25 times routine radiotherapy will be completed before the fifth or sixth immunotherapy.~During treatment participants will be assessed for curative effects and the occurrence of adverse events. Following treatment, participants will be assessed at a clinic visit every 3 months to collect survival information and follow-up treatment information. The planned sample size is 30 study participants.
|
Observational Study of Camrelizumab Combined With Apatinib and Hyperfractionated Radiotherapy for Renal Cell Carcinoma
|
Renal Cell Carcinoma
|
* Combination Product: camrelizumab+apatinib+hyperfractionated radiotherapy
|
Inclusion Criteria:~Patients with clear cell renal cell carcinoma were confirmed by histological or cytological;~Locally advanced/metastatic (the newly diagnosed stage IV RCC assessed by AJCC) or recurrent RCC;~Have not received or received systemic treatment for first-line advanced HCC (including but not limited to a variety of targeted therapies including TKI, VEGF and mTOR);~The number of measurable lesion is not more than 5, or although the number of measurable lesion is more than 5, but the radiotherapy department and imaging doctors evaluate that the measurable lesions that can accept radiotherapy are more than or equal to 3;~According to RECIST 1.1 standard, there will be clinically assessable lesions, and the target lesion has not received radiotherapy before;~Male or female,from 18 to 75 years;~The life expectancy will be longer than 6 months;~ECOG score will be 0 - 2;~The main organ functions are normal, and there is no serious blood, heart, lung, liver, kidney dysfunction and immune deficiency diseases. The results of laboratory test must be met the following criteria: Neutrophils: more than 1.5 × 109/L; ; Platelets: more than 100 × 109/L; Hemoglobin: more than 100g/L; serum albumin：more than 30 g/L; bilirubin：less than the upper normal limit (ULN); ALT and AST：less than 2.5 folds of the upper normal limit (ULN)，if there is liver metastasis, ALT and AST must be less than 5 folds of the upper normal limit (ULN) ; Serum Creatinine: less than 1.5×ULN; Blood Urea Nitrogen (BUN): less than 2.5×ULN; Thyroid Stimulating Hormone (TSH): ess than the upper normal limit (ULN)，if abnormal, the T3 and T4 levels should be examined, and the T3 and T4 levels are normal;~Be willing to comply with research and follow-up procedures;~Female and male subjects should take effective contraceptive measures from the beginning of treatment to within 6 months after the end of treatment.Agreeing to participate in this study and signing a written informed consent.~Exclusion Criteria:~Central nervous system metastasis (including brain metastasis, meningeal metastasis, etc.);~Other immunosuppressive drugs used within 14 days before before study drug administration, excluding nasal sprays and inhaled corticosteroids or physiological doses of systemic steroids (ie not more than 10 mg/day of prednisolone or Other corticosteroids of equivalent pharmacological physiological dose);~Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents: systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥ 90 mmHg;~Clinically significant cardiovascular diseases：Myocardial ischemia or myocardial infarction above grade II, ventricular arrhythmia which poorly controlled，QTc>450ms（male）/QTc>470ms (female)；Congestive heart failure (New York heart association (NYHA) class is Ⅲ～Ⅳ)；or cardiac color Doppler ultrasound examination revealed that the left ventricular ejection fraction (LVEF) <50%;~Accompanied by uncontrolled pleural effusion, pericardial effusion, or ascites that requires repeated drainage;~Patients with any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism;~Asthma that requires intermittent use of bronchodilators or other medical intervention should be excluded（Asthma has been completely relieved in childhood, and those without any intervention after adulthood can be included）;~Coagulation abnormalities (INR>1.5、PT>ULN+4s、APTT >1.5 ULN）, with bleeding tendency or are receiving thrombolytic or anticoagulant therapy;~Proteinuria ≥ (++) and 24 hours total urine protein > 1.0 g;~Received major surgery or suffered severe traumatic injury, fracture or ulcer within 4 weeks before enrollment;~Severe infections (such as intravenous infusion of antibiotics, antifungal or antiviral drugs) within 4 weeks before the first administration, or unexplained fever> 38.5°C during the screening period/before the first administration;~Clinically significant hemoptysis or more than half a teaspoon (2.5ml) of hemoptysis per day occurred within 2 months before enrollment; or Clinically significant bleeding symptoms or tendency, such as gastrointestinal bleeding, hemorrhagic Gastric ulcer, fecal occult blood≥++ at baseline, or vasculitis, etc.;~Arterial/venous thrombosis events occurred in the 12 months before enrollment, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;~History of immunodeficiency or human immunodeficiency virus (HIV) infection: HBV DNA>500 IU/ml, HCV RNA>1000copies/ml, HBsAg+ and anti-HCV+；~Has a known additional malignancy within the last 5 years, exceptions include basal cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer;~The patient is using other research or standard anti-tumor drugs;~Patients with a clear history of allergies may be potentially allergic or intolerant to camrelizumab and apatinib;~Patients who have a history of psychotropic drug abuse and cannot be quit or have mental disorders;~Other condition, illness, psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or stereotactic radiotherapy administration, or may interfere with the interpretation of study results and in the judgment of the investigator would make the patient inappropriate for entry into this study.
|
18 Years
|
75 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate（ORR） | Objective response rate, which is defined as the proportion of subjects who achieve a best response of complete response (CR) or partial response (PR) using the RECIST 1.1 criteria. | 3 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject safety | Number of Adverse Events using NCI CTCAE 5.0 | Date of signing of informed consent form until 12 weeks after the last medication |
| Progression free survival (PFS) | The date of first treatment until the date of progression using the RECIST 1.1 criteria, or death due to any cause, whichever comes first. | 3 years |
| Disease control rate(DCR) | Disease control rate, which is defined as the proportion of subjects who achieve a response of complete response，partial response and stable disease (PR+CR+SD) in the total number of evaluable subjects using the RECIST 1.1 criteria. | 3 years |
| Overall Survival(OS) | Overall survival, defined from the date of first treatment to the date of death due to any cause. | 3 years |
| Local Control Rate | Local Control Rate, which is defined as the proportion of subjects who achieve a response of remission and stable disease (PR+CR+SD) evaluated by RECIST 1.1 after radiotherapy. | 3 years |
| Quality of Life: EORTC QLQ-C30 questionnaire | Quality of life, which will be evaluated using the EORTC（The European Organization for Reasearch and Treatment of Cancer） QLQ-C30（Quality of Life Questionnare-Core 30） questionnaire. The questionnaire contains 30 items. Items 29 and 30 are divided into seven levels, which are counted from 1 to 7 points, 1 is very poor, and 7 is very good. Other items are divided into 4 levels: no at all, a little bit, a lot, and very, and they are directly rated from 1 to 4 points. | 3 years |
| Response rate of lesions that did not receive radiotherapy | Response rate of lesions that did not receive radiotherapy, which is defined as the percentage of the number of cases with tumors that have not received radiotherapy in remission and stable disease (PR+CR+SD) in the total number of evaluable cases using the RECIST 1.1 criteria. | 3 years |
| Pathology and genetic testing | The pathology of the primary tumor before treatment, the puncture specimen of the tumor after the end of radiotherapy, and the whole exome sequencing of the tumor pathology after the progression + blood ctDNA detection for the patients who agree to the examination. | 3 years |
|
Apatinib, Antineoplastic Agents, Protein Kinase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Camrelizumab+apatinib+Hypofractionated radiation therapy<br>Camrelizumab:200mg every 2 weeks for 1 years or until disease progression (as determined by RECIST 1.1), intolerance, or patient/physician decision to stop treatment.~Apatinib:250mg everyday until disease progression (as determined by RECIST 1.1), intolerance, or patient/physician decision to stop treatment.~Radiation: one week following completion of the second immunotherapy, hypofractionated radiotherapy with marginal dose of 50Gy/2Gy/25f and tumor center dose of local hyperfraction increase 24-32Gy/8-12Gy/3-4f will be performed 3-5 times. The routine radiotherapy will be started at the same time as the third immunotherapy and 25 times routine radiotherapy will be completed before the fifth or sixth immunotherapy. | Combination Product: camrelizumab+apatinib+hyperfractionated radiotherapy<br>* Immunotherapy, anti-angiogenesis targeted therapy combined with hyperfractionated radiotherapy<br>|
|
Observational Study of Camrelizumab Combined With Apatinib and Hyperfractionated Radiotherapy for Renal Cell Carcinoma
Study Overview
=================
Brief Summary
-----------------
This trial will explore effectiveness and safety using the combination therapy of camrelizumab，apatinib and hyperfractionated radiotherapy in patients with renal cell carcinoma(RCC). Hypofractionation is a technique that delivers higher daily doses of radiation over a shorter period of time.immunotherapy. hyperfractionated radiotherapy, represented by stereotactic body radiation therapy (SBRT), can significantly improve the radiotherapy sensitivity of RCC. This trial will also observe whether SBRT can bring about immune effects and explore the group and individual indicators that affect the treatment effect of RCC.
Detailed Description
-----------------
This trial is a prospective, single-center, observational clinical trial evaluating the combination therapy of camrelizumab，apatinib and hyperfractionated radiotherapy in patients with renal cell carcinoma(RCC). All enrolled patients will receive the following treatments: camrelizumab 200mg every 2 weeks for 1 years combined with apatinib 250mg everyday until disease progression (as determined by RECIST 1.1), intolerance, or patient/physician decision to stop treatment. One week following completion of the second immunotherapy, hypofractionated radiotherapy with marginal dose of 50Gy/2Gy/25f and tumor center dose of local hyperfraction increase 24-32Gy/8-12Gy/3-4f will be performed 3-5 times. The routine radiotherapy will be started at the same time as the third immunotherapy and 25 times routine radiotherapy will be completed before the fifth or sixth immunotherapy. During treatment participants will be assessed for curative effects and the occurrence of adverse events. Following treatment, participants will be assessed at a clinic visit every 3 months to collect survival information and follow-up treatment information. The planned sample size is 30 study participants.
Official Title
-----------------
Observational Study of Camrelizumab Combined With Apatinib and Hyperfractionated Radiotherapy for Renal Cell Carcinoma
Conditions
-----------------
Renal Cell Carcinoma
Intervention / Treatment
-----------------
* Combination Product: camrelizumab+apatinib+hyperfractionated radiotherapy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with clear cell renal cell carcinoma were confirmed by histological or cytological; Locally advanced/metastatic (the newly diagnosed stage IV RCC assessed by AJCC) or recurrent RCC; Have not received or received systemic treatment for first-line advanced HCC (including but not limited to a variety of targeted therapies including TKI, VEGF and mTOR); The number of measurable lesion is not more than 5, or although the number of measurable lesion is more than 5, but the radiotherapy department and imaging doctors evaluate that the measurable lesions that can accept radiotherapy are more than or equal to 3; According to RECIST 1.1 standard, there will be clinically assessable lesions, and the target lesion has not received radiotherapy before; Male or female,from 18 to 75 years; The life expectancy will be longer than 6 months; ECOG score will be 0 - 2; The main organ functions are normal, and there is no serious blood, heart, lung, liver, kidney dysfunction and immune deficiency diseases. The results of laboratory test must be met the following criteria: Neutrophils: more than 1.5 × 109/L; ; Platelets: more than 100 × 109/L; Hemoglobin: more than 100g/L; serum albumin：more than 30 g/L; bilirubin：less than the upper normal limit (ULN); ALT and AST：less than 2.5 folds of the upper normal limit (ULN)，if there is liver metastasis, ALT and AST must be less than 5 folds of the upper normal limit (ULN) ; Serum Creatinine: less than 1.5×ULN; Blood Urea Nitrogen (BUN): less than 2.5×ULN; Thyroid Stimulating Hormone (TSH): ess than the upper normal limit (ULN)，if abnormal, the T3 and T4 levels should be examined, and the T3 and T4 levels are normal; Be willing to comply with research and follow-up procedures; Female and male subjects should take effective contraceptive measures from the beginning of treatment to within 6 months after the end of treatment.Agreeing to participate in this study and signing a written informed consent. Exclusion Criteria: Central nervous system metastasis (including brain metastasis, meningeal metastasis, etc.); Other immunosuppressive drugs used within 14 days before before study drug administration, excluding nasal sprays and inhaled corticosteroids or physiological doses of systemic steroids (ie not more than 10 mg/day of prednisolone or Other corticosteroids of equivalent pharmacological physiological dose); Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents: systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥ 90 mmHg; Clinically significant cardiovascular diseases：Myocardial ischemia or myocardial infarction above grade II, ventricular arrhythmia which poorly controlled，QTc>450ms（male）/QTc>470ms (female)；Congestive heart failure (New York heart association (NYHA) class is Ⅲ～Ⅳ)；or cardiac color Doppler ultrasound examination revealed that the left ventricular ejection fraction (LVEF) <50%; Accompanied by uncontrolled pleural effusion, pericardial effusion, or ascites that requires repeated drainage; Patients with any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism; Asthma that requires intermittent use of bronchodilators or other medical intervention should be excluded（Asthma has been completely relieved in childhood, and those without any intervention after adulthood can be included）; Coagulation abnormalities (INR>1.5、PT>ULN+4s、APTT >1.5 ULN）, with bleeding tendency or are receiving thrombolytic or anticoagulant therapy; Proteinuria ≥ (++) and 24 hours total urine protein > 1.0 g; Received major surgery or suffered severe traumatic injury, fracture or ulcer within 4 weeks before enrollment; Severe infections (such as intravenous infusion of antibiotics, antifungal or antiviral drugs) within 4 weeks before the first administration, or unexplained fever> 38.5°C during the screening period/before the first administration; Clinically significant hemoptysis or more than half a teaspoon (2.5ml) of hemoptysis per day occurred within 2 months before enrollment; or Clinically significant bleeding symptoms or tendency, such as gastrointestinal bleeding, hemorrhagic Gastric ulcer, fecal occult blood≥++ at baseline, or vasculitis, etc.; Arterial/venous thrombosis events occurred in the 12 months before enrollment, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism; History of immunodeficiency or human immunodeficiency virus (HIV) infection: HBV DNA>500 IU/ml, HCV RNA>1000copies/ml, HBsAg+ and anti-HCV+； Has a known additional malignancy within the last 5 years, exceptions include basal cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer; The patient is using other research or standard anti-tumor drugs; Patients with a clear history of allergies may be potentially allergic or intolerant to camrelizumab and apatinib; Patients who have a history of psychotropic drug abuse and cannot be quit or have mental disorders; Other condition, illness, psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or stereotactic radiotherapy administration, or may interfere with the interpretation of study results and in the judgment of the investigator would make the patient inappropriate for entry into this study.
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?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Camrelizumab+apatinib+Hypofractionated radiation therapy<br>Camrelizumab:200mg every 2 weeks for 1 years or until disease progression (as determined by RECIST 1.1), intolerance, or patient/physician decision to stop treatment. Apatinib:250mg everyday until disease progression (as determined by RECIST 1.1), intolerance, or patient/physician decision to stop treatment. Radiation: one week following completion of the second immunotherapy, hypofractionated radiotherapy with marginal dose of 50Gy/2Gy/25f and tumor center dose of local hyperfraction increase 24-32Gy/8-12Gy/3-4f will be performed 3-5 times. The routine radiotherapy will be started at the same time as the third immunotherapy and 25 times routine radiotherapy will be completed before the fifth or sixth immunotherapy. | Combination Product: camrelizumab+apatinib+hyperfractionated radiotherapy<br>* Immunotherapy, anti-angiogenesis targeted therapy combined with hyperfractionated radiotherapy<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate（ORR） | Objective response rate, which is defined as the proportion of subjects who achieve a best response of complete response (CR) or partial response (PR) using the RECIST 1.1 criteria. | 3 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject safety | Number of Adverse Events using NCI CTCAE 5.0 | Date of signing of informed consent form until 12 weeks after the last medication |
| Progression free survival (PFS) | The date of first treatment until the date of progression using the RECIST 1.1 criteria, or death due to any cause, whichever comes first. | 3 years |
| Disease control rate(DCR) | Disease control rate, which is defined as the proportion of subjects who achieve a response of complete response，partial response and stable disease (PR+CR+SD) in the total number of evaluable subjects using the RECIST 1.1 criteria. | 3 years |
| Overall Survival(OS) | Overall survival, defined from the date of first treatment to the date of death due to any cause. | 3 years |
| Local Control Rate | Local Control Rate, which is defined as the proportion of subjects who achieve a response of remission and stable disease (PR+CR+SD) evaluated by RECIST 1.1 after radiotherapy. | 3 years |
| Quality of Life: EORTC QLQ-C30 questionnaire | Quality of life, which will be evaluated using the EORTC（The European Organization for Reasearch and Treatment of Cancer） QLQ-C30（Quality of Life Questionnare-Core 30） questionnaire. The questionnaire contains 30 items. Items 29 and 30 are divided into seven levels, which are counted from 1 to 7 points, 1 is very poor, and 7 is very good. Other items are divided into 4 levels: no at all, a little bit, a lot, and very, and they are directly rated from 1 to 4 points. | 3 years |
| Response rate of lesions that did not receive radiotherapy | Response rate of lesions that did not receive radiotherapy, which is defined as the percentage of the number of cases with tumors that have not received radiotherapy in remission and stable disease (PR+CR+SD) in the total number of evaluable cases using the RECIST 1.1 criteria. | 3 years |
| Pathology and genetic testing | The pathology of the primary tumor before treatment, the puncture specimen of the tumor after the end of radiotherapy, and the whole exome sequencing of the tumor pathology after the progression + blood ctDNA detection for the patients who agree to the examination. | 3 years |
|
||
NCT01256268
|
Carboplatin/Taxol/Ridaforolimus in Endometrial, Ovarian and Solids
|
The purpose of this study is to:~Test the safety of a new investigational drug called MK-8669 (ridaforolimus)~Determine the maximum tolerated dose of MK-8669~Determine the effectiveness of the maximum tolerated dose of MK-8669
|
This is a phase 1A/1B study. Phase 1A is designed to determine the maximal tolerated dose (MTD) and toxicity of ridaforolimus in combination with paclitaxel and carboplatin in patients with advanced or recurrent solid tumors. The MTD determined in this study will be the recommended dose to study in the phase 1B or in future phase 2 trials.
|
Phase 1A/B Study of Combination Carboplatin, Paclitaxel and Ridaforolimus in Patients With Solid, Endometrial, and Ovarian Cancers
|
Endometrial Cancer, Ovarian Cancer
|
* Drug: Ridaforolimus
* Drug: Paclitaxel
* Drug: carboplatin
|
Inclusion Criteria:~Must have measurable disease or evaluable disease. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be a minimum size of 10 mm by CT scan (CT scan slice thickness no greater than 5 mm), 10 mm caliper measurement by clinical exam or 20 mm by chest X-ray. Lymph node must be ≥ 15 mm in short axis when assessed by CT scan. Evaluable disease is disease evident on imaging that does not meet Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1, however, meets tumor marker evaluation, e.g., Gynecologic Cancer Intergroup (GCIG) criteria. Notes: i) If the patient's only disease is confined to a solitary lesion, its neoplastic nature must be confirmed by histology or cytology unless it is accompanied by GCIG criteria or can be clearly be shown as new disease when compared to prior imaging. ii) Disease in a previously irradiated field is acceptable as the only site of measurable disease only if there has been clear progression since completion of radiotherapy.~Age > 18 years and competent to give informed consent.~Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 and a life expectancy of at least 60 days.~Patients must have adequate: Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to 1,500/ul, equivalent to Common Toxicity Criteria (CTCAE v4.0) grade 1. Platelets greater than or equal to 100,000/ul.; Renal function: creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), CTCAE v4.0 grade 1.; Hepatic function: Bilirubin less than or equal to 1.5 x ULN (CTCAE v4.0 grade 1). serum glutamic oxaloacetic transaminase (SGOT) and alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v4.0 grade 1).; Neurologic function: Neuropathy (sensory and motor) less than or equal to CTCAE v4.0 grade 1.; No chemotherapy, radiotherapy, biologic, hormonal, or investigational drug therapy within 28 days prior to start of treatment on study.~Women of childbearing potential (WOCBP) must have a negative serum pregnancy test prior to the study entry and be practicing an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Prior to study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an intentional pregnancy.~Phase 1A - Additional criteria applicable to phase 1A~Must have pathologically confirmed solid cancer that is locally advanced or metastatic cancer.~Patient's physician believes that the cancer is advanced, recurrent or metastatic and not curable by local measures (i.e., surgery, radiation, other drugs).~Patient's physician believes the patient may potentially benefit from this combination of therapy.~Patients may have had up to three (3) prior cytotoxic chemotherapeutic regimens including prior treatment with carboplatin and paclitaxel. Chemotherapy drug changes and modifications made for reasons other than progression are not considered a separate regimen. Examples would be drug changes for toxicity or consolidation chemotherapy after adjuvant treatment. Patients may have received any number of prior non-cytotoxic regimens such as monoclonal antibodies, cytokines, signal transduction inhibitors, or hormonal therapy. Previous radiation therapy is allowed.~Phase 1B - Endometrial: Additional Inclusion Criteria~Epithelial endometrial cancer. (i.e. carcinosarcoma, leiomyosarcoma, and endometrial stromal sarcoma are excluded).~May have had up to one prior chemotherapy for endometrial cancer. Prior taxane or platinum therapy is allowed as long as it was received either as adjuvant therapy or if there were a response to prior therapy and at least 6 months have elapsed since platinum treatment. Radiation sensitizing chemotherapy will not count as a prior regimen.~Must have measurable disease~Phase 1B - Ovarian: Additional Inclusion Criteria~Recurrent epithelial ovarian cancer (no stromal or germ cell ovarian cancers)~Platinum-sensitive defined as a recurrence at least 6 months (180 days) after the last day of primary adjuvant chemotherapy. Patients may have been retreated with a salvage line of chemotherapy but there must be a platinum-free interval of 6 or more months.~Two (2) or less prior therapies including adjuvant chemotherapy~Measurable or evaluable disease~Exclusion Criteria:~An upper gastrointestinal or other condition that would impair swallowing or absorption of oral medication~Any serious illness or medical condition that would not permit the patient to be managed according to the protocol, including, but not limited to, any the following:~History of significant neurologic or psychiatric disorder (e.g., uncontrolled psychiatric disorders) that would impair the ability to obtain consent or limit compliance with study requirement~Active uncontrolled or serious infection~Active peptic ulcer disease~Patients who have the following cardiac conditions: Uncontrolled angina or myocardial infarction with the past six months; Diagnosed or suspected congenital long QT syndrome; Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes); Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec) on both the Fridericia and Bazett's correction~Uncontrolled hypertension defined as systolic greater than 180 and diastolic greater than 100.~History of other invasive malignancies in the last 3 years, with the exception of non-melanoma skin cancer, unless they have had no evidence of recurrence from that cancer for last two years.~Serum creatinine >1.5 times the institutional upper limits of normal~Patients taking certain concomitant medications (see below). Patients can enroll on protocol if they stop these medications and a wash-out period of ≥14 days, unless otherwise noted, is done prior to starting ridaforolimus.~There must be at least 14 days since prior (and no current expectations to receive) CYP3A4 inhibitors including, but not limited to, any of the following: Azole antifungals ( i.e., ketoconazole, itraconazole, miconazole, fluconazole); HIV protease inhibitors (i.e., indinavir, saquinavir, ritonavir, atazanavir, nelfinavir); Clarithromycin; Verapamil; Erythromycin; Delavirdine; Diltiazem; Nefazodone; Telithromycin~There must be at least 14 days since prior (and no current expectations to receive) CYP3A4 inducers including, but not limited to, any of the following~Rifampin~Phenytoin~Rifabutin~St.John's wort~Carbamazepine~Efavirenz~Phenobarbital~Tipranavir~Full dose anticoagulation with warfarin (coumadin) or other vitamin K dependent anticoagulant. Low-dose prophylactic warfarin (i.e. 1mg per day port prophylaxis) is allowable. Low molecular heparin (e.g., danaparoid, dalteparin, tinzaparin, enoxaparin) is allowable if patient has been established on therapy.~Have received an estimated dose of radiation therapy to >35% of the bone marrow.~Patients previously exposed to mTOR inhibitors are permitted in phase 1A but not allowed in phase 1B.~History of grade 3 hypersensitivity to paclitaxel. However, if after prior hypersensitivity the patient was subsequently successfully rechallenged without incident, the patient may be eligible at investigator's discretion.~Known hypersensitivity to the study drug ridaforolimus or its components. Ridaforolimus should be administered with caution to patients known to be hypersensitive to macrolide antibiotics, Tween80 (polysorbate 80), or any other excipient in the product formulation.~Significant lipid abnormalities: Serum cholesterol > 350mg/dL; Triglycerides > 400mg/dL
|
18 Years
| null |
Female
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1A - Maximum Tolerated Dose (MTD) | To determine the maximal tolerated dose of oral ridaforolimus in combination with paclitaxel and carboplatin during the first cycle of treatment. | Average of six months |
| Part 1B - Number of Participants With Response to Treatment as a Measure of Preliminary Efficacy | To determine the preliminary efficacy [defined as the response rate (complete and partial response rate), stable disease (neither progression or response after the completion of at least 2 cycles), and duration of response] of the 1A maximal tolerated dose (MTD) of oral ridaforolimus in combination with paclitaxel and carboplatin in two separate expansion cohorts. | Average of six months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1A - Number of Participants with Adverse Events as a Measure of Safety and Tolerability | To describe the toxicities of this combination of therapy. | Average of six months |
| Part 1B - Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability | The final safety analysis will include all patients who receive at least one dose of the treatment. The incidence of SAEs that are treatment related will be summarized by type and severity and the exact 95% confidence intervals for the rates of such SAEs will be computed based on the exact binomial distribution. | Average of six months |
|
metastatic, recurrent, Solid Cancer
|
Paclitaxel, Carboplatin, Antineoplastic Agents, Phytogenic, Antineoplastic Agents, Tubulin Modulators, Antimitotic Agents, Mitosis Modulators, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Endometrial Cancer<br>Phase 1A + Cohort 1B - Recurrent or Metastatic Endometrial Cancer. Patients with recurrent or metastatic endometrial cancer with up to 1 prior chemotherapy. Ridaforolimus at the Phase 1A MTD and schedule will be administered with paclitaxel at the Phase 1A MTD (175 mg/m2) IV and carboplatin at the phase 1 MTD (AUC 5 to 6) in mg/ml/min on day 1 of each 3 week cycle, ridaforolimus will be dosed at the time of initiation of paclitaxel infusion. Treatment will continue until disease progression or adverse events prohibit further therapy. | Drug: Ridaforolimus<br>* Phase 1A: Ridaforolimus 20-40 mg will be administered daily for 5 days per week (days 2-5, days 8-12, days 15-19) in the first cycle of therapy and for further cycles on days 1-5, days 8-12, days 15-19 throughout the remainder of therapy. On the day of coadministration of ridaforolimus with paclitaxel 175mg/m^2 IV and carboplatin AUC 5-6mg/ml/min on day 1 of each 3 week cycle, ridaforolimus will be dosed at the time of initiation of paclitaxel infusion. Phase 1B: as outlined in Treatment Arms.<br>* Other names: MK-8669;Drug: Paclitaxel<br>* Phase 1A: Paclitaxel 175mg/m2 IV. Phase 1B: As outlined in Treatment Arms.<br>* Other names: NSC #673089;Drug: carboplatin<br>* Phase 1A: Carboplatin AUC 5-6mg/ml/min on day 1 of each 3 week cycle. Phase 1B: As outlined in Treatment Arms.<br>* Other names: NSC #241240;|
| Experimental: Ovarian Cancer<br>Phase 1 A + Cohort 1B - Recurrent or Metastatic Ovarian Cancer. Patients with platinum-sensitive, recurrent ovarian cancer with up to 2 prior chemotherapy regimens. Ridaforolimus at the phase 1A MTD and schedule will be administered with paclitaxel at the phase 1 MTD (175 mg/m2) IV and carboplatin at the phase 1 MTD (AUC 5 to 6) in mg/ml/min on day 1 of each 3 week cycle, ridaforolimus will be dosed at the time of initiation of paclitaxel infusion. Treatment will continue until disease progression or adverse events prohibit further therapy. | Drug: Ridaforolimus<br>* Phase 1A: Ridaforolimus 20-40 mg will be administered daily for 5 days per week (days 2-5, days 8-12, days 15-19) in the first cycle of therapy and for further cycles on days 1-5, days 8-12, days 15-19 throughout the remainder of therapy. On the day of coadministration of ridaforolimus with paclitaxel 175mg/m^2 IV and carboplatin AUC 5-6mg/ml/min on day 1 of each 3 week cycle, ridaforolimus will be dosed at the time of initiation of paclitaxel infusion. Phase 1B: as outlined in Treatment Arms.<br>* Other names: MK-8669;Drug: Paclitaxel<br>* Phase 1A: Paclitaxel 175mg/m2 IV. Phase 1B: As outlined in Treatment Arms.<br>* Other names: NSC #673089;Drug: carboplatin<br>* Phase 1A: Carboplatin AUC 5-6mg/ml/min on day 1 of each 3 week cycle. Phase 1B: As outlined in Treatment Arms.<br>* Other names: NSC #241240;|
|
Carboplatin/Taxol/Ridaforolimus in Endometrial, Ovarian and Solids
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to: Test the safety of a new investigational drug called MK-8669 (ridaforolimus) Determine the maximum tolerated dose of MK-8669 Determine the effectiveness of the maximum tolerated dose of MK-8669
Detailed Description
-----------------
This is a phase 1A/1B study. Phase 1A is designed to determine the maximal tolerated dose (MTD) and toxicity of ridaforolimus in combination with paclitaxel and carboplatin in patients with advanced or recurrent solid tumors. The MTD determined in this study will be the recommended dose to study in the phase 1B or in future phase 2 trials.
Official Title
-----------------
Phase 1A/B Study of Combination Carboplatin, Paclitaxel and Ridaforolimus in Patients With Solid, Endometrial, and Ovarian Cancers
Conditions
-----------------
Endometrial Cancer, Ovarian Cancer
Intervention / Treatment
-----------------
* Drug: Ridaforolimus
* Drug: Paclitaxel
* Drug: carboplatin
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Must have measurable disease or evaluable disease. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be a minimum size of 10 mm by CT scan (CT scan slice thickness no greater than 5 mm), 10 mm caliper measurement by clinical exam or 20 mm by chest X-ray. Lymph node must be ≥ 15 mm in short axis when assessed by CT scan. Evaluable disease is disease evident on imaging that does not meet Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1, however, meets tumor marker evaluation, e.g., Gynecologic Cancer Intergroup (GCIG) criteria. Notes: i) If the patient's only disease is confined to a solitary lesion, its neoplastic nature must be confirmed by histology or cytology unless it is accompanied by GCIG criteria or can be clearly be shown as new disease when compared to prior imaging. ii) Disease in a previously irradiated field is acceptable as the only site of measurable disease only if there has been clear progression since completion of radiotherapy. Age > 18 years and competent to give informed consent. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 and a life expectancy of at least 60 days. Patients must have adequate: Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to 1,500/ul, equivalent to Common Toxicity Criteria (CTCAE v4.0) grade 1. Platelets greater than or equal to 100,000/ul.; Renal function: creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), CTCAE v4.0 grade 1.; Hepatic function: Bilirubin less than or equal to 1.5 x ULN (CTCAE v4.0 grade 1). serum glutamic oxaloacetic transaminase (SGOT) and alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v4.0 grade 1).; Neurologic function: Neuropathy (sensory and motor) less than or equal to CTCAE v4.0 grade 1.; No chemotherapy, radiotherapy, biologic, hormonal, or investigational drug therapy within 28 days prior to start of treatment on study. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test prior to the study entry and be practicing an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Prior to study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an intentional pregnancy. Phase 1A - Additional criteria applicable to phase 1A Must have pathologically confirmed solid cancer that is locally advanced or metastatic cancer. Patient's physician believes that the cancer is advanced, recurrent or metastatic and not curable by local measures (i.e., surgery, radiation, other drugs). Patient's physician believes the patient may potentially benefit from this combination of therapy. Patients may have had up to three (3) prior cytotoxic chemotherapeutic regimens including prior treatment with carboplatin and paclitaxel. Chemotherapy drug changes and modifications made for reasons other than progression are not considered a separate regimen. Examples would be drug changes for toxicity or consolidation chemotherapy after adjuvant treatment. Patients may have received any number of prior non-cytotoxic regimens such as monoclonal antibodies, cytokines, signal transduction inhibitors, or hormonal therapy. Previous radiation therapy is allowed. Phase 1B - Endometrial: Additional Inclusion Criteria Epithelial endometrial cancer. (i.e. carcinosarcoma, leiomyosarcoma, and endometrial stromal sarcoma are excluded). May have had up to one prior chemotherapy for endometrial cancer. Prior taxane or platinum therapy is allowed as long as it was received either as adjuvant therapy or if there were a response to prior therapy and at least 6 months have elapsed since platinum treatment. Radiation sensitizing chemotherapy will not count as a prior regimen. Must have measurable disease Phase 1B - Ovarian: Additional Inclusion Criteria Recurrent epithelial ovarian cancer (no stromal or germ cell ovarian cancers) Platinum-sensitive defined as a recurrence at least 6 months (180 days) after the last day of primary adjuvant chemotherapy. Patients may have been retreated with a salvage line of chemotherapy but there must be a platinum-free interval of 6 or more months. Two (2) or less prior therapies including adjuvant chemotherapy Measurable or evaluable disease Exclusion Criteria: An upper gastrointestinal or other condition that would impair swallowing or absorption of oral medication Any serious illness or medical condition that would not permit the patient to be managed according to the protocol, including, but not limited to, any the following: History of significant neurologic or psychiatric disorder (e.g., uncontrolled psychiatric disorders) that would impair the ability to obtain consent or limit compliance with study requirement Active uncontrolled or serious infection Active peptic ulcer disease Patients who have the following cardiac conditions: Uncontrolled angina or myocardial infarction with the past six months; Diagnosed or suspected congenital long QT syndrome; Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes); Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec) on both the Fridericia and Bazett's correction Uncontrolled hypertension defined as systolic greater than 180 and diastolic greater than 100. History of other invasive malignancies in the last 3 years, with the exception of non-melanoma skin cancer, unless they have had no evidence of recurrence from that cancer for last two years. Serum creatinine >1.5 times the institutional upper limits of normal Patients taking certain concomitant medications (see below). Patients can enroll on protocol if they stop these medications and a wash-out period of ≥14 days, unless otherwise noted, is done prior to starting ridaforolimus. There must be at least 14 days since prior (and no current expectations to receive) CYP3A4 inhibitors including, but not limited to, any of the following: Azole antifungals ( i.e., ketoconazole, itraconazole, miconazole, fluconazole); HIV protease inhibitors (i.e., indinavir, saquinavir, ritonavir, atazanavir, nelfinavir); Clarithromycin; Verapamil; Erythromycin; Delavirdine; Diltiazem; Nefazodone; Telithromycin There must be at least 14 days since prior (and no current expectations to receive) CYP3A4 inducers including, but not limited to, any of the following Rifampin Phenytoin Rifabutin St.John's wort Carbamazepine Efavirenz Phenobarbital Tipranavir Full dose anticoagulation with warfarin (coumadin) or other vitamin K dependent anticoagulant. Low-dose prophylactic warfarin (i.e. 1mg per day port prophylaxis) is allowable. Low molecular heparin (e.g., danaparoid, dalteparin, tinzaparin, enoxaparin) is allowable if patient has been established on therapy. Have received an estimated dose of radiation therapy to >35% of the bone marrow. Patients previously exposed to mTOR inhibitors are permitted in phase 1A but not allowed in phase 1B. History of grade 3 hypersensitivity to paclitaxel. However, if after prior hypersensitivity the patient was subsequently successfully rechallenged without incident, the patient may be eligible at investigator's discretion. Known hypersensitivity to the study drug ridaforolimus or its components. Ridaforolimus should be administered with caution to patients known to be hypersensitive to macrolide antibiotics, Tween80 (polysorbate 80), or any other excipient in the product formulation. Significant lipid abnormalities: Serum cholesterol > 350mg/dL; Triglycerides > 400mg/dL
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Endometrial Cancer<br>Phase 1A + Cohort 1B - Recurrent or Metastatic Endometrial Cancer. Patients with recurrent or metastatic endometrial cancer with up to 1 prior chemotherapy. Ridaforolimus at the Phase 1A MTD and schedule will be administered with paclitaxel at the Phase 1A MTD (175 mg/m2) IV and carboplatin at the phase 1 MTD (AUC 5 to 6) in mg/ml/min on day 1 of each 3 week cycle, ridaforolimus will be dosed at the time of initiation of paclitaxel infusion. Treatment will continue until disease progression or adverse events prohibit further therapy. | Drug: Ridaforolimus<br>* Phase 1A: Ridaforolimus 20-40 mg will be administered daily for 5 days per week (days 2-5, days 8-12, days 15-19) in the first cycle of therapy and for further cycles on days 1-5, days 8-12, days 15-19 throughout the remainder of therapy. On the day of coadministration of ridaforolimus with paclitaxel 175mg/m^2 IV and carboplatin AUC 5-6mg/ml/min on day 1 of each 3 week cycle, ridaforolimus will be dosed at the time of initiation of paclitaxel infusion. Phase 1B: as outlined in Treatment Arms.<br>* Other names: MK-8669;Drug: Paclitaxel<br>* Phase 1A: Paclitaxel 175mg/m2 IV. Phase 1B: As outlined in Treatment Arms.<br>* Other names: NSC #673089;Drug: carboplatin<br>* Phase 1A: Carboplatin AUC 5-6mg/ml/min on day 1 of each 3 week cycle. Phase 1B: As outlined in Treatment Arms.<br>* Other names: NSC #241240;|
| Experimental: Ovarian Cancer<br>Phase 1 A + Cohort 1B - Recurrent or Metastatic Ovarian Cancer. Patients with platinum-sensitive, recurrent ovarian cancer with up to 2 prior chemotherapy regimens. Ridaforolimus at the phase 1A MTD and schedule will be administered with paclitaxel at the phase 1 MTD (175 mg/m2) IV and carboplatin at the phase 1 MTD (AUC 5 to 6) in mg/ml/min on day 1 of each 3 week cycle, ridaforolimus will be dosed at the time of initiation of paclitaxel infusion. Treatment will continue until disease progression or adverse events prohibit further therapy. | Drug: Ridaforolimus<br>* Phase 1A: Ridaforolimus 20-40 mg will be administered daily for 5 days per week (days 2-5, days 8-12, days 15-19) in the first cycle of therapy and for further cycles on days 1-5, days 8-12, days 15-19 throughout the remainder of therapy. On the day of coadministration of ridaforolimus with paclitaxel 175mg/m^2 IV and carboplatin AUC 5-6mg/ml/min on day 1 of each 3 week cycle, ridaforolimus will be dosed at the time of initiation of paclitaxel infusion. Phase 1B: as outlined in Treatment Arms.<br>* Other names: MK-8669;Drug: Paclitaxel<br>* Phase 1A: Paclitaxel 175mg/m2 IV. Phase 1B: As outlined in Treatment Arms.<br>* Other names: NSC #673089;Drug: carboplatin<br>* Phase 1A: Carboplatin AUC 5-6mg/ml/min on day 1 of each 3 week cycle. Phase 1B: As outlined in Treatment Arms.<br>* Other names: NSC #241240;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1A - Maximum Tolerated Dose (MTD) | To determine the maximal tolerated dose of oral ridaforolimus in combination with paclitaxel and carboplatin during the first cycle of treatment. | Average of six months |
| Part 1B - Number of Participants With Response to Treatment as a Measure of Preliminary Efficacy | To determine the preliminary efficacy [defined as the response rate (complete and partial response rate), stable disease (neither progression or response after the completion of at least 2 cycles), and duration of response] of the 1A maximal tolerated dose (MTD) of oral ridaforolimus in combination with paclitaxel and carboplatin in two separate expansion cohorts. | Average of six months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1A - Number of Participants with Adverse Events as a Measure of Safety and Tolerability | To describe the toxicities of this combination of therapy. | Average of six months |
| Part 1B - Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability | The final safety analysis will include all patients who receive at least one dose of the treatment. The incidence of SAEs that are treatment related will be summarized by type and severity and the exact 95% confidence intervals for the rates of such SAEs will be computed based on the exact binomial distribution. | Average of six months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
metastatic, recurrent, Solid Cancer
|
NCT05426174
|
Phase I, Randomized, Modified Double-blind, Parallel-group, Active-controlled, Multi-arm, Dose-escalation Study to Assess the Safety and Immunogenicity of Monovalent mRNA NA Vaccine in Adult Participants 18 Years of Age and Older
|
This is a Phase I, first-in-human, randomized, modified double-blind, active-controlled, dose-escalation study to assess the safety and immunogenicity of up to 3 dose levels of mRNA NA vaccines, administered as a single IM injection in healthy adults aged 18 years and older. Two age groups, 18 to 64 years and ≥65 years, will be included in this study.
|
This study will include a screening visit, 6 study visits occurring on Days 1, 3, 9, 29, 91, and 181, and a safety follow-up telephone call on Day 366.
|
Study to Assess the Safety and Immunogenicity of Monovalent mRNA NA Vaccine in Adult Participants 18 Years of Age and Older
|
Healthy Volunteers, Influenza Immunization
|
* Biological: mRNA NA vaccine
* Biological: High Dose Quadrivalent Influenza Vaccine
|
Inclusion Criteria:~Aged 18 years or older on the day of inclusion.~A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies:~Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be postmenopausal for at least 1 year, or surgically sterile OR~Is of childbearing potential and agrees to use an effective contraceptive method or abstinence from at least 4 weeks prior to study intervention administration until at least 12 weeks after study intervention administration~A female participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 8 hours before administration of study intervention.~Informed consent form has been signed and dated.~Exclusion Criteria:~Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).~Known systemic hypersensitivity to any of the study intervention components; history of a life-threatening reaction to the study interventions used in the study or to a product containing any of the same substances~Moderate or severe acute illness/infection (according to investigator judgement) or febrile illness (temperature ≥100.4°F) on the day of study intervention administration.~Have known or recently active (12 months) neoplastic disease or a history of any hematologic malignancy.~Have any diagnosis, current or past, of autoimmune disease.~Body mass index of 40 kg/m2 or higher.~Receipt of immune globulins, blood, or blood-derived products in the past 3 months.~Have taken high-dose inhaled corticosteroid (≥500 μg of fluticasone) within 6 months prior to study vaccination.~Self-reported or documented seropositivity for HIV, hepatitis B virus, or hepatitis C virus.
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with immediate adverse events | Immediate adverse events are unsolicited systemic adverse events reported in the 30 minutes after vaccination | Within 30 minutes after vaccination |
| Number of participants with solicited injection site or systemic reaction | | From Day 1 to Day 8 |
| Number of participants with unsolicited adverse events | Unsolicited (spontaneously reported) adverse events not fulfilling criteria for solicited reactions | From Day 1 to Day 29 |
| Number of participants with serious adverse events | Serious adverse events are collected throughout the study | From Day 1 to Day 366 |
| Number of participants with adverse events of special interest | Adverse events of special interest are collected throughout the study | From Day 1 to Day 366 |
| Number of patients with clinically significant changes in clinical laboratory tests | Laboratory tests include hematology: complete blood count (CBC) with differential, platelet count, coagulation panel (prothrombin time and PTT) and serum chemistry: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total and fractionated bilirubin, C-reactive protein, serum creatinine, and blood urea nitrogen | From Day 1 to Day 8 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuraminidase inhibition (NAI) Antibodies at Day 1 and 29 | Antibody are expressed as GMTs at baseline and post-baseline | Day 1 and 29 |
| Individual Neuraminidase inhibition (NAI) titer | Antibody titers are expressed as GMTs at baseline and post-baseline | Day 1 and Day 29 |
| 2-fold and 4-fold rise in NAI antibody titers | Expressed as percentage post-baseline | From Day 1 to Day 29 |
| Percentage of participants with detectable antibody titers greater than or equal to (≥) 10 [1/dil] | Expressed as percentage at baseline and post-baseline | Day 1 and Day 29 |
|
Vaccines, Immunologic Factors, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 mRNA NA: Low dose Level<br>Participants will receive a low dose of mRNA vaccine | Biological: mRNA NA vaccine<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>|
| Experimental: Group 2 mRNA NA: Medium dose level<br>Participants will receive a medium dose of mRNA vaccine | Biological: mRNA NA vaccine<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>|
| Experimental: Group 3 mRNA NA: High dose level<br>Participants will receive a high dose of mRNA vaccine | Biological: mRNA NA vaccine<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>|
| Active Comparator: Group 4: QIV-HD<br>Participants will receive QIV-HD (high dose quadrivalent influenza) vaccine | Biological: High Dose Quadrivalent Influenza Vaccine<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>* Other names: Fluzone HD;|
|
Phase I, Randomized, Modified Double-blind, Parallel-group, Active-controlled, Multi-arm, Dose-escalation Study to Assess the Safety and Immunogenicity of Monovalent mRNA NA Vaccine in Adult Participants 18 Years of Age and Older
Study Overview
=================
Brief Summary
-----------------
This is a Phase I, first-in-human, randomized, modified double-blind, active-controlled, dose-escalation study to assess the safety and immunogenicity of up to 3 dose levels of mRNA NA vaccines, administered as a single IM injection in healthy adults aged 18 years and older. Two age groups, 18 to 64 years and ≥65 years, will be included in this study.
Detailed Description
-----------------
This study will include a screening visit, 6 study visits occurring on Days 1, 3, 9, 29, 91, and 181, and a safety follow-up telephone call on Day 366.
Official Title
-----------------
Study to Assess the Safety and Immunogenicity of Monovalent mRNA NA Vaccine in Adult Participants 18 Years of Age and Older
Conditions
-----------------
Healthy Volunteers, Influenza Immunization
Intervention / Treatment
-----------------
* Biological: mRNA NA vaccine
* Biological: High Dose Quadrivalent Influenza Vaccine
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 18 years or older on the day of inclusion. A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies: Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be postmenopausal for at least 1 year, or surgically sterile OR Is of childbearing potential and agrees to use an effective contraceptive method or abstinence from at least 4 weeks prior to study intervention administration until at least 12 weeks after study intervention administration A female participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 8 hours before administration of study intervention. Informed consent form has been signed and dated. Exclusion Criteria: Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months). Known systemic hypersensitivity to any of the study intervention components; history of a life-threatening reaction to the study interventions used in the study or to a product containing any of the same substances Moderate or severe acute illness/infection (according to investigator judgement) or febrile illness (temperature ≥100.4°F) on the day of study intervention administration. Have known or recently active (12 months) neoplastic disease or a history of any hematologic malignancy. Have any diagnosis, current or past, of autoimmune disease. Body mass index of 40 kg/m2 or higher. Receipt of immune globulins, blood, or blood-derived products in the past 3 months. Have taken high-dose inhaled corticosteroid (≥500 μg of fluticasone) within 6 months prior to study vaccination. Self-reported or documented seropositivity for HIV, hepatitis B virus, or hepatitis C virus.
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
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 mRNA NA: Low dose Level<br>Participants will receive a low dose of mRNA vaccine | Biological: mRNA NA vaccine<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>|
| Experimental: Group 2 mRNA NA: Medium dose level<br>Participants will receive a medium dose of mRNA vaccine | Biological: mRNA NA vaccine<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>|
| Experimental: Group 3 mRNA NA: High dose level<br>Participants will receive a high dose of mRNA vaccine | Biological: mRNA NA vaccine<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>|
| Active Comparator: Group 4: QIV-HD<br>Participants will receive QIV-HD (high dose quadrivalent influenza) vaccine | Biological: High Dose Quadrivalent Influenza Vaccine<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>* Other names: Fluzone HD;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with immediate adverse events | Immediate adverse events are unsolicited systemic adverse events reported in the 30 minutes after vaccination | Within 30 minutes after vaccination |
| Number of participants with solicited injection site or systemic reaction | | From Day 1 to Day 8 |
| Number of participants with unsolicited adverse events | Unsolicited (spontaneously reported) adverse events not fulfilling criteria for solicited reactions | From Day 1 to Day 29 |
| Number of participants with serious adverse events | Serious adverse events are collected throughout the study | From Day 1 to Day 366 |
| Number of participants with adverse events of special interest | Adverse events of special interest are collected throughout the study | From Day 1 to Day 366 |
| Number of patients with clinically significant changes in clinical laboratory tests | Laboratory tests include hematology: complete blood count (CBC) with differential, platelet count, coagulation panel (prothrombin time and PTT) and serum chemistry: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total and fractionated bilirubin, C-reactive protein, serum creatinine, and blood urea nitrogen | From Day 1 to Day 8 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuraminidase inhibition (NAI) Antibodies at Day 1 and 29 | Antibody are expressed as GMTs at baseline and post-baseline | Day 1 and 29 |
| Individual Neuraminidase inhibition (NAI) titer | Antibody titers are expressed as GMTs at baseline and post-baseline | Day 1 and Day 29 |
| 2-fold and 4-fold rise in NAI antibody titers | Expressed as percentage post-baseline | From Day 1 to Day 29 |
| Percentage of participants with detectable antibody titers greater than or equal to (≥) 10 [1/dil] | Expressed as percentage at baseline and post-baseline | Day 1 and Day 29 |
|
|
NCT02258373
|
A Trial Comparing Continuous Glucose Monitoring With and Without Routine Blood Glucose Monitoring in Adults With Type 1 Diabetes
|
The primary objective of the study is to determine whether the routine use of Continuous Glucose Monitoring (CGM) without Blood Glucose Monitoring (BGM) confirmation is as safe and effective as CGM used as an adjunct to BGM.
|
CGM offers the opportunity to improve glycemic control, including a reduction in hypoglycemia. Unlike home blood glucose monitors, CGM is not intended to be used directly for making therapy adjustments and is an adjunctive device to supplement information obtained from a standard blood glucose monitor. However, although the labeling for CGM requires a BGM measurement before making a therapy adjustment, many CGM users often decide on a meal bolus based on CGM alone.~A study comparing CGM used solely as an adjunctive device, as per the FDA labeling, versus CGM used largely in lieu of BGM measurements would provide valuable data. Since many individuals with T1D are often using CGM alone when bolusing insulin, obtaining data on the safety and efficacy of this approach will be important. If indeed insulin dosing decisions are proven to be safe and effective using CGM alone (without BGM confirmation) compared to CGM with BGM confirmations, this study would also pave the way for a new standard diabetes management protocol and therapy that would not require eight BGM measurements (i.e. finger sticks) a day and ease the burden of managing type 1 diabetes.~For this study, participants will be randomly assigned with 2:1 probability to the CGM Only and CGM+BGM groups, respectively. Prior to randomization, the study will be preceded by a run-in period of up to 10 weeks to collect blinded baseline CGM data, to train the participants on CGM use, to assess compliance with CGM use, and to initiate standard CGM use. During the standard CGM use run-in phase, visits will occur after 2, 4 and 8 weeks, with phone calls at 1, 3, and 6 weeks. Current CGM users may be eligible to skip part of the run-in phase. Participants successfully completing the run-in phase will be randomized.~Both groups will use CGM devices and BGM. The CGM device to be used in the study is the Dexcom G4 Platinum Continuous Glucose Monitoring System with modified algorithm. The CGM+BGM group will be instructed to measure the blood glucose whenever a diabetes management decision is made. The CGM Only group will be instructed to only measure the blood glucose (other than for calibration) with a standard BGM meter in certain circumstances and will use a blinded BGM meter at times when a standard BGM measurement is not done. Following randomization, there will be a phone contact during the first week (4 to 8 days following randomization) to address any questions the participant has about the protocol. Follow up visits will occur at 3, 6, 13, 19 and 26 weeks.
|
A Randomized Trial Comparing Continuous Glucose Monitoring With and Without Routine Blood Glucose Monitoring in Adults With Type 1 Diabetes
|
Type 1 Diabetes
|
* Device: CGM+BGM
* Device: CGM Only
|
Inclusion Criteria:~To be eligible, all participants must meet the following inclusion criteria:~Clinical diagnosis of type 1 diabetes (based on investigator's judgment)~Age >=18 years~T1D duration >=1~HbA1c <=9.0% (a local laboratory or DCA2000 or comparable point of care device will be used to assess eligibility)~Use of an insulin pump for insulin delivery for at least 3 months, with no plans to discontinue pump use during the next 8 months~Participant is able to manage his/her diabetes with respect to insulin administration and glucose monitoring, as assessed by the investigator during the screening visit~Participant understands the study protocol and agrees to comply with it, including willingness to use the study CGM and BGM~No expectation that participant will be moving out of the area of the clinical center during the time period of the study, unless the move will be to an area served by another study center~Exclusion Criteria:~Individuals who meet any of the following criteria are not eligible for the study:~Severe hypoglycemia in the last 12 months in which the assistance of another individual was needed or seizure/loss of consciousness in the past 3 years~Significant hypoglycemia unawareness based on the Clarke Hypoglycemia Unawareness Survey defined as at least one of the following being present:~Survey score >2~Survey Q1 is answered as 'I no longer have symptoms when my blood sugar is low'~Survey Q7 response indicates that symptoms of hypoglycemia are not felt until glucose level is <50 mg/dl~Survey Q8 response is never or rarely to the question 'to what extent can you tell by your symptoms that your blood sugar is low'~More than one DKA event in the past year~History of seizures other than due to hypoglycemia~Current use of a threshold suspend pump feature (note: participant is eligible if a pump with this feature was being used but the threshold suspend was not active)~Myocardial infarction or stroke in past 6 months~Estimated Glomerular Filtration Rate (GFR) <30 obtained within the prior 12 months as part of usual care or kidney transplant~Most recent thyroid function test results abnormal, obtained as part of usual care within the prior 2 years~The presence of a significant medical or psychiatric disorder or use of a medication that in the judgment of the investigator will affect the wearing of the sensors, the completion of any aspect of the protocol, or increase risk~Cognitive difficulties that, in the judgment of the investigator, could impair the individual's ability to follow the protocol or increase risk~Initiation of a non-insulin drug for glucose control during the past 3 months, planned initiation during the next 8 months, or discontinuation of a non-insulin drug for glucose control during the past 3 months (note: individuals using a non-insulin medication for glucose control for 3 or more months are eligible provided there is no expectation that the medication will be discontinued during the time period of study participation)~Use of a systemic beta blocker drug~Regular use of oral corticosteroids~Anticipated need to use acetaminophen during the time course of the study~Inpatient psychiatric treatment in the past 6 months~Currently pregnant or lactating or plan to attempt getting pregnant during the time period of the study~• Females with child-bearing potential will be queried about the possibility of pregnancy and a urine pregnancy test will be performed if there is uncertainty as to the possibility of pregnancy. They must agree to use appropriate birth control during the time period of the study. Participants will receive education regarding birth control methods which may be considered as highly effective, which are methods that can achieve a failure rate less than 1% per year when used consistently and correctly and include:~Combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)~Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)~Intrauterine device (IUD)~Intrauterine hormone-releasing system (IUS)~Bilateral tubal occlusion~Vasectomised partner~Sexual abstinence~Participation in an intervention study (including psychological studies) in past 6 weeks~Known adhesive allergy~From the blinded run-in phase (or from pre-study CGM use if criteria met to skip the blinded run-in phase), CGM values <60 mg/dl for more than 10.0% of the time~Unsuccessful completion of the run-in phases with respect to CGM or BGM use
|
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 |
| --- | --- | --- |
| Percentage of Time in Range of 70 to 180 mg/dl, Measured With CGM | | Between baseline (randomization) and 6 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Glucose | | Between baseline (randomization) and 6 months |
| Measures of Glycemic Variability: Coefficient of Variation | Coefficient of variation = SD/mean | Between baseline (randomization) and 6 months |
| Percentage of Time With Sensor Value <70 mg/dl, Measured With CGM | | Between baseline (randomization) and 6 months |
| Percentage of Time With Sensor Values <60 mg/dl, Measured With CGM | | Between baseline (randomization) and 6 months |
| Percentage of Time With Sensor Values <50 mg/dl, Measured With CGM | | Between baseline (randomization) and 6 months |
| Percentage of Days With at Least 20 Minutes of Sensor Glucose Values <60 mg/dl | | Between baseline (randomization) and 6 months |
| Percentage of Time With Sensor Values >180 mg/dl, Measured With CGM | | Between baseline (randomization) and 6 months |
| Percentage of Time With Sensor Values > 250 mg/dl, Measured With CGM | | Between baseline (randomization) and 6 months |
| Percentage of Time With Sensor Values > 300 mg/dl, Measured With CGM | | Between baseline (randomization) and 6 months |
| Percentage of Days With at Least 20 Minutes of Sensor Glucose Values >300 mg/dl | | Between baseline (randomization) and 6 months |
| Change in HbA1c | | Between baseline (randomization) and 6 months |
| Number of Participants With no Worsening of HbA1c by Greater Than 0.3% AND no Severe Hypoglycemia Event | | Between baseline (randomization) and 6 months |
| Number of Participants With >=1 Severe Hypoglycemia Events | | Between baseline (randomization) and 6 months |
| Number of Participants With >=1 Diabetic Ketoacidosis (DKA) Events | | Between baseline (randomization) and 6 months |
| Number of Participants With >=1 Ketotic Events Not Meeting Criteria for DKA With Blood Ketone Level >=0.6 mmol/L | | Between baseline (randomization) and 6 months |
| Number of Participants With >=1 Ketotic Events Not Meeting Criteria for DKA With Blood Ketone Level >=1.0 mmol/L | | Between baseline (randomization) and 6 months |
| Number of Participants With >=1 Serious Adverse Event Other Than SH | A serious adverse event is any untoward occurrence that:~Results in death.~Is life-threatening; (a non-life-threatening event which, had it been more severe, might have become life-threatening, is not necessarily considered a serious adverse event).~Requires inpatient hospitalization or prolongation of existing hospitalization.~Results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions (sight threatening).~Is a congenital anomaly or birth defect.~Is considered a significant medical event by the investigator based on medical judgment. | Between baseline (randomization) and 6 months |
|
Diabetes Mellitus, Continuous Glucose Monitoring
|
Diabetes Mellitus, Diabetes Mellitus, Type 1, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Autoimmune Diseases, Immune System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CGM Only<br>Participants will be instructed to check the blood glucose with the standard study BGM for calibration of the CGM and for specific circumstances that are specified in the protocol. This group will make management decisions based on the CGM glucose value without a BGM confirmation measurement as long as the participant is confident that the CGM glucose value is not erroneous.~In addition, participants will be instructed to make a BGM measurement on the blinded study BGM before going to bed, whenever an insulin bolus is given and when treating or attempting to prevent hypoglycemia and a standard BGM measurement has not been made. The participant may be asked to make post-prandial blinded BGM measurements at selected times. | Device: CGM Only<br>* Dexcom G4 Platinum Continuous Glucose Monitoring System with modified algorithm<br>|
| Active Comparator: CGM+BGM<br>Participants will be instructed to perform BGM measurements for sensor calibration according to Dexcom specifications and measure the blood glucose whenever a diabetes management decision is made. A BGM measurement is to be made on the study BGM before going to bed, whenever an insulin bolus is given and when treating or attempting to prevent hypoglycemia. Additional BGM measurements can be made on the study BGM at any time that the participant desires. | Device: CGM+BGM<br>* Dexcom G4 Platinum Continuous Glucose Monitoring System with modified algorithm + Abbot Precision Xtra Blood Glucose-Ketone Meter<br>|
|
A Trial Comparing Continuous Glucose Monitoring With and Without Routine Blood Glucose Monitoring in Adults With Type 1 Diabetes
Study Overview
=================
Brief Summary
-----------------
The primary objective of the study is to determine whether the routine use of Continuous Glucose Monitoring (CGM) without Blood Glucose Monitoring (BGM) confirmation is as safe and effective as CGM used as an adjunct to BGM.
Detailed Description
-----------------
CGM offers the opportunity to improve glycemic control, including a reduction in hypoglycemia. Unlike home blood glucose monitors, CGM is not intended to be used directly for making therapy adjustments and is an adjunctive device to supplement information obtained from a standard blood glucose monitor. However, although the labeling for CGM requires a BGM measurement before making a therapy adjustment, many CGM users often decide on a meal bolus based on CGM alone. A study comparing CGM used solely as an adjunctive device, as per the FDA labeling, versus CGM used largely in lieu of BGM measurements would provide valuable data. Since many individuals with T1D are often using CGM alone when bolusing insulin, obtaining data on the safety and efficacy of this approach will be important. If indeed insulin dosing decisions are proven to be safe and effective using CGM alone (without BGM confirmation) compared to CGM with BGM confirmations, this study would also pave the way for a new standard diabetes management protocol and therapy that would not require eight BGM measurements (i.e. finger sticks) a day and ease the burden of managing type 1 diabetes. For this study, participants will be randomly assigned with 2:1 probability to the CGM Only and CGM+BGM groups, respectively. Prior to randomization, the study will be preceded by a run-in period of up to 10 weeks to collect blinded baseline CGM data, to train the participants on CGM use, to assess compliance with CGM use, and to initiate standard CGM use. During the standard CGM use run-in phase, visits will occur after 2, 4 and 8 weeks, with phone calls at 1, 3, and 6 weeks. Current CGM users may be eligible to skip part of the run-in phase. Participants successfully completing the run-in phase will be randomized. Both groups will use CGM devices and BGM. The CGM device to be used in the study is the Dexcom G4 Platinum Continuous Glucose Monitoring System with modified algorithm. The CGM+BGM group will be instructed to measure the blood glucose whenever a diabetes management decision is made. The CGM Only group will be instructed to only measure the blood glucose (other than for calibration) with a standard BGM meter in certain circumstances and will use a blinded BGM meter at times when a standard BGM measurement is not done. Following randomization, there will be a phone contact during the first week (4 to 8 days following randomization) to address any questions the participant has about the protocol. Follow up visits will occur at 3, 6, 13, 19 and 26 weeks.
Official Title
-----------------
A Randomized Trial Comparing Continuous Glucose Monitoring With and Without Routine Blood Glucose Monitoring in Adults With Type 1 Diabetes
Conditions
-----------------
Type 1 Diabetes
Intervention / Treatment
-----------------
* Device: CGM+BGM
* Device: CGM Only
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: To be eligible, all participants must meet the following inclusion criteria: Clinical diagnosis of type 1 diabetes (based on investigator's judgment) Age >=18 years T1D duration >=1 HbA1c <=9.0% (a local laboratory or DCA2000 or comparable point of care device will be used to assess eligibility) Use of an insulin pump for insulin delivery for at least 3 months, with no plans to discontinue pump use during the next 8 months Participant is able to manage his/her diabetes with respect to insulin administration and glucose monitoring, as assessed by the investigator during the screening visit Participant understands the study protocol and agrees to comply with it, including willingness to use the study CGM and BGM No expectation that participant will be moving out of the area of the clinical center during the time period of the study, unless the move will be to an area served by another study center Exclusion Criteria: Individuals who meet any of the following criteria are not eligible for the study: Severe hypoglycemia in the last 12 months in which the assistance of another individual was needed or seizure/loss of consciousness in the past 3 years Significant hypoglycemia unawareness based on the Clarke Hypoglycemia Unawareness Survey defined as at least one of the following being present: Survey score >2 Survey Q1 is answered as 'I no longer have symptoms when my blood sugar is low' Survey Q7 response indicates that symptoms of hypoglycemia are not felt until glucose level is <50 mg/dl Survey Q8 response is never or rarely to the question 'to what extent can you tell by your symptoms that your blood sugar is low' More than one DKA event in the past year History of seizures other than due to hypoglycemia Current use of a threshold suspend pump feature (note: participant is eligible if a pump with this feature was being used but the threshold suspend was not active) Myocardial infarction or stroke in past 6 months Estimated Glomerular Filtration Rate (GFR) <30 obtained within the prior 12 months as part of usual care or kidney transplant Most recent thyroid function test results abnormal, obtained as part of usual care within the prior 2 years The presence of a significant medical or psychiatric disorder or use of a medication that in the judgment of the investigator will affect the wearing of the sensors, the completion of any aspect of the protocol, or increase risk Cognitive difficulties that, in the judgment of the investigator, could impair the individual's ability to follow the protocol or increase risk Initiation of a non-insulin drug for glucose control during the past 3 months, planned initiation during the next 8 months, or discontinuation of a non-insulin drug for glucose control during the past 3 months (note: individuals using a non-insulin medication for glucose control for 3 or more months are eligible provided there is no expectation that the medication will be discontinued during the time period of study participation) Use of a systemic beta blocker drug Regular use of oral corticosteroids Anticipated need to use acetaminophen during the time course of the study Inpatient psychiatric treatment in the past 6 months Currently pregnant or lactating or plan to attempt getting pregnant during the time period of the study • Females with child-bearing potential will be queried about the possibility of pregnancy and a urine pregnancy test will be performed if there is uncertainty as to the possibility of pregnancy. They must agree to use appropriate birth control during the time period of the study. Participants will receive education regarding birth control methods which may be considered as highly effective, which are methods that can achieve a failure rate less than 1% per year when used consistently and correctly and include: Combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) Intrauterine device (IUD) Intrauterine hormone-releasing system (IUS) Bilateral tubal occlusion Vasectomised partner Sexual abstinence Participation in an intervention study (including psychological studies) in past 6 weeks Known adhesive allergy From the blinded run-in phase (or from pre-study CGM use if criteria met to skip the blinded run-in phase), CGM values <60 mg/dl for more than 10.0% of the time Unsuccessful completion of the run-in phases with respect to CGM or BGM use
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: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CGM Only<br>Participants will be instructed to check the blood glucose with the standard study BGM for calibration of the CGM and for specific circumstances that are specified in the protocol. This group will make management decisions based on the CGM glucose value without a BGM confirmation measurement as long as the participant is confident that the CGM glucose value is not erroneous. In addition, participants will be instructed to make a BGM measurement on the blinded study BGM before going to bed, whenever an insulin bolus is given and when treating or attempting to prevent hypoglycemia and a standard BGM measurement has not been made. The participant may be asked to make post-prandial blinded BGM measurements at selected times. | Device: CGM Only<br>* Dexcom G4 Platinum Continuous Glucose Monitoring System with modified algorithm<br>|
| Active Comparator: CGM+BGM<br>Participants will be instructed to perform BGM measurements for sensor calibration according to Dexcom specifications and measure the blood glucose whenever a diabetes management decision is made. A BGM measurement is to be made on the study BGM before going to bed, whenever an insulin bolus is given and when treating or attempting to prevent hypoglycemia. Additional BGM measurements can be made on the study BGM at any time that the participant desires. | Device: CGM+BGM<br>* Dexcom G4 Platinum Continuous Glucose Monitoring System with modified algorithm + Abbot Precision Xtra Blood Glucose-Ketone Meter<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Time in Range of 70 to 180 mg/dl, Measured With CGM | | Between baseline (randomization) and 6 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Glucose | | Between baseline (randomization) and 6 months |
| Measures of Glycemic Variability: Coefficient of Variation | Coefficient of variation = SD/mean | Between baseline (randomization) and 6 months |
| Percentage of Time With Sensor Value <70 mg/dl, Measured With CGM | | Between baseline (randomization) and 6 months |
| Percentage of Time With Sensor Values <60 mg/dl, Measured With CGM | | Between baseline (randomization) and 6 months |
| Percentage of Time With Sensor Values <50 mg/dl, Measured With CGM | | Between baseline (randomization) and 6 months |
| Percentage of Days With at Least 20 Minutes of Sensor Glucose Values <60 mg/dl | | Between baseline (randomization) and 6 months |
| Percentage of Time With Sensor Values >180 mg/dl, Measured With CGM | | Between baseline (randomization) and 6 months |
| Percentage of Time With Sensor Values > 250 mg/dl, Measured With CGM | | Between baseline (randomization) and 6 months |
| Percentage of Time With Sensor Values > 300 mg/dl, Measured With CGM | | Between baseline (randomization) and 6 months |
| Percentage of Days With at Least 20 Minutes of Sensor Glucose Values >300 mg/dl | | Between baseline (randomization) and 6 months |
| Change in HbA1c | | Between baseline (randomization) and 6 months |
| Number of Participants With no Worsening of HbA1c by Greater Than 0.3% AND no Severe Hypoglycemia Event | | Between baseline (randomization) and 6 months |
| Number of Participants With >=1 Severe Hypoglycemia Events | | Between baseline (randomization) and 6 months |
| Number of Participants With >=1 Diabetic Ketoacidosis (DKA) Events | | Between baseline (randomization) and 6 months |
| Number of Participants With >=1 Ketotic Events Not Meeting Criteria for DKA With Blood Ketone Level >=0.6 mmol/L | | Between baseline (randomization) and 6 months |
| Number of Participants With >=1 Ketotic Events Not Meeting Criteria for DKA With Blood Ketone Level >=1.0 mmol/L | | Between baseline (randomization) and 6 months |
| Number of Participants With >=1 Serious Adverse Event Other Than SH | A serious adverse event is any untoward occurrence that: Results in death. Is life-threatening; (a non-life-threatening event which, had it been more severe, might have become life-threatening, is not necessarily considered a serious adverse event). Requires inpatient hospitalization or prolongation of existing hospitalization. Results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions (sight threatening). Is a congenital anomaly or birth defect. Is considered a significant medical event by the investigator based on medical judgment. | Between baseline (randomization) and 6 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diabetes Mellitus, Continuous Glucose Monitoring
|
NCT03827395
|
Safety Study of Hepatitis E Vaccine (HEV239)
|
This is a Phase I double-blind, randomized, placebo controlled trial (1:4 ratio of placebo to vaccine) of Hepatitis E virus vaccine containing a 239 amino acid subfragment of Hecolin(R) (HEV-239) in 25 US males and non-pregnant females ages 18 - 45 (inclusive) to assess the safety, reactogenicity, and immunogenicity of HEV-239. Subjects will receive 3 doses of study product on Days 1, 29, and 180. Subjects will remain in the study for up to 13 months (including screening). The study duration will be approximately 15 months. Subjects will be observed for 30 minutes after vaccination. The occurrence of solicited injection site and systemic reactogenicity events will be measured from the time of study vaccination through Day 8 after each vaccination. These will be ascertained through use of an electronic memory (e-memory) aid, a telephone call on day 4 after each dose of vaccine, a Day 8 clinic visit, and potentially at the Day 15 clinic visit after each dose of vaccine. Unsolicited adverse events will be collected from vaccination through Day 29 after each vaccination. Serious adverse events will be collected from the time of the first study vaccination through the last study visit (Day 360). The study includes multiple phlebotomy time points for immunogenicity and blood collection for future use at visit 1 and Days 8, 15, and 29 after each vaccination. The durability of the immune response and future use collection will be assessed at 5 months after the first boost (Day 180) and at 6 months after the second boost (Day 360). The primary objectives of the study are to; 1) assess the safety and reactogenicity of HEV-239 following delivery of each vaccine dose; and 2) assess the number of subjects with > / = 4 fold rise in Hepatitis E virus (HEV) immunoglobulin G (IgG) at any time after vaccination.
|
This is a Phase I double-blind, randomized, placebo controlled trial (1:4 ratio of placebo to vaccine) of Hepatitis E virus vaccine containing a 239 amino acid subfragment of Hecolin(R) (HEV-239) in 25 US males and non-pregnant females ages 18 - 45 (inclusive) to assess the safety, reactogenicity, and immunogenicity of HEV-239. Subjects will receive 3 doses of study product on Days 1, 29, and 180. Subjects will remain in the study for up to 13 months (including screening). The study duration will be approximately 15 months. Subjects will be observed for 30 minutes after vaccination. The occurrence of solicited injection site and systemic reactogenicity events will be measured from the time of study vaccination through Day 8 after each vaccination. These will be ascertained through use of an electronic memory (e-memory) aid, a telephone call on day 4 after each dose of vaccine, a Day 8 clinic visit, and potentially at the Day 15 clinic visit after each dose of vaccine. Unsolicited adverse events will be collected from vaccination through Day 29 after each vaccination. Serious adverse events will be collected from the time of the first study vaccination through the last study visit (Day 360). The study includes multiple phlebotomy time points for immunogenicity and blood collection for future use at visit 1 and Days 8, 15, and 29 after each vaccination. The durability of the immune response and future use collection will be assessed at 5 months after the first boost (Day 180) and at 6 months after the second boost (Day 360). The primary objectives of the study are to; 1) Assess the safety and reactogenicity of HEV-239 following delivery of each vaccine dose; and 2) Assess the number of subjects with > / = 4 fold rise in Hepatitis E virus (HEV) immunoglobulin G (IgG) at any time after vaccination. The secondary objectives are to; 1) Assess the number of subjects with HEV immunoglobulin M (IgM) seroconversion at any time after vaccination; 2) Assess the number of subjects with HEV IgG seroconversion at any time after vaccination; and 3) Assess the HEV IgG geometric mean concentrations (GMCs) at any time after vaccination.
|
A Phase 1, Double-Blinded, Placebo Controlled, Clinical Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of HEV-239 (Hecolin(R)) in a Healthy US Adult Population
|
Hepatitis E, Immunisation
|
* Biological: HEV 239
* Other: Placebo
|
Inclusion Criteria:~Subject must provide written informed consent.~Subject must be able to comprehend and willing to comply with all study visits and procedures (up to 13 months from enrollment).~Subject must be a man or a non-pregnant woman* aged 18-45 years (inclusive).~*Females of childbearing potential must have a negative serum human chorionic gonadotropin (beta-HCG) pregnancy test at screening and negative urine beta-HCG pregnancy test within 24 hours prior to (each) vaccination.~Subject must be in good general health as determined by medical history, vital signs*, body mass index (BMI)**, physical examination, and clinical judgment of the investigator.~*Oral temp < 38.0 Degrees Celsius /100.4 Degrees Fahrenheit; pulse 51 to 100 bpm; systolic blood pressure 90 to 140 mm Hg, and diastolic blood pressure 55 to 90 mm Hg.~**BMI > / = 18.5 and < 35 kg/m^2.~Subject's screening laboratory values*,** must be within site normal limits*** within 28 days of enrollment.~*Screening labs will include: White blood cell (WBC) count; Hemoglobin (HgB); Platelets; Absolute neutrophil count (ANC); Absolute eosinophil count (AEC); Creatinine; Glucose (random, must be < 140); Alanine Aminotransferase (ALT); HIV 1/2 antibody/antigen test, Hepatitis B surface antigen (HBsAg), and Hepatitis C virus (HCV) antibody.~**Minor abnormalities are considered acceptable if not clinically significant (e.g., Mean Corpuscular Volume (MCV)). Repeating the screening tests once is permitted for out-of-range values provided there is an alternative explanation for the out-of-range value. The alternative explanation for the out-of-range value should be documented in the subject's source documents.~***Creatinine, glucose, and ALT values lower than the normal range may be acceptable if the PI or a designated licensed clinician determines that these laboratory findings are not clinically significant. The HIV 1/2 antibody/antigen test, Hepatitis B surface antigen (HBsAg), and Hepatitis C virus (HCV) antibody must be non-reactive.~Subject's Hepatitis E Virus (HEV) - specific Immunoglobulin G (IgG) and Immunoglobulin M (IgM) are negative by ELISA at screening.~Subject agrees to not to participate in another clinical trial during the study period.~Subject agrees not to donate blood from screening through Day 270.~Female subjects must be of non-childbearing potential* OR must use an acceptable method of contraception** from 28 days before prime vaccination until at least 3 months after the last vaccination.~*Surgically sterile via tubal ligation, bilateral oophorectomy, hysterectomy or postmenopausal for > / = 1 year.~**Abstinence (defined as refraining from heterosexual intercourse), monogamous relationship with vasectomized partner, barrier methods such as male or female condoms with spermicide or diaphragms with spermicide, intrauterine devices, and licensed hormonal methods (such as birth control pills, skin patches, Implanon(R), Nexplanon(R), DepoProvera(R), or NuvaRing(R)).~Male subjects must be surgically sterile via vasectomy OR must use an acceptable method of contraception* from prime vaccination until at least 3 months after the last boost vaccination.~Abstinence (defined as refraining from heterosexual intercourse), or condoms with spermicide.~Subjects must have consistent access to the internet to perform electronic data entry.~Exclusion Criteria:~Has a previous HEV infection or chronic liver disease.~Has received any experimental agent* within 30 days prior to first vaccination, or the expected recipient of any experimental agent during this trial-reporting period.~*Including vaccines, drugs, biologics, devices, and/or blood products.~Female subject is pregnant (or has a positive pregnancy test prior to vaccination) or breast feeding, or planning to become pregnant within 3 months after the last boost vaccination.~Fever (> / = 38.0 Degrees Celsius / 100.4 Degrees Fahrenheit) or other acute illness within 3 days prior to first vaccination.~Infection requiring systemic antibiotics or antiviral treatment within the 7 days prior to first vaccination.~Has a positive urine drug screen for amphetamines*, cocaine, opiates, or phencyclidine.~*Prescription amphetamines are not exclusionary.~Chronic, clinically significant medical or psychiatric conditions* that, in the opinion of the investigator, may pose additional risk to the subject if she/he participates in the study.~*Permissible conditions include but are not limited to mild, well-controlled asthma, well-controlled depression, well-controlled anxiety, seasonal allergies, and well-controlled hypertension.~Receipt of immunosuppressive drugs*,**,*** or biologic agents within the 30 days prior to enrollment.~*This includes use of oral or parental prednisone. This also includes allergy desensitization injections from 14 days prior to each vaccination through 14 days after each vaccination. The use of topical steroids for mild uncomplicated dermatitis permissible after therapy is completed. Over-the-counter (OTC) corticosteroid nasal sprays for allergic rhinitis are permissible. The use of low or moderate dose inhaled steroids is permissible. Doses are defined as per age as using inhaled high-dose per reference chart in the National Heart, Lung and Blood Institute Guidelines for the Diagnosis and Management of Asthma (EPR-3) or other lists published in UPTODATE.~**Receipt of systemic, prescription medications for the treatment of chronic medical conditions or variations of normal physiologic functions may be permissible if, in the opinion of the investigator, they are used for conditions that are not clinically significant and would not impact the safety of the subject or the safety and immunogenicity outcomes of the protocol.~***Use of systemic, over-the-counter medications and PRN systemic, prescription medication may be allowed if, in the opinion of the investigator, they pose no additional risk to subject safety or assessment of immunogenicity/reactogenicity.~Has known neoplastic disease* anticancer therapy, or radiation therapy within 3 years prior to first study vaccination.~*Excluding non-melanoma skin cancer, such as squamous cell skin cancer or basal cell skin cancer, cured by surgical excision.~Has a history of any hematologic malignancy at any time.~Has a known or suspected congenital or acquired disease that impairs the immune system, including functional asplenia or immunosuppression as a result of underlying illness or treatment.~Has prior organ and/or stem cell transplant.~Has a history of abuse of alcohol or drugs that, in the opinion of the investigator, may interfere with the subject's ability to comply with the protocol.~Has behavioral or cognitive impairment or psychiatric conditions that, in the opinion of the investigator, may interfere with the subject's ability to participate in the trial.~Has received blood products or immunoglobulin within six months prior to vaccination.~Travel to Asia, the Middle East, Africa, or Central America or to an area with an active Hepatitis E outbreak* within the last 90 days or intention to travel to such areas during the study.~*Outbreaks within the last 3 years.~Receipt of any inactivated vaccine from 2 weeks prior to each vaccination through 2 weeks after each vaccination.~Receipt of any live vaccine from 4 weeks prior to each vaccination through 4 weeks after each vaccination.~Known hypersensitivity or allergy to aluminum, any component of the vaccine, or other serious adverse reactions to vaccines or vaccine products.~Subject who, in the opinion of the investigator, is unlikely to adhere to the requirements of the study.~Any condition that, in the opinion of the investigator, might interfere with assessing the study objectives.
|
18 Years
|
45 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Solicited Local Reactogenicity Events | Injection site Adverse Events (AEs) solicited on an e-memory aid available to participants included: pain, tenderness, pruritis/itching, ecchymosis/bruising, induration/swelling (functional grade based on interference with daily activities). Ecchymosis/bruising (any measured value >/= 25mm), induration/swelling (any measured value >/= 25mm), and erythema/redness (any measured value >/= 25mm). Participants are considered reporting the injection site AE if they reported mild or greater severity at any time during the 8 days at or following vaccination. | Post Dose 1 (Day 1 through Day 8), Post Dose 2 (Day 29 through Day 36), Post Dose 3 (Day 180 through Day 187) |
| Number of Participants With Solicited Systemic Reactogenicity Events | Systemic AEs solicited on an e-memory aid provided to participants included: feverishness, fatigue, malaise, myalgia, arthralgia, headache, nausea, vomiting, and elevated oral temperature (38.0 degrees Celsius/100.4 degrees Fahrenheit or greater). Participants are considered reporting the injection site AE if they reported mild or greater severity at any time during the 8 days at or following vaccination. | Post Dose 1 (Day 1 through Day 8), Post Dose 2 (Day 29 through Day 36), Post Dose 3 (Day 180 through Day 187) |
| Number of Participants With Vaccine-related Unsolicited Adverse Events (AEs) | Unsolicited adverse events were defined as any untoward medical occurrence in a participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Unsolicited AEs that were deemed vaccine-related were collected from participants from the time of vaccination through Day 29 after each study vaccination. | Post Dose 1 (Day 1 through Day 29), Post Dose 2 (Day 29 through Day 57), Post Dose 3 (Day 180 through Day 208) |
| Number of Participants With Clinical Safety Laboratory Adverse Events (AEs) - Chemistry | Chemistry parameters included: alanine aminotransferase (ALT) and creatinine. Thresholds for adverse events were considered as ALT 30 U/L or greater (female) or 47 U/L or greater (male); creatinine 1.11 mg/dL or greater (female) or 1.36 mg/dL or greater (male). | Baseline, Post Dose 1 (Day 8), Post Dose 2 (Day 36), Post Dose 3 (Day 187) |
| Number of Participants With Clinical Safety Laboratory Adverse Events (AEs) - Hematology | Hematology parameters included: hemoglobin, platelets, absolute neutrophil count (ANC), absolute eosinophil count (AEC), and white blood cells (WBC). Thresholds for adverse events were considered as hemoglobin 11.0 g/dL or greater (female) or 12.0 g/dL or greater (male); WBC increase 10.9 thousand/uL or greater; WBC decrease 3.7 thousand/uL or less; ANC decrease 1499 cells/uL or less; AEC increase 501 cells/uL or greater; platelet decrease 139 thousand/uL or less. | Baseline, Post Dose 1 (Day 8), Post Dose 2 (Day 36), Post Dose 3 (Day 187) |
| Number of Participants With Vaccine-related Serious Adverse Events (SAEs) | SAEs included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect; or any important medical event that may not result in death, be life-threatening, or require hospitalizations, that may be considered serious when, based on appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. | Day 1 through Day 360 |
| Percentage of Participants Showing >/=4-fold Rise in Serum Hepatitis E Virus Immunoglobulin G (IgG) Concentration | Blood was collected for IgG assay which was conducted with HEV as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean fold rise was calculated for each study arm from the available results at Day 8 and Day 15 post first study vaccination, Day 29 prior to second study vaccination, Day 36, Day 43, Day 57, Day 180 prior to third study vaccination, Day 187, Day 194, Day 208 and Day 360. A 4-fold rise was defined as a HEV IgG >/=0.154 Wu/mL in a participant that was HEV seronegative at Day 1. | Day 8, Day 15, Day 29 (Dose 2), Day 36, Day 43, Day 57, Day 180 (Dose 3), Day 187, Day 194, Day 208, Day 360 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Hepatitis E Virus Immunoglobulin M (IgM) Seroconversion | Blood was collected for the IgM assay conducted with HEV as the antigen. Each sample was tested in duplicate per the laboratory's standard operating procedure and retested in duplicate if a result was borderline (A / C.O. = 0.9-1.1). If any replicate was seropositive [A/C.O. >1.1 as defined by the Wantai HEV-IgM enzyme-linked immunosorbent assay (ELISA) package insert] the sample's result was positive. If no replicates were positive the sample's result was negative. Seroconversion was defined as a change from a seronegative result to a seropositive result. | Day 8, Day 15, Day 29 (Dose 2), Day 36, Day 43, Day 57, Day 180 (Dose 3), Day 187, Day 194, Day 208, Day 360 |
| Percentage of Participants With Hepatitis E Virus IgG Seroconversion | Blood was collected for the IgG assay conducted with HEV as the antigen. Each sample was tested in duplicate per the laboratory's standard operating procedure and retested in duplicate if a result was borderline (A / C.O. = 0.9-1.1). If any replicate was seropositive (A/C.O. >1.1 as defined by the Wantai HEV-IgG ELISA package insert) the sample's result was positive. If no replicates were positive the sample's result was negative. Seroconversion was defined as a change from a seronegative result to a seropositive result. | Day 8, Day 15, Day 29 (Dose 2), Day 36, Day 43, Day 57, Day 180 (Dose 3), Day 187, Day 194, Day 208, Day 360 |
| Geometric Mean Concentrations (GMC) of Hepatitis E Virus IgG | Blood was collected for IgG assay which was conducted with HEV as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean concentration (Wu/mL) was calculated for each study arm from the available results at each timepoint. | Day 1 (Dose 1), Day 8, Day 15, Day 29 (Dose 2), Day 36, Day 43, Day 57, Day 180 (Dose 3), Day 187, Day 194, Day 208, Day 360 |
|
Adult, Healthy, Hecolin, Hepatitis E, HEV239, Immunogenicity, Placebo, Population, Reactogenicity, Route, Safety, Vaccine
|
Hepatitis, Hepatitis A, Hepatitis E, Liver Diseases, Digestive System Diseases, Hepatitis, Viral, Human, Virus Diseases, Infections, Enterovirus Infections, Picornaviridae Infections, RNA Virus Infections
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HEV-239<br>0.5 mL of HEV-239 administered intramuscularly into the deltoid muscle as a single injection on Days 1, 29, and 180. N=20 | Biological: HEV 239<br>* Hepatitis E vaccine against HEV genotypes 1 and 4. The HEV 239 vaccine is a 26 kDa recombinant polypeptide corresponding to amino acid residues 368-606 of the capsid protein of a genotype 1 HEV strain. The vaccine is expressed in Escherichia coli (E. coli) and vaccine doses contain 30 µg of the purified antigen in 0.5 mL buffered saline adsorbed to 0.8 mg aluminium hydroxide.<br>|
| Placebo Comparator: Placebo<br>0.5 mL of HEV-239 placebo administered intramuscularly into the deltoid muscle as a single injection on Days 1, 29, and 180. N=5 | Other: Placebo<br>* 0.9% Sodium Chloride Injection, USP (Normal Saline) is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection (WFI). Each mL contains sodium chloride 9 mg and may contain HCl or NaOH for pH adjustment (pH 5.3 [4.5 - 7.0]).<br>|
|
Safety Study of Hepatitis E Vaccine (HEV239)
Study Overview
=================
Brief Summary
-----------------
This is a Phase I double-blind, randomized, placebo controlled trial (1:4 ratio of placebo to vaccine) of Hepatitis E virus vaccine containing a 239 amino acid subfragment of Hecolin(R) (HEV-239) in 25 US males and non-pregnant females ages 18 - 45 (inclusive) to assess the safety, reactogenicity, and immunogenicity of HEV-239. Subjects will receive 3 doses of study product on Days 1, 29, and 180. Subjects will remain in the study for up to 13 months (including screening). The study duration will be approximately 15 months. Subjects will be observed for 30 minutes after vaccination. The occurrence of solicited injection site and systemic reactogenicity events will be measured from the time of study vaccination through Day 8 after each vaccination. These will be ascertained through use of an electronic memory (e-memory) aid, a telephone call on day 4 after each dose of vaccine, a Day 8 clinic visit, and potentially at the Day 15 clinic visit after each dose of vaccine. Unsolicited adverse events will be collected from vaccination through Day 29 after each vaccination. Serious adverse events will be collected from the time of the first study vaccination through the last study visit (Day 360). The study includes multiple phlebotomy time points for immunogenicity and blood collection for future use at visit 1 and Days 8, 15, and 29 after each vaccination. The durability of the immune response and future use collection will be assessed at 5 months after the first boost (Day 180) and at 6 months after the second boost (Day 360). The primary objectives of the study are to; 1) assess the safety and reactogenicity of HEV-239 following delivery of each vaccine dose; and 2) assess the number of subjects with > / = 4 fold rise in Hepatitis E virus (HEV) immunoglobulin G (IgG) at any time after vaccination.
Detailed Description
-----------------
This is a Phase I double-blind, randomized, placebo controlled trial (1:4 ratio of placebo to vaccine) of Hepatitis E virus vaccine containing a 239 amino acid subfragment of Hecolin(R) (HEV-239) in 25 US males and non-pregnant females ages 18 - 45 (inclusive) to assess the safety, reactogenicity, and immunogenicity of HEV-239. Subjects will receive 3 doses of study product on Days 1, 29, and 180. Subjects will remain in the study for up to 13 months (including screening). The study duration will be approximately 15 months. Subjects will be observed for 30 minutes after vaccination. The occurrence of solicited injection site and systemic reactogenicity events will be measured from the time of study vaccination through Day 8 after each vaccination. These will be ascertained through use of an electronic memory (e-memory) aid, a telephone call on day 4 after each dose of vaccine, a Day 8 clinic visit, and potentially at the Day 15 clinic visit after each dose of vaccine. Unsolicited adverse events will be collected from vaccination through Day 29 after each vaccination. Serious adverse events will be collected from the time of the first study vaccination through the last study visit (Day 360). The study includes multiple phlebotomy time points for immunogenicity and blood collection for future use at visit 1 and Days 8, 15, and 29 after each vaccination. The durability of the immune response and future use collection will be assessed at 5 months after the first boost (Day 180) and at 6 months after the second boost (Day 360). The primary objectives of the study are to; 1) Assess the safety and reactogenicity of HEV-239 following delivery of each vaccine dose; and 2) Assess the number of subjects with > / = 4 fold rise in Hepatitis E virus (HEV) immunoglobulin G (IgG) at any time after vaccination. The secondary objectives are to; 1) Assess the number of subjects with HEV immunoglobulin M (IgM) seroconversion at any time after vaccination; 2) Assess the number of subjects with HEV IgG seroconversion at any time after vaccination; and 3) Assess the HEV IgG geometric mean concentrations (GMCs) at any time after vaccination.
Official Title
-----------------
A Phase 1, Double-Blinded, Placebo Controlled, Clinical Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of HEV-239 (Hecolin(R)) in a Healthy US Adult Population
Conditions
-----------------
Hepatitis E, Immunisation
Intervention / Treatment
-----------------
* Biological: HEV 239
* Other: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject must provide written informed consent. Subject must be able to comprehend and willing to comply with all study visits and procedures (up to 13 months from enrollment). Subject must be a man or a non-pregnant woman* aged 18-45 years (inclusive). *Females of childbearing potential must have a negative serum human chorionic gonadotropin (beta-HCG) pregnancy test at screening and negative urine beta-HCG pregnancy test within 24 hours prior to (each) vaccination. Subject must be in good general health as determined by medical history, vital signs*, body mass index (BMI)**, physical examination, and clinical judgment of the investigator. *Oral temp < 38.0 Degrees Celsius /100.4 Degrees Fahrenheit; pulse 51 to 100 bpm; systolic blood pressure 90 to 140 mm Hg, and diastolic blood pressure 55 to 90 mm Hg. **BMI > / = 18.5 and < 35 kg/m^2. Subject's screening laboratory values*,** must be within site normal limits*** within 28 days of enrollment. *Screening labs will include: White blood cell (WBC) count; Hemoglobin (HgB); Platelets; Absolute neutrophil count (ANC); Absolute eosinophil count (AEC); Creatinine; Glucose (random, must be < 140); Alanine Aminotransferase (ALT); HIV 1/2 antibody/antigen test, Hepatitis B surface antigen (HBsAg), and Hepatitis C virus (HCV) antibody. **Minor abnormalities are considered acceptable if not clinically significant (e.g., Mean Corpuscular Volume (MCV)). Repeating the screening tests once is permitted for out-of-range values provided there is an alternative explanation for the out-of-range value. The alternative explanation for the out-of-range value should be documented in the subject's source documents. ***Creatinine, glucose, and ALT values lower than the normal range may be acceptable if the PI or a designated licensed clinician determines that these laboratory findings are not clinically significant. The HIV 1/2 antibody/antigen test, Hepatitis B surface antigen (HBsAg), and Hepatitis C virus (HCV) antibody must be non-reactive. Subject's Hepatitis E Virus (HEV) - specific Immunoglobulin G (IgG) and Immunoglobulin M (IgM) are negative by ELISA at screening. Subject agrees to not to participate in another clinical trial during the study period. Subject agrees not to donate blood from screening through Day 270. Female subjects must be of non-childbearing potential* OR must use an acceptable method of contraception** from 28 days before prime vaccination until at least 3 months after the last vaccination. *Surgically sterile via tubal ligation, bilateral oophorectomy, hysterectomy or postmenopausal for > / = 1 year. **Abstinence (defined as refraining from heterosexual intercourse), monogamous relationship with vasectomized partner, barrier methods such as male or female condoms with spermicide or diaphragms with spermicide, intrauterine devices, and licensed hormonal methods (such as birth control pills, skin patches, Implanon(R), Nexplanon(R), DepoProvera(R), or NuvaRing(R)). Male subjects must be surgically sterile via vasectomy OR must use an acceptable method of contraception* from prime vaccination until at least 3 months after the last boost vaccination. Abstinence (defined as refraining from heterosexual intercourse), or condoms with spermicide. Subjects must have consistent access to the internet to perform electronic data entry. Exclusion Criteria: Has a previous HEV infection or chronic liver disease. Has received any experimental agent* within 30 days prior to first vaccination, or the expected recipient of any experimental agent during this trial-reporting period. *Including vaccines, drugs, biologics, devices, and/or blood products. Female subject is pregnant (or has a positive pregnancy test prior to vaccination) or breast feeding, or planning to become pregnant within 3 months after the last boost vaccination. Fever (> / = 38.0 Degrees Celsius / 100.4 Degrees Fahrenheit) or other acute illness within 3 days prior to first vaccination. Infection requiring systemic antibiotics or antiviral treatment within the 7 days prior to first vaccination. Has a positive urine drug screen for amphetamines*, cocaine, opiates, or phencyclidine. *Prescription amphetamines are not exclusionary. Chronic, clinically significant medical or psychiatric conditions* that, in the opinion of the investigator, may pose additional risk to the subject if she/he participates in the study. *Permissible conditions include but are not limited to mild, well-controlled asthma, well-controlled depression, well-controlled anxiety, seasonal allergies, and well-controlled hypertension. Receipt of immunosuppressive drugs*,**,*** or biologic agents within the 30 days prior to enrollment. *This includes use of oral or parental prednisone. This also includes allergy desensitization injections from 14 days prior to each vaccination through 14 days after each vaccination. The use of topical steroids for mild uncomplicated dermatitis permissible after therapy is completed. Over-the-counter (OTC) corticosteroid nasal sprays for allergic rhinitis are permissible. The use of low or moderate dose inhaled steroids is permissible. Doses are defined as per age as using inhaled high-dose per reference chart in the National Heart, Lung and Blood Institute Guidelines for the Diagnosis and Management of Asthma (EPR-3) or other lists published in UPTODATE. **Receipt of systemic, prescription medications for the treatment of chronic medical conditions or variations of normal physiologic functions may be permissible if, in the opinion of the investigator, they are used for conditions that are not clinically significant and would not impact the safety of the subject or the safety and immunogenicity outcomes of the protocol. ***Use of systemic, over-the-counter medications and PRN systemic, prescription medication may be allowed if, in the opinion of the investigator, they pose no additional risk to subject safety or assessment of immunogenicity/reactogenicity. Has known neoplastic disease* anticancer therapy, or radiation therapy within 3 years prior to first study vaccination. *Excluding non-melanoma skin cancer, such as squamous cell skin cancer or basal cell skin cancer, cured by surgical excision. Has a history of any hematologic malignancy at any time. Has a known or suspected congenital or acquired disease that impairs the immune system, including functional asplenia or immunosuppression as a result of underlying illness or treatment. Has prior organ and/or stem cell transplant. Has a history of abuse of alcohol or drugs that, in the opinion of the investigator, may interfere with the subject's ability to comply with the protocol. Has behavioral or cognitive impairment or psychiatric conditions that, in the opinion of the investigator, may interfere with the subject's ability to participate in the trial. Has received blood products or immunoglobulin within six months prior to vaccination. Travel to Asia, the Middle East, Africa, or Central America or to an area with an active Hepatitis E outbreak* within the last 90 days or intention to travel to such areas during the study. *Outbreaks within the last 3 years. Receipt of any inactivated vaccine from 2 weeks prior to each vaccination through 2 weeks after each vaccination. Receipt of any live vaccine from 4 weeks prior to each vaccination through 4 weeks after each vaccination. Known hypersensitivity or allergy to aluminum, any component of the vaccine, or other serious adverse reactions to vaccines or vaccine products. Subject who, in the opinion of the investigator, is unlikely to adhere to the requirements of the study. Any condition that, in the opinion of the investigator, might interfere with assessing the study objectives.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HEV-239<br>0.5 mL of HEV-239 administered intramuscularly into the deltoid muscle as a single injection on Days 1, 29, and 180. N=20 | Biological: HEV 239<br>* Hepatitis E vaccine against HEV genotypes 1 and 4. The HEV 239 vaccine is a 26 kDa recombinant polypeptide corresponding to amino acid residues 368-606 of the capsid protein of a genotype 1 HEV strain. The vaccine is expressed in Escherichia coli (E. coli) and vaccine doses contain 30 µg of the purified antigen in 0.5 mL buffered saline adsorbed to 0.8 mg aluminium hydroxide.<br>|
| Placebo Comparator: Placebo<br>0.5 mL of HEV-239 placebo administered intramuscularly into the deltoid muscle as a single injection on Days 1, 29, and 180. N=5 | Other: Placebo<br>* 0.9% Sodium Chloride Injection, USP (Normal Saline) is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection (WFI). Each mL contains sodium chloride 9 mg and may contain HCl or NaOH for pH adjustment (pH 5.3 [4.5 - 7.0]).<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Solicited Local Reactogenicity Events | Injection site Adverse Events (AEs) solicited on an e-memory aid available to participants included: pain, tenderness, pruritis/itching, ecchymosis/bruising, induration/swelling (functional grade based on interference with daily activities). Ecchymosis/bruising (any measured value >/= 25mm), induration/swelling (any measured value >/= 25mm), and erythema/redness (any measured value >/= 25mm). Participants are considered reporting the injection site AE if they reported mild or greater severity at any time during the 8 days at or following vaccination. | Post Dose 1 (Day 1 through Day 8), Post Dose 2 (Day 29 through Day 36), Post Dose 3 (Day 180 through Day 187) |
| Number of Participants With Solicited Systemic Reactogenicity Events | Systemic AEs solicited on an e-memory aid provided to participants included: feverishness, fatigue, malaise, myalgia, arthralgia, headache, nausea, vomiting, and elevated oral temperature (38.0 degrees Celsius/100.4 degrees Fahrenheit or greater). Participants are considered reporting the injection site AE if they reported mild or greater severity at any time during the 8 days at or following vaccination. | Post Dose 1 (Day 1 through Day 8), Post Dose 2 (Day 29 through Day 36), Post Dose 3 (Day 180 through Day 187) |
| Number of Participants With Vaccine-related Unsolicited Adverse Events (AEs) | Unsolicited adverse events were defined as any untoward medical occurrence in a participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Unsolicited AEs that were deemed vaccine-related were collected from participants from the time of vaccination through Day 29 after each study vaccination. | Post Dose 1 (Day 1 through Day 29), Post Dose 2 (Day 29 through Day 57), Post Dose 3 (Day 180 through Day 208) |
| Number of Participants With Clinical Safety Laboratory Adverse Events (AEs) - Chemistry | Chemistry parameters included: alanine aminotransferase (ALT) and creatinine. Thresholds for adverse events were considered as ALT 30 U/L or greater (female) or 47 U/L or greater (male); creatinine 1.11 mg/dL or greater (female) or 1.36 mg/dL or greater (male). | Baseline, Post Dose 1 (Day 8), Post Dose 2 (Day 36), Post Dose 3 (Day 187) |
| Number of Participants With Clinical Safety Laboratory Adverse Events (AEs) - Hematology | Hematology parameters included: hemoglobin, platelets, absolute neutrophil count (ANC), absolute eosinophil count (AEC), and white blood cells (WBC). Thresholds for adverse events were considered as hemoglobin 11.0 g/dL or greater (female) or 12.0 g/dL or greater (male); WBC increase 10.9 thousand/uL or greater; WBC decrease 3.7 thousand/uL or less; ANC decrease 1499 cells/uL or less; AEC increase 501 cells/uL or greater; platelet decrease 139 thousand/uL or less. | Baseline, Post Dose 1 (Day 8), Post Dose 2 (Day 36), Post Dose 3 (Day 187) |
| Number of Participants With Vaccine-related Serious Adverse Events (SAEs) | SAEs included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect; or any important medical event that may not result in death, be life-threatening, or require hospitalizations, that may be considered serious when, based on appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. | Day 1 through Day 360 |
| Percentage of Participants Showing >/=4-fold Rise in Serum Hepatitis E Virus Immunoglobulin G (IgG) Concentration | Blood was collected for IgG assay which was conducted with HEV as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean fold rise was calculated for each study arm from the available results at Day 8 and Day 15 post first study vaccination, Day 29 prior to second study vaccination, Day 36, Day 43, Day 57, Day 180 prior to third study vaccination, Day 187, Day 194, Day 208 and Day 360. A 4-fold rise was defined as a HEV IgG >/=0.154 Wu/mL in a participant that was HEV seronegative at Day 1. | Day 8, Day 15, Day 29 (Dose 2), Day 36, Day 43, Day 57, Day 180 (Dose 3), Day 187, Day 194, Day 208, Day 360 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Hepatitis E Virus Immunoglobulin M (IgM) Seroconversion | Blood was collected for the IgM assay conducted with HEV as the antigen. Each sample was tested in duplicate per the laboratory's standard operating procedure and retested in duplicate if a result was borderline (A / C.O. = 0.9-1.1). If any replicate was seropositive [A/C.O. >1.1 as defined by the Wantai HEV-IgM enzyme-linked immunosorbent assay (ELISA) package insert] the sample's result was positive. If no replicates were positive the sample's result was negative. Seroconversion was defined as a change from a seronegative result to a seropositive result. | Day 8, Day 15, Day 29 (Dose 2), Day 36, Day 43, Day 57, Day 180 (Dose 3), Day 187, Day 194, Day 208, Day 360 |
| Percentage of Participants With Hepatitis E Virus IgG Seroconversion | Blood was collected for the IgG assay conducted with HEV as the antigen. Each sample was tested in duplicate per the laboratory's standard operating procedure and retested in duplicate if a result was borderline (A / C.O. = 0.9-1.1). If any replicate was seropositive (A/C.O. >1.1 as defined by the Wantai HEV-IgG ELISA package insert) the sample's result was positive. If no replicates were positive the sample's result was negative. Seroconversion was defined as a change from a seronegative result to a seropositive result. | Day 8, Day 15, Day 29 (Dose 2), Day 36, Day 43, Day 57, Day 180 (Dose 3), Day 187, Day 194, Day 208, Day 360 |
| Geometric Mean Concentrations (GMC) of Hepatitis E Virus IgG | Blood was collected for IgG assay which was conducted with HEV as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean concentration (Wu/mL) was calculated for each study arm from the available results at each timepoint. | Day 1 (Dose 1), Day 8, Day 15, Day 29 (Dose 2), Day 36, Day 43, Day 57, Day 180 (Dose 3), Day 187, Day 194, Day 208, Day 360 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Adult, Healthy, Hecolin, Hepatitis E, HEV239, Immunogenicity, Placebo, Population, Reactogenicity, Route, Safety, Vaccine
|
NCT02480166
|
Comparative Efficacy of Fixed-dose Combination Sofosbuvir + Ledipasvir, 8 vs. 12 Weeks in Chronic Hepatitis C Genotype 6
|
The primary objectives of this study are to describe the efficacy of:~8-week treatment of SOF/LED for treatment-naïve, non-cirrhotic, HCV genotype 6~12-week treatment of SOF/LED for all other HCV-6 populations
|
The secondary objective of this study is to describe safety, persistency, and tolerability of SOF/LED in patients with HCV-6.
|
Comparative Efficacy of Fixed-dose Combination of Sofosbuvir and Ledipasvir for 8 or 12 Weeks for Chronic Hepatitis C Genotype 6
|
PT-NANBH
|
* Drug: 8 weeks SOF/LED
* Drug: 12 weeks SOF/LED
|
Inclusion Criteria:~Male or female, age ≥18 years~HCV genotype 6 or indeterminate and later assessed at Screening and confirmed as genotype 6~Selected to start on treatment by their treating providers~Willing and able to provide informed consent~Able to comply with dosing instructions for study drug administration and able to complete the study schedule of assessments~Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative pregnancy test on Baseline~Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception~Lactating females must agree to discontinue nursing before the study drug is administered~Exclusion Criteria:~Previous recipient of a liver transplant~Co-infection with human immunodeficiency virus (HIV) or hepatitis B (HBV)
|
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 |
| --- | --- | --- |
| Number of Participants With a Sustained Virologic Response (SVR) log10 HCV RNA PCR <25 IU/mL 12 Weeks Post-treatment | | 12 weeks after end of therapy |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced Serious Adverse Events (SAEs) and/or Adverse Events (AEs) From Informed Consent to 12 Weeks Post-treatment. | Adverse events were defined using Common Terminology Criteria for Adverse Events v3.0 (CTCAE) | Day 1 of treatment to 12 weeks post treatment |
|
hepatitis C, genotype 6
|
Ledipasvir, sofosbuvir drug combination, Antiviral Agents, Anti-Infective Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 8 weeks SOF/LED<br>Patients that are treatment naïve and without cirrhosis will be assigned to 8 weeks of treatment with fixed-dose combination sofosbuvir (400 mg) and ledipasvir (90 mg) daily. | Drug: 8 weeks SOF/LED<br>* Eligible and consenting patients will be treated with sofosbuvir 400 mg daily and ledipasvir 90 mg daily for 8 weeks. Patients that are treatment naïve and without cirrhosis will be assigned to 8 weeks of treatment. The drug will be administered orally, per manufacturers' instructions, and can be taken with or without food.<br>* Other names: Solvaldi;|
| Experimental: 12 weeks SOF/LED<br>Patients that are either treatment experienced or are cirrhotic will be assigned to 12 weeks of treatment with fixed-dose combination sofosbuvir (400 mg) and ledipasvir (90 mg) daily. | Drug: 12 weeks SOF/LED<br>* Eligible and consenting patients will be treated with sofosbuvir 400 mg daily and ledipasvir 90 mg daily for 8 weeks. Patients that are not treatment naïve or have cirrhosis will be assigned to 12 weeks of treatment. The drug will be administered orally, per manufacturers' instructions, and can be taken with or without food.<br>* Other names: Solvaldi;|
|
Comparative Efficacy of Fixed-dose Combination Sofosbuvir + Ledipasvir, 8 vs. 12 Weeks in Chronic Hepatitis C Genotype 6
Study Overview
=================
Brief Summary
-----------------
The primary objectives of this study are to describe the efficacy of: 8-week treatment of SOF/LED for treatment-naïve, non-cirrhotic, HCV genotype 6 12-week treatment of SOF/LED for all other HCV-6 populations
Detailed Description
-----------------
The secondary objective of this study is to describe safety, persistency, and tolerability of SOF/LED in patients with HCV-6.
Official Title
-----------------
Comparative Efficacy of Fixed-dose Combination of Sofosbuvir and Ledipasvir for 8 or 12 Weeks for Chronic Hepatitis C Genotype 6
Conditions
-----------------
PT-NANBH
Intervention / Treatment
-----------------
* Drug: 8 weeks SOF/LED
* Drug: 12 weeks SOF/LED
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, age ≥18 years HCV genotype 6 or indeterminate and later assessed at Screening and confirmed as genotype 6 Selected to start on treatment by their treating providers Willing and able to provide informed consent Able to comply with dosing instructions for study drug administration and able to complete the study schedule of assessments Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative pregnancy test on Baseline Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception Lactating females must agree to discontinue nursing before the study drug is administered Exclusion Criteria: Previous recipient of a liver transplant Co-infection with human immunodeficiency virus (HIV) or hepatitis B (HBV)
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: 8 weeks SOF/LED<br>Patients that are treatment naïve and without cirrhosis will be assigned to 8 weeks of treatment with fixed-dose combination sofosbuvir (400 mg) and ledipasvir (90 mg) daily. | Drug: 8 weeks SOF/LED<br>* Eligible and consenting patients will be treated with sofosbuvir 400 mg daily and ledipasvir 90 mg daily for 8 weeks. Patients that are treatment naïve and without cirrhosis will be assigned to 8 weeks of treatment. The drug will be administered orally, per manufacturers' instructions, and can be taken with or without food.<br>* Other names: Solvaldi;|
| Experimental: 12 weeks SOF/LED<br>Patients that are either treatment experienced or are cirrhotic will be assigned to 12 weeks of treatment with fixed-dose combination sofosbuvir (400 mg) and ledipasvir (90 mg) daily. | Drug: 12 weeks SOF/LED<br>* Eligible and consenting patients will be treated with sofosbuvir 400 mg daily and ledipasvir 90 mg daily for 8 weeks. Patients that are not treatment naïve or have cirrhosis will be assigned to 12 weeks of treatment. The drug will be administered orally, per manufacturers' instructions, and can be taken with or without food.<br>* Other names: Solvaldi;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Sustained Virologic Response (SVR) log10 HCV RNA PCR <25 IU/mL 12 Weeks Post-treatment | | 12 weeks after end of therapy |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced Serious Adverse Events (SAEs) and/or Adverse Events (AEs) From Informed Consent to 12 Weeks Post-treatment. | Adverse events were defined using Common Terminology Criteria for Adverse Events v3.0 (CTCAE) | Day 1 of treatment to 12 weeks post treatment |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hepatitis C, genotype 6
|
NCT00530595
|
Effects of Angiotensin Receptor Antagonist on Prohibiting Cardiovascular Events on Hemodialysis Patients
|
Cardiovascular disease is a leading cause of mortality in patients on hemodialysis therapy (HD), accounting for 30 to 50% of all death. Although angiotensin receptor blockers (ARBs) are effective for patients with diabetes and chronic kidney disease in reducing or preventing cardiovascular diseases, there has been no decisive study that demonstrated treatment with ARBs is effective in patients on HD.
| null |
Cardiovascular Disease
|
* Drug: candesartan or valsartan or losartan
|
Inclusion Criteria:~30 to 80 years of age~Receiving hemodialysis at least 12 months and less than 5 years~Pre-dialysis systolic blood pressure was more than 160 mmHg, or more than 150 mmHg if the patients received antihypertensive agents.~Exclusion Criteria:~Use of angiotensin receptor blocker or angiotensin converting enzyme inhibitor
|
30 Years
|
80 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
hemodialysis
|
Losartan, Valsartan, Candesartan, Candesartan cilexetil, Antihypertensive Agents, Angiotensin II Type 1 Receptor Blockers, Angiotensin Receptor Antagonists, Molecular Mechanisms of Pharmacological Action, Anti-Arrhythmia Agents
|
| Intervention/Treatment |
| --- |
|Drug: candesartan or valsartan or losartan|nan|
|
Effects of Angiotensin Receptor Antagonist on Prohibiting Cardiovascular Events on Hemodialysis Patients
Study Overview
=================
Brief Summary
-----------------
Cardiovascular disease is a leading cause of mortality in patients on hemodialysis therapy (HD), accounting for 30 to 50% of all death. Although angiotensin receptor blockers (ARBs) are effective for patients with diabetes and chronic kidney disease in reducing or preventing cardiovascular diseases, there has been no decisive study that demonstrated treatment with ARBs is effective in patients on HD.
Conditions
-----------------
Cardiovascular Disease
Intervention / Treatment
-----------------
* Drug: candesartan or valsartan or losartan
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 30 to 80 years of age Receiving hemodialysis at least 12 months and less than 5 years Pre-dialysis systolic blood pressure was more than 160 mmHg, or more than 150 mmHg if the patients received antihypertensive agents. Exclusion Criteria: Use of angiotensin receptor blocker or angiotensin converting enzyme inhibitor
Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 80 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Intervention/Treatment |
| --- |
|Drug: candesartan or valsartan or losartan|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
-----------------
hemodialysis
|
||
NCT03204149
|
Evaluation of Safety of Low Level Laser Device Treatment in Chronic Wounds
|
This is a randomized, double blind, placebo-controlled study to evaluate the safety of the low level laser MC-8XL device treatment in subjects with an unsuccessfully treated Diabetic Foot Ulcer (DFU) that has been present for at least 3 months.~Eligible subjects will be randomized to either Treatment group or Control group, following which, treatment of each subject will be provided by a qualified nurse at the clinic or in the home setting, everyday for up to 16 weeks.~Study assessments and adverse events monitoring will be also performed throughout the study.
|
Evaluation of Safety of Low Level Laser MC-8XL Device Treatment in Chronic Wounds
|
Diabetic Foot Ulcer
|
* Device: MC-8XL low level laser device and Standard wound care
* Device: Sham laser device and Standard wound care
|
Inclusion Criteria:~Provide signed and dated Informed Consent Form~Willing to comply with all study procedures and be available for the duration of the study~Male or female, aged 18 to 90~Having a DFU of at least 3 months duration that had not improved after prior standard wound treatments~HbA1c of <11.0~Size of wounds: 1-10 cm2~Having DFU of grades 2 or 3 according to Wagner's classification~Exclusion Criteria:~Immeasurable wounds or wounds that are unsuited to this laser treatment (usually due to the wound's location, e.g. in the area between the toes).~Uncontrolled Diabetes defined as an HbA1c of > 11.0~Arterial insufficiency, Doppler vascular assessment (if needed- Ankle Brachial Index (ABI) < 0.6)~Osteomyelitis in the bone.~Photosensitivity~Pregnancy~Presence of any suspicious pre-cancerous or cancerous lesions, or having cancer.~Being on medications that are immunosuppressive, may affect peripheral blood flow or may affect normal wound healing.~Being on medications that might cause photosensitivity.~Participation in any other clinical trial testing a device or drug.
|
18 Years
|
90 Years
|
All
|
No
|
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | assessing device related and general adverse events | On a weekly basis until the end of the 16 week treatment period |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wound Healing | Percent of wounds achieving complete wound closure, wound granulation and percent change in ulcer size/area | On a weekly basis until the end of the 16 week treatment period or until complete wound closure |
|
Leg Ulcer, Diabetes Mellitus, Diabetic Foot, Foot Ulcer, Diabetic Angiopathies, Vascular Diseases, Cardiovascular Diseases, Skin Ulcer, Skin Diseases, Diabetes Complications, Endocrine System Diseases, Diabetic Neuropathies, Foot Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>The treatment group will be treated with the MC-8XL laser device, emitting 808 nm laser beam with a green laser beam.~Intervention: MC-8XL low level laser device and Standard wound care | Device: MC-8XL low level laser device and Standard wound care<br>* The MC-8XL, a handheld Low Level Laser Therapy (LLLT) device, comprised of an infrared laser diode that generates wavelength of 808 nm and a green laser diode with a wavelength of 525 nm will be used to treat the experimental group.~Along with the active LLLT, generally accepted standard wound care procedures will be used during the clinical trial by a qualified study nurse or doctor. These procedures will include wound cleaning and drying before irradiation with the laser device (sham or active). Each ulcer will be also assessed and debrided if needed.~After irradiation, each ulcer will be dressed with saline gauze dressing and offloaded.<br>|
| Sham Comparator: Control group<br>The control group will receive treatment with a sham laser device, emitting a low power green light with inactive Infrared (IR) laser for indication only.~Intervention: Sham laser device and Standard wound care | Device: Sham laser device and Standard wound care<br>* The Sham device is of similar appearance, emitting only green light for indication with a wavelength of 525 nm of a low power, with inactive IR laser which will be used in the Control group.~Along with the sham device, the same generally accepted standard wound care procedures will be used.<br>|
|
Evaluation of Safety of Low Level Laser Device Treatment in Chronic Wounds
Study Overview
=================
Brief Summary
-----------------
This is a randomized, double blind, placebo-controlled study to evaluate the safety of the low level laser MC-8XL device treatment in subjects with an unsuccessfully treated Diabetic Foot Ulcer (DFU) that has been present for at least 3 months. Eligible subjects will be randomized to either Treatment group or Control group, following which, treatment of each subject will be provided by a qualified nurse at the clinic or in the home setting, everyday for up to 16 weeks. Study assessments and adverse events monitoring will be also performed throughout the study.
Official Title
-----------------
Evaluation of Safety of Low Level Laser MC-8XL Device Treatment in Chronic Wounds
Conditions
-----------------
Diabetic Foot Ulcer
Intervention / Treatment
-----------------
* Device: MC-8XL low level laser device and Standard wound care
* Device: Sham laser device and Standard wound care
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provide signed and dated Informed Consent Form Willing to comply with all study procedures and be available for the duration of the study Male or female, aged 18 to 90 Having a DFU of at least 3 months duration that had not improved after prior standard wound treatments HbA1c of <11.0 Size of wounds: 1-10 cm2 Having DFU of grades 2 or 3 according to Wagner's classification Exclusion Criteria: Immeasurable wounds or wounds that are unsuited to this laser treatment (usually due to the wound's location, e.g. in the area between the toes). Uncontrolled Diabetes defined as an HbA1c of > 11.0 Arterial insufficiency, Doppler vascular assessment (if needed- Ankle Brachial Index (ABI) < 0.6) Osteomyelitis in the bone. Photosensitivity Pregnancy Presence of any suspicious pre-cancerous or cancerous lesions, or having cancer. Being on medications that are immunosuppressive, may affect peripheral blood flow or may affect normal wound healing. Being on medications that might cause photosensitivity. Participation in any other clinical trial testing a device or drug.
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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>The treatment group will be treated with the MC-8XL laser device, emitting 808 nm laser beam with a green laser beam. Intervention: MC-8XL low level laser device and Standard wound care | Device: MC-8XL low level laser device and Standard wound care<br>* The MC-8XL, a handheld Low Level Laser Therapy (LLLT) device, comprised of an infrared laser diode that generates wavelength of 808 nm and a green laser diode with a wavelength of 525 nm will be used to treat the experimental group. Along with the active LLLT, generally accepted standard wound care procedures will be used during the clinical trial by a qualified study nurse or doctor. These procedures will include wound cleaning and drying before irradiation with the laser device (sham or active). Each ulcer will be also assessed and debrided if needed. After irradiation, each ulcer will be dressed with saline gauze dressing and offloaded.<br>|
| Sham Comparator: Control group<br>The control group will receive treatment with a sham laser device, emitting a low power green light with inactive Infrared (IR) laser for indication only. Intervention: Sham laser device and Standard wound care | Device: Sham laser device and Standard wound care<br>* The Sham device is of similar appearance, emitting only green light for indication with a wavelength of 525 nm of a low power, with inactive IR laser which will be used in the Control group. Along with the sham device, the same generally accepted standard wound care procedures will be used.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | assessing device related and general adverse events | On a weekly basis until the end of the 16 week treatment period |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wound Healing | Percent of wounds achieving complete wound closure, wound granulation and percent change in ulcer size/area | On a weekly basis until the end of the 16 week treatment period or until complete wound closure |
|
||
NCT04072978
|
Anterior Chamber Versus Scleral Fixated Intraocular Lens: Long-term Vision and Safety Outcomes
|
This is a prospective comparative non-randomized cohort study to understand the long-term vision outcomes, safety, and stability of anterior chamber intraocular lenses (AC IOLs) vs. scleral-fixated intraocular lenses (SF IOLs).
|
On the pre-operative visit, specular microscopy, biometry, applanation tonometry and ocular coherence tomography (OCT) will be performed. The patient will then undergo treatment as per surgeon's discussion/ decision with the patient for implantation of an AC-IOL or SF-IOL. Participation in the study will not impact the management plan in any way. Specular microscopy will be performed wit the CellChek XL (Konan Medical, Irvine, CA). Biometry will be performed with the IOLMASTER (Carl Ziess Meditec, Jena, Germany), and anterior segment and macular OCT will be performed with the Cirrus-HD OCT (Carl Zeiss Metidec, Jena, Germany). EC count, OCT (macula and anterior segment) and specular microscopy will be performed at baseline, week 1, month 1, month 6, 12 and 24.
|
Anterior Chamber Versus Scleral Fixated Intraocular Lens: Long-term Vision and Safety Outcomes
|
Corneal Endothelial Cell Loss, Secondary Intraocular Lens
|
* Device: Intraocular lens implantation
|
Inclusion Criteria:~Patients who are undergoing AC IOL or SF IOL implantation for any reason (including but not limited to aphakia, posterior capsular rupture, primary or secondary lens dislocation/ subluxation or IOL exchange).~Patients on whom imaging (specular microscopy, biometry and OCT) can be performed without delaying their treatment (i.e. based on availability of operator).~Decision makers able to provide informed consent.~Exclusion Criteria:~Inability to obtain adequate imaging, in the form of specular microscopy and OCT data at baseline.~Patients unable to attend follow-up visits.~Patients who have had a corneal transplant prior to secondary IOL implantation.
|
16 Years
|
99 Years
|
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial cell loss | Change in endothelial cell count from baseline compared to 24 months post-operatively. | Pre-operative (baseline) and 24 weeks post-operatively. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corrected distance visual acuity (CDVA) | CDVA will be measured using a standardized Early Treatment Diabetic Retinopathy Study (ETDRS) chart | Pre-operative (baseline), week 1, months 1, 6, 12 and 24 post-operatively. |
|
Corneal Endothelial Cell Loss, Corneal Diseases, Eye Diseases, Eye Manifestations, Postoperative Complications, Pathologic Processes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Intraocular lens implantation: AC IOL<br>Patients who are scheduled to undergo AC IOL (anterior chamber intraocular lens) implantation for any of the following indications:~primary or secondary aphakia~primary or secondary lens subluxation or dislocation | Device: Intraocular lens implantation<br>* Implantation of an intraocular lens using either an anterior chamber IOL or a scleral fixated IOL using the modified Yamane technique.<br>* Other names: IOL implantation;|
| Intraocular lens implantation: SF IOL<br>Patients who are scheduled to undergo SF IOL (scleral fixated intraocular lens) implantation for any of the following indications:~primary or secondary aphakia~primary or secondary lens subluxation or dislocation | Device: Intraocular lens implantation<br>* Implantation of an intraocular lens using either an anterior chamber IOL or a scleral fixated IOL using the modified Yamane technique.<br>* Other names: IOL implantation;|
|
Anterior Chamber Versus Scleral Fixated Intraocular Lens: Long-term Vision and Safety Outcomes
Study Overview
=================
Brief Summary
-----------------
This is a prospective comparative non-randomized cohort study to understand the long-term vision outcomes, safety, and stability of anterior chamber intraocular lenses (AC IOLs) vs. scleral-fixated intraocular lenses (SF IOLs).
Detailed Description
-----------------
On the pre-operative visit, specular microscopy, biometry, applanation tonometry and ocular coherence tomography (OCT) will be performed. The patient will then undergo treatment as per surgeon's discussion/ decision with the patient for implantation of an AC-IOL or SF-IOL. Participation in the study will not impact the management plan in any way. Specular microscopy will be performed wit the CellChek XL (Konan Medical, Irvine, CA). Biometry will be performed with the IOLMASTER (Carl Ziess Meditec, Jena, Germany), and anterior segment and macular OCT will be performed with the Cirrus-HD OCT (Carl Zeiss Metidec, Jena, Germany). EC count, OCT (macula and anterior segment) and specular microscopy will be performed at baseline, week 1, month 1, month 6, 12 and 24.
Official Title
-----------------
Anterior Chamber Versus Scleral Fixated Intraocular Lens: Long-term Vision and Safety Outcomes
Conditions
-----------------
Corneal Endothelial Cell Loss, Secondary Intraocular Lens
Intervention / Treatment
-----------------
* Device: Intraocular lens implantation
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients who are undergoing AC IOL or SF IOL implantation for any reason (including but not limited to aphakia, posterior capsular rupture, primary or secondary lens dislocation/ subluxation or IOL exchange). Patients on whom imaging (specular microscopy, biometry and OCT) can be performed without delaying their treatment (i.e. based on availability of operator). Decision makers able to provide informed consent. Exclusion Criteria: Inability to obtain adequate imaging, in the form of specular microscopy and OCT data at baseline. Patients unable to attend follow-up visits. Patients who have had a corneal transplant prior to secondary IOL implantation.
Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 99 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 |
| --- | --- |
| Intraocular lens implantation: AC IOL<br>Patients who are scheduled to undergo AC IOL (anterior chamber intraocular lens) implantation for any of the following indications: primary or secondary aphakia primary or secondary lens subluxation or dislocation | Device: Intraocular lens implantation<br>* Implantation of an intraocular lens using either an anterior chamber IOL or a scleral fixated IOL using the modified Yamane technique.<br>* Other names: IOL implantation;|
| Intraocular lens implantation: SF IOL<br>Patients who are scheduled to undergo SF IOL (scleral fixated intraocular lens) implantation for any of the following indications: primary or secondary aphakia primary or secondary lens subluxation or dislocation | Device: Intraocular lens implantation<br>* Implantation of an intraocular lens using either an anterior chamber IOL or a scleral fixated IOL using the modified Yamane technique.<br>* Other names: IOL implantation;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial cell loss | Change in endothelial cell count from baseline compared to 24 months post-operatively. | Pre-operative (baseline) and 24 weeks post-operatively. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corrected distance visual acuity (CDVA) | CDVA will be measured using a standardized Early Treatment Diabetic Retinopathy Study (ETDRS) chart | Pre-operative (baseline), week 1, months 1, 6, 12 and 24 post-operatively. |
|
||
NCT03044145
|
The Cultural Formulation Interview-Engagement Aid
|
This study consists of two projects:~Project 1: The study team will create and refine the CFI-EA by enrolling 3 clinicians and 9-12 patients to test the CFI-EA's feasibility and acceptability from patient and clinician feedback in a pre-pilot trial. The study team will first train clinicians in the CFI-EA by reading over the CFI-EA treatment manual and practicing how they can use it in behavioral simulations, and then check whether participants think they can do it (feasibility) and like it (acceptability) through standard measures. Following this the study team will revise the CFI-EA based on their feedback for the comparative open trial in Phase 2.~Project 2: The study team will test the revised CFI-EA against treatment as usual in a pilot trial. 3 clinicians and 12-15 patients will be enrolled in each arm. As before, the study team will first train clinicians in the revised CFI-EA by reading over the CFI-EA treatment manual and practicing how they can use it in behavioral simulations. Then, the study team will check whether participants think they can do it (feasibility) and like it (acceptability) through standard measures, and in addition will also explore any initial effects on communication behaviors among patients and clinicians and treatment engagement based on treatment retention.~The specific aims are:~For Project 1:~To pretest the CFI-EA intervention in a mental health setting through a pre-pilot open trial that explores communication mechanisms of action in terms of communication behavior and cultural content, and~To revise the CFI-EA intervention based on patient and clinician feedback on its feasibility and acceptability.~As real-world community stakeholders for whom the CFI-EA is being developed, patients and clinicians can provide helpful perspectives on how the CFI-EA can help clinicians tailor treatment plans around patient cultural views and treatment preferences to keep patients in care. The CFI-EA will be revised around areas of maximal agreement among patients and clinicians with the help of health disparities and communication experts.~For Project 2:~To test the revised CFI-EA's feasibility and acceptability among patients and clinicians in a pilot open trial against treatment as usual, and~To explore the relationship between the revised CFI-EA's effects on patient-clinician communication and treatment engagement.~The study team hypothesize that clinicians using the revised CFI-EA will show more positive communication behaviors compared to clinicians delivering treatment as usual and that CFI-EA patients will stay in treatment longer. Communication behaviors will be assessed through communication analysis techniques such as the Roter Interaction Analysis System.
|
Members of underserved racial/ethnic minority groups who participate more actively in the treatment process have almost three times the odds of staying in treatment and following up with appointments compared to standard treatment. Improving patient-clinician communication may therefore improve treatment engagement, from starting and participating in treatment actively to maintaining treatment for the successful resolution of symptoms and improvements in quality of life. Interventions that enhance communication behaviors by asking patients about their cultural views, using open-ended questions, establishing rapport, and using patient terms can increase patient participation and satisfaction. Interventions that expose clinicians to cultural content by asking patients about preferences for treatment, barriers to accessing services, the role of support from family or friends, and that encourage information exchange also improve treatment engagement. The goal of this study is to develop a communication intervention that improves treatment engagement for members of underserved racial and ethnic minority groups by improving clinician communication behaviors and exposing them to patient cultural content. Here, culture is understood as a dynamic process of meaning making between the patient and clinician. This intervention is not designed for patients belonging to a specific racial or ethnic group, but to improve general communication between patients and clinicians. The intervention improves communication by making communication behaviors and cultural content topics of explicit conversation rather than allowing clinicians to make cultural assumptions and take them for granted. We are focusing on racial and ethnic minorities because of significant evidence documenting disparities in health communication and care.~In session 1, the clinician does the full CFI in DSM-5 (~15 minutes) and then completes the full standard intake with information not already obtained through the CFI (~35 minutes). In sessions 2 and 3, the clinician integrates the CFI-EA (~5 minutes) within regular care in standard appointments. At JHMC, Session 2 lasts 60 minutes and is for treatment initiation. Session 3 lasts 20-30 minutes and is to check for treatment continuation. Because this is a grant to train in developing mental health interventions, the study team is following an NIMH model known as the Stage Model of Intervention Development. The first project is creating the intervention through patient and clinician feedback at JHMC and expert consensus with the K23 mentoring team. The second project is testing the intervention in a trial that compares the CFI-EA to treatment as usual. Patients for Project 1 will be recruited through a sample of convenience among patients accessing care on the days the research assistant is in the waiting area. For project 2, patients will be sampled consecutively by the JHMC's intake coordinator from the time that the project starts until the target enrollment is reached. The intake coordinator will keep a record of all patients who agree and do not agree to enroll in the study. Patients who agree to be enrolled during Project 2 will be recruited by the research assistant in the waiting area and then assigned randomly to either CFI-EA clinicians or treatment-as-usual clinicians based on a random number generator. The study team is using the same study measures in both projects to examine whether revisions to the CFI-EA conducted at the end of Project 1 show improvements in outcomes after Project 2.
|
The Cultural Formulation Interview-Engagement Aid for Mental Health Treatment
|
Communication, Adherence, Patient
|
* Behavioral: The Cultural Formulation Interview-Engagement Aid
* Behavioral: The Cultural Formulation Interview-Engagement Aid (Revised)
* Behavioral: Treatment as usual
|
For Project 1~Inclusion Criteria:~Male and female patients aged 18-80; Method of ascertainment: Self-report.~New patients at JHMC, referred by the intake coordinator; Method of ascertainment: Intake coordinator.~Willingness and ability to provide written informed consent after full explanation of study procedures. Method of ascertainment: RA informed consent interview that includes a capacity to consent screening form; Clinician referral.~Racial and ethnic minority (African-American, Latino/Hispanic, Asian-American/Pacific Islander, and Native American). Method of ascertainment: Self-report~Exclusion Criteria:~Actively suicidal or homicidal; Method of ascertainment: Self-report and clinician evaluation~In need of acute detoxification services; Method of ascertainment: Self-report and clinician evaluation~A condition that interferes with participation (i.e., dementia, mental retardation, or florid psychosis); Method of ascertainment: Clinician evaluation; patients ≥ 65 years of age will participate in a mini-cog exam.~Caucasian race; Method of ascertainment: self-report~For Project 2~Inclusion Criteria:~Male and female patients aged 18-80; Method of ascertainment: Self-report.~New patients at JHMC, referred by the intake coordinator; Method of ascertainment: Intake coordinator.~Willingness and ability to provide written informed consent after full explanation of study procedures. Method of ascertainment: RA informed consent interview that includes a capacity to consent screening form; Clinician referral.~Racial and ethnic minority (African-American, Latino/Hispanic, Asian-American/Pacific Islander, and Native American). Method of ascertainment: Self-report~Exclusion Criteria:~Actively suicidal or homicidal; Method of ascertainment: Self-report and clinician evaluation~In need of acute detoxification services; Method of ascertainment: Self-report and clinician evaluation~A condition that interferes with participation (i.e., dementia, mental retardation, or florid psychosis); Method of ascertainment: Clinician evaluation; patients ≥ 65 years of age will participate in a mini-cog exam.~Caucasian race; Method of ascertainment: self-report~Patients in Project 1 will be excluded from Participation in Project 2: Method of assessment: self-report and PI/RA evaluation.
|
18 Years
|
80 Years
|
All
|
No
|
Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This study follows an NIMH model known as the Stage Model of Intervention Development. The first project is creating a cross-cultural communication intervention designed to improve patient adherence in mental health services through patient and clinician feedback at JHMC and expert consensus with my K23 mentoring team. The second project is testing the intervention in a trial that compares the CFI-EA to treatment as usual.
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CFI-EA feasibility is defined as patient completion rates for all three sessions of the CFI-EA intervention. | CFI-EA feasibility is defined as patient completion rates for all three sessions of the CFI-EA intervention. | two months after the third session |
| CFI-EA acceptability is defined as patient scores on the CSQ-8. | CFI-EA acceptability is defined as patient scores on the CSQ-8. | the third session |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment engagement defined as the percentage of patients staying within treatment 2 months after the third and last session of the CFI-EA has been delivered. | Defined as the percentage of patients staying within treatment 2 months after the third and last session of the CFI-EA has been delivered. | 2 months after the last session of the CFI-EA |
|
Cultural Competence, Patient-Clinician communication
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Project 1: The Cultural Formulation Interview-Engagement Aid<br>The first project is creating the intervention through patient and clinician feedback at JHMC and expert consensus with the K23 mentoring team. The CFI-EA is a list of questions that clinicians can use to customize patient treatment plans based on a cultural competence assessment. | Behavioral: The Cultural Formulation Interview-Engagement Aid<br>* Culture affects how all people communicate and understand the world. Culture is important because patients and clinicians from different cultural backgrounds may have different preferences for communication. Mismatch in the clinician's approach and the patient's expectations of care can lead to patient dissatisfaction and discontinuation with treatment. Patients and clinicians may also have different views about what caused an illness, how it functions, what makes it better or worse, and the types of treatment needed. The CFI-EA is a series of questions over three sessions that clinicians can use to clarify patient views about treatment and communication so that patients stay in treatment longer. Clinicians can use the CFI-EA to customize their current treatment plans.<br>|
| Experimental: Project 2: The Cultural Formulation Interview-Engagement Aid<br>In this arm the study team will test the revised CFI-EA against treatment as usual in a pilot trial. | Behavioral: The Cultural Formulation Interview-Engagement Aid (Revised)<br>* The study team will revise the CFI-EA based on patient and clinician feedback. The study team expects that the revisions will consist of changes to the questions such as adding or subtracting specific items or revising the wording of the content. The study team do not anticipate other changes, though we will let our empirical data analyses guide revisions in consultation with the K23 mentor team.<br>|
| Active Comparator: Project 2: Treatment as usual<br>Treatment as usual at JHMC consists of clinicians creating treatment plans for patients without any specific training in medical communication or treatment negotiation. | Behavioral: Treatment as usual<br>* Standard mental health treatment at FHMC<br>|
|
The Cultural Formulation Interview-Engagement Aid
Study Overview
=================
Brief Summary
-----------------
This study consists of two projects: Project 1: The study team will create and refine the CFI-EA by enrolling 3 clinicians and 9-12 patients to test the CFI-EA's feasibility and acceptability from patient and clinician feedback in a pre-pilot trial. The study team will first train clinicians in the CFI-EA by reading over the CFI-EA treatment manual and practicing how they can use it in behavioral simulations, and then check whether participants think they can do it (feasibility) and like it (acceptability) through standard measures. Following this the study team will revise the CFI-EA based on their feedback for the comparative open trial in Phase 2. Project 2: The study team will test the revised CFI-EA against treatment as usual in a pilot trial. 3 clinicians and 12-15 patients will be enrolled in each arm. As before, the study team will first train clinicians in the revised CFI-EA by reading over the CFI-EA treatment manual and practicing how they can use it in behavioral simulations. Then, the study team will check whether participants think they can do it (feasibility) and like it (acceptability) through standard measures, and in addition will also explore any initial effects on communication behaviors among patients and clinicians and treatment engagement based on treatment retention. The specific aims are: For Project 1: To pretest the CFI-EA intervention in a mental health setting through a pre-pilot open trial that explores communication mechanisms of action in terms of communication behavior and cultural content, and To revise the CFI-EA intervention based on patient and clinician feedback on its feasibility and acceptability. As real-world community stakeholders for whom the CFI-EA is being developed, patients and clinicians can provide helpful perspectives on how the CFI-EA can help clinicians tailor treatment plans around patient cultural views and treatment preferences to keep patients in care. The CFI-EA will be revised around areas of maximal agreement among patients and clinicians with the help of health disparities and communication experts. For Project 2: To test the revised CFI-EA's feasibility and acceptability among patients and clinicians in a pilot open trial against treatment as usual, and To explore the relationship between the revised CFI-EA's effects on patient-clinician communication and treatment engagement. The study team hypothesize that clinicians using the revised CFI-EA will show more positive communication behaviors compared to clinicians delivering treatment as usual and that CFI-EA patients will stay in treatment longer. Communication behaviors will be assessed through communication analysis techniques such as the Roter Interaction Analysis System.
Detailed Description
-----------------
Members of underserved racial/ethnic minority groups who participate more actively in the treatment process have almost three times the odds of staying in treatment and following up with appointments compared to standard treatment. Improving patient-clinician communication may therefore improve treatment engagement, from starting and participating in treatment actively to maintaining treatment for the successful resolution of symptoms and improvements in quality of life. Interventions that enhance communication behaviors by asking patients about their cultural views, using open-ended questions, establishing rapport, and using patient terms can increase patient participation and satisfaction. Interventions that expose clinicians to cultural content by asking patients about preferences for treatment, barriers to accessing services, the role of support from family or friends, and that encourage information exchange also improve treatment engagement. The goal of this study is to develop a communication intervention that improves treatment engagement for members of underserved racial and ethnic minority groups by improving clinician communication behaviors and exposing them to patient cultural content. Here, culture is understood as a dynamic process of meaning making between the patient and clinician. This intervention is not designed for patients belonging to a specific racial or ethnic group, but to improve general communication between patients and clinicians. The intervention improves communication by making communication behaviors and cultural content topics of explicit conversation rather than allowing clinicians to make cultural assumptions and take them for granted. We are focusing on racial and ethnic minorities because of significant evidence documenting disparities in health communication and care. In session 1, the clinician does the full CFI in DSM-5 ( 15 minutes) and then completes the full standard intake with information not already obtained through the CFI ( 35 minutes). In sessions 2 and 3, the clinician integrates the CFI-EA ( 5 minutes) within regular care in standard appointments. At JHMC, Session 2 lasts 60 minutes and is for treatment initiation. Session 3 lasts 20-30 minutes and is to check for treatment continuation. Because this is a grant to train in developing mental health interventions, the study team is following an NIMH model known as the Stage Model of Intervention Development. The first project is creating the intervention through patient and clinician feedback at JHMC and expert consensus with the K23 mentoring team. The second project is testing the intervention in a trial that compares the CFI-EA to treatment as usual. Patients for Project 1 will be recruited through a sample of convenience among patients accessing care on the days the research assistant is in the waiting area. For project 2, patients will be sampled consecutively by the JHMC's intake coordinator from the time that the project starts until the target enrollment is reached. The intake coordinator will keep a record of all patients who agree and do not agree to enroll in the study. Patients who agree to be enrolled during Project 2 will be recruited by the research assistant in the waiting area and then assigned randomly to either CFI-EA clinicians or treatment-as-usual clinicians based on a random number generator. The study team is using the same study measures in both projects to examine whether revisions to the CFI-EA conducted at the end of Project 1 show improvements in outcomes after Project 2.
Official Title
-----------------
The Cultural Formulation Interview-Engagement Aid for Mental Health Treatment
Conditions
-----------------
Communication, Adherence, Patient
Intervention / Treatment
-----------------
* Behavioral: The Cultural Formulation Interview-Engagement Aid
* Behavioral: The Cultural Formulation Interview-Engagement Aid (Revised)
* Behavioral: Treatment as usual
Participation Criteria
=================
Eligibility Criteria
-----------------
For Project 1 Inclusion Criteria: Male and female patients aged 18-80; Method of ascertainment: Self-report. New patients at JHMC, referred by the intake coordinator; Method of ascertainment: Intake coordinator. Willingness and ability to provide written informed consent after full explanation of study procedures. Method of ascertainment: RA informed consent interview that includes a capacity to consent screening form; Clinician referral. Racial and ethnic minority (African-American, Latino/Hispanic, Asian-American/Pacific Islander, and Native American). Method of ascertainment: Self-report Exclusion Criteria: Actively suicidal or homicidal; Method of ascertainment: Self-report and clinician evaluation In need of acute detoxification services; Method of ascertainment: Self-report and clinician evaluation A condition that interferes with participation (i.e., dementia, mental retardation, or florid psychosis); Method of ascertainment: Clinician evaluation; patients ≥ 65 years of age will participate in a mini-cog exam. Caucasian race; Method of ascertainment: self-report For Project 2 Inclusion Criteria: Male and female patients aged 18-80; Method of ascertainment: Self-report. New patients at JHMC, referred by the intake coordinator; Method of ascertainment: Intake coordinator. Willingness and ability to provide written informed consent after full explanation of study procedures. Method of ascertainment: RA informed consent interview that includes a capacity to consent screening form; Clinician referral. Racial and ethnic minority (African-American, Latino/Hispanic, Asian-American/Pacific Islander, and Native American). Method of ascertainment: Self-report Exclusion Criteria: Actively suicidal or homicidal; Method of ascertainment: Self-report and clinician evaluation In need of acute detoxification services; Method of ascertainment: Self-report and clinician evaluation A condition that interferes with participation (i.e., dementia, mental retardation, or florid psychosis); Method of ascertainment: Clinician evaluation; patients ≥ 65 years of age will participate in a mini-cog exam. Caucasian race; Method of ascertainment: self-report Patients in Project 1 will be excluded from Participation in Project 2: Method of assessment: self-report and PI/RA evaluation.
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: Health Services Research
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This study follows an NIMH model known as the Stage Model of Intervention Development. The first project is creating a cross-cultural communication intervention designed to improve patient adherence in mental health services through patient and clinician feedback at JHMC and expert consensus with my K23 mentoring team. The second project is testing the intervention in a trial that compares the CFI-EA to treatment as usual.
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Project 1: The Cultural Formulation Interview-Engagement Aid<br>The first project is creating the intervention through patient and clinician feedback at JHMC and expert consensus with the K23 mentoring team. The CFI-EA is a list of questions that clinicians can use to customize patient treatment plans based on a cultural competence assessment. | Behavioral: The Cultural Formulation Interview-Engagement Aid<br>* Culture affects how all people communicate and understand the world. Culture is important because patients and clinicians from different cultural backgrounds may have different preferences for communication. Mismatch in the clinician's approach and the patient's expectations of care can lead to patient dissatisfaction and discontinuation with treatment. Patients and clinicians may also have different views about what caused an illness, how it functions, what makes it better or worse, and the types of treatment needed. The CFI-EA is a series of questions over three sessions that clinicians can use to clarify patient views about treatment and communication so that patients stay in treatment longer. Clinicians can use the CFI-EA to customize their current treatment plans.<br>|
| Experimental: Project 2: The Cultural Formulation Interview-Engagement Aid<br>In this arm the study team will test the revised CFI-EA against treatment as usual in a pilot trial. | Behavioral: The Cultural Formulation Interview-Engagement Aid (Revised)<br>* The study team will revise the CFI-EA based on patient and clinician feedback. The study team expects that the revisions will consist of changes to the questions such as adding or subtracting specific items or revising the wording of the content. The study team do not anticipate other changes, though we will let our empirical data analyses guide revisions in consultation with the K23 mentor team.<br>|
| Active Comparator: Project 2: Treatment as usual<br>Treatment as usual at JHMC consists of clinicians creating treatment plans for patients without any specific training in medical communication or treatment negotiation. | Behavioral: Treatment as usual<br>* Standard mental health treatment at FHMC<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CFI-EA feasibility is defined as patient completion rates for all three sessions of the CFI-EA intervention. | CFI-EA feasibility is defined as patient completion rates for all three sessions of the CFI-EA intervention. | two months after the third session |
| CFI-EA acceptability is defined as patient scores on the CSQ-8. | CFI-EA acceptability is defined as patient scores on the CSQ-8. | the third session |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment engagement defined as the percentage of patients staying within treatment 2 months after the third and last session of the CFI-EA has been delivered. | Defined as the percentage of patients staying within treatment 2 months after the third and last session of the CFI-EA has been delivered. | 2 months after the last session of the CFI-EA |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cultural Competence, Patient-Clinician communication
|
|
NCT03504254
|
A fMRI Study of Compressive Spinal Cord
|
Cervical myelopathy (CM), a chronically compressive spinal cord lesion, is the most common cause of non-traumatic paraparesis/quadriparesis among the elderly. Hong Kong is facing a heavy social economic burden from CM with the rapidly aging population. Surgical decompression is considered as the mainstay of the treatment for CM patients to relieve their symptoms and signs. Yet the surgical outcome is not always satisfactory. There is a pressing need for understanding the exact mechanism of surgical decompression on the recovery of myelopathic cord in order to improve the prognosis of CM patients in near future.This project will evaluate neuronal activities and axon regeneration by longitudinally monitoring at time zero, 3 and 6 month after the surgery in CM patients using UTE, BOLD-fMRI and DTI, and to investigate the relationship of preoperative neuronal activities of myelopathic cord with axon regeneration.
|
This study aims to monitor the structural and functional changes of chronically compressed spinal cords longitudinally after surgical decompression in vivo. Three kinds of MRI techniques will be used in this study. These are (1) axial T1-weighted (T1WI) and T2-weighted imaging (T2WI), UTE MRI, (2) BOLD-based fMRI, and (3) diffusion tensor imaging (DTI). To quantitatively investigate the structural deficits, T1/T2 MRIs will delineate the gross morphology of the spinal cord, CSF, and surrounding anatomical structures, while DTI will quantify the fiber orientation and integrity within the spinal cord. BOLD-based functional MRIs will assess the local hemodynamic changes and neuron activities in response to the motor or sensory stimulation along the C3 to C8 spinal nerve levels. The MRI evaluations will be applied to the same cervical myelopathy (CM) patient before surgery and 3 and 6 months post-surgery, when clinical recovery reaches a plateau9. Clinical examination will include neurological evaluation, Japanese Orthopaedic Association (JOA) scoring assessment, and clinical electrophysiological evaluation.
|
Plasticity of Chronically Compressive Spinal Cord After Surgical Decompression - A fMRI Study
|
Orthopedic Disorder of Spine, Neurologic Disorder
|
* Diagnostic Test: MRI examination
|
Inclusion Criteria:~The inclusion criteria are a clinical diagnosis of CM including the signs of corticospinal lesion/s together with the appropriate radiographic findings.~Exclusion Criteria:~Patients with acute spinal cord injuries, prior spinal intervention or claustrophobia will be excluded.
|
18 Years
|
90 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DTI indics | The mean diffusivities and fractional anisotropy will be measured in the DTI | Change between Enrollment and one year after surgery. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fMRI connextivity | Functional connectivity will be examined by calculating the averaged correlation coefficient of all regions of interest (ROIs) in gray matters. | Change between Enrollment and one year after surgery. |
|
cervical spondylotic myelopathy, diffusion tensor imaging, functional magnetic resonance imaging
|
Musculoskeletal Diseases, Spinal Diseases, Nervous System Diseases, Bone Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CSM<br>A total of 50 CM patients requiring surgical decompression will be recruited. The inclusion criteria are a clinical diagnosis of CM including the signs of corticospinal lesions together with the appropriate radiographic findings. Patients with acute spinal cord injuries, prior spinal intervention or claustrophobia will be excluded. | Diagnostic Test: MRI examination<br>* Three kinds of MRI techniques will be used in this study. These are (1) axial T1-weighted (T1WI) and T2-weighted imaging (T2WI), UTE MRI, (2) BOLD-based fMRI, and (3) diffusion tensor imaging (DTI).<br>|
|
A fMRI Study of Compressive Spinal Cord
Study Overview
=================
Brief Summary
-----------------
Cervical myelopathy (CM), a chronically compressive spinal cord lesion, is the most common cause of non-traumatic paraparesis/quadriparesis among the elderly. Hong Kong is facing a heavy social economic burden from CM with the rapidly aging population. Surgical decompression is considered as the mainstay of the treatment for CM patients to relieve their symptoms and signs. Yet the surgical outcome is not always satisfactory. There is a pressing need for understanding the exact mechanism of surgical decompression on the recovery of myelopathic cord in order to improve the prognosis of CM patients in near future.This project will evaluate neuronal activities and axon regeneration by longitudinally monitoring at time zero, 3 and 6 month after the surgery in CM patients using UTE, BOLD-fMRI and DTI, and to investigate the relationship of preoperative neuronal activities of myelopathic cord with axon regeneration.
Detailed Description
-----------------
This study aims to monitor the structural and functional changes of chronically compressed spinal cords longitudinally after surgical decompression in vivo. Three kinds of MRI techniques will be used in this study. These are (1) axial T1-weighted (T1WI) and T2-weighted imaging (T2WI), UTE MRI, (2) BOLD-based fMRI, and (3) diffusion tensor imaging (DTI). To quantitatively investigate the structural deficits, T1/T2 MRIs will delineate the gross morphology of the spinal cord, CSF, and surrounding anatomical structures, while DTI will quantify the fiber orientation and integrity within the spinal cord. BOLD-based functional MRIs will assess the local hemodynamic changes and neuron activities in response to the motor or sensory stimulation along the C3 to C8 spinal nerve levels. The MRI evaluations will be applied to the same cervical myelopathy (CM) patient before surgery and 3 and 6 months post-surgery, when clinical recovery reaches a plateau9. Clinical examination will include neurological evaluation, Japanese Orthopaedic Association (JOA) scoring assessment, and clinical electrophysiological evaluation.
Official Title
-----------------
Plasticity of Chronically Compressive Spinal Cord After Surgical Decompression - A fMRI Study
Conditions
-----------------
Orthopedic Disorder of Spine, Neurologic Disorder
Intervention / Treatment
-----------------
* Diagnostic Test: MRI examination
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The inclusion criteria are a clinical diagnosis of CM including the signs of corticospinal lesion/s together with the appropriate radiographic findings. Exclusion Criteria: Patients with acute spinal cord injuries, prior spinal intervention or claustrophobia will be excluded.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CSM<br>A total of 50 CM patients requiring surgical decompression will be recruited. The inclusion criteria are a clinical diagnosis of CM including the signs of corticospinal lesions together with the appropriate radiographic findings. Patients with acute spinal cord injuries, prior spinal intervention or claustrophobia will be excluded. | Diagnostic Test: MRI examination<br>* Three kinds of MRI techniques will be used in this study. These are (1) axial T1-weighted (T1WI) and T2-weighted imaging (T2WI), UTE MRI, (2) BOLD-based fMRI, and (3) diffusion tensor imaging (DTI).<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DTI indics | The mean diffusivities and fractional anisotropy will be measured in the DTI | Change between Enrollment and one year after surgery. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fMRI connextivity | Functional connectivity will be examined by calculating the averaged correlation coefficient of all regions of interest (ROIs) in gray matters. | Change between Enrollment and one year after surgery. |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cervical spondylotic myelopathy, diffusion tensor imaging, functional magnetic resonance imaging
|
|
NCT03799848
|
A Single Dose Study of Oral Vadadustat in Subjects With Normal and Impaired Hepatic Function
|
This is a Phase I open-label study to evaluate the pharmacokinetic (PK) profile of a single oral dose of vadadustat in subjects with hepatic impairment(HI) compared to healthy matched control subjects with normal hepatic function.
|
This is an open label, parallel-group, single dose, Phase 1 study to evaluate the PK profile, safety, and tolerability of a single oral 450 mg dose of vadadustat in subjects with hepatic impairment relative to control subjects with normal hepatic function. The study will enroll up to 24 subjects in 3 groups of 8 subjects at 2 study sites. Blood samples for vadadustat PK and its metabolites will be collected pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 60, and 72 hours post-dose.
|
Phase 1, Open-Label, Parallel-Group, Pharmacokinetic Single Dose Study of Oral Vadadustat in Subjects With Normal and Impaired Hepatic Function
|
Hepatic Impairment
|
* Drug: Vadadustat
|
Inclusion Criteria (All groups):~Male or female subjects between ≥18 years and ≤70 years of age~Have a body weight ≥45 kg and body mass index (BMI) ≥18.5 kg/m2 to 40.0 kg/m2~Additional Group-Specific Inclusion Criteria:~Group 1 (Moderate Hepatic Impairment Subjects):~Presence of Moderate hepatic impairment (Child-Pugh Class B)~Group 2 (Normal Hepatic Function Subjects):~Normal hepatic function~Group 3 (Mild Hepatic Impairment Subjects):~Presence of mild hepatic impairment ( Child-Pugh Class A)~Exclusion Criteria (all groups):~Renal impairment ≥ Stage 3 (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) study equation)~Any history of active malignancy within 2 years prior to or during screening, except for treated basal cell carcinoma of skin, curatively resected squamous cell carcinoma of skin, or cervical carcinoma in situ; any history of tuberculosis and/or prophylaxis for tuberculosis~Positive test for human immunodeficiency virus (HIV) antibody at Screening.~Hepatic or other organ or cell transplant~Subjects with alcoholic cirrhosis must be sober for a minimum of 6 months
|
18 Years
|
70 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Basic Science
Intervention Model: Sequential Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve from dosing to last measurable concentration (AUClast) | | Day 1, Day 4 |
| Area under the concentration-time curve from dosing to infinity (AUCinf) | | Day 1, Day 4 |
| Observed maximum concentration (Cmax). | | Day 1, Day 4 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to reach Cmax of vadadustat | | Day 1, Day 4 |
| Apparent total body clearance (CL/F) of vadadustat | | Day 1, Day 4 |
| Apparent volume of distribution (Vd/F) of vadadustat | | Day 1, Day 4 |
| Terminal half-life (t1/2) of vadadustat | | Day 1, Day 4 |
| Time to reach Tmax of vadadustat | | Day 1, Day 4 |
| Assessment of Treatment-Emergent Adverse Events (TEAEs) as reported by study subjects | | Up to 9 Weeks |
| Cmax related to free drug (Cmax, free) of Vadadustat Unbound | | Day 1, Day 4 |
| AUClast related to free drug (AUClast, free) of Vadadustat Unbound | | Day 1, Day 4 |
| AUCinf related to free drug (AUCinf, free) of Vadadustat Unbound | | Day 1, Day 4 |
| CL/F related to free drug (CL/Ffree) of Vadadustat Unbound | | Day 1, Day 4 |
| Terminal half-life (t1/2) of Vadadustat Unbound | | Day 1, Day 4 |
| The area under the concentration-time curve from dosing to last measurable concentration (AUClast) of Vadadustat metabolites | | Day 1, Day 4 |
| The area under the concentration-time curve from dosing to infinity (AUCinf) of Vadadustat metabolite | | Day 1, Day 4 |
| Time to reach Cmax of vadadustat metabolites | | Day 1, Day 4 |
| Terminal half-life (t1/2) of Vadadustat metabolites | | Day 1, Day 4 |
| Renal clearance (CLr) of Vadadustat/metabolite(s) Urine | | Day 1, Day 4 |
| Cumulative amount of drug excreted (Ae) of Vadadustat/metabolite(s) Urine | | Day 1, Day 4 |
| Cumulative fraction of drug excreted (Fe) of Vadadustat/metabolite(s) Urine | | Day 1, Day 4 |
|
Hepatic impairment, Healthy subjects, Child-pugh, Vadadustat
|
Liver Diseases, Digestive System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vadadustat<br>Group 1: Subjects with moderately impaired hepatic function (Child-Pugh Class B) Group 2: Normal healthy volunteers Group 3: Subjects with mildly impaired hepatic function (Child-Pugh Class A) | Drug: Vadadustat<br>* Oral tablet<br>* Other names: AKB-6548;|
|
A Single Dose Study of Oral Vadadustat in Subjects With Normal and Impaired Hepatic Function
Study Overview
=================
Brief Summary
-----------------
This is a Phase I open-label study to evaluate the pharmacokinetic (PK) profile of a single oral dose of vadadustat in subjects with hepatic impairment(HI) compared to healthy matched control subjects with normal hepatic function.
Detailed Description
-----------------
This is an open label, parallel-group, single dose, Phase 1 study to evaluate the PK profile, safety, and tolerability of a single oral 450 mg dose of vadadustat in subjects with hepatic impairment relative to control subjects with normal hepatic function. The study will enroll up to 24 subjects in 3 groups of 8 subjects at 2 study sites. Blood samples for vadadustat PK and its metabolites will be collected pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 60, and 72 hours post-dose.
Official Title
-----------------
Phase 1, Open-Label, Parallel-Group, Pharmacokinetic Single Dose Study of Oral Vadadustat in Subjects With Normal and Impaired Hepatic Function
Conditions
-----------------
Hepatic Impairment
Intervention / Treatment
-----------------
* Drug: Vadadustat
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria (All groups): Male or female subjects between ≥18 years and ≤70 years of age Have a body weight ≥45 kg and body mass index (BMI) ≥18.5 kg/m2 to 40.0 kg/m2 Additional Group-Specific Inclusion Criteria: Group 1 (Moderate Hepatic Impairment Subjects): Presence of Moderate hepatic impairment (Child-Pugh Class B) Group 2 (Normal Hepatic Function Subjects): Normal hepatic function Group 3 (Mild Hepatic Impairment Subjects): Presence of mild hepatic impairment ( Child-Pugh Class A) Exclusion Criteria (all groups): Renal impairment ≥ Stage 3 (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) study equation) Any history of active malignancy within 2 years prior to or during screening, except for treated basal cell carcinoma of skin, curatively resected squamous cell carcinoma of skin, or cervical carcinoma in situ; any history of tuberculosis and/or prophylaxis for tuberculosis Positive test for human immunodeficiency virus (HIV) antibody at Screening. Hepatic or other organ or cell transplant Subjects with alcoholic cirrhosis must be sober for a minimum of 6 months
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?
-----------------
Design Details
Primary Purpose: Basic Science
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vadadustat<br>Group 1: Subjects with moderately impaired hepatic function (Child-Pugh Class B) Group 2: Normal healthy volunteers Group 3: Subjects with mildly impaired hepatic function (Child-Pugh Class A) | Drug: Vadadustat<br>* Oral tablet<br>* Other names: AKB-6548;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve from dosing to last measurable concentration (AUClast) | | Day 1, Day 4 |
| Area under the concentration-time curve from dosing to infinity (AUCinf) | | Day 1, Day 4 |
| Observed maximum concentration (Cmax). | | Day 1, Day 4 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to reach Cmax of vadadustat | | Day 1, Day 4 |
| Apparent total body clearance (CL/F) of vadadustat | | Day 1, Day 4 |
| Apparent volume of distribution (Vd/F) of vadadustat | | Day 1, Day 4 |
| Terminal half-life (t1/2) of vadadustat | | Day 1, Day 4 |
| Time to reach Tmax of vadadustat | | Day 1, Day 4 |
| Assessment of Treatment-Emergent Adverse Events (TEAEs) as reported by study subjects | | Up to 9 Weeks |
| Cmax related to free drug (Cmax, free) of Vadadustat Unbound | | Day 1, Day 4 |
| AUClast related to free drug (AUClast, free) of Vadadustat Unbound | | Day 1, Day 4 |
| AUCinf related to free drug (AUCinf, free) of Vadadustat Unbound | | Day 1, Day 4 |
| CL/F related to free drug (CL/Ffree) of Vadadustat Unbound | | Day 1, Day 4 |
| Terminal half-life (t1/2) of Vadadustat Unbound | | Day 1, Day 4 |
| The area under the concentration-time curve from dosing to last measurable concentration (AUClast) of Vadadustat metabolites | | Day 1, Day 4 |
| The area under the concentration-time curve from dosing to infinity (AUCinf) of Vadadustat metabolite | | Day 1, Day 4 |
| Time to reach Cmax of vadadustat metabolites | | Day 1, Day 4 |
| Terminal half-life (t1/2) of Vadadustat metabolites | | Day 1, Day 4 |
| Renal clearance (CLr) of Vadadustat/metabolite(s) Urine | | Day 1, Day 4 |
| Cumulative amount of drug excreted (Ae) of Vadadustat/metabolite(s) Urine | | Day 1, Day 4 |
| Cumulative fraction of drug excreted (Fe) of Vadadustat/metabolite(s) Urine | | Day 1, Day 4 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatic impairment, Healthy subjects, Child-pugh, Vadadustat
|
NCT04875598
|
COMPARISON OF LAPAROSCOPY AND ULTRASOUND ASSISTED TRANSVERSUS ABDOMINIS PLANE BLOCK METHODS IN LAPAROSCOPIC TOTAL EXTRAPERITONEAL HERNIA REPAIR
|
While the rate of inguinal hernia repair operations in England is 10 per 100,000 people. The rate in the United States is found to be 28 per 100,000 people. Today, the effectiveness between open repair and laparoscopic repair in inguinal hernia repair is still debated. Laparoscopic approach offers many advantages over open repair. Regional blocks have an important place in the multi-modal anesthesia approach applied to reduce postoperative pain. In this sense, the Transversus Abdominis Plane Block (TAPB) emerges as an effective regional anesthesia method that reduces postoperative pain. This method can be applied with the help of ultrasound or laparoscopy. The aim of this study is to compare the ultrasound-assisted TAPB application and Laparoscopy-assisted TAPB application in Total Extraperitoneal hernia repair (TEP) to reveal the effects of postoperative pain.~A total of 60 patients will be included in the study; 30 of these patients will be injected with local anesthetic into the fascia between the transversus abdominis and internal oblique muscles with the help of ultrasound from the designated area (Before the operation starts, TAPB with 20 ml 0.25 % bupivacaine will be applied to the surgical side under ultrasonography); In the other 30 patients, local anesthetic injection will be made to the same area under laparoscopic direct vision. 50 mg Bupivacaine (0.25 % 20 ml bupivacaine solution) has been determined as the application dose and this amount will be applied in both groups.~10 cm visual analog scale (VAS) will be used in postoperative pain follow-up. 50 mg intravenous tramadol will be administered to patients with VAS > 4 and tramadol will be supplemented to 100 mg in patients with high pain levels after 30 minutes. Oral non-steroidal anti-inflammatory will be given at the postoperative 8th hour. Patients whose pain persists despite current therapy will be given 25 mg of meperidine intravenously as a rescue analgesic. The doses of analgesic administered in the postoperative period and the hours of administration will be recorded
|
While the rate of inguinal hernia repair operations in England is 10 per 100,000 people. The rate in the United States is found to be 28 per 100,000 people. Today, the effectiveness between open repair and laparoscopic repair in inguinal hernia repair is still debated. Laparoscopic approach offers many advantages over open repair. These are topics such as postoperative pain, quick recovery, and shortening of returning to work. Postoperative pain is the most important determinant of recovery after abdominal surgeries. Postoperative pain can be explained by two pathways connected to the peritoneum; The first is the parietal peritoneum, which has a very rich innervation, and the other is the visceral peritoneum stimulated by the vagus. In order to eliminate these peritoneal pains, surgeons have been injecting local anesthetic into various areas on the anterior abdominal wall and intraperitoneal space since 1950. Regional blocks have an important place in the multi-modal anesthesia approach applied to reduce postoperative pain. In this sense, the Transversus Abdominis Plane Block (TAPB) emerges as an effective regional anesthesia method that reduces postoperative pain. TAPB; It is a type of regional anesthesia applied to the facial plane between the internal oblique muscle and the transversus abdominis muscles, targeting the somatic nerves (T6 - L1). This method can be applied with the help of ultrasound or laparoscopy. The aim of this study is to compare the ultrasound-assisted TAPB application and Laparoscopy-assisted TAPB application in Total Extraperitoneal hernia repair (TEP) to reveal the effects of postoperative pain.~TEP will be performed with 2-3 mg / kg propofol, 2 mcg / kg fentanyl and 0.6 mg / kg rocuronium in patients who will undergo anesthesia induction with BIS < 60, after intubation, 40 % oxygen / 1.5 - 2 % sevoflurane inhalation will be applied to keep the BIS value between 40 - 60 in 60 % air. Before the operation starts, TAPB will be made with 20 ml 0.25 % bupivacaine in the direction of ultrasonography on the side to be operated. During the operation, if there is a 20 % increase in blood pressure and heart rate from baseline, 0.5 mcg / kg intravenous fentanyl will be administered and the administered fentanyl dose will be recorded. 1gr paracetamol 30 minutes before the end of the operation and 4 mg ondansetron 15 minutes before the end of the operation will be administered intravenously. With the help of a 22 G injector, local anesthetic injection will be made from the anterior to the area where the midaxillary line intersects the Bogros area. Digital examination will be performed to define the injection site and the injection area will be determined.~A total of 60 patients will be included in the study; 30 of these patients will be injected with local anesthetic into the fascia between the transversus abdominis and internal oblique muscles with the help of ultrasound from the designated area (Before the operation starts, TAPB with 20 ml 0.25 % bupivacaine will be applied to the surgical side under ultrasonography); In the other 30 patients, local anesthetic injection will be made to the same area under laparoscopic direct vision. 50 mg Bupivacaine (0.25 % 20 ml bupivacaine solution) has been determined as the application dose and this amount will be applied in both groups. Bart 3D anatomical polypropylene patch will be used in both groups and the patch will be attached with the help of 1 absorbable tacker. Carbon dioxide gas will be given to the preperitoneal area at a rate of 4 - 6 L / min and at a pressure of 15 mm Hg. 3 trocars will be used; One 10 mm camera trocar and two 5 mm working trocars will be entered through the midline below the navel. At the end of the operation, the patients will be extubated by antagonizing the muscle relaxant effect with 0.02 mg / kg atropine and 0.05 mg / kg neostigmine. 10 cm visual analog scale (VAS) will be used in postoperative pain follow-up. 50 mg intravenous tramadol will be administered to patients with VAS > 4 and tramadol will be supplemented to 100 mg in patients with high pain levels after 30 minutes. Oral non-steroidal anti-inflammatory will be given at the postoperative 8th hour. Patients whose pain persists despite current therapy will be given 25 mg of meperidine intravenously as a rescue analgesic. The doses of analgesic administered in the postoperative period and the hours of administration will be recorded.
|
COMPARISON OF LAPAROSCOPY AND ULTRASOUND ASSISTED TRANSVERSUS ABDOMINIS PLANE BLOCK METHODS IN LAPAROSCOPIC TOTAL EXTRAPERITONEAL HERNIA REPAIR
|
Postoperative Pain, Inguinal Hernia, Transversus Abdominis Plane Block
|
* Procedure: Ultrasound assisted - Laparoscopy assisted Transversus Abdominis Plane Block
|
Inclusion Criteria:~Patients over the age of 18~Patients who underwent total extraperitoneal hernia repair~Patients without any postoperative complications~Patients who cannot be drained for any reason~Exclusion Criteria:~Patients who underwent another hernia repair technique during surgery for any reason.~Patients who do not want to participate in the study~Patients with any complications after surgery
|
18 Years
|
90 Years
|
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: A total of 60 patients will be included in the study; Group 1: 30 patients will be injected with local anesthetic into the fascia between the transversus abdominis and internal oblique muscles with the help of ultrasound from the designated area (Before the operation starts, TAPBwith 20 ml 0.25 % bupivacaine will be applied to the surgical side under ultrasonography)~Group 2: 30 patients, local anesthetic injection will be made to the same area under laparoscopic direct vision. 50 mg Bupivacaine (0.25 % 20 ml bupivacaine solution) has been determined as the application dose and this amount will be applied in both groups.
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative pain | 10 cm visual analog scale (VAS) will be used in postoperative pain follow-up. 10: too much pain , 1: no pain | 24 hours |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| patient satisfaction | Patients will be evaluated with a patient satisfaction questionnaire after surgery. 5: Very satisfied , 1:Not satisfied | 24 hours |
|
inguinal hernia, Transversus abdominis plane block, postoperative pain, Total extraperitoneal hernia repair
|
Hernia, Pain, Postoperative, Hernia, Inguinal, Postoperative Complications, Pathologic Processes, Pain, Neurologic Manifestations, Pathological Conditions, Anatomical, Hernia, Abdominal
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>30 patients will be injected with local anesthetic into the fascia between the transversus abdominis and internal oblique muscles with the help of ultrasound from the designated area (Before the operation starts, TAPBwith 20 ml 0.25 % bupivacaine will be applied to the surgical side under ultrasonography) | Procedure: Ultrasound assisted - Laparoscopy assisted Transversus Abdominis Plane Block<br>* Ultrasound assisted TAPB application will be applied by an anesthesiology and reanimation specialist and Laparoscopy assisted TAPB application will be applied by the surgeon performing the operation.<br>|
| Active Comparator: Group 2<br>30 patients, local anesthetic injection will be made to the same area under laparoscopic direct vision. 50 mg Bupivacaine (0.25 % 20 ml bupivacaine solution) has been determined as the application dose and this amount will be applied in both groups. | Procedure: Ultrasound assisted - Laparoscopy assisted Transversus Abdominis Plane Block<br>* Ultrasound assisted TAPB application will be applied by an anesthesiology and reanimation specialist and Laparoscopy assisted TAPB application will be applied by the surgeon performing the operation.<br>|
|
COMPARISON OF LAPAROSCOPY AND ULTRASOUND ASSISTED TRANSVERSUS ABDOMINIS PLANE BLOCK METHODS IN LAPAROSCOPIC TOTAL EXTRAPERITONEAL HERNIA REPAIR
Study Overview
=================
Brief Summary
-----------------
While the rate of inguinal hernia repair operations in England is 10 per 100,000 people. The rate in the United States is found to be 28 per 100,000 people. Today, the effectiveness between open repair and laparoscopic repair in inguinal hernia repair is still debated. Laparoscopic approach offers many advantages over open repair. Regional blocks have an important place in the multi-modal anesthesia approach applied to reduce postoperative pain. In this sense, the Transversus Abdominis Plane Block (TAPB) emerges as an effective regional anesthesia method that reduces postoperative pain. This method can be applied with the help of ultrasound or laparoscopy. The aim of this study is to compare the ultrasound-assisted TAPB application and Laparoscopy-assisted TAPB application in Total Extraperitoneal hernia repair (TEP) to reveal the effects of postoperative pain. A total of 60 patients will be included in the study; 30 of these patients will be injected with local anesthetic into the fascia between the transversus abdominis and internal oblique muscles with the help of ultrasound from the designated area (Before the operation starts, TAPB with 20 ml 0.25 % bupivacaine will be applied to the surgical side under ultrasonography); In the other 30 patients, local anesthetic injection will be made to the same area under laparoscopic direct vision. 50 mg Bupivacaine (0.25 % 20 ml bupivacaine solution) has been determined as the application dose and this amount will be applied in both groups. 10 cm visual analog scale (VAS) will be used in postoperative pain follow-up. 50 mg intravenous tramadol will be administered to patients with VAS > 4 and tramadol will be supplemented to 100 mg in patients with high pain levels after 30 minutes. Oral non-steroidal anti-inflammatory will be given at the postoperative 8th hour. Patients whose pain persists despite current therapy will be given 25 mg of meperidine intravenously as a rescue analgesic. The doses of analgesic administered in the postoperative period and the hours of administration will be recorded
Detailed Description
-----------------
While the rate of inguinal hernia repair operations in England is 10 per 100,000 people. The rate in the United States is found to be 28 per 100,000 people. Today, the effectiveness between open repair and laparoscopic repair in inguinal hernia repair is still debated. Laparoscopic approach offers many advantages over open repair. These are topics such as postoperative pain, quick recovery, and shortening of returning to work. Postoperative pain is the most important determinant of recovery after abdominal surgeries. Postoperative pain can be explained by two pathways connected to the peritoneum; The first is the parietal peritoneum, which has a very rich innervation, and the other is the visceral peritoneum stimulated by the vagus. In order to eliminate these peritoneal pains, surgeons have been injecting local anesthetic into various areas on the anterior abdominal wall and intraperitoneal space since 1950. Regional blocks have an important place in the multi-modal anesthesia approach applied to reduce postoperative pain. In this sense, the Transversus Abdominis Plane Block (TAPB) emerges as an effective regional anesthesia method that reduces postoperative pain. TAPB; It is a type of regional anesthesia applied to the facial plane between the internal oblique muscle and the transversus abdominis muscles, targeting the somatic nerves (T6 - L1). This method can be applied with the help of ultrasound or laparoscopy. The aim of this study is to compare the ultrasound-assisted TAPB application and Laparoscopy-assisted TAPB application in Total Extraperitoneal hernia repair (TEP) to reveal the effects of postoperative pain. TEP will be performed with 2-3 mg / kg propofol, 2 mcg / kg fentanyl and 0.6 mg / kg rocuronium in patients who will undergo anesthesia induction with BIS < 60, after intubation, 40 % oxygen / 1.5 - 2 % sevoflurane inhalation will be applied to keep the BIS value between 40 - 60 in 60 % air. Before the operation starts, TAPB will be made with 20 ml 0.25 % bupivacaine in the direction of ultrasonography on the side to be operated. During the operation, if there is a 20 % increase in blood pressure and heart rate from baseline, 0.5 mcg / kg intravenous fentanyl will be administered and the administered fentanyl dose will be recorded. 1gr paracetamol 30 minutes before the end of the operation and 4 mg ondansetron 15 minutes before the end of the operation will be administered intravenously. With the help of a 22 G injector, local anesthetic injection will be made from the anterior to the area where the midaxillary line intersects the Bogros area. Digital examination will be performed to define the injection site and the injection area will be determined. A total of 60 patients will be included in the study; 30 of these patients will be injected with local anesthetic into the fascia between the transversus abdominis and internal oblique muscles with the help of ultrasound from the designated area (Before the operation starts, TAPB with 20 ml 0.25 % bupivacaine will be applied to the surgical side under ultrasonography); In the other 30 patients, local anesthetic injection will be made to the same area under laparoscopic direct vision. 50 mg Bupivacaine (0.25 % 20 ml bupivacaine solution) has been determined as the application dose and this amount will be applied in both groups. Bart 3D anatomical polypropylene patch will be used in both groups and the patch will be attached with the help of 1 absorbable tacker. Carbon dioxide gas will be given to the preperitoneal area at a rate of 4 - 6 L / min and at a pressure of 15 mm Hg. 3 trocars will be used; One 10 mm camera trocar and two 5 mm working trocars will be entered through the midline below the navel. At the end of the operation, the patients will be extubated by antagonizing the muscle relaxant effect with 0.02 mg / kg atropine and 0.05 mg / kg neostigmine. 10 cm visual analog scale (VAS) will be used in postoperative pain follow-up. 50 mg intravenous tramadol will be administered to patients with VAS > 4 and tramadol will be supplemented to 100 mg in patients with high pain levels after 30 minutes. Oral non-steroidal anti-inflammatory will be given at the postoperative 8th hour. Patients whose pain persists despite current therapy will be given 25 mg of meperidine intravenously as a rescue analgesic. The doses of analgesic administered in the postoperative period and the hours of administration will be recorded.
Official Title
-----------------
COMPARISON OF LAPAROSCOPY AND ULTRASOUND ASSISTED TRANSVERSUS ABDOMINIS PLANE BLOCK METHODS IN LAPAROSCOPIC TOTAL EXTRAPERITONEAL HERNIA REPAIR
Conditions
-----------------
Postoperative Pain, Inguinal Hernia, Transversus Abdominis Plane Block
Intervention / Treatment
-----------------
* Procedure: Ultrasound assisted - Laparoscopy assisted Transversus Abdominis Plane Block
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients over the age of 18 Patients who underwent total extraperitoneal hernia repair Patients without any postoperative complications Patients who cannot be drained for any reason Exclusion Criteria: Patients who underwent another hernia repair technique during surgery for any reason. Patients who do not want to participate in the study Patients with any complications after surgery
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: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: A total of 60 patients will be included in the study; Group 1: 30 patients will be injected with local anesthetic into the fascia between the transversus abdominis and internal oblique muscles with the help of ultrasound from the designated area (Before the operation starts, TAPBwith 20 ml 0.25 % bupivacaine will be applied to the surgical side under ultrasonography) Group 2: 30 patients, local anesthetic injection will be made to the same area under laparoscopic direct vision. 50 mg Bupivacaine (0.25 % 20 ml bupivacaine solution) has been determined as the application dose and this amount will be applied in both groups.
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>30 patients will be injected with local anesthetic into the fascia between the transversus abdominis and internal oblique muscles with the help of ultrasound from the designated area (Before the operation starts, TAPBwith 20 ml 0.25 % bupivacaine will be applied to the surgical side under ultrasonography) | Procedure: Ultrasound assisted - Laparoscopy assisted Transversus Abdominis Plane Block<br>* Ultrasound assisted TAPB application will be applied by an anesthesiology and reanimation specialist and Laparoscopy assisted TAPB application will be applied by the surgeon performing the operation.<br>|
| Active Comparator: Group 2<br>30 patients, local anesthetic injection will be made to the same area under laparoscopic direct vision. 50 mg Bupivacaine (0.25 % 20 ml bupivacaine solution) has been determined as the application dose and this amount will be applied in both groups. | Procedure: Ultrasound assisted - Laparoscopy assisted Transversus Abdominis Plane Block<br>* Ultrasound assisted TAPB application will be applied by an anesthesiology and reanimation specialist and Laparoscopy assisted TAPB application will be applied by the surgeon performing the operation.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative pain | 10 cm visual analog scale (VAS) will be used in postoperative pain follow-up. 10: too much pain , 1: no pain | 24 hours |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| patient satisfaction | Patients will be evaluated with a patient satisfaction questionnaire after surgery. 5: Very satisfied , 1:Not satisfied | 24 hours |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
inguinal hernia, Transversus abdominis plane block, postoperative pain, Total extraperitoneal hernia repair
|
NCT01606228
|
A Trial to Explore the Tolerability, Safety and Efficacy of Paliperidone Extended Release in Patients With Schizophrenia
|
The purpose of this study is to explore the tolerability, safety and efficacy of flexibly dosed paliperidone extended release (ER) among patients with schizophrenia.
|
This is a single arm (the same intervention is given to all patients), multicenter study that aimed to explore the tolerability, safety and efficacy of flexibly dosed paliperidone extended release (ER) among Filipino patients with schizophrenia who have not taken any antipsychotics in the past, and among newly diagnosed schizophrenia patients who have not taken any antipsychotics for at least one month prior to screening. Antipsychotics are drugs that are helpful in the treatment of psychosis and have a capacity to ameliorate thought disorders. Flexible dosing allows the investigators to adjust the dosage of each patient based on the individual needs.
|
An Open-Label Prospective Trial to Explore the Tolerability, Safety and Efficacy of Flexibly-Dosed Paliperidone ER Among Treatment-Naïve and Newly Diagnosed Patients With Schizophrenia
|
Schizophrenia
|
* Drug: Paliperidone ER
|
Inclusion Criteria:~Patients diagnosed with schizophrenia~Patient with Positive and Negative Syndrome Scale (PANSS) score of 80 to 120 at screening~Patients who have not taken any antipsychotics in the past, and those were newly diagnosed with schizophrenia who have not taken any antipsychotics for at least one month prior to screening~Patient healthy on the basis of a physical examination, laboratory examination, and vital signs~Women must have a negative pregnancy test, and agree to practice an effective method of birth control before entry and throughout the study~Exclusion Criteria:~Serious unstable medical condition, including known clinically relevant laboratory abnormalities~Judged to be at high risk for adverse events, violence or self-harm~Inability to swallow the study medication whole with the aid of water (patients may not chew, divide, dissolve, or crush the study medication)~Biochemistry results that are out of the laboratory's normal reference range and are deemed to be clinically significant by the investigator~Patients with a current use or known history (over the past 6 months) of substance dependence~Positive urine drug examination
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Patients Improving 20% in Total Positive and Negative Syndrome Scale (PANSS) at Endpoint (Day 90) | The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening. | Baseline, Day 90 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Syndrome Scale (PANSS) Scores at Baseline | The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening. | Baseline |
| Positive and Negative Syndrome Scale (PANSS) Scores at Day 90 | The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening. | Day 90 |
| Clinical Global Impression-Severity (CGIS) Scores at Baseline | The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a patient. The rating varies from Normal (not at all ill) to Extreme (among the most extremely ill patients). | Baseline |
| Clinical Global Impression-Severity (CGIS) Scores at Day 90 | The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a patient. The rating varies from Normal (not at all ill) to Extreme (among the most extremely ill patients). | Day 90 |
| Personal and Social Performance (PSP) Scores at Baseline | This PSP assesses the degree of a patient's dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. The score ranges from 1 to 100, divided into 10 equal intervals to rate the degree of difficulty (i, absent to vi, very severe) in each of the 4 domains. Based on the four domains there will be one total score. Patients with a score of 71 to 100 have a mild degree of difficulty; from 31 to 70, varying degrees of disability; =< 30, functioning so poorly as to require intensive supervision. | Baseline |
| Personal and Social Performance (PSP) Scores at Day 90 | This PSP assesses the degree of a patient's dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. The score ranges from 1 to 100, divided into 10 equal intervals to rate the degree of difficulty (i, absent to vi, very severe) in each of the 4 domains. Based on the four domains there will be one total score. Patients with a score of 71 to 100 have a mild degree of difficulty; from 31 to 70, varying degrees of disability; =< 30, functioning so poorly as to require intensive supervision. | Day 90 |
| Patient Satisfaction With Paliperidone Treatment | Patients will be interviewed to assess their satisfaction with the current treatment on a 5-point scale (very good, good, reasonable, moderate or poor). | 90 days |
| Quality of Sleep at Baseline | The quality of sleep is measured by a self-administered scale in which patients indicate how well they have slept in the previous 7 days, from 0 (very badly) to 100 (very well). | Baseline |
| Quality of Sleep at Day 90 | The quality of sleep is measured by a self-administered scale in which patients indicate how well they have slept in the previous 7 days, from 0 (very badly) to 100 (very well). | Day 90 |
| Daytime Drowsiness at Baseline | The daytime drowsiness is measured by a self-administered scale in which patients indicate how often they have felt drowsy within the previous 7 days, from 0 (not at all) to 100 (all the time). | Baseline |
| Daytime Drowsiness at Day 90 | The daytime drowsiness is measured by a self-administered scale in which patients indicate how often they have felt drowsy within the previous 7 days, from 0 (not at all) to 100 (all the time). | Day 90 |
|
Schizophrenia, Paliperidone ER, Treatment naive patients, Newly diagnosed patients
|
Paliperidone Palmitate, Antipsychotic Agents, Tranquilizing Agents, Central Nervous System Depressants, Physiological Effects of Drugs, Psychotropic Drugs, Serotonin 5-HT2 Receptor Antagonists, Serotonin Antagonists, Serotonin Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Dopamine D2 Receptor Antagonists, Dopamine Antagonists, Dopamine Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paliperidone ER<br> | Drug: Paliperidone ER<br>* Type= range, unit= mg/day, number= 3 to 12, form= tablet, route= oral use. Paliperidone ER 6 mg orally administered once daily for the first five days. Thereafter, flexible dosing in a range of 3 to 12 mg/day.<br>|
|
A Trial to Explore the Tolerability, Safety and Efficacy of Paliperidone Extended Release in Patients With Schizophrenia
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to explore the tolerability, safety and efficacy of flexibly dosed paliperidone extended release (ER) among patients with schizophrenia.
Detailed Description
-----------------
This is a single arm (the same intervention is given to all patients), multicenter study that aimed to explore the tolerability, safety and efficacy of flexibly dosed paliperidone extended release (ER) among Filipino patients with schizophrenia who have not taken any antipsychotics in the past, and among newly diagnosed schizophrenia patients who have not taken any antipsychotics for at least one month prior to screening. Antipsychotics are drugs that are helpful in the treatment of psychosis and have a capacity to ameliorate thought disorders. Flexible dosing allows the investigators to adjust the dosage of each patient based on the individual needs.
Official Title
-----------------
An Open-Label Prospective Trial to Explore the Tolerability, Safety and Efficacy of Flexibly-Dosed Paliperidone ER Among Treatment-Naïve and Newly Diagnosed Patients With Schizophrenia
Conditions
-----------------
Schizophrenia
Intervention / Treatment
-----------------
* Drug: Paliperidone ER
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients diagnosed with schizophrenia Patient with Positive and Negative Syndrome Scale (PANSS) score of 80 to 120 at screening Patients who have not taken any antipsychotics in the past, and those were newly diagnosed with schizophrenia who have not taken any antipsychotics for at least one month prior to screening Patient healthy on the basis of a physical examination, laboratory examination, and vital signs Women must have a negative pregnancy test, and agree to practice an effective method of birth control before entry and throughout the study Exclusion Criteria: Serious unstable medical condition, including known clinically relevant laboratory abnormalities Judged to be at high risk for adverse events, violence or self-harm Inability to swallow the study medication whole with the aid of water (patients may not chew, divide, dissolve, or crush the study medication) Biochemistry results that are out of the laboratory's normal reference range and are deemed to be clinically significant by the investigator Patients with a current use or known history (over the past 6 months) of substance dependence Positive urine drug examination
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: Paliperidone ER<br> | Drug: Paliperidone ER<br>* Type= range, unit= mg/day, number= 3 to 12, form= tablet, route= oral use. Paliperidone ER 6 mg orally administered once daily for the first five days. Thereafter, flexible dosing in a range of 3 to 12 mg/day.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Patients Improving 20% in Total Positive and Negative Syndrome Scale (PANSS) at Endpoint (Day 90) | The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening. | Baseline, Day 90 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Syndrome Scale (PANSS) Scores at Baseline | The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening. | Baseline |
| Positive and Negative Syndrome Scale (PANSS) Scores at Day 90 | The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening. | Day 90 |
| Clinical Global Impression-Severity (CGIS) Scores at Baseline | The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a patient. The rating varies from Normal (not at all ill) to Extreme (among the most extremely ill patients). | Baseline |
| Clinical Global Impression-Severity (CGIS) Scores at Day 90 | The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a patient. The rating varies from Normal (not at all ill) to Extreme (among the most extremely ill patients). | Day 90 |
| Personal and Social Performance (PSP) Scores at Baseline | This PSP assesses the degree of a patient's dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. The score ranges from 1 to 100, divided into 10 equal intervals to rate the degree of difficulty (i, absent to vi, very severe) in each of the 4 domains. Based on the four domains there will be one total score. Patients with a score of 71 to 100 have a mild degree of difficulty; from 31 to 70, varying degrees of disability; =< 30, functioning so poorly as to require intensive supervision. | Baseline |
| Personal and Social Performance (PSP) Scores at Day 90 | This PSP assesses the degree of a patient's dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. The score ranges from 1 to 100, divided into 10 equal intervals to rate the degree of difficulty (i, absent to vi, very severe) in each of the 4 domains. Based on the four domains there will be one total score. Patients with a score of 71 to 100 have a mild degree of difficulty; from 31 to 70, varying degrees of disability; =< 30, functioning so poorly as to require intensive supervision. | Day 90 |
| Patient Satisfaction With Paliperidone Treatment | Patients will be interviewed to assess their satisfaction with the current treatment on a 5-point scale (very good, good, reasonable, moderate or poor). | 90 days |
| Quality of Sleep at Baseline | The quality of sleep is measured by a self-administered scale in which patients indicate how well they have slept in the previous 7 days, from 0 (very badly) to 100 (very well). | Baseline |
| Quality of Sleep at Day 90 | The quality of sleep is measured by a self-administered scale in which patients indicate how well they have slept in the previous 7 days, from 0 (very badly) to 100 (very well). | Day 90 |
| Daytime Drowsiness at Baseline | The daytime drowsiness is measured by a self-administered scale in which patients indicate how often they have felt drowsy within the previous 7 days, from 0 (not at all) to 100 (all the time). | Baseline |
| Daytime Drowsiness at Day 90 | The daytime drowsiness is measured by a self-administered scale in which patients indicate how often they have felt drowsy within the previous 7 days, from 0 (not at all) to 100 (all the time). | Day 90 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Schizophrenia, Paliperidone ER, Treatment naive patients, Newly diagnosed patients
|
NCT03974048
|
Identification of the Epigenetic Response to Trauma
|
The objective of this study is to investigate potential early alterations in the DNA methylation profile after severe trauma and to investigate if the early marks persist.
|
Background: Severe trauma is an extreme physical exposure, which may have significant consequences for the patient. In addition to anatomical injury and hemodynamic compromise, severe trauma causes an immense and rapid systemic immune reaction. At the genomic level, trauma has been found to significantly increase gene expression in circulating leukocytes, and preliminary data is also emerging that trauma may even cause epigenetic (DNA methylation) alterations.~Epigenetics, including DNA methylation, have been suggested as a mediator of genetic risk and to play a significant role in subsequent non-traumatic disease. Within the field of trauma DNA methylation has only been sparsely studied, but a few studies of traumatized animals have suggested that DNA methylation alterations may occur in relation to trauma. Even though DNA methylation is highly dynamic, some marks have been found to be stable over time, and thus may have long-term consequences.~An increasing understanding of the role of epigenetics in disease development and response may pave the way for new treatment targets and modalities for multiple diseases including trauma.~Research question: Does trauma induce immediate (<4 hours) and persistent (30 days post-trauma) changes in the epigenome of peripheral blood cells, and do epigenetic changes correlate with patient recovery?~Objectives: To identify potential early alterations in the DNA methylation profile after severe trauma AND to investigate if the early marks persist.~Study design: A prospective, observational, cohort study of trauma patients admitted to RH's trauma center. The trauma cohort will be compared to a cohort of patients admitted for elective orthopedic surgery in terms of DNA methylation profile in blood cells pre-trauma/surgery, immediately post-trauma/surgery, and 30-45 days post-trauma/surgery.~DNA methylation profiles will be assessed by array technique using Illumina's MethylationEPIC Bead-Chip.~Primary outcome: Immediate (<4 hours) post-trauma DNA methylation profile in blood cells.~Secondary outcomes: Pre-trauma/surgery DNA methylation profile, change in DNA methylation from pre-trauma/surgery to immediately and 30 days post-trauma/surgery, occurrence of organ dysfunction, sepsis, septic shock, 30-day mortality, ICU admission > 24 hours, ICU length of stay (LOS), hospital LOS.
|
Identification of the Epigenetic Response to Trauma - a Prospective, Observational Study
|
Trauma, Injuries
|
* Diagnostic Test: Blood samples for DNA methylation analysis
|
Inclusion Criteria:~Age 18-65 years.~Trauma patients: Admitted to Rigshospitalet's trauma center generating a trauma team activation.~Surgical controls: Admitted for elective surgery (non-traumatic cause) at the orthopedics department AND~Only one surgical procedure planned from study day 0 to study day 45.~Expected procedure length of at least 60 minutes.~Exclusion Criteria:~Not able to obtain informed consent and not possible to obtain consent from a next-of-kin.~Trauma patients:~Secondary transfers.~Pre-hospital blood transfusion OR blood transfusion in the trauma center before the first blood sample is obtained.~First blood sample taken later than 4 hours after the trauma.~Patients in cardiac arrest before/after hospital admission.~Additional traumatic exposure requiring hospital admission between the collection of the primary blood sample and the follow-up blood sample (will cause exclusion from follow-up blood sample).~Surgery not related to the trauma between the collection of the primary blood sample and the follow-up blood sample (will cause exclusion from follow-up blood sample).~Surgical controls:~Surgical procedures due to cancer or fractures.~Traumatic exposure requiring hospital admission between the collection of the primary blood sample and the follow-up blood sample (will cause exclusion from follow-up blood sample).~Additional, unplanned surgery between the collection of the primary blood sample and the follow-up blood sample (will cause exclusion from follow-up blood sample).~First post-operative blood sample taken later than 4 hours after surgical end time.
|
18 Years
|
65 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immediate DNA methylation profile | Immediate (< 4 hours) post-trauma DNA methylation profile in blood cells compared to the pre-surgery (baseline) and immediate post-surgery (< 4 hours) DNA methylation profile in blood cells. | Day of trauma/surgery |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre-trauma/-surgery DNA methylation profile | Pre-trauma (if possible to obtain from an existing biobank) DNA methylation profile in blood cells compared to pre-surgery. | Pre-trauma/surgery |
| Stability of DNA methylation profile | Persistence of the DNA methylation profile in blood cells 30-45 days after the trauma compared to surgical patients. | 30-45 days after trauma/surgery |
| Change in DNA methylation profile; pre-trauma/-surgery to post-trauma/-surgery | Change in DNA methylation profile in blood cells from pre-trauma (if possible to obtain) to immediately post-trauma compared to surgical patients. | Day of trauma/surgery |
| Change in DNA methylation profile; immediately post-trauma/-surgery to one month post-trauma/-surgery | Change in DNA methylation profile in blood cells from immediately post-trauma to 30-45 days post-trauma compared to surgical patients. | 0 to 30-45 days after trauma/surgery |
| DNA methylation changes in relation to injury severity | Association of DNA methylation changes with injury severity. This will be done by comparing the DNA methylation profiles among patient with an injury severity score (ISS) < 15 and patients with an ISS > 15. | Day 0-45 after trauma/surgery |
| Organ dysfunction | Occurrence of organ dysfunction (increase of ≥ 2 in SOFA-score) | Day 30 after trauma/surgery |
| Sepsis/septic shock | Occurrence of sepsis or septic shock | Day 30 after trauma/surgery |
|
Epigenetics, DNA methylation, Trauma
|
Wounds and Injuries
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Trauma patients<br>All trauma patients admitted to Rigshospitalet's trauma center will have a blood sample taken during the initial treatment and 30 days after the trauma. | Diagnostic Test: Blood samples for DNA methylation analysis<br>* DNA from blood samples will be isolated and analyzed for genome-wide DNA methylation patterns using the Infinium HumanMethylationEPIC BeadChip (Illumina, San Diego, CA, USA).<br>|
| Patients admitted for elective orthopedic surgery<br>The patients will have a blood sample taken before and after surgery and again 30 days after the surgery. | Diagnostic Test: Blood samples for DNA methylation analysis<br>* DNA from blood samples will be isolated and analyzed for genome-wide DNA methylation patterns using the Infinium HumanMethylationEPIC BeadChip (Illumina, San Diego, CA, USA).<br>|
|
Identification of the Epigenetic Response to Trauma
Study Overview
=================
Brief Summary
-----------------
The objective of this study is to investigate potential early alterations in the DNA methylation profile after severe trauma and to investigate if the early marks persist.
Detailed Description
-----------------
Background: Severe trauma is an extreme physical exposure, which may have significant consequences for the patient. In addition to anatomical injury and hemodynamic compromise, severe trauma causes an immense and rapid systemic immune reaction. At the genomic level, trauma has been found to significantly increase gene expression in circulating leukocytes, and preliminary data is also emerging that trauma may even cause epigenetic (DNA methylation) alterations. Epigenetics, including DNA methylation, have been suggested as a mediator of genetic risk and to play a significant role in subsequent non-traumatic disease. Within the field of trauma DNA methylation has only been sparsely studied, but a few studies of traumatized animals have suggested that DNA methylation alterations may occur in relation to trauma. Even though DNA methylation is highly dynamic, some marks have been found to be stable over time, and thus may have long-term consequences. An increasing understanding of the role of epigenetics in disease development and response may pave the way for new treatment targets and modalities for multiple diseases including trauma. Research question: Does trauma induce immediate (<4 hours) and persistent (30 days post-trauma) changes in the epigenome of peripheral blood cells, and do epigenetic changes correlate with patient recovery? Objectives: To identify potential early alterations in the DNA methylation profile after severe trauma AND to investigate if the early marks persist. Study design: A prospective, observational, cohort study of trauma patients admitted to RH's trauma center. The trauma cohort will be compared to a cohort of patients admitted for elective orthopedic surgery in terms of DNA methylation profile in blood cells pre-trauma/surgery, immediately post-trauma/surgery, and 30-45 days post-trauma/surgery. DNA methylation profiles will be assessed by array technique using Illumina's MethylationEPIC Bead-Chip. Primary outcome: Immediate (<4 hours) post-trauma DNA methylation profile in blood cells. Secondary outcomes: Pre-trauma/surgery DNA methylation profile, change in DNA methylation from pre-trauma/surgery to immediately and 30 days post-trauma/surgery, occurrence of organ dysfunction, sepsis, septic shock, 30-day mortality, ICU admission > 24 hours, ICU length of stay (LOS), hospital LOS.
Official Title
-----------------
Identification of the Epigenetic Response to Trauma - a Prospective, Observational Study
Conditions
-----------------
Trauma, Injuries
Intervention / Treatment
-----------------
* Diagnostic Test: Blood samples for DNA methylation analysis
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-65 years. Trauma patients: Admitted to Rigshospitalet's trauma center generating a trauma team activation. Surgical controls: Admitted for elective surgery (non-traumatic cause) at the orthopedics department AND Only one surgical procedure planned from study day 0 to study day 45. Expected procedure length of at least 60 minutes. Exclusion Criteria: Not able to obtain informed consent and not possible to obtain consent from a next-of-kin. Trauma patients: Secondary transfers. Pre-hospital blood transfusion OR blood transfusion in the trauma center before the first blood sample is obtained. First blood sample taken later than 4 hours after the trauma. Patients in cardiac arrest before/after hospital admission. Additional traumatic exposure requiring hospital admission between the collection of the primary blood sample and the follow-up blood sample (will cause exclusion from follow-up blood sample). Surgery not related to the trauma between the collection of the primary blood sample and the follow-up blood sample (will cause exclusion from follow-up blood sample). Surgical controls: Surgical procedures due to cancer or fractures. Traumatic exposure requiring hospital admission between the collection of the primary blood sample and the follow-up blood sample (will cause exclusion from follow-up blood sample). Additional, unplanned surgery between the collection of the primary blood sample and the follow-up blood sample (will cause exclusion from follow-up blood sample). First post-operative blood sample taken later than 4 hours after surgical end time.
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?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Trauma patients<br>All trauma patients admitted to Rigshospitalet's trauma center will have a blood sample taken during the initial treatment and 30 days after the trauma. | Diagnostic Test: Blood samples for DNA methylation analysis<br>* DNA from blood samples will be isolated and analyzed for genome-wide DNA methylation patterns using the Infinium HumanMethylationEPIC BeadChip (Illumina, San Diego, CA, USA).<br>|
| Patients admitted for elective orthopedic surgery<br>The patients will have a blood sample taken before and after surgery and again 30 days after the surgery. | Diagnostic Test: Blood samples for DNA methylation analysis<br>* DNA from blood samples will be isolated and analyzed for genome-wide DNA methylation patterns using the Infinium HumanMethylationEPIC BeadChip (Illumina, San Diego, CA, USA).<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immediate DNA methylation profile | Immediate (< 4 hours) post-trauma DNA methylation profile in blood cells compared to the pre-surgery (baseline) and immediate post-surgery (< 4 hours) DNA methylation profile in blood cells. | Day of trauma/surgery |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre-trauma/-surgery DNA methylation profile | Pre-trauma (if possible to obtain from an existing biobank) DNA methylation profile in blood cells compared to pre-surgery. | Pre-trauma/surgery |
| Stability of DNA methylation profile | Persistence of the DNA methylation profile in blood cells 30-45 days after the trauma compared to surgical patients. | 30-45 days after trauma/surgery |
| Change in DNA methylation profile; pre-trauma/-surgery to post-trauma/-surgery | Change in DNA methylation profile in blood cells from pre-trauma (if possible to obtain) to immediately post-trauma compared to surgical patients. | Day of trauma/surgery |
| Change in DNA methylation profile; immediately post-trauma/-surgery to one month post-trauma/-surgery | Change in DNA methylation profile in blood cells from immediately post-trauma to 30-45 days post-trauma compared to surgical patients. | 0 to 30-45 days after trauma/surgery |
| DNA methylation changes in relation to injury severity | Association of DNA methylation changes with injury severity. This will be done by comparing the DNA methylation profiles among patient with an injury severity score (ISS) < 15 and patients with an ISS > 15. | Day 0-45 after trauma/surgery |
| Organ dysfunction | Occurrence of organ dysfunction (increase of ≥ 2 in SOFA-score) | Day 30 after trauma/surgery |
| Sepsis/septic shock | Occurrence of sepsis or septic shock | Day 30 after trauma/surgery |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Epigenetics, DNA methylation, Trauma
|
|
NCT05322486
|
Palliative Primary Tumor Resection in Minimally Symptomatic Patients With Colorectal Cancer and Synchronous Unresectable Metastases
|
Currently, the question remains whether palliative primary tumor resection could improve overall survival of minimally symptomatic patients with colorectal cancer and synchronous unresectable metastases. The aim of this study is to determine if there is an improvement in overall survival of palliative primary tumor resection followed by chemotherapy in minimally symptomatic patients with colorectal cancer and synchronous unresectable metastases compared to those of upfront chemotherapy/radiotherapy alone.
|
The present study is a single-center retrospective observational cohort study with a propensity score matching. Between 2016 and 2022 from our institutional database minimally symptomatic patients with colorectal cancer and synchronous unresectable metastases will be selected. Patients will be divided into two groups:~Surgical resection of the primary tumour before to systemic therapy~Systemic therapy without previous resection of the primary tumour. Propensity score matching (PSM) will be performed, to minimize the selection bias by adjusting variables that may affect the survival of patients. Categorical variables will be compared using the chi-square test or Fisher's exact test. Continuous variables will be compared using the Student's t-test or Mann-Whitney U test. Survival rate will be determined by using Kaplan-Meier analysis with a log-rank test. Univariate and multivariate analyses for survival will be conducted using Cox proportional hazard models. Statistical results will be considered significant at p values less than 0.05.
|
Palliative Primary Tumor Resection in Minimally Symptomatic Patients With Colorectal Cancer and Synchronous Unresectable Metastases Versus Chemotherapy Alone
|
Neoplasms by Site, Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms, Neoplasms, Second Primary, Neoplasm Metastasis, Digestive System Diseases, Gastrointestinal Diseases, Colonic Disease, Intestinal Diseases, Rectal Diseases
|
* Procedure: surgery of the primary tumour
* Drug: chemotherapy
|
Inclusion Criteria:~Histologically confirmed colorectal adenocarcinoma~Resectable minimally symptomatic primary tumor with unresectable synchronous metastasis~Age ≥ 18 years~Informed consent~Exclusion Criteria:~Synchronous cancers~Carcinomatosis~Prior surgery, chemotherapy, radiation therapy for the primary tumor or distant metastases
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | | 3 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thirty-day mortality | | 30 days |
| Rate of surgical intervention due to complication of treatment | | 1 year |
| Progression free survival (PFS) | PFS is defined as the time interval between the date of diagnosis and the first date of progression of the metastatic disease or death in both treatment arms. | 3 years |
|
Colorectal cancer, Primary tumor resection, Minimally symptomatic primary tumor, Unresectable metastases, Chemotherapy
|
Neoplasms, Colorectal Neoplasms, Neoplasm Metastasis, Neoplasms, Second Primary, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Intestinal Neoplasms, Gastrointestinal Diseases, Digestive System Diseases, Colonic Diseases, Intestinal Diseases, Rectal Diseases, Neoplastic Processes, Pathologic Processes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Primary tumour resection group.<br>Surgical resection of the primary tumour followed by chemotherapy +/- targeted therapy regime. | Procedure: surgery of the primary tumour<br>* Surgical resection of the colon tumour, R0. No surgical intervention on metastasis.<br>Drug: chemotherapy<br>* Chemotherapy with or without biological drugs.<br>|
| Chemotherapy group.<br>Chemotherapy +/- targeted therapy alone. | Drug: chemotherapy<br>* Chemotherapy with or without biological drugs.<br>|
|
Palliative Primary Tumor Resection in Minimally Symptomatic Patients With Colorectal Cancer and Synchronous Unresectable Metastases
Study Overview
=================
Brief Summary
-----------------
Currently, the question remains whether palliative primary tumor resection could improve overall survival of minimally symptomatic patients with colorectal cancer and synchronous unresectable metastases. The aim of this study is to determine if there is an improvement in overall survival of palliative primary tumor resection followed by chemotherapy in minimally symptomatic patients with colorectal cancer and synchronous unresectable metastases compared to those of upfront chemotherapy/radiotherapy alone.
Detailed Description
-----------------
The present study is a single-center retrospective observational cohort study with a propensity score matching. Between 2016 and 2022 from our institutional database minimally symptomatic patients with colorectal cancer and synchronous unresectable metastases will be selected. Patients will be divided into two groups: Surgical resection of the primary tumour before to systemic therapy Systemic therapy without previous resection of the primary tumour. Propensity score matching (PSM) will be performed, to minimize the selection bias by adjusting variables that may affect the survival of patients. Categorical variables will be compared using the chi-square test or Fisher's exact test. Continuous variables will be compared using the Student's t-test or Mann-Whitney U test. Survival rate will be determined by using Kaplan-Meier analysis with a log-rank test. Univariate and multivariate analyses for survival will be conducted using Cox proportional hazard models. Statistical results will be considered significant at p values less than 0.05.
Official Title
-----------------
Palliative Primary Tumor Resection in Minimally Symptomatic Patients With Colorectal Cancer and Synchronous Unresectable Metastases Versus Chemotherapy Alone
Conditions
-----------------
Neoplasms by Site, Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms, Neoplasms, Second Primary, Neoplasm Metastasis, Digestive System Diseases, Gastrointestinal Diseases, Colonic Disease, Intestinal Diseases, Rectal Diseases
Intervention / Treatment
-----------------
* Procedure: surgery of the primary tumour
* Drug: chemotherapy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed colorectal adenocarcinoma Resectable minimally symptomatic primary tumor with unresectable synchronous metastasis Age ≥ 18 years Informed consent Exclusion Criteria: Synchronous cancers Carcinomatosis Prior surgery, chemotherapy, radiation therapy for the primary tumor or distant metastases
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 |
| --- | --- |
| Primary tumour resection group.<br>Surgical resection of the primary tumour followed by chemotherapy +/- targeted therapy regime. | Procedure: surgery of the primary tumour<br>* Surgical resection of the colon tumour, R0. No surgical intervention on metastasis.<br>Drug: chemotherapy<br>* Chemotherapy with or without biological drugs.<br>|
| Chemotherapy group.<br>Chemotherapy +/- targeted therapy alone. | Drug: chemotherapy<br>* Chemotherapy with or without biological drugs.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | | 3 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thirty-day mortality | | 30 days |
| Rate of surgical intervention due to complication of treatment | | 1 year |
| Progression free survival (PFS) | PFS is defined as the time interval between the date of diagnosis and the first date of progression of the metastatic disease or death in both treatment arms. | 3 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Colorectal cancer, Primary tumor resection, Minimally symptomatic primary tumor, Unresectable metastases, Chemotherapy
|
|
NCT02802293
|
Treatment of Depression With Connectivity Guided Robotically Delivered rTMS
|
The purpose of this study is to determine the clinical effects (if any) of connectivity-guided repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder (MDD) to provide clues about the ideal neural networks to target for more robust clinical outcomes, and to identify potential biomarkers of treatment response including changes in brain network connectivity.
|
The investigators propose a randomized, double-blind, 4-week trial of TMS to the left dorsolateral prefrontal cortex (DLPFC) for subjects with MDD all of whom at the patient's treatment clinic are concurrently receiving pharmaceutical and psychotherapeutic interventions. Arm 1 delivers active rTMS to the left DLPFC using the standard aiming strategy. Arm 2 delivers active rTMS to the left anterior DLPFC using connectivity-based, image-guided aiming. Arm 3 delivers active rTMS to the left posterior DLPFC using connectivity-based, image-guided aiming. In all three arms, rTMS is administered in an image-guided, robotically-positioned TMS (irTMS) manner to ensure therapist blinding and equivalent subject experiences across arms. In all three arms, the following stimulation protocol will be used: 10 Hz irTMS delivered in 4 sec trains with 26 sec inter-train intervals, 37.5 minutes/session (i.e. 3,000 pulses/session), 5 sessions/week, for 4 weeks. Neuroimaging will be used both for treatment planning and to characterize any TMS-induced network plasticity using resting-state functional magnetic resonance imaging (rs-fMRI) at week 4 of each treatment arm. Clinical assessments will be administered weekly throughout treatment (weeks 1-4) at the patient's treatment clinic. Additional psychological tests will be performed at UT Health-San Antonio's Research Imaging Institute (RII) at the baseline and post-treatment visits in order to track patient progress.
|
Treatment of Depression With Connectivity Guided Robotically Delivered Repetitive Transcranial Magnetic Stimulation
|
Major Depressive Disorder
|
* Device: repetitive transcranial magnetic stimulation
* Device: robotic arm
|
Inclusion Criteria:~Males or females with MDD receiving treatment at the iKare Mood Trauma Recovery Clinic between the ages of 18-65 years;~Meeting the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria for MDD as determined using the Mini-International Psychiatric Interview (MINI)~Meeting the Patient Health Questionnaire-9 (PHQ-9 > 14) and/or the Structured Interview Guide for the Montgomery-Ashberg Depression Rating Scale (SIGMA>18) criteria for treatment resistance in MDD despite completing at least one adequate trial of an Selective Serotonin Reuptake Inhibitor (SSRI) or Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) at an FDA-recommended dose for at least 6-8 weeks.~Subjects on SSRIs or other antidepressants, hypnotic medications including modulators of Gamma-Aminobutryic Acid (GABA)-A receptor function, trazodone, atypical neuroleptic or other psychotropic medications such as prazosin may enter the study if they are deemed to be on a stable dose of their medication.~Able to provide written informed consent.~Able to read and write English.~Exclusion Criteria:~Subjects with a diagnostic history of bipolar disorder, schizophrenia or schizoaffective disorder or currently exhibiting psychotic features as confirmed by MINI.~Serious, active suicidal risk as assessed by evaluating psychiatrist. Serious active suicidal risk is determine as imminent risk of suicide reflected in a subject having a plan and intent to end his or her life. History of suicidality in itself is not exclusion for participation in this protocol so long as the evaluating psychiatrist determines that there is an absence of serious active suicidal risk and the means to keep subjects safe.~Substance use disorder during the 3 months prior to screening; except for Mild or Moderate Alcohol Use Disorder according to DSM-V criteria.~Any history or signs of serious medical or neurological illness including seizure disorders. Except for seizures, a subject with a clinical abnormality may be included only if the study clinician considers the illness will not introduce additional risk and will not interfere with the study procedures.~Females will be excluded if they are pregnant (i.e. positive pregnancy test identified after their intake at the treatment clinic).~History of traumatic brain injury (TBI) with loss of consciousness for 20 minutes or more as determined by the Brief Traumatic Brain Injury Screen (TBI Screening Tool).~Any history or signs of metal objects (e.g. surgical clips, cardiac pacemakers, metal implants, etc.) in the body at the time of screening. MRI can have risks for persons with foreign bodies implanted in their body.
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Depression Severity (MADRS) | Measured by the Montgomery-Ashberg Depression Rating Scale. This is a 10-item diagnostic questionnaire with an overall score range from 0 to 60. A higher score indicates more severe depression:~0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression. | Baseline to four weeks (the conclusion of rTMS treatment) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Depression Severity (MADRS) | Measured by the Montgomery-Ashberg Depression Rating Scale. This is a 10-item diagnostic questionnaire with an overall score range from 0 to 60. A higher score indicates more severe depression:~0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression. | Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment) |
| Clinically Significant Response (MADRS) | Defined as greater than or equal to a 50% decrease in the Montgomery-Ashberg Depression Rating Scale. This is a 10-item diagnostic questionnaire with an overall score range from 0 to 60. A higher score indicates more severe depression:~0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression. | Baseline to four weeks (the conclusion of rTMS treatment) |
| Clinically Significant Response (MADRS) | Defined as greater than or equal to a 50% decrease in the Montgomery-Ashberg Depression Rating Scale. This is a 10-item diagnostic questionnaire with an overall score range from 0 to 60. A higher score indicates more severe depression:~0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression. | Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment) |
| Remission From Depression (MADRS) | Defined as Montgomery-Ashberg Depression Rating Scale score less than or equal to 10. This is a 10-item diagnostic questionnaire with an overall score range from 0 to 60. A higher score indicates more severe depression:~0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression. | Baseline to four weeks (the conclusion of rTMS treatment) |
| Remission From Depression (MADRS) | Defined as Montgomery-Ashberg Depression Rating Scale score less than or equal to 10. This is a 10-item diagnostic questionnaire with an overall score range from 0 to 60. A higher score indicates more severe depression:~0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression. | Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment) |
| Functional Connectivity Changes of the Targeted Brain Network(s) Following rTMS Treatment | resting-state fMRI scan will also be used to assess, network-specific functional connectivity differences between each subject's pre-treatment and post-treatment scans.~The purpose of the Z score is to standardize distributions so that each has a mean of 0, and standard deviation as 1, so we can then make comparisons.~Standard Score, the Z-Score: A way to make a comparison between values on two different normal curves by converting the values to the number of standard deviations above or below the mean. | Baseline to four weeks (the conclusion of rTMS treatment) |
|
Repetitive Transcranial Magnetic Stimulation, Major Depressive Disorder
|
Depression, Depressive Disorder, Depressive Disorder, Major, Behavioral Symptoms, Mental Disorders, Mood Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard rTMS Aiming<br>Active repetitive transcranial magnetic stimulation (rTMS) will be delivered to the left DLPFC using the standard aiming strategy with the rTMS coil positioned using a robotic arm. In this arm, rTMS will be delivered at 10 Hz in 4 sec trains with 26 sec inter-train intervals, 37.5 minutes/session (i.e. 3,000 pulses/session), 5 sessions/week, for 4 weeks. | Device: repetitive transcranial magnetic stimulation<br>* The MagPro R30 is an advanced, high performance magnetic stimulator designed primarily for non-invasive clinical use. The non-invasive brain stimulation system will be used to deliver repetitive electromagnetic pulses in this research study's treatment of major depressive disorder.<br>* Other names: rTMS;Device: robotic arm<br>* This robotic system is based on a commercially available neurosurgical robot. The robot is mounted on a mobile (i.e. retractable wheels) cart which holds the robot controller and the TMS power supply and pulse-generation computer. The robotic system will be used for TMS coil positioning/targeting.<br>|
| Active Comparator: Anterior DLPFC targeting<br>Active rTMS will be delivered to the left anterior DLPFC using connectivity-based, image-guided aiming with the rTMS coil positioned using a robotic arm. In this arm, rTMS will be delivered at 10 Hz in 4 sec trains with 26 sec inter-train intervals, 37.5 minutes/session (i.e. 3,000 pulses/session), 5 sessions/week, for 4 weeks. | Device: repetitive transcranial magnetic stimulation<br>* The MagPro R30 is an advanced, high performance magnetic stimulator designed primarily for non-invasive clinical use. The non-invasive brain stimulation system will be used to deliver repetitive electromagnetic pulses in this research study's treatment of major depressive disorder.<br>* Other names: rTMS;Device: robotic arm<br>* This robotic system is based on a commercially available neurosurgical robot. The robot is mounted on a mobile (i.e. retractable wheels) cart which holds the robot controller and the TMS power supply and pulse-generation computer. The robotic system will be used for TMS coil positioning/targeting.<br>|
| Active Comparator: Posterior DLPFC targeting<br>Active rTMS will be delivered to the left posterior DLPFC using connectivity-based, image-guided aiming with the rTMS coil positioned using a robotic arm. In this arm, rTMS will be delivered at 10 Hz in 4 sec trains with 26 sec inter-train intervals, 37.5 minutes/session (i.e. 3,000 pulses/session), 5 sessions/week, for 4 weeks. | Device: repetitive transcranial magnetic stimulation<br>* The MagPro R30 is an advanced, high performance magnetic stimulator designed primarily for non-invasive clinical use. The non-invasive brain stimulation system will be used to deliver repetitive electromagnetic pulses in this research study's treatment of major depressive disorder.<br>* Other names: rTMS;Device: robotic arm<br>* This robotic system is based on a commercially available neurosurgical robot. The robot is mounted on a mobile (i.e. retractable wheels) cart which holds the robot controller and the TMS power supply and pulse-generation computer. The robotic system will be used for TMS coil positioning/targeting.<br>|
|
Treatment of Depression With Connectivity Guided Robotically Delivered rTMS
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the clinical effects (if any) of connectivity-guided repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder (MDD) to provide clues about the ideal neural networks to target for more robust clinical outcomes, and to identify potential biomarkers of treatment response including changes in brain network connectivity.
Detailed Description
-----------------
The investigators propose a randomized, double-blind, 4-week trial of TMS to the left dorsolateral prefrontal cortex (DLPFC) for subjects with MDD all of whom at the patient's treatment clinic are concurrently receiving pharmaceutical and psychotherapeutic interventions. Arm 1 delivers active rTMS to the left DLPFC using the standard aiming strategy. Arm 2 delivers active rTMS to the left anterior DLPFC using connectivity-based, image-guided aiming. Arm 3 delivers active rTMS to the left posterior DLPFC using connectivity-based, image-guided aiming. In all three arms, rTMS is administered in an image-guided, robotically-positioned TMS (irTMS) manner to ensure therapist blinding and equivalent subject experiences across arms. In all three arms, the following stimulation protocol will be used: 10 Hz irTMS delivered in 4 sec trains with 26 sec inter-train intervals, 37.5 minutes/session (i.e. 3,000 pulses/session), 5 sessions/week, for 4 weeks. Neuroimaging will be used both for treatment planning and to characterize any TMS-induced network plasticity using resting-state functional magnetic resonance imaging (rs-fMRI) at week 4 of each treatment arm. Clinical assessments will be administered weekly throughout treatment (weeks 1-4) at the patient's treatment clinic. Additional psychological tests will be performed at UT Health-San Antonio's Research Imaging Institute (RII) at the baseline and post-treatment visits in order to track patient progress.
Official Title
-----------------
Treatment of Depression With Connectivity Guided Robotically Delivered Repetitive Transcranial Magnetic Stimulation
Conditions
-----------------
Major Depressive Disorder
Intervention / Treatment
-----------------
* Device: repetitive transcranial magnetic stimulation
* Device: robotic arm
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males or females with MDD receiving treatment at the iKare Mood Trauma Recovery Clinic between the ages of 18-65 years; Meeting the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria for MDD as determined using the Mini-International Psychiatric Interview (MINI) Meeting the Patient Health Questionnaire-9 (PHQ-9 > 14) and/or the Structured Interview Guide for the Montgomery-Ashberg Depression Rating Scale (SIGMA>18) criteria for treatment resistance in MDD despite completing at least one adequate trial of an Selective Serotonin Reuptake Inhibitor (SSRI) or Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) at an FDA-recommended dose for at least 6-8 weeks. Subjects on SSRIs or other antidepressants, hypnotic medications including modulators of Gamma-Aminobutryic Acid (GABA)-A receptor function, trazodone, atypical neuroleptic or other psychotropic medications such as prazosin may enter the study if they are deemed to be on a stable dose of their medication. Able to provide written informed consent. Able to read and write English. Exclusion Criteria: Subjects with a diagnostic history of bipolar disorder, schizophrenia or schizoaffective disorder or currently exhibiting psychotic features as confirmed by MINI. Serious, active suicidal risk as assessed by evaluating psychiatrist. Serious active suicidal risk is determine as imminent risk of suicide reflected in a subject having a plan and intent to end his or her life. History of suicidality in itself is not exclusion for participation in this protocol so long as the evaluating psychiatrist determines that there is an absence of serious active suicidal risk and the means to keep subjects safe. Substance use disorder during the 3 months prior to screening; except for Mild or Moderate Alcohol Use Disorder according to DSM-V criteria. Any history or signs of serious medical or neurological illness including seizure disorders. Except for seizures, a subject with a clinical abnormality may be included only if the study clinician considers the illness will not introduce additional risk and will not interfere with the study procedures. Females will be excluded if they are pregnant (i.e. positive pregnancy test identified after their intake at the treatment clinic). History of traumatic brain injury (TBI) with loss of consciousness for 20 minutes or more as determined by the Brief Traumatic Brain Injury Screen (TBI Screening Tool). Any history or signs of metal objects (e.g. surgical clips, cardiac pacemakers, metal implants, etc.) in the body at the time of screening. MRI can have risks for persons with foreign bodies implanted in their body.
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: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard rTMS Aiming<br>Active repetitive transcranial magnetic stimulation (rTMS) will be delivered to the left DLPFC using the standard aiming strategy with the rTMS coil positioned using a robotic arm. In this arm, rTMS will be delivered at 10 Hz in 4 sec trains with 26 sec inter-train intervals, 37.5 minutes/session (i.e. 3,000 pulses/session), 5 sessions/week, for 4 weeks. | Device: repetitive transcranial magnetic stimulation<br>* The MagPro R30 is an advanced, high performance magnetic stimulator designed primarily for non-invasive clinical use. The non-invasive brain stimulation system will be used to deliver repetitive electromagnetic pulses in this research study's treatment of major depressive disorder.<br>* Other names: rTMS;Device: robotic arm<br>* This robotic system is based on a commercially available neurosurgical robot. The robot is mounted on a mobile (i.e. retractable wheels) cart which holds the robot controller and the TMS power supply and pulse-generation computer. The robotic system will be used for TMS coil positioning/targeting.<br>|
| Active Comparator: Anterior DLPFC targeting<br>Active rTMS will be delivered to the left anterior DLPFC using connectivity-based, image-guided aiming with the rTMS coil positioned using a robotic arm. In this arm, rTMS will be delivered at 10 Hz in 4 sec trains with 26 sec inter-train intervals, 37.5 minutes/session (i.e. 3,000 pulses/session), 5 sessions/week, for 4 weeks. | Device: repetitive transcranial magnetic stimulation<br>* The MagPro R30 is an advanced, high performance magnetic stimulator designed primarily for non-invasive clinical use. The non-invasive brain stimulation system will be used to deliver repetitive electromagnetic pulses in this research study's treatment of major depressive disorder.<br>* Other names: rTMS;Device: robotic arm<br>* This robotic system is based on a commercially available neurosurgical robot. The robot is mounted on a mobile (i.e. retractable wheels) cart which holds the robot controller and the TMS power supply and pulse-generation computer. The robotic system will be used for TMS coil positioning/targeting.<br>|
| Active Comparator: Posterior DLPFC targeting<br>Active rTMS will be delivered to the left posterior DLPFC using connectivity-based, image-guided aiming with the rTMS coil positioned using a robotic arm. In this arm, rTMS will be delivered at 10 Hz in 4 sec trains with 26 sec inter-train intervals, 37.5 minutes/session (i.e. 3,000 pulses/session), 5 sessions/week, for 4 weeks. | Device: repetitive transcranial magnetic stimulation<br>* The MagPro R30 is an advanced, high performance magnetic stimulator designed primarily for non-invasive clinical use. The non-invasive brain stimulation system will be used to deliver repetitive electromagnetic pulses in this research study's treatment of major depressive disorder.<br>* Other names: rTMS;Device: robotic arm<br>* This robotic system is based on a commercially available neurosurgical robot. The robot is mounted on a mobile (i.e. retractable wheels) cart which holds the robot controller and the TMS power supply and pulse-generation computer. The robotic system will be used for TMS coil positioning/targeting.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Depression Severity (MADRS) | Measured by the Montgomery-Ashberg Depression Rating Scale. This is a 10-item diagnostic questionnaire with an overall score range from 0 to 60. A higher score indicates more severe depression: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression. | Baseline to four weeks (the conclusion of rTMS treatment) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Depression Severity (MADRS) | Measured by the Montgomery-Ashberg Depression Rating Scale. This is a 10-item diagnostic questionnaire with an overall score range from 0 to 60. A higher score indicates more severe depression: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression. | Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment) |
| Clinically Significant Response (MADRS) | Defined as greater than or equal to a 50% decrease in the Montgomery-Ashberg Depression Rating Scale. This is a 10-item diagnostic questionnaire with an overall score range from 0 to 60. A higher score indicates more severe depression: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression. | Baseline to four weeks (the conclusion of rTMS treatment) |
| Clinically Significant Response (MADRS) | Defined as greater than or equal to a 50% decrease in the Montgomery-Ashberg Depression Rating Scale. This is a 10-item diagnostic questionnaire with an overall score range from 0 to 60. A higher score indicates more severe depression: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression. | Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment) |
| Remission From Depression (MADRS) | Defined as Montgomery-Ashberg Depression Rating Scale score less than or equal to 10. This is a 10-item diagnostic questionnaire with an overall score range from 0 to 60. A higher score indicates more severe depression: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression. | Baseline to four weeks (the conclusion of rTMS treatment) |
| Remission From Depression (MADRS) | Defined as Montgomery-Ashberg Depression Rating Scale score less than or equal to 10. This is a 10-item diagnostic questionnaire with an overall score range from 0 to 60. A higher score indicates more severe depression: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression. | Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment) |
| Functional Connectivity Changes of the Targeted Brain Network(s) Following rTMS Treatment | resting-state fMRI scan will also be used to assess, network-specific functional connectivity differences between each subject's pre-treatment and post-treatment scans. The purpose of the Z score is to standardize distributions so that each has a mean of 0, and standard deviation as 1, so we can then make comparisons. Standard Score, the Z-Score: A way to make a comparison between values on two different normal curves by converting the values to the number of standard deviations above or below the mean. | Baseline to four weeks (the conclusion of rTMS treatment) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Repetitive Transcranial Magnetic Stimulation, Major Depressive Disorder
|
NCT03136094
|
Suicide in Urban Natives: Detection and Networks to Combat Events
|
This study compares the effectiveness of a program to detect and manage suicide risk among American-Indian and Alaska Native (AI/AN) youth. Half of the participants will receive caring text messages to reduce suicidal thoughts, attempts, and hospitalizations and to increase engagement, social connectedness, and resilience in at-risk youth. The other half will receive usual care that does not include the caring text messages.
|
The study, Suicide in Urban Natives: Detection and Networks to Combat Events, builds on Screening, Brief Intervention and Referral to treatment (SBIRT), carried out through the primary care setting, to detect and manage suicide risk. This approach is multilevel, targeting both the healthcare system and the individual, and links screening to existing mobile phone technologies shown to promote resilience and to tap the protective benefits of social connectedness. This Collaborative Hub will conduct a randomized control trial that compares the effectiveness of enhancing these SBIRT programs by sending caring text messages to reduce suicidal ideation, attempts, and hospitalizations, and to increase engagement, social connectedness, and resilience. The Investigators' long-term goal is to disseminate and translate the lessons learned into practical policy, organizational changes, and preventive innovations that optimize patient-centered health outcomes and ultimately reduce or eliminate the dramatic and tragic suicide-related health disparities among urban AI/AN youth and young adults.
|
Collaborative Hub to Reduce the Burden of Suicide Among Urban American Indian and Alaska Native Young Adults
|
Suicide Prevention
|
* Behavioral: SBIRT+12
* Behavioral: SBIRT+Usual Care
|
Inclusion Criteria:~Self-identify as American Indian or Alaska Native;~Screen positive for mild, moderate, or severe risk of suicidality (referred by a clinical provider);~Have a text-enabled mobile phone;~Willing to be contacted by text;~Able to participate voluntarily;~Speak and read English;~Cognitively able to independently provide written informed consent~Exclusion Criteria:~Under age 18~In danger of imminent self-harm;~Hospitalized
|
18 Years
|
34 Years
|
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The Investigators will conduct a randomized controlled trial to test the effectiveness of an augmented Screening, Brief Intervention, and Referral to Treatment (SBIRT) model that includes sending caring text messages for 12 months after an at-risk patient is identified.
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Suicidal Ideation | The 15-item Suicidal Ideation Questionnaire Jr. assesses frequency of suicidal thoughts in the past month. Item content ranges from general thoughts of death and wishes that one were dead to specific thoughts of self-injurious behavior. Responses are on a 7-point scale ranging from never to almost daily. Items are summed for a total score (range 0-90). | Baseline, 6 months, 12 months |
| Change in Self-Reported Suicide Attempts | The investigators will use the interviewer-administered Suicide Attempt and Self-Injury Count to assess the method, intent, treatment received, and lethality for all suicide attempts over the respondent's lifetime. | Baseline, 6 months, 12 months |
| Change in Hospitalizations and Behavioral Health Treatment | The investigators will assess self-reported hospitalizations over the previous 12 months with a measure of health service use previously applied to AI/ANs. It captures information on inpatient and outpatient medical care, emergency room visits, and use of traditional practices. | Baseline, 6 months, 12 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Social Connectedness | The investigators will assess social connectedness with the Interpersonal Needs Questionnaire, a validated measure of feelings of connectedness to others and of being a burden on others. | Baseline, 6 months, 12 months |
| SBIRT Retention and Uptake of Referral to Therapy | Retention will be measured as binary indicators of complete participation in the appropriate level of intervention determined during the initial in-person session with the behavioral therapist before enrollment in the study, and as uptake of therapy services for people who are referred to this level of care. For each participant, we will create a 3-category indicator of retention (full, partial, none). | 6 months, 12 months |
|
American Indian, Alaska Native, Youth and Young Adult, SBIRT
|
Suicide, Suicide Prevention, Self-Injurious Behavior, Behavioral Symptoms
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: SBIRT+Usual Care<br>The control arm of the trial will receive the usual care prescribed in the Screening, Brief Intervention and Referral to Treatment (SBIRT) model. | Behavioral: SBIRT+Usual Care<br>* Patients receive usual SBIRT care<br>|
| Experimental: SBIRT+12<br>The standard SBIRT model is augmented by a 12 month period following identification of suicide risk during which participants will receive caring text messages adapted from empirically-based, effective interventions for suicide prevention among American Indian and Alaska Native young adults. | Behavioral: SBIRT+12<br>* The standard SBIRT model is augmented by a 12 month period following identification of suicide risk during which participants received caring text messages adapted from empirically-based, effective interventions for suicide prevention among American Indian and Alaska Native young adults.<br>|
|
Suicide in Urban Natives: Detection and Networks to Combat Events
Study Overview
=================
Brief Summary
-----------------
This study compares the effectiveness of a program to detect and manage suicide risk among American-Indian and Alaska Native (AI/AN) youth. Half of the participants will receive caring text messages to reduce suicidal thoughts, attempts, and hospitalizations and to increase engagement, social connectedness, and resilience in at-risk youth. The other half will receive usual care that does not include the caring text messages.
Detailed Description
-----------------
The study, Suicide in Urban Natives: Detection and Networks to Combat Events, builds on Screening, Brief Intervention and Referral to treatment (SBIRT), carried out through the primary care setting, to detect and manage suicide risk. This approach is multilevel, targeting both the healthcare system and the individual, and links screening to existing mobile phone technologies shown to promote resilience and to tap the protective benefits of social connectedness. This Collaborative Hub will conduct a randomized control trial that compares the effectiveness of enhancing these SBIRT programs by sending caring text messages to reduce suicidal ideation, attempts, and hospitalizations, and to increase engagement, social connectedness, and resilience. The Investigators' long-term goal is to disseminate and translate the lessons learned into practical policy, organizational changes, and preventive innovations that optimize patient-centered health outcomes and ultimately reduce or eliminate the dramatic and tragic suicide-related health disparities among urban AI/AN youth and young adults.
Official Title
-----------------
Collaborative Hub to Reduce the Burden of Suicide Among Urban American Indian and Alaska Native Young Adults
Conditions
-----------------
Suicide Prevention
Intervention / Treatment
-----------------
* Behavioral: SBIRT+12
* Behavioral: SBIRT+Usual Care
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Self-identify as American Indian or Alaska Native; Screen positive for mild, moderate, or severe risk of suicidality (referred by a clinical provider); Have a text-enabled mobile phone; Willing to be contacted by text; Able to participate voluntarily; Speak and read English; Cognitively able to independently provide written informed consent Exclusion Criteria: Under age 18 In danger of imminent self-harm; Hospitalized
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 34 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: The Investigators will conduct a randomized controlled trial to test the effectiveness of an augmented Screening, Brief Intervention, and Referral to Treatment (SBIRT) model that includes sending caring text messages for 12 months after an at-risk patient is identified.
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: SBIRT+Usual Care<br>The control arm of the trial will receive the usual care prescribed in the Screening, Brief Intervention and Referral to Treatment (SBIRT) model. | Behavioral: SBIRT+Usual Care<br>* Patients receive usual SBIRT care<br>|
| Experimental: SBIRT+12<br>The standard SBIRT model is augmented by a 12 month period following identification of suicide risk during which participants will receive caring text messages adapted from empirically-based, effective interventions for suicide prevention among American Indian and Alaska Native young adults. | Behavioral: SBIRT+12<br>* The standard SBIRT model is augmented by a 12 month period following identification of suicide risk during which participants received caring text messages adapted from empirically-based, effective interventions for suicide prevention among American Indian and Alaska Native young adults.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Suicidal Ideation | The 15-item Suicidal Ideation Questionnaire Jr. assesses frequency of suicidal thoughts in the past month. Item content ranges from general thoughts of death and wishes that one were dead to specific thoughts of self-injurious behavior. Responses are on a 7-point scale ranging from never to almost daily. Items are summed for a total score (range 0-90). | Baseline, 6 months, 12 months |
| Change in Self-Reported Suicide Attempts | The investigators will use the interviewer-administered Suicide Attempt and Self-Injury Count to assess the method, intent, treatment received, and lethality for all suicide attempts over the respondent's lifetime. | Baseline, 6 months, 12 months |
| Change in Hospitalizations and Behavioral Health Treatment | The investigators will assess self-reported hospitalizations over the previous 12 months with a measure of health service use previously applied to AI/ANs. It captures information on inpatient and outpatient medical care, emergency room visits, and use of traditional practices. | Baseline, 6 months, 12 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Social Connectedness | The investigators will assess social connectedness with the Interpersonal Needs Questionnaire, a validated measure of feelings of connectedness to others and of being a burden on others. | Baseline, 6 months, 12 months |
| SBIRT Retention and Uptake of Referral to Therapy | Retention will be measured as binary indicators of complete participation in the appropriate level of intervention determined during the initial in-person session with the behavioral therapist before enrollment in the study, and as uptake of therapy services for people who are referred to this level of care. For each participant, we will create a 3-category indicator of retention (full, partial, none). | 6 months, 12 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
American Indian, Alaska Native, Youth and Young Adult, SBIRT
|
NCT02251574
|
Effect of a Very Low Calorie and Low Calorie Diet on Moderate to Severe Obstructive Sleep Apnea in Obese Adults
|
The purpose of this study is to test the effectiveness of two different weight loss diets on obstructive sleep apnea (OSA) severity.
|
Sleep apnea is a sleep disorder in which breathing repeatedly stops and starts during sleep. The most common type is obstructive sleep apnea (OSA), which occurs when the muscles in your throat relax and block your airway during sleep. The most noticeable sign of OSA is snoring. OSA is a risk factor for other chronic conditions like type 2 diabetes, cardiovascular disease, and high blood pressure.~Although anyone can develop OSA, it commonly affects people who are obese. The more someone weighs, the more likely the OSA is to be severe. Weight loss is typically recommended for overweight individuals to help improve OSA. However, not enough research has been done for doctors to be able make specific recommendations to their patients.
|
Effect of a Very Low Calorie and Low Calorie Diet on Moderate to Severe Obstructive Sleep Apnea in Obese Adults
|
Obstructive Sleep Apnea
|
* Other: Low Calorie Diet
* Other: Very Low Calorie Diet
* Other: Standard Care
|
Inclusion Criteria:~AHI score of ≥ 5~Body mass index (BMI) between 30 to 49.9 kg/m2~Exclusion Criteria:~Report serious medical risk such as insulin-dependent diabetes, active cancer, recent cardiac event~Currently or planning to become pregnant during the next 9 months~Not weight stable (-4.6 kg) for 3 mos. prior to intake~Report current participation in a weight reduction program involving diet or PA~Unwilling to be randomized to 1 of 3 study groups~Report symptomology of an eating disorder as determined by the Eating Attitudes Test~Unable to participate in moderate intensity physical activity
|
21 Years
|
75 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Apnea Hypopnea Index (AHI) | The AHI measures sleep apnea severity and represents the number of apnea and hypopnea events per hour. | Change from Baseline to Month 3 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Apnea Hypopnea Index (AHI) | The AHI measures sleep apnea severity and represents the number of apnea and hypopnea events per hour. | Change from Baseline to Month 9 |
| Change in metabolic syndrome (MetS) risk factors | Risk factors to be measured include waist circumference, triglycerides, HDL-cholesterol, blood pressure, fasting glucose | Change from Baseline to Month 3 and Month 9 |
| Change in Quality of Life | Participants will complete the Calgary Sleep Apnea Quality of Life Index (SAQLI) that will assess participants response to the intervention/treatment. | Change from Baseline to Month 3 and Month 9 |
| Change in Daytime Sleepiness | Researchers will administer Epworth Sleepiness Scale. Results will be used to calculate daytime sleepiness changes for each participant. | Change from Baseline to Month 3 and Month 9 |
|
Apnea, Dyssomnias, Sleep Apnea Syndromes, Sleep Apnea, Obstructive, Respiration Disorders, Respiratory Tract Diseases, Signs and Symptoms, Respiratory, Sleep Disorders, Intrinsic, Sleep Wake Disorders, Nervous System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Calorie Diet<br>Participants will take part in an experimental weight management program involving a low calorie diet (LCD), about 1200-1500 calories per day. | Other: Low Calorie Diet<br>* Weight management program designed around a low calorie diet.<br>|
| Experimental: Very Low Calorie Diet<br>Participants will take part in an experimental weight management program involving a low calorie diet (LCD), about 520-800 calories per day. | Other: Very Low Calorie Diet<br>* Weight management program designed around a very low calorie diet.<br>|
| Active Comparator: Standard Care<br>Participants will receive normal care. | Other: Standard Care<br>* Care provided that would normally be given to people meeting eligibility criteria for this study.<br>|
|
Effect of a Very Low Calorie and Low Calorie Diet on Moderate to Severe Obstructive Sleep Apnea in Obese Adults
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to test the effectiveness of two different weight loss diets on obstructive sleep apnea (OSA) severity.
Detailed Description
-----------------
Sleep apnea is a sleep disorder in which breathing repeatedly stops and starts during sleep. The most common type is obstructive sleep apnea (OSA), which occurs when the muscles in your throat relax and block your airway during sleep. The most noticeable sign of OSA is snoring. OSA is a risk factor for other chronic conditions like type 2 diabetes, cardiovascular disease, and high blood pressure. Although anyone can develop OSA, it commonly affects people who are obese. The more someone weighs, the more likely the OSA is to be severe. Weight loss is typically recommended for overweight individuals to help improve OSA. However, not enough research has been done for doctors to be able make specific recommendations to their patients.
Official Title
-----------------
Effect of a Very Low Calorie and Low Calorie Diet on Moderate to Severe Obstructive Sleep Apnea in Obese Adults
Conditions
-----------------
Obstructive Sleep Apnea
Intervention / Treatment
-----------------
* Other: Low Calorie Diet
* Other: Very Low Calorie Diet
* Other: Standard Care
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: AHI score of ≥ 5 Body mass index (BMI) between 30 to 49.9 kg/m2 Exclusion Criteria: Report serious medical risk such as insulin-dependent diabetes, active cancer, recent cardiac event Currently or planning to become pregnant during the next 9 months Not weight stable (-4.6 kg) for 3 mos. prior to intake Report current participation in a weight reduction program involving diet or PA Unwilling to be randomized to 1 of 3 study groups Report symptomology of an eating disorder as determined by the Eating Attitudes Test Unable to participate in moderate intensity physical activity
Ages Eligible for Study
-----------------
Minimum Age: 21 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
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Calorie Diet<br>Participants will take part in an experimental weight management program involving a low calorie diet (LCD), about 1200-1500 calories per day. | Other: Low Calorie Diet<br>* Weight management program designed around a low calorie diet.<br>|
| Experimental: Very Low Calorie Diet<br>Participants will take part in an experimental weight management program involving a low calorie diet (LCD), about 520-800 calories per day. | Other: Very Low Calorie Diet<br>* Weight management program designed around a very low calorie diet.<br>|
| Active Comparator: Standard Care<br>Participants will receive normal care. | Other: Standard Care<br>* Care provided that would normally be given to people meeting eligibility criteria for this study.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Apnea Hypopnea Index (AHI) | The AHI measures sleep apnea severity and represents the number of apnea and hypopnea events per hour. | Change from Baseline to Month 3 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Apnea Hypopnea Index (AHI) | The AHI measures sleep apnea severity and represents the number of apnea and hypopnea events per hour. | Change from Baseline to Month 9 |
| Change in metabolic syndrome (MetS) risk factors | Risk factors to be measured include waist circumference, triglycerides, HDL-cholesterol, blood pressure, fasting glucose | Change from Baseline to Month 3 and Month 9 |
| Change in Quality of Life | Participants will complete the Calgary Sleep Apnea Quality of Life Index (SAQLI) that will assess participants response to the intervention/treatment. | Change from Baseline to Month 3 and Month 9 |
| Change in Daytime Sleepiness | Researchers will administer Epworth Sleepiness Scale. Results will be used to calculate daytime sleepiness changes for each participant. | Change from Baseline to Month 3 and Month 9 |
|
|
NCT05653024
|
INhaled Salbutamol vs Placebo for the Treatment of Acute IgE-mediated Abdominal Pain From Allergic Food REactions
|
The goal of this study is to assess the efficacy of inhaled salbutamol to treat abdominal pain during food allergic reactions.~Patients experiencing abominal pain as a result of a food allergic reaction during a food challenge in the allergy clinic will be invited to participate to the study.~They will receive either 8 puffs of salbutamol (asthma inhaler) or 8 puffs of a placebo inhaler.~The abdominal pain will then be followed using a numeric scale to see if patients receiving the medication experienced a faster improvement compared to those receiving the placebo.
|
This trial aims to compare the efficacy of inhaled salbutamol compared to placebo to decrease the duration of abdominal pain in children and adults with IgE-mediated food allergic reactions.~The population will be children and adults aged 6 to 55 presenting with moderate to severe IgE-mediated abdominal pain in the context of an oral food challenge or an oral immunotherapy dose increase at the allergy clinic.~Eligible participants will be randomized to receive an immediate treatement with either inhaled salbutamol 800 mcg or inhaled placebo, dispensed with a spacer, at a ratio of 1:1.~Participants will be asked to rate the evolution of their abdominal pain by the minute on the NRS-11 scale until it resolves completely or that they have been discharged.~Patients still presenting moderate to severe abdominal pain 30 minutes after the administration of the investigational product will receive an open-label treatment with 800 mcg of inhaled salbutamol.~The primary outcome is the time from treatment to a decrease of the abdominal pain down to a mild intensity (defined as a pain for which the patient would not normally seek treatment).~Participants will be contacted by phone after three days to document any adverse event.~The primary endpoint will be analysed using a log-rank test.
|
A Double-blind Randomized Controlled Trial of Inhaled Salbutamol vs Placebo for the Treatment of Acute Abdominal Pain From Food-induced IgE-mediated Reactions
|
IgE-mediated Abdominal Pain
|
* Drug: Salbutamol
* Drug: Placebo
|
Inclusion Criteria:~Subjects aged between 6 to 55 years old.~Undergoing an oral food challenge or an oral immunotherapy up-dosing visit for the diagnosis or treatment of an IgE-mediated food allergy.~Previous confirmation of the food allergy by either skin prick tests (SPT) or serum specific IgE;~Able to express the intensity of their pain using the NRS-11;~Willing to comply with all study requirements.~Exclusion Criteria:~Previous adverse reactions to salbutamol;~Known hypersensitivity to salbutamol or placebo or any of their components;~Any condition that could be considered a relative contra-indication to the use of salbutamol according to the investigator (e.g. patient with a history of hyperglycemia, arrhythmia or hypokalemia);~Patients receiving beta-blockers or a daily / long-acting beta agonists;~Patients needing to pass an anti-doping test for high-level sport in the following 24h.
|
6 Years
|
55 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to resolution of moderate-to-severe abdominal pain | Time from treatment to an abdominal pain of less than moderate intensity, defined as a pain for which the patient would not normally seek treatment | From time of administation of investigational product, until the pain decreases to a point where the patient would not normally seek treatment, assessed up to 30 minutes |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to complete resolution of the abdominal pain | Time from treatment to the complete resolution of the abdominal pain. | From time of administation of investigational product, until the pain is completely resolved, assessed up to 30 minutes |
| Time to any improvement in the abdominal pain | Time from treatment to any decrease in the 11-point numeric pain rating scale (NRS-11) | From time of administation of investigational product, until any decrease in the NRS-11, assessed up to 30 minutes |
| Epinephrine use | Overall rate of epinephrine administration following randomization | From randomization to three days after randomization |
| Adverse events | Overall rate of adverse events following randomization | From randomization to three days after randomization |
|
food allergy, anaphylaxis
|
Tocolytic Agents, Anti-Asthmatic Agents, Respiratory System Agents, Reproductive Control Agents, Adrenergic beta-Agonists, Albuterol, Bronchodilator Agents, Autonomic Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Adrenergic beta-2 Receptor Agonists, Adrenergic Agonists, Adrenergic Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhaled salbutamol<br>8 puffs of 100 mcg of inhaled salbutamol once | Drug: Salbutamol<br>* 8 puffs of 100 mcg inhaled salbutamol administered with spacer<br>|
| Placebo Comparator: Placebo<br>8 puffs of inhaled placebo once | Drug: Placebo<br>* 8 puffs of placebo inhaler administered with spacer<br>|
|
INhaled Salbutamol vs Placebo for the Treatment of Acute IgE-mediated Abdominal Pain From Allergic Food REactions
Study Overview
=================
Brief Summary
-----------------
The goal of this study is to assess the efficacy of inhaled salbutamol to treat abdominal pain during food allergic reactions. Patients experiencing abominal pain as a result of a food allergic reaction during a food challenge in the allergy clinic will be invited to participate to the study. They will receive either 8 puffs of salbutamol (asthma inhaler) or 8 puffs of a placebo inhaler. The abdominal pain will then be followed using a numeric scale to see if patients receiving the medication experienced a faster improvement compared to those receiving the placebo.
Detailed Description
-----------------
This trial aims to compare the efficacy of inhaled salbutamol compared to placebo to decrease the duration of abdominal pain in children and adults with IgE-mediated food allergic reactions. The population will be children and adults aged 6 to 55 presenting with moderate to severe IgE-mediated abdominal pain in the context of an oral food challenge or an oral immunotherapy dose increase at the allergy clinic. Eligible participants will be randomized to receive an immediate treatement with either inhaled salbutamol 800 mcg or inhaled placebo, dispensed with a spacer, at a ratio of 1:1. Participants will be asked to rate the evolution of their abdominal pain by the minute on the NRS-11 scale until it resolves completely or that they have been discharged. Patients still presenting moderate to severe abdominal pain 30 minutes after the administration of the investigational product will receive an open-label treatment with 800 mcg of inhaled salbutamol. The primary outcome is the time from treatment to a decrease of the abdominal pain down to a mild intensity (defined as a pain for which the patient would not normally seek treatment). Participants will be contacted by phone after three days to document any adverse event. The primary endpoint will be analysed using a log-rank test.
Official Title
-----------------
A Double-blind Randomized Controlled Trial of Inhaled Salbutamol vs Placebo for the Treatment of Acute Abdominal Pain From Food-induced IgE-mediated Reactions
Conditions
-----------------
IgE-mediated Abdominal Pain
Intervention / Treatment
-----------------
* Drug: Salbutamol
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects aged between 6 to 55 years old. Undergoing an oral food challenge or an oral immunotherapy up-dosing visit for the diagnosis or treatment of an IgE-mediated food allergy. Previous confirmation of the food allergy by either skin prick tests (SPT) or serum specific IgE; Able to express the intensity of their pain using the NRS-11; Willing to comply with all study requirements. Exclusion Criteria: Previous adverse reactions to salbutamol; Known hypersensitivity to salbutamol or placebo or any of their components; Any condition that could be considered a relative contra-indication to the use of salbutamol according to the investigator (e.g. patient with a history of hyperglycemia, arrhythmia or hypokalemia); Patients receiving beta-blockers or a daily / long-acting beta agonists; Patients needing to pass an anti-doping test for high-level sport in the following 24h.
Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 55 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhaled salbutamol<br>8 puffs of 100 mcg of inhaled salbutamol once | Drug: Salbutamol<br>* 8 puffs of 100 mcg inhaled salbutamol administered with spacer<br>|
| Placebo Comparator: Placebo<br>8 puffs of inhaled placebo once | Drug: Placebo<br>* 8 puffs of placebo inhaler administered with spacer<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to resolution of moderate-to-severe abdominal pain | Time from treatment to an abdominal pain of less than moderate intensity, defined as a pain for which the patient would not normally seek treatment | From time of administation of investigational product, until the pain decreases to a point where the patient would not normally seek treatment, assessed up to 30 minutes |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to complete resolution of the abdominal pain | Time from treatment to the complete resolution of the abdominal pain. | From time of administation of investigational product, until the pain is completely resolved, assessed up to 30 minutes |
| Time to any improvement in the abdominal pain | Time from treatment to any decrease in the 11-point numeric pain rating scale (NRS-11) | From time of administation of investigational product, until any decrease in the NRS-11, assessed up to 30 minutes |
| Epinephrine use | Overall rate of epinephrine administration following randomization | From randomization to three days after randomization |
| Adverse events | Overall rate of adverse events following randomization | From randomization to three days after randomization |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
food allergy, anaphylaxis
|
NCT04970823
|
The Effect of Interactive Games on Children Receiving Intravenous Injection
|
Pediatric intravenous injection is one of the most painful events that children may be exposed to during hospitalization or illness, and it is also the most routinely performed invasive procedure. The purpose of this study is to examine the effectiveness of somatosensory interactive games on intravenous pain relief for preschool children, and to establish a VR (virtual reality) game environment for school-age children. Using a randomized experimental study, the data came from the pediatric ward. The results will show whether there is a statistically significant difference between the experimental group and the control group.
|
Pediatric intravenous injection is one of the most painful events that children may be exposed to during hospitalization or illness, and it is also the most routinely performed invasive procedure. Non-pharmaceutical techniques can be used to relieve pain associated with intravenous injections. Distraction is a non-pharmacological technique that can take child's attention away from pain. The somatosensory interactive game is an independent nursing intervention that promotes pain relief. The purpose of this study is to examine the effectiveness of somatosensory interactive games on intravenous pain relief for preschool children, and to establish a VR (virtual reality) game environment for school-age children. Using a randomized experimental study, the data came from the pediatric ward. At least qualified 132 preschool children are in this study and their caregivers signed a consent form to participate in the study. Children are divided into experimental group and control group, and each group has at least 66 children. In addition to 60 school-age children, 30 played VR games for about 3 minutes during intravenous injection, and 30 received regular intravenous injection. The preschool experimental group and the school-age experimental group each took the parents of 5 children (10 in total) to conduct semi-structured qualitative interviews to understand the differences in experience before and after the intervention. This study is expected to accept a total of 202 children and parents. Data collection tools include WBFPS (Wong-Baker Faces Scale) to measure children's pain and CFS (Children's Fear scale) to measure children's fear. CEMS continue assessment negative emotion two days. The results will show whether there is a statistically significant difference between the experimental group and the control group. Qualitative study used semi-structed interviews were conducted with selected and their parent.
|
The Effect of Somatosensory Interactive Games on the Pain, Fear and Negative Emotions of Children Receiving Intravenous Injection
|
Pain, Fear, Emotions
|
* Device: The somatosensory interactive game for preschool children
* Device: A VR (virtual reality) game for school-age children
|
Inclusion criteria:~2-7 years old, normal consciousness, preschool children who need intravenous injection.~7-12 years old, normal consciousness, school-age children who need intravenous injection.~Parents of children need to be conscious and able to talk in Chinese.~Exclusion criteria:~2-7 years old preschool children with developmental delay, epilepsy, heart disease, chemotherapy, visual and hearing impaired, obese, and have received more than 2 intravenous injections.~7-12-year-old school-age children with developmental delay, epilepsy, heart disease, chemotherapy, visual and hearing impaired, obese, and have received more than 2 intravenous injections.~The child's parents cannot express and communicate effectively.
|
2 Years
|
12 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in children's pain from baseline to after intravenous injection | Using Wong-Baker Faces Pain Rating Scale to measure pain. There are 6 faces in the Wong-Baker Pain Scale. The first face represents a pain score of 0, and indicates no hurt. The second face represents a pain score of 2, and indicates hurts a little bit. The third face represents a pain score of 4, and indicates hurts a little more. The fourth face represents a pain score of 6, and indicates hurts even more. The fifth face represents a pain score of 8, and indicates hurts a whole lot; the sixth face represents a pain score of 10, and indicates hurts worst. Nurses, pre-school children by the assistance of caregivers, and school-age children were asked to evaluate the pain levels experienced by the children receiving intravenous injections. | O1 (before intervention); O2 (immediately after intravenous injection); O3 (1 day after intravenous injection) |
| Changes in children's fear from baseline to after intravenous injection | Using Children's Fear scale to measure the fear level. Score the chosen face from 0 (the left-most face) to 4 (the last face). This face [point to the left-most face] shows no anxiety at all, this faces shows a little bit more [point to second face from left], a bit more [sweep finger along scale], right up to extreme anxiety [point to the last face on the right]. Nurses, pre-school children by the assistance of caregivers, and school-age children were asked to evaluate the fear levels experienced by the children receiving intravenous injections. | O1 (before intervention); O2 (immediately after intravenous injection); O3 (1 day after intravenous injection) |
| Changes in children's emotion from baseline to after intravenous injection | Using Children's Emotional Management Scales to measure the emotion level. The scale includes five observed emotional behavior categories, facial expression, vocalization, activity, interaction, and level of cooperation. Each category is scored from 1-5 points, the lowest total score is 5 points, and the highest score is 25 points. The higher the score, the more negative emotional behavior. Nurses, pre-school children by the assistance of caregivers, and school-age children were asked to evaluate the emotion levels experienced by the children receiving intravenous injections. | O1 (before intervention); O2 (immediately after intravenous injection); O3 (1 day after intravenous injection) |
| semi-structed interviews | After intravenous injection, a semi-structured qualitative interview was conducted with selected and their parent to understand the differences in experience before and after intervention. | immediately after intravenous injection |
|
school-age children, injection, pain, Somatosensory interactive games
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The somatosensory interactive game<br>The somatosensory interactive game, an independent nursing intervention, promotes pain relief on the experimental group. | Device: The somatosensory interactive game for preschool children<br>* The somatosensory interactive game, an independent nursing intervention, promotes pain relief for preschool children.<br>|
| Experimental: A VR (virtual reality) game<br>A VR (virtual reality) game promotes pain relief on the experimental group. | Device: A VR (virtual reality) game for school-age children<br>* A VR (virtual reality) game environment promotes pain relief for school-age children.<br>|
|
The Effect of Interactive Games on Children Receiving Intravenous Injection
Study Overview
=================
Brief Summary
-----------------
Pediatric intravenous injection is one of the most painful events that children may be exposed to during hospitalization or illness, and it is also the most routinely performed invasive procedure. The purpose of this study is to examine the effectiveness of somatosensory interactive games on intravenous pain relief for preschool children, and to establish a VR (virtual reality) game environment for school-age children. Using a randomized experimental study, the data came from the pediatric ward. The results will show whether there is a statistically significant difference between the experimental group and the control group.
Detailed Description
-----------------
Pediatric intravenous injection is one of the most painful events that children may be exposed to during hospitalization or illness, and it is also the most routinely performed invasive procedure. Non-pharmaceutical techniques can be used to relieve pain associated with intravenous injections. Distraction is a non-pharmacological technique that can take child's attention away from pain. The somatosensory interactive game is an independent nursing intervention that promotes pain relief. The purpose of this study is to examine the effectiveness of somatosensory interactive games on intravenous pain relief for preschool children, and to establish a VR (virtual reality) game environment for school-age children. Using a randomized experimental study, the data came from the pediatric ward. At least qualified 132 preschool children are in this study and their caregivers signed a consent form to participate in the study. Children are divided into experimental group and control group, and each group has at least 66 children. In addition to 60 school-age children, 30 played VR games for about 3 minutes during intravenous injection, and 30 received regular intravenous injection. The preschool experimental group and the school-age experimental group each took the parents of 5 children (10 in total) to conduct semi-structured qualitative interviews to understand the differences in experience before and after the intervention. This study is expected to accept a total of 202 children and parents. Data collection tools include WBFPS (Wong-Baker Faces Scale) to measure children's pain and CFS (Children's Fear scale) to measure children's fear. CEMS continue assessment negative emotion two days. The results will show whether there is a statistically significant difference between the experimental group and the control group. Qualitative study used semi-structed interviews were conducted with selected and their parent.
Official Title
-----------------
The Effect of Somatosensory Interactive Games on the Pain, Fear and Negative Emotions of Children Receiving Intravenous Injection
Conditions
-----------------
Pain, Fear, Emotions
Intervention / Treatment
-----------------
* Device: The somatosensory interactive game for preschool children
* Device: A VR (virtual reality) game for school-age children
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: 2-7 years old, normal consciousness, preschool children who need intravenous injection. 7-12 years old, normal consciousness, school-age children who need intravenous injection. Parents of children need to be conscious and able to talk in Chinese. Exclusion criteria: 2-7 years old preschool children with developmental delay, epilepsy, heart disease, chemotherapy, visual and hearing impaired, obese, and have received more than 2 intravenous injections. 7-12-year-old school-age children with developmental delay, epilepsy, heart disease, chemotherapy, visual and hearing impaired, obese, and have received more than 2 intravenous injections. The child's parents cannot express and communicate effectively.
Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 12 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: The somatosensory interactive game<br>The somatosensory interactive game, an independent nursing intervention, promotes pain relief on the experimental group. | Device: The somatosensory interactive game for preschool children<br>* The somatosensory interactive game, an independent nursing intervention, promotes pain relief for preschool children.<br>|
| Experimental: A VR (virtual reality) game<br>A VR (virtual reality) game promotes pain relief on the experimental group. | Device: A VR (virtual reality) game for school-age children<br>* A VR (virtual reality) game environment promotes pain relief for school-age children.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in children's pain from baseline to after intravenous injection | Using Wong-Baker Faces Pain Rating Scale to measure pain. There are 6 faces in the Wong-Baker Pain Scale. The first face represents a pain score of 0, and indicates no hurt. The second face represents a pain score of 2, and indicates hurts a little bit. The third face represents a pain score of 4, and indicates hurts a little more. The fourth face represents a pain score of 6, and indicates hurts even more. The fifth face represents a pain score of 8, and indicates hurts a whole lot; the sixth face represents a pain score of 10, and indicates hurts worst. Nurses, pre-school children by the assistance of caregivers, and school-age children were asked to evaluate the pain levels experienced by the children receiving intravenous injections. | O1 (before intervention); O2 (immediately after intravenous injection); O3 (1 day after intravenous injection) |
| Changes in children's fear from baseline to after intravenous injection | Using Children's Fear scale to measure the fear level. Score the chosen face from 0 (the left-most face) to 4 (the last face). This face [point to the left-most face] shows no anxiety at all, this faces shows a little bit more [point to second face from left], a bit more [sweep finger along scale], right up to extreme anxiety [point to the last face on the right]. Nurses, pre-school children by the assistance of caregivers, and school-age children were asked to evaluate the fear levels experienced by the children receiving intravenous injections. | O1 (before intervention); O2 (immediately after intravenous injection); O3 (1 day after intravenous injection) |
| Changes in children's emotion from baseline to after intravenous injection | Using Children's Emotional Management Scales to measure the emotion level. The scale includes five observed emotional behavior categories, facial expression, vocalization, activity, interaction, and level of cooperation. Each category is scored from 1-5 points, the lowest total score is 5 points, and the highest score is 25 points. The higher the score, the more negative emotional behavior. Nurses, pre-school children by the assistance of caregivers, and school-age children were asked to evaluate the emotion levels experienced by the children receiving intravenous injections. | O1 (before intervention); O2 (immediately after intravenous injection); O3 (1 day after intravenous injection) |
| semi-structed interviews | After intravenous injection, a semi-structured qualitative interview was conducted with selected and their parent to understand the differences in experience before and after intervention. | immediately after intravenous injection |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
school-age children, injection, pain, Somatosensory interactive games
|
||
NCT01694043
|
The Effect of Watching a Television Show on the Liking of Snack Foods
|
The purpose of the study is to investigate the effect of watching a television show with healthy food commercials, unhealthy food commercials, or neutral commercials on the consumption of healthy snack foods or unhealthy snack foods. There are three hypotheses: 1) Women exposed to a television show with commercials imbedded advertising food will consume more food than women exposed to a television show with non-food related commercials.~2) Women will consume more food when exposed to a television show with commercials advertising unhealthy food as compared to a television show with commercials advertising healthy food.~3) Women will consume the most food when exposed to a television show with unhealthy food commercials and have unhealthy snack foods available to consume.
|
The objective of this investigation is to investigate the effect of television shows with commercials perceived as advertising healthy foods and television shows with commercials perceived as advertising unhealthy foods on the intake of either perceived healthy snack foods or perceived unhealthy snack foods in normal weight, dietary restrained females.~Forty-eight women will participate in this study and will be randomized to one of six conditions where they will be exposed to a 30-minute television show (Saturday Night Live) during which they will be given two different pre-measured snack foods to eat. The television show will have eight commercials imbedded within it. Of the eight commercials, five commercials will represent the study condition (five advertising healthy food, five advertising unhealthy food, or five non-food related commercials). The three additional commercials will advertise neutral products (banks) and will remain the same in each condition. Snack foods being used in this investigation are red grapes and baby carrots for the perceived healthy snack foods; and chocolate chip cookies and potato chips for the perceived unhealthy snack foods. The television commercials representing the unhealthy category include commercials advertising M&M's candies, Oreo cookies, Cheez-it crackers, 3 Musketeers chocolate bars, and Doritos chips. The television commercials representing the healthy category include commercials advertising Fiber One bars, Honey Bunches of Oats cereal, Nature's Path granola, Nestle fruit yogurt, and Musselman's apple sauce. The non-food related television commercials include commercials advertising All-State car insurance, Geico car insurance, State Farm car insurance, Travelers car insurance, and Liberty Mutual car insurance. The three neutral non-food related commercials that will remain the same in each condition are commercials advertising Fifth Third bank, Ally bank, and Capital One bank.~The specific aims and hypotheses are:~Women exposed to a television show with commercials imbedded advertising food will consume more food than women exposed to a television show with non-food related commercials.~Women will consume more food when exposed to a television show with commercials advertising unhealthy food as compared to a television show with commercials advertising healthy food.~Women will consume the most food when exposed to a television show with unhealthy food commercials and have unhealthy snack foods available to consume.
|
The Effect of Perceived Healthy and Unhealthy Commercials on Intake of Perceived Healthy and Unhealthy Snack Foods in Normal Weight, College-Aged, Dietary Restrained Women
|
Measure Grams and Kcals of Snack Foods Consumed in Each Condition
|
* Other: Healthy Foods
* Other: Unhealthy Snack Foods
|
Inclusion Criteria:~Age between 18 and 30 years~have a body mass index between 18.5 and 24.9 kg/m2~Be a restrained eater (scoring >12 on Three Factor Eating Questionnaire~Report being a non-smoker~Perceive foods and commercials used in the study as appropriately classified in the study.~Exclusion Criteria:~Currently dieting for weight loss~Currently taking any medications that affect appetite or food intake~Have a medical condition affecting eating or are currently following a therapeutic diet~Report disliking foods used in the investigation~Report having allergies to foods used in the investigation
|
18 Years
|
30 Years
|
Female
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total grams of snack foods consumed | The snack foods that will be used in this investigation are red grapes, baby carrots, Chips Ahoy! chocolate chip cookies (Kraft Foods Global Inc., Northfield, IL), and Lays potato chips (Frito-Lay Inc., Plano, TX). Participants will be provided with 200 grams of two different foods, depending on the condition to which they are randomized. Snack foods provided to participants in each condition will be measured in grams to the tenth decimal point on an electronic food scale (Denver Instrument Co., Arvada, CO) before and after the session. The weight of the container will also be measured. Total grams of snack food consumed during the session will be determined by subtracting pre- and post-consumption weight of snack food. | 1 year |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measured kilocalories consumed | The amount of kilocalories consumed in each session will be calculated by determining the weight of food consumed and calculating using food label. | 1 year |
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-Food Related Commercials<br>Participants will watch a 30-minute Saturday Night Live television show with non-food related commercials embedded. | Other: Healthy Foods<br>* While watching the tv show, participants will receive a healthy snack to eat (grapes and baby carrots).<br>Other: Unhealthy Snack Foods<br>* While watching the tv show, participants will receive an unhealthy snack to eat (potato chips and chocolate chip cookies).<br>|
| Experimental: Healthy Food Commercials<br>Participants will watch a 30-minute Saturday Night Live television show with healthy food commercials embedded. | Other: Healthy Foods<br>* While watching the tv show, participants will receive a healthy snack to eat (grapes and baby carrots).<br>Other: Unhealthy Snack Foods<br>* While watching the tv show, participants will receive an unhealthy snack to eat (potato chips and chocolate chip cookies).<br>|
| Experimental: Unhealthy Food Commericlas<br>Participants will watch a 30-minute Saturday Night Live television show with unhealthy food commercials imbedded. | Other: Healthy Foods<br>* While watching the tv show, participants will receive a healthy snack to eat (grapes and baby carrots).<br>Other: Unhealthy Snack Foods<br>* While watching the tv show, participants will receive an unhealthy snack to eat (potato chips and chocolate chip cookies).<br>|
|
The Effect of Watching a Television Show on the Liking of Snack Foods
Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to investigate the effect of watching a television show with healthy food commercials, unhealthy food commercials, or neutral commercials on the consumption of healthy snack foods or unhealthy snack foods. There are three hypotheses: 1) Women exposed to a television show with commercials imbedded advertising food will consume more food than women exposed to a television show with non-food related commercials. 2) Women will consume more food when exposed to a television show with commercials advertising unhealthy food as compared to a television show with commercials advertising healthy food. 3) Women will consume the most food when exposed to a television show with unhealthy food commercials and have unhealthy snack foods available to consume.
Detailed Description
-----------------
The objective of this investigation is to investigate the effect of television shows with commercials perceived as advertising healthy foods and television shows with commercials perceived as advertising unhealthy foods on the intake of either perceived healthy snack foods or perceived unhealthy snack foods in normal weight, dietary restrained females. Forty-eight women will participate in this study and will be randomized to one of six conditions where they will be exposed to a 30-minute television show (Saturday Night Live) during which they will be given two different pre-measured snack foods to eat. The television show will have eight commercials imbedded within it. Of the eight commercials, five commercials will represent the study condition (five advertising healthy food, five advertising unhealthy food, or five non-food related commercials). The three additional commercials will advertise neutral products (banks) and will remain the same in each condition. Snack foods being used in this investigation are red grapes and baby carrots for the perceived healthy snack foods; and chocolate chip cookies and potato chips for the perceived unhealthy snack foods. The television commercials representing the unhealthy category include commercials advertising M&M's candies, Oreo cookies, Cheez-it crackers, 3 Musketeers chocolate bars, and Doritos chips. The television commercials representing the healthy category include commercials advertising Fiber One bars, Honey Bunches of Oats cereal, Nature's Path granola, Nestle fruit yogurt, and Musselman's apple sauce. The non-food related television commercials include commercials advertising All-State car insurance, Geico car insurance, State Farm car insurance, Travelers car insurance, and Liberty Mutual car insurance. The three neutral non-food related commercials that will remain the same in each condition are commercials advertising Fifth Third bank, Ally bank, and Capital One bank. The specific aims and hypotheses are: Women exposed to a television show with commercials imbedded advertising food will consume more food than women exposed to a television show with non-food related commercials. Women will consume more food when exposed to a television show with commercials advertising unhealthy food as compared to a television show with commercials advertising healthy food. Women will consume the most food when exposed to a television show with unhealthy food commercials and have unhealthy snack foods available to consume.
Official Title
-----------------
The Effect of Perceived Healthy and Unhealthy Commercials on Intake of Perceived Healthy and Unhealthy Snack Foods in Normal Weight, College-Aged, Dietary Restrained Women
Conditions
-----------------
Measure Grams and Kcals of Snack Foods Consumed in Each Condition
Intervention / Treatment
-----------------
* Other: Healthy Foods
* Other: Unhealthy Snack Foods
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 18 and 30 years have a body mass index between 18.5 and 24.9 kg/m2 Be a restrained eater (scoring >12 on Three Factor Eating Questionnaire Report being a non-smoker Perceive foods and commercials used in the study as appropriately classified in the study. Exclusion Criteria: Currently dieting for weight loss Currently taking any medications that affect appetite or food intake Have a medical condition affecting eating or are currently following a therapeutic diet Report disliking foods used in the investigation Report having allergies to foods used in the investigation
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 30 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: Factorial Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-Food Related Commercials<br>Participants will watch a 30-minute Saturday Night Live television show with non-food related commercials embedded. | Other: Healthy Foods<br>* While watching the tv show, participants will receive a healthy snack to eat (grapes and baby carrots).<br>Other: Unhealthy Snack Foods<br>* While watching the tv show, participants will receive an unhealthy snack to eat (potato chips and chocolate chip cookies).<br>|
| Experimental: Healthy Food Commercials<br>Participants will watch a 30-minute Saturday Night Live television show with healthy food commercials embedded. | Other: Healthy Foods<br>* While watching the tv show, participants will receive a healthy snack to eat (grapes and baby carrots).<br>Other: Unhealthy Snack Foods<br>* While watching the tv show, participants will receive an unhealthy snack to eat (potato chips and chocolate chip cookies).<br>|
| Experimental: Unhealthy Food Commericlas<br>Participants will watch a 30-minute Saturday Night Live television show with unhealthy food commercials imbedded. | Other: Healthy Foods<br>* While watching the tv show, participants will receive a healthy snack to eat (grapes and baby carrots).<br>Other: Unhealthy Snack Foods<br>* While watching the tv show, participants will receive an unhealthy snack to eat (potato chips and chocolate chip cookies).<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total grams of snack foods consumed | The snack foods that will be used in this investigation are red grapes, baby carrots, Chips Ahoy! chocolate chip cookies (Kraft Foods Global Inc., Northfield, IL), and Lays potato chips (Frito-Lay Inc., Plano, TX). Participants will be provided with 200 grams of two different foods, depending on the condition to which they are randomized. Snack foods provided to participants in each condition will be measured in grams to the tenth decimal point on an electronic food scale (Denver Instrument Co., Arvada, CO) before and after the session. The weight of the container will also be measured. Total grams of snack food consumed during the session will be determined by subtracting pre- and post-consumption weight of snack food. | 1 year |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measured kilocalories consumed | The amount of kilocalories consumed in each session will be calculated by determining the weight of food consumed and calculating using food label. | 1 year |
|
||
NCT01977339
|
Efficacy of Single Injection Femoral Nerve Block With Liposomal Bupivacaine for Total Knee Arthroplasty
|
The purpose of this study is to compare the quality and duration of pain relief after a total knee replacement provided by a single shot of standard bupivacaine versus a single shot of liposomal bupivacaine, at the site of the femoral nerve. It is hypothesized that the liposomal bupivacaine formulation will provide more effective pain relief than standard bupivacaine.
|
A Randomized, Double-Blinded, Control Trial to Evaluate the Efficacy of Single Injection Femoral Nerve Block With Liposome Bupivacaine for Postsurgical Analgesia in Subjects Undergoing Unilateral Total Knee Arthroplasty
|
Total Knee Arthroplasty
|
* Drug: Liposome Bupivacaine
* Drug: Bupivacaine
|
Inclusion Criteria:~Male or female, ≥18 years of age~Scheduled to undergo primary unilateral TKA under general anesthesia.~American Society of Anesthesiology (ASA) Physical Status I-III~Able to demonstrate motor function by performing a 20-meter walk, and sensory function by exhibiting sensitivity to cold.~Able to provide informed consent, adhere to the study visit schedule, and complete all study assessments.~Exclusion Criteria:~Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration.~Planned concurrent surgical procedure (e.g., bilateral TKA).~Body weight < 50 kg (110 pounds) or a body mass index ≥ 40 kg/m2.~Contraindication to any of the pain-control agents planned for postsurgical use (i.e., morphine, hydromorphone, oxycodone, bupivacaine).~Previous participation in a liposome bupivacaine study.~History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.~Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the investigator, could interfere with study assessments or compliance.
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opiate consumption | Compare the cumulative 72 hour opiate consumption after total knee arthroplasty (TKA)in patients who received a single dose of liposome bupivacaine with those who received a single shot femoral nerve block with 0.25% bupivacaine. | 72 hours |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-operative VAS scores | Patients will be asked to describe the pain intensity under two circumstances: pain at rest, and pain on movement. Postoperative pain intensity will be evaluated using the Visual Analogue Scale (VAS) system at 1, 4, 8, 12, 24, 48 and 72 hours. The VAS used will be the 11 point verbal response pain scale with 0 being no pain at all and 10 being the worst possible pain. The patients will be asked to rate their pain levels using this numeric scale. | 1 hr, 4 hrs, 8 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs |
|
Femoral Nerve Block, Liposomal Bupivacaine
|
Bupivacaine, Anesthetics, Local, Anesthetics, Central Nervous System Depressants, Physiological Effects of Drugs, Sensory System Agents, Peripheral Nervous System Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liposome Bupivacaine<br>Single injection femoral nerve block of 10 cc of 266 mg liposome bupivacaine with 10 cc of normal saline | Drug: Liposome Bupivacaine<br>* 10 cc of 266 mg liposome bupivacaine with 10 cc of Normal Saline<br>* Other names: Exparel;|
| Active Comparator: Bupivacaine<br>Single shot femoral nerve block with 20cc of 0.25% bupivacaine | Drug: Bupivacaine<br>* 20 cc of 0.25% bupivacaine<br>|
|
Efficacy of Single Injection Femoral Nerve Block With Liposomal Bupivacaine for Total Knee Arthroplasty
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare the quality and duration of pain relief after a total knee replacement provided by a single shot of standard bupivacaine versus a single shot of liposomal bupivacaine, at the site of the femoral nerve. It is hypothesized that the liposomal bupivacaine formulation will provide more effective pain relief than standard bupivacaine.
Official Title
-----------------
A Randomized, Double-Blinded, Control Trial to Evaluate the Efficacy of Single Injection Femoral Nerve Block With Liposome Bupivacaine for Postsurgical Analgesia in Subjects Undergoing Unilateral Total Knee Arthroplasty
Conditions
-----------------
Total Knee Arthroplasty
Intervention / Treatment
-----------------
* Drug: Liposome Bupivacaine
* Drug: Bupivacaine
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, ≥18 years of age Scheduled to undergo primary unilateral TKA under general anesthesia. American Society of Anesthesiology (ASA) Physical Status I-III Able to demonstrate motor function by performing a 20-meter walk, and sensory function by exhibiting sensitivity to cold. Able to provide informed consent, adhere to the study visit schedule, and complete all study assessments. Exclusion Criteria: Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration. Planned concurrent surgical procedure (e.g., bilateral TKA). Body weight < 50 kg (110 pounds) or a body mass index ≥ 40 kg/m2. Contraindication to any of the pain-control agents planned for postsurgical use (i.e., morphine, hydromorphone, oxycodone, bupivacaine). Previous participation in a liposome bupivacaine study. History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years. Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the investigator, could interfere with study assessments or compliance.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liposome Bupivacaine<br>Single injection femoral nerve block of 10 cc of 266 mg liposome bupivacaine with 10 cc of normal saline | Drug: Liposome Bupivacaine<br>* 10 cc of 266 mg liposome bupivacaine with 10 cc of Normal Saline<br>* Other names: Exparel;|
| Active Comparator: Bupivacaine<br>Single shot femoral nerve block with 20cc of 0.25% bupivacaine | Drug: Bupivacaine<br>* 20 cc of 0.25% bupivacaine<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opiate consumption | Compare the cumulative 72 hour opiate consumption after total knee arthroplasty (TKA)in patients who received a single dose of liposome bupivacaine with those who received a single shot femoral nerve block with 0.25% bupivacaine. | 72 hours |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-operative VAS scores | Patients will be asked to describe the pain intensity under two circumstances: pain at rest, and pain on movement. Postoperative pain intensity will be evaluated using the Visual Analogue Scale (VAS) system at 1, 4, 8, 12, 24, 48 and 72 hours. The VAS used will be the 11 point verbal response pain scale with 0 being no pain at all and 10 being the worst possible pain. The patients will be asked to rate their pain levels using this numeric scale. | 1 hr, 4 hrs, 8 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Femoral Nerve Block, Liposomal Bupivacaine
|
|
NCT00097955
|
Safety and Efficacy of Aliskiren When Added to Standardized Losartan and Optimal Antihypertensive Therapy in Patients With Hypertension, Type 2 Diabetes and Proteinuria
|
Study of the efficacy and safety of aliskiren when added to losartan and optimal antihypertensive therapy in patients with hypertension, type 2 diabetes, and kidney disorders to monitor improvement in any of these conditions.
|
Safety and Efficacy of Aliskiren When Added to Standardized Losartan and Optimal Antihypertensive Therapy in Patients With Hypertension, Type 2 Diabetes and Proteinuria
|
Diabetic Nephropathy
|
* Drug: aliskiren
|
Inclusion Criteria:~Hypertension~Elevated urinary protein levels~Confirmed type 2 diabetes~Exclusion Criteria:~Certain diseases~Uncontrolled diabetes~Type 1 diabetes
|
18 Years
|
80 Years
|
All
|
No
|
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in urinary albumin creatinine ratio after 24 weeks | | |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Equal/more than 50% reduction from baseline in urinary albumin creatinine ratio after 24 weeks | | |
| Change from baseline in urinary albumin excretion rate after 24 weeks | | |
|
diabetes, nephropathy, hypertension, aliskiren, losartan
|
Kidney Diseases, Diabetic Nephropathies, Proteinuria, Hypertension, Vascular Diseases, Cardiovascular Diseases, Urologic Diseases, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Male Urogenital Diseases, Diabetes Complications, Diabetes Mellitus, Endocrine System Diseases, Urination Disorders, Urological Manifestations
|
| Intervention/Treatment |
| --- |
|Drug: aliskiren|nan|
|
Safety and Efficacy of Aliskiren When Added to Standardized Losartan and Optimal Antihypertensive Therapy in Patients With Hypertension, Type 2 Diabetes and Proteinuria
Study Overview
=================
Brief Summary
-----------------
Study of the efficacy and safety of aliskiren when added to losartan and optimal antihypertensive therapy in patients with hypertension, type 2 diabetes, and kidney disorders to monitor improvement in any of these conditions.
Official Title
-----------------
Safety and Efficacy of Aliskiren When Added to Standardized Losartan and Optimal Antihypertensive Therapy in Patients With Hypertension, Type 2 Diabetes and Proteinuria
Conditions
-----------------
Diabetic Nephropathy
Intervention / Treatment
-----------------
* Drug: aliskiren
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Hypertension Elevated urinary protein levels Confirmed type 2 diabetes Exclusion Criteria: Certain diseases Uncontrolled diabetes Type 1 diabetes
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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Intervention/Treatment |
| --- |
|Drug: aliskiren|nan|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in urinary albumin creatinine ratio after 24 weeks | | |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Equal/more than 50% reduction from baseline in urinary albumin creatinine ratio after 24 weeks | | |
| Change from baseline in urinary albumin excretion rate after 24 weeks | | |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
diabetes, nephropathy, hypertension, aliskiren, losartan
|
|
NCT05585684
|
Liquid Biopsy-informed Precision Oncology Study to Evaluate Utility of Plasma Genomic Profiling for Therapy Selection
|
Overall, this project has three main goals: first, to ascertain the feasibility of the approach and identify whether liquid biopsies can detect actionable mutations that can be utilized to generate precision oncology treatment recommendations. Second, the investigators will investigate whether enacting upon MTB recommendations would improve outcomes in terms of progression-free and overall survival. Third, the investigators aim to determine if molecular profiling via serial plasma tests after initiation of chemotherapy or other targeted treatment is sufficient to determine whether or not a patient is responding to therapy.
|
Quality assurance plan that addresses data validation and registry procedures, including any plans for site monitoring and auditing.~All information will be collected on study-specific case report forms (CRFs) hosted in Redcap and/or directly entered into a study database. The following measures will be taken to protect patient information:~The database will be password protected; only authorized staff may enter and view project data.~Passwords and system IDs will not be shared.~Physical security of the workstations/files will be maintained. Workstations with the database open will not be left unattended.~Staff will be trained on the data entry system and on security procedures.~The study data will be reviewed/monitored by the Sidney Kimmel Comprehensive Cancer Center Clinical Research Office and the Cancer Center Safety committee.~Data checks to compare data entered into the registry against predefined rules for range or consistency with other data fields in the registry.~Data checks will be performed per SKCCC SOP DM-01-04 CRF Documentation Standards.~Case Report Form (CRF): A printed, optical, or electronic document designed to record all of the protocol-required information to be reported to the sponsor on each trial subject. ICH GCP 1.11 Source Documents: Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, subjects' diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, and at the medicotechnical departments involved in the clinical trial). ICH GCP 1.52~Source data verification to assess the accuracy, completeness, or representativeness of registry data by comparing the data to external data sources (for example, medical records, paper or electronic case report forms, or interactive voice response systems).~All study data will be reviewed for completeness and accuracy by the Protocol Chair who will ensure the completeness and accuracy of the data generated. The designated research coordinator(s) participating in this project will collect clinical information associated with each participant. Such data could include, but is not limited to: medical record number, age, sex, treatment history, circulating tumor markers, tumor size, tumor grade, tumor receptor status, pathology report, smoking history, hormonal history, concomitant medications, and parity. Such information will be retrieved from existing clinical databases/EMR (e.g., EPIC) and patient questionnaire information, and may also include electronic scheduling and prescription systems.~Follow-up information will be collected by review of the medical records. In addition, participants may be reached by phone to help with any questions or clarifications, or additional follow-up requirements.~Data dictionary that contains detailed descriptions of each variable used by the registry, including the source of the variable, coding information if used (for example, World Health Organization Drug Dictionary, MedDRA), and normal ranges if relevant.~Source for data dictionary is included in Botsis et al., JCO CCI, 2023, in press.~Standard Operating Procedures to address registry operations and analysis activities, such as patient recruitment, data collection, data management, data analysis, reporting for adverse events, and change management.~These activities will be carried out in compliance with the study protocol and Good Clinical Practice principles. Information regarding study conduct and progress will be reported to our local Institutional Review Board (IRB) per current institutional standards. The study will undergo routine annual review as per current institutional standards.~Sample size assessment to specify the number of participants or participant years necessary to demonstrate an effect.~We will recruit 150 patients with solid tumors including non-adenocarcinoma NSCLC, small-cell lung cancer, neuroendocrine lung cancer, mesothelioma, esophageal cancer, breast cancer and head and neck cancer. Based on the liquid biopsy assay's analytical performance we expect to detect tumor-specific mutations in >85% of the individuals. We expect to complete the accrual in 1.5 years. The analysis is primarily descriptive for this feasibility study. A sample size of 150 patients will provide reasonable confidence around the observed estimate of proportions, e.g. percent of patients with variants of clinical significance. The width of 95% confidence interval will be narrower than 16.5%.~Plan for missing data to address situations where variables are reported as missing, unavailable, non-reported, uninterpretable, or considered missing because of data inconsistency or out-of-range results.~Missing data will be excluded from downstream analyses.~Statistical analysis plan describing the analytical principles and statistical techniques to be employed in order to address the primary and secondary objectives, as specified in the study protocol or plan.~Analysis of Primary Objectives:~The primary objectives are to determine the number and prevalence of variants with clinical significance across different levels of evidence (stratified by gene and alteration type), as described above and to determine the percentage of patients with an MTB treatment recommendation accordingly. Descriptive analysis will be performed to estimate the percentage of patients that harbor variants with clinical significance detected in ctDNA samples, along with 95% confidence intervals. The percentage of patients with an MTB treatment recommendation tailored to an actionable alteration according to the mutation profiles detected by liquid biopsies, and percentage of patients treated according to MTB recommendation will be estimated. The days from collection of liquid biopsies to MTB recommendation, and days from MTB recommendation to treatment initiation will be summarized by mean, median, standard deviation and range. We plan to summarize the data after every 30 patients.~Analysis of Secondary Objectives:~Time to subsequent cancer therapy is the time from initiation of treatment to the start of next cancer therapy according to treating physician's decision. Progression-free survival (PFS) is the time from initiation of therapy to radiographic progression per RECIST, clinical progression or worsening disease per treating physician's assessment. Overall survival (OS) is the time from initiation of therapy to death due to any cause. PFS and OS will be characteristics by Kaplan-Meier method, among patients who do and do not have an MTB recommendation, and for patients who do and do not receive recommended treatment.~Descriptive analysis will be performed to report the frequency of MTB-based treatment recommendations by therapeutic class (standard of care, clinical trial, off-label use), and the deviations from treatment recommendations and reasons (clinical deterioration, other protocol, patient ineligible, off-label treatment unavailable, clinical trial not feasible (e.g. physical distance), clinical trial not recruiting, physician's decision, patient's choice, etc.) The concordance of detected alterations obtained through liquid biopsy analyses at baseline compared to time-matched or archival tissue specimens will be summarized and quantified using Kappa statistics.~Descriptive analyses will also be performed to determine the cell-free DNA yield and ctDNA amount by tumor type obtained through liquid biopsy analyses. Additionally, the assay success rate by tumor type and by pre-analytical variables will be performed across minimum technical data elements, including:~Blood collection tube type~Sample composition~Shipping temperature~Blood fractionalization method~Time to fractionation~Analyte isolation method~Time to freezer~Storage temperature~Concentration: cellular concentration or molecular concentration~Assay method~Time to assay
|
Liquid Biopsy-informed Precision Oncology Study to Evaluate the Clinical Utility of Non-invasive Comprehensive Genomic Profiling for Cancer Treatment Selection
|
Solid Tumor
|
* Other: Non-invasive Comprehensive Genomic Profiling for Cancer Treatment Selection
|
Inclusion Criteria:~ECOG performance status of 0-1.~Patients with solid tumors, including esophageal cancer, non-adenocarcinoma NSCLC, small-cell lung cancer, head & neck cancer, mesothelioma, breast cancer and lung neuroendocrine cancer.~Patients who can provide whole blood collection to meet minimum of 20-30ml of blood at baseline, within 1-3 weeks from treatment initiation, at first radiographic imaging and at progression. Acquisition of an archival or time-matched tumor tissue specimen which meets the minimum sample input requirements (at least 20% tumor content and 100 ng) is preferred but not required.~Patients with metastatic disease will have progressed on the most recent treatment prior to enrollment. Patient can also be enrolled if their oncologist believes progression is imminent and test results would be used to inform next line of therapy. Patients considered for first-line SOC therapeutic options may be enrolled if the clinical efficacy of these therapies is not encouraging.~Patients must have disease evaluable for progression assessment; measurable disease is not required to participate in the study.~Able to voluntarily provide informed consent.~Exclusion Criteria:~Women who are known to be pregnant~History of another primary malignancy in the last 5 years prior to registration unless approved by the Protocol Chair/designee. Patients with prior history of in situ cancer or basal or localized squamous cell skin cancer are eligible.
|
18 Years
| null |
All
| null |
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of variants in ctDNA with clinical significance across different levels of evidence | To determine the prevalence of variants in ctDNA with clinical significance across different levels of evidence (stratified by gene and alteration type). In cases where tumor next-generation sequencing has been performed, tumor mutational profiles will be evaluated in conjunction with the liquid biopsy results. | Up to 2 years after enrollment |
| Percentage of patients with a molecular tumor board (MTB) treatment recommendation | To determine the percentage of patients with a molecular tumor board (MTB) treatment recommendation tailored to an actionable alteration according to the mutation profiles detected by liquid biopsies. | Up to 2 years after enrollment |
| Percentage of patients treated according to MTB recommendation | To determine percentage of patients treated according to MTB recommendation. | Up to 2 years after enrollment |
| Turnaround time from collection of liquid biopsy to MTB recommendation | To determine turnaround time from collection of liquid biopsy to MTB recommendation. | Up to 2 years after enrollment |
| Time from MTB recommendation to treatment initiation | To determine the time from MTB recommendation to treatment initiation. | Up to 2 years after enrollment |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to cancer therapy for patients who are treated according to MTB recommendation | To determine time to subsequent cancer therapy for patients who are treated according to MTB recommendation. | Up to 2 years after enrollment |
| Time to cancer therapy for patients who are not treated according to MTB recommendation | To determine time to subsequent cancer therapy for patients who are not treated according to MTB recommendation. | Up to 2 years after enrollment |
| Progression free-survival of patients who are treated according to the MTB recommendations | To determine the progression free-survival of patients who are treated according to the MTB recommendations. | Up to 2 years after enrollment |
| Progression free-survival of patients who are not treated according to the MTB recommendations | To determine the progression free-survival of patients who are not treated according to the MTB recommendations. | Up to 2 years after enrollment |
| Overall survival of patients who do receive treatment according to the MTB recommendations | To determine the overall survival of patients who do receive treatment according to the MTB recommendations. | Up to 2 years after enrollment |
| Overall survival of patients who do not receive treatment according to the MTB recommendations | To determine the overall survival of patients who do not receive treatment according to the MTB recommendations. | Up to 2 years after enrollment |
| MTB-based treatment recommendations stratified by therapeutic class | To determine MTB-based treatment recommendations stratified by therapeutic class (SOC, clinical trials, off-label use). | Up to 2 years after enrollment |
| Proportion of deviations from treatment recommendations | To determine the proportion of deviations from treatment recommendations. | Up to 2 years after enrollment |
| Reasons for deviations from treatment recommendations | To determine the reasons (clinical deterioration, other protocol, patient ineligible, off-label treatment unavailable, clinical trial not feasible (e.g. physical distance), clinical trial not recruiting, physician's decision, patient's choice, etc.) for deviations from treatment recommendations. | Up to 2 years after enrollment |
| Concordance of detected alterations obtained through liquid biopsy analyses | To determine the concordance of detected alterations obtained through liquid biopsy analyses at baseline compared to next generation sequencing of time-matched or archival tissue specimens. | Up to 2 years after enrollment |
| cfDNA yield obtained | To determine the cfDNA yield obtained through liquid biopsy analyses by tumor type. | Up to 2 years after enrollment |
| ctDNA amount obtained | To determine the ctDNA amount obtained through liquid biopsy analyses by tumor type. | Up to 2 years after enrollment |
| Liquid biopsy assay success rate | To determine the liquid biopsy assay success rate by tumor type and by pre-specified pre-analytical variables. | Up to 2 years after enrollment |
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Oncology Patients<br>All participants in the study. | Other: Non-invasive Comprehensive Genomic Profiling for Cancer Treatment Selection<br>* Use of liquid biopsy to evaluate the clinical utility of non-invasive comprehensive genomic profiling for cancer treatment selection.<br>|
|
Liquid Biopsy-informed Precision Oncology Study to Evaluate Utility of Plasma Genomic Profiling for Therapy Selection
Study Overview
=================
Brief Summary
-----------------
Overall, this project has three main goals: first, to ascertain the feasibility of the approach and identify whether liquid biopsies can detect actionable mutations that can be utilized to generate precision oncology treatment recommendations. Second, the investigators will investigate whether enacting upon MTB recommendations would improve outcomes in terms of progression-free and overall survival. Third, the investigators aim to determine if molecular profiling via serial plasma tests after initiation of chemotherapy or other targeted treatment is sufficient to determine whether or not a patient is responding to therapy.
Detailed Description
-----------------
Quality assurance plan that addresses data validation and registry procedures, including any plans for site monitoring and auditing. All information will be collected on study-specific case report forms (CRFs) hosted in Redcap and/or directly entered into a study database. The following measures will be taken to protect patient information: The database will be password protected; only authorized staff may enter and view project data. Passwords and system IDs will not be shared. Physical security of the workstations/files will be maintained. Workstations with the database open will not be left unattended. Staff will be trained on the data entry system and on security procedures. The study data will be reviewed/monitored by the Sidney Kimmel Comprehensive Cancer Center Clinical Research Office and the Cancer Center Safety committee. Data checks to compare data entered into the registry against predefined rules for range or consistency with other data fields in the registry. Data checks will be performed per SKCCC SOP DM-01-04 CRF Documentation Standards. Case Report Form (CRF): A printed, optical, or electronic document designed to record all of the protocol-required information to be reported to the sponsor on each trial subject. ICH GCP 1.11 Source Documents: Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, subjects' diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, and at the medicotechnical departments involved in the clinical trial). ICH GCP 1.52 Source data verification to assess the accuracy, completeness, or representativeness of registry data by comparing the data to external data sources (for example, medical records, paper or electronic case report forms, or interactive voice response systems). All study data will be reviewed for completeness and accuracy by the Protocol Chair who will ensure the completeness and accuracy of the data generated. The designated research coordinator(s) participating in this project will collect clinical information associated with each participant. Such data could include, but is not limited to: medical record number, age, sex, treatment history, circulating tumor markers, tumor size, tumor grade, tumor receptor status, pathology report, smoking history, hormonal history, concomitant medications, and parity. Such information will be retrieved from existing clinical databases/EMR (e.g., EPIC) and patient questionnaire information, and may also include electronic scheduling and prescription systems. Follow-up information will be collected by review of the medical records. In addition, participants may be reached by phone to help with any questions or clarifications, or additional follow-up requirements. Data dictionary that contains detailed descriptions of each variable used by the registry, including the source of the variable, coding information if used (for example, World Health Organization Drug Dictionary, MedDRA), and normal ranges if relevant. Source for data dictionary is included in Botsis et al., JCO CCI, 2023, in press. Standard Operating Procedures to address registry operations and analysis activities, such as patient recruitment, data collection, data management, data analysis, reporting for adverse events, and change management. These activities will be carried out in compliance with the study protocol and Good Clinical Practice principles. Information regarding study conduct and progress will be reported to our local Institutional Review Board (IRB) per current institutional standards. The study will undergo routine annual review as per current institutional standards. Sample size assessment to specify the number of participants or participant years necessary to demonstrate an effect. We will recruit 150 patients with solid tumors including non-adenocarcinoma NSCLC, small-cell lung cancer, neuroendocrine lung cancer, mesothelioma, esophageal cancer, breast cancer and head and neck cancer. Based on the liquid biopsy assay's analytical performance we expect to detect tumor-specific mutations in >85% of the individuals. We expect to complete the accrual in 1.5 years. The analysis is primarily descriptive for this feasibility study. A sample size of 150 patients will provide reasonable confidence around the observed estimate of proportions, e.g. percent of patients with variants of clinical significance. The width of 95% confidence interval will be narrower than 16.5%. Plan for missing data to address situations where variables are reported as missing, unavailable, non-reported, uninterpretable, or considered missing because of data inconsistency or out-of-range results. Missing data will be excluded from downstream analyses. Statistical analysis plan describing the analytical principles and statistical techniques to be employed in order to address the primary and secondary objectives, as specified in the study protocol or plan. Analysis of Primary Objectives: The primary objectives are to determine the number and prevalence of variants with clinical significance across different levels of evidence (stratified by gene and alteration type), as described above and to determine the percentage of patients with an MTB treatment recommendation accordingly. Descriptive analysis will be performed to estimate the percentage of patients that harbor variants with clinical significance detected in ctDNA samples, along with 95% confidence intervals. The percentage of patients with an MTB treatment recommendation tailored to an actionable alteration according to the mutation profiles detected by liquid biopsies, and percentage of patients treated according to MTB recommendation will be estimated. The days from collection of liquid biopsies to MTB recommendation, and days from MTB recommendation to treatment initiation will be summarized by mean, median, standard deviation and range. We plan to summarize the data after every 30 patients. Analysis of Secondary Objectives: Time to subsequent cancer therapy is the time from initiation of treatment to the start of next cancer therapy according to treating physician's decision. Progression-free survival (PFS) is the time from initiation of therapy to radiographic progression per RECIST, clinical progression or worsening disease per treating physician's assessment. Overall survival (OS) is the time from initiation of therapy to death due to any cause. PFS and OS will be characteristics by Kaplan-Meier method, among patients who do and do not have an MTB recommendation, and for patients who do and do not receive recommended treatment. Descriptive analysis will be performed to report the frequency of MTB-based treatment recommendations by therapeutic class (standard of care, clinical trial, off-label use), and the deviations from treatment recommendations and reasons (clinical deterioration, other protocol, patient ineligible, off-label treatment unavailable, clinical trial not feasible (e.g. physical distance), clinical trial not recruiting, physician's decision, patient's choice, etc.) The concordance of detected alterations obtained through liquid biopsy analyses at baseline compared to time-matched or archival tissue specimens will be summarized and quantified using Kappa statistics. Descriptive analyses will also be performed to determine the cell-free DNA yield and ctDNA amount by tumor type obtained through liquid biopsy analyses. Additionally, the assay success rate by tumor type and by pre-analytical variables will be performed across minimum technical data elements, including: Blood collection tube type Sample composition Shipping temperature Blood fractionalization method Time to fractionation Analyte isolation method Time to freezer Storage temperature Concentration: cellular concentration or molecular concentration Assay method Time to assay
Official Title
-----------------
Liquid Biopsy-informed Precision Oncology Study to Evaluate the Clinical Utility of Non-invasive Comprehensive Genomic Profiling for Cancer Treatment Selection
Conditions
-----------------
Solid Tumor
Intervention / Treatment
-----------------
* Other: Non-invasive Comprehensive Genomic Profiling for Cancer Treatment Selection
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ECOG performance status of 0-1. Patients with solid tumors, including esophageal cancer, non-adenocarcinoma NSCLC, small-cell lung cancer, head & neck cancer, mesothelioma, breast cancer and lung neuroendocrine cancer. Patients who can provide whole blood collection to meet minimum of 20-30ml of blood at baseline, within 1-3 weeks from treatment initiation, at first radiographic imaging and at progression. Acquisition of an archival or time-matched tumor tissue specimen which meets the minimum sample input requirements (at least 20% tumor content and 100 ng) is preferred but not required. Patients with metastatic disease will have progressed on the most recent treatment prior to enrollment. Patient can also be enrolled if their oncologist believes progression is imminent and test results would be used to inform next line of therapy. Patients considered for first-line SOC therapeutic options may be enrolled if the clinical efficacy of these therapies is not encouraging. Patients must have disease evaluable for progression assessment; measurable disease is not required to participate in the study. Able to voluntarily provide informed consent. Exclusion Criteria: Women who are known to be pregnant History of another primary malignancy in the last 5 years prior to registration unless approved by the Protocol Chair/designee. Patients with prior history of in situ cancer or basal or localized squamous cell skin cancer are eligible.
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 |
| --- | --- |
| Oncology Patients<br>All participants in the study. | Other: Non-invasive Comprehensive Genomic Profiling for Cancer Treatment Selection<br>* Use of liquid biopsy to evaluate the clinical utility of non-invasive comprehensive genomic profiling for cancer treatment selection.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of variants in ctDNA with clinical significance across different levels of evidence | To determine the prevalence of variants in ctDNA with clinical significance across different levels of evidence (stratified by gene and alteration type). In cases where tumor next-generation sequencing has been performed, tumor mutational profiles will be evaluated in conjunction with the liquid biopsy results. | Up to 2 years after enrollment |
| Percentage of patients with a molecular tumor board (MTB) treatment recommendation | To determine the percentage of patients with a molecular tumor board (MTB) treatment recommendation tailored to an actionable alteration according to the mutation profiles detected by liquid biopsies. | Up to 2 years after enrollment |
| Percentage of patients treated according to MTB recommendation | To determine percentage of patients treated according to MTB recommendation. | Up to 2 years after enrollment |
| Turnaround time from collection of liquid biopsy to MTB recommendation | To determine turnaround time from collection of liquid biopsy to MTB recommendation. | Up to 2 years after enrollment |
| Time from MTB recommendation to treatment initiation | To determine the time from MTB recommendation to treatment initiation. | Up to 2 years after enrollment |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to cancer therapy for patients who are treated according to MTB recommendation | To determine time to subsequent cancer therapy for patients who are treated according to MTB recommendation. | Up to 2 years after enrollment |
| Time to cancer therapy for patients who are not treated according to MTB recommendation | To determine time to subsequent cancer therapy for patients who are not treated according to MTB recommendation. | Up to 2 years after enrollment |
| Progression free-survival of patients who are treated according to the MTB recommendations | To determine the progression free-survival of patients who are treated according to the MTB recommendations. | Up to 2 years after enrollment |
| Progression free-survival of patients who are not treated according to the MTB recommendations | To determine the progression free-survival of patients who are not treated according to the MTB recommendations. | Up to 2 years after enrollment |
| Overall survival of patients who do receive treatment according to the MTB recommendations | To determine the overall survival of patients who do receive treatment according to the MTB recommendations. | Up to 2 years after enrollment |
| Overall survival of patients who do not receive treatment according to the MTB recommendations | To determine the overall survival of patients who do not receive treatment according to the MTB recommendations. | Up to 2 years after enrollment |
| MTB-based treatment recommendations stratified by therapeutic class | To determine MTB-based treatment recommendations stratified by therapeutic class (SOC, clinical trials, off-label use). | Up to 2 years after enrollment |
| Proportion of deviations from treatment recommendations | To determine the proportion of deviations from treatment recommendations. | Up to 2 years after enrollment |
| Reasons for deviations from treatment recommendations | To determine the reasons (clinical deterioration, other protocol, patient ineligible, off-label treatment unavailable, clinical trial not feasible (e.g. physical distance), clinical trial not recruiting, physician's decision, patient's choice, etc.) for deviations from treatment recommendations. | Up to 2 years after enrollment |
| Concordance of detected alterations obtained through liquid biopsy analyses | To determine the concordance of detected alterations obtained through liquid biopsy analyses at baseline compared to next generation sequencing of time-matched or archival tissue specimens. | Up to 2 years after enrollment |
| cfDNA yield obtained | To determine the cfDNA yield obtained through liquid biopsy analyses by tumor type. | Up to 2 years after enrollment |
| ctDNA amount obtained | To determine the ctDNA amount obtained through liquid biopsy analyses by tumor type. | Up to 2 years after enrollment |
| Liquid biopsy assay success rate | To determine the liquid biopsy assay success rate by tumor type and by pre-specified pre-analytical variables. | Up to 2 years after enrollment |
|
|||
NCT04970498
|
Application of MRI in Identifying Myelosuppression Risk of Neoadjuvant Chemoradiotherapy for Rectal Cancer
|
Rectal cancer patients who received neoadjuvant chemoradiotherapy in Peking University Third Hospital in 2021 are divided into acute myelosuppression group, chronic myelosuppression group and normal group. The differences of magnetic resonance parameters between the groups were compared. The risk identification model of acute and chronic myelosuppression after neoadjuvant chemoradiotherapy was established by clinical risk factors and quantitative parameters of magnetic resonance imaging, and the prediction efficiency of the model was evaluated.
|
The patients with locally advanced rectal cancer diagnosed in Peking University Third Hospital and undergoing neoadjuvant chemoradiotherapy were collected. The basic information of patients (including age, sex, BMI, TNM stage of rectal cancer (T2, T3 stage)) was collected. The blood routine was collected before radiotherapy, 1 week, 2 weeks and 90 days after radiotherapy. MRI including T1WI, DWI sequence and IDEAL-IQ sequence before radiotherapy, 1-2 weeks after radiotherapy and 90 days after radiotherapy were performed, and the corresponding parameters were obtained. The white blood cell values and quantitative parameters of magnetic resonance (including T1WI, DWI signal intensity (b = 1000) and proton density fat fraction (PDFF) of sacrilium and proximal femur were collected. Patients were divided into acute myelosuppression group and non-acute myelosuppression group according to blood routine results 14 days after radiotherapy, and chronic myelosuppression group and non-chronic myelosuppression group according to blood routine results 90 days after radiotherapy. The magnetic resonance parameters difference between 1-2 weeks after radiotherapy and before radiotherapy, and the magnetic resonance parameters difference between 90 days after radiotherapy and before radiotherapy were calculated. By comparing the differences of clinical risk factors and quantitative parameters of MRI between the two groups, the meaningful variables were screened out, and the risk identification model of acute and chronic myelosuppression was established.
|
Application of MRI Quantitative Parameters in Identifying Myelosuppression Risk of Neoadjuvant Chemoradiotherapy for Rectal Cancer
|
Rectal Cancer Stage II, Rectal Cancer Stage III
|
* Diagnostic Test: MRI
* Diagnostic Test: blood routine test
|
Inclusion Criteria:~From February 2021 to August 2022, patients with locally advanced rectal cancer were treated with neoadjuvant chemoradiotherapy in the Third Hospital of Peking University.~There were blood routine before radiotherapy, 1 week, 2 weeks and 90 days after radiotherapy, and MRI examination including routine MRI sequence and IDEAL-IQ sequence before radiotherapy, 1-2 weeks and 90 days after radiotherapy.~Each patient used the same chemotherapy regimen.~Exclusion Criteria:~Patients with metabolic bone diseases such as hyperparathyroidism and Cushing's syndrome.~Patients with history of pelvic radiotherapy or systemic chemotherapy.~Patients with leukocytes below 4.0×10^9/L or long-term severe anemia before radiotherapy.~Patients with tumor bone metastases; patients with pelvic trauma, fracture, and infectious diseases.
| null | null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of IDEAL-IQ sequence of MRI | The differences of PDFF(%) between the acute myelosuppression group and no suppression group | 1-2 weeks after radiotherapy |
| Changes of T1WI sequence of MRI | The differences of T1WI signal intensity（IU） between the acute myelosuppression group and no suppression group | 1-2 weeks after radiotherapy |
| Changes of DWI sequence of MRI | The differences of DWI signal intensity（IU）between the acute myelosuppression group and no suppression group | 1-2 weeks after radiotherapy |
| Changes of ADC map of MRI | The differences of ADC value（mm^2/s) between the acute myelosuppression group and no suppression group | 1-2 weeks after radiotherapy |
| Changes of IDEAL-IQ sequence of MRI | The differences of PDFF(%) between the chronic myelosuppression group and no suppression group | 90 days after radiotherapy |
| Changes of T1WI sequence of MRI | The differences T1WI signal intensity（IU）between the chronic myelosuppression group and no suppression group | 90 days after radiotherapy |
| Changes of DWI sequence of MRI | The differences of DWI signal intensity（IU）between the chronic myelosuppression group and no suppression group | 90 days after radiotherapy |
| Changes of ADC map of MRI | The differences of ADC value（mm^2/s) between the chronic myelosuppression group and no suppression group | 90 days after radiotherapy |
|
Rectal Cancer, Myelosuppression, magnetic resonance imaging, IDEAL-IQ
|
Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Intestinal Diseases, Rectal Diseases, Rectal Neoplasms, Colorectal Neoplasms, Intestinal Neoplasms
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| acute myelosuppression group<br>WBC <4.0×10^9 14 days after radiotherapy | Diagnostic Test: MRI<br>* MRI including T1WI, DWI sequence and IDEAL-IQ sequence before radiotherapy, 1-2 weeks after radiotherapy and 90 days after radiotherapy were performed<br>Diagnostic Test: blood routine test<br>* The blood routine was collected before radiotherapy, 1 week, 2 weeks and 90 days after radiotherapy.<br>|
| chronic myelosuppression group<br>WBC <4.0×10^9 90 days after radiotherapy | Diagnostic Test: MRI<br>* MRI including T1WI, DWI sequence and IDEAL-IQ sequence before radiotherapy, 1-2 weeks after radiotherapy and 90 days after radiotherapy were performed<br>Diagnostic Test: blood routine test<br>* The blood routine was collected before radiotherapy, 1 week, 2 weeks and 90 days after radiotherapy.<br>|
| no myelosuppression group<br>WBC >4.0×10^9 during radiotherapy | Diagnostic Test: MRI<br>* MRI including T1WI, DWI sequence and IDEAL-IQ sequence before radiotherapy, 1-2 weeks after radiotherapy and 90 days after radiotherapy were performed<br>Diagnostic Test: blood routine test<br>* The blood routine was collected before radiotherapy, 1 week, 2 weeks and 90 days after radiotherapy.<br>|
|
Application of MRI in Identifying Myelosuppression Risk of Neoadjuvant Chemoradiotherapy for Rectal Cancer
Study Overview
=================
Brief Summary
-----------------
Rectal cancer patients who received neoadjuvant chemoradiotherapy in Peking University Third Hospital in 2021 are divided into acute myelosuppression group, chronic myelosuppression group and normal group. The differences of magnetic resonance parameters between the groups were compared. The risk identification model of acute and chronic myelosuppression after neoadjuvant chemoradiotherapy was established by clinical risk factors and quantitative parameters of magnetic resonance imaging, and the prediction efficiency of the model was evaluated.
Detailed Description
-----------------
The patients with locally advanced rectal cancer diagnosed in Peking University Third Hospital and undergoing neoadjuvant chemoradiotherapy were collected. The basic information of patients (including age, sex, BMI, TNM stage of rectal cancer (T2, T3 stage)) was collected. The blood routine was collected before radiotherapy, 1 week, 2 weeks and 90 days after radiotherapy. MRI including T1WI, DWI sequence and IDEAL-IQ sequence before radiotherapy, 1-2 weeks after radiotherapy and 90 days after radiotherapy were performed, and the corresponding parameters were obtained. The white blood cell values and quantitative parameters of magnetic resonance (including T1WI, DWI signal intensity (b = 1000) and proton density fat fraction (PDFF) of sacrilium and proximal femur were collected. Patients were divided into acute myelosuppression group and non-acute myelosuppression group according to blood routine results 14 days after radiotherapy, and chronic myelosuppression group and non-chronic myelosuppression group according to blood routine results 90 days after radiotherapy. The magnetic resonance parameters difference between 1-2 weeks after radiotherapy and before radiotherapy, and the magnetic resonance parameters difference between 90 days after radiotherapy and before radiotherapy were calculated. By comparing the differences of clinical risk factors and quantitative parameters of MRI between the two groups, the meaningful variables were screened out, and the risk identification model of acute and chronic myelosuppression was established.
Official Title
-----------------
Application of MRI Quantitative Parameters in Identifying Myelosuppression Risk of Neoadjuvant Chemoradiotherapy for Rectal Cancer
Conditions
-----------------
Rectal Cancer Stage II, Rectal Cancer Stage III
Intervention / Treatment
-----------------
* Diagnostic Test: MRI
* Diagnostic Test: blood routine test
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: From February 2021 to August 2022, patients with locally advanced rectal cancer were treated with neoadjuvant chemoradiotherapy in the Third Hospital of Peking University. There were blood routine before radiotherapy, 1 week, 2 weeks and 90 days after radiotherapy, and MRI examination including routine MRI sequence and IDEAL-IQ sequence before radiotherapy, 1-2 weeks and 90 days after radiotherapy. Each patient used the same chemotherapy regimen. Exclusion Criteria: Patients with metabolic bone diseases such as hyperparathyroidism and Cushing's syndrome. Patients with history of pelvic radiotherapy or systemic chemotherapy. Patients with leukocytes below 4.0×10^9/L or long-term severe anemia before radiotherapy. Patients with tumor bone metastases; patients with pelvic trauma, fracture, and infectious diseases.
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| acute myelosuppression group<br>WBC <4.0×10^9 14 days after radiotherapy | Diagnostic Test: MRI<br>* MRI including T1WI, DWI sequence and IDEAL-IQ sequence before radiotherapy, 1-2 weeks after radiotherapy and 90 days after radiotherapy were performed<br>Diagnostic Test: blood routine test<br>* The blood routine was collected before radiotherapy, 1 week, 2 weeks and 90 days after radiotherapy.<br>|
| chronic myelosuppression group<br>WBC <4.0×10^9 90 days after radiotherapy | Diagnostic Test: MRI<br>* MRI including T1WI, DWI sequence and IDEAL-IQ sequence before radiotherapy, 1-2 weeks after radiotherapy and 90 days after radiotherapy were performed<br>Diagnostic Test: blood routine test<br>* The blood routine was collected before radiotherapy, 1 week, 2 weeks and 90 days after radiotherapy.<br>|
| no myelosuppression group<br>WBC >4.0×10^9 during radiotherapy | Diagnostic Test: MRI<br>* MRI including T1WI, DWI sequence and IDEAL-IQ sequence before radiotherapy, 1-2 weeks after radiotherapy and 90 days after radiotherapy were performed<br>Diagnostic Test: blood routine test<br>* The blood routine was collected before radiotherapy, 1 week, 2 weeks and 90 days after radiotherapy.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of IDEAL-IQ sequence of MRI | The differences of PDFF(%) between the acute myelosuppression group and no suppression group | 1-2 weeks after radiotherapy |
| Changes of T1WI sequence of MRI | The differences of T1WI signal intensity（IU） between the acute myelosuppression group and no suppression group | 1-2 weeks after radiotherapy |
| Changes of DWI sequence of MRI | The differences of DWI signal intensity（IU）between the acute myelosuppression group and no suppression group | 1-2 weeks after radiotherapy |
| Changes of ADC map of MRI | The differences of ADC value（mm^2/s) between the acute myelosuppression group and no suppression group | 1-2 weeks after radiotherapy |
| Changes of IDEAL-IQ sequence of MRI | The differences of PDFF(%) between the chronic myelosuppression group and no suppression group | 90 days after radiotherapy |
| Changes of T1WI sequence of MRI | The differences T1WI signal intensity（IU）between the chronic myelosuppression group and no suppression group | 90 days after radiotherapy |
| Changes of DWI sequence of MRI | The differences of DWI signal intensity（IU）between the chronic myelosuppression group and no suppression group | 90 days after radiotherapy |
| Changes of ADC map of MRI | The differences of ADC value（mm^2/s) between the chronic myelosuppression group and no suppression group | 90 days after radiotherapy |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Rectal Cancer, Myelosuppression, magnetic resonance imaging, IDEAL-IQ
|
||
NCT03412578
|
Effect of Tactile/Kinaesthetic Massage Therapy on DXA Parameter of Preterm Infants
|
The effect of Tactile/Kinaesthetic massage therapy on weight gain and different components of growth, as assessed by anthropometric measurements and DXA scan, and correlate these components with serum IGF-1, leptin and adiponectin in preterm infants.
|
Prospective open label randomized, single-blind, controlled trial was done in the NICU at Mansoura University Children's Hospital.~Stable preterm infants in the NICU awaiting for sustained pattern of weight gain were included in the study.~Massage therapy was started at corrected gestational age of 35 weeks and continued for 5 consecutive days. The protocol of massage therapy was performed as been described by Tiffany Field. Three consecutive, 15 minutes, sessions were performed daily after the noon feeding. Each treatment session was divided into 5 minutes of tactile stimulation, followed by 5 minutes of kinaesthetic stimulation, and then another 5 minutes of tactile stimulation.~During massage therapy, infant's behavioural reaction was observed for signs of distress (e.g., yawning, finger splaying, crying). Vital signs are measured 15 minutes before, 15 minutes during and 15 minutes after the massage procedure. If signs of physiologic distress developed (heart rate greater than 200 bpm), massage was discontinued for 15 seconds, or until a return to baseline levels.~The study was discontinued if five periods of observed behavioural or physiological stress occurred.~Body composition assessment using DXA scan was performed for total body All infants were studied on one occasion by the end of 5 days massage therapy. DXA scan was performed without sedation but a pacifier with non-metallic parts was used as needed. The scanning procedure was interrupted if movement artefacts is noted. In addition, analyses of different body regions were also performed. Regional analyses typically involved the head, each of the four extremities, and the trunk.~Blood samples were collected using standard technique at baseline and after 5 days for measurement of IGF-1, leptin and adiponectin levels using Enzyme-linked Immunosorbent Assay [ELISA kit supplied by Elabscience Biotechnology (No.1 Shizishan Street, Wuhan, Hubei, China) catalog No: E-EL-H0086].~Randomization Infants were assigned randomly, by a designated neonatologist, to treatment groups using internet based random table technique with cards in opaque sealed envelopes that were kept in the neonatal care unit. A written informed consent was obtained from the parents of each infant upon enrolment in the study. Procedures of MT, DXA scan, and laboratory analysis were performed by a designated personnel throughout the study to ensure consistency. Performers of DXA scan and laboratory measures were blinded to groups of intervention.
|
Effect of Tactile/Kinaesthetic Massage Therapy on Growth Parameters and Body Composition of Preterm Infants
|
Preterm Infant, Body Composition, Dual X-ray Absorptiometry (DXA) Scan
|
* Procedure: Massage Therapy
|
Inclusion Criteria:~Medically stable premature infants with gestational age at 28 to 37 weeks' admitted to the grower (step-down) nursery. Stability is defined as lack of need for supplemental oxygen, apneas and bradycardias, systemic antimicrobial therapy for infection, or a central line. On at least 100 ml/kg/d of feed (oral or tube feed) preterm formula. informed consent will be obtained from parents before enrollment in the study.~Exclusion Criteria:~History of necrotizing enterocolitis, receipt of postnatal steroids, active infection, congenital malformations, chromosomal abnormality, intracranial hemorrhage more than (>) grade 2, inborn errors of metabolism, meningitis or encephalopathy, need for surgery.
|
35 Weeks
|
36 Weeks
|
All
|
No
|
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth parameter (Weight) | Daily weight gain in grams and cumulative weight gain after 5 days of intervention | 5 days |
| Growth parameter (Length) | Daily length gain in cm and cumulative length gain after 5 days of intervention | 5 days |
| Growth parameter (Head circumference) | Daily head circumference gain in cm and cumulative head circumference gain after 5 days of intervention | 5 days |
| Growth parameter (Mid-arm circumference) | Daily mid-arm circumference gain in cm and cumulative mid-arm circumference gain after 5 days of intervention | 5 days |
| Growth parameter (Ponderal Index) | Daily changes in Ponderal Index and cumulative changes in Ponderal Index after 5 days of intervention | 5 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dual X-ray absorptiometry scan (DXA scan) | DXA scan will be performed prior to and 5 days after massage therapy to measure bone mineral density at different levels in the body | 5 days |
| Insulin-like Growth Factor 1 (IGF-1) | Serum level of IGF-1 will be measured at baseline and 5 days after massage therapy | 5 days |
| Serum Leptin | Serum level of Leptin will be measured at baseline and 5 days after massage therapy | 5 days |
| Serum adiponectin | Serum level of adiponectin will be measured at baseline and 5 days after massage therapy | 5 days |
|
Premature Birth, Obstetric Labor, Premature, Obstetric Labor Complications, Pregnancy Complications, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Infants in this group will receive ordinary supportive care and will not receive Massage Therapy | |
| Active Comparator: Massage group<br>Infants in this group will receive Massage Therapy Massage therapy was started at corrected gestational age of 35 weeks and continued for 5 consecutive days. The protocol of massage therapy was performed as been described by Tiffany Field (Field, Schanberg et al. 1986). Three consecutive, 15 minutes, sessions were performed daily after the noon feeding. Each treatment session was divided into 5 minutes of tactile stimulation, followed by 5 minutes of kinaesthetic stimulation, and then another 5 minutes of tactile stimulation (Field, Diego et al. 2006).~During massage therapy, infant's behavioural reaction was observed for signs of distress (e.g., yawning, finger splaying, crying). | Procedure: Massage Therapy<br>* Massage therapy was started at corrected gestational age of 35 weeks and continued for 5 consecutive days. The protocol of massage therapy was performed as been described by Tiffany Field (Field, Schanberg et al. 1986). Three consecutive, 15 minutes, sessions were performed daily after the noon feeding. Each treatment session was divided into 5 minutes of tactile stimulation, followed by 5 minutes of kinaesthetic stimulation, and then another 5 minutes of tactile stimulation (Field, Diego et al. 2006).<br>|
|
Effect of Tactile/Kinaesthetic Massage Therapy on DXA Parameter of Preterm Infants
Study Overview
=================
Brief Summary
-----------------
The effect of Tactile/Kinaesthetic massage therapy on weight gain and different components of growth, as assessed by anthropometric measurements and DXA scan, and correlate these components with serum IGF-1, leptin and adiponectin in preterm infants.
Detailed Description
-----------------
Prospective open label randomized, single-blind, controlled trial was done in the NICU at Mansoura University Children's Hospital. Stable preterm infants in the NICU awaiting for sustained pattern of weight gain were included in the study. Massage therapy was started at corrected gestational age of 35 weeks and continued for 5 consecutive days. The protocol of massage therapy was performed as been described by Tiffany Field. Three consecutive, 15 minutes, sessions were performed daily after the noon feeding. Each treatment session was divided into 5 minutes of tactile stimulation, followed by 5 minutes of kinaesthetic stimulation, and then another 5 minutes of tactile stimulation. During massage therapy, infant's behavioural reaction was observed for signs of distress (e.g., yawning, finger splaying, crying). Vital signs are measured 15 minutes before, 15 minutes during and 15 minutes after the massage procedure. If signs of physiologic distress developed (heart rate greater than 200 bpm), massage was discontinued for 15 seconds, or until a return to baseline levels. The study was discontinued if five periods of observed behavioural or physiological stress occurred. Body composition assessment using DXA scan was performed for total body All infants were studied on one occasion by the end of 5 days massage therapy. DXA scan was performed without sedation but a pacifier with non-metallic parts was used as needed. The scanning procedure was interrupted if movement artefacts is noted. In addition, analyses of different body regions were also performed. Regional analyses typically involved the head, each of the four extremities, and the trunk. Blood samples were collected using standard technique at baseline and after 5 days for measurement of IGF-1, leptin and adiponectin levels using Enzyme-linked Immunosorbent Assay [ELISA kit supplied by Elabscience Biotechnology (No.1 Shizishan Street, Wuhan, Hubei, China) catalog No: E-EL-H0086]. Randomization Infants were assigned randomly, by a designated neonatologist, to treatment groups using internet based random table technique with cards in opaque sealed envelopes that were kept in the neonatal care unit. A written informed consent was obtained from the parents of each infant upon enrolment in the study. Procedures of MT, DXA scan, and laboratory analysis were performed by a designated personnel throughout the study to ensure consistency. Performers of DXA scan and laboratory measures were blinded to groups of intervention.
Official Title
-----------------
Effect of Tactile/Kinaesthetic Massage Therapy on Growth Parameters and Body Composition of Preterm Infants
Conditions
-----------------
Preterm Infant, Body Composition, Dual X-ray Absorptiometry (DXA) Scan
Intervention / Treatment
-----------------
* Procedure: Massage Therapy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Medically stable premature infants with gestational age at 28 to 37 weeks' admitted to the grower (step-down) nursery. Stability is defined as lack of need for supplemental oxygen, apneas and bradycardias, systemic antimicrobial therapy for infection, or a central line. On at least 100 ml/kg/d of feed (oral or tube feed) preterm formula. informed consent will be obtained from parents before enrollment in the study. Exclusion Criteria: History of necrotizing enterocolitis, receipt of postnatal steroids, active infection, congenital malformations, chromosomal abnormality, intracranial hemorrhage more than (>) grade 2, inborn errors of metabolism, meningitis or encephalopathy, need for surgery.
Ages Eligible for Study
-----------------
Minimum Age: 35 Weeks
Maximum Age: 36 Weeks
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Infants in this group will receive ordinary supportive care and will not receive Massage Therapy | |
| Active Comparator: Massage group<br>Infants in this group will receive Massage Therapy Massage therapy was started at corrected gestational age of 35 weeks and continued for 5 consecutive days. The protocol of massage therapy was performed as been described by Tiffany Field (Field, Schanberg et al. 1986). Three consecutive, 15 minutes, sessions were performed daily after the noon feeding. Each treatment session was divided into 5 minutes of tactile stimulation, followed by 5 minutes of kinaesthetic stimulation, and then another 5 minutes of tactile stimulation (Field, Diego et al. 2006). During massage therapy, infant's behavioural reaction was observed for signs of distress (e.g., yawning, finger splaying, crying). | Procedure: Massage Therapy<br>* Massage therapy was started at corrected gestational age of 35 weeks and continued for 5 consecutive days. The protocol of massage therapy was performed as been described by Tiffany Field (Field, Schanberg et al. 1986). Three consecutive, 15 minutes, sessions were performed daily after the noon feeding. Each treatment session was divided into 5 minutes of tactile stimulation, followed by 5 minutes of kinaesthetic stimulation, and then another 5 minutes of tactile stimulation (Field, Diego et al. 2006).<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth parameter (Weight) | Daily weight gain in grams and cumulative weight gain after 5 days of intervention | 5 days |
| Growth parameter (Length) | Daily length gain in cm and cumulative length gain after 5 days of intervention | 5 days |
| Growth parameter (Head circumference) | Daily head circumference gain in cm and cumulative head circumference gain after 5 days of intervention | 5 days |
| Growth parameter (Mid-arm circumference) | Daily mid-arm circumference gain in cm and cumulative mid-arm circumference gain after 5 days of intervention | 5 days |
| Growth parameter (Ponderal Index) | Daily changes in Ponderal Index and cumulative changes in Ponderal Index after 5 days of intervention | 5 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dual X-ray absorptiometry scan (DXA scan) | DXA scan will be performed prior to and 5 days after massage therapy to measure bone mineral density at different levels in the body | 5 days |
| Insulin-like Growth Factor 1 (IGF-1) | Serum level of IGF-1 will be measured at baseline and 5 days after massage therapy | 5 days |
| Serum Leptin | Serum level of Leptin will be measured at baseline and 5 days after massage therapy | 5 days |
| Serum adiponectin | Serum level of adiponectin will be measured at baseline and 5 days after massage therapy | 5 days |
|
|
NCT05541042
|
Radiogenomics in Glioblastoma: Correlation Between Multiparametric Imaging Biomarkers and Genetic Biomarkers
|
The purpose of this study is to evaluate relationships between multiparametric imaging biomarkers and genetic analysis in glioblastoma patients.
|
To evaluate relationships between multiparametric imaging biomarkers(CT, PET/CT, MRI) and genetic analysis (tumor tissues and ctDNA in tumor in situ fluid) in glioblastoma patients
|
Radiogenomics in Glioblastoma: Correlation Between Multiparametric Imaging Biomarkers and Genetic Biomarkers Based on Tumor Tissues and ctDNA
|
Glioblastoma
|
* Other: Observational only
|
Inclusion Criteria:~Written informed consent and HIPAA authorization obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations~Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study~Histologically confirmed diagnosis of glioblastoma~Resection surgery done at the study center (Henan Provincial People's Hospital), with an reservoir intraoperatively implanted connecting the surgical cavity and the subscalp for postoperative noninvasive TISF collection~Able to tolerable PET/CT and CT imaging required by protocol~Karnofsky performance status (KPS) of 70 or higher~Exclusion Criteria:~Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results~Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring chronic and systemic immunosuppressive treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Subjects have any other condition requiring systemic treatment with corticosteroids or other immunosuppressive agents within 14 days. Inhaled or topical steroids and adrenal replacement doses >10mg daily prednisone equivalent are permitted in absence of active autoimmune disease~Clinically significant (i.e., active) cardiovascular disease, for example cerebrovascular accidents ≤ 6 months prior to study enrollment, myocardial infarction ≤ 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment~Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to start of study treatment. Any previous venous thromboembolism ≥ NCI CTCAE Grade 3 within 3 months prior to start of study treatment~History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation)~Current or recent (within 10 days of study enrollment) use of anticoagulants that, in the opinion of the investigator, would place the subject at significant risk for bleeding.~Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional and genomic profiling of glioblastoma | Prognostic stratification will be evaluated using following parameters:~Quantitative and qualitative parameters from CT, PET, MRI Genomic data of glioblastoma tumor samples and tumor in situ fluid samples | 3 years after diagnosis |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship between genomic and multiparametric imaging profiling | We will evaluate if certain relationship exists between changes in multiparametric imaging markers from CT, PET, MRI and genomic informations of glioblastoma. | 3 years after diagnosis |
|
Glioblastoma, Astrocytoma, Glioma, Neoplasms, Neuroepithelial, Neuroectodermal Tumors, Neoplasms, Germ Cell and Embryonal, Neoplasms by Histologic Type, Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms, Nerve Tissue
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| patients with glioblastoma<br> | Other: Observational only<br>* This is an observational study<br>|
|
Radiogenomics in Glioblastoma: Correlation Between Multiparametric Imaging Biomarkers and Genetic Biomarkers
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate relationships between multiparametric imaging biomarkers and genetic analysis in glioblastoma patients.
Detailed Description
-----------------
To evaluate relationships between multiparametric imaging biomarkers(CT, PET/CT, MRI) and genetic analysis (tumor tissues and ctDNA in tumor in situ fluid) in glioblastoma patients
Official Title
-----------------
Radiogenomics in Glioblastoma: Correlation Between Multiparametric Imaging Biomarkers and Genetic Biomarkers Based on Tumor Tissues and ctDNA
Conditions
-----------------
Glioblastoma
Intervention / Treatment
-----------------
* Other: Observational only
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent and HIPAA authorization obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study Histologically confirmed diagnosis of glioblastoma Resection surgery done at the study center (Henan Provincial People's Hospital), with an reservoir intraoperatively implanted connecting the surgical cavity and the subscalp for postoperative noninvasive TISF collection Able to tolerable PET/CT and CT imaging required by protocol Karnofsky performance status (KPS) of 70 or higher Exclusion Criteria: Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring chronic and systemic immunosuppressive treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Subjects have any other condition requiring systemic treatment with corticosteroids or other immunosuppressive agents within 14 days. Inhaled or topical steroids and adrenal replacement doses >10mg daily prednisone equivalent are permitted in absence of active autoimmune disease Clinically significant (i.e., active) cardiovascular disease, for example cerebrovascular accidents ≤ 6 months prior to study enrollment, myocardial infarction ≤ 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to start of study treatment. Any previous venous thromboembolism ≥ NCI CTCAE Grade 3 within 3 months prior to start of study treatment History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation) Current or recent (within 10 days of study enrollment) use of anticoagulants that, in the opinion of the investigator, would place the subject at significant risk for bleeding. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
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 glioblastoma<br> | Other: Observational only<br>* This is an observational study<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional and genomic profiling of glioblastoma | Prognostic stratification will be evaluated using following parameters: Quantitative and qualitative parameters from CT, PET, MRI Genomic data of glioblastoma tumor samples and tumor in situ fluid samples | 3 years after diagnosis |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship between genomic and multiparametric imaging profiling | We will evaluate if certain relationship exists between changes in multiparametric imaging markers from CT, PET, MRI and genomic informations of glioblastoma. | 3 years after diagnosis |
|
||
NCT05504213
|
A Phase Ib Study of HS-10352 Plus Fulvestrant in Patients With Advanced Breast Cancer
|
HS-10352 is a highly potent and selective small molecule inhibitor of phosphoinositide 3-kinase (p110α). The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK), and efficacy of HS-10352 plus fulvestrant in patients with hormone receptor (HR) positive, human epidermal growth factor 2 (HER2)-negative, advanced breast cancer (ABC) harboring PIK3CA mutations.
|
This is a Phase Ib open-label, 2-Part, multi-center study in China. The study will be conducted in two stages: Stage 1 is the dose-escalation part, which is designed to evaluate the safety, tolerability, PK and efficacy, as well as to determine the maximum tolerable dosage (MTD) or maximum applicable dose (MAD) of HS-10352 in combination with fulvestrant. Stage 2 is the dose-expansion part, which is aimed to further assess the efficacy, safety, tolerability and PK, and to establish the recommended phase 2 dose (RP2D) of HS-10352 in combination with fulvestrant.~All participants will be carefully monitored for adverse events (AE) during the study treatment and for 28 days after the last dose of study drug. The PK characteristics of HS-10352 and fulvestrant will be evaluated from C1 to C6. Subjects of this study will be assessed for progression once every 8 weeks until objective disease progression or withdrawal from the trial. As the disease progresses, survival follow-up is recommended bimonthly.
|
A Phase Ib, Open-label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-10352 in Combination With Fulvestrant in Patients With Hormone Receptor (HR) Positive, Human Epidermal Growth Factor 2 (HER2)-Negative, PIK3CA Mutation, Locally Advanced or Metastatic Breast Cancer
|
Breast Cancer
|
* Drug: HS-10352 combined with fulvestrant (Stage 1)
* Drug: HS-10352 combined with fulvestrant (Stage 2)
|
Inclusion Criteria:~Men or women aged more than or equal to (≥) 18 years~HR+ HER2- breast cancer confirmed by histology or cytology.~Locally advanced disease not amenable to curative treatment by surgery or metastatic disease.~Have adequate tumor tissue for the analysis of PIK3CA mutational status. At dose expansion stage, participants should be identified as PIK3CA-mutation positive before enrollment.~Females should have postmenopausal status due to either surgical/natural menopause or ovarian suppression with a luteinizing hormone releasing hormone (LHRH) agonist before enrollment. Males should be pre-treated with a LHRH agonist.~Have either measurable disease per RECIST v1.1 criteria or at least one predominantly lytic bone lesion must be present.~ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks.~Estimated life expectancy for at least three months~Females should be using adequate contraceptive measures and should not be breastfeeding at the time of screening, during the study and until 6 months after completion of the study; and have negative results of blood pregnancy test prior to C1D1.~Males should be using adequate contraceptive measures at the time of screening, during the study and until 6 months after completion of the study.~Have signed Informed Consent Form~Dose escalation stage-Cohort 1: subjects resistant to endocrine therapy Dose expansion stage-Cohort 2: subjects resistant to endocrine therapy Dose expansion stage-Cohort 3: endocrine therapy-sensitive or endocrine-naive subjects~Exclusion Criteria:~Participant with symptomatic visceral disease or any disease burden that makes the participant ineligible for endocrine therapy per the investigator's best judgment~Treatment with any of the following:~Previous or current treatment with PI3K, AKT or mTOR inhibitors~For expansion stage, prior treatment with fulvestrant~Any cytotoxic chemotherapy, investigational agents within 21 days of the first dose of study drug; anticancer drugs which have been received within 14 days before the first administration.~Radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study drug, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose.~Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of study drug.~With inflammatory breast cancer at screening.~Inadequate bone marrow reserve or organ function.~Uncontrolled pleural effusion or ascites or pericardial effusion.~Known and untreated, or active central nervous system metastases.~History of primary or secondary diabetes.~History of acute or chronic pancreatitis~Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow the study drug that would preclude adequate absorption of HS-10352 or fulvestrant.~History of hypersensitivity to any active or inactive ingredient of HS-10352/ fulvestrant or to drugs with a similar chemical structure or class to HS-10352.~Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.~Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| [Stage 1] Maximum tolerated dose (MTD) of HS-10352 in combination with fulvestrant | MTD is defined as the previous dose level at which 2 or more out of 2~6 subjects experienced a DLT. | Cycle 1 (28 days) |
| [Stage 1] Maximum applicable dose (MAD) of HS-10352 in combination with fulvestrant | MAD is defined as follows: a) based on PK data, it is anticipated that at this dose level, the dose-exposure plateau has been reached, b) based on existing safety data, it is judged that dose escalation following this dose level will have a large safety risk or subject intolerance, or c) based on the PK-PD model, it suggested that the optimal target concentration of safety and efficacy has been explored. | Cycle 1 (28 days) |
| [Stage 2] Objective response rate (ORR) of HS-10352 in combination with fulvestrant | ORR is defined as the proportion of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on assessment per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). | From the date of first dose until the date of disease progression or withdrawal from study, approximately 3 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| [Stage 1 and Stage 2] Incidence and severity of treatment-emergent adverse events | Assessed by number and severity of adverse events as evaluated according to NCI CTCAE v5.0. | From Cycle 1 Day 1 (C1D1) until 28 days after the final dose. A cycle is 28 days. |
| [Stage 1 and Stage 2] PK parameters: the maximum concentration (Cmax) of HS-10352 | Defines as the maximum plasma drug concentration of HS-10352 | Cycle 1 Day 1 (C1D1)，at the first day of Cycle 1 (each cycle is 28 days) |
| [Stage 1] PK parameters: the maximum concentration (Cmax) of fulvestrant | Defines as the maximum plasma drug concentration of fulvestrant | Cycle 1 (28 days) |
| [Stage 1 and Stage 2] PK parameters: time of the maximum concentration (Tmax) of HS-10352 | Defined as the time to reach maximum plasma concentration following drug administration of HS-10352 | Cycle 1 Day 1 (C1D1)，at the first day of Cycle 1 (each cycle is 28 days) |
| [Stage 1] PK parameters: time of the maximum concentration (Tmax) of fulvestrant | Defined as the time to reach maximum plasma concentration following drug administration of fulvestrant | Cycle 1 (28 days) |
| [Stage 1 and Stage 2] PK parameters: elimination half life (t1/2) of HS-10352 | Defines as the time measured for the concentration to decrease by one half. | Cycle 1 Day 1 (C1D1)，at the first day of Cycle 1 (each cycle is 28 days) |
| [Stage 1 and Stage 2] PK parameters: area under the concentration-time curve over 24 hours (AUC0-24) of HS-10352 | Defines as area under the plasma concentration versus time curve from time zero to the 24-hour sampling time. | Cycle 1 Day 1 (C1D1)，at the first day of Cycle 1 (each cycle is 28 days) |
| [Stage 1 and Stage 2] PK parameters: area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC0-t) of HS-10352 | Defines as area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). | Cycle 1 Day 1 (C1D1)，at the first day of Cycle 1 (each cycle is 28 days) |
| [Stage 1] PK parameters: area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC0-t) of fulvestrant | Defines as area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). | From Cycle 1 to Cycle 2， each cycle is 28 days |
| [Stage 1 and Stage 2] PK parameters: the maximum concentration at steady-state (Css,max) of HS-10352 | Defines as the maximum plasma drug concentration of HS-10352 at steady-state | Cycle 2 Day 1 (C2D1)，at the first day of Cycle 2 (each cycle is 28 days) each cycle is 28 days |
| [Stage 1] PK parameters: the maximum concentration at steady-state (Css,max) of fulvestrant | Defines as the maximum plasma drug concentration of fulvestrant at steady-state | Cycle 2 (28 days) |
| [Stage 1 and Stage 2] PK parameters: time of the maximum concentration at steady state (Tss,max) of HS-10352 | Defined as the time to reach maximum plasma concentration following drug administration of HS-10352 at steady-state | Cycle 2 Day 1 (C2D1)，at the first day of Cycle 1 (each cycle is 28 days) |
| [Stage 1] PK parameters: time of the maximum concentration at steady state (Tss,max) of fulvestrant | Defined as the time to reach maximum plasma concentration following drug administration of fulvestrant at steady-state | Cycle 2 (28 days) |
| [Stage 1 and Stage 2] PK parameters: the minimum concentration at steady-state (Css,min) of HS-10352 | Defines as the minimum plasma drug concentration of HS-10352 at steady-state | Cycle 2 Day 1 (C2D1)，at the first day of Cycle 1 (each cycle is 28 days) |
| [Stage 1 and Stage 2] PK parameters: the minimum concentration at steady-state (Css,min) of fulvestrant | Defines as the minimum plasma drug concentration of fulvestrant at steady-state | Cycle 2 (28 days) |
| [Stage 1] Efficacy of HS-10352 in combination with fulvestrant: ORR | ORR is defined as the proportion of participants with BOR of confirmed CR or confirmed PR based on assessment per RECIST v1.1. | From the date of first dose until the date of disease progression or withdrawal from study, approximately 3 years |
| [Stage 1 and Stage 2] Efficacy of HS-10352 in combination with fulvestrant: disease control rate (DCR) | The disease control was defined as the percentage of patients who have a best overall response (confirmed CR, PR, or stable disease for at least 6 weeks). | From the date of first dose until the date of disease progression or withdrawal from study, approximately 3 years |
| [Stage 1 and Stage 2] Efficacy of HS-10352 in combination with fulvestrant: duration of response (DoR) | DOR only applies to participants whose best overall response is CR or PR based on assessment per RECIST v1.1. The start date is the date of first documented response of CR or PR (i.e. the start date of observed response, not the date when response was confirmed), and the end date is defined as the date of the first documented progression or death due to underlying cancer. | From the date of CR, PR until the date of disease progression or withdrawal from study, approximately 3 years |
| [Stage 1 and Stage 2] Efficacy of HS-10352 in combination with fulvestrant: progression free survival (PFS) | PFS is defined as the time from the date of randomization or first dose (if randomization is not needed) to the date of the first documented progression or death due to any cause. PFS will be assessed per RECIST v1.1. | From the date of randomization or first dose (if randomization is not needed) until the date of disease progression or withdrawal from study, approximately 3 years |
| [Stage 2] Efficacy of HS-10352 in combination with fulvestrant: overall survival (OS) | OS is defined as the time from the date of randomization or first dose (if randomization is not needed) to the date of death due to any cause. For each participant who is not known to have died as of the cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive. | From the date of randomization or first dose (if randomization is not needed) until the documentation of death from any cause, approximately 6 years |
|
dose-escalation, dose-expansion, advanced breast cancer, hormone receptor positive, PIK3CA gene mutation
|
Fulvestrant, Antineoplastic Agents, Hormonal, Antineoplastic Agents, Estrogen Receptor Antagonists, Estrogen Antagonists, Hormone Antagonists, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Endocrine therapy-resistant (Stage 1)<br>Participants who are endocrine therapy pre-treated will be administrated at escalating doses orally of HS-10352 in combination with fulvestrant (500 mg, intramuscular). | Drug: HS-10352 combined with fulvestrant (Stage 1)<br>* Drug: HS-10352 HS-10352 will be administered at escalating doses orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 (C1D1) in a 28 day cycle.~Drug: Fulvestrant Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle 1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).<br>|
| Experimental: Cohort 2: Endocrine therapy-resistant (Stage 2)<br>Participants who are endocrine therapy-resistant will be treated with HS-10352 orally at the MTD/MAD identified in Stage 1 or/and lower dose in combination with fulvestrant (500 mg, intramuscular) | Drug: HS-10352 combined with fulvestrant (Stage 2)<br>* Drug: HS-10352 participants will be enrolled into Cohort 2 (endocrine therapy-resistant) and Cohort 3 (endocrine therapy-sensitive or naïve) respectively and HS-10352 will be administered at the recommended dose identified in Part 1.~Drug: Fulvestrant Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle 1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).<br>|
| Experimental: Cohort 3: Endocrine therapy-sensitive or endocrine-naïve (Stage 2)<br>Participants who are endocrine therapy-sensitive or naïve will be treated with HS-10352 orally at MTD/MAD or/and lower dose identified in Stage 1 in combination with fulvestrant (500 mg, intramuscular) | Drug: HS-10352 combined with fulvestrant (Stage 2)<br>* Drug: HS-10352 participants will be enrolled into Cohort 2 (endocrine therapy-resistant) and Cohort 3 (endocrine therapy-sensitive or naïve) respectively and HS-10352 will be administered at the recommended dose identified in Part 1.~Drug: Fulvestrant Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle 1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).<br>|
|
A Phase Ib Study of HS-10352 Plus Fulvestrant in Patients With Advanced Breast Cancer
Study Overview
=================
Brief Summary
-----------------
HS-10352 is a highly potent and selective small molecule inhibitor of phosphoinositide 3-kinase (p110α). The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK), and efficacy of HS-10352 plus fulvestrant in patients with hormone receptor (HR) positive, human epidermal growth factor 2 (HER2)-negative, advanced breast cancer (ABC) harboring PIK3CA mutations.
Detailed Description
-----------------
This is a Phase Ib open-label, 2-Part, multi-center study in China. The study will be conducted in two stages: Stage 1 is the dose-escalation part, which is designed to evaluate the safety, tolerability, PK and efficacy, as well as to determine the maximum tolerable dosage (MTD) or maximum applicable dose (MAD) of HS-10352 in combination with fulvestrant. Stage 2 is the dose-expansion part, which is aimed to further assess the efficacy, safety, tolerability and PK, and to establish the recommended phase 2 dose (RP2D) of HS-10352 in combination with fulvestrant. All participants will be carefully monitored for adverse events (AE) during the study treatment and for 28 days after the last dose of study drug. The PK characteristics of HS-10352 and fulvestrant will be evaluated from C1 to C6. Subjects of this study will be assessed for progression once every 8 weeks until objective disease progression or withdrawal from the trial. As the disease progresses, survival follow-up is recommended bimonthly.
Official Title
-----------------
A Phase Ib, Open-label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-10352 in Combination With Fulvestrant in Patients With Hormone Receptor (HR) Positive, Human Epidermal Growth Factor 2 (HER2)-Negative, PIK3CA Mutation, Locally Advanced or Metastatic Breast Cancer
Conditions
-----------------
Breast Cancer
Intervention / Treatment
-----------------
* Drug: HS-10352 combined with fulvestrant (Stage 1)
* Drug: HS-10352 combined with fulvestrant (Stage 2)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men or women aged more than or equal to (≥) 18 years HR+ HER2- breast cancer confirmed by histology or cytology. Locally advanced disease not amenable to curative treatment by surgery or metastatic disease. Have adequate tumor tissue for the analysis of PIK3CA mutational status. At dose expansion stage, participants should be identified as PIK3CA-mutation positive before enrollment. Females should have postmenopausal status due to either surgical/natural menopause or ovarian suppression with a luteinizing hormone releasing hormone (LHRH) agonist before enrollment. Males should be pre-treated with a LHRH agonist. Have either measurable disease per RECIST v1.1 criteria or at least one predominantly lytic bone lesion must be present. ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks. Estimated life expectancy for at least three months Females should be using adequate contraceptive measures and should not be breastfeeding at the time of screening, during the study and until 6 months after completion of the study; and have negative results of blood pregnancy test prior to C1D1. Males should be using adequate contraceptive measures at the time of screening, during the study and until 6 months after completion of the study. Have signed Informed Consent Form Dose escalation stage-Cohort 1: subjects resistant to endocrine therapy Dose expansion stage-Cohort 2: subjects resistant to endocrine therapy Dose expansion stage-Cohort 3: endocrine therapy-sensitive or endocrine-naive subjects Exclusion Criteria: Participant with symptomatic visceral disease or any disease burden that makes the participant ineligible for endocrine therapy per the investigator's best judgment Treatment with any of the following: Previous or current treatment with PI3K, AKT or mTOR inhibitors For expansion stage, prior treatment with fulvestrant Any cytotoxic chemotherapy, investigational agents within 21 days of the first dose of study drug; anticancer drugs which have been received within 14 days before the first administration. Radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study drug, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose. Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of study drug. With inflammatory breast cancer at screening. Inadequate bone marrow reserve or organ function. Uncontrolled pleural effusion or ascites or pericardial effusion. Known and untreated, or active central nervous system metastases. History of primary or secondary diabetes. History of acute or chronic pancreatitis Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow the study drug that would preclude adequate absorption of HS-10352 or fulvestrant. History of hypersensitivity to any active or inactive ingredient of HS-10352/ fulvestrant or to drugs with a similar chemical structure or class to HS-10352. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements. Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments.
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: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Endocrine therapy-resistant (Stage 1)<br>Participants who are endocrine therapy pre-treated will be administrated at escalating doses orally of HS-10352 in combination with fulvestrant (500 mg, intramuscular). | Drug: HS-10352 combined with fulvestrant (Stage 1)<br>* Drug: HS-10352 HS-10352 will be administered at escalating doses orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 (C1D1) in a 28 day cycle. Drug: Fulvestrant Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle 1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).<br>|
| Experimental: Cohort 2: Endocrine therapy-resistant (Stage 2)<br>Participants who are endocrine therapy-resistant will be treated with HS-10352 orally at the MTD/MAD identified in Stage 1 or/and lower dose in combination with fulvestrant (500 mg, intramuscular) | Drug: HS-10352 combined with fulvestrant (Stage 2)<br>* Drug: HS-10352 participants will be enrolled into Cohort 2 (endocrine therapy-resistant) and Cohort 3 (endocrine therapy-sensitive or naïve) respectively and HS-10352 will be administered at the recommended dose identified in Part 1. Drug: Fulvestrant Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle 1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).<br>|
| Experimental: Cohort 3: Endocrine therapy-sensitive or endocrine-naïve (Stage 2)<br>Participants who are endocrine therapy-sensitive or naïve will be treated with HS-10352 orally at MTD/MAD or/and lower dose identified in Stage 1 in combination with fulvestrant (500 mg, intramuscular) | Drug: HS-10352 combined with fulvestrant (Stage 2)<br>* Drug: HS-10352 participants will be enrolled into Cohort 2 (endocrine therapy-resistant) and Cohort 3 (endocrine therapy-sensitive or naïve) respectively and HS-10352 will be administered at the recommended dose identified in Part 1. Drug: Fulvestrant Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle 1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| [Stage 1] Maximum tolerated dose (MTD) of HS-10352 in combination with fulvestrant | MTD is defined as the previous dose level at which 2 or more out of 2 6 subjects experienced a DLT. | Cycle 1 (28 days) |
| [Stage 1] Maximum applicable dose (MAD) of HS-10352 in combination with fulvestrant | MAD is defined as follows: a) based on PK data, it is anticipated that at this dose level, the dose-exposure plateau has been reached, b) based on existing safety data, it is judged that dose escalation following this dose level will have a large safety risk or subject intolerance, or c) based on the PK-PD model, it suggested that the optimal target concentration of safety and efficacy has been explored. | Cycle 1 (28 days) |
| [Stage 2] Objective response rate (ORR) of HS-10352 in combination with fulvestrant | ORR is defined as the proportion of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on assessment per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). | From the date of first dose until the date of disease progression or withdrawal from study, approximately 3 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| [Stage 1 and Stage 2] Incidence and severity of treatment-emergent adverse events | Assessed by number and severity of adverse events as evaluated according to NCI CTCAE v5.0. | From Cycle 1 Day 1 (C1D1) until 28 days after the final dose. A cycle is 28 days. |
| [Stage 1 and Stage 2] PK parameters: the maximum concentration (Cmax) of HS-10352 | Defines as the maximum plasma drug concentration of HS-10352 | Cycle 1 Day 1 (C1D1)，at the first day of Cycle 1 (each cycle is 28 days) |
| [Stage 1] PK parameters: the maximum concentration (Cmax) of fulvestrant | Defines as the maximum plasma drug concentration of fulvestrant | Cycle 1 (28 days) |
| [Stage 1 and Stage 2] PK parameters: time of the maximum concentration (Tmax) of HS-10352 | Defined as the time to reach maximum plasma concentration following drug administration of HS-10352 | Cycle 1 Day 1 (C1D1)，at the first day of Cycle 1 (each cycle is 28 days) |
| [Stage 1] PK parameters: time of the maximum concentration (Tmax) of fulvestrant | Defined as the time to reach maximum plasma concentration following drug administration of fulvestrant | Cycle 1 (28 days) |
| [Stage 1 and Stage 2] PK parameters: elimination half life (t1/2) of HS-10352 | Defines as the time measured for the concentration to decrease by one half. | Cycle 1 Day 1 (C1D1)，at the first day of Cycle 1 (each cycle is 28 days) |
| [Stage 1 and Stage 2] PK parameters: area under the concentration-time curve over 24 hours (AUC0-24) of HS-10352 | Defines as area under the plasma concentration versus time curve from time zero to the 24-hour sampling time. | Cycle 1 Day 1 (C1D1)，at the first day of Cycle 1 (each cycle is 28 days) |
| [Stage 1 and Stage 2] PK parameters: area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC0-t) of HS-10352 | Defines as area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). | Cycle 1 Day 1 (C1D1)，at the first day of Cycle 1 (each cycle is 28 days) |
| [Stage 1] PK parameters: area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC0-t) of fulvestrant | Defines as area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). | From Cycle 1 to Cycle 2， each cycle is 28 days |
| [Stage 1 and Stage 2] PK parameters: the maximum concentration at steady-state (Css,max) of HS-10352 | Defines as the maximum plasma drug concentration of HS-10352 at steady-state | Cycle 2 Day 1 (C2D1)，at the first day of Cycle 2 (each cycle is 28 days) each cycle is 28 days |
| [Stage 1] PK parameters: the maximum concentration at steady-state (Css,max) of fulvestrant | Defines as the maximum plasma drug concentration of fulvestrant at steady-state | Cycle 2 (28 days) |
| [Stage 1 and Stage 2] PK parameters: time of the maximum concentration at steady state (Tss,max) of HS-10352 | Defined as the time to reach maximum plasma concentration following drug administration of HS-10352 at steady-state | Cycle 2 Day 1 (C2D1)，at the first day of Cycle 1 (each cycle is 28 days) |
| [Stage 1] PK parameters: time of the maximum concentration at steady state (Tss,max) of fulvestrant | Defined as the time to reach maximum plasma concentration following drug administration of fulvestrant at steady-state | Cycle 2 (28 days) |
| [Stage 1 and Stage 2] PK parameters: the minimum concentration at steady-state (Css,min) of HS-10352 | Defines as the minimum plasma drug concentration of HS-10352 at steady-state | Cycle 2 Day 1 (C2D1)，at the first day of Cycle 1 (each cycle is 28 days) |
| [Stage 1 and Stage 2] PK parameters: the minimum concentration at steady-state (Css,min) of fulvestrant | Defines as the minimum plasma drug concentration of fulvestrant at steady-state | Cycle 2 (28 days) |
| [Stage 1] Efficacy of HS-10352 in combination with fulvestrant: ORR | ORR is defined as the proportion of participants with BOR of confirmed CR or confirmed PR based on assessment per RECIST v1.1. | From the date of first dose until the date of disease progression or withdrawal from study, approximately 3 years |
| [Stage 1 and Stage 2] Efficacy of HS-10352 in combination with fulvestrant: disease control rate (DCR) | The disease control was defined as the percentage of patients who have a best overall response (confirmed CR, PR, or stable disease for at least 6 weeks). | From the date of first dose until the date of disease progression or withdrawal from study, approximately 3 years |
| [Stage 1 and Stage 2] Efficacy of HS-10352 in combination with fulvestrant: duration of response (DoR) | DOR only applies to participants whose best overall response is CR or PR based on assessment per RECIST v1.1. The start date is the date of first documented response of CR or PR (i.e. the start date of observed response, not the date when response was confirmed), and the end date is defined as the date of the first documented progression or death due to underlying cancer. | From the date of CR, PR until the date of disease progression or withdrawal from study, approximately 3 years |
| [Stage 1 and Stage 2] Efficacy of HS-10352 in combination with fulvestrant: progression free survival (PFS) | PFS is defined as the time from the date of randomization or first dose (if randomization is not needed) to the date of the first documented progression or death due to any cause. PFS will be assessed per RECIST v1.1. | From the date of randomization or first dose (if randomization is not needed) until the date of disease progression or withdrawal from study, approximately 3 years |
| [Stage 2] Efficacy of HS-10352 in combination with fulvestrant: overall survival (OS) | OS is defined as the time from the date of randomization or first dose (if randomization is not needed) to the date of death due to any cause. For each participant who is not known to have died as of the cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive. | From the date of randomization or first dose (if randomization is not needed) until the documentation of death from any cause, approximately 6 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
dose-escalation, dose-expansion, advanced breast cancer, hormone receptor positive, PIK3CA gene mutation
|
NCT00609622
|
Randomized Study Of Sunitinib Plus FOLFOX Versus Bevacizumab Plus FOLFOX In Metastatic Colorectal Cancer
|
This study will compare the safety and efficacy of sunitinib in combination with FOLFOX versus bevacizumab in combination with FOLFOX for the treatment of patients with metastatic colorectal cancer who have not been treated before.
|
The study was terminated on April 26, 2010 due to lack of efficacy, as determined during the interim analysis of data in April 2010, showing that the study did not meet its primary endpoint to demonstrate a statistically significant improvement in PFS. The decision to terminate the trial was not based on any safety concerns.
|
A Randomized, Phase 2B Study Of Sunitinib Plus Oxaliplatin, 5-Fluorouracil And Leucovorin (FOLFOX) Versus Bevacizumab Plus FOLFOX As First-Line Treatment In Patients With Metastatic Colorectal Cancer
|
Colorectal Neoplasms
|
* Drug: sunitinib
* Drug: mFOLFOX6
* Drug: bevacizumab
* Drug: mFOLFOX6
|
Inclusion Criteria:~Adenocarcinoma of the colon or rectum with locally advanced or metastatic disease~Evidence of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)~Eastern Cooperative Oncology Group (ECOG) 0 or 1~Exclusion Criteria:~Previous treatment with Sutent, Avastin, or any other systemic therapy for locally advanced or metastatic colorectal cancer~Less than 6 months since completion of adjuvant chemotherapy to documentation of recurrent disease~History of cardiac disease~Brain mets
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was Death). | Baseline, at every 8-week intervals for 18 months then every 12 weeks thereafter until disease progression (up to Week 115) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Time in weeks from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death). | Baseline, at every 8-week intervals for 18 months, and then every 12 weeks thereafter up to every 2 months until death (up to Week 115) |
| One Year Survival Probability | One year survival probability was defined as the probability of survival at one year after the first dose of study treatment. | Baseline, at every 8-week intervals for 18 months, and then every 12 weeks thereafter up to every 2 months until death (up to 1 year) |
| Two Year Survival Probability | Two year survival probability was defined as the probability of survival at two years after the first dose of study treatment. | Baseline, at every 8-week intervals for 18 months, and then every 12 weeks thereafter up to every 2 months until death (up to 2 years) |
| Percentage of Participants With Objective Response (OR) | Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and/or non target). PR were those with at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent. | Baseline until disease progression or discontinuation of the study, at every 8-week intervals for 18 months, and then every 12 weeks thereafter up to Week 115 |
| Duration of Response (DR) | Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response. | Baseline until disease progression or discontinuation of the study, at every 8-week intervals for 18 months, and then every 12 weeks thereafter up to Week 115 |
| Change From Baseline in Functional Assessment of Cancer Treatment - Colorectal (FACT-C) Score | FACT-C used for assessment of health-related quality of life (QoL) in participants with cancer. It consists of 36 items, summarized to 5 subscales:physical well-being (PWB) (7 items), functional well-being (FWB) (7 items), social/family well-being (SWB) (7 items); all 3 subscales range from 0 to 28, emotional well-being (EWB) (6 items) range from 0 to 24, colorectal cancer subscale (9 items) range from 0 to 36; higher subscale score=better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score range: 0 to 144. High scale score represents a better QoL. | Baseline [Day (D) 1 of Cycle (C) 1] then every 3 cycles thereafter and at the end of treatment (EOT) or withdrawal visit (up to Week 115) |
| Change From Baseline in Functional Assessment of Cancer Treatment - Gynecologic Oncology Group Oxaliplatin-Specific Neurotoxicity (FACT&GOG-Ntx) Score | FACT&GOG-Ntx has a 13-item, treatment-specific subscale for patients with neurotoxicity. It is the sum of the PWB (7 items), FWB (7 items), SWB (7 items) and EWB (6 items) subscales plus a 13 item neurotoxicity subscale. Subscale score ranges from 0 to 28 for PWB, FWB, SWB, 0 to 24 for EWB and 0 to 52 for neurotoxicity subscale. Total possible score range is 0 to 160. Higher scores indicates better QoL, fewer disease symptoms, and/or fewer side effects of treatment and lower scores indicate worse QoL and a greater impact of disease symptoms and/or side effects. | Baseline (D1 of C1) then every 3 cycles thereafter and at the EOT or withdrawal visit (up to 115 weeks) |
|
metastatic colorectal cancer sunitinib (Sutent) bevacizumab (Avastin) randomized study
|
Bevacizumab, Sunitinib, Antineoplastic Agents, Immunological, Antineoplastic Agents, Angiogenesis Inhibitors, Angiogenesis Modulating Agents, Growth Substances, Physiological Effects of Drugs, Growth Inhibitors, Protein Kinase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Treatment arm A - sunitinib plus mFOLFOX6 | Drug: sunitinib<br>* Sunitinib: 37.5 mg/day, oral, administered on an outpatient basis for 4 weeks on, 2 weeks off (Schedule 4/2).<br>* Other names: Sutent, SU011248;Drug: mFOLFOX6<br>* FOLFOX will be administered every 2 weeks, using the modified FOLFOX6 (mFOLFOX6) regimen, consisting of: - oxaliplatin 85 mg/ m^2 + leucovorin 400 mg/ m^2 (or 200 mg/ m^2 levo-leucovorin) as a 2-hr IV infusion followed by 5-fluorouracil 400 mg/ m^2 IV bolus on day 1 and 5-fluorouracil 2400 mg/ m^2 IV infusion over 46 hours on Days 1 and 2 of each 2 week cycle<br>|
| Active Comparator: B<br>Treatment arm B - bevacizumab plus mFOLFOX6 | Drug: bevacizumab<br>* Bevacizumab: 5 mg/kg, IV infusion, every 2 weeks.<br>* Other names: Avastin;Drug: mFOLFOX6<br>* FOLFOX will be administered every 2 weeks, using the modified FOLFOX6 (mFOLFOX6) regimen, consisting of: - oxaliplatin 85 mg/ m^2 + leucovorin 400 mg/ m^2 (or 200 mg/ m^2 levo-leucovorin) as a 2-hr IV infusion followed by 5-fluorouracil 400 mg/ m^2 IV bolus on day 1 and 5-fluorouracil 2400 mg/ m^2 IV infusion over 46 hours on Days 1 and 2 of each 2 week cycle<br>|
|
Randomized Study Of Sunitinib Plus FOLFOX Versus Bevacizumab Plus FOLFOX In Metastatic Colorectal Cancer
Study Overview
=================
Brief Summary
-----------------
This study will compare the safety and efficacy of sunitinib in combination with FOLFOX versus bevacizumab in combination with FOLFOX for the treatment of patients with metastatic colorectal cancer who have not been treated before.
Detailed Description
-----------------
The study was terminated on April 26, 2010 due to lack of efficacy, as determined during the interim analysis of data in April 2010, showing that the study did not meet its primary endpoint to demonstrate a statistically significant improvement in PFS. The decision to terminate the trial was not based on any safety concerns.
Official Title
-----------------
A Randomized, Phase 2B Study Of Sunitinib Plus Oxaliplatin, 5-Fluorouracil And Leucovorin (FOLFOX) Versus Bevacizumab Plus FOLFOX As First-Line Treatment In Patients With Metastatic Colorectal Cancer
Conditions
-----------------
Colorectal Neoplasms
Intervention / Treatment
-----------------
* Drug: sunitinib
* Drug: mFOLFOX6
* Drug: bevacizumab
* Drug: mFOLFOX6
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adenocarcinoma of the colon or rectum with locally advanced or metastatic disease Evidence of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Eastern Cooperative Oncology Group (ECOG) 0 or 1 Exclusion Criteria: Previous treatment with Sutent, Avastin, or any other systemic therapy for locally advanced or metastatic colorectal cancer Less than 6 months since completion of adjuvant chemotherapy to documentation of recurrent disease History of cardiac disease Brain mets
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: A<br>Treatment arm A - sunitinib plus mFOLFOX6 | Drug: sunitinib<br>* Sunitinib: 37.5 mg/day, oral, administered on an outpatient basis for 4 weeks on, 2 weeks off (Schedule 4/2).<br>* Other names: Sutent, SU011248;Drug: mFOLFOX6<br>* FOLFOX will be administered every 2 weeks, using the modified FOLFOX6 (mFOLFOX6) regimen, consisting of: - oxaliplatin 85 mg/ m^2 + leucovorin 400 mg/ m^2 (or 200 mg/ m^2 levo-leucovorin) as a 2-hr IV infusion followed by 5-fluorouracil 400 mg/ m^2 IV bolus on day 1 and 5-fluorouracil 2400 mg/ m^2 IV infusion over 46 hours on Days 1 and 2 of each 2 week cycle<br>|
| Active Comparator: B<br>Treatment arm B - bevacizumab plus mFOLFOX6 | Drug: bevacizumab<br>* Bevacizumab: 5 mg/kg, IV infusion, every 2 weeks.<br>* Other names: Avastin;Drug: mFOLFOX6<br>* FOLFOX will be administered every 2 weeks, using the modified FOLFOX6 (mFOLFOX6) regimen, consisting of: - oxaliplatin 85 mg/ m^2 + leucovorin 400 mg/ m^2 (or 200 mg/ m^2 levo-leucovorin) as a 2-hr IV infusion followed by 5-fluorouracil 400 mg/ m^2 IV bolus on day 1 and 5-fluorouracil 2400 mg/ m^2 IV infusion over 46 hours on Days 1 and 2 of each 2 week cycle<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was Death). | Baseline, at every 8-week intervals for 18 months then every 12 weeks thereafter until disease progression (up to Week 115) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Time in weeks from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death). | Baseline, at every 8-week intervals for 18 months, and then every 12 weeks thereafter up to every 2 months until death (up to Week 115) |
| One Year Survival Probability | One year survival probability was defined as the probability of survival at one year after the first dose of study treatment. | Baseline, at every 8-week intervals for 18 months, and then every 12 weeks thereafter up to every 2 months until death (up to 1 year) |
| Two Year Survival Probability | Two year survival probability was defined as the probability of survival at two years after the first dose of study treatment. | Baseline, at every 8-week intervals for 18 months, and then every 12 weeks thereafter up to every 2 months until death (up to 2 years) |
| Percentage of Participants With Objective Response (OR) | Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and/or non target). PR were those with at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent. | Baseline until disease progression or discontinuation of the study, at every 8-week intervals for 18 months, and then every 12 weeks thereafter up to Week 115 |
| Duration of Response (DR) | Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response. | Baseline until disease progression or discontinuation of the study, at every 8-week intervals for 18 months, and then every 12 weeks thereafter up to Week 115 |
| Change From Baseline in Functional Assessment of Cancer Treatment - Colorectal (FACT-C) Score | FACT-C used for assessment of health-related quality of life (QoL) in participants with cancer. It consists of 36 items, summarized to 5 subscales:physical well-being (PWB) (7 items), functional well-being (FWB) (7 items), social/family well-being (SWB) (7 items); all 3 subscales range from 0 to 28, emotional well-being (EWB) (6 items) range from 0 to 24, colorectal cancer subscale (9 items) range from 0 to 36; higher subscale score=better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score range: 0 to 144. High scale score represents a better QoL. | Baseline [Day (D) 1 of Cycle (C) 1] then every 3 cycles thereafter and at the end of treatment (EOT) or withdrawal visit (up to Week 115) |
| Change From Baseline in Functional Assessment of Cancer Treatment - Gynecologic Oncology Group Oxaliplatin-Specific Neurotoxicity (FACT&GOG-Ntx) Score | FACT&GOG-Ntx has a 13-item, treatment-specific subscale for patients with neurotoxicity. It is the sum of the PWB (7 items), FWB (7 items), SWB (7 items) and EWB (6 items) subscales plus a 13 item neurotoxicity subscale. Subscale score ranges from 0 to 28 for PWB, FWB, SWB, 0 to 24 for EWB and 0 to 52 for neurotoxicity subscale. Total possible score range is 0 to 160. Higher scores indicates better QoL, fewer disease symptoms, and/or fewer side effects of treatment and lower scores indicate worse QoL and a greater impact of disease symptoms and/or side effects. | Baseline (D1 of C1) then every 3 cycles thereafter and at the EOT or withdrawal visit (up to 115 weeks) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
metastatic colorectal cancer sunitinib (Sutent) bevacizumab (Avastin) randomized study
|
NCT00414258
|
The Holding Study: Feeding Analgesia in Preterm Infants
|
The purpose of this study is to compare the effects of mothers' skin-to-skin holding during feeding via a soother trainer with the effects of pacifier sucking on preterm infant biobehavioural responses during and immediately after a painful procedure~Hypothesis:~When held by their mothers during blood collection, preterm infants will show less pain reaction than when sucking on a pacifier.~Following holding during the blood collection, mothers will find no differences in their infants' feeding ability.
|
Research Method:~In a between subjects, randomized design, 20 stable preterm infants born between 30-35 weeks gestational age will be studied. Infants will be randomized to one of two interventions which will take place during blood collections that are required for clinical management. For the standard care condition, infants will remain in their isolettes and will be positioned in prone and given a pacifier to suck on throughout the blood collection. For the holding condition, infants will be held skin-to-skin by their mothers and given breast milk using a soother trainer during the blood collection.
|
The Holding Pilot Study: Feeding Analgesia in Preterm Infants
|
Pain
|
* Procedure: breastfeeding
|
Inclusion Criteria:~Born between 30-35 weeks gestational age~Mother has fluent English~Exclusion Criteria:~CNS injury~congenital anomaly~active infection~has had no surgeries or analgesics/sedatives in last 72 hours~history of maternal drug exposure
|
3 Days
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Videotaped and recorded at Baseline, Lance and Recovery:Neonatal Facial Coding System - total facial score; Heart Rate | | |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Videotaped and Recorded at Baseline, Lance and Recovery:Hand Movements; Sleep/Wake States | | |
| Samples taken at baseline and recovery;Salivary Cortisol sample | | |
|
Pain Response
|
| Intervention/Treatment |
| --- |
|Procedure: breastfeeding|See detailed description.|
|
The Holding Study: Feeding Analgesia in Preterm Infants
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare the effects of mothers' skin-to-skin holding during feeding via a soother trainer with the effects of pacifier sucking on preterm infant biobehavioural responses during and immediately after a painful procedure Hypothesis: When held by their mothers during blood collection, preterm infants will show less pain reaction than when sucking on a pacifier. Following holding during the blood collection, mothers will find no differences in their infants' feeding ability.
Detailed Description
-----------------
Research Method: In a between subjects, randomized design, 20 stable preterm infants born between 30-35 weeks gestational age will be studied. Infants will be randomized to one of two interventions which will take place during blood collections that are required for clinical management. For the standard care condition, infants will remain in their isolettes and will be positioned in prone and given a pacifier to suck on throughout the blood collection. For the holding condition, infants will be held skin-to-skin by their mothers and given breast milk using a soother trainer during the blood collection.
Official Title
-----------------
The Holding Pilot Study: Feeding Analgesia in Preterm Infants
Conditions
-----------------
Pain
Intervention / Treatment
-----------------
* Procedure: breastfeeding
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Born between 30-35 weeks gestational age Mother has fluent English Exclusion Criteria: CNS injury congenital anomaly active infection has had no surgeries or analgesics/sedatives in last 72 hours history of maternal drug exposure
Ages Eligible for Study
-----------------
Minimum Age: 3 Days
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
| Intervention/Treatment |
| --- |
|Procedure: breastfeeding|See detailed description.|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Videotaped and recorded at Baseline, Lance and Recovery:Neonatal Facial Coding System - total facial score; Heart Rate | | |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Videotaped and Recorded at Baseline, Lance and Recovery:Hand Movements; Sleep/Wake States | | |
| Samples taken at baseline and recovery;Salivary Cortisol sample | | |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pain Response
|
|
NCT00106158
|
Safety Study of NY-ESO-1 Protein Vaccine to Treat Cancer Expressing NY-ESO-1
|
The purpose of this study is to assess the safety of repeated doses of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein (CHP-NY-ESO-1) and describe the NY-ESO-1 specific-humoral and cellular immune response to immunization with CHP-NY-ESO-1 in patients with cancer expressing NY-ESO-1.
|
NY-ESO-1 was isolated by serological analysis of recombinant cDNA expression libraries (SEREX), using tumor mRNA and autologous serum from an esophageal cancer patient. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that NY-ESO-1 displayed the typical expression pattern of CT antigens. NY-ESO-1 mRNA was expressed only in testis of normal tissues tested and in various types of cancer, including lung cancer, breast cancer, malignant melanoma and bladder cancer. LAGE-1 was identified by the representational difference analysis and revealed to display 84% amino acid homology with NY-ESO-1. In most cases, expression of LAGE-1 parallels the expression of NY-ESO-1. Since testis is an immune privileged organ where HLA molecules are not expressed, these antigens can be considered tumor-specific.~Because of frequent NY-ESO-1 mRNA expression and high immunogenicity in advanced cancer, NY-ESO-1 is an attractive target molecule for a cancer vaccine. Current therapies against advanced cancer have limited effectiveness. The idea of vaccination with NY-ESO-1 protein in cancer patients with tumors expressing NY-ESO-1 mRNA is based on two findings: 1) the number of CD8+ T cell epitopes identified in NY-ESO-1 molecule are limited to those binding to HLA-A0201, A31, Cw3 and Cw6. These HLA subtypes are carried by a minor Japanese population; 2) CD8+ T cell responses specific to NY-ESO-1 are polyclonal. Protein vaccination may induce immune response more effectively against tumors expressing NY-ESO-1 than peptide immunization.
|
Immunization of Patients With Tumors Expressing NY-ESO-1 or LAGE Antigen With Complex of NY-ESO-1 Protein and Cholesterol-bearing Hydrophobized Pullulan (CHP)
|
Neoplasms
|
* Biological: protein vaccination
|
Inclusion Criteria:~Histologically proven cancer~Confirmed NY-ESO-1 expression~No other effective therapy available~4 weeks since conventional therapy before start of the current protocol~Performance status < 2 (ECOG scale)~Age > 18~Able and willing to give written informed consent~Exclusion Criteria:~Serious illness~Metastatic diseases to central nervous system~Concomitant systemic treatment with corticosteroids, anti-histaminic drugs or NSAIDs~HIV positive~Mental impairment that may compromise the ability to give written informed consent~Pregnancy and breastfeeding
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NY-ESO-1-specific immune responses | | |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tumor responses | | |
|
cancer/testis antigen, cancer vaccine, recombinant protein
|
| Intervention/Treatment |
| --- |
|Biological: protein vaccination|nan|
|
Safety Study of NY-ESO-1 Protein Vaccine to Treat Cancer Expressing NY-ESO-1
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the safety of repeated doses of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein (CHP-NY-ESO-1) and describe the NY-ESO-1 specific-humoral and cellular immune response to immunization with CHP-NY-ESO-1 in patients with cancer expressing NY-ESO-1.
Detailed Description
-----------------
NY-ESO-1 was isolated by serological analysis of recombinant cDNA expression libraries (SEREX), using tumor mRNA and autologous serum from an esophageal cancer patient. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that NY-ESO-1 displayed the typical expression pattern of CT antigens. NY-ESO-1 mRNA was expressed only in testis of normal tissues tested and in various types of cancer, including lung cancer, breast cancer, malignant melanoma and bladder cancer. LAGE-1 was identified by the representational difference analysis and revealed to display 84% amino acid homology with NY-ESO-1. In most cases, expression of LAGE-1 parallels the expression of NY-ESO-1. Since testis is an immune privileged organ where HLA molecules are not expressed, these antigens can be considered tumor-specific. Because of frequent NY-ESO-1 mRNA expression and high immunogenicity in advanced cancer, NY-ESO-1 is an attractive target molecule for a cancer vaccine. Current therapies against advanced cancer have limited effectiveness. The idea of vaccination with NY-ESO-1 protein in cancer patients with tumors expressing NY-ESO-1 mRNA is based on two findings: 1) the number of CD8+ T cell epitopes identified in NY-ESO-1 molecule are limited to those binding to HLA-A0201, A31, Cw3 and Cw6. These HLA subtypes are carried by a minor Japanese population; 2) CD8+ T cell responses specific to NY-ESO-1 are polyclonal. Protein vaccination may induce immune response more effectively against tumors expressing NY-ESO-1 than peptide immunization.
Official Title
-----------------
Immunization of Patients With Tumors Expressing NY-ESO-1 or LAGE Antigen With Complex of NY-ESO-1 Protein and Cholesterol-bearing Hydrophobized Pullulan (CHP)
Conditions
-----------------
Neoplasms
Intervention / Treatment
-----------------
* Biological: protein vaccination
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically proven cancer Confirmed NY-ESO-1 expression No other effective therapy available 4 weeks since conventional therapy before start of the current protocol Performance status < 2 (ECOG scale) Age > 18 Able and willing to give written informed consent Exclusion Criteria: Serious illness Metastatic diseases to central nervous system Concomitant systemic treatment with corticosteroids, anti-histaminic drugs or NSAIDs HIV positive Mental impairment that may compromise the ability to give written informed consent Pregnancy and breastfeeding
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Intervention/Treatment |
| --- |
|Biological: protein vaccination|nan|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NY-ESO-1-specific immune responses | | |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tumor responses | | |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cancer/testis antigen, cancer vaccine, recombinant protein
|
|
NCT01191502
|
Comparative Study of Photopic and Mesopic Distance, Intermediate and Near Visual Acuity, and Spectacle Independence
|
The purpose of this study is to evaluate visual acuity in different lighting conditions (daylight and night time) and distances (distance, near and intermediate), and the independence of glasses, in patients who have had binocular implantation of the Tecnis Multifocal IOL or the Crystalens™ HD Accommodating IOL.
|
Comparative Study of Photopic and Mesopic Distance Intermediate and Near Visual Acuity, and Spectacle Independence With Binocular Implantation of the Tecnis Multifocal (TMF) Intraocular Lens or Crystalens HD (CHD) Intraocular Lens
|
Visual Acuity
|
Inclusion Criteria:~18 years of age or older~Status post bilateral cataract or refractive lens surgery (with or without LRI) and implantation of Tecnis™ Multifocal IOL or Crystalens™ HD Accommodating IOL~Best-corrected ETDRS equivalent visual acuity of 20/30 or better in each eye~Naturally dilated pupil size (in dim light) > 3.5 mm (with no dilation medications) for both eyes~Clear intraocular media (no posterior capsular opacification, or status post YAG capsulotomy)~Availability, willingness, and sufficient cognitive awareness to comply with examination procedures~Exclusion Criteria:~Ocular disease which could potentially limit uncorrected visual acuity or visual performance.~Use of systemic or ocular medications that may affect visual outcomes~Acute or chronic disease or illness that would increase risk or confound study results (e.g. diabetes mellitus, immunocompromised, etc.)~Uncontrolled systemic or ocular disease~History of ocular trauma~History of ocular surgery other than that required for inclusion in this study~Amblyopia or strabismus~Known pathology that may affect visual acuity; particularly retinal changes that affect vision (macular degeneration, cystoid macular edema, proliferative diabetic retinopathy, etc.)~Diagnosed degenerative visual disorders (e.g. macular degeneration, or other retinal disorders) that are predicted to cause future acuity losses to a level of worse than 20/30~Subjects who may be expected to require retinal laser treatment or other surgical intervention~Capsule or zonular abnormalities that may affect postoperative centration or tilt of the lens (e.g. pseudoexfoliation syndrome)~Pupil abnormalities (non-reactive, tonic pupils or abnormally shaped pupils)
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Manifest refraction (monocular) | | 1 year |
| Uncorrected visual acuity (UCVA) ETDRS testing at distance, intermediate and near in photopic lighting (monocular and binocular) | | 1 year |
| Best distance-corrected visual acuity (BDCVA) ETDRS testing at distance, intermediate and near in photopic lighting (monocular and binocular) | | 1 year |
| Uncorrected visual acuity (UCVA) ETDRS testing at distance, intermediate and near in mesopic lighting (monocular and binocular) | | 1 year |
| Best distance-corrected visual acuity (BDCVA) ETDRS testing at distance, intermediate and near in mesopic lighting (monocular and binocular) | | 1 year |
| Photopic and mesopic pupillometry | | 1 year |
|
Patients who have had binocular implantation of the Tecnis Multifocal IOL or the Crystalens™ HD Accommodating IOL.
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| TECNIS MULTIFOCAL (TMF) INTRAOCULAR LENS<br> | |
| CRYSTALENS HD (CHD) INTRAOCULAR LENS<br> | |
|
Comparative Study of Photopic and Mesopic Distance, Intermediate and Near Visual Acuity, and Spectacle Independence
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate visual acuity in different lighting conditions (daylight and night time) and distances (distance, near and intermediate), and the independence of glasses, in patients who have had binocular implantation of the Tecnis Multifocal IOL or the Crystalens™ HD Accommodating IOL.
Official Title
-----------------
Comparative Study of Photopic and Mesopic Distance Intermediate and Near Visual Acuity, and Spectacle Independence With Binocular Implantation of the Tecnis Multifocal (TMF) Intraocular Lens or Crystalens HD (CHD) Intraocular Lens
Conditions
-----------------
Visual Acuity
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years of age or older Status post bilateral cataract or refractive lens surgery (with or without LRI) and implantation of Tecnis™ Multifocal IOL or Crystalens™ HD Accommodating IOL Best-corrected ETDRS equivalent visual acuity of 20/30 or better in each eye Naturally dilated pupil size (in dim light) > 3.5 mm (with no dilation medications) for both eyes Clear intraocular media (no posterior capsular opacification, or status post YAG capsulotomy) Availability, willingness, and sufficient cognitive awareness to comply with examination procedures Exclusion Criteria: Ocular disease which could potentially limit uncorrected visual acuity or visual performance. Use of systemic or ocular medications that may affect visual outcomes Acute or chronic disease or illness that would increase risk or confound study results (e.g. diabetes mellitus, immunocompromised, etc.) Uncontrolled systemic or ocular disease History of ocular trauma History of ocular surgery other than that required for inclusion in this study Amblyopia or strabismus Known pathology that may affect visual acuity; particularly retinal changes that affect vision (macular degeneration, cystoid macular edema, proliferative diabetic retinopathy, etc.) Diagnosed degenerative visual disorders (e.g. macular degeneration, or other retinal disorders) that are predicted to cause future acuity losses to a level of worse than 20/30 Subjects who may be expected to require retinal laser treatment or other surgical intervention Capsule or zonular abnormalities that may affect postoperative centration or tilt of the lens (e.g. pseudoexfoliation syndrome) Pupil abnormalities (non-reactive, tonic pupils or abnormally shaped pupils)
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 |
| --- | --- |
| TECNIS MULTIFOCAL (TMF) INTRAOCULAR LENS<br> | |
| CRYSTALENS HD (CHD) INTRAOCULAR LENS<br> | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Manifest refraction (monocular) | | 1 year |
| Uncorrected visual acuity (UCVA) ETDRS testing at distance, intermediate and near in photopic lighting (monocular and binocular) | | 1 year |
| Best distance-corrected visual acuity (BDCVA) ETDRS testing at distance, intermediate and near in photopic lighting (monocular and binocular) | | 1 year |
| Uncorrected visual acuity (UCVA) ETDRS testing at distance, intermediate and near in mesopic lighting (monocular and binocular) | | 1 year |
| Best distance-corrected visual acuity (BDCVA) ETDRS testing at distance, intermediate and near in mesopic lighting (monocular and binocular) | | 1 year |
| Photopic and mesopic pupillometry | | 1 year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Patients who have had binocular implantation of the Tecnis Multifocal IOL or the Crystalens™ HD Accommodating IOL.
|
|||||
NCT02315066
|
Study Of OX40 Agonist PF-04518600 Alone And In Combination With 4-1BB Agonist PF-05082566
|
To assess the safety and tolerability at increasing dose levels of PF-04518600 alone or in combination wtih PF-05082566 in patients with select advanced or metastatic carcinoma in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.
|
A PHASE 1, OPEN-LABEL, DOSE ESCALATION STUDY OF PF-04518600 AS A SINGLE AGENT AND IN COMBINATION WITH PF-05082566 IN PATIENTS WITH SELECTED LOCALLY ADVANCED OR METASTATIC CANCERS
|
Neoplasms
|
* Drug: PF-04518600
* Drug: PF-04518600
* Drug: PF-04518600 plus PF-05082566
* Drug: PF-04518600 plus PF-05082566
|
Inclusion Criteria:~Part A1 only: Patients with histological or cytological diagnosis of HNSCC, HCC, melanoma, or clear cell RCC who progressed on or are intolerant to standard therapy, for which no standard therapy is available or who decline standard therapy.~Part A2 only: Patients with histological or cytological diagnosis of advanced/metastatic HCC who are treatment naïve and have declined standard of care, or have had at least 1 prior line of systemic therapy. Prior anti PD L1/PD 1 therapy is allowed.~Part B1 only: Patients with histological or cytological diagnosis of NSCLC, HNSCC, melanoma, urothelial bladder carcinoma (including renal pelvis, ureters, urinary bladder, and urethra), gastric or squamous cell carcinoma of the uterine cervix who progressed on or are intolerant to standard therapy, for which no standard therapy is available, or who decline standard therapy.~Part B2~Arm 1 only:~Ocular melanoma patients with advanced/metastatic disease, or~Cutaneous/acral melanoma patients with advanced/metastatic disease who have received checkpoint inhibitor (anti PD L1, anti PD 1, or anti CTLA4) based treatment on which disease progressed. [Note: Checkpoint inhibitor may have been part of a combination therapy, as long as the combination did not contain OX40 or 4 1BB agonist.] Any questions on prior treatment may be discussed with the Sponsor.~Arm 2 only:~Histological or cytological diagnosis of NSCLC with advanced/metastatic disease. Patients must have previously received prior anti PD L1 or anti PD 1 mAb on which disease progressed. [Note: Previous anti PD L1 or anti PD 1 mAb may have been part of a combination therapy, eg, in combination with chemotherapy, as long as the combination did not contain OX40 or 4 1BB agonist.]~Performance Status of 0 or 1 - Adequate bone marrow, kidney and liver function~Exclusion Criteria:~Brain metastases requiring steroids~Major surgery, Radiation therapy within 4 weeks of starting study treatment (except: palliative radiotherapy to a limited field is allowed after consultation with sponsor's medical monitor at any time during study participation, including during screening), or systemic anti-cancer therapy within 4 weeks of study treatment start (6 weeks for mitomycin C or nitrosoureas)~Active and clinically significant bacterial, fungal, or viral infection~History of active autoimmune disorders~History of immune-mediated adverse events requiring immunosuppressive therapy or were grade 3 or higher related to prior immune-modulatory therapy~Prior treatment with an OX40 agonist and 4-1BB agonist (for Part B1/B2)~Prior anthracycline treatment and at risk of cardiac failure (New York Heart Association Class 2)
|
18 Years
| 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 Participants With Dose Limiting Toxicities (DLTs) in Part A1 | DLT was defined as any of the following adverse events occurring in the first two cycle of treatment (28 days), unless there was a clear alternative explanation: hematologic: grade 4 neutropenia lasting >7 days, febrile neutropenia; grade ≥3 neutropenic infection; grade ≥3 thrombocytopenia with clinically significant bleeding or requiring medical intervention; grade 4 thrombocytopenia; grade 4 anemia; grade ≥3 anemia related to hemolysis or autoimmune disease. non hematologic: grade ≥3 toxicities that were considered clinically significant, including cytokine release syndrome, infusion reactions and allergic reactions, except those that had not been maximally treated or could be easily treated. The severity of adverse events was graded as per common terminology criteria for adverse events(CTCAE) version 4.03, and there were no DLTs reported. | The first 2 cycles of treatment (Day 1 up to Day 28) |
| Number of Participants With All-Causality Treatment Emergent Adverse Events(TEAEs) and Serious Adverse Event(SAEs), Treatment-Related TEAEs and SAEs in Part A | Adverse event (AE) was graded by the investigator according to CTCAE version 4.03 and coded using the Medical Dictionary for Regulatory Activities (MedDRA): Grade 3 (Severe) events=unacceptable or intolerable events. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events=death related to an AE. Treatment-emergent events=between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. TEAEs were defined as those with initial onset or increasing in severity after the first dose of study medication. Serious adverse event (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. | AEs: The informed consent date up to the last dosing date + 28 days or all drug-related toxicities resolved date. SAEs: The informed consent date through first dosing date + 98 days or up to the last dosing date + 60 days, and any post-reporting period. |
| Number of Participants With Laboratory Test Abnormalities in Part A | Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, partial thromboplastin time (PTT), Prothrombin (PT), PT international ratio); liver function (aspartate aminotransferase(AST), alanine aminotransferase(ALT), total bilirubin, gamma-glutamyl transpeptidase(GT), alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium , phosphate, magnesium); clinical chemistry (glucose, creatine kinase, thyroxine (T4), thyroid stimulating hormone(TSH)), Amylase, Lipase), urinalysis (dipstick [protein, blood], microscopy [urine red blood cell (RBC), white blood cell (WBC), Epithelial Cells], miscellaneous [urine casts and bacteria]). | The first dosing date to the earlier date between the last dosing date + 35 days and the first new anti-cancer therapy date (if applicable) |
| Number of Participants With DLTs in Part B1 | DLT was defined as any of the following adverse events occurring in the first two cycle of treatment (28 days), unless there was a clear alternative explanation: hematologic: grade 4 neutropenia lasting >7 days, febrile neutropenia; grade ≥3 neutropenic infection; grade ≥3 thrombocytopenia with clinically significant bleeding or requiring medical intervention; grade 4 thrombocytopenia; grade 4 anemia; grade ≥3 anemia related to hemolysis or autoimmune disease. non hematologic: grade ≥3 toxicities that were considered clinically significant, including cytokine release syndrome, infusion reactions and allergic reactions, except those that had not been maximally treated or could be easily treated. The severity of adverse events was graded as per common terminology criteria for adverse events(CTCAE) version 4.03, and there were no DLTs reported. | The First 2 Cycles of Treatment (Day 1 up to Day 28) |
| Number of Participants With All-causality TEAEs and SAEs, and Treatment-Related TEAEs and SAEs in Part B | Adverse event (AE) was graded by the investigator according to CTCAE version 4.03 and coded using the Medical Dictionary for Regulatory Activities (MedDRA): Grade 3 (Severe) events=unacceptable or intolerable events. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events=death related to an AE. Treatment-emergent events=between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. TEAEs were defined as those with initial onset or increasing in severity after the first dose of study medication. Serious adverse event (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. | AEs: The informed consent date up to the last dosing date + 60 days or all drug-related toxicities resolved date. SAEs: The informed consent date through first dosing date + 98 days or up to the last dosing date + 60 days, and any post-reporting period. |
| Number of Participants With Laboratory Test Abnormalities in Part B | Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, partial thromboplastin time (PTT), Prothrombin (PT), PT international ratio); liver function (aspartate aminotransferase(AST), alanine aminotransferase(ALT), total bilirubin, gamma-glutamyl transpeptidase(GT), alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium , phosphate, magnesium); clinical chemistry (glucose, creatine kinase, thyroxine (T4), thyroid stimulating hormone(TSH)), Amylase, Lipase), urinalysis (dipstick [protein, blood], microscopy [urine red blood cell (RBC), white blood cell (WBC), Epithelial Cells], miscellaneous [urine casts and bacteria]). | The first dosing date to the earlier date between the last dosing date + 35 days and the first new anti-cancer therapy date (if applicable) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) Assessed by Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 and Immune Related Response Evaluation Criteria in Solid Tumors (irRECIST) in Part A | ORR was defined as the percentage of patients with best overall response (BOR) of CR or PR relative to the appropriate analysis set.~CR: Complete response is defined (per RECIST 1.1) as disappearance of all target and non target lesions. Any pathological lymph nodes (whether target or non target) must have reduction in short axis to <10 mm.~PR: Partial response is difined (per RECIST 1.1) as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.~Overall immune related complete response (irCR): Complete disappearance of all lesions (whether measurable or not) and no new lesions. All measurable lymph nodes also must have a reduction in short axis to <10 mm.~Overall immune related partial response (irPR): Sum of the diameters (longest for non nodal lesions, shortest for nodal lesions) of target and new measurable lesions decreases ≥30%. | Baseline up to 24 months post first dose. |
| Kaplan-Meier Estimate of Median Progression-Free Survival (PFS) in Part A | PFS was defined as the time from randomization date to date of first documentation of progressive disease(PD) based on RECIST, irRECIST or death due to any cause.~PD was progression documented after start date and not qualifying as CR, PR or SD per RECIST. | Baseline up to 24 months post first dose |
| Kaplan-Meier Estimate of Median Time to Progression (TTP) in Part A | TTP was defined as the time from start date to the date of the first documentation of PD. PD was documented after start date and not qualifying as CR, PR or SD per RECIST. | Baseline up to 24 months post first dose |
| Number of Participants Having Stable Disease (SD) in Part A | SD was defined as persistence of any non target lesions and/or tumor marker level above the normal limits. | Baseline up to 24 months post first dose. |
| Kaplan-Meier Estimate of Median Duration of Response (DoR) in Part A | DoR was defined as the time from first documentation of PR or CR to date of first documentation of PD or death due to any cause for patients with an objective response.~CR was defined as complete disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis <10 mm) and all target lesions must be assessed.~PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions and all target lesions must be assessed. | Baseline up to 24 months post first dose. |
| Kaplan-Meier Estimate of Median Overall Survival (OS) in Part A | OS was defined as time in months from the start of study treatment to date of death due to any cause. OS was calculated as the death date or last known alive date (if death date unavailable) minus the date of first dose of study medication plus 1 divided by 30.44. | Baseline up to 24 months post first dose. |
| Overall Survival Rates at Months 6, 12, and 24 in Part A | Probability of survival at 6, 12, and 24 months after the first dose of study treatment. | Baseline up to 24 months post first dose. |
| Maximum Serum Concentration (Cmax) of PF-04518600 Following Single Dose on Cycle 1 Day 1 (C1D1) and Steady-State Maximum Serum Concentration(Css,Max) Following Multiple Doses on Cycle 3 Day 1 (C3D1) in Part A | Cmax was defined as maximum observed serum concentration and can be observed directly from data.~Css,max was the Cmax on C3D1. | For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part A | AUCtau was defined as area under the concentration curve from time 0 to end of dosing interval where dosing interval was 2 weeks. | For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Area Under the Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part A | AUCinf was defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It was obtained from AUC (0-t) plus AUC (t-inf). | For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Terminal Half-Life (t1/2) of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part A | t1/2 was defined as the time measured for the serum concentration to decrease by one half of the initial concentration. | For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Lowest Serum Concentration Observed During the Dosing Interval (Cmin) of PF-04518600 Following Multiple Doses on C3D1 in Part A. | Cmin was defined as Lowest concentration observed during the dosing interval and can be observed directly from data. | For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Average Serum Concentration Over the Dosing Interval (Cav) of PF-04518600 Following Multiple Doses on C3D1 in Part A | Cav was defined as average serum concentration over the dosing interval. | For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Clearance (CL) of PF-04518600 Following Multiple Doses on C3D1 in Part A | Drug clearance was a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). CL=Dose/AUCss,tau | For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Apparent Volume of Distribution at Steady State (Vss) of PF-04518600 Following Multiple Doses on C3D1 in Part A. | Vss was defined as volume of distribution at steady state. | For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Accumulation Ratio (Rac) of PF-04518600 at C3D1 Following Multiple Doses on C3D1 in Part A | Accumulation ratio was calculated as, Rac obtained from Area Under the Concentration Time Curve (AUC) from Cycle 3 Day 1 divided by AUC from Cycle1 Day 1. | For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Number of Participants With Anti Drug Antibody (ADA) and Neutralizing Antibody (NAb) Against PF-04518600 in Part A | ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point. nAb never-positive was defined as no positive nAb results at any time point and nAb ever-positive was defined as at least one positive nAb result at any time point. | Baseline up to end of treatment (maximum of 14 weeks). |
| Mean Unbound Cell Surface OX40 in Part A1 | Mean unbound cell surface OX40 in peripheral blood was measured to characterize the degree of target engagement (TE) by PF-04518600 at baseline and multiple doses. | Pre-dose, 4 and 24 hours post dose on Cycle 1 Day 1, and Day 8 on Cycles 1 to 3, then pre-dose on Cycles 4 and 7 and end of treatment in Part A1 |
| ORR Assessed by RECIST Version 1.1 and irRECIST in Part B | ORR was defined as the percentage of patients with best overall response (BOR) of CR or PR relative to the appropriate analysis set.~CR: Complete response is defined (per RECIST 1.1) as disappearance of all target and non target lesions. Any pathological lymph nodes (whether target or non target) must have reduction in short axis to <10 mm.~PR: Partial response is difined (per RECIST 1.1) as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.~Overall immune related complete response (irCR): Complete disappearance of all lesions (whether measurable or not) and no new lesions. All measurable lymph nodes also must have a reduction in short axis to <10 mm.~Overall immune related partial response (irPR): Sum of the diameters (longest for non nodal lesions, shortest for nodal lesions) of target and new measurable lesions decreases ≥30%. | Baseline up to 24 months post first dose. |
| Kaplan-Meier Estimate of Median PFS in Part B | PFS was defined as the time from randomization date to date of first documentation of progressive disease(PD) based on RECIST, irRECIST or death due to any cause.~PD was progression documented after start date and not qualifying as CR, PR or SD per RECIST. | Baseline up to 24 months post first dose. |
| Kaplan-Meier Estimate of Median TTP in Part B | TTP was defined as the time from start date to the date of the first documentation of PD. PD was documented after start date and not qualifying as CR, PR or SD per RECIST. | Baseline up to 24 months post first dose. |
| Number of Participants Having SD in Part B | SD was defined as persistence of any non target lesions and/or tumor marker level above the normal limits. | Baseline up to 24 months post first dose. |
| Kaplan-Meier Estimate of Median DoR in Part B | DoR was defined as the time from first documentation of PR or CR to date of first documentation of PD or death due to any cause for patients with an objective response.~CR was defined as complete disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis <10 mm) and all target lesions must be assessed.~PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions and all target lesions must be assessed. | Baseline up to 24 months post first dose. |
| Kaplan-Meier Estimate of Median OS in Part B | OS was defined as time in weeks or months from the start of study treatment to date of death due to any cause. OS was calculated as the death date or last known alive date (if death date unavailable) minus the date of first dose of study medication plus 1 divided by 7 or 30.44 if in months. | Baseline up to 24 months post first dose. |
| Overall Survival Rates at Months 6, 12, and 24 in Part B | Probability of survival at 6, 12, and 24 months after the first dose of study treatment. | Baseline up to 24 months post first dose. |
| Cmax of PF-04518600 Following Single Dose on C1D1 and Css,Max Following Multiple Doses on C3D1 in Part B | Cmax was defined as maximum observed serum concentration and can be observed directly from data.~Css,max was the Cmax on C3D1. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| AUCtau of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B | AUCtau was defined as area under the concentration curve from time 0 to end of dosing interval where dosing interval was 2 weeks. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| AUCinf of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B | AUCinf was defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It was obtained from AUC (0-t) plus AUC (t-inf). | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| t1/2 of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B | t1/2 was defined as the time measured for the serum concentration to decrease by one half of the initial concentration. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Cmin of PF-04518600 Following Multiple Doses on C3D1 in Part B | Cmin was defined as Lowest concentration observed during the dosing interval and can be observed directly from data. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Cav of PF-04518600 Following Multiple Doses on C3D1 in Part B | Cav was defined as average serum concentration over the dosing interval. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| CL of PF-04518600 Following Multiple Doses on C3D1 in Part B | Drug clearance was a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). CL=Dose/AUCss,tau | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Vss of PF-04518600 Following Multiple Doses on C3D1 in Part B | Vss was defined as volume of distribution at steady state. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Rac of PF-04518600 Following Multiple Doses on C3D1 in Part B | Accumulation ratio was calculated as, Rac obtained from Area Under the Concentration Time Curve (AUC) from Cycle 3 Day 1 divided by AUC from Cycle1 Day 1. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Cmax of Utomilumab Following Single Dose on C1D1 and Css,Max Following Multiple Doses on C3D1 in Part B | Cmax was defined as maximum observed serum concentration and can be observed directly from data.~Css,max was the Cmax on C3D1. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| AUCtau of Utomilumab Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B | AUCtau was defined as area under the concentration curve from time 0 to end of dosing interval where dosing interval was 2 weeks. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| AUCinf of Utomilumab Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B | AUCinf was defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It was obtained from AUC (0-t) plus AUC (t-inf). | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| t1/2 of Utomilumab Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B | t1/2 was defined as the time measured for the serum concentration to decrease by one half of the initial concentration. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Cmin of Utomilumab Following Multiple Doses on C3D1 in Part B | Cmin was defined as Lowest concentration observed during the dosing interval and can be observed directly from data. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Cav of Utomilumab Following Multiple Doses on C3D1 in Part B | Cav was defined as average serum concentration over the dosing interval. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| CL of Utomilumab Following Multiple Doses on C3D1 in Part B | Drug clearance was a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). CL=Dose/AUCss,tau | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Vss of Utomilumab Following Multiple Doses on C3D1 in Part B | Vss was defined as volume of distribution at steady state. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Rac of Utomilumab Following Multiple Doses on C3D1 in Part B | Accumulation ratio was calculated as, Rac obtained from Area Under the Concentration Time Curve (AUC) from Cycle 3 Day 1 divided by AUC from Cycle1 Day 1. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Number of Participants With ADA and NAb Against PF-04518600 in Part B | ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point. nAb never-positive was defined as no positive nAb results at any time point and nAb ever-positive was defined as at least one positive nAb result at any time point. | Baseline up to end of treatment (maximum of 14 weeks). |
| Number of Participants With ADA and NAb Against Utomilumab in Part B | ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point. nAb never-positive was defined as no positive nAb results at any time point and nAb ever-positive was defined as at least one positive nAb result at any time point. | Baseline up to end of treatment (maximum of 14 weeks). |
|
Immunotherapy, PF-04518600, PF-05082566, solid tumors, tumors, neoplasm metastasis, Phase 1, hepatocellular carcinoma, HCC, liver cancer, ocular melanoma, melanoma, clear cell renal cell carcinoma, RCC, kidney cancer, head and neck squamous cell carcinoma, HNSCC, head and neck cancer, cervical cancer, cancer of the cervix, gastric cancer, stomach cancer, non small cell lung cancer, NSCLC, lung cancer, urothelial bladder carcinoma, bladder cancer, OX40, 4-1BB
|
Antibodies, Monoclonal, Immunoglobulin G, Immunologic Factors, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-04518600<br>OX40 agonist | Drug: PF-04518600<br>* Part A1 - PF-04518600 will be administered intravenously every 14 days in cohorts of 2 or more patients starting at a dose of 0.01 mg/kg. Increases in dose will continue until MTD is determined<br>Drug: PF-04518600<br>* Part A2 - patients with hepatocellular carcinoma will be randomized to receive treatment with PF-04518600 at various doses administered intravenously<br>|
| Experimental: PF-04518600 plus PF-05082566<br>OX40 (CD134) agonist plus 4-1BB (CD137) agonist | Drug: PF-04518600 plus PF-05082566<br>* Part B1 -In cohorts of 2 or more patients, PF-04518600 will be administered intravenously every 2 weeks starting at a dose of 0.1 mg/kg and PF-05082566 will be administered intravenously 4 weeks starting at a dose of 20 mg. Increases in dose will continue until MTD is determined.<br>Drug: PF-04518600 plus PF-05082566<br>* Part B2 - patients with select tumor types (ocular melanoma, cutaneous/acral melanoma or non-small cell lung cancer) will be treated at dose levels based on the OBD selected in Part 1.<br>|
|
Study Of OX40 Agonist PF-04518600 Alone And In Combination With 4-1BB Agonist PF-05082566
Study Overview
=================
Brief Summary
-----------------
To assess the safety and tolerability at increasing dose levels of PF-04518600 alone or in combination wtih PF-05082566 in patients with select advanced or metastatic carcinoma in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.
Official Title
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A PHASE 1, OPEN-LABEL, DOSE ESCALATION STUDY OF PF-04518600 AS A SINGLE AGENT AND IN COMBINATION WITH PF-05082566 IN PATIENTS WITH SELECTED LOCALLY ADVANCED OR METASTATIC CANCERS
Conditions
-----------------
Neoplasms
Intervention / Treatment
-----------------
* Drug: PF-04518600
* Drug: PF-04518600
* Drug: PF-04518600 plus PF-05082566
* Drug: PF-04518600 plus PF-05082566
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Part A1 only: Patients with histological or cytological diagnosis of HNSCC, HCC, melanoma, or clear cell RCC who progressed on or are intolerant to standard therapy, for which no standard therapy is available or who decline standard therapy. Part A2 only: Patients with histological or cytological diagnosis of advanced/metastatic HCC who are treatment naïve and have declined standard of care, or have had at least 1 prior line of systemic therapy. Prior anti PD L1/PD 1 therapy is allowed. Part B1 only: Patients with histological or cytological diagnosis of NSCLC, HNSCC, melanoma, urothelial bladder carcinoma (including renal pelvis, ureters, urinary bladder, and urethra), gastric or squamous cell carcinoma of the uterine cervix who progressed on or are intolerant to standard therapy, for which no standard therapy is available, or who decline standard therapy. Part B2 Arm 1 only: Ocular melanoma patients with advanced/metastatic disease, or Cutaneous/acral melanoma patients with advanced/metastatic disease who have received checkpoint inhibitor (anti PD L1, anti PD 1, or anti CTLA4) based treatment on which disease progressed. [Note: Checkpoint inhibitor may have been part of a combination therapy, as long as the combination did not contain OX40 or 4 1BB agonist.] Any questions on prior treatment may be discussed with the Sponsor. Arm 2 only: Histological or cytological diagnosis of NSCLC with advanced/metastatic disease. Patients must have previously received prior anti PD L1 or anti PD 1 mAb on which disease progressed. [Note: Previous anti PD L1 or anti PD 1 mAb may have been part of a combination therapy, eg, in combination with chemotherapy, as long as the combination did not contain OX40 or 4 1BB agonist.] Performance Status of 0 or 1 - Adequate bone marrow, kidney and liver function Exclusion Criteria: Brain metastases requiring steroids Major surgery, Radiation therapy within 4 weeks of starting study treatment (except: palliative radiotherapy to a limited field is allowed after consultation with sponsor's medical monitor at any time during study participation, including during screening), or systemic anti-cancer therapy within 4 weeks of study treatment start (6 weeks for mitomycin C or nitrosoureas) Active and clinically significant bacterial, fungal, or viral infection History of active autoimmune disorders History of immune-mediated adverse events requiring immunosuppressive therapy or were grade 3 or higher related to prior immune-modulatory therapy Prior treatment with an OX40 agonist and 4-1BB agonist (for Part B1/B2) Prior anthracycline treatment and at risk of cardiac failure (New York Heart Association Class 2)
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: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-04518600<br>OX40 agonist | Drug: PF-04518600<br>* Part A1 - PF-04518600 will be administered intravenously every 14 days in cohorts of 2 or more patients starting at a dose of 0.01 mg/kg. Increases in dose will continue until MTD is determined<br>Drug: PF-04518600<br>* Part A2 - patients with hepatocellular carcinoma will be randomized to receive treatment with PF-04518600 at various doses administered intravenously<br>|
| Experimental: PF-04518600 plus PF-05082566<br>OX40 (CD134) agonist plus 4-1BB (CD137) agonist | Drug: PF-04518600 plus PF-05082566<br>* Part B1 -In cohorts of 2 or more patients, PF-04518600 will be administered intravenously every 2 weeks starting at a dose of 0.1 mg/kg and PF-05082566 will be administered intravenously 4 weeks starting at a dose of 20 mg. Increases in dose will continue until MTD is determined.<br>Drug: PF-04518600 plus PF-05082566<br>* Part B2 - patients with select tumor types (ocular melanoma, cutaneous/acral melanoma or non-small cell lung cancer) will be treated at dose levels based on the OBD selected in Part 1.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicities (DLTs) in Part A1 | DLT was defined as any of the following adverse events occurring in the first two cycle of treatment (28 days), unless there was a clear alternative explanation: hematologic: grade 4 neutropenia lasting >7 days, febrile neutropenia; grade ≥3 neutropenic infection; grade ≥3 thrombocytopenia with clinically significant bleeding or requiring medical intervention; grade 4 thrombocytopenia; grade 4 anemia; grade ≥3 anemia related to hemolysis or autoimmune disease. non hematologic: grade ≥3 toxicities that were considered clinically significant, including cytokine release syndrome, infusion reactions and allergic reactions, except those that had not been maximally treated or could be easily treated. The severity of adverse events was graded as per common terminology criteria for adverse events(CTCAE) version 4.03, and there were no DLTs reported. | The first 2 cycles of treatment (Day 1 up to Day 28) |
| Number of Participants With All-Causality Treatment Emergent Adverse Events(TEAEs) and Serious Adverse Event(SAEs), Treatment-Related TEAEs and SAEs in Part A | Adverse event (AE) was graded by the investigator according to CTCAE version 4.03 and coded using the Medical Dictionary for Regulatory Activities (MedDRA): Grade 3 (Severe) events=unacceptable or intolerable events. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events=death related to an AE. Treatment-emergent events=between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. TEAEs were defined as those with initial onset or increasing in severity after the first dose of study medication. Serious adverse event (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. | AEs: The informed consent date up to the last dosing date + 28 days or all drug-related toxicities resolved date. SAEs: The informed consent date through first dosing date + 98 days or up to the last dosing date + 60 days, and any post-reporting period. |
| Number of Participants With Laboratory Test Abnormalities in Part A | Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, partial thromboplastin time (PTT), Prothrombin (PT), PT international ratio); liver function (aspartate aminotransferase(AST), alanine aminotransferase(ALT), total bilirubin, gamma-glutamyl transpeptidase(GT), alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium , phosphate, magnesium); clinical chemistry (glucose, creatine kinase, thyroxine (T4), thyroid stimulating hormone(TSH)), Amylase, Lipase), urinalysis (dipstick [protein, blood], microscopy [urine red blood cell (RBC), white blood cell (WBC), Epithelial Cells], miscellaneous [urine casts and bacteria]). | The first dosing date to the earlier date between the last dosing date + 35 days and the first new anti-cancer therapy date (if applicable) |
| Number of Participants With DLTs in Part B1 | DLT was defined as any of the following adverse events occurring in the first two cycle of treatment (28 days), unless there was a clear alternative explanation: hematologic: grade 4 neutropenia lasting >7 days, febrile neutropenia; grade ≥3 neutropenic infection; grade ≥3 thrombocytopenia with clinically significant bleeding or requiring medical intervention; grade 4 thrombocytopenia; grade 4 anemia; grade ≥3 anemia related to hemolysis or autoimmune disease. non hematologic: grade ≥3 toxicities that were considered clinically significant, including cytokine release syndrome, infusion reactions and allergic reactions, except those that had not been maximally treated or could be easily treated. The severity of adverse events was graded as per common terminology criteria for adverse events(CTCAE) version 4.03, and there were no DLTs reported. | The First 2 Cycles of Treatment (Day 1 up to Day 28) |
| Number of Participants With All-causality TEAEs and SAEs, and Treatment-Related TEAEs and SAEs in Part B | Adverse event (AE) was graded by the investigator according to CTCAE version 4.03 and coded using the Medical Dictionary for Regulatory Activities (MedDRA): Grade 3 (Severe) events=unacceptable or intolerable events. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events=death related to an AE. Treatment-emergent events=between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. TEAEs were defined as those with initial onset or increasing in severity after the first dose of study medication. Serious adverse event (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. | AEs: The informed consent date up to the last dosing date + 60 days or all drug-related toxicities resolved date. SAEs: The informed consent date through first dosing date + 98 days or up to the last dosing date + 60 days, and any post-reporting period. |
| Number of Participants With Laboratory Test Abnormalities in Part B | Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, partial thromboplastin time (PTT), Prothrombin (PT), PT international ratio); liver function (aspartate aminotransferase(AST), alanine aminotransferase(ALT), total bilirubin, gamma-glutamyl transpeptidase(GT), alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium , phosphate, magnesium); clinical chemistry (glucose, creatine kinase, thyroxine (T4), thyroid stimulating hormone(TSH)), Amylase, Lipase), urinalysis (dipstick [protein, blood], microscopy [urine red blood cell (RBC), white blood cell (WBC), Epithelial Cells], miscellaneous [urine casts and bacteria]). | The first dosing date to the earlier date between the last dosing date + 35 days and the first new anti-cancer therapy date (if applicable) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) Assessed by Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 and Immune Related Response Evaluation Criteria in Solid Tumors (irRECIST) in Part A | ORR was defined as the percentage of patients with best overall response (BOR) of CR or PR relative to the appropriate analysis set. CR: Complete response is defined (per RECIST 1.1) as disappearance of all target and non target lesions. Any pathological lymph nodes (whether target or non target) must have reduction in short axis to <10 mm. PR: Partial response is difined (per RECIST 1.1) as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall immune related complete response (irCR): Complete disappearance of all lesions (whether measurable or not) and no new lesions. All measurable lymph nodes also must have a reduction in short axis to <10 mm. Overall immune related partial response (irPR): Sum of the diameters (longest for non nodal lesions, shortest for nodal lesions) of target and new measurable lesions decreases ≥30%. | Baseline up to 24 months post first dose. |
| Kaplan-Meier Estimate of Median Progression-Free Survival (PFS) in Part A | PFS was defined as the time from randomization date to date of first documentation of progressive disease(PD) based on RECIST, irRECIST or death due to any cause. PD was progression documented after start date and not qualifying as CR, PR or SD per RECIST. | Baseline up to 24 months post first dose |
| Kaplan-Meier Estimate of Median Time to Progression (TTP) in Part A | TTP was defined as the time from start date to the date of the first documentation of PD. PD was documented after start date and not qualifying as CR, PR or SD per RECIST. | Baseline up to 24 months post first dose |
| Number of Participants Having Stable Disease (SD) in Part A | SD was defined as persistence of any non target lesions and/or tumor marker level above the normal limits. | Baseline up to 24 months post first dose. |
| Kaplan-Meier Estimate of Median Duration of Response (DoR) in Part A | DoR was defined as the time from first documentation of PR or CR to date of first documentation of PD or death due to any cause for patients with an objective response. CR was defined as complete disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis <10 mm) and all target lesions must be assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions and all target lesions must be assessed. | Baseline up to 24 months post first dose. |
| Kaplan-Meier Estimate of Median Overall Survival (OS) in Part A | OS was defined as time in months from the start of study treatment to date of death due to any cause. OS was calculated as the death date or last known alive date (if death date unavailable) minus the date of first dose of study medication plus 1 divided by 30.44. | Baseline up to 24 months post first dose. |
| Overall Survival Rates at Months 6, 12, and 24 in Part A | Probability of survival at 6, 12, and 24 months after the first dose of study treatment. | Baseline up to 24 months post first dose. |
| Maximum Serum Concentration (Cmax) of PF-04518600 Following Single Dose on Cycle 1 Day 1 (C1D1) and Steady-State Maximum Serum Concentration(Css,Max) Following Multiple Doses on Cycle 3 Day 1 (C3D1) in Part A | Cmax was defined as maximum observed serum concentration and can be observed directly from data. Css,max was the Cmax on C3D1. | For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part A | AUCtau was defined as area under the concentration curve from time 0 to end of dosing interval where dosing interval was 2 weeks. | For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Area Under the Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part A | AUCinf was defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It was obtained from AUC (0-t) plus AUC (t-inf). | For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Terminal Half-Life (t1/2) of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part A | t1/2 was defined as the time measured for the serum concentration to decrease by one half of the initial concentration. | For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Lowest Serum Concentration Observed During the Dosing Interval (Cmin) of PF-04518600 Following Multiple Doses on C3D1 in Part A. | Cmin was defined as Lowest concentration observed during the dosing interval and can be observed directly from data. | For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Average Serum Concentration Over the Dosing Interval (Cav) of PF-04518600 Following Multiple Doses on C3D1 in Part A | Cav was defined as average serum concentration over the dosing interval. | For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Clearance (CL) of PF-04518600 Following Multiple Doses on C3D1 in Part A | Drug clearance was a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). CL=Dose/AUCss,tau | For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Apparent Volume of Distribution at Steady State (Vss) of PF-04518600 Following Multiple Doses on C3D1 in Part A. | Vss was defined as volume of distribution at steady state. | For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Accumulation Ratio (Rac) of PF-04518600 at C3D1 Following Multiple Doses on C3D1 in Part A | Accumulation ratio was calculated as, Rac obtained from Area Under the Concentration Time Curve (AUC) from Cycle 3 Day 1 divided by AUC from Cycle1 Day 1. | For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Number of Participants With Anti Drug Antibody (ADA) and Neutralizing Antibody (NAb) Against PF-04518600 in Part A | ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point. nAb never-positive was defined as no positive nAb results at any time point and nAb ever-positive was defined as at least one positive nAb result at any time point. | Baseline up to end of treatment (maximum of 14 weeks). |
| Mean Unbound Cell Surface OX40 in Part A1 | Mean unbound cell surface OX40 in peripheral blood was measured to characterize the degree of target engagement (TE) by PF-04518600 at baseline and multiple doses. | Pre-dose, 4 and 24 hours post dose on Cycle 1 Day 1, and Day 8 on Cycles 1 to 3, then pre-dose on Cycles 4 and 7 and end of treatment in Part A1 |
| ORR Assessed by RECIST Version 1.1 and irRECIST in Part B | ORR was defined as the percentage of patients with best overall response (BOR) of CR or PR relative to the appropriate analysis set. CR: Complete response is defined (per RECIST 1.1) as disappearance of all target and non target lesions. Any pathological lymph nodes (whether target or non target) must have reduction in short axis to <10 mm. PR: Partial response is difined (per RECIST 1.1) as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall immune related complete response (irCR): Complete disappearance of all lesions (whether measurable or not) and no new lesions. All measurable lymph nodes also must have a reduction in short axis to <10 mm. Overall immune related partial response (irPR): Sum of the diameters (longest for non nodal lesions, shortest for nodal lesions) of target and new measurable lesions decreases ≥30%. | Baseline up to 24 months post first dose. |
| Kaplan-Meier Estimate of Median PFS in Part B | PFS was defined as the time from randomization date to date of first documentation of progressive disease(PD) based on RECIST, irRECIST or death due to any cause. PD was progression documented after start date and not qualifying as CR, PR or SD per RECIST. | Baseline up to 24 months post first dose. |
| Kaplan-Meier Estimate of Median TTP in Part B | TTP was defined as the time from start date to the date of the first documentation of PD. PD was documented after start date and not qualifying as CR, PR or SD per RECIST. | Baseline up to 24 months post first dose. |
| Number of Participants Having SD in Part B | SD was defined as persistence of any non target lesions and/or tumor marker level above the normal limits. | Baseline up to 24 months post first dose. |
| Kaplan-Meier Estimate of Median DoR in Part B | DoR was defined as the time from first documentation of PR or CR to date of first documentation of PD or death due to any cause for patients with an objective response. CR was defined as complete disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis <10 mm) and all target lesions must be assessed. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions and all target lesions must be assessed. | Baseline up to 24 months post first dose. |
| Kaplan-Meier Estimate of Median OS in Part B | OS was defined as time in weeks or months from the start of study treatment to date of death due to any cause. OS was calculated as the death date or last known alive date (if death date unavailable) minus the date of first dose of study medication plus 1 divided by 7 or 30.44 if in months. | Baseline up to 24 months post first dose. |
| Overall Survival Rates at Months 6, 12, and 24 in Part B | Probability of survival at 6, 12, and 24 months after the first dose of study treatment. | Baseline up to 24 months post first dose. |
| Cmax of PF-04518600 Following Single Dose on C1D1 and Css,Max Following Multiple Doses on C3D1 in Part B | Cmax was defined as maximum observed serum concentration and can be observed directly from data. Css,max was the Cmax on C3D1. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| AUCtau of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B | AUCtau was defined as area under the concentration curve from time 0 to end of dosing interval where dosing interval was 2 weeks. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| AUCinf of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B | AUCinf was defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It was obtained from AUC (0-t) plus AUC (t-inf). | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| t1/2 of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B | t1/2 was defined as the time measured for the serum concentration to decrease by one half of the initial concentration. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Cmin of PF-04518600 Following Multiple Doses on C3D1 in Part B | Cmin was defined as Lowest concentration observed during the dosing interval and can be observed directly from data. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Cav of PF-04518600 Following Multiple Doses on C3D1 in Part B | Cav was defined as average serum concentration over the dosing interval. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| CL of PF-04518600 Following Multiple Doses on C3D1 in Part B | Drug clearance was a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). CL=Dose/AUCss,tau | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Vss of PF-04518600 Following Multiple Doses on C3D1 in Part B | Vss was defined as volume of distribution at steady state. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Rac of PF-04518600 Following Multiple Doses on C3D1 in Part B | Accumulation ratio was calculated as, Rac obtained from Area Under the Concentration Time Curve (AUC) from Cycle 3 Day 1 divided by AUC from Cycle1 Day 1. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Cmax of Utomilumab Following Single Dose on C1D1 and Css,Max Following Multiple Doses on C3D1 in Part B | Cmax was defined as maximum observed serum concentration and can be observed directly from data. Css,max was the Cmax on C3D1. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| AUCtau of Utomilumab Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B | AUCtau was defined as area under the concentration curve from time 0 to end of dosing interval where dosing interval was 2 weeks. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| AUCinf of Utomilumab Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B | AUCinf was defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It was obtained from AUC (0-t) plus AUC (t-inf). | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| t1/2 of Utomilumab Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B | t1/2 was defined as the time measured for the serum concentration to decrease by one half of the initial concentration. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Cmin of Utomilumab Following Multiple Doses on C3D1 in Part B | Cmin was defined as Lowest concentration observed during the dosing interval and can be observed directly from data. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Cav of Utomilumab Following Multiple Doses on C3D1 in Part B | Cav was defined as average serum concentration over the dosing interval. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| CL of Utomilumab Following Multiple Doses on C3D1 in Part B | Drug clearance was a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). CL=Dose/AUCss,tau | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Vss of Utomilumab Following Multiple Doses on C3D1 in Part B | Vss was defined as volume of distribution at steady state. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Rac of Utomilumab Following Multiple Doses on C3D1 in Part B | Accumulation ratio was calculated as, Rac obtained from Area Under the Concentration Time Curve (AUC) from Cycle 3 Day 1 divided by AUC from Cycle1 Day 1. | For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3. |
| Number of Participants With ADA and NAb Against PF-04518600 in Part B | ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point. nAb never-positive was defined as no positive nAb results at any time point and nAb ever-positive was defined as at least one positive nAb result at any time point. | Baseline up to end of treatment (maximum of 14 weeks). |
| Number of Participants With ADA and NAb Against Utomilumab in Part B | ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point. nAb never-positive was defined as no positive nAb results at any time point and nAb ever-positive was defined as at least one positive nAb result at any time point. | Baseline up to end of treatment (maximum of 14 weeks). |
Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunotherapy, PF-04518600, PF-05082566, solid tumors, tumors, neoplasm metastasis, Phase 1, hepatocellular carcinoma, HCC, liver cancer, ocular melanoma, melanoma, clear cell renal cell carcinoma, RCC, kidney cancer, head and neck squamous cell carcinoma, HNSCC, head and neck cancer, cervical cancer, cancer of the cervix, gastric cancer, stomach cancer, non small cell lung cancer, NSCLC, lung cancer, urothelial bladder carcinoma, bladder cancer, OX40, 4-1BB
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NCT02842580
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De-escalation Chemotherapies Versus Escalation in Non Pre-treated Unresectable Patients With Metastatic Colorectal Cancer
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The intensity of tumour response appears to be correlated with the feasibility and the duration of a therapeutic pause or of a reduced maintenance therapy maintained until progression in patients initially controlled by so-called induction chemotherapy. Bevacizumab combined with cytotoxic chemotherapy (5-FU, irinotecan and/or oxaliplatin) has shown that it is possible to improve the tumour response rate and patient prognosis in 1st and 2nd lines. With a very favourable safety profile , it is an excellent candidate as induction treatment and also as maintenance treatment. Prospective data from recent trials have actually demonstrated improvement in PFS and/or overall survival with bevacizumab maintenance alone or in combination with 5FU (or capecitabine) after induction chemotherapy (FOLFIRI or FOLFOX + bevacizumab).~At the same time, the maintenance of anti-angiogenic pressure after progression in 1st line metastatic has demonstrated its benefit in terms of PFS and overall survival. Bevacizumab maintenance in 2nd line metastatic, despite progression, thus appears to be a valid strategy.
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Thus, the objective of this work is to combine continuous blocking of angiogenesis by bevacizumab given on the first 3 metastatic lines in a randomised phase II trial evaluating a descending strategy of immediate optimisation by 4 cycles of FOLFOXIRI-bevacizumab and 4 cycles of FOLFIRI-bevacizumab, followed by maintenance treatment with 5FU-bevacizumab until progression (re-introduction of induction in case of progression) and evaluate an ascending strategy with 5FU-bevacizumab immediately followed, at progression, by the introduction of irinotecan, then oxaliplatin, with maintenance of blocking of angiogenesis by bevacizumab.
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Randomized Phase II Study Assessing the Efficacy and Safety of 2 Therapeutic Strategies Combining Bevacizumab With Chemotherapy: De-escalation Versus Escalation in Patients With Non-pretreated Unresectable Metastatic Colorectal Cancer
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Colorectal Neoplasms
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* Drug: 5 FLUOROURACYL
* Drug: acide folinique
* Drug: irinotecan
* Drug: Oxaliplatin
* Drug: capécitabine
* Drug: bevacizumab
|
Inclusion Criteria:~Metastatic colorectal cancer, histologically proven (on primary tumour and/or metastases)~Unresectable and non-pretreated metastases~BRAF wild-type~Patient considered able to receive 3 lines of chemotherapy~At least one measurable target lesion > 1 cm according to RECIST 1.1 (Appendix 4)~Tumour assessment according to RECIST, performed 4 weeks or less prior to randomization~Age ≥ 18 years~WHO performance status ≤ 2 (Appendix 5)~No major surgery within 4 weeks prior to randomisation. Wound healing must be complete~Life expectancy greater than 3 months~Laboratory tests: Neutrophils ≥ 1500/mm3, platelets ≥ 100,000/mm3, haemoglobin > 9 g/dL~Creatinine clearance > 30 mL /min (capecitabine dose modification if the creatinine clearance < 30-50 mL/min), serum creatinine < 1.25 x ULN~Liver function tests: bilirubin < 1.25 x ULN, AST/ALT < 5 x ULN~Women of childbearing age and men (who have sexual relations with women of childbearing age) must agree to use effective contraception without interruption throughout the duration of treatment and for 6 months after the last administration~Signed informed consent~Exclusion Criteria:~Patient with a potentially resectable colorectal cancer; i.e. for whom the goal of chemotherapy would be to make all metastases resectable~Patients with symptomatic metastases~Patient with aggressive disease and a large tumour volume~Active gastroduodenal ulcer, wound or bone fracture~At least one of the following laboratory values: Neutrophils <1500/mm3, platelets < 100,000/mm3, haemoglobin < 9 g/dL, total bilirubin > 1.5 N, alkaline phosphatase > 2.5 N (or > 5 N in case of hepatic involvement), serum creatinine > 1.5 N, 24 hr proteinuria > 1 g~Chronic inflammatory bowel disease, extensive resection of the small bowel~Clinically significant coronary artery disease or a history of myocardial infraction within the last 6 months. Uncontrolled hypertension while receiving chronic medication~Abdominal or major extra-abdominal surgical procedure (except diagnostic biopsy) or radiation within 4 weeks before starting treatment~Previous treatment with an anti-angiogenic or irinotecan~Known or suspected central nervous system metastasis CNS metastases, or suspected CNS metastases~Other previous malignancies within 5 years, except for basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix - Peritoneal macro-nodular carcinomatosis~History of haemoptysis ≥ grade 2 (defined as ≥ 2.5 mL of bright red blood per episode) in the month prior to inclusion~Known hypersensitivity to any component of bevacizumab or to one of the study treatments~Active infection requiring intravenous antibiotics at start of treatment~History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess or active gastrointestinal bleeding within 6 months prior to treatment start~Pregnant or breastfeeding women~Concomitant participation in another clinical study involving a drug during the treatment phase and 30 days before starting the study treatment~Patient unable to undergo medical treatment for geographical, social, psychological or legal reasons.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary objective is the percentage of patients without failure of the strategy 16 months after the randomization. | The failure of the strategy is defined by:~Progression (under certain condition) using RECIST version 1.1~Death (all causes)~Toxicity leading to definitive stop of chemotherapy (oxaliplatine and/or irinotecan). | 16 months after randomization |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best response rate (using RECIST version 1.1) at 16 months | Assessed on the CT scans performed during treatment | 16 months after randomization |
| Overall survival (OS) at 2 years and at 3 years | | 2 years and 3 years |
| Progression free survival (PFS) at 2 years and at 3 years | Time between the date of randomization and the date of the first radiologic progression or death (all causes) | 2 years and 3 years |
|
colorectal, cancer, metastasis
|
Vitamin B Complex, Leucovorin, Bevacizumab, Capecitabine, Oxaliplatin, Irinotecan, Levoleucovorin, Antineoplastic Agents, Immunological, Antineoplastic Agents, Angiogenesis Inhibitors, Angiogenesis Modulating Agents, Growth Substances, Physiological Effects of Drugs, Growth Inhibitors, Antimetabolites, Antineoplastic, Antimetabolites, Molecular Mechanisms of Pharmacological Action, Topoisomerase I Inhibitors, Topoisomerase Inhibitors, Enzyme Inhibitors, Antidotes, Protective Agents, Vitamins, Micronutrients
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard arm (escalation strategy - arm A)<br>LV5FU2 (5 FLUOROURACYL)+avastin. After progression: FOLFIRI + avastin. after the 2nd progression:FOLFOX4 (eloxatine)+ avastin. | Drug: 5 FLUOROURACYL<br>* Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as a 2 hr infusion.~The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2).~The cycles will last 14 days. For this 1st line chemotherapy, the investigator has the choice of using capecitabine instead of LV5FU2; in this case the cycle lasts 21 days.<br>* Other names: FLUOROURACILE EBEWE;Drug: acide folinique<br>* 200 mg/m² if Elvorine<br>* Other names: ELVORINE;Drug: irinotecan<br>* Irinotecan is administered IV at a dose of 180 mg/m² over 90 minutes. Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as an infusion over 2 hours, to be given in Y along with irinotecan.~The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2).~The cycles will last 14 days.<br>* Other names: CAMPTO;Drug: Oxaliplatin<br>* Oxaliplatin is administered IV at a dose of 85 mg/m² over 120 minutes. Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as an infusion over 2 hours, to be given in Y along with oxaliplatin.~The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2).~The cycles will last 14 days.<br>* Other names: ELOXATINE 5 mg/ml;Drug: capécitabine<br>* For this 1st line chemotherapy, the investigator has the choice of using capecitabine instead of LV5FU2; in this case the cycle lasts 21 days.<br>* Other names: XELODA;Drug: bevacizumab<br>* Bevacizumab is administered IV at a dose of 5 mg/kg over 90 min at cycle 1, then 60 min at cycle 2 and 30 min in subsequent cycles. Bevacizumab is administered every 2 weeks before the start of chemotherapy<br>* Other names: AVASTIN;|
| Experimental: Experimental arm (de-escalation strategy -arm B)<br>(4 cycles of FOLFOXIRI (campto) + avastin and 4 cycles of FOLFIRI + avastin) is followed by maintenance with capecitabine | Drug: 5 FLUOROURACYL<br>* Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as a 2 hr infusion.~The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2).~The cycles will last 14 days. For this 1st line chemotherapy, the investigator has the choice of using capecitabine instead of LV5FU2; in this case the cycle lasts 21 days.<br>* Other names: FLUOROURACILE EBEWE;Drug: acide folinique<br>* 200 mg/m² if Elvorine<br>* Other names: ELVORINE;Drug: irinotecan<br>* Irinotecan is administered IV at a dose of 180 mg/m² over 90 minutes. Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as an infusion over 2 hours, to be given in Y along with irinotecan.~The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2).~The cycles will last 14 days.<br>* Other names: CAMPTO;Drug: Oxaliplatin<br>* Oxaliplatin is administered IV at a dose of 85 mg/m² over 120 minutes. Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as an infusion over 2 hours, to be given in Y along with oxaliplatin.~The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2).~The cycles will last 14 days.<br>* Other names: ELOXATINE 5 mg/ml;Drug: capécitabine<br>* For this 1st line chemotherapy, the investigator has the choice of using capecitabine instead of LV5FU2; in this case the cycle lasts 21 days.<br>* Other names: XELODA;Drug: bevacizumab<br>* Bevacizumab is administered IV at a dose of 5 mg/kg over 90 min at cycle 1, then 60 min at cycle 2 and 30 min in subsequent cycles. Bevacizumab is administered every 2 weeks before the start of chemotherapy<br>* Other names: AVASTIN;|
|
De-escalation Chemotherapies Versus Escalation in Non Pre-treated Unresectable Patients With Metastatic Colorectal Cancer
Study Overview
=================
Brief Summary
-----------------
The intensity of tumour response appears to be correlated with the feasibility and the duration of a therapeutic pause or of a reduced maintenance therapy maintained until progression in patients initially controlled by so-called induction chemotherapy. Bevacizumab combined with cytotoxic chemotherapy (5-FU, irinotecan and/or oxaliplatin) has shown that it is possible to improve the tumour response rate and patient prognosis in 1st and 2nd lines. With a very favourable safety profile , it is an excellent candidate as induction treatment and also as maintenance treatment. Prospective data from recent trials have actually demonstrated improvement in PFS and/or overall survival with bevacizumab maintenance alone or in combination with 5FU (or capecitabine) after induction chemotherapy (FOLFIRI or FOLFOX + bevacizumab). At the same time, the maintenance of anti-angiogenic pressure after progression in 1st line metastatic has demonstrated its benefit in terms of PFS and overall survival. Bevacizumab maintenance in 2nd line metastatic, despite progression, thus appears to be a valid strategy.
Detailed Description
-----------------
Thus, the objective of this work is to combine continuous blocking of angiogenesis by bevacizumab given on the first 3 metastatic lines in a randomised phase II trial evaluating a descending strategy of immediate optimisation by 4 cycles of FOLFOXIRI-bevacizumab and 4 cycles of FOLFIRI-bevacizumab, followed by maintenance treatment with 5FU-bevacizumab until progression (re-introduction of induction in case of progression) and evaluate an ascending strategy with 5FU-bevacizumab immediately followed, at progression, by the introduction of irinotecan, then oxaliplatin, with maintenance of blocking of angiogenesis by bevacizumab.
Official Title
-----------------
Randomized Phase II Study Assessing the Efficacy and Safety of 2 Therapeutic Strategies Combining Bevacizumab With Chemotherapy: De-escalation Versus Escalation in Patients With Non-pretreated Unresectable Metastatic Colorectal Cancer
Conditions
-----------------
Colorectal Neoplasms
Intervention / Treatment
-----------------
* Drug: 5 FLUOROURACYL
* Drug: acide folinique
* Drug: irinotecan
* Drug: Oxaliplatin
* Drug: capécitabine
* Drug: bevacizumab
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Metastatic colorectal cancer, histologically proven (on primary tumour and/or metastases) Unresectable and non-pretreated metastases BRAF wild-type Patient considered able to receive 3 lines of chemotherapy At least one measurable target lesion > 1 cm according to RECIST 1.1 (Appendix 4) Tumour assessment according to RECIST, performed 4 weeks or less prior to randomization Age ≥ 18 years WHO performance status ≤ 2 (Appendix 5) No major surgery within 4 weeks prior to randomisation. Wound healing must be complete Life expectancy greater than 3 months Laboratory tests: Neutrophils ≥ 1500/mm3, platelets ≥ 100,000/mm3, haemoglobin > 9 g/dL Creatinine clearance > 30 mL /min (capecitabine dose modification if the creatinine clearance < 30-50 mL/min), serum creatinine < 1.25 x ULN Liver function tests: bilirubin < 1.25 x ULN, AST/ALT < 5 x ULN Women of childbearing age and men (who have sexual relations with women of childbearing age) must agree to use effective contraception without interruption throughout the duration of treatment and for 6 months after the last administration Signed informed consent Exclusion Criteria: Patient with a potentially resectable colorectal cancer; i.e. for whom the goal of chemotherapy would be to make all metastases resectable Patients with symptomatic metastases Patient with aggressive disease and a large tumour volume Active gastroduodenal ulcer, wound or bone fracture At least one of the following laboratory values: Neutrophils <1500/mm3, platelets < 100,000/mm3, haemoglobin < 9 g/dL, total bilirubin > 1.5 N, alkaline phosphatase > 2.5 N (or > 5 N in case of hepatic involvement), serum creatinine > 1.5 N, 24 hr proteinuria > 1 g Chronic inflammatory bowel disease, extensive resection of the small bowel Clinically significant coronary artery disease or a history of myocardial infraction within the last 6 months. Uncontrolled hypertension while receiving chronic medication Abdominal or major extra-abdominal surgical procedure (except diagnostic biopsy) or radiation within 4 weeks before starting treatment Previous treatment with an anti-angiogenic or irinotecan Known or suspected central nervous system metastasis CNS metastases, or suspected CNS metastases Other previous malignancies within 5 years, except for basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix - Peritoneal macro-nodular carcinomatosis History of haemoptysis ≥ grade 2 (defined as ≥ 2.5 mL of bright red blood per episode) in the month prior to inclusion Known hypersensitivity to any component of bevacizumab or to one of the study treatments Active infection requiring intravenous antibiotics at start of treatment History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess or active gastrointestinal bleeding within 6 months prior to treatment start Pregnant or breastfeeding women Concomitant participation in another clinical study involving a drug during the treatment phase and 30 days before starting the study treatment Patient unable to undergo medical treatment for geographical, social, psychological or legal reasons.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard arm (escalation strategy - arm A)<br>LV5FU2 (5 FLUOROURACYL)+avastin. After progression: FOLFIRI + avastin. after the 2nd progression:FOLFOX4 (eloxatine)+ avastin. | Drug: 5 FLUOROURACYL<br>* Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as a 2 hr infusion. The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2). The cycles will last 14 days. For this 1st line chemotherapy, the investigator has the choice of using capecitabine instead of LV5FU2; in this case the cycle lasts 21 days.<br>* Other names: FLUOROURACILE EBEWE;Drug: acide folinique<br>* 200 mg/m² if Elvorine<br>* Other names: ELVORINE;Drug: irinotecan<br>* Irinotecan is administered IV at a dose of 180 mg/m² over 90 minutes. Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as an infusion over 2 hours, to be given in Y along with irinotecan. The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2). The cycles will last 14 days.<br>* Other names: CAMPTO;Drug: Oxaliplatin<br>* Oxaliplatin is administered IV at a dose of 85 mg/m² over 120 minutes. Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as an infusion over 2 hours, to be given in Y along with oxaliplatin. The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2). The cycles will last 14 days.<br>* Other names: ELOXATINE 5 mg/ml;Drug: capécitabine<br>* For this 1st line chemotherapy, the investigator has the choice of using capecitabine instead of LV5FU2; in this case the cycle lasts 21 days.<br>* Other names: XELODA;Drug: bevacizumab<br>* Bevacizumab is administered IV at a dose of 5 mg/kg over 90 min at cycle 1, then 60 min at cycle 2 and 30 min in subsequent cycles. Bevacizumab is administered every 2 weeks before the start of chemotherapy<br>* Other names: AVASTIN;|
| Experimental: Experimental arm (de-escalation strategy -arm B)<br>(4 cycles of FOLFOXIRI (campto) + avastin and 4 cycles of FOLFIRI + avastin) is followed by maintenance with capecitabine | Drug: 5 FLUOROURACYL<br>* Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as a 2 hr infusion. The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2). The cycles will last 14 days. For this 1st line chemotherapy, the investigator has the choice of using capecitabine instead of LV5FU2; in this case the cycle lasts 21 days.<br>* Other names: FLUOROURACILE EBEWE;Drug: acide folinique<br>* 200 mg/m² if Elvorine<br>* Other names: ELVORINE;Drug: irinotecan<br>* Irinotecan is administered IV at a dose of 180 mg/m² over 90 minutes. Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as an infusion over 2 hours, to be given in Y along with irinotecan. The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2). The cycles will last 14 days.<br>* Other names: CAMPTO;Drug: Oxaliplatin<br>* Oxaliplatin is administered IV at a dose of 85 mg/m² over 120 minutes. Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as an infusion over 2 hours, to be given in Y along with oxaliplatin. The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2). The cycles will last 14 days.<br>* Other names: ELOXATINE 5 mg/ml;Drug: capécitabine<br>* For this 1st line chemotherapy, the investigator has the choice of using capecitabine instead of LV5FU2; in this case the cycle lasts 21 days.<br>* Other names: XELODA;Drug: bevacizumab<br>* Bevacizumab is administered IV at a dose of 5 mg/kg over 90 min at cycle 1, then 60 min at cycle 2 and 30 min in subsequent cycles. Bevacizumab is administered every 2 weeks before the start of chemotherapy<br>* Other names: AVASTIN;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary objective is the percentage of patients without failure of the strategy 16 months after the randomization. | The failure of the strategy is defined by: Progression (under certain condition) using RECIST version 1.1 Death (all causes) Toxicity leading to definitive stop of chemotherapy (oxaliplatine and/or irinotecan). | 16 months after randomization |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best response rate (using RECIST version 1.1) at 16 months | Assessed on the CT scans performed during treatment | 16 months after randomization |
| Overall survival (OS) at 2 years and at 3 years | | 2 years and 3 years |
| Progression free survival (PFS) at 2 years and at 3 years | Time between the date of randomization and the date of the first radiologic progression or death (all causes) | 2 years and 3 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
colorectal, cancer, metastasis
|
NCT02666651
|
Regional Tolvaptan Registry
|
Low blood sodium is a common observation in patients presenting with heart failure and is associated with increased mortality, prolonged hospital stay, and repeat hospital visits. Tolvaptan is a new and approved medication to treat low sodium levels in patients who present with symptoms of heart failure, however, it is not currently available as a treatment option due to high costs not covered by our provincial plan. In this observational, non-randomized study the drug will be provided to all subjects free of charge and given only during their hospital stay. After discharge subjects will be followed for 6 months (3 visits).
|
Purpose: A prospective, open-label, real life registry of Tolvaptan in hospitalized heart failure patients with hyponatremia.~Hypothesis: Administration of Tolvaptan in hospitalized patients with heart failure and hyponatremia will demonstrate improvements in patient symptom status and cost savings from decreased healthcare utilization.~Justification: In clinical trials, Tolvaptan has been shown to quickly, effectively, and safely improve sodium levels in heart failure patients, and decrease the length of hospital stay and improve symptom status compared to placebo. Although Tolvaptan is an approved drug in Canada for the treatment of patients hospitalized with heart failure and hyponatremia, its availability is limited to private buyers and not available on hospital formularies due to cost constraints. There are no alternatives to this first in class agent.~Objectives: The primary endpoint is reduction in length of stay for heart failure in registry participants compared to length of stay in the Vancouver Coastal Health (VCH) administrative data set. Secondary endpoints will include recurrent hospitalization, change in quality of life, and B-type Natriuretic Peptide (BNP) levels over the study period.~Research Method: Patients admitted to Vancouver General Hospital (VGH) with heart failure and hyponatremia will be identified through clinical referral by cardiologists who have ensured that all other measures have been undertaken to improve the patient's clinical status.~Tolvaptan is dispensed according to product monograph and clinician discretion, and will be discontinued once serum sodium is normalized, or in the case of a drug related adverse event or hospital discharge. Bloodwork will be drawn to monitor liver function and electrolytes during hospitalization and in follow up. Data will be captured from time of consent until 6 months after hospital discharge.
|
Regional Tolvaptan Registry
|
Decompensated Heart Failure, Hyponatremia
|
* Drug: Tolvaptan
* Other: No intervention
|
Inclusion Criteria:~Patient has clinical evidence of heart failure AND elevated BNP or evidence of left ventricular dysfunction (left ventricular ejection fraction (LVEF) < 40%) on diagnostic imaging.~Serum sodium < 130 mmol/L OR serum sodium 131-134 mmol/L and symptomatic.~Sodium and fluid restriction ongoing.~Trial of optimal diuretic therapy (at prescribing physician's clinical discretion).~Discontinuation of non-essential medications/treatments that are known to cause hyponatremia.~Exclusion Criteria:~Life expectancy < 6 months~Documented adverse events with tolvaptan in the past~Meet exclusion criteria from the Study of Ascending Levels of Tolvaptan in Hyponatremia (SALT Trial):~Serum sodium < 120mmol/L if neurologic impairment~Confounding disease (e.g. recent stroke or myocardial infarction (MI), recent surgery, uncontrolled diabetes, etc.)
|
19 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital length of stay | Hospital length of stay for heart failure in the treatment group will be measured as days and compared to administrative regional data describing patient outcomes from the local health authority. | Subjects are followed for 6 months after discharge |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrent hospitalization. | This will be measured by the number of times a patient is readmitted to hospital following their discharge from the initial hospitalization. | Subjects are followed for 6 months after discharge |
| Change in quality of life. | This will be assessed by administrating the Minnesota Living with Heart Failure questionnaire at initial hospitalization, 1 month follow-up, 3 month follow-up, and 6 month follow-up timepoints. | Subjects are followed for 6 months after discharge |
| BNP (Brain-Type Natriuretic Peptide) levels | BNP is an established biomarker of CHF severity and blood samples will be collected at 1, 3, and 6 month visits. Values will be collected as a continuous variable. | Subjects are followed for 6 months after discharge |
|
Tolvaptan, Antidiuretic Hormone Receptor Antagonists, Molecular Mechanisms of Pharmacological Action, Natriuretic Agents, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test group<br>Administration of oral tolvaptan (15-60mg PO titration) during admission for decompensated heart failure | Drug: Tolvaptan<br>* Tolvaptan is dispensed during hospitalization according to its product monograph and clinician discretion. It will be discontinued once serum sodium is normalized, or in the case of a drug related adverse event or hospital discharge.<br>* Other names: Samsca;|
| Other: Control group<br>There is no intervention planned for the Control group. Aggregate administrative regional data describing patient outcomes from the local health authority | Other: No intervention<br>* There is no intervention planned for the Control group. Aggregate administrative regional data describing patient outcomes from the local health authority will be used as a comparator.<br>|
|
Regional Tolvaptan Registry
Study Overview
=================
Brief Summary
-----------------
Low blood sodium is a common observation in patients presenting with heart failure and is associated with increased mortality, prolonged hospital stay, and repeat hospital visits. Tolvaptan is a new and approved medication to treat low sodium levels in patients who present with symptoms of heart failure, however, it is not currently available as a treatment option due to high costs not covered by our provincial plan. In this observational, non-randomized study the drug will be provided to all subjects free of charge and given only during their hospital stay. After discharge subjects will be followed for 6 months (3 visits).
Detailed Description
-----------------
Purpose: A prospective, open-label, real life registry of Tolvaptan in hospitalized heart failure patients with hyponatremia. Hypothesis: Administration of Tolvaptan in hospitalized patients with heart failure and hyponatremia will demonstrate improvements in patient symptom status and cost savings from decreased healthcare utilization. Justification: In clinical trials, Tolvaptan has been shown to quickly, effectively, and safely improve sodium levels in heart failure patients, and decrease the length of hospital stay and improve symptom status compared to placebo. Although Tolvaptan is an approved drug in Canada for the treatment of patients hospitalized with heart failure and hyponatremia, its availability is limited to private buyers and not available on hospital formularies due to cost constraints. There are no alternatives to this first in class agent. Objectives: The primary endpoint is reduction in length of stay for heart failure in registry participants compared to length of stay in the Vancouver Coastal Health (VCH) administrative data set. Secondary endpoints will include recurrent hospitalization, change in quality of life, and B-type Natriuretic Peptide (BNP) levels over the study period. Research Method: Patients admitted to Vancouver General Hospital (VGH) with heart failure and hyponatremia will be identified through clinical referral by cardiologists who have ensured that all other measures have been undertaken to improve the patient's clinical status. Tolvaptan is dispensed according to product monograph and clinician discretion, and will be discontinued once serum sodium is normalized, or in the case of a drug related adverse event or hospital discharge. Bloodwork will be drawn to monitor liver function and electrolytes during hospitalization and in follow up. Data will be captured from time of consent until 6 months after hospital discharge.
Official Title
-----------------
Regional Tolvaptan Registry
Conditions
-----------------
Decompensated Heart Failure, Hyponatremia
Intervention / Treatment
-----------------
* Drug: Tolvaptan
* Other: No intervention
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient has clinical evidence of heart failure AND elevated BNP or evidence of left ventricular dysfunction (left ventricular ejection fraction (LVEF) < 40%) on diagnostic imaging. Serum sodium < 130 mmol/L OR serum sodium 131-134 mmol/L and symptomatic. Sodium and fluid restriction ongoing. Trial of optimal diuretic therapy (at prescribing physician's clinical discretion). Discontinuation of non-essential medications/treatments that are known to cause hyponatremia. Exclusion Criteria: Life expectancy < 6 months Documented adverse events with tolvaptan in the past Meet exclusion criteria from the Study of Ascending Levels of Tolvaptan in Hyponatremia (SALT Trial): Serum sodium < 120mmol/L if neurologic impairment Confounding disease (e.g. recent stroke or myocardial infarction (MI), recent surgery, uncontrolled diabetes, etc.)
Ages Eligible for Study
-----------------
Minimum Age: 19 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: Test group<br>Administration of oral tolvaptan (15-60mg PO titration) during admission for decompensated heart failure | Drug: Tolvaptan<br>* Tolvaptan is dispensed during hospitalization according to its product monograph and clinician discretion. It will be discontinued once serum sodium is normalized, or in the case of a drug related adverse event or hospital discharge.<br>* Other names: Samsca;|
| Other: Control group<br>There is no intervention planned for the Control group. Aggregate administrative regional data describing patient outcomes from the local health authority | Other: No intervention<br>* There is no intervention planned for the Control group. Aggregate administrative regional data describing patient outcomes from the local health authority will be used as a comparator.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital length of stay | Hospital length of stay for heart failure in the treatment group will be measured as days and compared to administrative regional data describing patient outcomes from the local health authority. | Subjects are followed for 6 months after discharge |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrent hospitalization. | This will be measured by the number of times a patient is readmitted to hospital following their discharge from the initial hospitalization. | Subjects are followed for 6 months after discharge |
| Change in quality of life. | This will be assessed by administrating the Minnesota Living with Heart Failure questionnaire at initial hospitalization, 1 month follow-up, 3 month follow-up, and 6 month follow-up timepoints. | Subjects are followed for 6 months after discharge |
| BNP (Brain-Type Natriuretic Peptide) levels | BNP is an established biomarker of CHF severity and blood samples will be collected at 1, 3, and 6 month visits. Values will be collected as a continuous variable. | Subjects are followed for 6 months after discharge |
|
|
NCT03006510
|
Hypoglycemia Prediction Model
|
Our goal for this Learning Healthcare System Demonstration Project is to reduce the rate of inpatient hypoglycemia. Hypoglycemia can result in longer lengths of stay and increased morbidity and mortality (ie falls and cardiovascular or cerebral events).~The group at Washington University (WSL) developed a predictive hypoglycemia risk score. Using current glucose, body weight, creatinine clearance, insulin type and dosing, and oral diabetic therapy, they identified patients at high risk for hypoglycemia and then provided in-person education to the providers of these patients. This resulted in a 68% reduction in severe hypoglycemia (blood glucose < 40 mg/dL). This approach required significant personnel hours and is difficult to replicate in other systems.~The investigators will implement an EHR-based intervention at UCSF to predict which patients are at high risk of inpatient hypoglycemia and take action to prevent the hypoglycemic event. In real time, all adult (non OB) patients with a glucose < 90, and a high risk of future hypoglycemia (based on the WSL formula) will be identified. Patients will be randomly assigned to intervention or no intervention (current standard care). The intervention will consist of an automated provider alert with recommendations on what adjustments could be made to avoid a potentially serious hypoglycemic event.~The outcomes that will be measured include: 1) reductions in serious hypoglycemic events, 2) monitor the changes made by providers as a result of alerts in order to study provider behavior and identify future areas of intervention, and 3) provider satisfaction with the alert system.
|
Leveraging the Power of the EMR: Using a Real Time Prediction Model to Decrease Inpatient Hypoglycemic Events
|
Hypoglycemia
|
* Other: Hypoglycemia prediction alert
|
Inclusion Criteria:~All adult inpatients having glucoses measured (point of care)~Exclusion Criteria:~adults admitted to obstetrics
|
18 Years
| null |
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients (in each group) who ultimately have a hypoglycemic event | | 72 hours |
|
inpatient diabetes, hypoglycemia
|
Hypoglycemia, Glucose Metabolism Disorders, Metabolic Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Alert<br>If glucose <90 mg/dl and hypoglycemia prediction score >35, then alert with suggestion for intervention sent to treating team | Other: Hypoglycemia prediction alert<br>* In real time, for a patient with a glucose <90 mg/d, using a hypoglycemia prediction model that takes into account patient weight, renal function, eating and insulin dosing a risk score is produced.~If the Risk score is >35, then the patient is determined to be at risk for hypoglycemia in the next 72 hours.~If a patient is determined to be at risk for hypoglycemia, the following will occur:~Alert will be generated and sent via careweb a pager alert system that sends the alert specifically to the current oncall provider The alert also points the provider to the EMR order section where a formal more detailed alert gives recommendationsd for changes in insulin dosing to potentially prevent hypoglycemia.<br>|
| No Intervention: No alert<br>Routine standard care. If glucose <90 mg/dl and hypoglycemia prediction score >35, then report for investigators will be collected, but no active alert will be sent to teams. | |
|
Hypoglycemia Prediction Model
Study Overview
=================
Brief Summary
-----------------
Our goal for this Learning Healthcare System Demonstration Project is to reduce the rate of inpatient hypoglycemia. Hypoglycemia can result in longer lengths of stay and increased morbidity and mortality (ie falls and cardiovascular or cerebral events). The group at Washington University (WSL) developed a predictive hypoglycemia risk score. Using current glucose, body weight, creatinine clearance, insulin type and dosing, and oral diabetic therapy, they identified patients at high risk for hypoglycemia and then provided in-person education to the providers of these patients. This resulted in a 68% reduction in severe hypoglycemia (blood glucose < 40 mg/dL). This approach required significant personnel hours and is difficult to replicate in other systems. The investigators will implement an EHR-based intervention at UCSF to predict which patients are at high risk of inpatient hypoglycemia and take action to prevent the hypoglycemic event. In real time, all adult (non OB) patients with a glucose < 90, and a high risk of future hypoglycemia (based on the WSL formula) will be identified. Patients will be randomly assigned to intervention or no intervention (current standard care). The intervention will consist of an automated provider alert with recommendations on what adjustments could be made to avoid a potentially serious hypoglycemic event. The outcomes that will be measured include: 1) reductions in serious hypoglycemic events, 2) monitor the changes made by providers as a result of alerts in order to study provider behavior and identify future areas of intervention, and 3) provider satisfaction with the alert system.
Official Title
-----------------
Leveraging the Power of the EMR: Using a Real Time Prediction Model to Decrease Inpatient Hypoglycemic Events
Conditions
-----------------
Hypoglycemia
Intervention / Treatment
-----------------
* Other: Hypoglycemia prediction alert
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All adult inpatients having glucoses measured (point of care) Exclusion Criteria: adults admitted to obstetrics
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: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Alert<br>If glucose <90 mg/dl and hypoglycemia prediction score >35, then alert with suggestion for intervention sent to treating team | Other: Hypoglycemia prediction alert<br>* In real time, for a patient with a glucose <90 mg/d, using a hypoglycemia prediction model that takes into account patient weight, renal function, eating and insulin dosing a risk score is produced. If the Risk score is >35, then the patient is determined to be at risk for hypoglycemia in the next 72 hours. If a patient is determined to be at risk for hypoglycemia, the following will occur: Alert will be generated and sent via careweb a pager alert system that sends the alert specifically to the current oncall provider The alert also points the provider to the EMR order section where a formal more detailed alert gives recommendationsd for changes in insulin dosing to potentially prevent hypoglycemia.<br>|
| No Intervention: No alert<br>Routine standard care. If glucose <90 mg/dl and hypoglycemia prediction score >35, then report for investigators will be collected, but no active alert will be sent to teams. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients (in each group) who ultimately have a hypoglycemic event | | 72 hours |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
inpatient diabetes, hypoglycemia
|
||
NCT00788853
|
A Survey to Evaluate Diabetes Management, Control, Chronic Complications, Psychosocial Aspects of Diabetic Subjects in Indonesia
|
This study is conducted in Asia. The aim of this observational study is to evaluate current status of diabetes management, control, complications in diabetic subjects in Asia. Further perceptions and practices of physicians and subjects about diabetes management in Asia will be evaluated.
|
DiabCare Asia 2008. A Cross-sectional Survey to Evaluate Diabetes Management, Control, Complications, Psychosocial Aspects of Diabetic Patients in Asia and to Evaluate Perceptions and Practices of Physicians and Patients About Diabetes Management in Asia. DiabCare Asia 2008 - Indonesia
|
Diabetes, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2
|
* Other: No treatment given
|
Inclusion Criteria:~Diabetic patients registered in the particular centre for more than 12 months.~Patients should have visited the centre at least once in the last 3-6 months before the initial study visit.~Patients willing to sign informed consent form.~Exclusion Criteria:~Repetition of any patient as patients should not be included twice for any reason.~Unwilling to participate or unable to comply with protocol requirements.
| null | null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean age of onset of either type 1 or type 2 diabetes mellitus | | study visit |
| Mean duration of treatment of type 2 diabetes mellitus. | | study visit |
| Percentage of patients on either insulin therapy or OAD (oral anti-diabetic drug) therapy. | | study visit |
| Mean duration of diabetes in type 1 and type 2 diabetes patients respectively. | | study visit |
| Mean FPG (fasting plasma glucose),PPG (post prandial glucose) and HbA1c of diabetic patients. | | study visit |
| Percentage of diabetic patients with HbA1c target below or equal to 7.0%. | | study visit |
| Percentage of diabetic patients with HbA1c target below or equal to 6.5%. | | study visit |
| Percentage of diabetic patients having dyslipidemia and hypertension | | study visit |
| Percentage of diabetic patients having cardiovascular complications | | study visit |
| Percentage of diabetic patients having peripheral vascular disease | | study visit |
| Percentage of diabetic patients having diabetic nephropathy | | study visit |
| Percentage of diabetic patients having diabetic eye complications | | study visit |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients' perception will be analysed through Patient questionnaire measuring:Psychological well-being, Quality of life and Patients' compliant to treatment | | study visit |
| Physician questionnaire measuring awareness about:HbA1c test and its goal, Anti-diabetic treatment and Barriers towards optimum diabetes control | | study visit |
| Duration of diabetes associated with highest number of diabetic complications | | study visit |
| Minimum duration of diabetes associated with 10% incidence of diabetic complications (CVD, nephropathy and retinopathy) | | study visit |
|
DiabCare Asia 2008, Cross-sectional survey, Glycemic control, Psychosocial well-being, Diabetic complications, Quality of life.
|
Diabetes Mellitus, Diabetes Mellitus, Type 2, Diabetes Mellitus, Type 1, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Autoimmune Diseases, Immune System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| A<br> | Other: No treatment given<br>* No treatment is given<br>|
|
A Survey to Evaluate Diabetes Management, Control, Chronic Complications, Psychosocial Aspects of Diabetic Subjects in Indonesia
Study Overview
=================
Brief Summary
-----------------
This study is conducted in Asia. The aim of this observational study is to evaluate current status of diabetes management, control, complications in diabetic subjects in Asia. Further perceptions and practices of physicians and subjects about diabetes management in Asia will be evaluated.
Official Title
-----------------
DiabCare Asia 2008. A Cross-sectional Survey to Evaluate Diabetes Management, Control, Complications, Psychosocial Aspects of Diabetic Patients in Asia and to Evaluate Perceptions and Practices of Physicians and Patients About Diabetes Management in Asia. DiabCare Asia 2008 - Indonesia
Conditions
-----------------
Diabetes, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2
Intervention / Treatment
-----------------
* Other: No treatment given
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diabetic patients registered in the particular centre for more than 12 months. Patients should have visited the centre at least once in the last 3-6 months before the initial study visit. Patients willing to sign informed consent form. Exclusion Criteria: Repetition of any patient as patients should not be included twice for any reason. Unwilling to participate or unable to comply with protocol requirements.
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| A<br> | Other: No treatment given<br>* No treatment is given<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean age of onset of either type 1 or type 2 diabetes mellitus | | study visit |
| Mean duration of treatment of type 2 diabetes mellitus. | | study visit |
| Percentage of patients on either insulin therapy or OAD (oral anti-diabetic drug) therapy. | | study visit |
| Mean duration of diabetes in type 1 and type 2 diabetes patients respectively. | | study visit |
| Mean FPG (fasting plasma glucose),PPG (post prandial glucose) and HbA1c of diabetic patients. | | study visit |
| Percentage of diabetic patients with HbA1c target below or equal to 7.0%. | | study visit |
| Percentage of diabetic patients with HbA1c target below or equal to 6.5%. | | study visit |
| Percentage of diabetic patients having dyslipidemia and hypertension | | study visit |
| Percentage of diabetic patients having cardiovascular complications | | study visit |
| Percentage of diabetic patients having peripheral vascular disease | | study visit |
| Percentage of diabetic patients having diabetic nephropathy | | study visit |
| Percentage of diabetic patients having diabetic eye complications | | study visit |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients' perception will be analysed through Patient questionnaire measuring:Psychological well-being, Quality of life and Patients' compliant to treatment | | study visit |
| Physician questionnaire measuring awareness about:HbA1c test and its goal, Anti-diabetic treatment and Barriers towards optimum diabetes control | | study visit |
| Duration of diabetes associated with highest number of diabetic complications | | study visit |
| Minimum duration of diabetes associated with 10% incidence of diabetic complications (CVD, nephropathy and retinopathy) | | study visit |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
DiabCare Asia 2008, Cross-sectional survey, Glycemic control, Psychosocial well-being, Diabetic complications, Quality of life.
|
||
NCT03870607
|
Prebiotics and Probiotics During Definitive Treatment With Chemotherapy-radiotherapy SCC of the Anal Canal (BISQUIT)
|
Phase II randomized study of the use of pre-and probiotics during the definitive treatment of chemotherapy-radiotherapy (Ch-RT) for patients with localized anal canal squamous cell cancer (ACSCC) with the objective of increasing the effectiveness of conventional treatment based on the assumptions of that there is a need for research that increases the cure rates of the definitive treatment of Ch-RT in the ACSCC; ACSCC is a virus-associated tumor in many cases and therefore potentially immunogenic; immunotherapy is a promising strategy in ACSCC; and that pre- and probiotics can stimulate the immune system through modulation of the intestinal microbiota, and improve oncological outcomes.
|
Although anal canal squamous cell carcinoma (ACSCC) is rare in developed countries, it has shown an annual increase of 4% in its incidence in Brazil, and according to data from the Oncocenter Foundation of São Paulo (FOSP), 2,338 cases were diagnosed in 2000 and 2016.~The standard treatment for localized ACSCC (without distant metastases) is definitive chemo-radiotherapy (Ch-RT) concomitant with administration of a fluoropyrimidine (5FU or capecitabine) combined with mitomycin or cisplatin, which provides cure rates of 60-80 % depending on the staging. When there is no complete remission, surgical rescue through anal amputation is the only potentially curative modality. However, this strategy is associated with great morbidity, besides negative emotional and social impacts, with consequent reduction of quality of life. Therefore, interventions that may increase the chance of cure in ACSCC should be investigated.~The main risk factors for ACSCC are human papillomavirus (HPV) infections and immunosuppression, including human immunodeficiency virus (HIV) infection. Chronic HPV infection and HIV-induced immunosuppression point to research strategies that strengthen the immune system to reduce the risk of developing ACSCC. In the metastatic setting, the use of immune checkpoint inhibitors, such as anti-programmed death protein-1 (PD1) antibodies, were shown to be promising in ACSCC patients, promoting response rates of approximately 25%. However, there is no evidence of modulation interventions of the immune system in patients with localized ACSCC.~Recently, studies have shown that the composition of the intestinal microbiota influences the onset of colorectal cancer, and may even disrupt the effects of chemotherapy in this neoplasm. A preclinical study in animal model showed that E. coli impaired the antitumor effect of fluoropyrimidines, drug used in colorectal cancer and ACSCC. The intestinal microbiota also participates in a large set of metabolic processes (such as reduction, hydrolysis, dehydroxylation, etc.) involved in drug metabolism. For example, some intestinal bacteria have β-glucuronidases that cleave glucuronide from the inactive metabolite of irinotecan (SN-38G), a drug used in gastrointestinal tumors, releasing active metabolite (SN38) in the intestine, causing diarrhea and colitis. Ciprofloxacin has been shown to inhibit this enzyme by suppressing the diarrhea associated with irinotecan in an experimental model of mice. Mycoplasma hyorhinis encodes a thymidine phosphorylase that strongly restricts the cytostatic activity of pyrimidine nucleoside analogues.~On the other hand, the replacement of the intestinal microbiota carcinogenic (Fusobacterium spp and Bacteriodes fragilis) by a protective microbiota (Bifidobacterium and Lactobacillus) has been the reason of numerous investigations with prebiotics and probiotics. According to the International Scientific Association of Probiotics and Prebiotics, probiotics are composed of living organisms which, when administered, promote health benefits, such as antimicrobial action against intestinal pathogens, modulation of the immune system, reduction of cholesterol levels, reduction of colitis and prevention of colorectal cancer. Kefir is an example of probiotic. Already prebiotics are inert ingredients that promote alteration in the composition or activity of the gastrointestinal microflora, conferring health benefits. Example of prebiotic is polysaccharide inulin. Studies with these compounds have been conducted, showing promising results. A small placebo-controlled trial using B. breve breve (Yakut®) in children undergoing chemotherapy for a variety of neoplasms has shown that this group had fewer episodes of fever and less frequency of use of intravenous antibiotics compared to controls. There are also studies that suggest that the alteration of the intestinal flora can increase the effectiveness of immunotherapy as a form of modulation of the immune system in several animal models of colorectal cancer. In addition, the use of this strategy could have a modulatory effect on local and systemic toxicity of the treatment, possibly reducing the morbidity of the treatment, as already suggested by studies in cervical carcinomas.~Despite the strong scientific rationale, there are no studies that have evaluated the use of probiotics or prebiotics in order to increase the effectiveness of conventional Ch-RT treatment in ACSCC. Therefore, based on the assumptions that there is a need for research that increases the cure rates of the definitive treatment of Ch-RT in ACSCC; ACSCC is a virus-associated tumor in many cases and therefore potentially immunogenic; immunotherapy is a promising strategy in ACSCC; and that pre- and probiotics can stimulate the immune system through modulation of the intestinal microbiota, and improve oncological outcomes, the investigators propose a randomized phase II study of the use of pre-probiotics during definitive treatment of Ch-RT for patients with ACSCC located.~The primary hypothesis of this study is that addition of pre- and probiotics increases the proportion of patients with complete clinical and radiological response after Ch-RT to ACSCC. Secondary hypotheses are that pre- and probiotics increase the metabolic response measured by positron emission computed tomography (PET-CT) with 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (18-FDG) and promote greater control of local disease after Ch-RT; and reduce local and systemic toxicity of treatment.
|
A Randomized Phase II Study of the Administration of Prebiotics and Probiotics During Definitive Treatment With Chemotherapy-radiotherapy for Patients With Squamous Cell Carcinoma of the Anal Canal (BISQUIT)
|
Anal Cancer Squamous Cell
|
* Dietary Supplement: prebiotics in combination with probiotics
|
Inclusion Criteria:~Patients older than 18 years;~Confirmed histological diagnosis of squamous cell carcinoma / squamous cell carcinoma of the anal canal (ACSCC);~Patients with localized ACSCC (≥ T2N0M0, according to American Joint Committee on Cancer (AJCC) 8th edition) staged by conventional imaging methods according to institutional routine;~Indication of starting definitive treatment with Ch-RT in the institution. HIV-positive patients may be included;~Free and informed consent signed by the patient or legal representative~Exclusion Criteria:~Diagnosis of perianal squamous cell carcinomas;~Clinical condition leading to difficulty in swallowing;~Patients with a contraindication to receiving Ch-RT, ie receiving only radiotherapy or not receiving polychemotherapy;~Clinical condition that, due to the investigator's judgment, prevents adherence to the study~Active infection requiring antibiotic therapy
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible patients who consent to participate in this study will be randomized 1: 1 in two groups: Group A or experimental and Group B or control
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (clinical and radiological) | absence of visible disease at the clinical examination and magnetic resonance imaging (MRI) of the pelvis (or pelvic tomography, if contraindicated to MRI) and without disease at a distance, through tomography of the chest and abdomen. | Six to eight weeks from the end of Ch-RT |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolic response by 18-FDG PET-CT | Comparing the mean pre-and post-Ch-RT volume-capture measurements of each patient at 6-8 weeks post Ch-RT | Six to eight weeks from the end of Ch-RT |
| Complete clinical and radiological response rate | defined as absence of disease visible to clinical and pelvic MRI (or pelvic tomography) exams and without disease at a distance, through tomography of the chest and abdomen; | Six months |
| Progression / disease free survival | defined as the time from day1 cycle 1 of Ch-RT treatment to local or remote relapse, or death from any cause, whichever occurs first. | through study completion, an average of 5 years |
| Proportion of patients without colostomy | Proportion of patients without colostomy 12 months after Ch-RT termination. | Twelve months |
| Incidence of Adverse Events Treatment-related | Adverse events of grade 2 or higher by the Common Adverse Event Toxicity Criteria (CTCAE) version 4.0. | through study completion, an average of 5 years |
| Incidence of HPV in tumor tissue | Incidence of positivity for HPV screening in tumor tissue through genotyping | through study completion, an average of 3 years |
| Variation of systemic immune parameters | Defined by variation in total number of lymphocytes, neutrophil / lymphocyte ratio (NLR) and lymphocyte / monocyte ratio (LMR) | through study completion, an average of 3 years |
|
probiotics, prebiotics, microbiome
|
Anus Neoplasms, Rectal Neoplasms, Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Intestinal Diseases, Anus Diseases, Rectal Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prebiotics and probiotics group<br>This group will receive standard nutritional guidance from the institutional routine and prebiotics in combination with probiotics, starting one week before the start of Ch-RT and daily throughout the treatment up to 6 to 8 weeks post Ch-RT at the time of evaluation response (primary outcome). | Dietary Supplement: prebiotics in combination with probiotics<br>* Administration of prebiotics in combination with probiotics before the start of Ch-RT<br>* Other names: Symbioflor;|
| No Intervention: Control group<br>This group will lead nutritionally based just before starting Ch-RT. | |
|
Prebiotics and Probiotics During Definitive Treatment With Chemotherapy-radiotherapy SCC of the Anal Canal (BISQUIT)
Study Overview
=================
Brief Summary
-----------------
Phase II randomized study of the use of pre-and probiotics during the definitive treatment of chemotherapy-radiotherapy (Ch-RT) for patients with localized anal canal squamous cell cancer (ACSCC) with the objective of increasing the effectiveness of conventional treatment based on the assumptions of that there is a need for research that increases the cure rates of the definitive treatment of Ch-RT in the ACSCC; ACSCC is a virus-associated tumor in many cases and therefore potentially immunogenic; immunotherapy is a promising strategy in ACSCC; and that pre- and probiotics can stimulate the immune system through modulation of the intestinal microbiota, and improve oncological outcomes.
Detailed Description
-----------------
Although anal canal squamous cell carcinoma (ACSCC) is rare in developed countries, it has shown an annual increase of 4% in its incidence in Brazil, and according to data from the Oncocenter Foundation of São Paulo (FOSP), 2,338 cases were diagnosed in 2000 and 2016. The standard treatment for localized ACSCC (without distant metastases) is definitive chemo-radiotherapy (Ch-RT) concomitant with administration of a fluoropyrimidine (5FU or capecitabine) combined with mitomycin or cisplatin, which provides cure rates of 60-80 % depending on the staging. When there is no complete remission, surgical rescue through anal amputation is the only potentially curative modality. However, this strategy is associated with great morbidity, besides negative emotional and social impacts, with consequent reduction of quality of life. Therefore, interventions that may increase the chance of cure in ACSCC should be investigated. The main risk factors for ACSCC are human papillomavirus (HPV) infections and immunosuppression, including human immunodeficiency virus (HIV) infection. Chronic HPV infection and HIV-induced immunosuppression point to research strategies that strengthen the immune system to reduce the risk of developing ACSCC. In the metastatic setting, the use of immune checkpoint inhibitors, such as anti-programmed death protein-1 (PD1) antibodies, were shown to be promising in ACSCC patients, promoting response rates of approximately 25%. However, there is no evidence of modulation interventions of the immune system in patients with localized ACSCC. Recently, studies have shown that the composition of the intestinal microbiota influences the onset of colorectal cancer, and may even disrupt the effects of chemotherapy in this neoplasm. A preclinical study in animal model showed that E. coli impaired the antitumor effect of fluoropyrimidines, drug used in colorectal cancer and ACSCC. The intestinal microbiota also participates in a large set of metabolic processes (such as reduction, hydrolysis, dehydroxylation, etc.) involved in drug metabolism. For example, some intestinal bacteria have β-glucuronidases that cleave glucuronide from the inactive metabolite of irinotecan (SN-38G), a drug used in gastrointestinal tumors, releasing active metabolite (SN38) in the intestine, causing diarrhea and colitis. Ciprofloxacin has been shown to inhibit this enzyme by suppressing the diarrhea associated with irinotecan in an experimental model of mice. Mycoplasma hyorhinis encodes a thymidine phosphorylase that strongly restricts the cytostatic activity of pyrimidine nucleoside analogues. On the other hand, the replacement of the intestinal microbiota carcinogenic (Fusobacterium spp and Bacteriodes fragilis) by a protective microbiota (Bifidobacterium and Lactobacillus) has been the reason of numerous investigations with prebiotics and probiotics. According to the International Scientific Association of Probiotics and Prebiotics, probiotics are composed of living organisms which, when administered, promote health benefits, such as antimicrobial action against intestinal pathogens, modulation of the immune system, reduction of cholesterol levels, reduction of colitis and prevention of colorectal cancer. Kefir is an example of probiotic. Already prebiotics are inert ingredients that promote alteration in the composition or activity of the gastrointestinal microflora, conferring health benefits. Example of prebiotic is polysaccharide inulin. Studies with these compounds have been conducted, showing promising results. A small placebo-controlled trial using B. breve breve (Yakut®) in children undergoing chemotherapy for a variety of neoplasms has shown that this group had fewer episodes of fever and less frequency of use of intravenous antibiotics compared to controls. There are also studies that suggest that the alteration of the intestinal flora can increase the effectiveness of immunotherapy as a form of modulation of the immune system in several animal models of colorectal cancer. In addition, the use of this strategy could have a modulatory effect on local and systemic toxicity of the treatment, possibly reducing the morbidity of the treatment, as already suggested by studies in cervical carcinomas. Despite the strong scientific rationale, there are no studies that have evaluated the use of probiotics or prebiotics in order to increase the effectiveness of conventional Ch-RT treatment in ACSCC. Therefore, based on the assumptions that there is a need for research that increases the cure rates of the definitive treatment of Ch-RT in ACSCC; ACSCC is a virus-associated tumor in many cases and therefore potentially immunogenic; immunotherapy is a promising strategy in ACSCC; and that pre- and probiotics can stimulate the immune system through modulation of the intestinal microbiota, and improve oncological outcomes, the investigators propose a randomized phase II study of the use of pre-probiotics during definitive treatment of Ch-RT for patients with ACSCC located. The primary hypothesis of this study is that addition of pre- and probiotics increases the proportion of patients with complete clinical and radiological response after Ch-RT to ACSCC. Secondary hypotheses are that pre- and probiotics increase the metabolic response measured by positron emission computed tomography (PET-CT) with 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (18-FDG) and promote greater control of local disease after Ch-RT; and reduce local and systemic toxicity of treatment.
Official Title
-----------------
A Randomized Phase II Study of the Administration of Prebiotics and Probiotics During Definitive Treatment With Chemotherapy-radiotherapy for Patients With Squamous Cell Carcinoma of the Anal Canal (BISQUIT)
Conditions
-----------------
Anal Cancer Squamous Cell
Intervention / Treatment
-----------------
* Dietary Supplement: prebiotics in combination with probiotics
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients older than 18 years; Confirmed histological diagnosis of squamous cell carcinoma / squamous cell carcinoma of the anal canal (ACSCC); Patients with localized ACSCC (≥ T2N0M0, according to American Joint Committee on Cancer (AJCC) 8th edition) staged by conventional imaging methods according to institutional routine; Indication of starting definitive treatment with Ch-RT in the institution. HIV-positive patients may be included; Free and informed consent signed by the patient or legal representative Exclusion Criteria: Diagnosis of perianal squamous cell carcinomas; Clinical condition leading to difficulty in swallowing; Patients with a contraindication to receiving Ch-RT, ie receiving only radiotherapy or not receiving polychemotherapy; Clinical condition that, due to the investigator's judgment, prevents adherence to the study Active infection requiring antibiotic therapy
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible patients who consent to participate in this study will be randomized 1: 1 in two groups: Group A or experimental and Group B or control
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prebiotics and probiotics group<br>This group will receive standard nutritional guidance from the institutional routine and prebiotics in combination with probiotics, starting one week before the start of Ch-RT and daily throughout the treatment up to 6 to 8 weeks post Ch-RT at the time of evaluation response (primary outcome). | Dietary Supplement: prebiotics in combination with probiotics<br>* Administration of prebiotics in combination with probiotics before the start of Ch-RT<br>* Other names: Symbioflor;|
| No Intervention: Control group<br>This group will lead nutritionally based just before starting Ch-RT. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (clinical and radiological) | absence of visible disease at the clinical examination and magnetic resonance imaging (MRI) of the pelvis (or pelvic tomography, if contraindicated to MRI) and without disease at a distance, through tomography of the chest and abdomen. | Six to eight weeks from the end of Ch-RT |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolic response by 18-FDG PET-CT | Comparing the mean pre-and post-Ch-RT volume-capture measurements of each patient at 6-8 weeks post Ch-RT | Six to eight weeks from the end of Ch-RT |
| Complete clinical and radiological response rate | defined as absence of disease visible to clinical and pelvic MRI (or pelvic tomography) exams and without disease at a distance, through tomography of the chest and abdomen; | Six months |
| Progression / disease free survival | defined as the time from day1 cycle 1 of Ch-RT treatment to local or remote relapse, or death from any cause, whichever occurs first. | through study completion, an average of 5 years |
| Proportion of patients without colostomy | Proportion of patients without colostomy 12 months after Ch-RT termination. | Twelve months |
| Incidence of Adverse Events Treatment-related | Adverse events of grade 2 or higher by the Common Adverse Event Toxicity Criteria (CTCAE) version 4.0. | through study completion, an average of 5 years |
| Incidence of HPV in tumor tissue | Incidence of positivity for HPV screening in tumor tissue through genotyping | through study completion, an average of 3 years |
| Variation of systemic immune parameters | Defined by variation in total number of lymphocytes, neutrophil / lymphocyte ratio (NLR) and lymphocyte / monocyte ratio (LMR) | through study completion, an average of 3 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
probiotics, prebiotics, microbiome
|
NCT00680602
|
Group Cognitive Behavioral Therapy Versus Fluoxetine for Obsessive-Compulsive Disorder: a Practical Trial
|
First line treatments fo Obsessive Compulsive Disorder (OCD) are Selective Serotonin Recapture Inhibitors (SSRIs) and Cognitive Behaviour Therapy (CBT) including exposure with response prevention. The aim of the present study is to evaluate the clinical efficacy of GCBT and SSRIs for OCD patients. Other clinical trials have compared these treatments, but with OCD patients without any other psychiatric disorder. In this study patients with current age between 18 and 65 years, with YBOCS score of at least 16 and psychiatric comorbidities will be not excluded. Exclusion criteria will be: OCD secondary to brain trauma, stroke or malformation; current abuse of alcohol or other psychoactive substance, current presence of psychotic symptoms, suicidal risk, psychiatric or clinical comorbidity that might get worse with the medications used in the trial. So, the present study investigates the efficacy of these treatments for a heterogeneous OCD population, trying to identify if the usual treatments are efficient when applied in the public health system that treat not just patients with only OCD diagnosis. Patients will be randomized for GCBT and SSRI, and after treatment will be evaluated by researchers blind to the treatment received.
|
During the last decades, different pharmacological and psychotherapeutic strategies have been used to treat patients with obsessive compulsive disorder (OCD). Drugs that inhibit the serotonin recapture and the cognitive behavior therapy, that includes the exposure with response prevention and cognitive strategies, have been the most efficient treatment so far. This study's aims are to compare group cognitive-behavior therapy and standard pharmacological treatment (SRIs) in a world real population, using broader inclusion criteria. DSM-IV diagnostic criteria for OCD will be used (APA, 1994) and patients will be interviewed with the following instruments: SCID-I and Y-BOCS. Inclusion criteria are: (1) OCD diagnosis, (2) YBOCS score ≥ 16 (for patients with both obsessions and compulsions) or ≥ 10 (for patients with only obsessions or compulsions), (3) informed consent to participate in this clinical trial. Exclusion criteria are: (1) patients with clinical or neurological diseases that may be worsen by the medications included in treatment protocol, (2) Current substance dependence, (3) Current psychotic symptoms, (4) Current suicide risk. Patients will be randomized in blocks of 12 and with stratification for the following parameters: current SSRI, age, sex and previous response to treatment. Rates of improvement will be based on the results of the YBOCS scores for obsessions and compulsions and on the results of the clinical global impression scale. Pos-treatment measures will be assessed by psychiatrists or psychologists not involved in the patients treatment that will be blind for the treatment being received by the patient. The patient will be considered responsive to treatment when he or she presents a reduction in YBOCS score ≥ 35% of the initial score and a CGI score of 1 (very much improved) or 2 (much improved). The results of this study will help us to identify better health politics planning to a heterogeneous OCD population. So, it will improve our knowledge about the efficacy of the first line treatments in a real world OCD population.
|
Group Cognitive Behavioral Therapy Versus Fluoxetine for Obsessive-Compulsive Disorder: a Randomized Open Trial for Any Patient.
|
Obsessive Compulsive Disorder
|
* Behavioral: Group Cognitive Behavior Therapy
* Drug: SSRI (fluoxetine, sertraline, paroxetine, citalopram)
|
Inclusion Criteria:~Having been diagnosed with primary OCD according to the criteria set forth in the DSM-IV;~Current symptoms causing significant distress (YBOCS score greater than 16);~Not receiving current adequate treatment;~Accepting to participate in the study~Exclusion Criteria:~Having a clinical or neurological disease that might be worsened by the medicines included in the treatment protocol;~Presenting current substance dependence or abuse;~Exhibiting current psychotic symptoms; being currently at risk for suicide;~And, being pregnant or having the intention to become pregnant prior to the end of the treatment protocol
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) (Goodman et al., 1989) and Clinical Global Impressions (CGI) (Guy, 1976) will be implemented at pre and post treatment by a blind evaluator to the treatment received. | | 12 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life measured by SF 36 and social adjustment measured by EAS. | | 12 weeks |
|
behavior therapy, group therapy, psychopharmacology
|
Sertraline, Fluoxetine, Paroxetine, Citalopram, Antidepressive Agents, Psychotropic Drugs, Selective Serotonin Reuptake Inhibitors, Neurotransmitter Uptake Inhibitors, Membrane Transport Modulators, Molecular Mechanisms of Pharmacological Action, Neurotransmitter Agents, Serotonin Agents, Physiological Effects of Drugs, Antidepressive Agents, Second-Generation, Cytochrome P-450 CYP2D6 Inhibitors, Cytochrome P-450 Enzyme Inhibitors, Enzyme Inhibitors
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Group Cognitive Behavior Therapy | Behavioral: Group Cognitive Behavior Therapy<br>* Structured protocol described by Cordioli et al., 2003<br>* Other names: group psychotherapy;|
| Active Comparator: 2<br>Selective Serotonin Reuptake Inhibitor | Drug: SSRI (fluoxetine, sertraline, paroxetine, citalopram)<br>* Fluoxetine (80mg/day or maximum tolerated dosage) Sertraline (200mg/day or maximum tolerated dosage) Paroxetine (60 mg/day or maximum tolerated dosage) Citalopram (60 mg/day or maximum tolerated dosage)<br>* Other names: Cipramil;|
|
Group Cognitive Behavioral Therapy Versus Fluoxetine for Obsessive-Compulsive Disorder: a Practical Trial
Study Overview
=================
Brief Summary
-----------------
First line treatments fo Obsessive Compulsive Disorder (OCD) are Selective Serotonin Recapture Inhibitors (SSRIs) and Cognitive Behaviour Therapy (CBT) including exposure with response prevention. The aim of the present study is to evaluate the clinical efficacy of GCBT and SSRIs for OCD patients. Other clinical trials have compared these treatments, but with OCD patients without any other psychiatric disorder. In this study patients with current age between 18 and 65 years, with YBOCS score of at least 16 and psychiatric comorbidities will be not excluded. Exclusion criteria will be: OCD secondary to brain trauma, stroke or malformation; current abuse of alcohol or other psychoactive substance, current presence of psychotic symptoms, suicidal risk, psychiatric or clinical comorbidity that might get worse with the medications used in the trial. So, the present study investigates the efficacy of these treatments for a heterogeneous OCD population, trying to identify if the usual treatments are efficient when applied in the public health system that treat not just patients with only OCD diagnosis. Patients will be randomized for GCBT and SSRI, and after treatment will be evaluated by researchers blind to the treatment received.
Detailed Description
-----------------
During the last decades, different pharmacological and psychotherapeutic strategies have been used to treat patients with obsessive compulsive disorder (OCD). Drugs that inhibit the serotonin recapture and the cognitive behavior therapy, that includes the exposure with response prevention and cognitive strategies, have been the most efficient treatment so far. This study's aims are to compare group cognitive-behavior therapy and standard pharmacological treatment (SRIs) in a world real population, using broader inclusion criteria. DSM-IV diagnostic criteria for OCD will be used (APA, 1994) and patients will be interviewed with the following instruments: SCID-I and Y-BOCS. Inclusion criteria are: (1) OCD diagnosis, (2) YBOCS score ≥ 16 (for patients with both obsessions and compulsions) or ≥ 10 (for patients with only obsessions or compulsions), (3) informed consent to participate in this clinical trial. Exclusion criteria are: (1) patients with clinical or neurological diseases that may be worsen by the medications included in treatment protocol, (2) Current substance dependence, (3) Current psychotic symptoms, (4) Current suicide risk. Patients will be randomized in blocks of 12 and with stratification for the following parameters: current SSRI, age, sex and previous response to treatment. Rates of improvement will be based on the results of the YBOCS scores for obsessions and compulsions and on the results of the clinical global impression scale. Pos-treatment measures will be assessed by psychiatrists or psychologists not involved in the patients treatment that will be blind for the treatment being received by the patient. The patient will be considered responsive to treatment when he or she presents a reduction in YBOCS score ≥ 35% of the initial score and a CGI score of 1 (very much improved) or 2 (much improved). The results of this study will help us to identify better health politics planning to a heterogeneous OCD population. So, it will improve our knowledge about the efficacy of the first line treatments in a real world OCD population.
Official Title
-----------------
Group Cognitive Behavioral Therapy Versus Fluoxetine for Obsessive-Compulsive Disorder: a Randomized Open Trial for Any Patient.
Conditions
-----------------
Obsessive Compulsive Disorder
Intervention / Treatment
-----------------
* Behavioral: Group Cognitive Behavior Therapy
* Drug: SSRI (fluoxetine, sertraline, paroxetine, citalopram)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Having been diagnosed with primary OCD according to the criteria set forth in the DSM-IV; Current symptoms causing significant distress (YBOCS score greater than 16); Not receiving current adequate treatment; Accepting to participate in the study Exclusion Criteria: Having a clinical or neurological disease that might be worsened by the medicines included in the treatment protocol; Presenting current substance dependence or abuse; Exhibiting current psychotic symptoms; being currently at risk for suicide; And, being pregnant or having the intention to become pregnant prior to the end of the treatment protocol
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: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Group Cognitive Behavior Therapy | Behavioral: Group Cognitive Behavior Therapy<br>* Structured protocol described by Cordioli et al., 2003<br>* Other names: group psychotherapy;|
| Active Comparator: 2<br>Selective Serotonin Reuptake Inhibitor | Drug: SSRI (fluoxetine, sertraline, paroxetine, citalopram)<br>* Fluoxetine (80mg/day or maximum tolerated dosage) Sertraline (200mg/day or maximum tolerated dosage) Paroxetine (60 mg/day or maximum tolerated dosage) Citalopram (60 mg/day or maximum tolerated dosage)<br>* Other names: Cipramil;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) (Goodman et al., 1989) and Clinical Global Impressions (CGI) (Guy, 1976) will be implemented at pre and post treatment by a blind evaluator to the treatment received. | | 12 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life measured by SF 36 and social adjustment measured by EAS. | | 12 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
behavior therapy, group therapy, psychopharmacology
|
NCT03014024
|
Low-level Laser Therapy in Distal Radius Fractures
|
Conservative treatment of distal radius fracture is immobilisation with cast for 4-6 weeks. After removing the cast, it is common to still have pain, swelling and reduced mobility in the wrist. The aim of this study is to evaluate the influence of LLLT on the hand.
|
Patient with distal radius fractures are after removal of the cast are recruited form Bergen Emergency Department, where the are randomly divided into two groups with concealed allocation. Patient will be treated 3 times a week, for 3 week. After removal of the cast, the patients pain threshold, swelling, AROM, strength and function is measured. The patients will meet for following-up controls until 26 weeks after injury.~Changes in outcome measures during the study:~Due to covid 19 virus restrictions, we had to abandon the objective physical measurements as planned. Primary outcome measures were retrieved allowing no physical contact with the participants (Ipad, telephone or e-mail).
|
A Double-blind Placebo-controlled Study of Low-level Laser Therapy After Removal of Cast in Distal Radius Fractures
|
Colles' Fracture
|
* Other: Low-Level Laser Therapy
* Other: Placebo Low Level Laser therapy
|
Inclusion Criteria:~Patients with distal radius fracture, with or without ulna fracture (Colles' fracture~The breach must be closed~after reduction: 0 degrees dorsal displacement of radius~Under 5 degrees shortening of the radius~Under 3 mm step in the joint~18+ years~Exclusion Criteria:~People who do not speak Norwegian or English~If the patient is pregnant~Patient with Smith fracture~Wounds over fracture area~If the patient hav a peripheral neve injury~If the patient had (previously) operated the wrist~Persons with verified osteoporosis at the time of injury, systemic inflammatory disease (rheumatism), mental illness, stroke, Parkinson's disease, multiple sclerosis, cancer or congenital malformations in wrist~If the laser treatment can not be started within 3 days after removal of the cast
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Function and pain | Function will be assessed using Patient Rating Wrist and Hand Evaluation (PRWHE), and questions about night pain/pain killers | 26 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain assessed using Pressure Algometer | Pressure Algometer | 26 weeks |
| Swelling will be assessed using measurement tape | Swelling will be assessed using measurement tape | 26 weeks |
| Active range of motion will be assessed using goniometer | Active range of motion will be assessed using goniometer | 26 weeks |
| Strength will be assessed using dynamometer | Strength will be assessed using dynamometer | 26 weeks |
|
Distal Radius Fracture, Low Level Laser Therapy
|
Colles' Fracture, Fractures, Bone, Radius Fractures, Wrist Fractures, Wounds and Injuries, Forearm Injuries, Arm Injuries, Wrist Injuries, Fracture Dislocation, Joint Dislocations, Joint Diseases, Musculoskeletal Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-Level Laser therapy<br>After inclusion in the study, patients will be treated with LLLT. The laser is a super pulsed infrared laser with a wavelength of 904 nm, belonging to laser class 3B. Patient will be treated from dorsal side of the wrist on the fracture area, and distal ulna area from the palmar side. Total 20 second on each side (3 points), with 3,6 J/cm2. the light from the laser is not visible to the eye, and will not give any perceptible stimulus. The x-ray will be used to find the fracture line. | Other: Low-Level Laser Therapy<br>* The laser is an infrared (invisible) 60 mW 904 nm, made by Irradia Midlaser<br>|
| Placebo Comparator: Placebo Low-Level Laser therapy<br>After inclusion in the study, patients will be treated with placebo LLLT. This placebo laser is identical in appearance to the other super pulsed infrared laser with a wavelength of 904 nm, belonging to laser class 3B. Patient will be treated on the same areas, and have the same procedure and time. Since the light from the laser is invisible neither the participant nor the therapist will know whether the laser is a placebo. | Other: Placebo Low Level Laser therapy<br>* This i laser is not giving any irradiation, but is identical to the infrared (invisible) 60 mW 904 nm Irradia Midlaser, made by Irradia.<br>|
|
Low-level Laser Therapy in Distal Radius Fractures
Study Overview
=================
Brief Summary
-----------------
Conservative treatment of distal radius fracture is immobilisation with cast for 4-6 weeks. After removing the cast, it is common to still have pain, swelling and reduced mobility in the wrist. The aim of this study is to evaluate the influence of LLLT on the hand.
Detailed Description
-----------------
Patient with distal radius fractures are after removal of the cast are recruited form Bergen Emergency Department, where the are randomly divided into two groups with concealed allocation. Patient will be treated 3 times a week, for 3 week. After removal of the cast, the patients pain threshold, swelling, AROM, strength and function is measured. The patients will meet for following-up controls until 26 weeks after injury. Changes in outcome measures during the study: Due to covid 19 virus restrictions, we had to abandon the objective physical measurements as planned. Primary outcome measures were retrieved allowing no physical contact with the participants (Ipad, telephone or e-mail).
Official Title
-----------------
A Double-blind Placebo-controlled Study of Low-level Laser Therapy After Removal of Cast in Distal Radius Fractures
Conditions
-----------------
Colles' Fracture
Intervention / Treatment
-----------------
* Other: Low-Level Laser Therapy
* Other: Placebo Low Level Laser therapy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with distal radius fracture, with or without ulna fracture (Colles' fracture The breach must be closed after reduction: 0 degrees dorsal displacement of radius Under 5 degrees shortening of the radius Under 3 mm step in the joint 18+ years Exclusion Criteria: People who do not speak Norwegian or English If the patient is pregnant Patient with Smith fracture Wounds over fracture area If the patient hav a peripheral neve injury If the patient had (previously) operated the wrist Persons with verified osteoporosis at the time of injury, systemic inflammatory disease (rheumatism), mental illness, stroke, Parkinson's disease, multiple sclerosis, cancer or congenital malformations in wrist If the laser treatment can not be started within 3 days after removal of the cast
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-Level Laser therapy<br>After inclusion in the study, patients will be treated with LLLT. The laser is a super pulsed infrared laser with a wavelength of 904 nm, belonging to laser class 3B. Patient will be treated from dorsal side of the wrist on the fracture area, and distal ulna area from the palmar side. Total 20 second on each side (3 points), with 3,6 J/cm2. the light from the laser is not visible to the eye, and will not give any perceptible stimulus. The x-ray will be used to find the fracture line. | Other: Low-Level Laser Therapy<br>* The laser is an infrared (invisible) 60 mW 904 nm, made by Irradia Midlaser<br>|
| Placebo Comparator: Placebo Low-Level Laser therapy<br>After inclusion in the study, patients will be treated with placebo LLLT. This placebo laser is identical in appearance to the other super pulsed infrared laser with a wavelength of 904 nm, belonging to laser class 3B. Patient will be treated on the same areas, and have the same procedure and time. Since the light from the laser is invisible neither the participant nor the therapist will know whether the laser is a placebo. | Other: Placebo Low Level Laser therapy<br>* This i laser is not giving any irradiation, but is identical to the infrared (invisible) 60 mW 904 nm Irradia Midlaser, made by Irradia.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Function and pain | Function will be assessed using Patient Rating Wrist and Hand Evaluation (PRWHE), and questions about night pain/pain killers | 26 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain assessed using Pressure Algometer | Pressure Algometer | 26 weeks |
| Swelling will be assessed using measurement tape | Swelling will be assessed using measurement tape | 26 weeks |
| Active range of motion will be assessed using goniometer | Active range of motion will be assessed using goniometer | 26 weeks |
| Strength will be assessed using dynamometer | Strength will be assessed using dynamometer | 26 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Distal Radius Fracture, Low Level Laser Therapy
|
NCT01224145
|
Assess the Feasibility and Efficacy of the CollaRx® Bupivacaine Implant Laparoscopic Inguinal or Umbilical Herniorrhaphy
|
This study will assess pain intensity for the first 72 hrs after aggravated movement (cough) following Laparoscopic Inguinal or Umbilical Herniorrhaphy.
|
Inguinal herniorrhaphy is a common surgery; approximately 2,800 per million people in the United States (US) undergo the procedure annually.Common surgical methods of herniorrhaphy include open and laparoscopic placement of synthetic mesh. Studies have shown that the use of synthetic mesh greatly reduces the risk of hernia recurrence regardless of the method used for its placement. Furthermore, utilizing the laparoscopic approach for umbilical hernia repair, specifically with the use of mesh, may also reduce the risk of infection.~Bupivacaine is a local anesthetic (pain medicine) that has an established safety profile. Collagen is a protein that is found in all mammals. The CollaRx Bupivacaine implant is a thin flat sponge made out of collagen that comes from cow tendons and contains bupivacaine. When inserted into a surgical site, the collagen breaks down and bupivacaine is released at the site but very little is absorbed into the blood stream. The high levels of bupivacaine at the surgical site may result in less pain for several days after surgery.~This open-label study will assess pain intensity after surgery in patients who receive the CollaRx Bupivacaine implant as well as determine the feasibility of the use of the laparoscope for sponge placement in laparoscopic hernia repair.
|
A Phase II, Single-dose, Open-label Study to Investigate the Feasibility and Efficacy of the CollaRx® Bupivacaine Implant (200 mg Bupivacaine Hydrochloride) in Men After Laparoscopic Inguinal or Umbilical Herniorrhaphy
|
Hernia, Postoperative Pain
|
* Drug: 5x5cm bupivacaine collagen sponges
|
Inclusion Criteria:~Man ≥18 years~Has a planned unilateral inguinal herniorrhaphy (laparoscopy, transabdominal preperitoneal [TAPP] approach or totally extraperitoneal [TEP] approach) or laparoscopic umbilical herniorrhaphy to be performed according to standard surgical technique under general anesthesia.~Willing to use opioid rescue analgesia.~Exclusion Criteria:~Has a known hypersensitivity to amide local anesthetics, opioids, or bovine products.~Scheduled for bilateral inguinal herniorrhaphy.~Undergone a prior herniorrhaphy at the location scheduled for repair.~Undergone major surgery within 3 months of the scheduled herniorrhaphy.
|
18 Years
| null |
Male
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: laparoscope for bupivacaine sponge (200 mg bupivacaine hydrochloride) placement in laparoscopic hernia repair.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Use of Opioid Analgesia - Morphine Equivalence (mg) | Dosages of 1 to 2 mg per dose were titrated to patient comfort according to institutional standards and at the investigator's discretion. Once patients could tolerate oral medication, they were offered oral morphine (15 mg tablets) as rescue analgesia if necessary. The dose for patients who weighed less than 75kg was 15mg every 3 to 4 hours as needed for pain control. The dose for patients who weighed 75kg or more was 1-2 tablets (15-30 mg) every 3-4 hours for pain control. Morphine was the preferred rescue medication. | 0 to 24 hours after surgery |
| Total Use of Opioid Rescue Analgesia - Morphine Equivalence (mg) | Dosages of 1 to 2 mg per dose were titrated to patient comfort according to institutional standards and at the investigator's discretion. Once patients could tolerate oral medication, they were offered oral morphine (15 mg tablets) as rescue analgesia if necessary. The dose for patients who weighed less than 75kg was 15mg every 3 to 4 hours as needed for pain control. The dose for patients who weighed 75kg or more was 1-2 tablets (15-30 mg) every 3-4 hours for pain control. Morphine was the preferred rescue medication. | 25-48 hours |
| Total Use of Opioid Rescue Analgesia - Morphine Equivalence (mg) | Dosages of 1 to 2 mg per dose were titrated to patient comfort according to institutional standards and at the investigator's discretion. Once patients could tolerate oral medication, they were offered oral morphine (15 mg tablets) as rescue analgesia if necessary. The dose for patients who weighed less than 75kg was 15mg every 3 to 4 hours as needed for pain control. The dose for patients who weighed 75kg or more was 1-2 tablets (15-30 mg) every 3-4 hours for pain control. Morphine was the preferred rescue medication. | 49-72 Hours |
| Total Use of Opioid Rescue Analgesia Morphine Equivalence (mg) | Dosages of 1 to 2 mg per dose were titrated to patient comfort according to institutional standards and at the investigator's discretion. Once patients could tolerate oral medication, they were offered oral morphine (15 mg tablets) as rescue analgesia if necessary. The dose for patients who weighed less than 75kg was 15mg every 3 to 4 hours as needed for pain control. The dose for patients who weighed 75kg or more was 1-2 tablets (15-30 mg) every 3-4 hours for pain control. Morphine was the preferred rescue medication. | 0-48 hours) |
| Total Use of Opioid Rescue Analgesia - Morphine Equivalence (mg) | Dosages of 1 to 2 mg per dose were titrated to patient comfort according to institutional standards and at the investigator's discretion. Once patients could tolerate oral medication, they were offered oral morphine (15 mg tablets) as rescue analgesia if necessary. The dose for patients who weighed less than 75kg was 15mg every 3 to 4 hours as needed for pain control. The dose for patients who weighed 75kg or more was 1-2 tablets (15-30 mg) every 3-4 hours for pain control. Morphine was the preferred rescue medication. | 0-72 hours |
|
Bupivacaine, Anesthetics, Local, Anesthetics, Central Nervous System Depressants, Physiological Effects of Drugs, Sensory System Agents, Peripheral Nervous System Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug: Bupivacaine Collagen Sponge<br>bupivacaine collagen sponges | Drug: 5x5cm bupivacaine collagen sponges<br> <br> * Other names: Bupivacaine collagen implant;|
|
Assess the Feasibility and Efficacy of the CollaRx® Bupivacaine Implant Laparoscopic Inguinal or Umbilical Herniorrhaphy
Study Overview
=================
Brief Summary
-----------------
This study will assess pain intensity for the first 72 hrs after aggravated movement (cough) following Laparoscopic Inguinal or Umbilical Herniorrhaphy.
Detailed Description
-----------------
Inguinal herniorrhaphy is a common surgery; approximately 2,800 per million people in the United States (US) undergo the procedure annually.Common surgical methods of herniorrhaphy include open and laparoscopic placement of synthetic mesh. Studies have shown that the use of synthetic mesh greatly reduces the risk of hernia recurrence regardless of the method used for its placement. Furthermore, utilizing the laparoscopic approach for umbilical hernia repair, specifically with the use of mesh, may also reduce the risk of infection. Bupivacaine is a local anesthetic (pain medicine) that has an established safety profile. Collagen is a protein that is found in all mammals. The CollaRx Bupivacaine implant is a thin flat sponge made out of collagen that comes from cow tendons and contains bupivacaine. When inserted into a surgical site, the collagen breaks down and bupivacaine is released at the site but very little is absorbed into the blood stream. The high levels of bupivacaine at the surgical site may result in less pain for several days after surgery. This open-label study will assess pain intensity after surgery in patients who receive the CollaRx Bupivacaine implant as well as determine the feasibility of the use of the laparoscope for sponge placement in laparoscopic hernia repair.
Official Title
-----------------
A Phase II, Single-dose, Open-label Study to Investigate the Feasibility and Efficacy of the CollaRx® Bupivacaine Implant (200 mg Bupivacaine Hydrochloride) in Men After Laparoscopic Inguinal or Umbilical Herniorrhaphy
Conditions
-----------------
Hernia, Postoperative Pain
Intervention / Treatment
-----------------
* Drug: 5x5cm bupivacaine collagen sponges
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Man ≥18 years Has a planned unilateral inguinal herniorrhaphy (laparoscopy, transabdominal preperitoneal [TAPP] approach or totally extraperitoneal [TEP] approach) or laparoscopic umbilical herniorrhaphy to be performed according to standard surgical technique under general anesthesia. Willing to use opioid rescue analgesia. Exclusion Criteria: Has a known hypersensitivity to amide local anesthetics, opioids, or bovine products. Scheduled for bilateral inguinal herniorrhaphy. Undergone a prior herniorrhaphy at the location scheduled for repair. Undergone major surgery within 3 months of the scheduled herniorrhaphy.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
Male
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: laparoscope for bupivacaine sponge (200 mg bupivacaine hydrochloride) placement in laparoscopic hernia repair.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug: Bupivacaine Collagen Sponge<br>bupivacaine collagen sponges | Drug: 5x5cm bupivacaine collagen sponges<br> <br> * Other names: Bupivacaine collagen implant;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Use of Opioid Analgesia - Morphine Equivalence (mg) | Dosages of 1 to 2 mg per dose were titrated to patient comfort according to institutional standards and at the investigator's discretion. Once patients could tolerate oral medication, they were offered oral morphine (15 mg tablets) as rescue analgesia if necessary. The dose for patients who weighed less than 75kg was 15mg every 3 to 4 hours as needed for pain control. The dose for patients who weighed 75kg or more was 1-2 tablets (15-30 mg) every 3-4 hours for pain control. Morphine was the preferred rescue medication. | 0 to 24 hours after surgery |
| Total Use of Opioid Rescue Analgesia - Morphine Equivalence (mg) | Dosages of 1 to 2 mg per dose were titrated to patient comfort according to institutional standards and at the investigator's discretion. Once patients could tolerate oral medication, they were offered oral morphine (15 mg tablets) as rescue analgesia if necessary. The dose for patients who weighed less than 75kg was 15mg every 3 to 4 hours as needed for pain control. The dose for patients who weighed 75kg or more was 1-2 tablets (15-30 mg) every 3-4 hours for pain control. Morphine was the preferred rescue medication. | 25-48 hours |
| Total Use of Opioid Rescue Analgesia - Morphine Equivalence (mg) | Dosages of 1 to 2 mg per dose were titrated to patient comfort according to institutional standards and at the investigator's discretion. Once patients could tolerate oral medication, they were offered oral morphine (15 mg tablets) as rescue analgesia if necessary. The dose for patients who weighed less than 75kg was 15mg every 3 to 4 hours as needed for pain control. The dose for patients who weighed 75kg or more was 1-2 tablets (15-30 mg) every 3-4 hours for pain control. Morphine was the preferred rescue medication. | 49-72 Hours |
| Total Use of Opioid Rescue Analgesia Morphine Equivalence (mg) | Dosages of 1 to 2 mg per dose were titrated to patient comfort according to institutional standards and at the investigator's discretion. Once patients could tolerate oral medication, they were offered oral morphine (15 mg tablets) as rescue analgesia if necessary. The dose for patients who weighed less than 75kg was 15mg every 3 to 4 hours as needed for pain control. The dose for patients who weighed 75kg or more was 1-2 tablets (15-30 mg) every 3-4 hours for pain control. Morphine was the preferred rescue medication. | 0-48 hours) |
| Total Use of Opioid Rescue Analgesia - Morphine Equivalence (mg) | Dosages of 1 to 2 mg per dose were titrated to patient comfort according to institutional standards and at the investigator's discretion. Once patients could tolerate oral medication, they were offered oral morphine (15 mg tablets) as rescue analgesia if necessary. The dose for patients who weighed less than 75kg was 15mg every 3 to 4 hours as needed for pain control. The dose for patients who weighed 75kg or more was 1-2 tablets (15-30 mg) every 3-4 hours for pain control. Morphine was the preferred rescue medication. | 0-72 hours |
|
||
NCT00045721
|
Carmustine Implants and O(6)-Benzylguanine in Treating Children With Recurrent Malignant Glioma
|
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemotherapy placed into the surrounding tissue after surgery to remove the tumor may kill any remaining tumor cells. O(6)-benzylguanine may increase the effectiveness of carmustine by making tumor cells more sensitive to the drug.~PURPOSE: Phase I trial to study the safety of combining O(6)-benzylguanine with carmustine implants in treating children who have recurrent malignant glioma.
|
OBJECTIVES:~Determine the dose of O(6)-benzylguanine that reliably inhibits alkylguanine-DNA alkyltransferase activity in pediatric patients with recurrent malignant glioma.~Describe the toxic effects of O(6)-benzylguanine with carmustine implant (Gliadel) in these patients.~Investigate antitumor response in patients treated with this regimen.~Characterize the pharmacokinetics of O(6)-benzylguanine when administered continuously over a 9-day period.~OUTLINE: This is a multicenter, dose-escalation study of O(6)-benzylguanine.~Patients receive O(6)-benzylguanine (O6-BG) IV over 1 hour immediately followed by O6-BG IV continuously for 9 days. Two days after initiation of continuous infusion of O6-BG, patients undergo maximal tumor debulking. At the time of surgery, patients receive up to 8 polifeprosan 20 wafers with carmustine (Gliadel) implanted into the resection cavity.~Cohorts of up to 14 patients receive escalating doses of continuous infusion O6-BG until the optimally biologically effective dose (BED) is determined. The BED is defined as the dose at which at least 11 of 14 patients meet the target of complete suppression of alkylguanine-DNA alkyltransferase levels.~Patients are followed at day 11, at weeks 2, 4, 6, 8, and 12, at months 6, 9, and 12, every 6 months for 4 years, and then annually for 5 years.~PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study within 2 years.
|
Phase I Trial of GLIADEL and O(6)-Benzylguanine in Pediatric Patients With Recurrent Malignant Gliomas
|
Brain and Central Nervous System Tumors
|
* Drug: O6-benzylguanine
* Drug: polifeprosan 20 with carmustine implant
* Procedure: adjuvant therapy
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy
|
DISEASE CHARACTERISTICS:~Histologically confirmed progressive supratentorial anaplastic astrocytoma or glioblastoma multiforme~No multifocal disease or leptomeningeal dissemination of tumor~No evidence of tumor crossing midline~Limited intraventricular involvement~Measurable unilateral mass at least 10 mm by contrast-enhanced MRI~Received prior involved-field radiotherapy as a component of prior therapy~Amenable to and in need of significant debulking~PATIENT CHARACTERISTICS:~Age~3 to 21~Performance status~Karnofsky 60-100% OR~Lansky 60-100%~Life expectancy~More than 8 weeks~Hematopoietic~Absolute neutrophil count greater than 1,000/mm3*~Platelet count greater than 100,000/mm3*~Hemoglobin greater than 8 g/dL (transfusions allowed) NOTE: * Transfusion independent~Hepatic~Bilirubin no greater than 1.5 times normal~AST and ALT less than 3 times normal~Albumin at least 2 g/dL~No overt hepatic disease~Renal~Creatinine clearance no greater than 1.5 times normal OR~Glomerular filtration rate greater than 70 mL/min~No overt renal disease~Cardiovascular~No overt cardiac disease~Pulmonary~No overt pulmonary disease~Other~Neurological deficits must be stable for at least the past week~No uncontrolled infection~No known hypersensitivity to nitrosoureas or polyethylene glycol~Not pregnant or nursing~Negative pregnancy test~Fertile patients must use effective contraception~PRIOR CONCURRENT THERAPY:~Biologic therapy~At least 6 months since prior bone marrow transplantation~More than 2 weeks since prior colony-stimulating growth factors (e.g., filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa)~Chemotherapy~No more than 2 prior cytotoxic chemotherapy regimens~No more than 3 prior chemotherapy regimens total~More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered~Prior systemic carmustine (or other nitrosourea) allowed provided patient did not experience non-hematopoietic grade III/IV toxicity~Endocrine therapy~Concurrent dexamethasone allowed if on a stable dose for at least the past week~Radiotherapy~See Disease Characteristics~At least 3 months since prior radiotherapy~No prior craniospinal irradiation for metastatic disease~Surgery~See Disease Characteristics~Prior biopsy or cytoreductive surgery allowed~Other~Concurrent anticonvulsants allowed~No other concurrent anticancer or investigational drugs
|
3 Years
|
21 Years
|
All
|
No
|
Primary Purpose: Treatment
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biologically effective dose of O(6)-benzylguanine administered continuously in pediatric patients with recurrent malignant glioma | | |
| Toxicities associated with the administration of O(6)-benzylguanine and carmustine implants. | | |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response | | |
|
recurrent childhood cerebral astrocytoma
|
Carmustine, O(6)-benzylguanine, Antineoplastic Agents, Alkylating, Alkylating Agents, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents, Enzyme Inhibitors
|
| Intervention/Treatment |
| --- |
|Drug: O6-benzylguanine|nan|
|Drug: polifeprosan 20 with carmustine implant|nan|
|Procedure: adjuvant therapy|nan|
|Procedure: conventional surgery|nan|
|Procedure: neoadjuvant therapy|nan|
|
Carmustine Implants and O(6)-Benzylguanine in Treating Children With Recurrent Malignant Glioma
Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemotherapy placed into the surrounding tissue after surgery to remove the tumor may kill any remaining tumor cells. O(6)-benzylguanine may increase the effectiveness of carmustine by making tumor cells more sensitive to the drug. PURPOSE: Phase I trial to study the safety of combining O(6)-benzylguanine with carmustine implants in treating children who have recurrent malignant glioma.
Detailed Description
-----------------
OBJECTIVES: Determine the dose of O(6)-benzylguanine that reliably inhibits alkylguanine-DNA alkyltransferase activity in pediatric patients with recurrent malignant glioma. Describe the toxic effects of O(6)-benzylguanine with carmustine implant (Gliadel) in these patients. Investigate antitumor response in patients treated with this regimen. Characterize the pharmacokinetics of O(6)-benzylguanine when administered continuously over a 9-day period. OUTLINE: This is a multicenter, dose-escalation study of O(6)-benzylguanine. Patients receive O(6)-benzylguanine (O6-BG) IV over 1 hour immediately followed by O6-BG IV continuously for 9 days. Two days after initiation of continuous infusion of O6-BG, patients undergo maximal tumor debulking. At the time of surgery, patients receive up to 8 polifeprosan 20 wafers with carmustine (Gliadel) implanted into the resection cavity. Cohorts of up to 14 patients receive escalating doses of continuous infusion O6-BG until the optimally biologically effective dose (BED) is determined. The BED is defined as the dose at which at least 11 of 14 patients meet the target of complete suppression of alkylguanine-DNA alkyltransferase levels. Patients are followed at day 11, at weeks 2, 4, 6, 8, and 12, at months 6, 9, and 12, every 6 months for 4 years, and then annually for 5 years. PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study within 2 years.
Official Title
-----------------
Phase I Trial of GLIADEL and O(6)-Benzylguanine in Pediatric Patients With Recurrent Malignant Gliomas
Conditions
-----------------
Brain and Central Nervous System Tumors
Intervention / Treatment
-----------------
* Drug: O6-benzylguanine
* Drug: polifeprosan 20 with carmustine implant
* Procedure: adjuvant therapy
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy
Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed progressive supratentorial anaplastic astrocytoma or glioblastoma multiforme No multifocal disease or leptomeningeal dissemination of tumor No evidence of tumor crossing midline Limited intraventricular involvement Measurable unilateral mass at least 10 mm by contrast-enhanced MRI Received prior involved-field radiotherapy as a component of prior therapy Amenable to and in need of significant debulking PATIENT CHARACTERISTICS: Age 3 to 21 Performance status Karnofsky 60-100% OR Lansky 60-100% Life expectancy More than 8 weeks Hematopoietic Absolute neutrophil count greater than 1,000/mm3* Platelet count greater than 100,000/mm3* Hemoglobin greater than 8 g/dL (transfusions allowed) NOTE: * Transfusion independent Hepatic Bilirubin no greater than 1.5 times normal AST and ALT less than 3 times normal Albumin at least 2 g/dL No overt hepatic disease Renal Creatinine clearance no greater than 1.5 times normal OR Glomerular filtration rate greater than 70 mL/min No overt renal disease Cardiovascular No overt cardiac disease Pulmonary No overt pulmonary disease Other Neurological deficits must be stable for at least the past week No uncontrolled infection No known hypersensitivity to nitrosoureas or polyethylene glycol Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy At least 6 months since prior bone marrow transplantation More than 2 weeks since prior colony-stimulating growth factors (e.g., filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa) Chemotherapy No more than 2 prior cytotoxic chemotherapy regimens No more than 3 prior chemotherapy regimens total More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered Prior systemic carmustine (or other nitrosourea) allowed provided patient did not experience non-hematopoietic grade III/IV toxicity Endocrine therapy Concurrent dexamethasone allowed if on a stable dose for at least the past week Radiotherapy See Disease Characteristics At least 3 months since prior radiotherapy No prior craniospinal irradiation for metastatic disease Surgery See Disease Characteristics Prior biopsy or cytoreductive surgery allowed Other Concurrent anticonvulsants allowed No other concurrent anticancer or investigational drugs
Ages Eligible for Study
-----------------
Minimum Age: 3 Years
Maximum Age: 21 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Arms and Interventions
| Intervention/Treatment |
| --- |
|Drug: O6-benzylguanine|nan|
|Drug: polifeprosan 20 with carmustine implant|nan|
|Procedure: adjuvant therapy|nan|
|Procedure: conventional surgery|nan|
|Procedure: neoadjuvant therapy|nan|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biologically effective dose of O(6)-benzylguanine administered continuously in pediatric patients with recurrent malignant glioma | | |
| Toxicities associated with the administration of O(6)-benzylguanine and carmustine implants. | | |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response | | |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent childhood cerebral astrocytoma
|
NCT02563834
|
A Novel Positron Emission Tomography (PET) Approach to Measuring Myocardial Metabolism
|
Studies of myocardial fuel selection using a novel palmitate-based PET probe
|
A novel Positron Emission Tomography (PET) probe, 16- 18-F-fluoro-4-thiapalmitate, will be used to evaluate myocardial atty acid uptake. Studies will be done in humans with type 2 diabetes mellitus, and in controls. Studies will take place on 2 separate days, under fasting conditions and under insulin clamp conditions.
|
A Novel Positron Emission Tomography (PET) Approach to Measuring Myocardial Metabolism
|
Type 2 Diabetes Mellitus
|
* Drug: thiapalmitate tracer
* Drug: Saline
* Drug: Insulin
|
Inclusion Criteria:~Lean:~BMI<25 kg/m2~normal glucose tolerance by 75g oral glucose tolerance test~Type 2 diabetes mellitus:~BMI >25 kg/m2~previously diagnosed type 2 diabetes mellitus~on oral and/or injected insulin treatment.~Exclusion Criteria:~Lean:~*Use of any chronic medications~Type 2 diabetes mellitus~known microvascular disease~known coronary or other macro vascular disease~use of PPARgamma class antidiabetic agents within 6 months
|
18 Years
|
45 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial Fatty Acid Uptake Rate | PET measure of fatty acid uptake rate | 4 Hours |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial Oxidation Rate | PET measure of total oxidation rate | 4 Hours |
| Myocardial Perfusion Rate | PET measure of total myocardial perfusion (blood flow) | 4 Hours |
|
Insulin, Hypoglycemic Agents, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Saline<br>Studies will be performed on one day under fasting conditions, using a saline infusion. All subjects will receive infusions of radiolabeled acetate and radiolabeled thiapalmitate tracer (16-18-F-fluoro-4-thiapalmitate). | Drug: thiapalmitate tracer<br>* Radiolabeled tracer infusion; occurs in all treatment arms<br>* Other names: 16- 18-F-fluoro-4-thiapalmitate;Drug: Saline<br>* Saline infusion for control<br>|
| Experimental: Insulin Clamp<br>Studies will be performed on a separate day under fasting conditions, using an insulin infusion to achieve steady state insulin/glucose clamp conditions. Studies will be performed on one day under fasting conditions, using a saline infusion. All subjects will receive infusions of radiolabeled acetate and radiolabeled thiapalmitate tracer (16-18-F-fluoro-4-thiapalmitate). | Drug: thiapalmitate tracer<br>* Radiolabeled tracer infusion; occurs in all treatment arms<br>* Other names: 16- 18-F-fluoro-4-thiapalmitate;Drug: Insulin<br>* Insulin infusion for insulin/glucose clamp procedure<br>|
|
A Novel Positron Emission Tomography (PET) Approach to Measuring Myocardial Metabolism
Study Overview
=================
Brief Summary
-----------------
Studies of myocardial fuel selection using a novel palmitate-based PET probe
Detailed Description
-----------------
A novel Positron Emission Tomography (PET) probe, 16- 18-F-fluoro-4-thiapalmitate, will be used to evaluate myocardial atty acid uptake. Studies will be done in humans with type 2 diabetes mellitus, and in controls. Studies will take place on 2 separate days, under fasting conditions and under insulin clamp conditions.
Official Title
-----------------
A Novel Positron Emission Tomography (PET) Approach to Measuring Myocardial Metabolism
Conditions
-----------------
Type 2 Diabetes Mellitus
Intervention / Treatment
-----------------
* Drug: thiapalmitate tracer
* Drug: Saline
* Drug: Insulin
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Lean: BMI<25 kg/m2 normal glucose tolerance by 75g oral glucose tolerance test Type 2 diabetes mellitus: BMI >25 kg/m2 previously diagnosed type 2 diabetes mellitus on oral and/or injected insulin treatment. Exclusion Criteria: Lean: *Use of any chronic medications Type 2 diabetes mellitus known microvascular disease known coronary or other macro vascular disease use of PPARgamma class antidiabetic agents within 6 months
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Saline<br>Studies will be performed on one day under fasting conditions, using a saline infusion. All subjects will receive infusions of radiolabeled acetate and radiolabeled thiapalmitate tracer (16-18-F-fluoro-4-thiapalmitate). | Drug: thiapalmitate tracer<br>* Radiolabeled tracer infusion; occurs in all treatment arms<br>* Other names: 16- 18-F-fluoro-4-thiapalmitate;Drug: Saline<br>* Saline infusion for control<br>|
| Experimental: Insulin Clamp<br>Studies will be performed on a separate day under fasting conditions, using an insulin infusion to achieve steady state insulin/glucose clamp conditions. Studies will be performed on one day under fasting conditions, using a saline infusion. All subjects will receive infusions of radiolabeled acetate and radiolabeled thiapalmitate tracer (16-18-F-fluoro-4-thiapalmitate). | Drug: thiapalmitate tracer<br>* Radiolabeled tracer infusion; occurs in all treatment arms<br>* Other names: 16- 18-F-fluoro-4-thiapalmitate;Drug: Insulin<br>* Insulin infusion for insulin/glucose clamp procedure<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial Fatty Acid Uptake Rate | PET measure of fatty acid uptake rate | 4 Hours |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial Oxidation Rate | PET measure of total oxidation rate | 4 Hours |
| Myocardial Perfusion Rate | PET measure of total myocardial perfusion (blood flow) | 4 Hours |
|
|
NCT00006270
|
Study of the Approximate Entropy of Adrenocorticotropic Hormone and Cortisol Secretion in Patients With Head Injury
|
OBJECTIVES: I. Determine the randomness of adrenocorticotropic hormone (ACTH) and cortisol secretion using approximate entropy in patients who have sustained a head injury.~II. Determine the correlation between randomness of ACTH and cortisol secretion and stages of sleep in these patients.
|
PROTOCOL OUTLINE: Patients are stratified according to type of injury (closed head injury due to trauma vs vascular accidents). Patients are admitted two times for overnight assessment.~Admission 1: Patients receive cosyntropin IV. Blood is drawn at 30 and 60 minutes after IV infusion. Patients receive oral metyrapone before sleep. A sham sleep study is conducted through the night and patients' blood is drawn in the morning.~Admission 2: At least 2 weeks after admission 1, patients return for an overnight admission. Starting in the evening, blood is drawn every 15 minutes for 12 hours. A sleep study is conducted through the night.
| null |
Brain Injury, Craniocerebral Trauma
|
* Drug: cosyntropin
* Drug: metyrapone
|
PROTOCOL ENTRY CRITERIA:~--Disease Characteristics--~Patients who have sustained head injury~Closed head injury from trauma OR~Vascular accidents like strokes and hemorrhages~--Prior/Concurrent Therapy--~Endocrine therapy: No concurrent cortisol replacement~Other: No blood donation during and for 1 month after study~--Patient Characteristics--~Hematopoietic: Hemoglobin normal~Other:~No hypopituitarism~No body mass index of 28 or greater~Not pregnant or nursing~Must have normal menstrual cycles~No severe mental impairment~Must not require legal guardian
|
20 Years
|
35 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
brain injury, neurologic and psychiatric disorders, rare disease
|
Cosyntropin, Metyrapone, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs, Antimetabolites, Molecular Mechanisms of Pharmacological Action, Enzyme Inhibitors
|
| Intervention/Treatment |
| --- |
|Drug: cosyntropin|nan|
|Drug: metyrapone|nan|
|
Study of the Approximate Entropy of Adrenocorticotropic Hormone and Cortisol Secretion in Patients With Head Injury
Study Overview
=================
Brief Summary
-----------------
OBJECTIVES: I. Determine the randomness of adrenocorticotropic hormone (ACTH) and cortisol secretion using approximate entropy in patients who have sustained a head injury. II. Determine the correlation between randomness of ACTH and cortisol secretion and stages of sleep in these patients.
Detailed Description
-----------------
PROTOCOL OUTLINE: Patients are stratified according to type of injury (closed head injury due to trauma vs vascular accidents). Patients are admitted two times for overnight assessment. Admission 1: Patients receive cosyntropin IV. Blood is drawn at 30 and 60 minutes after IV infusion. Patients receive oral metyrapone before sleep. A sham sleep study is conducted through the night and patients' blood is drawn in the morning. Admission 2: At least 2 weeks after admission 1, patients return for an overnight admission. Starting in the evening, blood is drawn every 15 minutes for 12 hours. A sleep study is conducted through the night.
Conditions
-----------------
Brain Injury, Craniocerebral Trauma
Intervention / Treatment
-----------------
* Drug: cosyntropin
* Drug: metyrapone
Participation Criteria
=================
Eligibility Criteria
-----------------
PROTOCOL ENTRY CRITERIA: --Disease Characteristics-- Patients who have sustained head injury Closed head injury from trauma OR Vascular accidents like strokes and hemorrhages --Prior/Concurrent Therapy-- Endocrine therapy: No concurrent cortisol replacement Other: No blood donation during and for 1 month after study --Patient Characteristics-- Hematopoietic: Hemoglobin normal Other: No hypopituitarism No body mass index of 28 or greater Not pregnant or nursing Must have normal menstrual cycles No severe mental impairment Must not require legal guardian
Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 35 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Intervention/Treatment |
| --- |
|Drug: cosyntropin|nan|
|Drug: metyrapone|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
-----------------
brain injury, neurologic and psychiatric disorders, rare disease
|
||
NCT00443833
|
Genetic Analysis of Thyrotoxic Periodic Paralysis
|
Thyrotoxic periodic paralysis (TPP) is characterized by episodes of reversible hypokalemia and weakness in thyrotoxic patients. It is commonly found in males of Asian descent and is also seen in individuals having Native American or Hispanic ancestry. Therefore genetic etiology has been hypothesized. This study, we aim to find the susceptibility genes that associate with TPP. Both candidate genes approach and genome wide association study have been conducted.
|
This study is a genetic association study. It included 50 cases of TPP patients and 80 cases of male, hyperthyroid patients who didn't have hypokalemia as a well characterized controls. After informed consent were obtained, genomic DNA from leukocyte were extracted. Pooled DNA were constructed and whole genome scan using 10K GeneChip microarray were genotyped on pooled genomic DNA.
|
Genetic Analysis of Thai Patients With Thyrotoxic Periodic Paralysis
|
Thyrotoxic Periodic Paralysis
|
Inclusion Criteria:~TPP~Hyperthyroid patients from any causes~Evidence of hypokalemia (k<3.5 mg/dl)from intracellular shift (Urine K<15 mg/dl, TTKG<2)~Episodic paralysis~Exclusion Criteria:~Hypokalemia from GI or renal loss
|
15 Years
| null |
Male
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
Thyrotoxicosis, genetic association study, periodic paralysis, whole genome scan
|
Paralysis, Neurologic Manifestations, Nervous System Diseases
|
Genetic Analysis of Thyrotoxic Periodic Paralysis
Study Overview
=================
Brief Summary
-----------------
Thyrotoxic periodic paralysis (TPP) is characterized by episodes of reversible hypokalemia and weakness in thyrotoxic patients. It is commonly found in males of Asian descent and is also seen in individuals having Native American or Hispanic ancestry. Therefore genetic etiology has been hypothesized. This study, we aim to find the susceptibility genes that associate with TPP. Both candidate genes approach and genome wide association study have been conducted.
Detailed Description
-----------------
This study is a genetic association study. It included 50 cases of TPP patients and 80 cases of male, hyperthyroid patients who didn't have hypokalemia as a well characterized controls. After informed consent were obtained, genomic DNA from leukocyte were extracted. Pooled DNA were constructed and whole genome scan using 10K GeneChip microarray were genotyped on pooled genomic DNA.
Official Title
-----------------
Genetic Analysis of Thai Patients With Thyrotoxic Periodic Paralysis
Conditions
-----------------
Thyrotoxic Periodic Paralysis
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: TPP Hyperthyroid patients from any causes Evidence of hypokalemia (k<3.5 mg/dl)from intracellular shift (Urine K<15 mg/dl, TTKG<2) Episodic paralysis Exclusion Criteria: Hypokalemia from GI or renal loss
Ages Eligible for Study
-----------------
Minimum Age: 15 Years
Sexes Eligible for Study
-----------------
Male
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
-----------------
Thyrotoxicosis, genetic association study, periodic paralysis, whole genome scan
|
||||
NCT02638818
|
Outcomes in Minimally Invasive Versus Open Pancreaticoduodenectomy
|
The purpose of this study is to evaluate the impact of the quality of life in patients undergoing the Whipple procedure (pancreaticoduodenectomy, PD) for pancreatic cancer. The Whipple procedure can be done by laparoscopic (small incisions) or an open procedure (large incision) to treat the patients cancer. The goal of this study is to see if there is any difference in quality of life between patients who undergo the laparoscopic or the open Whipple procedure. Surgical technique (minimally invasive versus open) will be at the discretion of the operating surgeon. Patients will not be randomized to a treatment arm.~A subset of these patients will also be asked to take part in a pre- and postoperative in-depth interview to explore the lived experiences of patients with resectable pancreatic cancer.
|
A Pilot Study Evaluating Health-related Quality of Life Endpoints in Patients Undergoing Minimally Invasive Versus Open Pancreaticoduodenectomy
|
Pancreatic Disease
|
* Procedure: minimally invasive pancreaticoduodenectomy
* Procedure: traditional pancreaticoduodenectomy
|
Inclusion Criteria:~All patients scheduled for pancreaticoduodenectomy will be eligible for this study.~Subject must be at least 18 years of age and at least the minimum Age of Majority according to applicable State or Country Law.~Subject is a suitable surgical candidate, i.e. is able to undergo general anesthesia and PD for diagnosis of cancer~Subject is willing and able to cooperate with survey participation.~Subject has been informed of the study procedures and the treatment and has signed an informed consent form~Exclusion Criteria:~• Subject is not a suitable candidate for PD
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in quality of life, as measured by FACT-Hep score | The summed overall FACT-Hep score (0-180) will be the primary outcome. | Baseline (before surgery), at hospital discharge (up to approximately 14 days), at first clinic visit (within 2 weeks after discharge), 3 months |
|
pancreaticoduodenectomy, Whipple
|
Pancreatic Diseases, Digestive System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| minimally invasive whipple<br>Surgical technique (minimally invasive vs open) will be at the discretion of the operating surgeon. Patients will not be randomized to a treatment arm. | Procedure: minimally invasive pancreaticoduodenectomy<br>* Surgical technique (minimally invasive versus open) will be at the discretion of the operating surgeon. Patients will not be randomized to a treatment arm.<br>|
| traditional whipple<br>Surgical technique (minimally invasive versus open) will be at the discretion of the operating surgeon. Patients will not be randomized to a treatment arm. | Procedure: traditional pancreaticoduodenectomy<br>* Surgical technique (minimally invasive versus open) will be at the discretion of the operating surgeon. Patients will not be randomized to a treatment arm.<br>|
|
Outcomes in Minimally Invasive Versus Open Pancreaticoduodenectomy
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the impact of the quality of life in patients undergoing the Whipple procedure (pancreaticoduodenectomy, PD) for pancreatic cancer. The Whipple procedure can be done by laparoscopic (small incisions) or an open procedure (large incision) to treat the patients cancer. The goal of this study is to see if there is any difference in quality of life between patients who undergo the laparoscopic or the open Whipple procedure. Surgical technique (minimally invasive versus open) will be at the discretion of the operating surgeon. Patients will not be randomized to a treatment arm. A subset of these patients will also be asked to take part in a pre- and postoperative in-depth interview to explore the lived experiences of patients with resectable pancreatic cancer.
Official Title
-----------------
A Pilot Study Evaluating Health-related Quality of Life Endpoints in Patients Undergoing Minimally Invasive Versus Open Pancreaticoduodenectomy
Conditions
-----------------
Pancreatic Disease
Intervention / Treatment
-----------------
* Procedure: minimally invasive pancreaticoduodenectomy
* Procedure: traditional pancreaticoduodenectomy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All patients scheduled for pancreaticoduodenectomy will be eligible for this study. Subject must be at least 18 years of age and at least the minimum Age of Majority according to applicable State or Country Law. Subject is a suitable surgical candidate, i.e. is able to undergo general anesthesia and PD for diagnosis of cancer Subject is willing and able to cooperate with survey participation. Subject has been informed of the study procedures and the treatment and has signed an informed consent form Exclusion Criteria: • Subject is not a suitable candidate for PD
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 |
| --- | --- |
| minimally invasive whipple<br>Surgical technique (minimally invasive vs open) will be at the discretion of the operating surgeon. Patients will not be randomized to a treatment arm. | Procedure: minimally invasive pancreaticoduodenectomy<br>* Surgical technique (minimally invasive versus open) will be at the discretion of the operating surgeon. Patients will not be randomized to a treatment arm.<br>|
| traditional whipple<br>Surgical technique (minimally invasive versus open) will be at the discretion of the operating surgeon. Patients will not be randomized to a treatment arm. | Procedure: traditional pancreaticoduodenectomy<br>* Surgical technique (minimally invasive versus open) will be at the discretion of the operating surgeon. Patients will not be randomized to a treatment arm.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in quality of life, as measured by FACT-Hep score | The summed overall FACT-Hep score (0-180) will be the primary outcome. | Baseline (before surgery), at hospital discharge (up to approximately 14 days), at first clinic visit (within 2 weeks after discharge), 3 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pancreaticoduodenectomy, Whipple
|
|||
NCT03130608
|
Inspiratory Muscle Training Post-Liver Transplant
|
Individuals with chronic liver disease develop significant muscle wasting that remains post-liver transplant. The transplant surgery additionally challenges respiratory mechanics. Respiratory muscle strength has been measured to be impaired in individuals post liver transplant. This study proposes an 8 week intervention designed to increase respiratory muscle strength and pulmonary function that we hypothesize will correlate to improved functional performance and quality of life post-liver transplant.~Pre-test post-test design, that will randomize subjects into an experimental group that will receive the inspiratory muscle strengthening exercise in addition to usual post-liver transplant care and a control group that will only receive the usual post-transplant care.~Up to 50 subjects will be recruited from the Post-Liver Transplant Outpatient Clinic at the Miami Transplant Institute.~The subjects will have repeated measurements of respiratory muscle strength, pulmonary function, functional mobility performance, and quality of life at baseline, 4 weeks, and 8 weeks.
|
Comparison of Inspiratory Muscle Training and Usual Care in Individuals Post-Liver Transplant
|
Liver Disease Chronic, Muscle Weakness, Respiratory Insufficiency
|
* Other: Inspiratory Muscle Training
|
Inclusion Criteria:~1. Subjects must have undergone liver transplantation for chronic liver disease of any origin other than cancer.~Exclusion Criteria:~Severe cardiopulmonary disease such as recent Myocardial infarction, Congestive Heart Failure, Pulmonary edema, Chronic Obstructive Pulmonary Disease, and Asthma,~Severe osteoarthritis~Blindness~Wheelchair bound individuals~Individuals with neurological / neuromuscular disorders including but not limited to: cerebral vascular accident, Parkinsonism, Alzheimer's disease, dystonia, multiple sclerosis, and polio.~Severe Cognitive impairment where individuals cannot follow commands and are unable to sign informed consent -
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline Maximal Inspiratory Pressure (MIP) at 4 weeks and 8 weeks. | MIP is a measure of inspiratory muscle strength . Inspiratory testing will be performed using a Micro Mouth Pressure Manometer. 92887) Measurements will be performed in the testing position with subjects in the seated position and the trunk at a 90 degree angle to the hips. Subjects will wear a nose clip during testing.~Each measurement will be performed 3 times with the maximal score recorded. | Baseline, 4 weeks, and 8 weeks. |
| Change from baseline Forced Expiratory Volume (FEV1) at 4 weeks and 8 weeks | FEV1 is how much air can be exhaled during a forced exhalation at one second. Inspiratory testing will be performed using a Micro Mouth Pressure Manometer. 92887) Measurements will be performed in the testing position with subjects in the seated position and the trunk at a 90 degree angle to the hips. Subjects will wear a nose clip during testing.~Each measurement will be performed 3 times with the maximal score recorded. | Baseline, 4th week, and 8th week |
| Change from baseline 6 Minute Walk Distance at 4 weeks and 8 weeks. | In a 100ft. straight hallway the subject will walk back and forth, from one end to the other, as many times as they can in 6 minutes. The subject will have the option to rest at any time during the six minutes. The clock will keep running whether the subject is walking or resting. The subject will be provided standardized cues to prevent unequal encouragement. The distance walked over the 6 minutes will be recorded. Throughout the walking test, the investigator will be walking nearby to guard patient from loss of balance or fall. | Baseline, 4 weeks, and 8 weeks |
| Change from baseline 30 Second Chair Stand Repetitions at 4 weeks and 8 weeks. | From a straight back chair the subject will come to a complete stand and then return to sitting with arms across chest. The number of times the subject can stand in 30 seconds will be recorded. The investigator will be standing nearby guarding the subject to protect from any loss of balance or fall. | Baseline, 4 weeks, and 8 weeks |
| Change from baseline Chronic Liver Disease Questionnaire (CLDQ) Score at 4 weeks and 8 weeks. | This is a paper and pencil questionnaire consisting of 29 items in 6 domains: 1) Abdominal Symptoms 2) Activity: eating habits and movement of heavy objects 3) Emotional Function 4) Fatigue: perception of decreased energy and sleepiness 5) Systemic symptoms 6) Worry: concerns regarding disease progression and family. Summary scores for each domain range from 1(most impaired) to 7 (least impaired). All items refer to the previous 2 weeks. Higher scores indicate less impairment. | Baseline, 4 weeks, and 8 weeks |
| Change from baseline Karnovsky Performance Status Score at 4 weeks and 8 weeks. | This is a paper pencil questionnaire measuring functional impairment. The questionnaire is divided into three groups for classifying patient's ability to work, to carry on normal activity, and to care for themselves. The groups are further divided into eleven categories covering all level so functioning from normal (100) to dead (0). The lower the Karnovsky score, the worse the functional ability and survival for most serious illness. The liver transplant team records this measure prior to transplant. We will obtained pre-transplant scores from medical record for use in correlational analysis. This measure will also performed at baseline and post-testing. | Baseline, 4 weeks, and 8 weeks |
| Change from baseline Sustained Maximal Inspiratory Pressure (SMIP) at 4 weeks and 8 weeks. | SMIP will be measured from residual volume to total lung capacity representing single breath work/endurance. Inspiratory testing will be performed using a Micro Mouth Pressure Manometer. 92887) Measurements will be performed in the testing position with subjects in the seated position and the trunk at a 90 degree angle to the hips. Subjects will wear a nose clip during testing. | Baseline, 4 weeks, and 8 weeks |
| Change from baseline Inspiratory Duration (ID) at 4 weeks and 8 weeks | ID is the inspiratory flow during maximal inspiration effort with an isokinetic like resistance from the mouthpiece. Inspiratory testing will be performed using a Micro Mouth Pressure Manometer. 92887) Measurements will be performed in the testing position with subjects in the seated position and the trunk at a 90 degree angle to the hips. Subjects will wear a nose clip during testing. | Baseline, 4 weeks, and 8 weeks |
| Change from baseline Maximal Expiratory Pressure (MEP) at 4 weeks and 8 weeks. | MEP is a measure of expiratory muscle strength measured from total lung capacity. Inspiratory testing will be performed using a Micro Mouth Pressure Manometer. 92887) Measurements will be performed in the testing position with subjects in the seated position and the trunk at a 90 degree angle to the hips. Subjects will wear a nose clip during testing. | Baseline, 4 weeks, and 8 weeks |
| Change from baseline Forced Vital Capacity (FVC) at 4 weeks and 8 weeks. | FVC is the total amount of air exhaled during a pulmonary function test. Expiratory testing will be performed using the Jones Satellite Spirometer (Jones Medical Instrument Company, Oakbrook, Illinois 65021) Measurements will be performed in the manner described using American Thoracic Society guidelines with subjects in the seated position and the trunk at a 90 degree angle to the hips. Subjects will wear a nose clip during testing.~Each measurement will be performed 3 times with the maximal score recorded. | Baseline, 4 weeks, 8 weeks. |
| Change from baseline Forced Expiratory Flow (FEF25-75%) at 4weeks and 8 weeks. | FEF25-75% is the flow rate at 25% to 75% of Forced Vital Capacity. Expiratory testing will be performed using the Jones Satellite Spirometer (Jones Medical Instrument Company, Oakbrook, Illinois 65021) Measurements will be performed in the manner described using American Thoracic Society guidelines with subjects in the seated position and the trunk at a 90 degree angle to the hips. Subjects will wear a nose clip during testing.~Each measurement will be performed 3 times with the maximal score recorded. | Baseline, 4 weeks, 8 weeks. |
| Change from baseline Peak Expiratory Flow Rate (PEFR) at 4weeks and 8 weeks. | PEFR is a measure of how fast a person can exhale. Expiratory testing will be performed using the Jones Satellite Spirometer (Jones Medical Instrument Company, Oakbrook, Illinois 65021) Measurements will be performed in the manner described using American Thoracic Society guidelines with subjects in the seated position and the trunk at a 90 degree angle to the hips. Subjects will wear a nose clip during testing.~Each measurement will be performed 3 times with the maximal score recorded. | Baseline, 4 weeks, 8 weeks. |
|
liver disease, transplant, muscle wasting, breathing exercise
|
Liver Diseases, Neuromuscular Manifestations, Neurologic Manifestations, Muscle Weakness, Respiratory Insufficiency, Digestive System Diseases, Respiration Disorders, Respiratory Tract Diseases, Pathologic Processes, Muscular Diseases, Musculoskeletal Diseases, Nervous System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inspiratory Muscle Training<br>The experimental group will perform Inspiratory Muscle Training (IMT) using a THRESHOLD device, a simple hand held one way valve.~In addition, the experimental group will gradually increase their activity as part of their usual care post-transplant. | Other: Inspiratory Muscle Training<br>* Subjects will breath through a hand held valve that has adjustable resistance to strengthen the muscles used for breathing. Subjects will perform the exercise approximately 20-30 minutes, twice a day for 8 weeks.<br>|
| No Intervention: Usual Care<br>Receive the usual post-liver transplant care of gradually increase their activity. | |
|
Inspiratory Muscle Training Post-Liver Transplant
Study Overview
=================
Brief Summary
-----------------
Individuals with chronic liver disease develop significant muscle wasting that remains post-liver transplant. The transplant surgery additionally challenges respiratory mechanics. Respiratory muscle strength has been measured to be impaired in individuals post liver transplant. This study proposes an 8 week intervention designed to increase respiratory muscle strength and pulmonary function that we hypothesize will correlate to improved functional performance and quality of life post-liver transplant. Pre-test post-test design, that will randomize subjects into an experimental group that will receive the inspiratory muscle strengthening exercise in addition to usual post-liver transplant care and a control group that will only receive the usual post-transplant care. Up to 50 subjects will be recruited from the Post-Liver Transplant Outpatient Clinic at the Miami Transplant Institute. The subjects will have repeated measurements of respiratory muscle strength, pulmonary function, functional mobility performance, and quality of life at baseline, 4 weeks, and 8 weeks.
Official Title
-----------------
Comparison of Inspiratory Muscle Training and Usual Care in Individuals Post-Liver Transplant
Conditions
-----------------
Liver Disease Chronic, Muscle Weakness, Respiratory Insufficiency
Intervention / Treatment
-----------------
* Other: Inspiratory Muscle Training
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Subjects must have undergone liver transplantation for chronic liver disease of any origin other than cancer. Exclusion Criteria: Severe cardiopulmonary disease such as recent Myocardial infarction, Congestive Heart Failure, Pulmonary edema, Chronic Obstructive Pulmonary Disease, and Asthma, Severe osteoarthritis Blindness Wheelchair bound individuals Individuals with neurological / neuromuscular disorders including but not limited to: cerebral vascular accident, Parkinsonism, Alzheimer's disease, dystonia, multiple sclerosis, and polio. Severe Cognitive impairment where individuals cannot follow commands and are unable to sign 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
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inspiratory Muscle Training<br>The experimental group will perform Inspiratory Muscle Training (IMT) using a THRESHOLD device, a simple hand held one way valve. In addition, the experimental group will gradually increase their activity as part of their usual care post-transplant. | Other: Inspiratory Muscle Training<br>* Subjects will breath through a hand held valve that has adjustable resistance to strengthen the muscles used for breathing. Subjects will perform the exercise approximately 20-30 minutes, twice a day for 8 weeks.<br>|
| No Intervention: Usual Care<br>Receive the usual post-liver transplant care of gradually increase their activity. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline Maximal Inspiratory Pressure (MIP) at 4 weeks and 8 weeks. | MIP is a measure of inspiratory muscle strength . Inspiratory testing will be performed using a Micro Mouth Pressure Manometer. 92887) Measurements will be performed in the testing position with subjects in the seated position and the trunk at a 90 degree angle to the hips. Subjects will wear a nose clip during testing. Each measurement will be performed 3 times with the maximal score recorded. | Baseline, 4 weeks, and 8 weeks. |
| Change from baseline Forced Expiratory Volume (FEV1) at 4 weeks and 8 weeks | FEV1 is how much air can be exhaled during a forced exhalation at one second. Inspiratory testing will be performed using a Micro Mouth Pressure Manometer. 92887) Measurements will be performed in the testing position with subjects in the seated position and the trunk at a 90 degree angle to the hips. Subjects will wear a nose clip during testing. Each measurement will be performed 3 times with the maximal score recorded. | Baseline, 4th week, and 8th week |
| Change from baseline 6 Minute Walk Distance at 4 weeks and 8 weeks. | In a 100ft. straight hallway the subject will walk back and forth, from one end to the other, as many times as they can in 6 minutes. The subject will have the option to rest at any time during the six minutes. The clock will keep running whether the subject is walking or resting. The subject will be provided standardized cues to prevent unequal encouragement. The distance walked over the 6 minutes will be recorded. Throughout the walking test, the investigator will be walking nearby to guard patient from loss of balance or fall. | Baseline, 4 weeks, and 8 weeks |
| Change from baseline 30 Second Chair Stand Repetitions at 4 weeks and 8 weeks. | From a straight back chair the subject will come to a complete stand and then return to sitting with arms across chest. The number of times the subject can stand in 30 seconds will be recorded. The investigator will be standing nearby guarding the subject to protect from any loss of balance or fall. | Baseline, 4 weeks, and 8 weeks |
| Change from baseline Chronic Liver Disease Questionnaire (CLDQ) Score at 4 weeks and 8 weeks. | This is a paper and pencil questionnaire consisting of 29 items in 6 domains: 1) Abdominal Symptoms 2) Activity: eating habits and movement of heavy objects 3) Emotional Function 4) Fatigue: perception of decreased energy and sleepiness 5) Systemic symptoms 6) Worry: concerns regarding disease progression and family. Summary scores for each domain range from 1(most impaired) to 7 (least impaired). All items refer to the previous 2 weeks. Higher scores indicate less impairment. | Baseline, 4 weeks, and 8 weeks |
| Change from baseline Karnovsky Performance Status Score at 4 weeks and 8 weeks. | This is a paper pencil questionnaire measuring functional impairment. The questionnaire is divided into three groups for classifying patient's ability to work, to carry on normal activity, and to care for themselves. The groups are further divided into eleven categories covering all level so functioning from normal (100) to dead (0). The lower the Karnovsky score, the worse the functional ability and survival for most serious illness. The liver transplant team records this measure prior to transplant. We will obtained pre-transplant scores from medical record for use in correlational analysis. This measure will also performed at baseline and post-testing. | Baseline, 4 weeks, and 8 weeks |
| Change from baseline Sustained Maximal Inspiratory Pressure (SMIP) at 4 weeks and 8 weeks. | SMIP will be measured from residual volume to total lung capacity representing single breath work/endurance. Inspiratory testing will be performed using a Micro Mouth Pressure Manometer. 92887) Measurements will be performed in the testing position with subjects in the seated position and the trunk at a 90 degree angle to the hips. Subjects will wear a nose clip during testing. | Baseline, 4 weeks, and 8 weeks |
| Change from baseline Inspiratory Duration (ID) at 4 weeks and 8 weeks | ID is the inspiratory flow during maximal inspiration effort with an isokinetic like resistance from the mouthpiece. Inspiratory testing will be performed using a Micro Mouth Pressure Manometer. 92887) Measurements will be performed in the testing position with subjects in the seated position and the trunk at a 90 degree angle to the hips. Subjects will wear a nose clip during testing. | Baseline, 4 weeks, and 8 weeks |
| Change from baseline Maximal Expiratory Pressure (MEP) at 4 weeks and 8 weeks. | MEP is a measure of expiratory muscle strength measured from total lung capacity. Inspiratory testing will be performed using a Micro Mouth Pressure Manometer. 92887) Measurements will be performed in the testing position with subjects in the seated position and the trunk at a 90 degree angle to the hips. Subjects will wear a nose clip during testing. | Baseline, 4 weeks, and 8 weeks |
| Change from baseline Forced Vital Capacity (FVC) at 4 weeks and 8 weeks. | FVC is the total amount of air exhaled during a pulmonary function test. Expiratory testing will be performed using the Jones Satellite Spirometer (Jones Medical Instrument Company, Oakbrook, Illinois 65021) Measurements will be performed in the manner described using American Thoracic Society guidelines with subjects in the seated position and the trunk at a 90 degree angle to the hips. Subjects will wear a nose clip during testing. Each measurement will be performed 3 times with the maximal score recorded. | Baseline, 4 weeks, 8 weeks. |
| Change from baseline Forced Expiratory Flow (FEF25-75%) at 4weeks and 8 weeks. | FEF25-75% is the flow rate at 25% to 75% of Forced Vital Capacity. Expiratory testing will be performed using the Jones Satellite Spirometer (Jones Medical Instrument Company, Oakbrook, Illinois 65021) Measurements will be performed in the manner described using American Thoracic Society guidelines with subjects in the seated position and the trunk at a 90 degree angle to the hips. Subjects will wear a nose clip during testing. Each measurement will be performed 3 times with the maximal score recorded. | Baseline, 4 weeks, 8 weeks. |
| Change from baseline Peak Expiratory Flow Rate (PEFR) at 4weeks and 8 weeks. | PEFR is a measure of how fast a person can exhale. Expiratory testing will be performed using the Jones Satellite Spirometer (Jones Medical Instrument Company, Oakbrook, Illinois 65021) Measurements will be performed in the manner described using American Thoracic Society guidelines with subjects in the seated position and the trunk at a 90 degree angle to the hips. Subjects will wear a nose clip during testing. Each measurement will be performed 3 times with the maximal score recorded. | Baseline, 4 weeks, 8 weeks. |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
liver disease, transplant, muscle wasting, breathing exercise
|
||
NCT04029129
|
Reducing Traffic Pollution Exposure Improves Blood Pressure
|
This randomized trial assessed the effect of modifying building envelop and level of air filtration on blood pressure over two hour exposure sessions.
|
Living close to major roadways is associated with elevated blood pressure (BP) amongst other adverse health effects. There is growing evidence that ultrafine particles (UFP, <100 nm in diameter), which are elevated near major roads and highways, contribute to such risks. We assessed the efficacy of high efficiency particulate arrestance (HEPA) filtration and building envelope adjustment at reducing exposure to and health effects of air pollution next to major highways.~We used a randomized three-period crossover trial design to assign 77 participants (aged 40-75 and without diagnosis of hypertension) to three two-hour exposure sessions. Sessions were conducted in one of two rooms immediately adjacent to highways. High, medium and low exposures were attained by varying the degree of air exchange and amount of HEPA filtration in the room. During high exposure sessions, the room was ventilated with outdoor air and no filtration was used. During low exposure sessions, leakage of outdoor air into the room was minimized and HEPA filtration was maximized. During medium exposure sessions, a moderate amount of HEPA filtration was used (less than half of that used in low sessions). Indoor particle number and black carbon (BC) concentrations (i.e., markers of traffic-related air pollution) were monitored continuously.~During each session participants sat quietly and wore noise-cancelling headphones, while their BP was monitored every ten minutes using an ambulatory BP monitor. We monitored pulse and oxygen saturation continuously.
|
Near Highway Pollution: From Research to Action
|
Air Pollution
|
* Other: Air filtration and building envelop modifications
|
Inclusion Criteria:~The inclusion criterion was age 40-75 years.~There was a preference for people who were otherwise healthy, but overweight or obese.~Exclusion Criteria:~A history of a major cardiovascular outcome (including myocardial ischemia (MI), stroke, angina)~Other serious health problems (current asthma or COPD)~Taking anti-hypertensive medications~Smoking or living with a smoker~Cognitive impairment~Working at a job with high combustion exposure (taxi/truck driver, restaurant cook)~High combustion exposure in the preceding 24 hours (driving on the highway, cooking in a restaurant, driving a truck)~Not speaking English or Chinese.
|
40 Years
|
75 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized cross over trial
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic Blood Pressure (SBP) | Systolic blood pressure measured with ambulatory blood pressure monitors in mmHg. | Over 2 hour exposure period, we measured SBP after 20 minutes with the objective to assess change in SBP in a time series of measurements over that time period. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diastolic Blood Pressure (DBP) | The unit of measurement, mmHg for the diastolic blood pressure. | Over a 2 hour exposure period with the objective to assess change in DBP measured after 10 minutes in a time series of measurements over that time period. |
|
Traffic-related air pollution, Air filtration, Blood pressure, Controlled exposure
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High exposure<br>Ambient air was allowed freely into the room. | Other: Air filtration and building envelop modifications<br>* Air filters and closing and sealing of windows and doors was used to reduce infiltration of air pollution from outdoors in rooms next to major highways at rush hour.<br>|
| Experimental: Medium exposure<br>Limited air filtration was used to partially reduce levels of pollution in the room relative to outside. | Other: Air filtration and building envelop modifications<br>* Air filters and closing and sealing of windows and doors was used to reduce infiltration of air pollution from outdoors in rooms next to major highways at rush hour.<br>|
| Experimental: Low exposure<br>Doors and windows were closed and sealed and full filtration was used to maximally reduce pollution in the room. | Other: Air filtration and building envelop modifications<br>* Air filters and closing and sealing of windows and doors was used to reduce infiltration of air pollution from outdoors in rooms next to major highways at rush hour.<br>|
|
Reducing Traffic Pollution Exposure Improves Blood Pressure
Study Overview
=================
Brief Summary
-----------------
This randomized trial assessed the effect of modifying building envelop and level of air filtration on blood pressure over two hour exposure sessions.
Detailed Description
-----------------
Living close to major roadways is associated with elevated blood pressure (BP) amongst other adverse health effects. There is growing evidence that ultrafine particles (UFP, <100 nm in diameter), which are elevated near major roads and highways, contribute to such risks. We assessed the efficacy of high efficiency particulate arrestance (HEPA) filtration and building envelope adjustment at reducing exposure to and health effects of air pollution next to major highways. We used a randomized three-period crossover trial design to assign 77 participants (aged 40-75 and without diagnosis of hypertension) to three two-hour exposure sessions. Sessions were conducted in one of two rooms immediately adjacent to highways. High, medium and low exposures were attained by varying the degree of air exchange and amount of HEPA filtration in the room. During high exposure sessions, the room was ventilated with outdoor air and no filtration was used. During low exposure sessions, leakage of outdoor air into the room was minimized and HEPA filtration was maximized. During medium exposure sessions, a moderate amount of HEPA filtration was used (less than half of that used in low sessions). Indoor particle number and black carbon (BC) concentrations (i.e., markers of traffic-related air pollution) were monitored continuously. During each session participants sat quietly and wore noise-cancelling headphones, while their BP was monitored every ten minutes using an ambulatory BP monitor. We monitored pulse and oxygen saturation continuously.
Official Title
-----------------
Near Highway Pollution: From Research to Action
Conditions
-----------------
Air Pollution
Intervention / Treatment
-----------------
* Other: Air filtration and building envelop modifications
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The inclusion criterion was age 40-75 years. There was a preference for people who were otherwise healthy, but overweight or obese. Exclusion Criteria: A history of a major cardiovascular outcome (including myocardial ischemia (MI), stroke, angina) Other serious health problems (current asthma or COPD) Taking anti-hypertensive medications Smoking or living with a smoker Cognitive impairment Working at a job with high combustion exposure (taxi/truck driver, restaurant cook) High combustion exposure in the preceding 24 hours (driving on the highway, cooking in a restaurant, driving a truck) Not speaking English or Chinese.
Ages Eligible for Study
-----------------
Minimum Age: 40 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: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized cross over trial
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High exposure<br>Ambient air was allowed freely into the room. | Other: Air filtration and building envelop modifications<br>* Air filters and closing and sealing of windows and doors was used to reduce infiltration of air pollution from outdoors in rooms next to major highways at rush hour.<br>|
| Experimental: Medium exposure<br>Limited air filtration was used to partially reduce levels of pollution in the room relative to outside. | Other: Air filtration and building envelop modifications<br>* Air filters and closing and sealing of windows and doors was used to reduce infiltration of air pollution from outdoors in rooms next to major highways at rush hour.<br>|
| Experimental: Low exposure<br>Doors and windows were closed and sealed and full filtration was used to maximally reduce pollution in the room. | Other: Air filtration and building envelop modifications<br>* Air filters and closing and sealing of windows and doors was used to reduce infiltration of air pollution from outdoors in rooms next to major highways at rush hour.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic Blood Pressure (SBP) | Systolic blood pressure measured with ambulatory blood pressure monitors in mmHg. | Over 2 hour exposure period, we measured SBP after 20 minutes with the objective to assess change in SBP in a time series of measurements over that time period. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diastolic Blood Pressure (DBP) | The unit of measurement, mmHg for the diastolic blood pressure. | Over a 2 hour exposure period with the objective to assess change in DBP measured after 10 minutes in a time series of measurements over that time period. |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Traffic-related air pollution, Air filtration, Blood pressure, Controlled exposure
|
|
NCT02393937
|
A Therapeutic Equivalence Study of Two Metronidazole Gel 1% Topical Treatments of Rosacea
|
The purpose of this study is to compare the efficacy of two Metronidazole Gels 1%, in the treatment of Rosacea.
|
A Multi-center, Double-blind, Randomized, Vehicle-controlled, Parallel-group Study Comparing Metronidazole Gel 1%, to Metrogel® (Metronidazole Gel) 1% in the Treatment of Rosacea
|
Papulopustular Rosacea, Erythematotelangiectatic Rosacea
|
* Drug: Reference: Metronidazole Gel 1%
* Drug: Test: Metronidazole Gel 1%
* Drug: Placebo Gel
|
Inclusion Criteria:~Male or Female subjects with at least 18 years of age;~Read and signed ICF;~Clinical Diagnosis of Rosacea;~Exclusion Criteria:~Females who are pregnant, lactating or of childbearing potential who are not using or do not agree to use an acceptable form of contraception;~Any skin condition that would interfere with treatment of rosacea~Use of prohibited medications
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the test and reference products of metronidazole topical gel 1% with regard to the mean percent change from Baseline of the inflammatory lesion counts of rosacea. | | 70 Days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the test and reference product of metronidazole topical gel 1% with regard to the Investigator's Global Evaluation (IGE) of disease severity | | 70 Days |
|
Antiprotozoal Agents, Metronidazole, Anti-Infective Agents, Anti-Bacterial Agents, Antiparasitic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test: Metronidazole Gel 1%<br>Metronidazole Gel 1% once daily for 70 days. | Drug: Test: Metronidazole Gel 1%<br>* Participants are assigned to one of three groups in parallel for the duration of the study<br>|
| Active Comparator: Reference: Metronidazole Gel 1%<br>Metronidazole Gel, 1% (MetroGel) Galderma S.A. once daily for 70 days. | Drug: Reference: Metronidazole Gel 1%<br>* Participants are assigned to one of three groups in parallel for the duration of the study<br>* Other names: MetroGel;|
| Placebo Comparator: Placebo<br>Placebo Gel once daily for 70 days. | Drug: Placebo Gel<br>* Participants are assigned to one of three groups in parallel for the duration of the study<br>|
|
A Therapeutic Equivalence Study of Two Metronidazole Gel 1% Topical Treatments of Rosacea
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare the efficacy of two Metronidazole Gels 1%, in the treatment of Rosacea.
Official Title
-----------------
A Multi-center, Double-blind, Randomized, Vehicle-controlled, Parallel-group Study Comparing Metronidazole Gel 1%, to Metrogel® (Metronidazole Gel) 1% in the Treatment of Rosacea
Conditions
-----------------
Papulopustular Rosacea, Erythematotelangiectatic Rosacea
Intervention / Treatment
-----------------
* Drug: Reference: Metronidazole Gel 1%
* Drug: Test: Metronidazole Gel 1%
* Drug: Placebo Gel
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or Female subjects with at least 18 years of age; Read and signed ICF; Clinical Diagnosis of Rosacea; Exclusion Criteria: Females who are pregnant, lactating or of childbearing potential who are not using or do not agree to use an acceptable form of contraception; Any skin condition that would interfere with treatment of rosacea Use of prohibited medications
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: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test: Metronidazole Gel 1%<br>Metronidazole Gel 1% once daily for 70 days. | Drug: Test: Metronidazole Gel 1%<br>* Participants are assigned to one of three groups in parallel for the duration of the study<br>|
| Active Comparator: Reference: Metronidazole Gel 1%<br>Metronidazole Gel, 1% (MetroGel) Galderma S.A. once daily for 70 days. | Drug: Reference: Metronidazole Gel 1%<br>* Participants are assigned to one of three groups in parallel for the duration of the study<br>* Other names: MetroGel;|
| Placebo Comparator: Placebo<br>Placebo Gel once daily for 70 days. | Drug: Placebo Gel<br>* Participants are assigned to one of three groups in parallel for the duration of the study<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the test and reference products of metronidazole topical gel 1% with regard to the mean percent change from Baseline of the inflammatory lesion counts of rosacea. | | 70 Days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the test and reference product of metronidazole topical gel 1% with regard to the Investigator's Global Evaluation (IGE) of disease severity | | 70 Days |
|
||
NCT02870881
|
[Trial of device that is not approved or cleared by the U.S. FDA]
|
[Trial of device that is not approved or cleared by the U.S. FDA]
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
[Trial of device that is not approved or cleared by the U.S. FDA]
Study Overview
=================
Official Title
-----------------
[Trial of device that is not approved or cleared by the U.S. FDA]
Participation Criteria
=================
Ages Eligible for Study
-----------------
Minimum Age:
Maximum Age:
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
||||||||||||||
NCT02036632
|
Eye Patch Therapy for Central Serous Retinopathy (CSR)
|
First, this study will investigate the viability of 24-hour eye patching as a potential treatment modality for CSR. Second, this study will assess a potential physiologic explanation for CSR, namely if inhibition of photic stimulation of the diseased retina will aid in ameliorating disease severity and disease duration.
|
Eye Patching as a Potential Treatment Modality for and a Possible Etiological Insight on Central Serous Retinopathy
|
Central Serous Retinopathy (CSR)
|
* Device: Eye Patching
|
Inclusion Criteria:~Adults 18 years of age and older~Both males and females~Patients diagnosed with active central serous retinopathy~Patients who are willing to use an eye patch in the affected eye for 24 hours~Patients who are able to make the follow up appointments as required by the study~Exclusion Criteria:~Individuals under 18 years of age~Patients with vision less than 20/40 in the unaffected eye.~Patients who are not able to undergo mfERG testing in a realiable manner.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in multi-focal ERG response and macular thickness after 24-hour patch therapy in patients with CSR | This study is a prospective control trial that will compare 24-hour eye patch therapy with the current standard of care in patients with central serous retinopathy (CSR). | 24 hours |
| Change in multi-focal ERG response | | 24 hours |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| macular thickness | | 24 hours |
|
Retinal Diseases, Central Serous Chorioretinopathy, Eye Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Eye Patching<br>Intervention | Device: Eye Patching<br> <br> |
|
Eye Patch Therapy for Central Serous Retinopathy (CSR)
Study Overview
=================
Brief Summary
-----------------
First, this study will investigate the viability of 24-hour eye patching as a potential treatment modality for CSR. Second, this study will assess a potential physiologic explanation for CSR, namely if inhibition of photic stimulation of the diseased retina will aid in ameliorating disease severity and disease duration.
Official Title
-----------------
Eye Patching as a Potential Treatment Modality for and a Possible Etiological Insight on Central Serous Retinopathy
Conditions
-----------------
Central Serous Retinopathy (CSR)
Intervention / Treatment
-----------------
* Device: Eye Patching
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults 18 years of age and older Both males and females Patients diagnosed with active central serous retinopathy Patients who are willing to use an eye patch in the affected eye for 24 hours Patients who are able to make the follow up appointments as required by the study Exclusion Criteria: Individuals under 18 years of age Patients with vision less than 20/40 in the unaffected eye. Patients who are not able to undergo mfERG testing in a realiable manner.
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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Eye Patching<br>Intervention | Device: Eye Patching<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in multi-focal ERG response and macular thickness after 24-hour patch therapy in patients with CSR | This study is a prospective control trial that will compare 24-hour eye patch therapy with the current standard of care in patients with central serous retinopathy (CSR). | 24 hours |
| Change in multi-focal ERG response | | 24 hours |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| macular thickness | | 24 hours |
|
||
NCT00072904
|
Diabetes Therapy to Improve BMI and Lung Function in CF
|
To recruit 150 adult patients with cystic fibrosis related diabetes (CFRD) without fasting hyperglycemia for a multi-center, twelve month, placebo-controlled intervention trial testing the ability of insulin or repaglinide to improve body mass index (BMI) and stabilize pulmonary function in cystic fibrosis (CF).
|
The primary objective of this research is to determine whether treatment with either insulin or an oral diabetes agent that increases endogenous insulin secretion will improve BMI and pulmonary function in cystic fibrosis patients who have diabetes without fasting hyperglycemia.
|
Diabetes Therapy to Improve BMI and Lung Function in CF
|
Cystic Fibrosis, Diabetes Mellitus
|
* Drug: Insulin Asparte
* Drug: Repaglinide
|
Diabetic glucose pattern by oral glucose tolerance test (OGTT) of >200 at 120 min. (stable and healthy at time of OGTT)~Fasting glucose levels <126.~Weight stable within 5% in previous 3 months.~Free from illness for two months.~Male and female 16 and older, who are done growing~Willing to come in for visits every 3 months.~Patients receiving infrequent short bursts of systemic glucocorticoids may be considered for the study inclusion if: a. they have not received systemic glucocorticoids steroids for at least one month, b. they did not receive the steroids for more than 14 consecutive days or 28 days total in six months
|
16 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary objective of this research is to determine whether treatment with either insulin or an oral diabetes agent that increases endogenous insulin secretion will improve BMI and pulmonary function in cystic fibrosis patients who have diabetes | | 12 months |
|
Cystic Fibrosis Related Diabetes, Diabetes without Fasting Hyperglycemia
|
Repaglinide, Hypoglycemic Agents, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: III<br>Placebo take half tab with meals tid | Drug: Insulin Asparte<br>* Insulin asparte given 0.5 units per carb per meal<br>Drug: Repaglinide<br>* 0.5mg tab with meals tid<br>|
|
Diabetes Therapy to Improve BMI and Lung Function in CF
Study Overview
=================
Brief Summary
-----------------
To recruit 150 adult patients with cystic fibrosis related diabetes (CFRD) without fasting hyperglycemia for a multi-center, twelve month, placebo-controlled intervention trial testing the ability of insulin or repaglinide to improve body mass index (BMI) and stabilize pulmonary function in cystic fibrosis (CF).
Detailed Description
-----------------
The primary objective of this research is to determine whether treatment with either insulin or an oral diabetes agent that increases endogenous insulin secretion will improve BMI and pulmonary function in cystic fibrosis patients who have diabetes without fasting hyperglycemia.
Official Title
-----------------
Diabetes Therapy to Improve BMI and Lung Function in CF
Conditions
-----------------
Cystic Fibrosis, Diabetes Mellitus
Intervention / Treatment
-----------------
* Drug: Insulin Asparte
* Drug: Repaglinide
Participation Criteria
=================
Eligibility Criteria
-----------------
Diabetic glucose pattern by oral glucose tolerance test (OGTT) of >200 at 120 min. (stable and healthy at time of OGTT) Fasting glucose levels <126. Weight stable within 5% in previous 3 months. Free from illness for two months. Male and female 16 and older, who are done growing Willing to come in for visits every 3 months. Patients receiving infrequent short bursts of systemic glucocorticoids may be considered for the study inclusion if: a. they have not received systemic glucocorticoids steroids for at least one month, b. they did not receive the steroids for more than 14 consecutive days or 28 days total in six months
Ages Eligible for Study
-----------------
Minimum Age: 16 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: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: III<br>Placebo take half tab with meals tid | Drug: Insulin Asparte<br>* Insulin asparte given 0.5 units per carb per meal<br>Drug: Repaglinide<br>* 0.5mg tab with meals tid<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary objective of this research is to determine whether treatment with either insulin or an oral diabetes agent that increases endogenous insulin secretion will improve BMI and pulmonary function in cystic fibrosis patients who have diabetes | | 12 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cystic Fibrosis Related Diabetes, Diabetes without Fasting Hyperglycemia
|
|
NCT00992667
|
Inhaled Apocynin Decreases Reactive Oxygen Species Concentrations in Exhaled Breath Condensate in Mild Asthmatics
|
The aim of the study is to investigate the effect of inhaled apocynin on ROS (reactive oxygen species) and NOS (reactive nitrogen species) synthesis in 10 nonsmoking mild asthmatics. Effects of nebulized apocynin (0.5 mg/ml, 6 ml) are assessed in exhaled breath condensate (EBC) after 30, 60 and 120 minutes.
|
The study had a double-blind, placebo-controlled, cross-over design, consisted of 2 visits, separated 30 ± 10 days. If during the first visit the drug was used, in the second visit - placebo or vice versa. Before and after procedure, safety measures (arterial blood pressure, heart rate value, and cough scale) were performed. The effect of a possible inhibitor of ROS formation was performed using corticosteroid-naive asthmatic subjects, which are more prone to oxidative stress than healthy non-smoking subjects. The study protocol was approved by the Ethics Committee of Medical University of Lodz (no. RNN/12/08/KE) and written consent was obtained from every subject prior to the study.~EBC was collected using a modification of the method described previously by Doniec et al.2005. The subjects breathed spontaneously through a mouthpiece for 20 min. Each subject wore a nose clip during this procedure. Approximately 2 ml of condensate was collected and immediately stored at -80°C until the procedure of H2O2, NO2- and NO3- measurement.~6 ml of apocynin of total dose 3 mg (0.5 mg/ml) has been nebulized through the mouthpiece with using of a nose clip.~The H2O2 concentration in EBC was measured according to the method applied previously by Nowak et al.2001. Determination of NO2- and NO3- with Griess solution was performed by micromethod, carried out in 96-well plates, according to Griess' method, modified the method described by Dziedzic et al.2003.
|
Inhaled Apocynin Decreases Reactive Oxygen Species Concentrations in Exhaled Breath Condensate in Mild Asthmatics
|
Bronchial Asthma
|
* Drug: Apocynin nebulization
|
Inclusion Criteria:~patients suffering from bronchial asthma (mild)~patients free of any medication at least 7 days before research~patients had not suffered from any infectious diseases including upper respiratory tract infections for at least 3 months prior to the study~Exclusion Criteria:~patients suffering from moderate or severe asthma~patients taking medication 7 or less days before the study~infectious diseases that had occurred 3 months or less before the study
|
22 Years
|
56 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| blood pressure, peripheral blood differential count, lung functional tests, single breath carbon monoxide diffusing capacity | | 6 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| determination of H2O2, NO2- and NO3- concentrations in exhaled breath condensate, determination of NO2 concentration in serum, blood pressure, peripheral blood differential count, lung functional tests, single breath carbon monoxide diffusing capacity | | 6 months |
|
apocynin, asthma
|
Acetovanillone, Anti-Inflammatory Agents, Non-Steroidal, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anti-Inflammatory Agents, Antirheumatic Agents, Antioxidants, Molecular Mechanisms of Pharmacological Action, Protective Agents, Enzyme Inhibitors
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Asthmatics<br>Ten nonsmoking patients, suffering from mild bronchial asthma participated in the study (mean age 30±9 years, 5 men, 5 women). Asthma was diagnosed based on GINA 2008 criteria. The patients were free of any medication, at least 7 days before, and had not suffered from any infectious diseases including upper respiratory tract infections for at least 3 months prior to the study. Patients who did not meet these criteria were excluded from the study. | Drug: Apocynin nebulization<br>* 6 ml of apocynin of total dose 3 mg (0.5 mg/ml dissolved in sterile 0.9% NaCl as the study drug) has been nebulized for 15-20 min through the mouthpiece with using of a nose clip. A nebulizer Pulmo Aide AP-50 (DeVilbiss; Richmond, VA) was used (mass median aerosol diameter 3.1 mm, output 0.3 ml/min.)<br>* Other names: acetovanillone;|
|
Inhaled Apocynin Decreases Reactive Oxygen Species Concentrations in Exhaled Breath Condensate in Mild Asthmatics
Study Overview
=================
Brief Summary
-----------------
The aim of the study is to investigate the effect of inhaled apocynin on ROS (reactive oxygen species) and NOS (reactive nitrogen species) synthesis in 10 nonsmoking mild asthmatics. Effects of nebulized apocynin (0.5 mg/ml, 6 ml) are assessed in exhaled breath condensate (EBC) after 30, 60 and 120 minutes.
Detailed Description
-----------------
The study had a double-blind, placebo-controlled, cross-over design, consisted of 2 visits, separated 30 ± 10 days. If during the first visit the drug was used, in the second visit - placebo or vice versa. Before and after procedure, safety measures (arterial blood pressure, heart rate value, and cough scale) were performed. The effect of a possible inhibitor of ROS formation was performed using corticosteroid-naive asthmatic subjects, which are more prone to oxidative stress than healthy non-smoking subjects. The study protocol was approved by the Ethics Committee of Medical University of Lodz (no. RNN/12/08/KE) and written consent was obtained from every subject prior to the study. EBC was collected using a modification of the method described previously by Doniec et al.2005. The subjects breathed spontaneously through a mouthpiece for 20 min. Each subject wore a nose clip during this procedure. Approximately 2 ml of condensate was collected and immediately stored at -80°C until the procedure of H2O2, NO2- and NO3- measurement. 6 ml of apocynin of total dose 3 mg (0.5 mg/ml) has been nebulized through the mouthpiece with using of a nose clip. The H2O2 concentration in EBC was measured according to the method applied previously by Nowak et al.2001. Determination of NO2- and NO3- with Griess solution was performed by micromethod, carried out in 96-well plates, according to Griess' method, modified the method described by Dziedzic et al.2003.
Official Title
-----------------
Inhaled Apocynin Decreases Reactive Oxygen Species Concentrations in Exhaled Breath Condensate in Mild Asthmatics
Conditions
-----------------
Bronchial Asthma
Intervention / Treatment
-----------------
* Drug: Apocynin nebulization
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patients suffering from bronchial asthma (mild) patients free of any medication at least 7 days before research patients had not suffered from any infectious diseases including upper respiratory tract infections for at least 3 months prior to the study Exclusion Criteria: patients suffering from moderate or severe asthma patients taking medication 7 or less days before the study infectious diseases that had occurred 3 months or less before the study
Ages Eligible for Study
-----------------
Minimum Age: 22 Years
Maximum Age: 56 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: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Asthmatics<br>Ten nonsmoking patients, suffering from mild bronchial asthma participated in the study (mean age 30±9 years, 5 men, 5 women). Asthma was diagnosed based on GINA 2008 criteria. The patients were free of any medication, at least 7 days before, and had not suffered from any infectious diseases including upper respiratory tract infections for at least 3 months prior to the study. Patients who did not meet these criteria were excluded from the study. | Drug: Apocynin nebulization<br>* 6 ml of apocynin of total dose 3 mg (0.5 mg/ml dissolved in sterile 0.9% NaCl as the study drug) has been nebulized for 15-20 min through the mouthpiece with using of a nose clip. A nebulizer Pulmo Aide AP-50 (DeVilbiss; Richmond, VA) was used (mass median aerosol diameter 3.1 mm, output 0.3 ml/min.)<br>* Other names: acetovanillone;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| blood pressure, peripheral blood differential count, lung functional tests, single breath carbon monoxide diffusing capacity | | 6 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| determination of H2O2, NO2- and NO3- concentrations in exhaled breath condensate, determination of NO2 concentration in serum, blood pressure, peripheral blood differential count, lung functional tests, single breath carbon monoxide diffusing capacity | | 6 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
apocynin, asthma
|
NCT04712669
|
A Study of Rodatristat Ethyl in Patients With Pulmonary Arterial Hypertension (ELEVATE 2)
|
The purpose of this study is to assess the safety and efficacy of Rodatristat Ethyl in pulmonary arterial hypertension (PAH) patients.
|
Rodatristat Ethyl is a peripherally restricted TPH inhibitor being studied as a potential treatment for PAH. This dose-ranging, randomized, double-blind, placebo-controlled, multicenter study will evaluate the effect of Rodatristat Ethyl from baseline on pulmonary vascular resistance as measured at right heart catheterization.~Patients will be enrolled into a main study with an option to enroll into an open label extension.~The study is expected to enroll patients in the USA, Canada and Europe.
|
A Phase 2, Dose-Ranging, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Rodatristat Ethyl in Patients With Pulmonary Arterial Hypertension
|
Pulmonary Arterial Hypertension
|
* Drug: rodatristat ethyl 300 mg tablet BID
* Drug: rodatristat ethyl 600 mg BID
* Drug: Placebo
|
Inclusion Criteria:~1. Male and female 18 years or older 2. Body Mass Index (BMI) >18kg/m2 to <=40kg/m2 3. Symptomatic PAH belonging to one of the following 2018 WHO Clinical Group 1 subtypes:~a. Idiopathic PAH b. Heritable PAH c. Drug- or toxin-induced d. PAH associated with:~Connective tissue disease~Congenital systemic to pulmonary shunt (atrial septal defect, ventricular septal defect, patent ductus arteriosus) repaired at least one year prior to Screening~Human immunodeficiency virus (HIV) infection - if diagnosed with HIV, must have stable disease status defined as follows:~stable treatment with HIV medications for at least 8 weeks prior to Screening~no active opportunistic infection during the Screening Period~no hospitalizations due to HIV for at least 4 weeks prior to Screening~WHO FC II or III~Confirmed diagnosis of PAH and meet all the following hemodynamic criteria by means of a screening RHC completed prior to randomization:~mPAP of >20 mmHg~PVR ≥ 350 dyne•sec/cm5~Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) of ≤ 12 mmHg if PVR ≥ 350 and < 500 dyne•sec/cm5, or PCWP/LVEDP ≤ 15 mmHg if PVR ≥ 500 dyne•sec/cm5~6MWD of 100 to 550 meters at Screening~Currently on a stable treatment regimen with one or more treatments approved for PAH. Stable therapy is defined as receiving the same medication(s) for ≥ 12 weeks prior to the screening RHC and at a stable dose level for each for ≥ 8 weeks prior to the screening RHC (see Protocol Section 6.6.2 for approved PAH medications). Any instances where doses of a medication have been missed prior to RHC must be discussed with the Medical Monitor prior to performing the RHC.~Meet all of the following criteria determined by pulmonary function tests completed no more than 24 weeks prior to Screening (performed with or without bronchodilation):~Forced expiratory volume in one second (FEV1) ≥ 60% of predicted normal, and~Total lung capacity (TLC) ≥ 70% of predicted normal or FVC ≥ 70% predicted if TLC is not available; For subjects with CTD associated PAH, if TLC is ≥ 60% of predicted but < 70% of predicted of if FVC ≥ 60% or predicted but < 70% of predicted, high resolution computed tomography [HRCT] obtained within 6 months of screening may be utilized to demonstrate limited interstitial lung disease~If participating in an exercise program for pulmonary rehabilitation, the program must have been initiated ≥ 12 weeks prior to Screening, and patient must agree to maintain the current level of rehabilitation for the first 24 weeks of receiving IP. If not participating in an exercise training program for pulmonary rehabilitation, patient must agree not to enroll in an exercise training program for pulmonary rehabilitation during the Screening Period and the first 24 weeks of receiving IP.~Exclusion Criteria:~Women of childbearing potential who are pregnant, planning to become pregnant, or lactating or female/male patients unwilling to use effective contraception~WHO pulmonary hypertension (PH) Group 1 PAH associated with portal hypertension or schistosomiasis; PH due to left heart disease (WHO PH Group 2), lung diseases and/or hypoxia (WHO PH Group 3), chronic thromboembolic PH (WHO PH Group 4), or PH with unclear multifactorial mechanisms (WHO PH Group 5)~PH associated with significant venous or capillary involvement (PCWP > 15 mmHg), pulmonary capillary hemangiomatosis, portal hypertension, or unrepaired congenital heart defects (CHD)~Three or more of the following risk factors for left ventricular disease:~BMI > 30 kg/m2~Diagnosis of essential hypertension that is actively treated~Diabetes mellitus~History of significant coronary artery disease (e.g., chronic stable angina, history of coronary intervention within the last 3 months, or a stenosis > 70% at coronary angiography)~Atrial fibrillation~Left atrial volume index > 41 mL/m2 [or left atrial diameter (LA) > 4 cm if LAVi unavailable]~Known genetic hypertrophic cardiomyopathy~Known cardiac sarcoidosis or amyloidosis~The patient has a history of, or currently has, a constrictive cardiomyopathy.~Known history of any left ventricular ejection fraction (LVEF) < 40% by echocardiogram within 3 years of randomization (Note: a transient decline in LVEF below 40% that occurred and recovered more than 6 months before the start of Screening and was associated with an acute intercurrent condition [e.g., atrial fibrillation] is allowed).~Hemodynamically significant valvular heart disease as determined by the Investigator, including:~greater than mild aortic and/or mitral stenosis and/or~severe mitral and/or aortic regurgitation (> Grade 3)~Severe arthritis, musculoskeletal problems, or morbid obesity that, in the opinion of the Investigator, is the cause of the patient's functional limitation and would affect the patient's ability to perform or complete the 6MWT.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Following screening assessments, Patients will be enrolled into 1 of 3 treatment arms in a 1:1:1 randomization.
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline of pulmonary vascular resistance (PVR) as measured by right heart catheterization between active and placebo | | From initiation of treatment to Week 24 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who improve in WHO World Health Organization (WHO) Functional Class (FC) | | From initiation of treatment to Week 24 |
| Change from baseline in 6MWD | | From initiation of treatment to Week 24 |
| Change from baseline in N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) levels | | From initiation of treatment to Week 24 |
|
PAH
|
Pulmonary Arterial Hypertension, Familial Primary Pulmonary Hypertension, Hypertension, Vascular Diseases, Cardiovascular Diseases, Hypertension, Pulmonary, Lung Diseases, Respiratory Tract Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rodatristat Ethyl 300 mg BID<br>Rodatristat ethyl 300 mg tablet BID + standard of care medication(s) taken for 24 weeks | Drug: rodatristat ethyl 300 mg tablet BID<br>* rodatristat ethyl 300 mg tablet + matching placebo tablet twice daily on top of standard of care<br>|
| Experimental: Rodatristat Ethyl 600 mg BID<br>Rodatristat ethyl 600 mg tablet BID + standard of care medication(s) taken for 24 weeks | Drug: rodatristat ethyl 600 mg BID<br>* 2 rodatristat ethyl 300 mg tablets twice daily on top of standard of care<br>|
| Placebo Comparator: Placebo<br>Matching placebo tablet + standard of care medication(s) taken for 24 weeks | Drug: Placebo<br>* 2 matching placebo tablets on top of standard of care<br>|
|
A Study of Rodatristat Ethyl in Patients With Pulmonary Arterial Hypertension (ELEVATE 2)
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the safety and efficacy of Rodatristat Ethyl in pulmonary arterial hypertension (PAH) patients.
Detailed Description
-----------------
Rodatristat Ethyl is a peripherally restricted TPH inhibitor being studied as a potential treatment for PAH. This dose-ranging, randomized, double-blind, placebo-controlled, multicenter study will evaluate the effect of Rodatristat Ethyl from baseline on pulmonary vascular resistance as measured at right heart catheterization. Patients will be enrolled into a main study with an option to enroll into an open label extension. The study is expected to enroll patients in the USA, Canada and Europe.
Official Title
-----------------
A Phase 2, Dose-Ranging, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Rodatristat Ethyl in Patients With Pulmonary Arterial Hypertension
Conditions
-----------------
Pulmonary Arterial Hypertension
Intervention / Treatment
-----------------
* Drug: rodatristat ethyl 300 mg tablet BID
* Drug: rodatristat ethyl 600 mg BID
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Male and female 18 years or older 2. Body Mass Index (BMI) >18kg/m2 to <=40kg/m2 3. Symptomatic PAH belonging to one of the following 2018 WHO Clinical Group 1 subtypes: a. Idiopathic PAH b. Heritable PAH c. Drug- or toxin-induced d. PAH associated with: Connective tissue disease Congenital systemic to pulmonary shunt (atrial septal defect, ventricular septal defect, patent ductus arteriosus) repaired at least one year prior to Screening Human immunodeficiency virus (HIV) infection - if diagnosed with HIV, must have stable disease status defined as follows: stable treatment with HIV medications for at least 8 weeks prior to Screening no active opportunistic infection during the Screening Period no hospitalizations due to HIV for at least 4 weeks prior to Screening WHO FC II or III Confirmed diagnosis of PAH and meet all the following hemodynamic criteria by means of a screening RHC completed prior to randomization: mPAP of >20 mmHg PVR ≥ 350 dyne•sec/cm5 Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) of ≤ 12 mmHg if PVR ≥ 350 and < 500 dyne•sec/cm5, or PCWP/LVEDP ≤ 15 mmHg if PVR ≥ 500 dyne•sec/cm5 6MWD of 100 to 550 meters at Screening Currently on a stable treatment regimen with one or more treatments approved for PAH. Stable therapy is defined as receiving the same medication(s) for ≥ 12 weeks prior to the screening RHC and at a stable dose level for each for ≥ 8 weeks prior to the screening RHC (see Protocol Section 6.6.2 for approved PAH medications). Any instances where doses of a medication have been missed prior to RHC must be discussed with the Medical Monitor prior to performing the RHC. Meet all of the following criteria determined by pulmonary function tests completed no more than 24 weeks prior to Screening (performed with or without bronchodilation): Forced expiratory volume in one second (FEV1) ≥ 60% of predicted normal, and Total lung capacity (TLC) ≥ 70% of predicted normal or FVC ≥ 70% predicted if TLC is not available; For subjects with CTD associated PAH, if TLC is ≥ 60% of predicted but < 70% of predicted of if FVC ≥ 60% or predicted but < 70% of predicted, high resolution computed tomography [HRCT] obtained within 6 months of screening may be utilized to demonstrate limited interstitial lung disease If participating in an exercise program for pulmonary rehabilitation, the program must have been initiated ≥ 12 weeks prior to Screening, and patient must agree to maintain the current level of rehabilitation for the first 24 weeks of receiving IP. If not participating in an exercise training program for pulmonary rehabilitation, patient must agree not to enroll in an exercise training program for pulmonary rehabilitation during the Screening Period and the first 24 weeks of receiving IP. Exclusion Criteria: Women of childbearing potential who are pregnant, planning to become pregnant, or lactating or female/male patients unwilling to use effective contraception WHO pulmonary hypertension (PH) Group 1 PAH associated with portal hypertension or schistosomiasis; PH due to left heart disease (WHO PH Group 2), lung diseases and/or hypoxia (WHO PH Group 3), chronic thromboembolic PH (WHO PH Group 4), or PH with unclear multifactorial mechanisms (WHO PH Group 5) PH associated with significant venous or capillary involvement (PCWP > 15 mmHg), pulmonary capillary hemangiomatosis, portal hypertension, or unrepaired congenital heart defects (CHD) Three or more of the following risk factors for left ventricular disease: BMI > 30 kg/m2 Diagnosis of essential hypertension that is actively treated Diabetes mellitus History of significant coronary artery disease (e.g., chronic stable angina, history of coronary intervention within the last 3 months, or a stenosis > 70% at coronary angiography) Atrial fibrillation Left atrial volume index > 41 mL/m2 [or left atrial diameter (LA) > 4 cm if LAVi unavailable] Known genetic hypertrophic cardiomyopathy Known cardiac sarcoidosis or amyloidosis The patient has a history of, or currently has, a constrictive cardiomyopathy. Known history of any left ventricular ejection fraction (LVEF) < 40% by echocardiogram within 3 years of randomization (Note: a transient decline in LVEF below 40% that occurred and recovered more than 6 months before the start of Screening and was associated with an acute intercurrent condition [e.g., atrial fibrillation] is allowed). Hemodynamically significant valvular heart disease as determined by the Investigator, including: greater than mild aortic and/or mitral stenosis and/or severe mitral and/or aortic regurgitation (> Grade 3) Severe arthritis, musculoskeletal problems, or morbid obesity that, in the opinion of the Investigator, is the cause of the patient's functional limitation and would affect the patient's ability to perform or complete the 6MWT.
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: Following screening assessments, Patients will be enrolled into 1 of 3 treatment arms in a 1:1:1 randomization.
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rodatristat Ethyl 300 mg BID<br>Rodatristat ethyl 300 mg tablet BID + standard of care medication(s) taken for 24 weeks | Drug: rodatristat ethyl 300 mg tablet BID<br>* rodatristat ethyl 300 mg tablet + matching placebo tablet twice daily on top of standard of care<br>|
| Experimental: Rodatristat Ethyl 600 mg BID<br>Rodatristat ethyl 600 mg tablet BID + standard of care medication(s) taken for 24 weeks | Drug: rodatristat ethyl 600 mg BID<br>* 2 rodatristat ethyl 300 mg tablets twice daily on top of standard of care<br>|
| Placebo Comparator: Placebo<br>Matching placebo tablet + standard of care medication(s) taken for 24 weeks | Drug: Placebo<br>* 2 matching placebo tablets on top of standard of care<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline of pulmonary vascular resistance (PVR) as measured by right heart catheterization between active and placebo | | From initiation of treatment to Week 24 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who improve in WHO World Health Organization (WHO) Functional Class (FC) | | From initiation of treatment to Week 24 |
| Change from baseline in 6MWD | | From initiation of treatment to Week 24 |
| Change from baseline in N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) levels | | From initiation of treatment to Week 24 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PAH
|
NCT04455711
|
The Effect of Lidocaine on Smooth Emergence With Double Lumen Tube
|
Cough suppression during emergence and tracheal extubation from general anaesthesia has become an important issue as part of patient safety. Cough arised from the mechanical irritation of endotracheal tube and cuff could be accompanied by various adverse effects such as laryngospasm, hypertension, tachycardia, arrhythmia and increase of intracranial, intraocular, or intra-abdominal pressure.~Several cough-preventing strategies have been proposed for smooth emergence, such as opioids, dexmedetomidine or lidocaine. Maintenance of remifentanil infusion during emergence has been reported to be an effective method in reducing cough and cardiovascular change without delay of recovery. In previous studies, the effetive effect-site concentraions for 95% of adults (EC95) for preventing cough are a little different depending on anaestheic agent, type of surgery and sex, ranged from 2.14 to 2.94 ng/ml. However, since most of these studies are for sing lumen endotracheal tube, similar preventing effect would not be expected for double lumen tube (DLT) because of its large diameter and long length. Another problem is higher concentration of remifentanil more than 2.5 ng/ml could not guarantee the safety after extubation. The efficacy of a single IV bolus of lidocaine for the prevention of cough has been the subject of numerous trials.~Therefore, combined use of lidocaine and remifentanil could effectively prevent emergence cough for DLT without the risk of high concentration of remifentanil.
|
The Efficacy of Intravenous Lidocaine With Continuous Infusion of Remifentanil for Attenuating Double Lumen Tube Induced Cough During Emergence
|
Cough, Lidocaine
|
* Drug: Lidocaine Iv
* Drug: Remifentanil
|
Inclusion Criteria:~Patients needs for double lumen tube intubation for one lung ventilation during surgery with ASA (American society of Anesthesiologists) class I or II~Exclusion Criteria:~Gastroesophageal reflux disease~Obese patients (BMI > 30)~Recent upper respiratory infection history (within 3 weeks)~Asthma history~Anticipating difficult airway
|
19 Years
|
75 Years
|
Male
|
No
|
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cough incidence | | from the time of end of the operation up to 10 min after extubation |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cough severity | cough severity is graded as follows; mild cough (1 cough without lifting head), moderate cough ( more than 1 cough not sustained more than 5 seconds), severe cough (cough sustained more than 5 seconds) | from the time of end of the operation up to 10 min after extubation |
| hoarseness | | 30 min at the recovery room |
|
Analgesics, Opioid, Narcotics, Analgesics, Membrane Transport Modulators, Sodium Channel Blockers, Lidocaine, Remifentanil, 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, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Remifentanil group<br>Emerge with continuous infusion of remifentanil 1.5 ng/ml | Drug: Remifentanil<br>* Continuous infusion of remifentanil 1.5 ng/ml until extubation<br>|
| Experimental: Lidocaine group<br>Emerge with continuous infusion of remifentanil 1.5 ng/ml with IV bolus of lidocaine 1.5 mg/kg | Drug: Lidocaine Iv<br>* Bolus dose of 1.5 mg/kg lidocaine was injected immediate after operation.<br>Drug: Remifentanil<br>* Continuous infusion of remifentanil 1.5 ng/ml until extubation<br>|
|
The Effect of Lidocaine on Smooth Emergence With Double Lumen Tube
Study Overview
=================
Brief Summary
-----------------
Cough suppression during emergence and tracheal extubation from general anaesthesia has become an important issue as part of patient safety. Cough arised from the mechanical irritation of endotracheal tube and cuff could be accompanied by various adverse effects such as laryngospasm, hypertension, tachycardia, arrhythmia and increase of intracranial, intraocular, or intra-abdominal pressure. Several cough-preventing strategies have been proposed for smooth emergence, such as opioids, dexmedetomidine or lidocaine. Maintenance of remifentanil infusion during emergence has been reported to be an effective method in reducing cough and cardiovascular change without delay of recovery. In previous studies, the effetive effect-site concentraions for 95% of adults (EC95) for preventing cough are a little different depending on anaestheic agent, type of surgery and sex, ranged from 2.14 to 2.94 ng/ml. However, since most of these studies are for sing lumen endotracheal tube, similar preventing effect would not be expected for double lumen tube (DLT) because of its large diameter and long length. Another problem is higher concentration of remifentanil more than 2.5 ng/ml could not guarantee the safety after extubation. The efficacy of a single IV bolus of lidocaine for the prevention of cough has been the subject of numerous trials. Therefore, combined use of lidocaine and remifentanil could effectively prevent emergence cough for DLT without the risk of high concentration of remifentanil.
Official Title
-----------------
The Efficacy of Intravenous Lidocaine With Continuous Infusion of Remifentanil for Attenuating Double Lumen Tube Induced Cough During Emergence
Conditions
-----------------
Cough, Lidocaine
Intervention / Treatment
-----------------
* Drug: Lidocaine Iv
* Drug: Remifentanil
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients needs for double lumen tube intubation for one lung ventilation during surgery with ASA (American society of Anesthesiologists) class I or II Exclusion Criteria: Gastroesophageal reflux disease Obese patients (BMI > 30) Recent upper respiratory infection history (within 3 weeks) Asthma history Anticipating difficult airway
Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 75 Years
Sexes Eligible for Study
-----------------
Male
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Remifentanil group<br>Emerge with continuous infusion of remifentanil 1.5 ng/ml | Drug: Remifentanil<br>* Continuous infusion of remifentanil 1.5 ng/ml until extubation<br>|
| Experimental: Lidocaine group<br>Emerge with continuous infusion of remifentanil 1.5 ng/ml with IV bolus of lidocaine 1.5 mg/kg | Drug: Lidocaine Iv<br>* Bolus dose of 1.5 mg/kg lidocaine was injected immediate after operation.<br>Drug: Remifentanil<br>* Continuous infusion of remifentanil 1.5 ng/ml until extubation<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cough incidence | | from the time of end of the operation up to 10 min after extubation |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cough severity | cough severity is graded as follows; mild cough (1 cough without lifting head), moderate cough ( more than 1 cough not sustained more than 5 seconds), severe cough (cough sustained more than 5 seconds) | from the time of end of the operation up to 10 min after extubation |
| hoarseness | | 30 min at the recovery room |
|
||
NCT05522842
|
Corneal Endothelium in Diabetics Undergoing Phacoemulsification
|
evaluate and compare the changes in corneal endothelial cell count density between diabetic and non diabetic patients undergoing phacoemulsification surgery, and to evaluate the effect of duration, and control of diabetes on corneal morphology.
|
Diabetes mellitus (DM) is a major health hazard reaching epidemic proportions. Worldwide more than 285 million people are affected by DM; this number is expected to increase to 439 million by 2030 according to the international diabetes federation. DM affects every part of the body and the eye is not an exception.~Diabetes mellitus has been found to be detrimental to corneal endothelium . Patients with diabetes have been found to have morphologically abnormal endothelium, including pleomorphism and polymegethism. Also, elderly patients with diabetes mellitus undergo phacoemulsification is particularly vulnerable to greater endothelial damage during surgery than non diabetics.~Several studies showed that diabetes mellitus has a lower impact on corneal cell density and morphology in patients with good glycemic control , also patients with diabetes over 10 years have more corneal morphological abnormalities than those having diabetes under 10 years duration.~Patients with DM tend to develop cataract more frequently and earlier than non diabetics.~Corneal endothelium plays an important role in maintaining dehydrated state and transparency of cornea throughout life, by pumping excess fluid out of stroma through active transport mechanism and barrier function. Any compromise in these factors leads to direct effect on corneal endothelium .~Cataract has been documented to be the most significant cause of bilateral blindness .~Cataract extraction with phacoemulsification is one of the most common surgical procedure performed nowadays, with an estimated 19 million operation performed annually worldwide. The WHO states that this number will increase to 32 million by 2025, however corneal endothelium is known to undergo damage during phacoemulsification in many different ways, it may be injured mechanically as result of instrumentation causing postoperative complication such as corneal edema.~Specular microscopy is used for non invasive viewing and recording of the image of corneal endothelial cell layer. Several studies have used specular microscopy for quantitative assessment of the corneal damage associated with phacoemulsification by measuring the degree of decrease in the corneal cell density.
|
Evaluation of Corneal Endothelium in Diabetic Patients Undergoing Phacoemulsification Using Specular Microscopy
|
Corneal Endothelial Cell Loss
|
Inclusion Criteria:~Age from 40 to 70~Any degree of cataract~No previous ocular surgery~Exclusion Criteria:~Any corneal pathology, infection, or active inflammation~pseudoexofoliation~History of ocular trauma or surgery
|
40 Years
|
70 Years
|
All
| null |
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| corneal endothelium cell count | normal range of 1500 to 3500 cells/mm2 (age, 40-90) | baseline |
| corneal endothelial cell size | their dimension being roughly 50-70 μm long, 10-30 μm wide and 0.1-10 μm thick | baseline |
| corneal endothelial cell shape | a single layer of cells organized in a characteristic honeycomb pattern | baseline |
|
Corneal Endothelial Cell Loss, Corneal Diseases, Eye Diseases, Eye Manifestations, Postoperative Complications, Pathologic Processes
|
Corneal Endothelium in Diabetics Undergoing Phacoemulsification
Study Overview
=================
Brief Summary
-----------------
evaluate and compare the changes in corneal endothelial cell count density between diabetic and non diabetic patients undergoing phacoemulsification surgery, and to evaluate the effect of duration, and control of diabetes on corneal morphology.
Detailed Description
-----------------
Diabetes mellitus (DM) is a major health hazard reaching epidemic proportions. Worldwide more than 285 million people are affected by DM; this number is expected to increase to 439 million by 2030 according to the international diabetes federation. DM affects every part of the body and the eye is not an exception. Diabetes mellitus has been found to be detrimental to corneal endothelium . Patients with diabetes have been found to have morphologically abnormal endothelium, including pleomorphism and polymegethism. Also, elderly patients with diabetes mellitus undergo phacoemulsification is particularly vulnerable to greater endothelial damage during surgery than non diabetics. Several studies showed that diabetes mellitus has a lower impact on corneal cell density and morphology in patients with good glycemic control , also patients with diabetes over 10 years have more corneal morphological abnormalities than those having diabetes under 10 years duration. Patients with DM tend to develop cataract more frequently and earlier than non diabetics. Corneal endothelium plays an important role in maintaining dehydrated state and transparency of cornea throughout life, by pumping excess fluid out of stroma through active transport mechanism and barrier function. Any compromise in these factors leads to direct effect on corneal endothelium . Cataract has been documented to be the most significant cause of bilateral blindness . Cataract extraction with phacoemulsification is one of the most common surgical procedure performed nowadays, with an estimated 19 million operation performed annually worldwide. The WHO states that this number will increase to 32 million by 2025, however corneal endothelium is known to undergo damage during phacoemulsification in many different ways, it may be injured mechanically as result of instrumentation causing postoperative complication such as corneal edema. Specular microscopy is used for non invasive viewing and recording of the image of corneal endothelial cell layer. Several studies have used specular microscopy for quantitative assessment of the corneal damage associated with phacoemulsification by measuring the degree of decrease in the corneal cell density.
Official Title
-----------------
Evaluation of Corneal Endothelium in Diabetic Patients Undergoing Phacoemulsification Using Specular Microscopy
Conditions
-----------------
Corneal Endothelial Cell Loss
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age from 40 to 70 Any degree of cataract No previous ocular surgery Exclusion Criteria: Any corneal pathology, infection, or active inflammation pseudoexofoliation History of ocular trauma or surgery
Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 70 Years
Sexes Eligible for Study
-----------------
All
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| corneal endothelium cell count | normal range of 1500 to 3500 cells/mm2 (age, 40-90) | baseline |
| corneal endothelial cell size | their dimension being roughly 50-70 μm long, 10-30 μm wide and 0.1-10 μm thick | baseline |
| corneal endothelial cell shape | a single layer of cells organized in a characteristic honeycomb pattern | baseline |
|
|||||
NCT00858962
|
Buprenorphine/Raltegravir Pharmacokinetic Interaction Study
|
The main purpose of this protocol is to study the effect of an HIV medication known as Raltegravir on Buprenorphine in people who have been receiving the same dose of Buprenorphine for at least 3 weeks before study entry. This will be determined by giving Raltegravir along with Buprenorphine and by measuring the amount of Raltegravir and Buprenorphine in the blood. The investigators will also learn about the effects of Buprenorphine on Raltegravir and about the safety of taking these two medications together.
|
A large number of people who are infected with HIV have acquired it through injection drug use. Some of these people are currently being treated with Buprenorphine for their addiction and with medications for HIV infection. Raltegravir is a medication that was approved by the Food and Drug Administration (FDA) for the treatment of HIV infection. Raltegravir acts by making it more difficult for the virus that causes AIDS to multiply and cause more damage to the immune system in someone who is HIV infected.~Earlier studies looking at the effect of Buprenorphine and HIV medications have shown that Buprenorphine and some HIV medications act differently when taken together. It is important to learn if taking Buprenorphine and HIV medications together results in changes in the blood level of either medication. If the HIV medication affects the level of Buprenorphine in the blood, an individual taking Buprenorphine and HIV medications may experience symptoms of withdrawal, even while taking their usual dose of Buprenorphine. On the other hand, if Buprenorphine decreases the amount of HIV medication in the blood, then the HIV medication may be less effective in controlling HIV infection. It is therefore important to learn if Raltegravir and Buprenorphine will affect each other when taken together.~In order to learn about the effects of Buprenorphine and Raltegravir, we will need to measure the amount of Buprenorphine in your blood for 24 hours before you have taken Raltegravir and then compare that to the amount of Buprenorphine in your blood after you have taken Buprenorphine and Raltegravir together .
|
A Study of the Pharmacokinetic and Pharmacodynamic Interactions Between Raltegravir (Isentress) and Buprenorphine
|
HIV Infection, HIV Infections
|
* Drug: Raltegravir
|
Inclusion Criteria:~Patients who are opioid dependent on long-term buprenorphine/naloxone (BUP/NLX) maintenance (minimum of 4 weeks) and who must remain at a stable dose of buprenorphine for at least 3 weeks deemed by the investigator to have acceptable medical history, physical examination and clinical laboratory evaluations consistent with BUP maintenance will be eligible to participate in the study.~Body weight >60 kg for males and >40 kg for females~Male or females, ages > 21 to < 60 years.~Women of childbearing potential (WOCBP) must not be nursing or pregnant and must be on adequate non-hormonal contraception to avoid pregnancy. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of Study Day 1.~Exclusion Criteria:~WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks before and after the study.~Use of an oral, injectable or implantable hormonal contraceptive agent within 3 months of enrollment and throughout the study.~Women who are currently pregnant or breastfeeding.~History or current evidence of any significant acute or chronic medical illness that, within the investigator's discretion, would interfere with the conduct or interpretation of the study.~Proven or suspected acute hepatitis at the time of study entry~Any major surgery within 4 weeks of enrollment. Minor surgical procedures requiring local anesthesia are exceptions.~Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within 4 weeks of enrollment.~Blood transfusion within 4 weeks of enrollment.~Inability to tolerate oral medication.~Inability to tolerate venipuncture and/or absence of secure venous access.~Inability to refrain from smoking during in-residence period~Evidence of organ dysfunction or any clinically relevant (as determined by the investigator) deviations from the norms observed in a buprenorphine/naloxone treated population in physical examination, vital signs, or clinical laboratory determinations.~Positive breathalyzer alcohol test, or positive urine screen for barbiturates, benzodiazepines, amphetamines, cocaine or opioids other than buprenorphine/naloxone.~Subjects with AST, ALT or bilirubin > 3.0X the upper limit of normal~Hemoglobin < 9 g/dL, and platelet count < 75,000/mm3.~Positive serum or urine for HCG.~History of any significant drug allergy, drug rash or sensitivity to any class of drugs relevant to the study drugs.~HIV antibody positive~Exposure to any investigational drug within 4 weeks of enrollment and throughout the study.~Prior exposure to Raltegravir.~Use of any agent (prescribed or otherwise) within 2 weeks of dosing, that is known or suspected to induce or inhibit drug metabolizing enzymes (e.g., cimetidine and compounds in the barbiturate and phenothiazine classes), affect renal tubular secretion (e.g., probenecid, beta-lactam antibiotics), gastrointestinal motility (e.g., metoclopramide, propantheline, loperamide, or narcotic analgesics or opioids other than buprenorphine/naloxone), or uric acid metabolism (e.g., allopurinol) or gastrointestinal pH (including antacids, H2-receptor antagonists, proton pump inhibitors etc.).~Use of over-the-counter medications and herbal preparations, within 1 week prior to enrollment and throughout the study.~Use of St. John's Wort (Hypericum) within four weeks prior to study enrollment and throughout the study.~Consumption of grapefruit or grapefruit juice within 1 week of study entry and throughout the study.
|
21 Years
|
60 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve (AUC) of BUP/NLX With Raltegravir (hr*ng/mL) | PK parameters of BUP were determined by non-compartmental methods. AUC of BUP was determined by use of the trapezoidal rule. | 6-14 days after beginning co-administration of drugs |
|
HIV, Pharmacokinetics, Pharmacodynamics, Buprenorphine, Raltegravir, HIV seronegativity, Interaction
|
Molecular Mechanisms of Pharmacological Action, Raltegravir Potassium, Anti-HIV Agents, Anti-Retroviral Agents, Antiviral Agents, Anti-Infective Agents, HIV Integrase Inhibitors, Integrase Inhibitors, Enzyme Inhibitors
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bup/Ral<br>Buprenorphine and Raltegravir co-administration | Drug: Raltegravir<br>* 400 mg of raltegravir orally twice daily together with normally prescribed stable dose of buprenorphine for a minimum of 4 days and up to 14 days.<br>* Other names: Isentress;|
|
Buprenorphine/Raltegravir Pharmacokinetic Interaction Study
Study Overview
=================
Brief Summary
-----------------
The main purpose of this protocol is to study the effect of an HIV medication known as Raltegravir on Buprenorphine in people who have been receiving the same dose of Buprenorphine for at least 3 weeks before study entry. This will be determined by giving Raltegravir along with Buprenorphine and by measuring the amount of Raltegravir and Buprenorphine in the blood. The investigators will also learn about the effects of Buprenorphine on Raltegravir and about the safety of taking these two medications together.
Detailed Description
-----------------
A large number of people who are infected with HIV have acquired it through injection drug use. Some of these people are currently being treated with Buprenorphine for their addiction and with medications for HIV infection. Raltegravir is a medication that was approved by the Food and Drug Administration (FDA) for the treatment of HIV infection. Raltegravir acts by making it more difficult for the virus that causes AIDS to multiply and cause more damage to the immune system in someone who is HIV infected. Earlier studies looking at the effect of Buprenorphine and HIV medications have shown that Buprenorphine and some HIV medications act differently when taken together. It is important to learn if taking Buprenorphine and HIV medications together results in changes in the blood level of either medication. If the HIV medication affects the level of Buprenorphine in the blood, an individual taking Buprenorphine and HIV medications may experience symptoms of withdrawal, even while taking their usual dose of Buprenorphine. On the other hand, if Buprenorphine decreases the amount of HIV medication in the blood, then the HIV medication may be less effective in controlling HIV infection. It is therefore important to learn if Raltegravir and Buprenorphine will affect each other when taken together. In order to learn about the effects of Buprenorphine and Raltegravir, we will need to measure the amount of Buprenorphine in your blood for 24 hours before you have taken Raltegravir and then compare that to the amount of Buprenorphine in your blood after you have taken Buprenorphine and Raltegravir together .
Official Title
-----------------
A Study of the Pharmacokinetic and Pharmacodynamic Interactions Between Raltegravir (Isentress) and Buprenorphine
Conditions
-----------------
HIV Infection, HIV Infections
Intervention / Treatment
-----------------
* Drug: Raltegravir
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients who are opioid dependent on long-term buprenorphine/naloxone (BUP/NLX) maintenance (minimum of 4 weeks) and who must remain at a stable dose of buprenorphine for at least 3 weeks deemed by the investigator to have acceptable medical history, physical examination and clinical laboratory evaluations consistent with BUP maintenance will be eligible to participate in the study. Body weight >60 kg for males and >40 kg for females Male or females, ages > 21 to < 60 years. Women of childbearing potential (WOCBP) must not be nursing or pregnant and must be on adequate non-hormonal contraception to avoid pregnancy. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of Study Day 1. Exclusion Criteria: WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks before and after the study. Use of an oral, injectable or implantable hormonal contraceptive agent within 3 months of enrollment and throughout the study. Women who are currently pregnant or breastfeeding. History or current evidence of any significant acute or chronic medical illness that, within the investigator's discretion, would interfere with the conduct or interpretation of the study. Proven or suspected acute hepatitis at the time of study entry Any major surgery within 4 weeks of enrollment. Minor surgical procedures requiring local anesthesia are exceptions. Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within 4 weeks of enrollment. Blood transfusion within 4 weeks of enrollment. Inability to tolerate oral medication. Inability to tolerate venipuncture and/or absence of secure venous access. Inability to refrain from smoking during in-residence period Evidence of organ dysfunction or any clinically relevant (as determined by the investigator) deviations from the norms observed in a buprenorphine/naloxone treated population in physical examination, vital signs, or clinical laboratory determinations. Positive breathalyzer alcohol test, or positive urine screen for barbiturates, benzodiazepines, amphetamines, cocaine or opioids other than buprenorphine/naloxone. Subjects with AST, ALT or bilirubin > 3.0X the upper limit of normal Hemoglobin < 9 g/dL, and platelet count < 75,000/mm3. Positive serum or urine for HCG. History of any significant drug allergy, drug rash or sensitivity to any class of drugs relevant to the study drugs. HIV antibody positive Exposure to any investigational drug within 4 weeks of enrollment and throughout the study. Prior exposure to Raltegravir. Use of any agent (prescribed or otherwise) within 2 weeks of dosing, that is known or suspected to induce or inhibit drug metabolizing enzymes (e.g., cimetidine and compounds in the barbiturate and phenothiazine classes), affect renal tubular secretion (e.g., probenecid, beta-lactam antibiotics), gastrointestinal motility (e.g., metoclopramide, propantheline, loperamide, or narcotic analgesics or opioids other than buprenorphine/naloxone), or uric acid metabolism (e.g., allopurinol) or gastrointestinal pH (including antacids, H2-receptor antagonists, proton pump inhibitors etc.). Use of over-the-counter medications and herbal preparations, within 1 week prior to enrollment and throughout the study. Use of St. John's Wort (Hypericum) within four weeks prior to study enrollment and throughout the study. Consumption of grapefruit or grapefruit juice within 1 week of study entry and throughout the study.
Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 60 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bup/Ral<br>Buprenorphine and Raltegravir co-administration | Drug: Raltegravir<br>* 400 mg of raltegravir orally twice daily together with normally prescribed stable dose of buprenorphine for a minimum of 4 days and up to 14 days.<br>* Other names: Isentress;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve (AUC) of BUP/NLX With Raltegravir (hr*ng/mL) | PK parameters of BUP were determined by non-compartmental methods. AUC of BUP was determined by use of the trapezoidal rule. | 6-14 days after beginning co-administration of drugs |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV, Pharmacokinetics, Pharmacodynamics, Buprenorphine, Raltegravir, HIV seronegativity, Interaction
|
|
NCT03098407
|
Opioid Dependence Treatment Therapies in Pregnancy
|
The incidence of opioid dependence in pregnancy increased over the last decade from 1.2 to 5.8 per 1,000 hospital births per year.1 While methadone is the current, standard treatment for opioid dependent (OD) pregnant women, buprenorphine recently emerged as an alternative. In a recent clinical trial (MOTHER), buprenorphine was associated with superior neonatal outcomes such as shorter duration of treatment for neonatal abstinence syndrome (NAS) compared to methadone. However, buprenorphine was also associated with greater study discontinuation (33% vs. 18%) and illicit opioid use (33% vs. 23%) compared to methadone. Treatment dropout often leads to relapse and resumption of high-risk behaviors, overshadowing any short-term improvement in neonatal outcomes. Therefore, The goal of this K23 proposal is to conduct a pilot study to establish the feasibility and acceptability of a randomized comparative effectiveness clinical trial comparing office-based buprenorphine vs. federally licensed methadone programs for the treatment of OD pregnant women.~A pilot study is critical to develop the outcome measures, assessment tools and participant tracking techniques necessary for a future, large-scale comparative effectiveness clinical trial. An examination of feasibility and acceptability will also allow use to characterize the subpopulations of OD pregnant women willing to participate in treatment randomization, identify patient and provider characteristics associated with established treatment preferences and inform the development of strategies to improve participation and enhance the generalizability of the future large-scale clinical trial.
|
Objective:~The goal of this proposal is to conduct a pilot study to establish the feasibility and acceptability of a randomized comparative effectiveness clinical trial comparing office-based buprenorphine vs. federally licensed methadone programs for the treatment of opioid dependent pregnant women.~Specific Aims:~Aim 1: Evaluate the feasibility of conducting a randomized study comparing office-based buprenorphine vs. federally licensed methadone programs for the treatment of OD pregnant women. OD pregnant women (n=50) will be randomized (1:1) to office-based buprenorphine vs. a federally licensed methadone program. Feasibility will be assessed by measuring the proportion of OD pregnant women who are eligible, who enroll, who remain in the study and by the ability to monitor treatment program factors (e.g. compliance with treatment provider/facility visits, counseling sessions, prenatal care visits, social services involvement) and maternal treatment outcomes such as treatment retention, illicit drug use and HIV risk behavior.~Aim 2: Describe the perspectives of OD pregnant women and their providers regarding buprenorphine vs. methadone for the treatment of opioid dependence in pregnancy. Study acceptability will be assessed by conducting qualitative semi-structured interviews with three groups: (1) pilot participants to determine their satisfaction with the assigned treatment program and identify mismatches between treatment program services and participants' needs; (2) prenatal care and opioid treatment providers to identify ways to improve the treatment process in pregnancy and to suggest ideas for care coordination; (3) OD pregnant women who are ineligible or who choose not to participate in the pilot trial will also be asked to participate in an interview to gain a broader perspective of attitudes and perspectives regarding opioid treatment programs in pregnancy.~Aim 3: Identify barriers and facilitators to treatment retention in the postpartum period and identify key functional outcomes relevant to reductions in illicit drug use during pregnancy. Illicit drug use relapse is most common in the immediate postpartum period when stresses associated with motherhood are the greatest. Therefore, pilot participants will be followed at 3, 6, 9 and 12 weeks postpartum to identify barriers and facilitators specific to the postpartum period that may impact treatment retention. The relationship between postpartum treatment retention and maternal functional outcomes will also be explored (e.g. breastfeeding, postpartum depression, motherhood satisfaction, infant custody, employment, and criminality).~Background:~The incidence of opioid dependence in pregnancy increased over the last decade from 1.2 to 5.8 per 1,000 hospital births per year. While methadone is the current, standard treatment for opioid dependent (OD) pregnant women, buprenorphine recently emerged as an alternative. In a recent clinical trial (MOTHER), buprenorphine was associated with superior neonatal outcomes such as shorter duration of treatment for neonatal abstinence syndrome (NAS) compared to methadone. However, buprenorphine was also associated with greater study discontinuation (33% vs. 18%) and illicit opioid use (33% vs. 23%) compared to methadone. Treatment dropout often leads to relapse and resumption of high-risk behaviors, overshadowing any short-term improvement in neonatal outcomes. Therefore, the next research question that emerges is which is the most effective treatment (buprenorphine vs. methadone) for a particular patient during pregnancy?~In clinical settings, differences in maternal characteristics, treatment program structure and patient and provider preferences may surpass the impact of pharmacology on maternal treatment outcomes (treatment retention, illicit drug use, HIV risk behavior). Buprenorphine is dispensed in office-based settings by a variety of providers and with less regulatory oversight than methadone. Methadone is dispensed from federally licensed facilities that often incorporate counseling and support services into treatment protocols. Successful office-based treatment relies on shared power and responsibility, close patient-provider relationships and careful attention to psychosocial co-morbidities. Failure to match patient problem severity to differences in treatment program structure may contribute to adverse maternal outcomes. Therefore, to understand the comparative effectiveness of buprenorphine vs. methadone in pregnancy, the impact of patient problem severity and treatment program structure on maternal (vs. neonatal) outcomes must be compared.~Significance:~Findings from this project will provide the preliminary data to support a comparative effectiveness clinical trial designed to compare the impact of office-based buprenorphine vs. federally licensed methadone programs on maternal treatment and postpartum functional outcomes in OD women. The ultimate goal of this line of research is develop evidence-based clinical guidelines to guide provider decision-making regarding the most effective treatment (buprenorphine vs. methadone) for a particular patient during pregnancy.
|
A Pilot Randomized Comparative Effectiveness Clinical Trial of Buprenorphine vs. Methadone for the Treatment of Opioid Dependence in Pregnancy.
|
Opioid-Related Disorders, Pregnancy
|
* Drug: Buprenorphine
* Drug: Methadone
|
Inclusion Criteria:~Pregnant women 18+ years old, with a singleton pregnancy ≤ 28 weeks gestation confirmed by ultrasound, who meet Diagnostic and Statistical Manual-IV criteria for opioid dependence confirmed by urine drug screen (UDS), who are interested in opioid maintenance treatment and plan to receive prenatal care and deliver at Magee Womens Hospital (MWH) will be recruited.~Exclusion Criteria:~(1) active, current dependence on benzodiazepines or alcohol~(2) acute severe psychiatric condition in need of immediate treatment (e.g. suicidal ideations)~(3) pending or legal action that could prohibit or interfere with participation (e.g. incarceration)~(4) current, established treatment with methadone or buprenorphine. Exclusion criteria are based on the Substance Abuse and Mental Health Services Administration (SAMHSA) recommendations for office-based buprenorphine use.
|
18 Years
| null |
Female
|
Accepts Healthy Volunteers
|
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who are recruited, enrolled, retained, and who complete the study. | evaluate a minimum of 9 OD pregnant women per month for possible participation and enrollment, randomize a minimum of 4 participants per month to office-based buprenorphine (PRC) or methadone treatment facility (NATP) for a total of 50 participants over a 12 month enrollment period, retain ≥ 80% of randomized participants until 12 weeks postpartum, and maintain < 5% of incomplete data. | 12 Months |
|
Buprenorphine, Methadone, Analgesics, Opioid, Narcotics, Central Nervous System Depressants, Physiological Effects of Drugs, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Narcotic Antagonists, Antitussive Agents, Respiratory System Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Buprenorphine Maintenance Treatment<br>Buprenorphine Maintenance Treatment patients will receive instructions regarding a follow-up, outpatient appointment with the Pregnancy Recovery Center at Magee-Womens Hospital, which specializes in Opioid maintenance treatment for pregnant patients, for the next day following enrollment in the study for induction onto buprenorphine maintenance treatment. | Drug: Buprenorphine<br>* This is a pilot study to establish the feasibility and acceptability of a randomized comparative effectiveness clinical trial comparing office-based buprenorphine vs. federally licensed methadone treatment programs for OD pregnant women.<br>|
| Other: Methadone Maintenance Treatment<br>Methadone Maintenance Treatment patients will be immediately admitted to Magee-Womens Hospital for an inpatient induction onto methadone maintenance treatment. | Drug: Methadone<br>* This is a pilot study to establish the feasibility and acceptability of a randomized comparative effectiveness clinical trial comparing office-based buprenorphine vs. federally licensed methadone treatment programs for OD pregnant women.<br>|
|
Opioid Dependence Treatment Therapies in Pregnancy
Study Overview
=================
Brief Summary
-----------------
The incidence of opioid dependence in pregnancy increased over the last decade from 1.2 to 5.8 per 1,000 hospital births per year.1 While methadone is the current, standard treatment for opioid dependent (OD) pregnant women, buprenorphine recently emerged as an alternative. In a recent clinical trial (MOTHER), buprenorphine was associated with superior neonatal outcomes such as shorter duration of treatment for neonatal abstinence syndrome (NAS) compared to methadone. However, buprenorphine was also associated with greater study discontinuation (33% vs. 18%) and illicit opioid use (33% vs. 23%) compared to methadone. Treatment dropout often leads to relapse and resumption of high-risk behaviors, overshadowing any short-term improvement in neonatal outcomes. Therefore, The goal of this K23 proposal is to conduct a pilot study to establish the feasibility and acceptability of a randomized comparative effectiveness clinical trial comparing office-based buprenorphine vs. federally licensed methadone programs for the treatment of OD pregnant women. A pilot study is critical to develop the outcome measures, assessment tools and participant tracking techniques necessary for a future, large-scale comparative effectiveness clinical trial. An examination of feasibility and acceptability will also allow use to characterize the subpopulations of OD pregnant women willing to participate in treatment randomization, identify patient and provider characteristics associated with established treatment preferences and inform the development of strategies to improve participation and enhance the generalizability of the future large-scale clinical trial.
Detailed Description
-----------------
Objective: The goal of this proposal is to conduct a pilot study to establish the feasibility and acceptability of a randomized comparative effectiveness clinical trial comparing office-based buprenorphine vs. federally licensed methadone programs for the treatment of opioid dependent pregnant women. Specific Aims: Aim 1: Evaluate the feasibility of conducting a randomized study comparing office-based buprenorphine vs. federally licensed methadone programs for the treatment of OD pregnant women. OD pregnant women (n=50) will be randomized (1:1) to office-based buprenorphine vs. a federally licensed methadone program. Feasibility will be assessed by measuring the proportion of OD pregnant women who are eligible, who enroll, who remain in the study and by the ability to monitor treatment program factors (e.g. compliance with treatment provider/facility visits, counseling sessions, prenatal care visits, social services involvement) and maternal treatment outcomes such as treatment retention, illicit drug use and HIV risk behavior. Aim 2: Describe the perspectives of OD pregnant women and their providers regarding buprenorphine vs. methadone for the treatment of opioid dependence in pregnancy. Study acceptability will be assessed by conducting qualitative semi-structured interviews with three groups: (1) pilot participants to determine their satisfaction with the assigned treatment program and identify mismatches between treatment program services and participants' needs; (2) prenatal care and opioid treatment providers to identify ways to improve the treatment process in pregnancy and to suggest ideas for care coordination; (3) OD pregnant women who are ineligible or who choose not to participate in the pilot trial will also be asked to participate in an interview to gain a broader perspective of attitudes and perspectives regarding opioid treatment programs in pregnancy. Aim 3: Identify barriers and facilitators to treatment retention in the postpartum period and identify key functional outcomes relevant to reductions in illicit drug use during pregnancy. Illicit drug use relapse is most common in the immediate postpartum period when stresses associated with motherhood are the greatest. Therefore, pilot participants will be followed at 3, 6, 9 and 12 weeks postpartum to identify barriers and facilitators specific to the postpartum period that may impact treatment retention. The relationship between postpartum treatment retention and maternal functional outcomes will also be explored (e.g. breastfeeding, postpartum depression, motherhood satisfaction, infant custody, employment, and criminality). Background: The incidence of opioid dependence in pregnancy increased over the last decade from 1.2 to 5.8 per 1,000 hospital births per year. While methadone is the current, standard treatment for opioid dependent (OD) pregnant women, buprenorphine recently emerged as an alternative. In a recent clinical trial (MOTHER), buprenorphine was associated with superior neonatal outcomes such as shorter duration of treatment for neonatal abstinence syndrome (NAS) compared to methadone. However, buprenorphine was also associated with greater study discontinuation (33% vs. 18%) and illicit opioid use (33% vs. 23%) compared to methadone. Treatment dropout often leads to relapse and resumption of high-risk behaviors, overshadowing any short-term improvement in neonatal outcomes. Therefore, the next research question that emerges is which is the most effective treatment (buprenorphine vs. methadone) for a particular patient during pregnancy? In clinical settings, differences in maternal characteristics, treatment program structure and patient and provider preferences may surpass the impact of pharmacology on maternal treatment outcomes (treatment retention, illicit drug use, HIV risk behavior). Buprenorphine is dispensed in office-based settings by a variety of providers and with less regulatory oversight than methadone. Methadone is dispensed from federally licensed facilities that often incorporate counseling and support services into treatment protocols. Successful office-based treatment relies on shared power and responsibility, close patient-provider relationships and careful attention to psychosocial co-morbidities. Failure to match patient problem severity to differences in treatment program structure may contribute to adverse maternal outcomes. Therefore, to understand the comparative effectiveness of buprenorphine vs. methadone in pregnancy, the impact of patient problem severity and treatment program structure on maternal (vs. neonatal) outcomes must be compared. Significance: Findings from this project will provide the preliminary data to support a comparative effectiveness clinical trial designed to compare the impact of office-based buprenorphine vs. federally licensed methadone programs on maternal treatment and postpartum functional outcomes in OD women. The ultimate goal of this line of research is develop evidence-based clinical guidelines to guide provider decision-making regarding the most effective treatment (buprenorphine vs. methadone) for a particular patient during pregnancy.
Official Title
-----------------
A Pilot Randomized Comparative Effectiveness Clinical Trial of Buprenorphine vs. Methadone for the Treatment of Opioid Dependence in Pregnancy.
Conditions
-----------------
Opioid-Related Disorders, Pregnancy
Intervention / Treatment
-----------------
* Drug: Buprenorphine
* Drug: Methadone
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pregnant women 18+ years old, with a singleton pregnancy ≤ 28 weeks gestation confirmed by ultrasound, who meet Diagnostic and Statistical Manual-IV criteria for opioid dependence confirmed by urine drug screen (UDS), who are interested in opioid maintenance treatment and plan to receive prenatal care and deliver at Magee Womens Hospital (MWH) will be recruited. Exclusion Criteria: (1) active, current dependence on benzodiazepines or alcohol (2) acute severe psychiatric condition in need of immediate treatment (e.g. suicidal ideations) (3) pending or legal action that could prohibit or interfere with participation (e.g. incarceration) (4) current, established treatment with methadone or buprenorphine. Exclusion criteria are based on the Substance Abuse and Mental Health Services Administration (SAMHSA) recommendations for office-based buprenorphine use.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
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 |
| --- | --- |
| Other: Buprenorphine Maintenance Treatment<br>Buprenorphine Maintenance Treatment patients will receive instructions regarding a follow-up, outpatient appointment with the Pregnancy Recovery Center at Magee-Womens Hospital, which specializes in Opioid maintenance treatment for pregnant patients, for the next day following enrollment in the study for induction onto buprenorphine maintenance treatment. | Drug: Buprenorphine<br>* This is a pilot study to establish the feasibility and acceptability of a randomized comparative effectiveness clinical trial comparing office-based buprenorphine vs. federally licensed methadone treatment programs for OD pregnant women.<br>|
| Other: Methadone Maintenance Treatment<br>Methadone Maintenance Treatment patients will be immediately admitted to Magee-Womens Hospital for an inpatient induction onto methadone maintenance treatment. | Drug: Methadone<br>* This is a pilot study to establish the feasibility and acceptability of a randomized comparative effectiveness clinical trial comparing office-based buprenorphine vs. federally licensed methadone treatment programs for OD pregnant women.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who are recruited, enrolled, retained, and who complete the study. | evaluate a minimum of 9 OD pregnant women per month for possible participation and enrollment, randomize a minimum of 4 participants per month to office-based buprenorphine (PRC) or methadone treatment facility (NATP) for a total of 50 participants over a 12 month enrollment period, retain ≥ 80% of randomized participants until 12 weeks postpartum, and maintain < 5% of incomplete data. | 12 Months |
|
||
NCT04362137
|
Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm
|
This was a randomized, double-blind, placebo-controlled, 29-day, multicenter study to assess the efficacy and safety of ruxolitinib + standard-of-care (SoC) therapy, compared with placebo + SoC therapy, in patients aged ≥12 years with COVID-19 disease.
|
This was a Phase III, multicenter, double-blind, randomized, placebo-controlled study to assess the efficacy and safety of ruxolitinib in patients aged ≥12 years with COVID-19 disease. The study enrolled patients to ruxolitinib or placebo, in addition to standard of care (SoC) per local practice. Patients who meet the inclusion/exclusion criteria were randomized in a 2:1 ratio to either oral ruxolitinib 5 mg twice daily + SoC or oral matching-image placebo + SoC for a total of 14 days. An additional 14 days of study drug could be given if in the opinion of the investigator the patient's clinical signs and symptoms did not improve, or worsen, and the potential benefit outweighed the potential risk.~The study included:~Screening period of 0-2 days.~Study period of 29 days (treatment of 14 days with possible extension of treatment to 28 days).~The primary objective was to evaluate the efficacy (as measured by a composite endpoint of proportion of patients who die, develop respiratory failure [require mechanical ventilation], or require intensive care unit care) of ruxolitinib + standard-of-care (SoC) therapy compared with placebo + SoC therapy, for the treatment of COVID-19 by Day 29.
|
Phase 3 Randomized, Double-blind, Placebo-controlled Multi-center Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm (RUXCOVID)
|
Cytokine Storm (Covid-19)
|
* Drug: Ruxolitinib
* Drug: Placebo
|
Inclusion Criteria:~Patient or guardian/health proxy must provide informed consent (and assent if applicable) before any study assessment is performed.~Male and female patients aged ≥ 12 years (or ≥ the lower age limit allowed by Health Authority and/or Ethics Committee/Institutional Review Board approvals).~Patients with coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) test or another rapid test from the respiratory tract prior to randomization.~Patients currently hospitalized or will be hospitalized prior to randomization.~Patients, who meet at least one of the below criteria:~Pulmonary infiltrates (chest X ray or chest CT scan);~Respiratory frequency ≥ 30/min;~Requiring supplemental oxygen;~Oxygen saturation ≤ 94% on room air;~Arterial oxygen partial pressure (PaO2)/ fraction of inspired oxygen (FiO2) < 300mmHg (1mmHg=0.133kPa) (corrective formulation should be used for higher altitude regions (over 1000m).~Exclusion Criteria:~History of hypersensitivity to any drugs or metabolites of similar chemical classes as ruxolitinib.~Presence of severely impaired renal function defined by serum creatinine > 2 mg/dL (>176.8 μmol/L), or have estimated creatinine clearance < 30 ml/min measured or calculated by Cockroft Gault equation or calculated by the updated bedside Schwartz equation.~Suspected uncontrolled bacterial, fungal, viral, or other infection (besides COVID-19).~Currently intubated or intubated between screening and randomization. In intensive care unit (ICU) at time of randomization. Intubated or in ICU for COVID-19 disease prior to screening. Patients who are on anti-rejection, immunosuppressant or immunomodulatory drugs (i.e. tocilizumab, ruxolitinib, canakinumab, sarilumab, anakinra).~Unable to ingest tablets at randomization. Pregnant or nursing (lactating) women
|
12 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Who Die, Develop Respiratory Failure [Require Mechanical Ventilation] or Require Intensive Care Unit (ICU) Care | Efficacy is measured by a composite endpoint of proportion of patients who die, develop respiratory failure [require mechanical ventilation], or require intensive care unit [ICU] care for the treatment of COVID-19. Analyses are cumulative, thus analysis on Day 29 includes all events till that day. Patients who developed respiratory failure and/or required ICU at randomization are excluded from the analysis. | Day 1 - Day 29 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Status | Clinical status is measured with the 9-point ordinal scale.~The scoring is:~Uninfected patients have a score 0 (no clinical or virological evidence of infection).~Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities).~Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as peripheral oxygen saturation (SpO2) ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs).~Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)).~Patients who die have a score 8. | Baseline, Day 15, Day 29 |
| Percentage of Patients With at Least Two-point Improvement From Baseline in Clinical Status | Percentage of patients with at least two points improvement in clinical status on the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are treated as non-responders. | Baseline, Day 15, Day 29 |
| Percentage of Patients With at Least One-point Improvement From Baseline in Clinical Status | Percentage of patients with at least one point improvement in clinical status on the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are treated as non-responders. | Baseline, Day 15, Day 29 |
| Percentage of Patients With at Least One-point Deterioration From Baseline in Clinical Status | Percentage of patients with at least one point deterioration in clinical status on the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are treated as non-responders. | Baseline, Day 15, Day 29 |
| Time to Improvement in Clinical Status | Time to improvement in clinical status from baseline category to one less severe category of the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment.~Median time to improvement is estimated by Kaplan-Meier method, with dead patients being censored at the maximum follow-up time in the study. Patients who did not achieve improvement and did not die are censored at their last clinical status assessment date. | 29 days |
| Mean Change From Baseline in the Clinical Status | Mean change from baseline in the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are excluded from the analysis.~A negative change from baseline in the clinical status is a favorable outcome. | Baseline, Day 15, Day 29 |
| Mortality Rate | Mortality rate is determined as the proportion of participants who died by study Day 15 and Day 29 | Day 15, Day 29 |
| Proportion of Patients Requiring Mechanical Ventilation | Proportion of patients requiring mechanical ventilation. Analyses are cumulative, thus analysis on Day 29 includes all events till that day. Patients who required mechanical ventilation at randomization are excluded from the analysis. | Day 1 - Day 29 |
| Duration of Hospitalization | Duration of hospitalization is defined as time to hospital discharge. Median time to hospital discharge is estimated by Kaplan-Meier method, with dead patients being censored at the maximum follow-up time in the study. Patients who were not discharged and did not die are censored at their last assessment date. | 29 days |
| Time to Hospital Discharge or to a NEWS2 Score of ≤2 | The time to hospital discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and maintained for 24 hours whichever comes first.~The NEWS2 is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst).~Median time is estimated by Kaplan-Meier method, with dead patients being censored at the maximum follow-up time in the study. | 29 days |
| Change From Baseline in NEWS2 Score | The National Early Warning Score 2 (NEWS2) is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst). At each visit, only patients with a value at both baseline and the respective visit are included.~A negative change from baseline in NEWS2 score is a favorable outcome. | Baseline, Days 3, 5, 8, 11, 15, and 29 |
| Change From Baseline in SpO2/FiO2 Ratio | Change from baseline in peripheral oxygen saturation / fraction of inspired oxygen ratio (SpO2/FiO2 ratio). At each visit, only patients with a value at both baseline and the respective visit are included.~A positive change from baseline in SpO2/FiO2 ratio is a favorable outcome. | Baseline, Day 15, Day 29 |
| Proportion of Patients With no Oxygen Therapy | Proportion of patients with no oxygen therapy (defined as oxygen saturation ≥ 94% on room air) at Days 15 and 29. Analyses are cumulative, thus analysis on each day includes all events till that day.~Patients with missing data at Day 15 and/or Day 29 are excluded from the analysis. | Day 15, Day 29 |
|
COVID-19 pneumonia, cytokine release syndrome, SARS-COV-2, ruxolitinib
|
COVID-19, Cytokine Release Syndrome, Pneumonia, Viral, Pneumonia, Respiratory Tract Infections, Infections, Virus Diseases, Coronavirus Infections, Coronaviridae Infections, Nidovirales Infections, RNA Virus Infections, Lung Diseases, Respiratory Tract Diseases, Systemic Inflammatory Response Syndrome, Inflammation, Pathologic Processes, Shock
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruxolitinib 5 mg<br>Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days | Drug: Ruxolitinib<br>* Ruxolitinib 5 mg tablets<br>* Other names: INC424;|
| Placebo Comparator: Placebo<br>Matching-image placebo for 14 days with possible extension of treatment to 28 days | Drug: Placebo<br>* Matching-image placebo<br>|
|
Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm
Study Overview
=================
Brief Summary
-----------------
This was a randomized, double-blind, placebo-controlled, 29-day, multicenter study to assess the efficacy and safety of ruxolitinib + standard-of-care (SoC) therapy, compared with placebo + SoC therapy, in patients aged ≥12 years with COVID-19 disease.
Detailed Description
-----------------
This was a Phase III, multicenter, double-blind, randomized, placebo-controlled study to assess the efficacy and safety of ruxolitinib in patients aged ≥12 years with COVID-19 disease. The study enrolled patients to ruxolitinib or placebo, in addition to standard of care (SoC) per local practice. Patients who meet the inclusion/exclusion criteria were randomized in a 2:1 ratio to either oral ruxolitinib 5 mg twice daily + SoC or oral matching-image placebo + SoC for a total of 14 days. An additional 14 days of study drug could be given if in the opinion of the investigator the patient's clinical signs and symptoms did not improve, or worsen, and the potential benefit outweighed the potential risk. The study included: Screening period of 0-2 days. Study period of 29 days (treatment of 14 days with possible extension of treatment to 28 days). The primary objective was to evaluate the efficacy (as measured by a composite endpoint of proportion of patients who die, develop respiratory failure [require mechanical ventilation], or require intensive care unit care) of ruxolitinib + standard-of-care (SoC) therapy compared with placebo + SoC therapy, for the treatment of COVID-19 by Day 29.
Official Title
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Phase 3 Randomized, Double-blind, Placebo-controlled Multi-center Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm (RUXCOVID)
Conditions
-----------------
Cytokine Storm (Covid-19)
Intervention / Treatment
-----------------
* Drug: Ruxolitinib
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient or guardian/health proxy must provide informed consent (and assent if applicable) before any study assessment is performed. Male and female patients aged ≥ 12 years (or ≥ the lower age limit allowed by Health Authority and/or Ethics Committee/Institutional Review Board approvals). Patients with coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) test or another rapid test from the respiratory tract prior to randomization. Patients currently hospitalized or will be hospitalized prior to randomization. Patients, who meet at least one of the below criteria: Pulmonary infiltrates (chest X ray or chest CT scan); Respiratory frequency ≥ 30/min; Requiring supplemental oxygen; Oxygen saturation ≤ 94% on room air; Arterial oxygen partial pressure (PaO2)/ fraction of inspired oxygen (FiO2) < 300mmHg (1mmHg=0.133kPa) (corrective formulation should be used for higher altitude regions (over 1000m). Exclusion Criteria: History of hypersensitivity to any drugs or metabolites of similar chemical classes as ruxolitinib. Presence of severely impaired renal function defined by serum creatinine > 2 mg/dL (>176.8 μmol/L), or have estimated creatinine clearance < 30 ml/min measured or calculated by Cockroft Gault equation or calculated by the updated bedside Schwartz equation. Suspected uncontrolled bacterial, fungal, viral, or other infection (besides COVID-19). Currently intubated or intubated between screening and randomization. In intensive care unit (ICU) at time of randomization. Intubated or in ICU for COVID-19 disease prior to screening. Patients who are on anti-rejection, immunosuppressant or immunomodulatory drugs (i.e. tocilizumab, ruxolitinib, canakinumab, sarilumab, anakinra). Unable to ingest tablets at randomization. Pregnant or nursing (lactating) women
Ages Eligible for Study
-----------------
Minimum Age: 12 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: Ruxolitinib 5 mg<br>Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days | Drug: Ruxolitinib<br>* Ruxolitinib 5 mg tablets<br>* Other names: INC424;|
| Placebo Comparator: Placebo<br>Matching-image placebo for 14 days with possible extension of treatment to 28 days | Drug: Placebo<br>* Matching-image placebo<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Who Die, Develop Respiratory Failure [Require Mechanical Ventilation] or Require Intensive Care Unit (ICU) Care | Efficacy is measured by a composite endpoint of proportion of patients who die, develop respiratory failure [require mechanical ventilation], or require intensive care unit [ICU] care for the treatment of COVID-19. Analyses are cumulative, thus analysis on Day 29 includes all events till that day. Patients who developed respiratory failure and/or required ICU at randomization are excluded from the analysis. | Day 1 - Day 29 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Status | Clinical status is measured with the 9-point ordinal scale. The scoring is: Uninfected patients have a score 0 (no clinical or virological evidence of infection). Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as peripheral oxygen saturation (SpO2) ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). Patients who die have a score 8. | Baseline, Day 15, Day 29 |
| Percentage of Patients With at Least Two-point Improvement From Baseline in Clinical Status | Percentage of patients with at least two points improvement in clinical status on the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are treated as non-responders. | Baseline, Day 15, Day 29 |
| Percentage of Patients With at Least One-point Improvement From Baseline in Clinical Status | Percentage of patients with at least one point improvement in clinical status on the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are treated as non-responders. | Baseline, Day 15, Day 29 |
| Percentage of Patients With at Least One-point Deterioration From Baseline in Clinical Status | Percentage of patients with at least one point deterioration in clinical status on the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are treated as non-responders. | Baseline, Day 15, Day 29 |
| Time to Improvement in Clinical Status | Time to improvement in clinical status from baseline category to one less severe category of the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Median time to improvement is estimated by Kaplan-Meier method, with dead patients being censored at the maximum follow-up time in the study. Patients who did not achieve improvement and did not die are censored at their last clinical status assessment date. | 29 days |
| Mean Change From Baseline in the Clinical Status | Mean change from baseline in the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are excluded from the analysis. A negative change from baseline in the clinical status is a favorable outcome. | Baseline, Day 15, Day 29 |
| Mortality Rate | Mortality rate is determined as the proportion of participants who died by study Day 15 and Day 29 | Day 15, Day 29 |
| Proportion of Patients Requiring Mechanical Ventilation | Proportion of patients requiring mechanical ventilation. Analyses are cumulative, thus analysis on Day 29 includes all events till that day. Patients who required mechanical ventilation at randomization are excluded from the analysis. | Day 1 - Day 29 |
| Duration of Hospitalization | Duration of hospitalization is defined as time to hospital discharge. Median time to hospital discharge is estimated by Kaplan-Meier method, with dead patients being censored at the maximum follow-up time in the study. Patients who were not discharged and did not die are censored at their last assessment date. | 29 days |
| Time to Hospital Discharge or to a NEWS2 Score of ≤2 | The time to hospital discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and maintained for 24 hours whichever comes first. The NEWS2 is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst). Median time is estimated by Kaplan-Meier method, with dead patients being censored at the maximum follow-up time in the study. | 29 days |
| Change From Baseline in NEWS2 Score | The National Early Warning Score 2 (NEWS2) is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst). At each visit, only patients with a value at both baseline and the respective visit are included. A negative change from baseline in NEWS2 score is a favorable outcome. | Baseline, Days 3, 5, 8, 11, 15, and 29 |
| Change From Baseline in SpO2/FiO2 Ratio | Change from baseline in peripheral oxygen saturation / fraction of inspired oxygen ratio (SpO2/FiO2 ratio). At each visit, only patients with a value at both baseline and the respective visit are included. A positive change from baseline in SpO2/FiO2 ratio is a favorable outcome. | Baseline, Day 15, Day 29 |
| Proportion of Patients With no Oxygen Therapy | Proportion of patients with no oxygen therapy (defined as oxygen saturation ≥ 94% on room air) at Days 15 and 29. Analyses are cumulative, thus analysis on each day includes all events till that day. Patients with missing data at Day 15 and/or Day 29 are excluded from the analysis. | Day 15, Day 29 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COVID-19 pneumonia, cytokine release syndrome, SARS-COV-2, ruxolitinib
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NCT04759300
|
Effectiveness of C-MAC Video-stylet Versus C-MAC D- Blade Video-laryngoscope for Tracheal Intubation
|
Videolaryngoscopy provides a better laryngeal view and do not need airway alignment for tracheal intubation.
|
The C-MAC-VS can be connected easily to the same C- MAC monitor and Pocket Monitor without requiring any additional light source and camera. This device is great for cases with limited mouth opening, airway obstruction and difficult intubation. C-MAC-VS has no lumens so it's very easy to clean and it can accommodates a size ETT 6.0 and greater.
|
Effectiveness of C-MAC Video-stylet Versus C-MAC D- Blade Video-laryngoscope for Tracheal Intubation in Patients With Predicted Difficult Airway: Randomized Comparative Study
|
Difficult Mask Ventilation, Difficult Intubation
|
* Device: C-MAC VS
* Device: C-MAC VL D -blade
|
Inclusion Criteria:~patients with BMI ≥ 30 kg/m2,~presence of any predictors of difficult intubation;~Mallampati score > =3;~inter-incisor distance < 3 cm;~thyromental distance < 6 cm;~neck extension < 80°from neck flexion;~cervical spine instability; history of difficult endotracheal intubation or difficult mask ventilation~Exclusion Criteria:~patients have increased risk of pulmonary aspiration;~have significant medical diseases in term of cardiac, respiratory, hepatic, renal
|
18 Years
|
60 Years
|
All
|
No
|
Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The patients will be randomly assigned into two equal groups using computer-generated randomization technique. Group C-MAC VS (VS group) included patients undergoing tracheal intubation using the C-MAC VS. Group C-MAC VL D -blade (D group) included patients undergoing intubation using the C-MAC VL D-blade.
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| duration of intubation procedure | assess duration of intubation procedure by using C-MAC VS versus C-MAC D-blade in patients with anticipated difficult airway. | 10 minutes |
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group C-MAC VS<br>patients undergoing tracheal intubation using the C-MAC VS. | Device: C-MAC VS<br>* patients undergoing tracheal intubation using the C-MAC VS<br>|
| Placebo Comparator: Group C-MAC VL D -blade<br>patients undergoing intubation using the C-MAC VL D-blade. | Device: C-MAC VL D -blade<br>* patients undergoing intubation using the C-MAC VL D-blade.<br>|
|
Effectiveness of C-MAC Video-stylet Versus C-MAC D- Blade Video-laryngoscope for Tracheal Intubation
Study Overview
=================
Brief Summary
-----------------
Videolaryngoscopy provides a better laryngeal view and do not need airway alignment for tracheal intubation.
Detailed Description
-----------------
The C-MAC-VS can be connected easily to the same C- MAC monitor and Pocket Monitor without requiring any additional light source and camera. This device is great for cases with limited mouth opening, airway obstruction and difficult intubation. C-MAC-VS has no lumens so it's very easy to clean and it can accommodates a size ETT 6.0 and greater.
Official Title
-----------------
Effectiveness of C-MAC Video-stylet Versus C-MAC D- Blade Video-laryngoscope for Tracheal Intubation in Patients With Predicted Difficult Airway: Randomized Comparative Study
Conditions
-----------------
Difficult Mask Ventilation, Difficult Intubation
Intervention / Treatment
-----------------
* Device: C-MAC VS
* Device: C-MAC VL D -blade
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patients with BMI ≥ 30 kg/m2, presence of any predictors of difficult intubation; Mallampati score > =3; inter-incisor distance < 3 cm; thyromental distance < 6 cm; neck extension < 80°from neck flexion; cervical spine instability; history of difficult endotracheal intubation or difficult mask ventilation Exclusion Criteria: patients have increased risk of pulmonary aspiration; have significant medical diseases in term of cardiac, respiratory, hepatic, renal
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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The patients will be randomly assigned into two equal groups using computer-generated randomization technique. Group C-MAC VS (VS group) included patients undergoing tracheal intubation using the C-MAC VS. Group C-MAC VL D -blade (D group) included patients undergoing intubation using the C-MAC VL D-blade.
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group C-MAC VS<br>patients undergoing tracheal intubation using the C-MAC VS. | Device: C-MAC VS<br>* patients undergoing tracheal intubation using the C-MAC VS<br>|
| Placebo Comparator: Group C-MAC VL D -blade<br>patients undergoing intubation using the C-MAC VL D-blade. | Device: C-MAC VL D -blade<br>* patients undergoing intubation using the C-MAC VL D-blade.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| duration of intubation procedure | assess duration of intubation procedure by using C-MAC VS versus C-MAC D-blade in patients with anticipated difficult airway. | 10 minutes |
|
|||
NCT00915902
|
Fish Oil Study for High Triglyceride Levels in Children
|
High triglyceride levels are increasingly recognized in children, particularly those who are overweight. There are no studies of treatment of high triglycerides in children and adolescents. Fish oil is attractive because it is considered safe and effective for treating high triglycerides in adults and has been used safely for other purposes in children. The investigators will conduct a randomized study of Lovaza (the only prescription omega-3 fish oil medication) in 44 children and adolescents to study efficacy in lowering triglycerides, safety, and possible mechanisms of beneficial effects.
|
Participants (n = 42, age 14 + 2 yrs) with hypertriglyceridemia and LDL cholesterol < 160 mg/dl were enrolled in a randomized double blind cross over trial comparing 4 g fish oil daily with placebo. Treatment interval was 8 weeks with a 4 week wash out, between the two treatment intervals. Lipid profile, lipoprotein particle distribution and size, glucose, insulin, high sensitivity C reactive protien (CRP), interleukin-6, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and thrombin generation were measured.~Patients were evaluated at 6 time points: Visit 1/baseline (week 0), Visit 2/randomization (week 4), Visit 3/after treatment 1 (week 12) , Visit 4/after wash out (week 16), Visit 5/after treatment 2 (week 24) and Visit 6/close out (week 28) . Patients were advised to maintain a stable diet and not alter baseline fish consumption . One participant took an oral contraceptive throughout the trial. Any fish oil supplements were discontinued. Advice on a heart healthy diet was provided. Blood pressure (right arm sitting with appropriate sized cuff, taken 3 times, last measurement used), height, and weight were measured at the beginning of the study, after the first wash out period, and close out. Participant phone contact was made during each treatment arm to assess diet stability. Fasting lipid profile was performed at every visit. Red blood cell fatty acid profile and secondary endpoints were performed at all visits except baseline.
|
Fish Oil Treatment for Dyslipidemia Associated With Children and Adolescents
|
Hypertriglyceridemia
|
* Drug: Omega-3-acid ethyl esters
* Drug: Placebo
|
Inclusion Criteria:~Male or female patients who are 10-17 years of age~Fasting triglyceride level >150 mg/dl and < 750 mg/dl measured on 2 separate occasions.~Ability to follow the study procedures and adhere to the diet counseling recommendations~Written parental permission and assent are obtained prior to any research procedures~Exclusion Criteria:~Bleeding disorders~Diabetes mellitus (impaired glucose tolerance is not an exclusion)~Uncontrolled hypothyroidism~Liver disease~Allergy to fish/shellfish~Patients requiring chronic use of aspirin and non-steroidal anti-inflammatory agents~Patients requiring lipid lowering agents~LDL-Cholesterol levels >160 mg/dl~Current participation in another clinical study or within the previous 30 days~Alcohol use~Currently pregnant or planning to become pregnant during the course of this trial (confirmed by pregnancy testing)~Any significant medical condition which the investigator believes would interfere with the patient's ability to safely participate in this trial
|
10 Years
|
17 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Triglyceride Level | | after 8 week treatment or placebo period |
|
Hypertriglyceridemia, Hyperlipidemias, Dyslipidemias, Lipid Metabolism Disorders, Metabolic Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omega-3-acid ethyl esters (Lovaza)<br>This randomized, double-blind, placebo, crossover trial consisted of two 8-week treatment periods, separated by a 4-week washout. Eligible patients were randomized to receive either fish oil 4 g daily or corn oil placebo during the first 8-week treatment period; patients received the alternate treatment during the next treatment period. GlaxoSmithKline supplied the study drug and the placebo. The study drug, Omega-3-acid ethyl esters (Lovaza) was given to patients PO daily as two, 1 g capsules taken twice daily during the duration of their 8-week treatment period. The study drug contained minimally 1.5 g DHA (docosahexaenoic acid) and 1.86 g EPA (eicosapentaenoic acid). | Drug: Omega-3-acid ethyl esters<br>* Omega-3-acid ethyl esters (Lovaza), two 1-gram capsules taken twice daily for 8 weeks<br>* Other names: Lovaza;|
| Placebo Comparator: Placebo<br>This randomized, double-blind, placebo, crossover trial consisted of two 8-week treatment periods, separated by a 4-week washout. Eligible patients were randomized to receive either fish oil 4 g daily or corn oil placebo during the first 8-week treatment period; patients received the alternate treatment during the next treatment period. The corn oil placebo was given to patients PO daily as two, 1 g capsules taken twice daily during the duration of their 8-week non-treatment (placebo) period. | Drug: Placebo<br>* Placebo (corn oil), two 1-gram capsules taken twice daily for 8 weeks<br>* Other names: Corn Oil;|
|
Fish Oil Study for High Triglyceride Levels in Children
Study Overview
=================
Brief Summary
-----------------
High triglyceride levels are increasingly recognized in children, particularly those who are overweight. There are no studies of treatment of high triglycerides in children and adolescents. Fish oil is attractive because it is considered safe and effective for treating high triglycerides in adults and has been used safely for other purposes in children. The investigators will conduct a randomized study of Lovaza (the only prescription omega-3 fish oil medication) in 44 children and adolescents to study efficacy in lowering triglycerides, safety, and possible mechanisms of beneficial effects.
Detailed Description
-----------------
Participants (n = 42, age 14 + 2 yrs) with hypertriglyceridemia and LDL cholesterol < 160 mg/dl were enrolled in a randomized double blind cross over trial comparing 4 g fish oil daily with placebo. Treatment interval was 8 weeks with a 4 week wash out, between the two treatment intervals. Lipid profile, lipoprotein particle distribution and size, glucose, insulin, high sensitivity C reactive protien (CRP), interleukin-6, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and thrombin generation were measured. Patients were evaluated at 6 time points: Visit 1/baseline (week 0), Visit 2/randomization (week 4), Visit 3/after treatment 1 (week 12) , Visit 4/after wash out (week 16), Visit 5/after treatment 2 (week 24) and Visit 6/close out (week 28) . Patients were advised to maintain a stable diet and not alter baseline fish consumption . One participant took an oral contraceptive throughout the trial. Any fish oil supplements were discontinued. Advice on a heart healthy diet was provided. Blood pressure (right arm sitting with appropriate sized cuff, taken 3 times, last measurement used), height, and weight were measured at the beginning of the study, after the first wash out period, and close out. Participant phone contact was made during each treatment arm to assess diet stability. Fasting lipid profile was performed at every visit. Red blood cell fatty acid profile and secondary endpoints were performed at all visits except baseline.
Official Title
-----------------
Fish Oil Treatment for Dyslipidemia Associated With Children and Adolescents
Conditions
-----------------
Hypertriglyceridemia
Intervention / Treatment
-----------------
* Drug: Omega-3-acid ethyl esters
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female patients who are 10-17 years of age Fasting triglyceride level >150 mg/dl and < 750 mg/dl measured on 2 separate occasions. Ability to follow the study procedures and adhere to the diet counseling recommendations Written parental permission and assent are obtained prior to any research procedures Exclusion Criteria: Bleeding disorders Diabetes mellitus (impaired glucose tolerance is not an exclusion) Uncontrolled hypothyroidism Liver disease Allergy to fish/shellfish Patients requiring chronic use of aspirin and non-steroidal anti-inflammatory agents Patients requiring lipid lowering agents LDL-Cholesterol levels >160 mg/dl Current participation in another clinical study or within the previous 30 days Alcohol use Currently pregnant or planning to become pregnant during the course of this trial (confirmed by pregnancy testing) Any significant medical condition which the investigator believes would interfere with the patient's ability to safely participate in this trial
Ages Eligible for Study
-----------------
Minimum Age: 10 Years
Maximum Age: 17 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: Omega-3-acid ethyl esters (Lovaza)<br>This randomized, double-blind, placebo, crossover trial consisted of two 8-week treatment periods, separated by a 4-week washout. Eligible patients were randomized to receive either fish oil 4 g daily or corn oil placebo during the first 8-week treatment period; patients received the alternate treatment during the next treatment period. GlaxoSmithKline supplied the study drug and the placebo. The study drug, Omega-3-acid ethyl esters (Lovaza) was given to patients PO daily as two, 1 g capsules taken twice daily during the duration of their 8-week treatment period. The study drug contained minimally 1.5 g DHA (docosahexaenoic acid) and 1.86 g EPA (eicosapentaenoic acid). | Drug: Omega-3-acid ethyl esters<br>* Omega-3-acid ethyl esters (Lovaza), two 1-gram capsules taken twice daily for 8 weeks<br>* Other names: Lovaza;|
| Placebo Comparator: Placebo<br>This randomized, double-blind, placebo, crossover trial consisted of two 8-week treatment periods, separated by a 4-week washout. Eligible patients were randomized to receive either fish oil 4 g daily or corn oil placebo during the first 8-week treatment period; patients received the alternate treatment during the next treatment period. The corn oil placebo was given to patients PO daily as two, 1 g capsules taken twice daily during the duration of their 8-week non-treatment (placebo) period. | Drug: Placebo<br>* Placebo (corn oil), two 1-gram capsules taken twice daily for 8 weeks<br>* Other names: Corn Oil;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Triglyceride Level | | after 8 week treatment or placebo period |
|
||
NCT04771026
|
The Effectiveness of Preemptive Nebulized Dexamethasone in Reducing Post-Operative Sore Throat in Supraglottic Airway
|
This study aims to study the effectiveness of preoperatively nebulized dexamethasone in reducing the incidence and severity of Post Operative Sore Throat, POST in patients undergoing surgery under general anesthesia using the Ambu® AuraGainTM SGA device, with secondary aims of determining the effectiveness of dexamethasone in reducing post-operative cough severity and hoarseness of voice
|
The role of dexamethasone in reducing the incidence and severity of postoperative sore throat (POST) with ETT use is established in few studies. Some of the studies had done were found to have result on pertaining to efficacy of steroids in reducing incidences of POST in usage of SGA device, hence we decided to undertake this double-blinded, randomized study in patients undergoing general anaesthesia using the Ambu® AuraGainTM SGA device.~Dexamethasone which is 26.6 and 6.6 more potent than cortisol and prednisolone, acts via anti-inflammatory effects; inhibiting and reducing the release of inflammatory mediators. Hence this study aims to study the effectiveness of preoperative nebulized dexamethasone in reducing the incidence and severity of POST to improve patient satisfaction following general anaesthesia,and reduce morbidity.~OBJECTIVES~General:~To determine the effectiveness of preoperatively nebulized dexamethasone in reducing the incidence of post-operative sore throat following Ambu® AuraGainTM SGA device use.~Specific:~To compare the incidence of post-operative sore throat (POST) with pre-operatively nebulized dexamethasone following insertion of Ambu® AuraGainTM SGA device at 30 minutes and 24 hours post operatively.~To compare the severity of POST with pre-operatively nebulized dexamethasone using a visual analogue scale (VAS) following insertion of Ambu® AuraGainTM SGA device at 30 minutes and 24 hours post-operatively.~To compare the incidence and severity of cough with pre-operatively nebulized dexamethasone using a 4-point scale grading at 30 minutes and 24 hours post-operatively following the insertion of Ambu® AuraGainTM SGA device.~To compare the incidence and severity of hoarseness of voice with pre-operatively nebulized dexamethasone using a 4-point scale grading at 30 minutes and 24 hours post-operatively following the insertion of Ambu® AuraGainTM SGA device.~HYPOTHESIS~Null hypothesis H0:~There is no difference in terms of efficacy of pre-operatively nebulised dexamethasone in reducing the incidence and severity of POST Sore throat, cough and hoarseness will be graded as per Tazeh-Kand et al's study~Alternative hypothesis H1:~Pre-operatively nebulised dexamethasone is effective in reducing the incidence and severity of POST Sore throat, cough and hoarseness will be graded as per Tazeh-Kand et al's study~RESEARCH DESIGN The proposed study design is a single-centre, randomized, double-blind, controlled, parallel-group interventional study conducted in Kelantan, Malaysia.~Patients will be randomized (using a block randomization software) to 2 study arms (1:1 ratio), into Groups C and D whereby:~Group C: Control group, patients receiving usual standard of care in practice of SGA device (including analgesics), without receiving any active drug.~Group D: Patients receiving nebulised dexamethasone 8mg (2ml) with 3mls of normal saline 0.9% 30 minutes prior to induction of anaesthesia in the pre-operative receiving room via a wall-mounted oxygen source at 15L/minute.~After randomization, each patient will stay in their assigned treatment arm for the duration of the study.~This will be a double-blinded randomized controlled study, carried out by a single operator and assessor. Both operator/ assessor and patient will be blinded.~STUDY AREA Operating theatres in Hospital Universiti Sains Malaysia, HUSM, Kubang Kerian.~INTERVENTIONS Group C: Control group, patients receiving usual standard of care in practice of SGA device (including analgesics), without receiving any active drug.~Group D: Patients receiving nebulised dexamethasone 8mg (2ml) with 3mls of normal saline 0.9% 30 minutes prior to induction of anaesthesia in the pre-operative receiving room via a wall-mounted oxygen source at 15L/minute.~SAMPLE SIZE ESTIMATION The sample size was estimated using the PS Software version 3.1.2 (Dupont and Plummer 1997) based on comparing 2 proportions for incidence of sore throat, And G*Power version 3.1.9.4 (Erdfelder, Faul, & Buchner, 1996) based on a 3 point scale for determining the severity of sore throat, cough and hoarseness of voice.~Where:~Alpha: 0.05~Power: 80%~Based on the parameters in the study by Tazeh-Kand NF, Eslami B, Mohammadian K. Inhaled fluticasone propionate reduces postoperative sore throat, cough, and hoarseness. Anesth Analg. 2010 Oct;111(4):895-8 (23).~The largest sample size generated was 128 (for 64 patients in each arm) for incidence of cough 1 hour post-operatively to detect a 30% difference in prevalence of cough between 2 study groups with a alpha value of 0.05 and power of 80%.~DATA COLLECTION METHOD After written consent pre-operatively, patients will be randomized as 2 groups~- Group C, and Group D. Group C: Patients receiving normal conduct of anaesthesia Group D: Patients receiving dexamethasone 8mg (2ml) with 3mls of normal saline 0.9%.~Patients will receive a sealed, opaque envelope containing a code with either N or D according to the randomization software pre-operatively, which will be opened by an anesthesiologist or nurse not involved in the study. The anesthesiologist or nurse opening the envelope will be told to withhold this information from the operator/investigator and patient. If the envelope contains the letter D, the said nurse/ anesthesiologist will be told to prepare and administer the nebulised drug as described, also without the knowledge of the operator/investigator. The operator/investigator will have no contact with the patient once the envelope is opened, and will remain away from the preoperative receiving room for 30 minutes from the arrival of patient.~Patients in group D will receive a total of 5mls of nebulized drug 30 minutes prior to induction of anaesthesia in the pre-operative receiving room via a wall-mounted oxygen source at 15L/minute.~After nebulisation for 30 minutes in the pre-operative receiving area, patients will be brought to the respective operating theatre. Monitoring according to standards will be applied - Non-invasive blood pressure, ECG, oxygen saturation, and capnography.~A humidified gas exchanger will be used for all patients.~Conduct of anesthesia will be as follows:~Patients will not be premedicated~Patients will be pre-oxygenated with 100% oxygen for 3-5 minutes or until an end-tidal oxygen fraction of 85 is achieved~Intravenous induction with IV Fentanyl 1-2 mcg/kg, IV Propofol 1-3mg/kg, with no use of neuromuscular blockade of IV Dexamethasone.~The insertion of a fully deflated SGA AMBU AURAGAIN® lubricated with Lignocaine 2% on the posterior aspect using the appropriate size according to patients' weight once there is loss of eyelash reflex by the operator using a standardized technique. The cuff will then be inflated with appropriate amount of air according to LMA size~Cuff pressure will be measured immediately once the airway is secured, and subsequently measured hourly using a handheld pressure gauge. Cuff pressure of not more than 60 cmH20 will be maintained~Anaesthesia will be maintained using Sevoflurane, titrated to a Minimum Alveolar Concentration (MAC) of 0.9-1.0 in 50/50 oxygen/air mixture with SIMV (Pressure or volume control) mode~At the end of anaesthesia, the oral airway will be suctioned once gently and 100% oxygen will be administered until the SGA removed without deflation once regular, spontaneous ventilation has returned with opening of eyes to calling of name~Patients will be transferred to the recovery area where all patient will receive supplemental oxygen via face mask at 5L/minute until discharged from the post-operative recovery unit.~The 4 point questionnaire on POST will be applied at 30 minutes to 1 hour and 24 hours post-operatively in the ward by the same operator. If the patient is discharged prior to the 24 hour interview, they will be followed up via phone.~Scoring System for Sore Throat, Cough and Hoarseness, from Tazeh-kand et al:
|
The Effectiveness of Preemptive Nebulized Dexamethasone in Reducing Post- Operative Sore Throat Following the Use of AMBU® AURAGAINTM Device: A Double Blind, Randomised Clinical Trial
|
Sore Throat, Hoarseness, Dexamethasone, Supraglottic Airway Devices
|
* Drug: Dexamethasone
|
Inclusion Criteria:~Between the ages of 18-70 years~American Society of Anaesthesiology (ASA) physical status of 1 and 2~Patients undergoing elective procedures under general anaesthesia between the data collection period suitable for SGA device~Exclusion Criteria:~Pre-existing sore throat/hoarseness on pre-operative assessment~Patients with history of postoperative nausea or vomiting~Recent (2 weeks) upper or lower respiratory tract infection~Known hypersensitivity to dexamethasone or on regular steroids~Uncontrolled diabetes of capillary blood sugar more than 10mmol/l on pre-operative assessment~Morbidly obese with BMI > 40 kg/m2~Procedure exceeding 3 hours duration~Procedure requiring prone or Trendelenburg position or manipulation of head post-induction~Oral and neck surgeries~Pregnant patients~Patients with cognitive disabilities~Patients requiring nasogastric tube or nasal temperature probe insertion~Patient refusal
|
18 Years
|
70 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of POST up to 24 hours post-operatively in patients who received pre-operative nebulized dexamethasone | Patients will be evaluated using scoring system for sore throat, cough and hoarseness | up to 24 hours post-operatively |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of cough up to 24 hours post-operatively in patients who received pre-operative nebulized dexamethasone | Patients will be evaluated using scoring system for sore throat, cough and hoarseness | up to 24 hours post-operatively |
| Incidence of hoarseness of voice up to 24 hours post-operatively in patients who received pre-operative nebulized dexamethasone | Patients will be evaluated using scoring system for sore throat, cough and hoarseness | up to 24 hours post-operatively |
|
Dexamethasone, Supraglottic airway device, Post operative Sore throat, Post operative hoarseness of voice
|
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 |
| --- | --- |
| No Intervention: Control<br>Receiving routine conduct of general anaesthesia for supraglottic airway device | |
| Experimental: Dexamethasone<br>Receiving pre-operatively single dose nebulised dexamethasone 8mg prior to induction of general anaesthesia | Drug: Dexamethasone<br>* Pre-operatively nebuliser dexamethasone 8mg prior to induction of anesthesia<br>* Other names: Decan;|
|
The Effectiveness of Preemptive Nebulized Dexamethasone in Reducing Post-Operative Sore Throat in Supraglottic Airway
Study Overview
=================
Brief Summary
-----------------
This study aims to study the effectiveness of preoperatively nebulized dexamethasone in reducing the incidence and severity of Post Operative Sore Throat, POST in patients undergoing surgery under general anesthesia using the Ambu® AuraGainTM SGA device, with secondary aims of determining the effectiveness of dexamethasone in reducing post-operative cough severity and hoarseness of voice
Detailed Description
-----------------
The role of dexamethasone in reducing the incidence and severity of postoperative sore throat (POST) with ETT use is established in few studies. Some of the studies had done were found to have result on pertaining to efficacy of steroids in reducing incidences of POST in usage of SGA device, hence we decided to undertake this double-blinded, randomized study in patients undergoing general anaesthesia using the Ambu® AuraGainTM SGA device. Dexamethasone which is 26.6 and 6.6 more potent than cortisol and prednisolone, acts via anti-inflammatory effects; inhibiting and reducing the release of inflammatory mediators. Hence this study aims to study the effectiveness of preoperative nebulized dexamethasone in reducing the incidence and severity of POST to improve patient satisfaction following general anaesthesia,and reduce morbidity. OBJECTIVES General: To determine the effectiveness of preoperatively nebulized dexamethasone in reducing the incidence of post-operative sore throat following Ambu® AuraGainTM SGA device use. Specific: To compare the incidence of post-operative sore throat (POST) with pre-operatively nebulized dexamethasone following insertion of Ambu® AuraGainTM SGA device at 30 minutes and 24 hours post operatively. To compare the severity of POST with pre-operatively nebulized dexamethasone using a visual analogue scale (VAS) following insertion of Ambu® AuraGainTM SGA device at 30 minutes and 24 hours post-operatively. To compare the incidence and severity of cough with pre-operatively nebulized dexamethasone using a 4-point scale grading at 30 minutes and 24 hours post-operatively following the insertion of Ambu® AuraGainTM SGA device. To compare the incidence and severity of hoarseness of voice with pre-operatively nebulized dexamethasone using a 4-point scale grading at 30 minutes and 24 hours post-operatively following the insertion of Ambu® AuraGainTM SGA device. HYPOTHESIS Null hypothesis H0: There is no difference in terms of efficacy of pre-operatively nebulised dexamethasone in reducing the incidence and severity of POST Sore throat, cough and hoarseness will be graded as per Tazeh-Kand et al's study Alternative hypothesis H1: Pre-operatively nebulised dexamethasone is effective in reducing the incidence and severity of POST Sore throat, cough and hoarseness will be graded as per Tazeh-Kand et al's study RESEARCH DESIGN The proposed study design is a single-centre, randomized, double-blind, controlled, parallel-group interventional study conducted in Kelantan, Malaysia. Patients will be randomized (using a block randomization software) to 2 study arms (1:1 ratio), into Groups C and D whereby: Group C: Control group, patients receiving usual standard of care in practice of SGA device (including analgesics), without receiving any active drug. Group D: Patients receiving nebulised dexamethasone 8mg (2ml) with 3mls of normal saline 0.9% 30 minutes prior to induction of anaesthesia in the pre-operative receiving room via a wall-mounted oxygen source at 15L/minute. After randomization, each patient will stay in their assigned treatment arm for the duration of the study. This will be a double-blinded randomized controlled study, carried out by a single operator and assessor. Both operator/ assessor and patient will be blinded. STUDY AREA Operating theatres in Hospital Universiti Sains Malaysia, HUSM, Kubang Kerian. INTERVENTIONS Group C: Control group, patients receiving usual standard of care in practice of SGA device (including analgesics), without receiving any active drug. Group D: Patients receiving nebulised dexamethasone 8mg (2ml) with 3mls of normal saline 0.9% 30 minutes prior to induction of anaesthesia in the pre-operative receiving room via a wall-mounted oxygen source at 15L/minute. SAMPLE SIZE ESTIMATION The sample size was estimated using the PS Software version 3.1.2 (Dupont and Plummer 1997) based on comparing 2 proportions for incidence of sore throat, And G*Power version 3.1.9.4 (Erdfelder, Faul, & Buchner, 1996) based on a 3 point scale for determining the severity of sore throat, cough and hoarseness of voice. Where: Alpha: 0.05 Power: 80% Based on the parameters in the study by Tazeh-Kand NF, Eslami B, Mohammadian K. Inhaled fluticasone propionate reduces postoperative sore throat, cough, and hoarseness. Anesth Analg. 2010 Oct;111(4):895-8 (23). The largest sample size generated was 128 (for 64 patients in each arm) for incidence of cough 1 hour post-operatively to detect a 30% difference in prevalence of cough between 2 study groups with a alpha value of 0.05 and power of 80%. DATA COLLECTION METHOD After written consent pre-operatively, patients will be randomized as 2 groups - Group C, and Group D. Group C: Patients receiving normal conduct of anaesthesia Group D: Patients receiving dexamethasone 8mg (2ml) with 3mls of normal saline 0.9%. Patients will receive a sealed, opaque envelope containing a code with either N or D according to the randomization software pre-operatively, which will be opened by an anesthesiologist or nurse not involved in the study. The anesthesiologist or nurse opening the envelope will be told to withhold this information from the operator/investigator and patient. If the envelope contains the letter D, the said nurse/ anesthesiologist will be told to prepare and administer the nebulised drug as described, also without the knowledge of the operator/investigator. The operator/investigator will have no contact with the patient once the envelope is opened, and will remain away from the preoperative receiving room for 30 minutes from the arrival of patient. Patients in group D will receive a total of 5mls of nebulized drug 30 minutes prior to induction of anaesthesia in the pre-operative receiving room via a wall-mounted oxygen source at 15L/minute. After nebulisation for 30 minutes in the pre-operative receiving area, patients will be brought to the respective operating theatre. Monitoring according to standards will be applied - Non-invasive blood pressure, ECG, oxygen saturation, and capnography. A humidified gas exchanger will be used for all patients. Conduct of anesthesia will be as follows: Patients will not be premedicated Patients will be pre-oxygenated with 100% oxygen for 3-5 minutes or until an end-tidal oxygen fraction of 85 is achieved Intravenous induction with IV Fentanyl 1-2 mcg/kg, IV Propofol 1-3mg/kg, with no use of neuromuscular blockade of IV Dexamethasone. The insertion of a fully deflated SGA AMBU AURAGAIN® lubricated with Lignocaine 2% on the posterior aspect using the appropriate size according to patients' weight once there is loss of eyelash reflex by the operator using a standardized technique. The cuff will then be inflated with appropriate amount of air according to LMA size Cuff pressure will be measured immediately once the airway is secured, and subsequently measured hourly using a handheld pressure gauge. Cuff pressure of not more than 60 cmH20 will be maintained Anaesthesia will be maintained using Sevoflurane, titrated to a Minimum Alveolar Concentration (MAC) of 0.9-1.0 in 50/50 oxygen/air mixture with SIMV (Pressure or volume control) mode At the end of anaesthesia, the oral airway will be suctioned once gently and 100% oxygen will be administered until the SGA removed without deflation once regular, spontaneous ventilation has returned with opening of eyes to calling of name Patients will be transferred to the recovery area where all patient will receive supplemental oxygen via face mask at 5L/minute until discharged from the post-operative recovery unit. The 4 point questionnaire on POST will be applied at 30 minutes to 1 hour and 24 hours post-operatively in the ward by the same operator. If the patient is discharged prior to the 24 hour interview, they will be followed up via phone. Scoring System for Sore Throat, Cough and Hoarseness, from Tazeh-kand et al:
Official Title
-----------------
The Effectiveness of Preemptive Nebulized Dexamethasone in Reducing Post- Operative Sore Throat Following the Use of AMBU® AURAGAINTM Device: A Double Blind, Randomised Clinical Trial
Conditions
-----------------
Sore Throat, Hoarseness, Dexamethasone, Supraglottic Airway Devices
Intervention / Treatment
-----------------
* Drug: Dexamethasone
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Between the ages of 18-70 years American Society of Anaesthesiology (ASA) physical status of 1 and 2 Patients undergoing elective procedures under general anaesthesia between the data collection period suitable for SGA device Exclusion Criteria: Pre-existing sore throat/hoarseness on pre-operative assessment Patients with history of postoperative nausea or vomiting Recent (2 weeks) upper or lower respiratory tract infection Known hypersensitivity to dexamethasone or on regular steroids Uncontrolled diabetes of capillary blood sugar more than 10mmol/l on pre-operative assessment Morbidly obese with BMI > 40 kg/m2 Procedure exceeding 3 hours duration Procedure requiring prone or Trendelenburg position or manipulation of head post-induction Oral and neck surgeries Pregnant patients Patients with cognitive disabilities Patients requiring nasogastric tube or nasal temperature probe insertion Patient refusal
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?
-----------------
Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Receiving routine conduct of general anaesthesia for supraglottic airway device | |
| Experimental: Dexamethasone<br>Receiving pre-operatively single dose nebulised dexamethasone 8mg prior to induction of general anaesthesia | Drug: Dexamethasone<br>* Pre-operatively nebuliser dexamethasone 8mg prior to induction of anesthesia<br>* Other names: Decan;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of POST up to 24 hours post-operatively in patients who received pre-operative nebulized dexamethasone | Patients will be evaluated using scoring system for sore throat, cough and hoarseness | up to 24 hours post-operatively |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of cough up to 24 hours post-operatively in patients who received pre-operative nebulized dexamethasone | Patients will be evaluated using scoring system for sore throat, cough and hoarseness | up to 24 hours post-operatively |
| Incidence of hoarseness of voice up to 24 hours post-operatively in patients who received pre-operative nebulized dexamethasone | Patients will be evaluated using scoring system for sore throat, cough and hoarseness | up to 24 hours post-operatively |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Dexamethasone, Supraglottic airway device, Post operative Sore throat, Post operative hoarseness of voice
|
NCT04042974
|
Vaginal Dinoprostone Prior to Diagnostic Office Hysteroscopy in Primarily Infertile Patients
|
To compare the effectiveness of vaginal dinoprostone with placebo in minimizing the pain experienced by primarily infertile patients during diagnostic office hysteroscopy and to assess the ease of insertion of hysteroscope as reported by the hysteroscopist.
|
hysteroscopy is commonly used in the diagnosis and treatment of intrauterine lesions such as polyps, fibroids, septa, and adhesions, and in the presence of abnormal bleeding and during the removal of an intrauterine device or foreign body. Cervical ripening is made possible by the use of medication through different routes. The most commonly used agent is misoprostol, a synthetic prostaglandin E1 (PGE1) analog that is frequently administered in off-label use in obstetrics and gynecology for medical abortion, labor induction, endometrial biopsy, dilatation and curettage, intrauterine device insertion, myomectomy, postpartum haemorrhage, and cervical ripening. In contrast, dinoprostone, a natural PGE2, is mostly used in obstetrics for cervical ripening and the stimulation of uterine contractions to induce labor.
|
Vaginal Dinoprostone Prior to Diagnostic Office Hysteroscopy in Primarily Infertile Patients:a Randomized Controlled Trial
|
Hysteroscopy
|
* Drug: vaginal dinoprostone
* Drug: placebo
|
Inclusion Criteria:~nulliparous women with primary infertility requiring a diagnostic hysteroscopy as a part of an infertility diagnosis workup~Exclusion Criteria:~• women with suspected pregnancy~heavy vaginal bleeding~recent pelvic infection~those known to have hypersensitivity or contraindication to dinoprostone~those who received analgesics prior to OH~a concomitant neurologic disease that could affect the correct evaluation of pain
|
15 Years
|
40 Years
|
Female
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensity of pain | Pain intensity will be assessed by visual analogue scale during the procedure.visual analogue scale ranging from 0 to 10 | an expected average of 10 minutes |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensity of pain | Pain intensity will be assessed by visual analogue scale 30 minutes after the procedure.visual analogue scale ranging from 0 to 10 | 30 minutes after the procedure |
| Operative time | From the introduction of hysteroscope into the vagina till compilation of hysteroscopic examination | an expected average 10 minutes |
|
Dinoprostone, Oxytocics, Reproductive Control Agents, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dinoprostone<br>1 vaginal tablet of dinoprostone (3mg) (prostin® E2, Pharmacia & Upjohn, Puurs, Belgium) inserted by the patient 12 hours before the scheduled office hysteroscopy. | Drug: vaginal dinoprostone<br>* 1 vaginal tablet of dinoprostone (3mg) (prostin® E2, Pharmacia & Upjohn, Puurs, Belgium) inserted by the patient 12 hours before the scheduled office hysteroscopy.<br>|
| Placebo Comparator: placebo<br>one tablet of placebo inserted by the patient 12 hours before the scheduled office hysteroscopy. | Drug: placebo<br>* one tablet of placebo inserted by the patient 12 hours before the scheduled office hysteroscopy.<br>|
|
Vaginal Dinoprostone Prior to Diagnostic Office Hysteroscopy in Primarily Infertile Patients
Study Overview
=================
Brief Summary
-----------------
To compare the effectiveness of vaginal dinoprostone with placebo in minimizing the pain experienced by primarily infertile patients during diagnostic office hysteroscopy and to assess the ease of insertion of hysteroscope as reported by the hysteroscopist.
Detailed Description
-----------------
hysteroscopy is commonly used in the diagnosis and treatment of intrauterine lesions such as polyps, fibroids, septa, and adhesions, and in the presence of abnormal bleeding and during the removal of an intrauterine device or foreign body. Cervical ripening is made possible by the use of medication through different routes. The most commonly used agent is misoprostol, a synthetic prostaglandin E1 (PGE1) analog that is frequently administered in off-label use in obstetrics and gynecology for medical abortion, labor induction, endometrial biopsy, dilatation and curettage, intrauterine device insertion, myomectomy, postpartum haemorrhage, and cervical ripening. In contrast, dinoprostone, a natural PGE2, is mostly used in obstetrics for cervical ripening and the stimulation of uterine contractions to induce labor.
Official Title
-----------------
Vaginal Dinoprostone Prior to Diagnostic Office Hysteroscopy in Primarily Infertile Patients:a Randomized Controlled Trial
Conditions
-----------------
Hysteroscopy
Intervention / Treatment
-----------------
* Drug: vaginal dinoprostone
* Drug: placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: nulliparous women with primary infertility requiring a diagnostic hysteroscopy as a part of an infertility diagnosis workup Exclusion Criteria: • women with suspected pregnancy heavy vaginal bleeding recent pelvic infection those known to have hypersensitivity or contraindication to dinoprostone those who received analgesics prior to OH a concomitant neurologic disease that could affect the correct evaluation of pain
Ages Eligible for Study
-----------------
Minimum Age: 15 Years
Maximum Age: 40 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dinoprostone<br>1 vaginal tablet of dinoprostone (3mg) (prostin® E2, Pharmacia & Upjohn, Puurs, Belgium) inserted by the patient 12 hours before the scheduled office hysteroscopy. | Drug: vaginal dinoprostone<br>* 1 vaginal tablet of dinoprostone (3mg) (prostin® E2, Pharmacia & Upjohn, Puurs, Belgium) inserted by the patient 12 hours before the scheduled office hysteroscopy.<br>|
| Placebo Comparator: placebo<br>one tablet of placebo inserted by the patient 12 hours before the scheduled office hysteroscopy. | Drug: placebo<br>* one tablet of placebo inserted by the patient 12 hours before the scheduled office hysteroscopy.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensity of pain | Pain intensity will be assessed by visual analogue scale during the procedure.visual analogue scale ranging from 0 to 10 | an expected average of 10 minutes |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensity of pain | Pain intensity will be assessed by visual analogue scale 30 minutes after the procedure.visual analogue scale ranging from 0 to 10 | 30 minutes after the procedure |
| Operative time | From the introduction of hysteroscope into the vagina till compilation of hysteroscopic examination | an expected average 10 minutes |
|
|
NCT00777322
|
T-Cat Laser & Cross-linking for Keratoconus
|
The purpose of this study is to determine whether excimer laser corneal surface ablation (T-Cat) can be safely combined with simultaneous corneal collagen cross-linking treatment to produce an improved and stable corneal profile in the treatment of keratoconus.
|
Theoretical framework:~Corneal ectasia is a relative weakness in the structure of the cornea, which produces a progressive change in its shape with resultant visual distortion.~Excimer laser surface ablation can be used to re-shape the corneal profile. When the corneal shape is very irregular, corneal topography data gives the best information as to how to re-shape the cornea into a normal profile, and this Topography-Computer Assisted Treatment (T-Cat) will be used to modulate the surface corneal shape.~It is known that collagen cross-linking in the cornea occurs naturally with age, and in diabetes, both of which seem to prevent progressive ectasia. Corneal collagen cross-linking with riboflavin has been shown to stabilize the cornea in keratoconus, and prevents progression of the disease. If cross-linking is performed at that moment that the cornea has been re-shaped by T-Cat treatment, it should help prevent the corneal thinning resultant from the laser treatment from destabilising the cornea and causing progressive ectasia.~Purpose:~To determine whether excimer laser corneal surface ablation (T-Cat) can be safely combined with simultaneous corneal collagen cross-linking treatment to produce an improved and stable corneal profile.~Design:~Prospective, interventional trial.
|
Pilot Study of Excimer Laser Topography-Computer Assisted Treatment (T-Cat) Combined With Corneal Collagen Cross-linking With Riboflavin and UV Light
|
Keratoconus, Pellucid Marginal Degeneration
|
* Procedure: Excimer laser ablation, and collagen cross-linking
|
Inclusion Criteria:~Patients with known keratoconus or pellucid marginal degeneration.~Exclusion Criteria:~Age < 18 years > 50 years.~Minimal corneal pachymetry in eye to be treated of < 400μ.~Evidence of other corneal disease in the eye to be treated (e.g. Herpes simplex keratitis).~Women who are pregnant or nursing at the time of the initial treatment.~Presence of significant central corneal opacity.~Patients unwilling to not wear rigid contact lenses in the eye to be operated on for at least one month before baseline examination, and for the first six months post-operatively.
|
18 Years
|
50 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 difference in the pre- and post-operative unaided visual acuity, best corrected visual acuity, and refraction. | | At six months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corneal topographic profile. | | At six months |
|
keratoconus, pellucid marginal degeneration, corneal ectasia, collagen cross-linking, riboflavin, UV light, excimer laser, Topography-Computer Assisted Treatment (T-Cat), Wavelight Allegretto laser
|
Riboflavin, Dextrans, Vitamin B Complex, Vitamins, Micronutrients, Physiological Effects of Drugs, Photosensitizing Agents, Dermatologic Agents, Anticoagulants, Plasma Substitutes, Blood Substitutes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional study<br>Patients with known keratoconus or pellucid marginal degeneration will be invited to join the study. The study is partly a continuation in the management of patients who have had previous keratophakia, who will have near-normal or supra-physiological levels of corneal thickness. It is also intended for patients with relatively mild keratoconus who have sufficient corneal thickness to allow a limited laser ablation whilst still leaving a residual stromal bed of at least 350μ. | Procedure: Excimer laser ablation, and collagen cross-linking<br>* Surgery is performed with topical anaesthesia. The central corneal epithelium is removed. Excimer laser ablation is applied (typically 15-30 seconds). Residual bed thickness is checked with an ultrasonic pachymeter. Topical application of riboflavin 0.1% in dextran is commenced at 5 minute intervals. When an adequate saturation of the anterior chamber with riboflavin has been achieved, cross-linking treatment will proceed. Output from the UV light generating equipment is measured with a UV light meter and set at 3mW/cm². Thirty minutes of treatment is given, interrupted at five minute intervals by the application of more topical riboflavin drops. Finally the eye has a bandage soft contact lens placed, with preservative free topical antibiotic, steroid, and cycloplegic drop application.<br>* Other names: Pecshke UV-X illumination system;|
|
T-Cat Laser & Cross-linking for Keratoconus
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether excimer laser corneal surface ablation (T-Cat) can be safely combined with simultaneous corneal collagen cross-linking treatment to produce an improved and stable corneal profile in the treatment of keratoconus.
Detailed Description
-----------------
Theoretical framework: Corneal ectasia is a relative weakness in the structure of the cornea, which produces a progressive change in its shape with resultant visual distortion. Excimer laser surface ablation can be used to re-shape the corneal profile. When the corneal shape is very irregular, corneal topography data gives the best information as to how to re-shape the cornea into a normal profile, and this Topography-Computer Assisted Treatment (T-Cat) will be used to modulate the surface corneal shape. It is known that collagen cross-linking in the cornea occurs naturally with age, and in diabetes, both of which seem to prevent progressive ectasia. Corneal collagen cross-linking with riboflavin has been shown to stabilize the cornea in keratoconus, and prevents progression of the disease. If cross-linking is performed at that moment that the cornea has been re-shaped by T-Cat treatment, it should help prevent the corneal thinning resultant from the laser treatment from destabilising the cornea and causing progressive ectasia. Purpose: To determine whether excimer laser corneal surface ablation (T-Cat) can be safely combined with simultaneous corneal collagen cross-linking treatment to produce an improved and stable corneal profile. Design: Prospective, interventional trial.
Official Title
-----------------
Pilot Study of Excimer Laser Topography-Computer Assisted Treatment (T-Cat) Combined With Corneal Collagen Cross-linking With Riboflavin and UV Light
Conditions
-----------------
Keratoconus, Pellucid Marginal Degeneration
Intervention / Treatment
-----------------
* Procedure: Excimer laser ablation, and collagen cross-linking
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with known keratoconus or pellucid marginal degeneration. Exclusion Criteria: Age < 18 years > 50 years. Minimal corneal pachymetry in eye to be treated of < 400μ. Evidence of other corneal disease in the eye to be treated (e.g. Herpes simplex keratitis). Women who are pregnant or nursing at the time of the initial treatment. Presence of significant central corneal opacity. Patients unwilling to not wear rigid contact lenses in the eye to be operated on for at least one month before baseline examination, and for the first six months post-operatively.
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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional study<br>Patients with known keratoconus or pellucid marginal degeneration will be invited to join the study. The study is partly a continuation in the management of patients who have had previous keratophakia, who will have near-normal or supra-physiological levels of corneal thickness. It is also intended for patients with relatively mild keratoconus who have sufficient corneal thickness to allow a limited laser ablation whilst still leaving a residual stromal bed of at least 350μ. | Procedure: Excimer laser ablation, and collagen cross-linking<br>* Surgery is performed with topical anaesthesia. The central corneal epithelium is removed. Excimer laser ablation is applied (typically 15-30 seconds). Residual bed thickness is checked with an ultrasonic pachymeter. Topical application of riboflavin 0.1% in dextran is commenced at 5 minute intervals. When an adequate saturation of the anterior chamber with riboflavin has been achieved, cross-linking treatment will proceed. Output from the UV light generating equipment is measured with a UV light meter and set at 3mW/cm². Thirty minutes of treatment is given, interrupted at five minute intervals by the application of more topical riboflavin drops. Finally the eye has a bandage soft contact lens placed, with preservative free topical antibiotic, steroid, and cycloplegic drop application.<br>* Other names: Pecshke UV-X illumination system;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference in the pre- and post-operative unaided visual acuity, best corrected visual acuity, and refraction. | | At six months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corneal topographic profile. | | At six months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
keratoconus, pellucid marginal degeneration, corneal ectasia, collagen cross-linking, riboflavin, UV light, excimer laser, Topography-Computer Assisted Treatment (T-Cat), Wavelight Allegretto laser
|
NCT02826759
|
Serum Sphingolipidomic Analyses in Healthy, Diabetic and Prediabetic Subjects
|
This study is designed to compare the serum sphingolipidomic analyses in healthy, pre-diabetic and diabetic subjects. age, sex and BMI are matched among these three groups. As ceramide, sphingosine, sphingosine-1-phosphate and sphinganine are involved in inflammation, immunity and cancer, investigators proposed a hypothesis that sphingosine-1-phosphate and other sphingolipids may be associated with the progress of type 2 diabetes. sphingolipids may be a biomarker for diabetes.
|
The first purpose of this study is to determine whether serum sphingolipid metabolites associate significantly with the weight among type 2 diabetes. 60 patients with diagnosed type 2 diabetes will be recruited. The serum concentrations of sphingolipid metabolites of 20 type 2 diabetic patients with obesity will be compared to age- and sex-matched series of 40 type 2 patients without obesity.~The second purpose of this study is to determine whether serum sphingolipid metabolites associate significantly with the process and severity of type 2 diabetes. The serum concentrations of sphingolipid metabolites of 20 subjects with type 2 diabetes will be compared to age-, sex- and BMI-matched series of healthy and pre-diabetic subjects. Investigators speculate that the serum concentration of sphingolipid metabolites are positively related with the progression of diabetes. In order to discover why serum sphingolipid metabolites correlates with the progression of diabetes, detailed information on HbA1c, duration of diabetes history and insulin resistance defined by homeostatic model assessment (HOMA-IR) will be analysed. These three parameters may affect the serum concentrations of sphingolipid metabolites.
|
Comparison of Serum Sphingolipidomic Analyses in Healthy, Pre-diabetic and Diabetic Subjects
|
Diabetes Mellitus, Type 2, Prediabetic State
|
* Other: diabetes
|
Inclusion Criteria:~clinical diagnosis of diabetes mellitus, type 2~clinical diagnosis of prediabetic status~older than 18 and younger than 90 years-old~clinical diagnosis of insulin-resistance~clinical diagnosis of newly onset of diabetes mellitus, type 2~those who are willing to participate in the trial and sign the consent form~Exclusion Criteria:~any cardiovascular disease (myocardial infarction, heart failure, cerebrovascular accident)~missing information of BMI~sever liver, kidney dysfunction~sever pancreatitis or those who received pancreatectomy~on medications of hormone, immunosuppressive therapy or drugs that may affect the bioactivity or concentration of sphingolipids (e.g. asprin )~patients on pregnancy~sever systematic diseases including carcinoma, mental disorder, sever anemia et al.
|
18 Years
|
90 Years
|
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum concentration of sphingosine-1-phosphate, micromol per liter | | Nov, 2016 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum concentration of sphingosine, micromol per liter | | Nov, 2016 |
| serum concentration of sphinganine-1-phosphate, micromol per liter | | Nov, 2016 |
| serum concentration of sphinganine, micromol per liter | | Nov, 2016 |
| serum concentration of ceramide, micromol per liter | | Nov, 2016 |
|
sphingolipid, diabetes mellitus, biomarker, obesity, insulin resistance
|
Insulin, Hypoglycemic Agents, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| serum sphingolipid metabolites in healthy subjects<br>Healthy subjects are classified according to BMI into three subgroups: healthy normal weight subjects, healthy overweight subjects and healthy subjects with obesity. Age and sex are matched among three subgroups. serum sphingolipid metabolites including sphingosine-1-phosphate will be compared. | |
| serum sphingolipid metabolites in diabetic subjects<br>Diagnosed diabetic patients are divided into three subgroups: diabetic patients with normal weight, overweight and obesity. age and sex are matched. | Other: diabetes<br>* the exposure of interests are obesity, diabetes and insulin-resistance<br>* Other names: insulin-resistance;|
| serum sphingolipid metabolites in the progression of diabetes<br>serum sphingolipid metabolites are compared among three age-, sex- and body mass index-matched subgroups: healthy subjects, subjects with pre-diabetes, subjects with diabetes | Other: diabetes<br>* the exposure of interests are obesity, diabetes and insulin-resistance<br>* Other names: insulin-resistance;|
| serum sphingolipid metabolites and HbA1c<br>diabetic subjects are divided by HbA1c level. the cut-offs are 7% and 9%. serum sphingolipid metabolites will be tested among diabetic patients with HbA1c <7%, 7%-9% and >9% | Other: diabetes<br>* the exposure of interests are obesity, diabetes and insulin-resistance<br>* Other names: insulin-resistance;|
| serum sphingolipid metabolites in insulin-resistant subjects<br>comparison of serum sphingolipid metabolites in newly diagnosed insulin-resistant subjects and age-, sex- and BMI-matched healthy controls. | Other: diabetes<br>* the exposure of interests are obesity, diabetes and insulin-resistance<br>* Other names: insulin-resistance;|
|
Serum Sphingolipidomic Analyses in Healthy, Diabetic and Prediabetic Subjects
Study Overview
=================
Brief Summary
-----------------
This study is designed to compare the serum sphingolipidomic analyses in healthy, pre-diabetic and diabetic subjects. age, sex and BMI are matched among these three groups. As ceramide, sphingosine, sphingosine-1-phosphate and sphinganine are involved in inflammation, immunity and cancer, investigators proposed a hypothesis that sphingosine-1-phosphate and other sphingolipids may be associated with the progress of type 2 diabetes. sphingolipids may be a biomarker for diabetes.
Detailed Description
-----------------
The first purpose of this study is to determine whether serum sphingolipid metabolites associate significantly with the weight among type 2 diabetes. 60 patients with diagnosed type 2 diabetes will be recruited. The serum concentrations of sphingolipid metabolites of 20 type 2 diabetic patients with obesity will be compared to age- and sex-matched series of 40 type 2 patients without obesity. The second purpose of this study is to determine whether serum sphingolipid metabolites associate significantly with the process and severity of type 2 diabetes. The serum concentrations of sphingolipid metabolites of 20 subjects with type 2 diabetes will be compared to age-, sex- and BMI-matched series of healthy and pre-diabetic subjects. Investigators speculate that the serum concentration of sphingolipid metabolites are positively related with the progression of diabetes. In order to discover why serum sphingolipid metabolites correlates with the progression of diabetes, detailed information on HbA1c, duration of diabetes history and insulin resistance defined by homeostatic model assessment (HOMA-IR) will be analysed. These three parameters may affect the serum concentrations of sphingolipid metabolites.
Official Title
-----------------
Comparison of Serum Sphingolipidomic Analyses in Healthy, Pre-diabetic and Diabetic Subjects
Conditions
-----------------
Diabetes Mellitus, Type 2, Prediabetic State
Intervention / Treatment
-----------------
* Other: diabetes
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: clinical diagnosis of diabetes mellitus, type 2 clinical diagnosis of prediabetic status older than 18 and younger than 90 years-old clinical diagnosis of insulin-resistance clinical diagnosis of newly onset of diabetes mellitus, type 2 those who are willing to participate in the trial and sign the consent form Exclusion Criteria: any cardiovascular disease (myocardial infarction, heart failure, cerebrovascular accident) missing information of BMI sever liver, kidney dysfunction sever pancreatitis or those who received pancreatectomy on medications of hormone, immunosuppressive therapy or drugs that may affect the bioactivity or concentration of sphingolipids (e.g. asprin ) patients on pregnancy sever systematic diseases including carcinoma, mental disorder, sever anemia et al.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 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 |
| --- | --- |
| serum sphingolipid metabolites in healthy subjects<br>Healthy subjects are classified according to BMI into three subgroups: healthy normal weight subjects, healthy overweight subjects and healthy subjects with obesity. Age and sex are matched among three subgroups. serum sphingolipid metabolites including sphingosine-1-phosphate will be compared. | |
| serum sphingolipid metabolites in diabetic subjects<br>Diagnosed diabetic patients are divided into three subgroups: diabetic patients with normal weight, overweight and obesity. age and sex are matched. | Other: diabetes<br>* the exposure of interests are obesity, diabetes and insulin-resistance<br>* Other names: insulin-resistance;|
| serum sphingolipid metabolites in the progression of diabetes<br>serum sphingolipid metabolites are compared among three age-, sex- and body mass index-matched subgroups: healthy subjects, subjects with pre-diabetes, subjects with diabetes | Other: diabetes<br>* the exposure of interests are obesity, diabetes and insulin-resistance<br>* Other names: insulin-resistance;|
| serum sphingolipid metabolites and HbA1c<br>diabetic subjects are divided by HbA1c level. the cut-offs are 7% and 9%. serum sphingolipid metabolites will be tested among diabetic patients with HbA1c <7%, 7%-9% and >9% | Other: diabetes<br>* the exposure of interests are obesity, diabetes and insulin-resistance<br>* Other names: insulin-resistance;|
| serum sphingolipid metabolites in insulin-resistant subjects<br>comparison of serum sphingolipid metabolites in newly diagnosed insulin-resistant subjects and age-, sex- and BMI-matched healthy controls. | Other: diabetes<br>* the exposure of interests are obesity, diabetes and insulin-resistance<br>* Other names: insulin-resistance;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum concentration of sphingosine-1-phosphate, micromol per liter | | Nov, 2016 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum concentration of sphingosine, micromol per liter | | Nov, 2016 |
| serum concentration of sphinganine-1-phosphate, micromol per liter | | Nov, 2016 |
| serum concentration of sphinganine, micromol per liter | | Nov, 2016 |
| serum concentration of ceramide, micromol per liter | | Nov, 2016 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
sphingolipid, diabetes mellitus, biomarker, obesity, insulin resistance
|
|
NCT03110679
|
Randomized Double-blind Study on the Treatment of Osteoarthritis of the Bilateral Knee: Autologous Bone Marrow Concentrate vs. Hyaluronic Acid
|
OA-bi-Blind is a randomized double-blind study on the treatment of osteoarthritis of the Bilateral knee: autologous bone marrow concentrate vs. hyaluronic acid.
|
a randomized, controlled, double-blind study and we will be evaluated and compared the clinical and radiological results of concentrated autologous bone marrow against the hyaluronic acid in patients with bilateral knee osteoarthrosis . In randomization, one knee will be treated with autologous bone marrow concentrate and other knee with hyaluronic acid, then every patient is considered both in control and treatment group, limiting the heterogenity between groups and will not be informed of the knee assigned to the treatment group.
|
Randomized Double-blind Study on the Treatment of Osteoarthritis of the Bilateral Knee: Autologous Bone Marrow Concentrate vs. Hyaluronic Acid
|
Osteoarthritis, Knee
|
* Biological: injection of autologous bone marrow concentrate
* Biological: injection of hyaluronic acid.
|
Inclusion Criteria:~Male or female patients, aged between 18 and 75 years;~Bilateral symptomatic knee osteoarthritis (Kellgren-Lawrence grade 1-4);~Failure after two months of conservative treatment;~Capacity and consent of patients to participate actively in the rehabilitation protocol, follow-up clinic and radiology protocol;~Signature of informed consent.~Exclusion Criteria:~Patients incapable of discernment;~Patients with malignancy~Patients with rheumatic diseases;~Patients with diabetes;~Patients with metabolic disorders of the thyroid;~Patients belonging abuse of alcohol, drugs or medications;~Patients with misalignment of the lower limbs than 10 °;~Body Mass Index> 40;~Patients with a history of trauma or intra-articular infiltration of therapeutic substances within 6 months prior to treatment.
|
18 Years
|
75 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: autologous bone marrow concentrate vs. hyaluronic acid.
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International Knee Documentation Committee (IKDC)-Subjective score | Clinical improvement, measured by the change in scores IKDC Subjective | Time Frame: 6 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International Knee Documentation Committee (IKDC)-Subjective score | Stability of the initial clinical improvement between 6 and 24 months | Time Frame: 1,3,6, 12, 24 months evaluation |
| Knee Injury and Osteoarthritis Outcome Score (KOOS). | Stability of the initial clinical improvement between 6 and 24 months of the KOOS pain score | Time Frame: 1,3,6, 12, 24 months evaluation |
|
osteoarthritis, autologous bone marrow concentrate
|
Viscosupplements, Protective Agents, Hyaluronic Acid, Adjuvants, Immunologic, Immunologic Factors, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: autologous bone marrow concentrate<br>concentration of bone marrow taken from the patient's right tibia using Bio-MAC® suction catheter, company Biologic Therapies, Inc., and concentrated by centrifuge Bio.SPINTM Magellan®, company Biologic Therapies , Inc., and its injection in the intra-articular. | Biological: injection of autologous bone marrow concentrate<br> <br> |
| Experimental: hyaluronic acid.<br>single injection of intra-articular hyaluronic acid 60mg (4 cc), and serve as a control. | Biological: injection of hyaluronic acid.<br> <br> |
|
Randomized Double-blind Study on the Treatment of Osteoarthritis of the Bilateral Knee: Autologous Bone Marrow Concentrate vs. Hyaluronic Acid
Study Overview
=================
Brief Summary
-----------------
OA-bi-Blind is a randomized double-blind study on the treatment of osteoarthritis of the Bilateral knee: autologous bone marrow concentrate vs. hyaluronic acid.
Detailed Description
-----------------
a randomized, controlled, double-blind study and we will be evaluated and compared the clinical and radiological results of concentrated autologous bone marrow against the hyaluronic acid in patients with bilateral knee osteoarthrosis . In randomization, one knee will be treated with autologous bone marrow concentrate and other knee with hyaluronic acid, then every patient is considered both in control and treatment group, limiting the heterogenity between groups and will not be informed of the knee assigned to the treatment group.
Official Title
-----------------
Randomized Double-blind Study on the Treatment of Osteoarthritis of the Bilateral Knee: Autologous Bone Marrow Concentrate vs. Hyaluronic Acid
Conditions
-----------------
Osteoarthritis, Knee
Intervention / Treatment
-----------------
* Biological: injection of autologous bone marrow concentrate
* Biological: injection of hyaluronic acid.
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female patients, aged between 18 and 75 years; Bilateral symptomatic knee osteoarthritis (Kellgren-Lawrence grade 1-4); Failure after two months of conservative treatment; Capacity and consent of patients to participate actively in the rehabilitation protocol, follow-up clinic and radiology protocol; Signature of informed consent. Exclusion Criteria: Patients incapable of discernment; Patients with malignancy Patients with rheumatic diseases; Patients with diabetes; Patients with metabolic disorders of the thyroid; Patients belonging abuse of alcohol, drugs or medications; Patients with misalignment of the lower limbs than 10 °; Body Mass Index> 40; Patients with a history of trauma or intra-articular infiltration of therapeutic substances within 6 months prior to treatment.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: autologous bone marrow concentrate vs. hyaluronic acid.
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: autologous bone marrow concentrate<br>concentration of bone marrow taken from the patient's right tibia using Bio-MAC® suction catheter, company Biologic Therapies, Inc., and concentrated by centrifuge Bio.SPINTM Magellan®, company Biologic Therapies , Inc., and its injection in the intra-articular. | Biological: injection of autologous bone marrow concentrate<br> <br> |
| Experimental: hyaluronic acid.<br>single injection of intra-articular hyaluronic acid 60mg (4 cc), and serve as a control. | Biological: injection of hyaluronic acid.<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International Knee Documentation Committee (IKDC)-Subjective score | Clinical improvement, measured by the change in scores IKDC Subjective | Time Frame: 6 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International Knee Documentation Committee (IKDC)-Subjective score | Stability of the initial clinical improvement between 6 and 24 months | Time Frame: 1,3,6, 12, 24 months evaluation |
| Knee Injury and Osteoarthritis Outcome Score (KOOS). | Stability of the initial clinical improvement between 6 and 24 months of the KOOS pain score | Time Frame: 1,3,6, 12, 24 months evaluation |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
osteoarthritis, autologous bone marrow concentrate
|
NCT03586245
|
Iron Absorption From Iron Enriched Aspergillus Oryzae in Females Using Stable Isotope Methodology
|
The objective of this study was to compare the iron absorption from ferric pyrophosphate enriched Aspergillus oryzae (ASP-p) to commonly used ferric pyrophosphate (FePP) and ferrous sulfate (FeSO4) when fortified in chicken bouillon, using stable isotope methodology.
|
Iron deficiency anemia (IDA) remains the most common nutrient deficiency, globally. Consequences such as decreased cognition, growth impairment, and morbidity and mortality arise from inadequate iron intake. Many technological challenges are presented in fortifying foods with iron, as inorganic iron salts are known to cause organoleptic problems in the food. As a result, finding an iron fortificant that doesn't alter taste, smell or stability of the food is ideal, however most suitable iron fortificants contain low bioavailability. Thirty-five non-anemic female subjects with ferritin ≤ 40 µg/L were recruited for both studies (17 in study I; 18 in study II). In both studies, each meal contained a total of 4.2 mg of added iron fortificants to a test meal containing 6.6 g of chicken bouillon. Participants were randomized to consume either meal A or B, followed by B or C. In study I, subjects consumed a total of 10 mg 57Fe as FePP and 2 mg 58Fe as ASP-p each over three consecutive days. Study II, subjects consumed a total of 10 mg 57Fe as FeSO4 and 2 mg 58Fe as ASP-p over 2 weekends. Blood samples collected at baseline were used to measure iron status indicators such as serum ferritin, C-reactive protein, hepcidin and hematocrit. Fourteen days following final isotope dosing, whole blood samples were collected and the fractional iron absorption of each iron fortificant containing labelled stable isotopes was measured via thermal ionization mass spectrometry with estimation of 80% incorporation into the hemoglobin.
|
Iron Absorption From Iron Enriched Aspergillus Oryzae in Females Using Stable Iron Isotope Methodology.
|
Iron Absorption
|
* Dietary Supplement: Ferric pyrophosphate
* Dietary Supplement: Aspiron
* Dietary Supplement: Ferrous sulfate
|
Inclusion Criteria:~Suboptimal iron stores (Serum ferritin < 40 µg/L)~BMI in range 18.5 - 24.9 kg/m2~Willing to consumed meals containing iron supplement~Willing to discontinue blood donation two weeks prior and during the study~Willing to discontinue vitamin and mineral supplement use during the study~Willing to provide a 15 ml blood for initial screening and 30 ml blood during the study (15 ml at each visit for 2 times in 24 days)~Willing to attend 8 lab visits during the study~Exclusion Criteria:~Pregnant~Lactating~Smoker~Anemic (hemoglobin < 120 g/L)~Has gastrointestinal disease/condition that can affect absorption~Vegetarian~Allergic to corn, wheat, soybean nor fungal supplements
|
18 Years
|
35 Years
|
Female
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Subjects consumed two stable isotopes (57Fe and 58Fe). Study I, three consecutive days of meal A followed by crossover of three days meal B were consumed. Study II was a crossover between meal B and meal C.
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Fractional Iron absorption of FePP, FeS)4 and ASP | Isotope enrichment in the whole blood samples after 14 days of feeding the meals assuming 80% incorporation of iron into the hemoglobin. Circulating iron was calculated from blood volume, height (cm), weight (kg) and hemoglobin (g/dL). | Whole blood collected 14 days following isotope consumption to allow for enrichment. |
|
Iron Bioavailability, Iron Fortification, ferrous sulfate, ferric pyrophosphate, aspergillus oryzae, stable isotope
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ferric pyrophosphate<br>Study I group was required to consume a total of 3 meals. Each meal contained 4.2 mg added iron compounds.~57FePP (95.8%) 3.49 mg~Aspergillus oryzae (unenriched) 0.025 mg~FePP natural abundance 0.685 mg.~Subjects received iron fortificants in a meal composed of zucchini, cabbage, carrot (42g each), onion (24g), corn oil (6.3 g), jasmine rice (75g dw), and flavored granulated chicken bouillon (6.6g). All meals were consumed in a fasted state with nothing to eat or drink (besides water) for 3 hours following consumption. | Dietary Supplement: Ferric pyrophosphate<br>* 57 Iron isotopically labeled FePP powder.<br>|
| Experimental: Aspiron<br>The Aspiron group was required to follow the same protocol as the 57Fe as FePP, with the exception of consuming 58Fe ASP.~ASP-p (8% Fe; natural abundance) 3.516 mg~58ASP-p (5% Fe; 99.5% enrichment) 0.68 mg~4.2 total mg of Fe | Dietary Supplement: Aspiron<br>* 58 Iron isotope intrinsically labeled Aspergillus oryzae.<br>|
| Other: Ferrous sulfate<br>The FeSO4 study group was required to consume a total of 3 meals. Each meal contained 4.2 mg added iron compounds. .~Aspergillus oryzae (unenriched) 0.027 mg~57FeSO4 (95.4%) 3.18 mg~4.2 total mg of Fe | Dietary Supplement: Ferrous sulfate<br>* 57 Iron isotopically labeled FeSO4 powder.<br>|
|
Iron Absorption From Iron Enriched Aspergillus Oryzae in Females Using Stable Isotope Methodology
Study Overview
=================
Brief Summary
-----------------
The objective of this study was to compare the iron absorption from ferric pyrophosphate enriched Aspergillus oryzae (ASP-p) to commonly used ferric pyrophosphate (FePP) and ferrous sulfate (FeSO4) when fortified in chicken bouillon, using stable isotope methodology.
Detailed Description
-----------------
Iron deficiency anemia (IDA) remains the most common nutrient deficiency, globally. Consequences such as decreased cognition, growth impairment, and morbidity and mortality arise from inadequate iron intake. Many technological challenges are presented in fortifying foods with iron, as inorganic iron salts are known to cause organoleptic problems in the food. As a result, finding an iron fortificant that doesn't alter taste, smell or stability of the food is ideal, however most suitable iron fortificants contain low bioavailability. Thirty-five non-anemic female subjects with ferritin ≤ 40 µg/L were recruited for both studies (17 in study I; 18 in study II). In both studies, each meal contained a total of 4.2 mg of added iron fortificants to a test meal containing 6.6 g of chicken bouillon. Participants were randomized to consume either meal A or B, followed by B or C. In study I, subjects consumed a total of 10 mg 57Fe as FePP and 2 mg 58Fe as ASP-p each over three consecutive days. Study II, subjects consumed a total of 10 mg 57Fe as FeSO4 and 2 mg 58Fe as ASP-p over 2 weekends. Blood samples collected at baseline were used to measure iron status indicators such as serum ferritin, C-reactive protein, hepcidin and hematocrit. Fourteen days following final isotope dosing, whole blood samples were collected and the fractional iron absorption of each iron fortificant containing labelled stable isotopes was measured via thermal ionization mass spectrometry with estimation of 80% incorporation into the hemoglobin.
Official Title
-----------------
Iron Absorption From Iron Enriched Aspergillus Oryzae in Females Using Stable Iron Isotope Methodology.
Conditions
-----------------
Iron Absorption
Intervention / Treatment
-----------------
* Dietary Supplement: Ferric pyrophosphate
* Dietary Supplement: Aspiron
* Dietary Supplement: Ferrous sulfate
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Suboptimal iron stores (Serum ferritin < 40 µg/L) BMI in range 18.5 - 24.9 kg/m2 Willing to consumed meals containing iron supplement Willing to discontinue blood donation two weeks prior and during the study Willing to discontinue vitamin and mineral supplement use during the study Willing to provide a 15 ml blood for initial screening and 30 ml blood during the study (15 ml at each visit for 2 times in 24 days) Willing to attend 8 lab visits during the study Exclusion Criteria: Pregnant Lactating Smoker Anemic (hemoglobin < 120 g/L) Has gastrointestinal disease/condition that can affect absorption Vegetarian Allergic to corn, wheat, soybean nor fungal supplements
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 35 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: Crossover Assignment
Interventional Model Description: Subjects consumed two stable isotopes (57Fe and 58Fe). Study I, three consecutive days of meal A followed by crossover of three days meal B were consumed. Study II was a crossover between meal B and meal C.
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ferric pyrophosphate<br>Study I group was required to consume a total of 3 meals. Each meal contained 4.2 mg added iron compounds. 57FePP (95.8%) 3.49 mg Aspergillus oryzae (unenriched) 0.025 mg FePP natural abundance 0.685 mg. Subjects received iron fortificants in a meal composed of zucchini, cabbage, carrot (42g each), onion (24g), corn oil (6.3 g), jasmine rice (75g dw), and flavored granulated chicken bouillon (6.6g). All meals were consumed in a fasted state with nothing to eat or drink (besides water) for 3 hours following consumption. | Dietary Supplement: Ferric pyrophosphate<br>* 57 Iron isotopically labeled FePP powder.<br>|
| Experimental: Aspiron<br>The Aspiron group was required to follow the same protocol as the 57Fe as FePP, with the exception of consuming 58Fe ASP. ASP-p (8% Fe; natural abundance) 3.516 mg 58ASP-p (5% Fe; 99.5% enrichment) 0.68 mg 4.2 total mg of Fe | Dietary Supplement: Aspiron<br>* 58 Iron isotope intrinsically labeled Aspergillus oryzae.<br>|
| Other: Ferrous sulfate<br>The FeSO4 study group was required to consume a total of 3 meals. Each meal contained 4.2 mg added iron compounds. . Aspergillus oryzae (unenriched) 0.027 mg 57FeSO4 (95.4%) 3.18 mg 4.2 total mg of Fe | Dietary Supplement: Ferrous sulfate<br>* 57 Iron isotopically labeled FeSO4 powder.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Fractional Iron absorption of FePP, FeS)4 and ASP | Isotope enrichment in the whole blood samples after 14 days of feeding the meals assuming 80% incorporation of iron into the hemoglobin. Circulating iron was calculated from blood volume, height (cm), weight (kg) and hemoglobin (g/dL). | Whole blood collected 14 days following isotope consumption to allow for enrichment. |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Iron Bioavailability, Iron Fortification, ferrous sulfate, ferric pyrophosphate, aspergillus oryzae, stable isotope
|
||
NCT00675467
|
Palliative Care and Symptom Management for the Pediatric Oncology Patient
|
The goal of this study is to learn about the communication, decision-making, symptom management, emotional adjustment, and spiritual needs of parents and pediatric patients treated at the Children's Cancer Hospital at M. D. Anderson (MCACC).~Primary Objectives:~Determine the palliative care service needs of pediatric cancer patients and their parents, including communication, decision-making, symptom management, emotional and spiritual support when receiving treatment for early cancer, treatment for advanced disease, and treatment in the end-of-life period.~Identify intra-group differences in the categories listed in Objective 1 for pediatric cancer patients receiving treatment (a) for early cancer, (b) for advanced disease, and (c) at end-of-life.~Secondary Objectives:~1. Inform the development of a Pediatric Palliative Care Program at the Children's Cancer Hospital at The University of Texas M. D. Anderson Cancer Center (MCACC or MDACC) based on identified needs as determined by primary study aims 1 and 2.
|
PARENT:~The Focus Group:~If you agree to take part in this study, you will attend a 1 1/2 hour group session with 3-9 other caregivers. The group will be led by a group leader and an assistant. The group leader will ask questions to the group about communication, decision-making, symptom management, emotional adjustment, and spirituality experiences and needs during your child's treatment. If you have a child who is also taking part in this study, you will meet separately from your child.~At the time of your arrival and before the beginning of the focus group session, you will be asked to complete a questionnaire. You will be asked about you and your child's age, sex, where you live, your religion (if any), your ethnicity and race, and if there are other children in the family. You will be asked about when you found out your child had cancer, the type of cancer, and when the cancer got worse or came back (if applicable). You will be asked whether others have shared parenting responsibilities, your education level, and if you work and what type of work you do. The questionnaire will take about 5 minutes to complete.~Audiotapes/Transcripts:~The assistant will take notes and the session will be recorded on an audiotape. All audiotapes will be stored in locked cabinets maintained by the study chair. The audiotapes will be destroyed once the study and analyses are complete.~The audiotape will be recorded onto paper transcripts. The completed focus group transcriptions will be placed in a database secured with a password and identification protected. Transcribed results will have all identifiable markers removed and kept in the investigators' locked files. Only the researchers will be able to view the transcriptions.~Length of Study:~Your participation on this study is complete once you finish the group meeting.~PEDIATRIC PARTICIPANT:~The Focus Group:~If you agree to take part in this study, you will go to a 1 1/2 hour group session with 3-9 other patients. The group will be led by a group leader and an assistant. The group leader will ask questions to the group about who you talk with about the disease, how you make a decision, how you manage any symptoms you may have, how you are feeling about the disease, and how religion has helped you during your treatment. If your parent is also taking part in this study, you will meet separately from your parent.~At the time of your arrival and before the beginning of the focus group session, your parent will be asked to complete a questionnaire. Your parent will be asked about their age and sex, your age and sex, where you live, your religion (if any), your ethnicity and race, and if there are other children in the family. Your parent will be asked when they found out you had cancer, the type of cancer, and when the cancer got worse or came back (if applicable). Your parent will be asked whether others have shared parenting responsibilities, their education level, and if they work and about the type of work they do. The questionnaire will take about 5 minutes to complete.~Audiotapes/Transcripts:~The assistant will take notes and the session will be recorded on an audiotape. All audiotapes will be stored in locked cabinets taken care of by the study chair. The audiotapes will be destroyed once the study is over and the researchers have finished looking at the information.~The audiotape will be recorded onto paper transcripts. The completed focus group transcriptions will be placed in a database secured with a password and identification protected. Any personal information about you will be removed from these papers and the papers will be kept in the investigators' locked files. Only the researchers will be able to view the transcriptions.~Length of Study:~Your participation on this study is over once you complete the focus group.
|
Palliative Care and Symptom Management for the Pediatric Oncology Patient
|
Pediatric Cancers
|
* Behavioral: Focus Group - Parent/Caregiver
* Behavioral: Focus Group - Pediatric Patient
|
Inclusion Criteria:~Inclusion for Children:~10-18 years of age~MD Anderson Children's Cancer Center (MCACC) cancer patient~receiving anti-cancer treatment for disease that is not recurrent or metastatic for cancer diagnosed in the past 3-12 mos or receiving anti-cancer treatment for recurrent or metastatic cancer diagnosed within the past 3-12 months~speak & understand English~reside in the Greater Houston area~provide IRB-approved pediatric assent or informed consent, as age appropriate~if < 18 years of age, provide Internal Review Board (IRB)-approved parental permission~child's eligibility is not contingent upon parent's decision to participate~Inclusion for parents:~self-identified parent(s) that has(have) a child eligible for study, per the inclusion and exclusion criteria noted above or has had a child (0-18 yrs of age at time of death) treated for cancer at MCACC who has died in the last 1 to 2 years~speak and understand English~reside in the Houston metropolitan area~provide IRB-approved informed consent~attend different focus groups if more than one eligible parent per child (max 2 parents per child)~parent's eligibility is not contingent upon the child's decision to participate~Exclusion Criteria:~Exclusion for Children:~have cognitive impairment, developmental delay, or emotional distress that would limit participation in a group discussion, as determined by the clinical judgment of the investigator~younger than 10 years or older than 18 years of age~Exclusion for Caregiver:~have cognitive impairment, developmental delay, or emotional distress that would limit participation in a group discussion, as determined by the clinical judgment of the investigator.
|
10 Years
|
18 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Palliative Care Service Needs of Pediatric Cancer Patients + Their Parents | Qualitative data collection. | 3 Years |
|
Pediatric Cancer, Focus Group, Pediatric cancer patients, Parents of Pediatric cancer patients, Pediatric Palliative Care Program
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1<br>Early cancer group-children ages 10-13 years | Behavioral: Focus Group - Parent/Caregiver<br>* A 1 1/2 hour group session with other parents/caregivers.<br>Behavioral: Focus Group - Pediatric Patient<br>* A 1 1/2 hour group session with other pediatric patients.<br>|
| Group 2<br>Early cancer group-children ages 14 to 18 years | Behavioral: Focus Group - Parent/Caregiver<br>* A 1 1/2 hour group session with other parents/caregivers.<br>Behavioral: Focus Group - Pediatric Patient<br>* A 1 1/2 hour group session with other pediatric patients.<br>|
| Group 3<br>Early cancer group-parents of patients ages 10-18 years | Behavioral: Focus Group - Parent/Caregiver<br>* A 1 1/2 hour group session with other parents/caregivers.<br>Behavioral: Focus Group - Pediatric Patient<br>* A 1 1/2 hour group session with other pediatric patients.<br>|
| Group 4<br>Advanced cancer group-children ages 10-13 years | Behavioral: Focus Group - Parent/Caregiver<br>* A 1 1/2 hour group session with other parents/caregivers.<br>Behavioral: Focus Group - Pediatric Patient<br>* A 1 1/2 hour group session with other pediatric patients.<br>|
| Group 5<br>Advanced cancer group-children ages 14-18 years | Behavioral: Focus Group - Parent/Caregiver<br>* A 1 1/2 hour group session with other parents/caregivers.<br>Behavioral: Focus Group - Pediatric Patient<br>* A 1 1/2 hour group session with other pediatric patients.<br>|
| Group 6<br>Advanced cancer group-parents of children ages 10-18 years | Behavioral: Focus Group - Parent/Caregiver<br>* A 1 1/2 hour group session with other parents/caregivers.<br>Behavioral: Focus Group - Pediatric Patient<br>* A 1 1/2 hour group session with other pediatric patients.<br>|
| Group 7<br>End of life group - parents of children ages birth to 18 years of age at time of death | Behavioral: Focus Group - Parent/Caregiver<br>* A 1 1/2 hour group session with other parents/caregivers.<br>Behavioral: Focus Group - Pediatric Patient<br>* A 1 1/2 hour group session with other pediatric patients.<br>|
|
Palliative Care and Symptom Management for the Pediatric Oncology Patient
Study Overview
=================
Brief Summary
-----------------
The goal of this study is to learn about the communication, decision-making, symptom management, emotional adjustment, and spiritual needs of parents and pediatric patients treated at the Children's Cancer Hospital at M. D. Anderson (MCACC). Primary Objectives: Determine the palliative care service needs of pediatric cancer patients and their parents, including communication, decision-making, symptom management, emotional and spiritual support when receiving treatment for early cancer, treatment for advanced disease, and treatment in the end-of-life period. Identify intra-group differences in the categories listed in Objective 1 for pediatric cancer patients receiving treatment (a) for early cancer, (b) for advanced disease, and (c) at end-of-life. Secondary Objectives: 1. Inform the development of a Pediatric Palliative Care Program at the Children's Cancer Hospital at The University of Texas M. D. Anderson Cancer Center (MCACC or MDACC) based on identified needs as determined by primary study aims 1 and 2.
Detailed Description
-----------------
PARENT: The Focus Group: If you agree to take part in this study, you will attend a 1 1/2 hour group session with 3-9 other caregivers. The group will be led by a group leader and an assistant. The group leader will ask questions to the group about communication, decision-making, symptom management, emotional adjustment, and spirituality experiences and needs during your child's treatment. If you have a child who is also taking part in this study, you will meet separately from your child. At the time of your arrival and before the beginning of the focus group session, you will be asked to complete a questionnaire. You will be asked about you and your child's age, sex, where you live, your religion (if any), your ethnicity and race, and if there are other children in the family. You will be asked about when you found out your child had cancer, the type of cancer, and when the cancer got worse or came back (if applicable). You will be asked whether others have shared parenting responsibilities, your education level, and if you work and what type of work you do. The questionnaire will take about 5 minutes to complete. Audiotapes/Transcripts: The assistant will take notes and the session will be recorded on an audiotape. All audiotapes will be stored in locked cabinets maintained by the study chair. The audiotapes will be destroyed once the study and analyses are complete. The audiotape will be recorded onto paper transcripts. The completed focus group transcriptions will be placed in a database secured with a password and identification protected. Transcribed results will have all identifiable markers removed and kept in the investigators' locked files. Only the researchers will be able to view the transcriptions. Length of Study: Your participation on this study is complete once you finish the group meeting. PEDIATRIC PARTICIPANT: The Focus Group: If you agree to take part in this study, you will go to a 1 1/2 hour group session with 3-9 other patients. The group will be led by a group leader and an assistant. The group leader will ask questions to the group about who you talk with about the disease, how you make a decision, how you manage any symptoms you may have, how you are feeling about the disease, and how religion has helped you during your treatment. If your parent is also taking part in this study, you will meet separately from your parent. At the time of your arrival and before the beginning of the focus group session, your parent will be asked to complete a questionnaire. Your parent will be asked about their age and sex, your age and sex, where you live, your religion (if any), your ethnicity and race, and if there are other children in the family. Your parent will be asked when they found out you had cancer, the type of cancer, and when the cancer got worse or came back (if applicable). Your parent will be asked whether others have shared parenting responsibilities, their education level, and if they work and about the type of work they do. The questionnaire will take about 5 minutes to complete. Audiotapes/Transcripts: The assistant will take notes and the session will be recorded on an audiotape. All audiotapes will be stored in locked cabinets taken care of by the study chair. The audiotapes will be destroyed once the study is over and the researchers have finished looking at the information. The audiotape will be recorded onto paper transcripts. The completed focus group transcriptions will be placed in a database secured with a password and identification protected. Any personal information about you will be removed from these papers and the papers will be kept in the investigators' locked files. Only the researchers will be able to view the transcriptions. Length of Study: Your participation on this study is over once you complete the focus group.
Official Title
-----------------
Palliative Care and Symptom Management for the Pediatric Oncology Patient
Conditions
-----------------
Pediatric Cancers
Intervention / Treatment
-----------------
* Behavioral: Focus Group - Parent/Caregiver
* Behavioral: Focus Group - Pediatric Patient
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Inclusion for Children: 10-18 years of age MD Anderson Children's Cancer Center (MCACC) cancer patient receiving anti-cancer treatment for disease that is not recurrent or metastatic for cancer diagnosed in the past 3-12 mos or receiving anti-cancer treatment for recurrent or metastatic cancer diagnosed within the past 3-12 months speak & understand English reside in the Greater Houston area provide IRB-approved pediatric assent or informed consent, as age appropriate if < 18 years of age, provide Internal Review Board (IRB)-approved parental permission child's eligibility is not contingent upon parent's decision to participate Inclusion for parents: self-identified parent(s) that has(have) a child eligible for study, per the inclusion and exclusion criteria noted above or has had a child (0-18 yrs of age at time of death) treated for cancer at MCACC who has died in the last 1 to 2 years speak and understand English reside in the Houston metropolitan area provide IRB-approved informed consent attend different focus groups if more than one eligible parent per child (max 2 parents per child) parent's eligibility is not contingent upon the child's decision to participate Exclusion Criteria: Exclusion for Children: have cognitive impairment, developmental delay, or emotional distress that would limit participation in a group discussion, as determined by the clinical judgment of the investigator younger than 10 years or older than 18 years of age Exclusion for Caregiver: have cognitive impairment, developmental delay, or emotional distress that would limit participation in a group discussion, as determined by the clinical judgment of the investigator.
Ages Eligible for Study
-----------------
Minimum Age: 10 Years
Maximum 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 |
| --- | --- |
| Group 1<br>Early cancer group-children ages 10-13 years | Behavioral: Focus Group - Parent/Caregiver<br>* A 1 1/2 hour group session with other parents/caregivers.<br>Behavioral: Focus Group - Pediatric Patient<br>* A 1 1/2 hour group session with other pediatric patients.<br>|
| Group 2<br>Early cancer group-children ages 14 to 18 years | Behavioral: Focus Group - Parent/Caregiver<br>* A 1 1/2 hour group session with other parents/caregivers.<br>Behavioral: Focus Group - Pediatric Patient<br>* A 1 1/2 hour group session with other pediatric patients.<br>|
| Group 3<br>Early cancer group-parents of patients ages 10-18 years | Behavioral: Focus Group - Parent/Caregiver<br>* A 1 1/2 hour group session with other parents/caregivers.<br>Behavioral: Focus Group - Pediatric Patient<br>* A 1 1/2 hour group session with other pediatric patients.<br>|
| Group 4<br>Advanced cancer group-children ages 10-13 years | Behavioral: Focus Group - Parent/Caregiver<br>* A 1 1/2 hour group session with other parents/caregivers.<br>Behavioral: Focus Group - Pediatric Patient<br>* A 1 1/2 hour group session with other pediatric patients.<br>|
| Group 5<br>Advanced cancer group-children ages 14-18 years | Behavioral: Focus Group - Parent/Caregiver<br>* A 1 1/2 hour group session with other parents/caregivers.<br>Behavioral: Focus Group - Pediatric Patient<br>* A 1 1/2 hour group session with other pediatric patients.<br>|
| Group 6<br>Advanced cancer group-parents of children ages 10-18 years | Behavioral: Focus Group - Parent/Caregiver<br>* A 1 1/2 hour group session with other parents/caregivers.<br>Behavioral: Focus Group - Pediatric Patient<br>* A 1 1/2 hour group session with other pediatric patients.<br>|
| Group 7<br>End of life group - parents of children ages birth to 18 years of age at time of death | Behavioral: Focus Group - Parent/Caregiver<br>* A 1 1/2 hour group session with other parents/caregivers.<br>Behavioral: Focus Group - Pediatric Patient<br>* A 1 1/2 hour group session with other pediatric patients.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Palliative Care Service Needs of Pediatric Cancer Patients + Their Parents | Qualitative data collection. | 3 Years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pediatric Cancer, Focus Group, Pediatric cancer patients, Parents of Pediatric cancer patients, Pediatric Palliative Care Program
|
|||
NCT00619489
|
Long Term Safety of Vedolizumab (MLN0002) in Patients With Ulcerative Colitis and Crohn's Disease
|
This was an open-label study to provide an opportunity for participants with Ulcerative Colitis (UC) who previously completed Study C13002 (NCT01177228), and for treatment-naïve participants with UC or Crohn's Disease (CD) to receive treatment with vedolizumab, and to determine the long term safety of vedolizumab in patients afflicted with these diseases.
|
This was a phase 2, multiple-dose, open-label study of vedolizumab administered intravenously (IV) every 8 weeks. The study population included treatment-naïve ulcerative colitis (UC) or Crohn's Disease (CD) participants, as well as 38 UC participants who had tolerated vedolizumab well during Study C13002 (NCT01177228).~In the original study protocol, all participants were randomized to receive vedolizumab at doses of either 6 mg/kg or 10 mg/kg. With the implementation of Amendment 1, the assigned doses of vedolizumab were decreased to 2.0 mg/kg and 6.0 mg/kg. To implement the dose changes, instead of randomizing all participants across both doses, those who rolled over from Study C13002 were reassigned to receive the 2.0 mg/kg dose and all participants who entered C13004 naïve to treatment were to receive the 6.0 mg/kg dose, starting on the next scheduled dosing day. Also, if participants assigned to the 2 mg/kg dose experienced flare, they were to receive the higher 6 mg/kg dose.~In the results analyses for this study, participants are grouped according to the lowest dose received, i.e., 2.0 mg/kg or 6.0 mg/kg vedolizumab.
|
Phase 2, Multiple Dose, Open-Label Study to Determine the Long Term Safety of MLN0002 in Patients With Ulcerative Colitis and Crohn's Disease
|
Ulcerative Colitis, Crohn's Disease
|
* Drug: vedolizumab
|
Inclusion Criteria:~Confirmed and active ulcerative colitis (UC) or Crohn's Disease (CD)~Crohn's Disease Activity Index (CDAI) Score of 220 - 450 for participants with CD~Partial Mayo score of 2 - 7 for participants with UC~Patient should be appropriate candidate for biologic therapy per guidelines~Up-to-date on cancer screening~No severe systemic disease~Patients with evidence of abscess~Agree to comply with study procedures including contraception~Exclusion Criteria:~Low lymphocyte counts~History of imaging abnormalities, multiple sclerosis (MS), brain tumor or other neurological illness~Active or recent serious infections~Recent treatment with biologic (i.e., Remicade) or investigational drug~Impending surgery~Any participants with vedolizumab human anti-human antibody (HAHA) titers ≥1:125 or with a previous immediate hypersensitivity reaction during or shortly after vedolizumab infusion
|
18 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product, which does not necessarily have a causal relationship with the treatment. The investigator systematically collected information adequate to determine both the outcome and severity of the AE, and whether or not it was drug-related or met the criteria for classification as a serious adverse event (SAE). An SAE was defined as an AE that resulted in (or posed risk for) death, inpatient hospitalization (or prolonging hospitalization), or congenital, persistent or significant disability/incapacity.~The intensity for each AE was defined according to the following criteria:~Mild: Awareness of sign or symptom, but easily tolerated; Moderate: Discomfort enough to cause interference with normal daily activities; Severe: Inability to perform normal daily activities. | From Day 1 to Day 637 |
| Number of Participants With Clinically Significant Laboratory Findings | Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are enzymes in the blood. | through Day 637 |
| Number of Participants With Signs and Symptoms of Progressive Multifocal Leukoencephalopathy (PML) | At every visit, before receiving study treatment participants were evaluated by clinic staff for signs of PML using a PML symptom checklist. | through Day 637 |
| Number of Participants With Human Anti-human Antibodies (HAHA) | | Samples collected prior to dosing on Days 1, 43, 155, 267, 379, 491, and 637. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Concentration of Vedolizumab Before Dosing | Vedolizumab serum concentrations were measured from serum samples collected for pharmacokinetic (PK) analysis within 2 hours prior to dosing. The original protocol specified that PK parameters, including but not limited to minimum plasma concentration (Cmin), were to be estimated; however, due to intrapatient dose modification with Amendment 1, it was no longer feasible to perform a full PK parameter estimation. The summaries of pre-infusion data (i.e., trough levels) are presented at time points where at least 50% of participants had quantifiable vedolizumab concentrations, using a value of 0 for results below a measurable range. This provides information on the pharmacokinetic behavior of vedolizumab when administered as long-term therapy. | Days 43, 99, 155 and 267, predose |
| Saturation of Receptors by Vedolizumab Before Dosing on Days 1, 43, 99, 155 and 267 by ACT-1 Assay | The target of vedolizumab is α4β7 integrin, a receptor found on inflammatory immune cells that guides these inflammatory cells to the gut and binds to the Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) on gut endothelial cells. The extent of the α4β7 receptor saturation by vedolizumab was assessed using the ACT-1 binding interference assay. ACT-1 is a mouse antibody similar to vedolizumab that also binds α4β7 integrin. The assay measures the percentage of cells bearing α4β7 that were not saturated with vedolizumab at the time of sampling. | Days 43, 99, 155 and 267, predose |
| Saturation of Receptors by Vedolizumab Before Dosing Using the MAdCAM-1-Fc Assay | The target of vedolizumab is α4β7 integrin, a receptor found on inflammatory immune cells that guides these inflammatory cells to the gut and binds to the mucosal address in cell adhesion molecule-1 (MAdCAM-1) on gut endothelial cells. The extent of the α4β7 receptor saturation by vedolizumab was assessed using the MAdCAM-1-Fc binding interference assay at time points where at least 50% of participants in the analysis set had non-missing results. MAdCAM-1-Fc is a fusion of human MAdCAM-1 with parts of a mouse monoclonal antibody. The assay measures the percentage of cells bearing α4β7 that were not saturated with vedolizumab at the time of sampling. | Days 43, 99, 155 and 267, predose |
|
Vedolizumab, Gastrointestinal Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vedolizumab 2 mg/kg<br>Participants received vedolizumab, 2 mg/kg, intravenously (IV), on Days 1, 15 and 43, and thereafter once every 8 weeks for up to 78 weeks. | Drug: vedolizumab<br>* Vedolizumab for intravenous (IV) infusion<br>* Other names: LDP-02;|
| Experimental: Vedolizumab 6 mg/kg<br>Participants received vedolizumab, 6 mg/kg, IV, on Days 1, 15 and 43, and thereafter once every 8 weeks for up to 78 weeks. | Drug: vedolizumab<br>* Vedolizumab for intravenous (IV) infusion<br>* Other names: LDP-02;|
|
Long Term Safety of Vedolizumab (MLN0002) in Patients With Ulcerative Colitis and Crohn's Disease
Study Overview
=================
Brief Summary
-----------------
This was an open-label study to provide an opportunity for participants with Ulcerative Colitis (UC) who previously completed Study C13002 (NCT01177228), and for treatment-naïve participants with UC or Crohn's Disease (CD) to receive treatment with vedolizumab, and to determine the long term safety of vedolizumab in patients afflicted with these diseases.
Detailed Description
-----------------
This was a phase 2, multiple-dose, open-label study of vedolizumab administered intravenously (IV) every 8 weeks. The study population included treatment-naïve ulcerative colitis (UC) or Crohn's Disease (CD) participants, as well as 38 UC participants who had tolerated vedolizumab well during Study C13002 (NCT01177228). In the original study protocol, all participants were randomized to receive vedolizumab at doses of either 6 mg/kg or 10 mg/kg. With the implementation of Amendment 1, the assigned doses of vedolizumab were decreased to 2.0 mg/kg and 6.0 mg/kg. To implement the dose changes, instead of randomizing all participants across both doses, those who rolled over from Study C13002 were reassigned to receive the 2.0 mg/kg dose and all participants who entered C13004 naïve to treatment were to receive the 6.0 mg/kg dose, starting on the next scheduled dosing day. Also, if participants assigned to the 2 mg/kg dose experienced flare, they were to receive the higher 6 mg/kg dose. In the results analyses for this study, participants are grouped according to the lowest dose received, i.e., 2.0 mg/kg or 6.0 mg/kg vedolizumab.
Official Title
-----------------
Phase 2, Multiple Dose, Open-Label Study to Determine the Long Term Safety of MLN0002 in Patients With Ulcerative Colitis and Crohn's Disease
Conditions
-----------------
Ulcerative Colitis, Crohn's Disease
Intervention / Treatment
-----------------
* Drug: vedolizumab
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Confirmed and active ulcerative colitis (UC) or Crohn's Disease (CD) Crohn's Disease Activity Index (CDAI) Score of 220 - 450 for participants with CD Partial Mayo score of 2 - 7 for participants with UC Patient should be appropriate candidate for biologic therapy per guidelines Up-to-date on cancer screening No severe systemic disease Patients with evidence of abscess Agree to comply with study procedures including contraception Exclusion Criteria: Low lymphocyte counts History of imaging abnormalities, multiple sclerosis (MS), brain tumor or other neurological illness Active or recent serious infections Recent treatment with biologic (i.e., Remicade) or investigational drug Impending surgery Any participants with vedolizumab human anti-human antibody (HAHA) titers ≥1:125 or with a previous immediate hypersensitivity reaction during or shortly after vedolizumab infusion
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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vedolizumab 2 mg/kg<br>Participants received vedolizumab, 2 mg/kg, intravenously (IV), on Days 1, 15 and 43, and thereafter once every 8 weeks for up to 78 weeks. | Drug: vedolizumab<br>* Vedolizumab for intravenous (IV) infusion<br>* Other names: LDP-02;|
| Experimental: Vedolizumab 6 mg/kg<br>Participants received vedolizumab, 6 mg/kg, IV, on Days 1, 15 and 43, and thereafter once every 8 weeks for up to 78 weeks. | Drug: vedolizumab<br>* Vedolizumab for intravenous (IV) infusion<br>* Other names: LDP-02;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product, which does not necessarily have a causal relationship with the treatment. The investigator systematically collected information adequate to determine both the outcome and severity of the AE, and whether or not it was drug-related or met the criteria for classification as a serious adverse event (SAE). An SAE was defined as an AE that resulted in (or posed risk for) death, inpatient hospitalization (or prolonging hospitalization), or congenital, persistent or significant disability/incapacity. The intensity for each AE was defined according to the following criteria: Mild: Awareness of sign or symptom, but easily tolerated; Moderate: Discomfort enough to cause interference with normal daily activities; Severe: Inability to perform normal daily activities. | From Day 1 to Day 637 |
| Number of Participants With Clinically Significant Laboratory Findings | Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are enzymes in the blood. | through Day 637 |
| Number of Participants With Signs and Symptoms of Progressive Multifocal Leukoencephalopathy (PML) | At every visit, before receiving study treatment participants were evaluated by clinic staff for signs of PML using a PML symptom checklist. | through Day 637 |
| Number of Participants With Human Anti-human Antibodies (HAHA) | | Samples collected prior to dosing on Days 1, 43, 155, 267, 379, 491, and 637. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Concentration of Vedolizumab Before Dosing | Vedolizumab serum concentrations were measured from serum samples collected for pharmacokinetic (PK) analysis within 2 hours prior to dosing. The original protocol specified that PK parameters, including but not limited to minimum plasma concentration (Cmin), were to be estimated; however, due to intrapatient dose modification with Amendment 1, it was no longer feasible to perform a full PK parameter estimation. The summaries of pre-infusion data (i.e., trough levels) are presented at time points where at least 50% of participants had quantifiable vedolizumab concentrations, using a value of 0 for results below a measurable range. This provides information on the pharmacokinetic behavior of vedolizumab when administered as long-term therapy. | Days 43, 99, 155 and 267, predose |
| Saturation of Receptors by Vedolizumab Before Dosing on Days 1, 43, 99, 155 and 267 by ACT-1 Assay | The target of vedolizumab is α4β7 integrin, a receptor found on inflammatory immune cells that guides these inflammatory cells to the gut and binds to the Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) on gut endothelial cells. The extent of the α4β7 receptor saturation by vedolizumab was assessed using the ACT-1 binding interference assay. ACT-1 is a mouse antibody similar to vedolizumab that also binds α4β7 integrin. The assay measures the percentage of cells bearing α4β7 that were not saturated with vedolizumab at the time of sampling. | Days 43, 99, 155 and 267, predose |
| Saturation of Receptors by Vedolizumab Before Dosing Using the MAdCAM-1-Fc Assay | The target of vedolizumab is α4β7 integrin, a receptor found on inflammatory immune cells that guides these inflammatory cells to the gut and binds to the mucosal address in cell adhesion molecule-1 (MAdCAM-1) on gut endothelial cells. The extent of the α4β7 receptor saturation by vedolizumab was assessed using the MAdCAM-1-Fc binding interference assay at time points where at least 50% of participants in the analysis set had non-missing results. MAdCAM-1-Fc is a fusion of human MAdCAM-1 with parts of a mouse monoclonal antibody. The assay measures the percentage of cells bearing α4β7 that were not saturated with vedolizumab at the time of sampling. | Days 43, 99, 155 and 267, predose |
|
|
NCT02719730
|
Upgrade the Grains Study: Increasing Whole Grain Consumption in Low-income Children With Obesity
|
This study will assess the impact of a randomized intervention aimed at increasing consumption of whole grain foods among children from low-income households that participate in the Special Nutrition Assistance Program (SNAP, or food stamps). A total of 60 obese children (8 to 16 years) will be recruited from a clinical population (Healthy Eating Active Living Program) at University of California San Francisco (UCSF) Benioff Children's Hospital Oakland. Participants and their caregivers will all receive education about whole grain foods, and will be randomized to either an intervention or control group. The intervention group will receive a monthly reimbursement allotment of up to 10% of their usual SNAP benefit for specific whole grain foods purchased during the three month study period. The control group will not have the financial incentive for purchasing whole grain foods during the 12 week study period. The investigators will assess the feasibility of the intervention, the impact of the intervention on household grocery purchases, and the impact on the child's anthropometrics, dietary intake of whole grain foods (24-hour recall), and markers of metabolic risk.
|
RUN-IN PHASE (Weeks -4 to 0)~Participants will participate in a run-in phase where they will be asked to keep all grocery receipts for a 4 week period~RANDOMIZATION (Week 0)~Child participants with caregivers who are able to successfully complete the run-in phase are then randomized at that point to be either in the intervention arm or the control arm.~Patients will be block randomized by age group (8-11 and 12-16).~ACTIVE PHASE (Weeks 0-12)~Participants will be given education about whole grains and whole grain preparation. Intervention and control participant activities described elsewhere.~RETURN VISIT (Week 24)~12 weeks after the completion of the active phase of the study, patients will be asked to return for a final visit at the research center, during which they will also have blood tests and other study activities repeated for one final time.
|
The Metabolic Impact of Concurrent Food Insecurity and Obesity
|
Obesity
|
* Behavioral: Reimbursement for whole grain purchases
|
Inclusion Criteria:~Obese (BMI greater than 95th percentile for age and gender)~Low-income family currently participating in SNAP (food stamps)~Participant and caregiver speaks either English or Spanish~Exclusion Criteria:~medications to lower lipid levels (statins), which would affect insulin sensitivity (e.g. metformin, abilify) or which are known to affect serum cholesterol (e.g. carbamazepine).~Type II diabetes
|
8 Years
|
16 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in whole grains consumption (ounce equivalents) | Using the Nutrition Data System for Research (NDSR) for 24-hour food recall, intake of whole grains (and refined grains, and proportion of grains that are whole) will be assessed. The change in this dietary outcome at the end of 3 months will be evaluated for intervention participants compared to controls. | Baseline and 3 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum triglycerides (mg/dl) | Fasting lipid panel at the end of three month period will be compared to baseline lipid panel: serum triglycerides will be an outcome of particular interest given the intervention. | Baseline and 3 months |
| Change in TG/HDL ratio | Fasting lipid panel at the end of three month period will be compared to baseline lipid panel: the ratio of serum triglycerides (TG) to high-density lipoprotein (HDL-C) will be an outcome of particular interest given the intervention. | Baseline and 3 months |
| Change in body mass index (BMI, or kg/m2) | The change in BMI after the 3 month intervention period will be examined for intervention group compared to control group. | Baseline and 3 months |
| Change in waist to height ratio (WHtR) | Change in waist to height ratio at the end of the 3 month period will be examined for intervention group compared to control group. | Baseline and 3 months |
| Change in proportion of subjects with pre-diabetes | The proportion of subjects with prediabetes (using both criteria of Hemoglobin A1c greater than or equal to 5.7% and fasting glucose greater than or equal to 100 mg/dl) after the 3 month intervention period will be compared for intervention and control groups. | Baseline and 3 months |
| Change in percent of monthly SNAP benefit spent on whole grain purchases (dollars) | Using collected grocery receipts, monthly expenditure (as a percentage of the household's monthly SNAP benefit) for whole grain foods in the third month of the intervention period will be compared to the percent of the SNAP benefit during the baseline month (run-in phase). The change in this expenditure amount will be evaluated for intervention participants compared to controls. | Baseline and 3 months |
|
Obesity, Overweight, Overnutrition, Nutrition Disorders, Body Weight
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reimbursement arm<br>Participating caregivers will turn in receipts from grocery store purchases. At each of three study visits, participants in the reimbursement arm will receive reimbursement of up to 10% of their usual SNAP benefits for specific whole grain foods purchased at one of two chain stores in the previous month. | Behavioral: Reimbursement for whole grain purchases<br>* All participants will receive education about whole grain foods. Those in the experimental arm will have a monthly financial incentive for purchases of specific whole grain foods foods during the 12-week study period, whereas the control group will not have a financial incentive for whole grain purchases during the study period.<br>|
| No Intervention: Control arm<br>Participating caregivers will mail in receipts from grocery store purchases. Participants in the control arm will also be given the same guidance about preferred whole grain foods and whole grain products but will have no specific financial incentive related to purchases of whole grain foods during the 12-week study period. | |
|
Upgrade the Grains Study: Increasing Whole Grain Consumption in Low-income Children With Obesity
Study Overview
=================
Brief Summary
-----------------
This study will assess the impact of a randomized intervention aimed at increasing consumption of whole grain foods among children from low-income households that participate in the Special Nutrition Assistance Program (SNAP, or food stamps). A total of 60 obese children (8 to 16 years) will be recruited from a clinical population (Healthy Eating Active Living Program) at University of California San Francisco (UCSF) Benioff Children's Hospital Oakland. Participants and their caregivers will all receive education about whole grain foods, and will be randomized to either an intervention or control group. The intervention group will receive a monthly reimbursement allotment of up to 10% of their usual SNAP benefit for specific whole grain foods purchased during the three month study period. The control group will not have the financial incentive for purchasing whole grain foods during the 12 week study period. The investigators will assess the feasibility of the intervention, the impact of the intervention on household grocery purchases, and the impact on the child's anthropometrics, dietary intake of whole grain foods (24-hour recall), and markers of metabolic risk.
Detailed Description
-----------------
RUN-IN PHASE (Weeks -4 to 0) Participants will participate in a run-in phase where they will be asked to keep all grocery receipts for a 4 week period RANDOMIZATION (Week 0) Child participants with caregivers who are able to successfully complete the run-in phase are then randomized at that point to be either in the intervention arm or the control arm. Patients will be block randomized by age group (8-11 and 12-16). ACTIVE PHASE (Weeks 0-12) Participants will be given education about whole grains and whole grain preparation. Intervention and control participant activities described elsewhere. RETURN VISIT (Week 24) 12 weeks after the completion of the active phase of the study, patients will be asked to return for a final visit at the research center, during which they will also have blood tests and other study activities repeated for one final time.
Official Title
-----------------
The Metabolic Impact of Concurrent Food Insecurity and Obesity
Conditions
-----------------
Obesity
Intervention / Treatment
-----------------
* Behavioral: Reimbursement for whole grain purchases
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Obese (BMI greater than 95th percentile for age and gender) Low-income family currently participating in SNAP (food stamps) Participant and caregiver speaks either English or Spanish Exclusion Criteria: medications to lower lipid levels (statins), which would affect insulin sensitivity (e.g. metformin, abilify) or which are known to affect serum cholesterol (e.g. carbamazepine). Type II diabetes
Ages Eligible for Study
-----------------
Minimum Age: 8 Years
Maximum Age: 16 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: Reimbursement arm<br>Participating caregivers will turn in receipts from grocery store purchases. At each of three study visits, participants in the reimbursement arm will receive reimbursement of up to 10% of their usual SNAP benefits for specific whole grain foods purchased at one of two chain stores in the previous month. | Behavioral: Reimbursement for whole grain purchases<br>* All participants will receive education about whole grain foods. Those in the experimental arm will have a monthly financial incentive for purchases of specific whole grain foods foods during the 12-week study period, whereas the control group will not have a financial incentive for whole grain purchases during the study period.<br>|
| No Intervention: Control arm<br>Participating caregivers will mail in receipts from grocery store purchases. Participants in the control arm will also be given the same guidance about preferred whole grain foods and whole grain products but will have no specific financial incentive related to purchases of whole grain foods during the 12-week study period. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in whole grains consumption (ounce equivalents) | Using the Nutrition Data System for Research (NDSR) for 24-hour food recall, intake of whole grains (and refined grains, and proportion of grains that are whole) will be assessed. The change in this dietary outcome at the end of 3 months will be evaluated for intervention participants compared to controls. | Baseline and 3 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum triglycerides (mg/dl) | Fasting lipid panel at the end of three month period will be compared to baseline lipid panel: serum triglycerides will be an outcome of particular interest given the intervention. | Baseline and 3 months |
| Change in TG/HDL ratio | Fasting lipid panel at the end of three month period will be compared to baseline lipid panel: the ratio of serum triglycerides (TG) to high-density lipoprotein (HDL-C) will be an outcome of particular interest given the intervention. | Baseline and 3 months |
| Change in body mass index (BMI, or kg/m2) | The change in BMI after the 3 month intervention period will be examined for intervention group compared to control group. | Baseline and 3 months |
| Change in waist to height ratio (WHtR) | Change in waist to height ratio at the end of the 3 month period will be examined for intervention group compared to control group. | Baseline and 3 months |
| Change in proportion of subjects with pre-diabetes | The proportion of subjects with prediabetes (using both criteria of Hemoglobin A1c greater than or equal to 5.7% and fasting glucose greater than or equal to 100 mg/dl) after the 3 month intervention period will be compared for intervention and control groups. | Baseline and 3 months |
| Change in percent of monthly SNAP benefit spent on whole grain purchases (dollars) | Using collected grocery receipts, monthly expenditure (as a percentage of the household's monthly SNAP benefit) for whole grain foods in the third month of the intervention period will be compared to the percent of the SNAP benefit during the baseline month (run-in phase). The change in this expenditure amount will be evaluated for intervention participants compared to controls. | Baseline and 3 months |
|
|
NCT04198714
|
Pudendal Nerve Block in Vaginal Surgery
|
The objective of this this randomized controlled study is to determine whether a pudendal nerve block at the time of vaginal surgery is associated with improved postoperative pain control and decrease opioid consumption compared to a sham pudendal nerve block in patients undergoing vaginal surgery.
|
The Effect of Pudendal Nerve Block Analgesia on Postoperative Pain Control in Patients Undergoing Vaginal Surgery: A Randomized Double-blind Placebo-controlled Trial
|
Nerve Block, Pain, Postoperative, Pelvic Floor Disorders, Pelvic Organ Prolapse, Pudendal Neuralgia, Surgery
|
* Procedure: Pudendal block
|
Inclusion Criteria:~Consenting, English speaking women between ages 18 and 80 who will undergo vaginal surgery~Ability to read VAS Scores~Specific vaginal procedures include, but are not limited to:~Perineoplasty Complete vaginectomy Le Forte colpocleisis Anterior repair, posterior repair, and/or enterocele repair Transvaginal mesh use Transvaginal mesh excision Sacrospinous ligament fixation Uterosacral ligament suspension Vaginal paravaginal defect repair Midurethral sling placement Sphincteroplasty Vaginal hysterectomy, with or without removal of tube(s) and/or ovary(s), with or without repair of enterocele~Exclusion Criteria:~History of chronic pelvic pain~Currently taking sedatives~Liver disease~Renal disease~Women who did not consent for the study.~Intraoperative concern for increased blood loss~Unable to speak English~Unable to understand VAS Scores~Undergoing concomitant abdominal or laparoscopic procedures~Allergy to bupivacaine or triamcinolone~Planned abdominal or laparoscopic procedures.~Patients who are ineligible for non-narcotic pain medications, such as an allergy to acetaminophen or NSAIDs
|
18 Years
|
80 Years
|
Female
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind, placebo-controlled randomized controlled trial
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scores at 7am after surgery | Visual analog score: 0 (No pain) - 10 (The worst imaginable pain) | Postoperative day 1 at 7am |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual analog scores at discharge from post-anesthesia care unit | Visual analog score: 0 (No pain) - 10 (The worst imaginable pain) | At the time of discharge from post-anesthesia care unit, on average 1-3 hours |
| Pain Scores 96 hours after surgery | Numeric rating pain scale: 0 (No pain) - 10 (The worst imaginable pain) | 96 hours postoperatively |
| Quality of Recovery scores on post op day 1 (7AM) | Quality of Recovery score: Part A 18 (very poor) - 90 (excellent); Part B 22 (excellent) - 110 (very poor) | 7am on postoperative day 1 |
| Satisfaction scores in the morning after surgery (7AM) | Satisfaction with overall pain control: 0 (Not satisfied at all) - 10 (Extremely satisfied) | 7am on postoperative day 1 |
| Satisfaction scores 96 hours after surgery | Satisfaction with overall pain control: 0 (Not satisfied at all) - 10 (Extremely satisfied) | 96 hours postoperatively |
| Length of stay | Length of inpatient hospitalization after surgery | Through the time of hospital discharge, on average 15-20 hours |
| Opioid analgesic use in the post-anesthesia care unit | Total dose of opioids administered in the post-anesthesia care unit, in morphine equivalents. | Through the time of discharge from the post-anesthesia care unit, on average 1-3 hours |
| Total postoperative opioid use | Total dose of opioids administered during the first 24 hours after surgery, in morphine equivalents. | Through the time of hospital discharge, on average 15-20 hours |
| Severity of postoperative non-pain symptoms | Quality of Recovery Score, Part B Comfort: 8 (none of the time) - 40 (All of the time) | Postoperative day 1 (7AM) |
| Postoperative bladder function. | Incidence of urinary retention | Up to 96 hours after surgery |
| Postoperative bowel function. | Time to first bowel movement | Up to 96 hours after surgery |
|
Neuralgia, Pudendal Neuralgia, Pelvic Floor Disorders, Prolapse, Pain, Postoperative, Pelvic Organ Prolapse, Pathological Conditions, Anatomical, Postoperative Complications, Pathologic Processes, Neurologic Manifestations, Peripheral Nervous System Diseases, Neuromuscular Diseases, Nervous System Diseases, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Pregnancy Complications, Male Urogenital Diseases, Nerve Compression Syndromes, Pain
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pudendal block<br>9cc of 0.25% Marcaine + 1cc of 40mg/mL triamcinolone. 5cc will be injected transvaginally in the area of the pudendal nerve on each side. | Procedure: Pudendal block<br>* Administration of a pudendal block at the conclusion of vaginal surgery.<br>|
| Sham Comparator: Sham injection<br>10cc normal saline. 5cc will be injected transvaginally in the area of the pudendal nerve on each side. | Procedure: Pudendal block<br>* Administration of a pudendal block at the conclusion of vaginal surgery.<br>|
|
Pudendal Nerve Block in Vaginal Surgery
Study Overview
=================
Brief Summary
-----------------
The objective of this this randomized controlled study is to determine whether a pudendal nerve block at the time of vaginal surgery is associated with improved postoperative pain control and decrease opioid consumption compared to a sham pudendal nerve block in patients undergoing vaginal surgery.
Official Title
-----------------
The Effect of Pudendal Nerve Block Analgesia on Postoperative Pain Control in Patients Undergoing Vaginal Surgery: A Randomized Double-blind Placebo-controlled Trial
Conditions
-----------------
Nerve Block, Pain, Postoperative, Pelvic Floor Disorders, Pelvic Organ Prolapse, Pudendal Neuralgia, Surgery
Intervention / Treatment
-----------------
* Procedure: Pudendal block
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Consenting, English speaking women between ages 18 and 80 who will undergo vaginal surgery Ability to read VAS Scores Specific vaginal procedures include, but are not limited to: Perineoplasty Complete vaginectomy Le Forte colpocleisis Anterior repair, posterior repair, and/or enterocele repair Transvaginal mesh use Transvaginal mesh excision Sacrospinous ligament fixation Uterosacral ligament suspension Vaginal paravaginal defect repair Midurethral sling placement Sphincteroplasty Vaginal hysterectomy, with or without removal of tube(s) and/or ovary(s), with or without repair of enterocele Exclusion Criteria: History of chronic pelvic pain Currently taking sedatives Liver disease Renal disease Women who did not consent for the study. Intraoperative concern for increased blood loss Unable to speak English Unable to understand VAS Scores Undergoing concomitant abdominal or laparoscopic procedures Allergy to bupivacaine or triamcinolone Planned abdominal or laparoscopic procedures. Patients who are ineligible for non-narcotic pain medications, such as an allergy to acetaminophen or NSAIDs
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind, placebo-controlled randomized controlled trial
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pudendal block<br>9cc of 0.25% Marcaine + 1cc of 40mg/mL triamcinolone. 5cc will be injected transvaginally in the area of the pudendal nerve on each side. | Procedure: Pudendal block<br>* Administration of a pudendal block at the conclusion of vaginal surgery.<br>|
| Sham Comparator: Sham injection<br>10cc normal saline. 5cc will be injected transvaginally in the area of the pudendal nerve on each side. | Procedure: Pudendal block<br>* Administration of a pudendal block at the conclusion of vaginal surgery.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scores at 7am after surgery | Visual analog score: 0 (No pain) - 10 (The worst imaginable pain) | Postoperative day 1 at 7am |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual analog scores at discharge from post-anesthesia care unit | Visual analog score: 0 (No pain) - 10 (The worst imaginable pain) | At the time of discharge from post-anesthesia care unit, on average 1-3 hours |
| Pain Scores 96 hours after surgery | Numeric rating pain scale: 0 (No pain) - 10 (The worst imaginable pain) | 96 hours postoperatively |
| Quality of Recovery scores on post op day 1 (7AM) | Quality of Recovery score: Part A 18 (very poor) - 90 (excellent); Part B 22 (excellent) - 110 (very poor) | 7am on postoperative day 1 |
| Satisfaction scores in the morning after surgery (7AM) | Satisfaction with overall pain control: 0 (Not satisfied at all) - 10 (Extremely satisfied) | 7am on postoperative day 1 |
| Satisfaction scores 96 hours after surgery | Satisfaction with overall pain control: 0 (Not satisfied at all) - 10 (Extremely satisfied) | 96 hours postoperatively |
| Length of stay | Length of inpatient hospitalization after surgery | Through the time of hospital discharge, on average 15-20 hours |
| Opioid analgesic use in the post-anesthesia care unit | Total dose of opioids administered in the post-anesthesia care unit, in morphine equivalents. | Through the time of discharge from the post-anesthesia care unit, on average 1-3 hours |
| Total postoperative opioid use | Total dose of opioids administered during the first 24 hours after surgery, in morphine equivalents. | Through the time of hospital discharge, on average 15-20 hours |
| Severity of postoperative non-pain symptoms | Quality of Recovery Score, Part B Comfort: 8 (none of the time) - 40 (All of the time) | Postoperative day 1 (7AM) |
| Postoperative bladder function. | Incidence of urinary retention | Up to 96 hours after surgery |
| Postoperative bowel function. | Time to first bowel movement | Up to 96 hours after surgery |
|
||
NCT01591772
|
Structural and Functional Imaging and Cognitive Functions in Ovarian Cancer
|
The purpose of this study is to learn about possible changes in brain anatomy and function, and in thinking abilities, such as memory skills, in patients with ovarian cancer who receive treatment with chemotherapy. Cancer patients treated with chemotherapy may experience changes in thinking abilities, and these may interfere with quality of life. Most of the research to date has involved patients with breast cancer, and there are no studies in women with ovarian cancer looking at at treatment-related changes in brain anatomy and function.
|
Structural and Functional Imaging and Cognitive Functions in Ovarian Cancer
|
Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cancer
|
* Other: Neuroimaging & Neuropsychological Evaluation
* Other: Neuroimaging & Neuropsychological Evaluation
|
Inclusion Criteria:~diagnosed with stage I-IV ovarian, peritoneal or fallopian tube cancer~completed first-line taxane and platinum-based chemotherapy 1-4 months prior to being enrolled in the study (can be on bevacizumab maintenance)~in remission of their disease at the time of enrollment between 21 and 70 years of age~fluent in English~in the judgment of the consenting professional, have capacity to give consent~Healthy Control Inclusion Criteria:~no diagnosis of cancer except basal cell carcinoma~between 21 and 70 years of age~fluent in English~has a mini-mental state exam (MMSE) score of 26 or higher~in the judgment of the consenting professional, have capacity to give consent~Exclusion Criteria:~active or recurrent disease, or diagnosis of another cancer (except basal cell carcinoma) as per medical records at the time of enrollment~exposure to chemotherapy or radiation therapy for any medical condition unrelated to ovarian cancer~on hormonal therapy at the time of enrollment~neurological disorder or moderate to severe head trauma (loss of consciousness > 60 min)~neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, etc.~self-reported Axis I psychiatric disorder (DSM-IV), major affective disorder (untreated), bipolar disorder, schizophrenia~unable to complete cognitive tests~with standard contraindications to MRI examinations~Healthy Control Exclusion Criteria:~exposure to chemotherapy or radiation therapy for any medical condition~on hormone replacement therapy at the time of enrollment~neurological disorder or moderate to severe head trauma (loss of consciousness > 60 min)~neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, etc.
|
21 Years
|
70 Years
|
Female
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| alterations in regional brain volume | will undergo structural MRI scans on a Siemens 3T Magnetom Tim Trio research scanner located at the Citigroup Biomedical Imaging Center at Weill Cornell Medical Center (WCMC), which is adjacent to the MSKCC campus. Three to five T1 weighted sagittal slices are collected to localize the anterior and posterior commissures. Functional imaging: Blood Oxygenation Level-Dependent (BOLD) contrast imaging, which reflects changes in venous deoxyhemoglobin associated with neuronal activity, will be used. | 1 year |
| dorsolateral prefrontal cortex | will undergo functional MRI scans on a Siemens 3T Magnetom Tim Trio research scanner located at the Citigroup Biomedical Imaging Center at Weill Cornell Medical Center (WCMC), which is adjacent to the MSKCC campus.Three to five T1 weighted sagittal slices are collected to localize the anterior and posterior commissures. Functional imaging: Blood Oxygenation Level-Dependent (BOLD) contrast imaging, which reflects changes in venous deoxyhemoglobin associated with neuronal activity, will be used. | 1 year |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| neuropsychological functions | Patients will undergo a brief neuropsychological test battery at MSKCC or at Citigroup Biomedical Imaging Center at WCMC. All subjects will undergo a neuropsychological evaluation including standardized tests of attention and working memory, executive functions, and memory considering that these domains have been shown to be particularly sensitive to cancer treatment-induced cognitive dysfunction. | 1 year |
|
12-075, structural MRI, FALLOPIAN TUBE, OVARY, PERITONEUM, Quality of Life, functional MRI, neuropsychological assessment
|
Ovarian Neoplasms, Carcinoma, Ovarian Epithelial, Fallopian Tube Neoplasms, Endocrine Gland Neoplasms, Neoplasms by Site, Neoplasms, Ovarian Diseases, Adnexal Diseases, Genital Diseases, Female, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Genital Neoplasms, Female, Urogenital Neoplasms, Genital Diseases, Endocrine System Diseases, Gonadal Disorders, Carcinoma, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Fallopian Tube Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| diagnosed with ovarian that recieved chemo<br> | Other: Neuroimaging & Neuropsychological Evaluation<br>* Will undergo structural and functional MRI scans on a Siemens 3T Magnetom Tim Trio research scanner located at the Citigroup Biomedical Imaging Center at Weill Cornell Medical Center (WCMC), which is adjacent to the MSKCC campus. Patients do not undergo routine clinical brain MRIs as part of their assessment and treatment, and the brain MRI scans to be performed in this study are for research purposes only. The MRI scan takes approximately 60 minutes to complete, and about 15 minutes will be required for instructions prior to initiating the study. The MRI studies will be reviewed by a neuroradiologist (Dr. Karimi) to rule out gross structural CNS abnormalities; in case any abnormalities considered to require clinical follow-up are detected, the subject will be contacted and referred for follow-up with their treating physician. Patients will undergo a brief neuropsychological test battery at MSKCC or at Citigroup Biomedical Imaging Center at WCMC<br>|
| healthy controls<br> | Other: Neuroimaging & Neuropsychological Evaluation<br>* Will undergo structural and functional MRI scans on a Siemens 3T Magnetom Tim Trio research scanner located at the Citigroup Biomedical Imaging Center at Weill Cornell Medical Center (WCMC), which is adjacent to the MSKCC campus. Patients do not undergo routine clinical brain MRIs as part of their assessment and treatment, and the brain MRI scans to be performed in this study are for research purposes only. The MRI scan takes approximately 60 minutes to complete, and about 15 minutes will be required for instructions prior to initiating the study. The MRI studies will be reviewed by a neuroradiologist (Dr. Karimi) to rule out gross structural CNS abnormalities; in case any abnormalities considered to require clinical follow-up are detected, the subject will be contacted and referred for follow-up with their treating physician. Patients will undergo a brief neuropsychological test battery at MSKCC or at Citigroup Biomedical Imaging Center at WCMC<br>|
|
Structural and Functional Imaging and Cognitive Functions in Ovarian Cancer
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to learn about possible changes in brain anatomy and function, and in thinking abilities, such as memory skills, in patients with ovarian cancer who receive treatment with chemotherapy. Cancer patients treated with chemotherapy may experience changes in thinking abilities, and these may interfere with quality of life. Most of the research to date has involved patients with breast cancer, and there are no studies in women with ovarian cancer looking at at treatment-related changes in brain anatomy and function.
Official Title
-----------------
Structural and Functional Imaging and Cognitive Functions in Ovarian Cancer
Conditions
-----------------
Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cancer
Intervention / Treatment
-----------------
* Other: Neuroimaging & Neuropsychological Evaluation
* Other: Neuroimaging & Neuropsychological Evaluation
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: diagnosed with stage I-IV ovarian, peritoneal or fallopian tube cancer completed first-line taxane and platinum-based chemotherapy 1-4 months prior to being enrolled in the study (can be on bevacizumab maintenance) in remission of their disease at the time of enrollment between 21 and 70 years of age fluent in English in the judgment of the consenting professional, have capacity to give consent Healthy Control Inclusion Criteria: no diagnosis of cancer except basal cell carcinoma between 21 and 70 years of age fluent in English has a mini-mental state exam (MMSE) score of 26 or higher in the judgment of the consenting professional, have capacity to give consent Exclusion Criteria: active or recurrent disease, or diagnosis of another cancer (except basal cell carcinoma) as per medical records at the time of enrollment exposure to chemotherapy or radiation therapy for any medical condition unrelated to ovarian cancer on hormonal therapy at the time of enrollment neurological disorder or moderate to severe head trauma (loss of consciousness > 60 min) neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, etc. self-reported Axis I psychiatric disorder (DSM-IV), major affective disorder (untreated), bipolar disorder, schizophrenia unable to complete cognitive tests with standard contraindications to MRI examinations Healthy Control Exclusion Criteria: exposure to chemotherapy or radiation therapy for any medical condition on hormone replacement therapy at the time of enrollment neurological disorder or moderate to severe head trauma (loss of consciousness > 60 min) neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, etc.
Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 70 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| diagnosed with ovarian that recieved chemo<br> | Other: Neuroimaging & Neuropsychological Evaluation<br>* Will undergo structural and functional MRI scans on a Siemens 3T Magnetom Tim Trio research scanner located at the Citigroup Biomedical Imaging Center at Weill Cornell Medical Center (WCMC), which is adjacent to the MSKCC campus. Patients do not undergo routine clinical brain MRIs as part of their assessment and treatment, and the brain MRI scans to be performed in this study are for research purposes only. The MRI scan takes approximately 60 minutes to complete, and about 15 minutes will be required for instructions prior to initiating the study. The MRI studies will be reviewed by a neuroradiologist (Dr. Karimi) to rule out gross structural CNS abnormalities; in case any abnormalities considered to require clinical follow-up are detected, the subject will be contacted and referred for follow-up with their treating physician. Patients will undergo a brief neuropsychological test battery at MSKCC or at Citigroup Biomedical Imaging Center at WCMC<br>|
| healthy controls<br> | Other: Neuroimaging & Neuropsychological Evaluation<br>* Will undergo structural and functional MRI scans on a Siemens 3T Magnetom Tim Trio research scanner located at the Citigroup Biomedical Imaging Center at Weill Cornell Medical Center (WCMC), which is adjacent to the MSKCC campus. Patients do not undergo routine clinical brain MRIs as part of their assessment and treatment, and the brain MRI scans to be performed in this study are for research purposes only. The MRI scan takes approximately 60 minutes to complete, and about 15 minutes will be required for instructions prior to initiating the study. The MRI studies will be reviewed by a neuroradiologist (Dr. Karimi) to rule out gross structural CNS abnormalities; in case any abnormalities considered to require clinical follow-up are detected, the subject will be contacted and referred for follow-up with their treating physician. Patients will undergo a brief neuropsychological test battery at MSKCC or at Citigroup Biomedical Imaging Center at WCMC<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| alterations in regional brain volume | will undergo structural MRI scans on a Siemens 3T Magnetom Tim Trio research scanner located at the Citigroup Biomedical Imaging Center at Weill Cornell Medical Center (WCMC), which is adjacent to the MSKCC campus. Three to five T1 weighted sagittal slices are collected to localize the anterior and posterior commissures. Functional imaging: Blood Oxygenation Level-Dependent (BOLD) contrast imaging, which reflects changes in venous deoxyhemoglobin associated with neuronal activity, will be used. | 1 year |
| dorsolateral prefrontal cortex | will undergo functional MRI scans on a Siemens 3T Magnetom Tim Trio research scanner located at the Citigroup Biomedical Imaging Center at Weill Cornell Medical Center (WCMC), which is adjacent to the MSKCC campus.Three to five T1 weighted sagittal slices are collected to localize the anterior and posterior commissures. Functional imaging: Blood Oxygenation Level-Dependent (BOLD) contrast imaging, which reflects changes in venous deoxyhemoglobin associated with neuronal activity, will be used. | 1 year |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| neuropsychological functions | Patients will undergo a brief neuropsychological test battery at MSKCC or at Citigroup Biomedical Imaging Center at WCMC. All subjects will undergo a neuropsychological evaluation including standardized tests of attention and working memory, executive functions, and memory considering that these domains have been shown to be particularly sensitive to cancer treatment-induced cognitive dysfunction. | 1 year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
12-075, structural MRI, FALLOPIAN TUBE, OVARY, PERITONEUM, Quality of Life, functional MRI, neuropsychological assessment
|
||
NCT00006445
|
Down Syndrome - Comparison of Screening Methods in the 1st and 2nd Trimesters
|
Too much or too little genetic information (chromosome material) can cause abnormal development of the fetus or death. Each year approximately 2.5 million pregnant women are screened for Down Syndrome using invasive screening methods (amniocentesis or chorionic villus sampling). This 11 center study of 38,000 women will compare the accuracy of the several non-invasive tests in the first and second trimesters of pregnancy versus amniocentesis or diagnosis at birth to diagnose aneuploidy or Down Syndrome.
|
The FASTER (First and Second Trimester Evaluation of Risk) Trial is a multicenter prospective study comparing the accuracy of first and second trimester non-invasive screening methods for Down syndrome and other aneuploidies to diagnosis at delivery or miscarriage/fetal loss). All women will receive the two non-invasive test batteries in both the first and second trimesters. The accuracy of the results of different combinations of non-invasive tests will be compared with diagnosis at delivery or at miscarriage or later fetal loss.~First trimester screening will involve ultrasound measurement of fetal nuchal translucency (NT) thickness at 10-14 weeks gestation, together with maternal age, and serum levels of pregnancy associated plasma protein-A (PPAP-A) and free-beta human chorionic gonadotropin (FbhCG). Second trimester screening will be based on the current standard of care serum triple screen, which consists of alpha fetoprotein (AFP), unconjugated estriol (uE3), and hCG, performed at 15-18 weeks gestation, together with maternal age and the new serum marker inhibin-A. If patients screen positive (risk >/= 1 in 380), the patients are notified and offered invasive testing at 15 weeks (a serum quad test, an additional tube of blood for analysis of the presence of fetal nucleated erythrocytes in maternal blood [NIFTY: National Institute of Child Health and Human Development Fetal Cell Study]), and amniocentesis on those who accept). True positive cases receive counseling. True negative cases, those who decline invasive testing, and those who screen negative after the serum quad test, receive routine care with final pediatric outcome. Patients with an a priori risk for Down Syndrome may elect to have invasive fetal testing at 15 weeks after quad testing. For all fetuses with a NT measurement greater than 3 mm, and where karyotype is found to be normal after amniocentesis, will be followed with a repeat ultrasound examination at 18 to 20 weeks gestation, to evaluate fetal anatomy, particularly fetal cardiac structure. Final pediatric examination information will be obtained following delivery. If pregnancy results in miscarriage or later fetal loss, attempts will be made to karyotype any fetal tissue. This is especially important for those pregnancies that abort spontaneously between the time of the first and second trimester methods of screening. Pregnancy outcome data will be obtained in all cases.
|
First and 2nd Trimester Evaluation of the Risk of Aneuploidy
|
Down Syndrome, Chromosome Abnormalities
|
* Procedure: Ultrasound
* Procedure: Serum screen
|
Inclusion Criteria:~Women 16 to 45 years old~Enrolled by participating obstetrical center before 10-14 weeks gestation~Gestational age 10 weeks three days to 13 weeks six days, with a minimum sonographic crown rump length of 38 mm, maximum 84mm~Informed consent of patient~English fluent or accompanied by appropriate interpreter~Healthy (although co-existing diseases allowed)~Exclusion Criteria:~Multiple gestation
|
16 Years
|
45 Years
|
Female
|
Accepts Healthy Volunteers
|
Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
Pregnancy, Ultrasound, Serum screen, Pregnancy associated plasma protein-A (PAPP-A), Free-beta human chorionic gonadotropin (FbhCG), Alpha fetoprotein, Unconjugated estriol, Inhibin-A, Down syndrome, Aneuploidy
|
Nervous System Diseases, Syndrome, Down Syndrome, Chromosome Disorders, Chromosome Aberrations, Disease, Pathologic Processes, Congenital Abnormalities, Intellectual Disability, Neurobehavioral Manifestations, Neurologic Manifestations, Abnormalities, Multiple, Genetic Diseases, Inborn
|
| Intervention/Treatment |
| --- |
|Procedure: Ultrasound|nan|
|Procedure: Serum screen|nan|
|
Down Syndrome - Comparison of Screening Methods in the 1st and 2nd Trimesters
Study Overview
=================
Brief Summary
-----------------
Too much or too little genetic information (chromosome material) can cause abnormal development of the fetus or death. Each year approximately 2.5 million pregnant women are screened for Down Syndrome using invasive screening methods (amniocentesis or chorionic villus sampling). This 11 center study of 38,000 women will compare the accuracy of the several non-invasive tests in the first and second trimesters of pregnancy versus amniocentesis or diagnosis at birth to diagnose aneuploidy or Down Syndrome.
Detailed Description
-----------------
The FASTER (First and Second Trimester Evaluation of Risk) Trial is a multicenter prospective study comparing the accuracy of first and second trimester non-invasive screening methods for Down syndrome and other aneuploidies to diagnosis at delivery or miscarriage/fetal loss). All women will receive the two non-invasive test batteries in both the first and second trimesters. The accuracy of the results of different combinations of non-invasive tests will be compared with diagnosis at delivery or at miscarriage or later fetal loss. First trimester screening will involve ultrasound measurement of fetal nuchal translucency (NT) thickness at 10-14 weeks gestation, together with maternal age, and serum levels of pregnancy associated plasma protein-A (PPAP-A) and free-beta human chorionic gonadotropin (FbhCG). Second trimester screening will be based on the current standard of care serum triple screen, which consists of alpha fetoprotein (AFP), unconjugated estriol (uE3), and hCG, performed at 15-18 weeks gestation, together with maternal age and the new serum marker inhibin-A. If patients screen positive (risk >/= 1 in 380), the patients are notified and offered invasive testing at 15 weeks (a serum quad test, an additional tube of blood for analysis of the presence of fetal nucleated erythrocytes in maternal blood [NIFTY: National Institute of Child Health and Human Development Fetal Cell Study]), and amniocentesis on those who accept). True positive cases receive counseling. True negative cases, those who decline invasive testing, and those who screen negative after the serum quad test, receive routine care with final pediatric outcome. Patients with an a priori risk for Down Syndrome may elect to have invasive fetal testing at 15 weeks after quad testing. For all fetuses with a NT measurement greater than 3 mm, and where karyotype is found to be normal after amniocentesis, will be followed with a repeat ultrasound examination at 18 to 20 weeks gestation, to evaluate fetal anatomy, particularly fetal cardiac structure. Final pediatric examination information will be obtained following delivery. If pregnancy results in miscarriage or later fetal loss, attempts will be made to karyotype any fetal tissue. This is especially important for those pregnancies that abort spontaneously between the time of the first and second trimester methods of screening. Pregnancy outcome data will be obtained in all cases.
Official Title
-----------------
First and 2nd Trimester Evaluation of the Risk of Aneuploidy
Conditions
-----------------
Down Syndrome, Chromosome Abnormalities
Intervention / Treatment
-----------------
* Procedure: Ultrasound
* Procedure: Serum screen
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women 16 to 45 years old Enrolled by participating obstetrical center before 10-14 weeks gestation Gestational age 10 weeks three days to 13 weeks six days, with a minimum sonographic crown rump length of 38 mm, maximum 84mm Informed consent of patient English fluent or accompanied by appropriate interpreter Healthy (although co-existing diseases allowed) Exclusion Criteria: Multiple gestation
Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 45 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Intervention/Treatment |
| --- |
|Procedure: Ultrasound|nan|
|Procedure: Serum screen|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
-----------------
Pregnancy, Ultrasound, Serum screen, Pregnancy associated plasma protein-A (PAPP-A), Free-beta human chorionic gonadotropin (FbhCG), Alpha fetoprotein, Unconjugated estriol, Inhibin-A, Down syndrome, Aneuploidy
|
|
NCT00537277
|
Efficacy and Safety of Biphasic Insulin Aspart 30 in Type 2 Diabetes Mellitus When Failing on OADs
|
This trial is conducted in Europe.~This is a clinical trial investigating the effectiveness and the safety of using biphasic insulin aspart 30 both for initiation and intensification of insulin treatment in type 2 diabetes.
|
A Titrate-To-Target Study of the Efficacy and Safety of Biphasic Insulin Aspart 30 in Subjects With Type 2 Diabetes Mellitus Not Achieving Glycaemic Targets on OADs With / Without Once Daily Basal Insulin Therapy
|
Diabetes, Diabetes Mellitus, Type 2
|
* Drug: biphasic insulin aspart
|
Inclusion Criteria:~Type 2 Diabetes Mellitus for more than 12 months~HbA1c: 7.5 - 11.0%~An antidiabetic regimen that has been stable for at least 3 months prior to screening~An antidiabetic regimen that includes a minimum of 2 oral anti-diabetic drugs (OADs) or 1 OAD plus evening or bedtime basal insulin~OADs dosed at 50% or more of the maximum recommended dose~Exclusion Criteria:~Use of any insulin preparations other than NPH or glargine within the past 6 months~Use of more than 60 units of insulin per day~Morning time insulin administration~Use of more than one insulin dose daily
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving the Treatment Target of Glycosylated Haemoglobin (HbA1c) Below 7.0% | | week 48 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Trial Completers Achieving the Treatment Target of Glycosylated Haemoglobin (HbA1c) Below 7.0% | | week 48 |
| Number of Hypoglycaemic Episodes | Total number of hypoglycaemic episodes experienced from baseline (week 0) to end of trial (week 48). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose (PG) below 3.1 mmol/L or 56 mg/dL. Symptoms only if subject was able to treat her/himself and with either no PG or blood glucose measurement or PG higher than or equal to 3.1 mmol/L or 56 mg/dL. | weeks 0-48 |
| Number of Diurnal Hypoglycaemic Episodes | Total number of hypoglycaemic episodes during the day (diurnal) experienced in the trial from baseline (week 0) to end of trial (week 48). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose (PG) below 3.1 mmol/L or 56 mg/dL. Symptoms only if subject was able to treat her/himself and with either no PG or blood glucose measurement or PG higher than or equal to 3.1 mmol/L or 56 mg/dL. | weeks 0-48 |
| Number of Nocturnal Hypoglycaemic Episodes | Total number of hypoglycaemic episodes during the night (nocturnal) experienced in the trial from baseline (week 0) to end of trial (week 48). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose (PG) below 3.1 mmol/L or 56 mg/dL. Symptoms only if subject was able to treat her/himself and with either no PG or blood glucose measurement or PG higher than or equal to 3.1 mmol/L or 56 mg/dL. | weeks 0-48 |
| Number of Treatment Emergent Serious Adverse Events (SAEs) | Total number of treatment emergent SAEs experienced from baseline (week 0) to end of trial (week 48). A treatment emergent SAE were defined as an adverse event which occurred in the trial treatment period. | weeks 0-48 |
|
Insulin Aspart, Biphasic Insulins, Insulin aspart, insulin aspart protamine drug combination 30:70, Hypoglycemic Agents, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIAsp 30<br>Biphasic insulin aspart 30 administered once daily for 16 weeks. If HbA1c is higher than 7.0 % after 16 weeks of treatment, dose is increased to twice daily for another 16 weeks. If HbA1c is higher than 7.0 % after 32 weeks of treatment, dose is increased to three times daily until week 48 (end of trial). | Drug: biphasic insulin aspart<br>* Treat-to-target dose titration scheme (dose individually adjusted), injected s.c. (under the skin)<br>* Other names: NovoMix 30;|
|
Efficacy and Safety of Biphasic Insulin Aspart 30 in Type 2 Diabetes Mellitus When Failing on OADs
Study Overview
=================
Brief Summary
-----------------
This trial is conducted in Europe. This is a clinical trial investigating the effectiveness and the safety of using biphasic insulin aspart 30 both for initiation and intensification of insulin treatment in type 2 diabetes.
Official Title
-----------------
A Titrate-To-Target Study of the Efficacy and Safety of Biphasic Insulin Aspart 30 in Subjects With Type 2 Diabetes Mellitus Not Achieving Glycaemic Targets on OADs With / Without Once Daily Basal Insulin Therapy
Conditions
-----------------
Diabetes, Diabetes Mellitus, Type 2
Intervention / Treatment
-----------------
* Drug: biphasic insulin aspart
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Type 2 Diabetes Mellitus for more than 12 months HbA1c: 7.5 - 11.0% An antidiabetic regimen that has been stable for at least 3 months prior to screening An antidiabetic regimen that includes a minimum of 2 oral anti-diabetic drugs (OADs) or 1 OAD plus evening or bedtime basal insulin OADs dosed at 50% or more of the maximum recommended dose Exclusion Criteria: Use of any insulin preparations other than NPH or glargine within the past 6 months Use of more than 60 units of insulin per day Morning time insulin administration Use of more than one insulin dose daily
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: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIAsp 30<br>Biphasic insulin aspart 30 administered once daily for 16 weeks. If HbA1c is higher than 7.0 % after 16 weeks of treatment, dose is increased to twice daily for another 16 weeks. If HbA1c is higher than 7.0 % after 32 weeks of treatment, dose is increased to three times daily until week 48 (end of trial). | Drug: biphasic insulin aspart<br>* Treat-to-target dose titration scheme (dose individually adjusted), injected s.c. (under the skin)<br>* Other names: NovoMix 30;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving the Treatment Target of Glycosylated Haemoglobin (HbA1c) Below 7.0% | | week 48 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Trial Completers Achieving the Treatment Target of Glycosylated Haemoglobin (HbA1c) Below 7.0% | | week 48 |
| Number of Hypoglycaemic Episodes | Total number of hypoglycaemic episodes experienced from baseline (week 0) to end of trial (week 48). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose (PG) below 3.1 mmol/L or 56 mg/dL. Symptoms only if subject was able to treat her/himself and with either no PG or blood glucose measurement or PG higher than or equal to 3.1 mmol/L or 56 mg/dL. | weeks 0-48 |
| Number of Diurnal Hypoglycaemic Episodes | Total number of hypoglycaemic episodes during the day (diurnal) experienced in the trial from baseline (week 0) to end of trial (week 48). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose (PG) below 3.1 mmol/L or 56 mg/dL. Symptoms only if subject was able to treat her/himself and with either no PG or blood glucose measurement or PG higher than or equal to 3.1 mmol/L or 56 mg/dL. | weeks 0-48 |
| Number of Nocturnal Hypoglycaemic Episodes | Total number of hypoglycaemic episodes during the night (nocturnal) experienced in the trial from baseline (week 0) to end of trial (week 48). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose (PG) below 3.1 mmol/L or 56 mg/dL. Symptoms only if subject was able to treat her/himself and with either no PG or blood glucose measurement or PG higher than or equal to 3.1 mmol/L or 56 mg/dL. | weeks 0-48 |
| Number of Treatment Emergent Serious Adverse Events (SAEs) | Total number of treatment emergent SAEs experienced from baseline (week 0) to end of trial (week 48). A treatment emergent SAE were defined as an adverse event which occurred in the trial treatment period. | weeks 0-48 |
|
||
NCT04397393
|
Does Camel Milk Consumption Decrease The Efficacy Of Midazolam For Sedation
|
The primary aim is to verify if camel milk consumption has an impact on the amount of Midazolam needed to achieve a satisfactory level of sedation for oocyte retrieval, compared to patients never having consumed camel milk.
|
A pilot study will be performed on patients undergoing oocyte retrieval (OPU) for the first time, and correlated to camel milk consumption versus never consumed camel milk, as well as age, BMI (body mass index), number of follicles at the time of OPU, number of previous OPUs in other clinics, previous vaginal delivery, past medical history positive for chemo therapy, alcohol consumption, use of prescribed or illicit drugs, or chronic pain medication.~The main objective is to analyse if the consumption of camel milk, the frequency, or lack thereof correlates with the amount of the sedative drug Midazolam needed to achieve an acceptable level of sedation in order to estimate the dosage needed in both patient groups more adequately, reducing either discomfort felt at a too low an initial dosage, as well as avoiding a deeper level of sedation than needed with subsequent prolonged stay in recovery and unpleasant feelings of dizziness and drowsiness, potentially requiring antagonizing Midazolam by the use of Flumazenil, and reducing overall costs and length of stay in recovery and bed occupancy and enhancing patient experience and satisfaction.~Would this study enable the Investigators to determine further effect of camel milk on other drugs used for various other purposes, and lead to a change in dose regimen?
|
Does Camel Milk Consumption Decrease The Efficacy Of Midazolam For Sedation: A Pilot Study
|
IVF, Anesthesia
|
* Drug: Midazolam
|
Inclusion Criteria:~Arab origin~Female 18 -48 years of age~BMI < 37 kg/m2~All ovarian stimulation protocols~Exclusion Criteria:~Previous oocyte retrieval at our center~Post chemo therapy~Illicit drug use~Chronic pain medication~Medication which is known to increase the activity of liver enzymes~Any alcohol consumption~Previous vaginal delivery
|
18 Years
|
48 Years
|
Female
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dosage of Midazolam (in mg) needed to achieve satisfactory level of sedation to perform the OPU | Mean dosage of Midazolam for both groups (Camel milk consumption vs no camel milk consumption | 1 day |
|
Anesthetics, General, Midazolam, Adjuvants, Anesthesia, Hypnotics and Sedatives, Central Nervous System Depressants, Physiological Effects of Drugs, Anti-Anxiety Agents, Tranquilizing Agents, Psychotropic Drugs, Anesthetics, Intravenous, Anesthetics, GABA Modulators, GABA Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| non-camel milk consumption<br>non-camel milk consumption over life time | Drug: Midazolam<br>* Dosage of Midazolam (in mg) needed to achieve satisfactory level of sedation to perform OPU<br>|
| camel milk consumption<br>camel milk consumption at least once during lifetime, with 2 subgroups of camel milk consumption: once, twice, three times; as well as regularly (daily, once per week, once per month, once per year). | Drug: Midazolam<br>* Dosage of Midazolam (in mg) needed to achieve satisfactory level of sedation to perform OPU<br>|
|
Does Camel Milk Consumption Decrease The Efficacy Of Midazolam For Sedation
Study Overview
=================
Brief Summary
-----------------
The primary aim is to verify if camel milk consumption has an impact on the amount of Midazolam needed to achieve a satisfactory level of sedation for oocyte retrieval, compared to patients never having consumed camel milk.
Detailed Description
-----------------
A pilot study will be performed on patients undergoing oocyte retrieval (OPU) for the first time, and correlated to camel milk consumption versus never consumed camel milk, as well as age, BMI (body mass index), number of follicles at the time of OPU, number of previous OPUs in other clinics, previous vaginal delivery, past medical history positive for chemo therapy, alcohol consumption, use of prescribed or illicit drugs, or chronic pain medication. The main objective is to analyse if the consumption of camel milk, the frequency, or lack thereof correlates with the amount of the sedative drug Midazolam needed to achieve an acceptable level of sedation in order to estimate the dosage needed in both patient groups more adequately, reducing either discomfort felt at a too low an initial dosage, as well as avoiding a deeper level of sedation than needed with subsequent prolonged stay in recovery and unpleasant feelings of dizziness and drowsiness, potentially requiring antagonizing Midazolam by the use of Flumazenil, and reducing overall costs and length of stay in recovery and bed occupancy and enhancing patient experience and satisfaction. Would this study enable the Investigators to determine further effect of camel milk on other drugs used for various other purposes, and lead to a change in dose regimen?
Official Title
-----------------
Does Camel Milk Consumption Decrease The Efficacy Of Midazolam For Sedation: A Pilot Study
Conditions
-----------------
IVF, Anesthesia
Intervention / Treatment
-----------------
* Drug: Midazolam
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Arab origin Female 18 -48 years of age BMI < 37 kg/m2 All ovarian stimulation protocols Exclusion Criteria: Previous oocyte retrieval at our center Post chemo therapy Illicit drug use Chronic pain medication Medication which is known to increase the activity of liver enzymes Any alcohol consumption Previous vaginal delivery
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 48 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| non-camel milk consumption<br>non-camel milk consumption over life time | Drug: Midazolam<br>* Dosage of Midazolam (in mg) needed to achieve satisfactory level of sedation to perform OPU<br>|
| camel milk consumption<br>camel milk consumption at least once during lifetime, with 2 subgroups of camel milk consumption: once, twice, three times; as well as regularly (daily, once per week, once per month, once per year). | Drug: Midazolam<br>* Dosage of Midazolam (in mg) needed to achieve satisfactory level of sedation to perform OPU<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dosage of Midazolam (in mg) needed to achieve satisfactory level of sedation to perform the OPU | Mean dosage of Midazolam for both groups (Camel milk consumption vs no camel milk consumption | 1 day |
|
|||
NCT01289093
|
Quality of Life After Laparoscopic Inguinal- Incisional and Umbilical Herniotomy.
|
LIFE-IN. Quality of life after operation for hernias are not well investigated and lack a good and easy-to-understand-tool to measure it. Carolina Comfort Scale (CCS) is a disease-specific quality of life questionnaire, designed by an American group, to monitor quality of life in patients undergoing operation for hernias.~The investigators wish to test this questionnaire against Visual Analogue Scale (VAS) scores for core-hernia symptoms, to see if the CCS is a good way to monitor the changes in quality of life and other well-known core-symptoms before and after herniotomies.
|
The investigators include consecutively all in all 140 patients. 100 with inguinal hernias; 50 who is getting a Lichtenstein operation and 50 who is getting a laparoscopic operation. Furthermore minimum 20 patients who is getting a laparoscopic operation for incisional hernia and minimum 20 who went through umbilical herniotomy. The investigators monitor their pain, sensation of mesh, movement limitations, over-all well-being, fatigue and life-quality, with both CCS and VAS questionnaires 5 times. One time preoperative and 4 times after operation, on the 1sth, 7th, 30th and 90th day after operation.
|
Quality of Life After Laparoscopic Inguinal- Incisional- and Umbilical Herniotomy.
|
Inguinal Hernia, Incisional Hernia, Umbilical Hernias
|
Inclusion Criteria:~elective laparoscopic and open operations for inguinal hernia~elective laparoscopic operation for incisional- and umbilical hernia~primary hernia~uni-bilateral hernias and one or more incisional hernias~Exclusion Criteria:~expected bad compliance to the study~acute operations~re-operations~secondary operations~primary operation with reoperation within 30 days
|
18 Years
|
80 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| quality of life | pain, sensation of mesh, movement limitations, over-all well-being, fatigue and quality of life. These core symptoms will be measured 5 times with the 2 questionnaires CCS and VAS. One time before and 4 times after the operation with both the CCS and VAS, to see if the is a graphical correlation between the to questionnaires and to find out which of the two questionnaires is best. | before operation until 90 days postoperative |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| acceptability | The investigators measure the patients satisfaction with the instruments and which one (VAS or CCS) they prefer. | preoperative untill 90 days postoperative |
|
inguinal hernia, incisional hernia, quality of life, disease-specific
|
Hernia, Umbilical, Hernia, Hernia, Inguinal, Incisional Hernia, Pathological Conditions, Anatomical, Hernia, Abdominal, Postoperative Complications, Pathologic Processes, Infant, Newborn, Diseases, Hernia, Ventral
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| laparoscopic ingunal herniotomy<br> | |
| laparoscopic incisional herniotomy<br> | |
| Lichtenstein inguinal herniotomy<br> | |
| laparoscopic umbilical hernia repair<br> | |
|
Quality of Life After Laparoscopic Inguinal- Incisional and Umbilical Herniotomy.
Study Overview
=================
Brief Summary
-----------------
LIFE-IN. Quality of life after operation for hernias are not well investigated and lack a good and easy-to-understand-tool to measure it. Carolina Comfort Scale (CCS) is a disease-specific quality of life questionnaire, designed by an American group, to monitor quality of life in patients undergoing operation for hernias. The investigators wish to test this questionnaire against Visual Analogue Scale (VAS) scores for core-hernia symptoms, to see if the CCS is a good way to monitor the changes in quality of life and other well-known core-symptoms before and after herniotomies.
Detailed Description
-----------------
The investigators include consecutively all in all 140 patients. 100 with inguinal hernias; 50 who is getting a Lichtenstein operation and 50 who is getting a laparoscopic operation. Furthermore minimum 20 patients who is getting a laparoscopic operation for incisional hernia and minimum 20 who went through umbilical herniotomy. The investigators monitor their pain, sensation of mesh, movement limitations, over-all well-being, fatigue and life-quality, with both CCS and VAS questionnaires 5 times. One time preoperative and 4 times after operation, on the 1sth, 7th, 30th and 90th day after operation.
Official Title
-----------------
Quality of Life After Laparoscopic Inguinal- Incisional- and Umbilical Herniotomy.
Conditions
-----------------
Inguinal Hernia, Incisional Hernia, Umbilical Hernias
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: elective laparoscopic and open operations for inguinal hernia elective laparoscopic operation for incisional- and umbilical hernia primary hernia uni-bilateral hernias and one or more incisional hernias Exclusion Criteria: expected bad compliance to the study acute operations re-operations secondary operations primary operation with reoperation within 30 days
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?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| laparoscopic ingunal herniotomy<br> | |
| laparoscopic incisional herniotomy<br> | |
| Lichtenstein inguinal herniotomy<br> | |
| laparoscopic umbilical hernia repair<br> | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| quality of life | pain, sensation of mesh, movement limitations, over-all well-being, fatigue and quality of life. These core symptoms will be measured 5 times with the 2 questionnaires CCS and VAS. One time before and 4 times after the operation with both the CCS and VAS, to see if the is a graphical correlation between the to questionnaires and to find out which of the two questionnaires is best. | before operation until 90 days postoperative |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| acceptability | The investigators measure the patients satisfaction with the instruments and which one (VAS or CCS) they prefer. | preoperative untill 90 days postoperative |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
inguinal hernia, incisional hernia, quality of life, disease-specific
|
||
NCT03821129
|
GORE® CARDIOFORM Septal Occluder and Antiplatelet Medical Management for Reduction of Recurrent Stroke in Patients With Patent Foramen Ovale (PFO): the REDUCE Post Approval Study
|
This study will assess the safety and effectiveness of GORE® CARDIOFORM Septal Occluder in a post approval setting and evaluate the quality of operator education and training and transferability of trial experience to a post-market setting.
|
A maximum of 636 adult subjects will be enrolled at up to 40 U.S. centers. Subjects will have follow-up at 1 month, 6 months, 12 months and annually thereafter through 5 years post implant.
|
GORE® CARDIOFORM Septal Occluder and Antiplatelet Medical Management for Reduction of Recurrent Stroke in Patients With Patent Foramen Ovale (PFO): the REDUCE Post Approval Study
|
Stroke, PFO - Patent Foramen Ovale
|
* Device: PFO closure with GORE® CARDIOFORM Septal Occluder
|
Inclusion Criteria:~Diagnosed with an ischemic stroke presumed to be an embolic stroke of undetermined source (ESUS) verified by a neurologist within the last 365 days prior to enrollment.~Presence of Patent Foramen Ovale (PFO), as determined initially by positive bubble study utilizing transesophageal echocardiography (TEE) and/or transcranial Doppler (TCD), demonstrating spontaneous right-to-left shunting or right-to-left shunting during Valsalva maneuver.~Patient is able to tolerate antiplatelet therapy~Note: Additional Inclusion Criteria may apply~Exclusion Criteria:~History of or ongoing atrial fibrillation/flutter~Other co-morbidities including, but not limited to, mural thrombus, dilated cardiomyopathy, cardiac prosthetics (valves), severe native valve disease (including mitral valve stenosis), severe ventricular wall motion abnormalities, aortic dissection, significant atherosclerosis, vasculitis, pre-existing non-vascular neurologic disorders, pulmonary arteriovenous malformations, prior intracranial hemorrhage, severe disability related to prior stroke, autoimmune disorders that would increase the risk of stroke or thromboembolism, or associated with increased risk of infection or procedural complications, in the opinion of the investigator, left ventricular ejection fraction of <40%, coexistent cause or intra-cardiac shunting (e.g. VSD or ASD)~Previous Myocardial Infarction~Rankin Scale sore greater than or equal to 3 at the time of procedure~Active infection that cannot be treated successfully prior to enrollment~Neurological deficits not due to stroke that may affect the patient's neurologic assessments~Evidence of hypercoagulable state, Uncontrolled diabetes mellitus, uncontrolled systemic hypertension or pulmonary hypertension at the time of screening or procedure~Sensitivity or contraindication to all proposed medical treatments or any device components~Pregnant, lactating, or intent on becoming pregnant through 24 months after enrollment.~Indications outside the parameters accepted for placement of GSO, including extensive congenital cardiac anomalies and defect diameters considered too large for closure with the device.~Atrial septal anatomy that is expected to necessitate placement of more than one GORE® CARDIOFORM Septal Occluder~Need for concomitant procedure(s) that may confound detection of adverse events related to device placement~Note: Additional Exclusion Criteria may apply
|
18 Years
|
70 Years
|
All
|
No
|
Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with recurrent ischemic stroke post study device implant (Primary Effectiveness Outcome) | Proportion of subjects with recurrent ischemic stroke post study device implant | 24 months |
| Proportion of subjects with device- or procedure-related serious adverse events at 30 days (Primary Safety Endpoint) | Device- or procedure- related serious adverse events post study device implant | 30 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effective PFO Closure defined as complete PFO closure or a trivial or small residual shunt by Echocardiographic assessment | Complete PFO closure or a trivial or small residual shunt~Proportion of subjects with complete PFO closure or a trivial or small residual shunt | 12 months |
| Clinically Significant New Atrial Arrhythmia | Any new atrial fibrillation or flutter | 60 months |
| Clinically Significant New Atrial Arrhythmia by Age | Any new atrial fibrillation or flutter in patients greater and less than 60 years of age | 60 months |
| Residual Shunt Characterization via assessment of shunt in patients by Echo | Assessment of shunt in patients by Echo | 24 months |
| Technical Success defined as successful delivery and retention of the GSO device based on physician reporting | Successful delivery and retention of the GSO device | Index procedure |
| Procedural Success defined as successful implantation of the GSO device with no reported in-hospital Serious Adverse Events (SAEs) | Successful implantation of the GSO device with no reported in-hospital SAEs | Enrollment through discharge, approximately 1 day |
|
Occluder, Patent Foramen Ovale, PFO, Stroke, Gore Septal Occluder
|
Heart Diseases, Stroke, Foramen Ovale, Patent, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Vascular Diseases, Cardiovascular Diseases, Heart Septal Defects, Atrial, Heart Septal Defects, Heart Defects, Congenital, Cardiovascular Abnormalities, Congenital Abnormalities
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: GORE® CARDIOFORM Septal Occluder<br>Single Arm Commercially available GORE® CARDIOFORM Septal Occluder | Device: PFO closure with GORE® CARDIOFORM Septal Occluder<br>* PFO closure with GORE® CARDIOFORM Septal Occluder in patients with ischemic stroke<br>|
|
GORE® CARDIOFORM Septal Occluder and Antiplatelet Medical Management for Reduction of Recurrent Stroke in Patients With Patent Foramen Ovale (PFO): the REDUCE Post Approval Study
Study Overview
=================
Brief Summary
-----------------
This study will assess the safety and effectiveness of GORE® CARDIOFORM Septal Occluder in a post approval setting and evaluate the quality of operator education and training and transferability of trial experience to a post-market setting.
Detailed Description
-----------------
A maximum of 636 adult subjects will be enrolled at up to 40 U.S. centers. Subjects will have follow-up at 1 month, 6 months, 12 months and annually thereafter through 5 years post implant.
Official Title
-----------------
GORE® CARDIOFORM Septal Occluder and Antiplatelet Medical Management for Reduction of Recurrent Stroke in Patients With Patent Foramen Ovale (PFO): the REDUCE Post Approval Study
Conditions
-----------------
Stroke, PFO - Patent Foramen Ovale
Intervention / Treatment
-----------------
* Device: PFO closure with GORE® CARDIOFORM Septal Occluder
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosed with an ischemic stroke presumed to be an embolic stroke of undetermined source (ESUS) verified by a neurologist within the last 365 days prior to enrollment. Presence of Patent Foramen Ovale (PFO), as determined initially by positive bubble study utilizing transesophageal echocardiography (TEE) and/or transcranial Doppler (TCD), demonstrating spontaneous right-to-left shunting or right-to-left shunting during Valsalva maneuver. Patient is able to tolerate antiplatelet therapy Note: Additional Inclusion Criteria may apply Exclusion Criteria: History of or ongoing atrial fibrillation/flutter Other co-morbidities including, but not limited to, mural thrombus, dilated cardiomyopathy, cardiac prosthetics (valves), severe native valve disease (including mitral valve stenosis), severe ventricular wall motion abnormalities, aortic dissection, significant atherosclerosis, vasculitis, pre-existing non-vascular neurologic disorders, pulmonary arteriovenous malformations, prior intracranial hemorrhage, severe disability related to prior stroke, autoimmune disorders that would increase the risk of stroke or thromboembolism, or associated with increased risk of infection or procedural complications, in the opinion of the investigator, left ventricular ejection fraction of <40%, coexistent cause or intra-cardiac shunting (e.g. VSD or ASD) Previous Myocardial Infarction Rankin Scale sore greater than or equal to 3 at the time of procedure Active infection that cannot be treated successfully prior to enrollment Neurological deficits not due to stroke that may affect the patient's neurologic assessments Evidence of hypercoagulable state, Uncontrolled diabetes mellitus, uncontrolled systemic hypertension or pulmonary hypertension at the time of screening or procedure Sensitivity or contraindication to all proposed medical treatments or any device components Pregnant, lactating, or intent on becoming pregnant through 24 months after enrollment. Indications outside the parameters accepted for placement of GSO, including extensive congenital cardiac anomalies and defect diameters considered too large for closure with the device. Atrial septal anatomy that is expected to necessitate placement of more than one GORE® CARDIOFORM Septal Occluder Need for concomitant procedure(s) that may confound detection of adverse events related to device placement Note: Additional Exclusion Criteria may apply
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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: GORE® CARDIOFORM Septal Occluder<br>Single Arm Commercially available GORE® CARDIOFORM Septal Occluder | Device: PFO closure with GORE® CARDIOFORM Septal Occluder<br>* PFO closure with GORE® CARDIOFORM Septal Occluder in patients with ischemic stroke<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with recurrent ischemic stroke post study device implant (Primary Effectiveness Outcome) | Proportion of subjects with recurrent ischemic stroke post study device implant | 24 months |
| Proportion of subjects with device- or procedure-related serious adverse events at 30 days (Primary Safety Endpoint) | Device- or procedure- related serious adverse events post study device implant | 30 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effective PFO Closure defined as complete PFO closure or a trivial or small residual shunt by Echocardiographic assessment | Complete PFO closure or a trivial or small residual shunt Proportion of subjects with complete PFO closure or a trivial or small residual shunt | 12 months |
| Clinically Significant New Atrial Arrhythmia | Any new atrial fibrillation or flutter | 60 months |
| Clinically Significant New Atrial Arrhythmia by Age | Any new atrial fibrillation or flutter in patients greater and less than 60 years of age | 60 months |
| Residual Shunt Characterization via assessment of shunt in patients by Echo | Assessment of shunt in patients by Echo | 24 months |
| Technical Success defined as successful delivery and retention of the GSO device based on physician reporting | Successful delivery and retention of the GSO device | Index procedure |
| Procedural Success defined as successful implantation of the GSO device with no reported in-hospital Serious Adverse Events (SAEs) | Successful implantation of the GSO device with no reported in-hospital SAEs | Enrollment through discharge, approximately 1 day |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Occluder, Patent Foramen Ovale, PFO, Stroke, Gore Septal Occluder
|
NCT01888354
|
Pilot Clinical Trial of ACTHar Gel 14 Days Subcutaneous (SQ)Versus ACTHar Gel Five Days SQ for the Treatment of MS Exacerbations
|
This pilot study is designed as a prospective cohort study to determine whether standard subcutaneous (SQ) Highly-Purified (HP) Acthar Gel 14 days is superior to SQ HP Acthar Gel 5 days in the treatment of relapses or attacks in multiple sclerosis (MS).
|
Evaluations and treatment will be administered as an outpatient in the Neurology Clinic. Each subject will be seen for MS relapse or exacerbation in the Neurology Clinic during a routine or semi-emergent visit. Patients will be offered an FDA approved treatment (ACTHar Gel) for MS attacks under a standard 14 day SQ protocol (standard 14 day SQ protocol (80 IU x 14 days) or a 5 day SQ protocol - (5 day subcutaneous protocol (80 IU x 5 days). Both protocols are within package insert guidelines. The subjects will be evaluated for Extended Disability Status Scales (EDSS), a standardized measure of clinical status in MS and the initial visit and 28 days later (and 90 days later). We will compare the change in EDSS outcomes between day 0 and day 28 (day 90) to determine if the 14 days is superior to 5 day protocol may be clinically equivalent. Patients will also be evaluated for walking, upper extremity function (9 hole peg test), cognition and vision.
|
Pilot Clinical Trial of ACTHar Gel 14 Days Subcutaneous (SQ) Versus ACTHar Gel Five Days SQ for the Treatment of MS Exacerbations
|
Multiple Sclerosis (MS)
|
* Drug: H.P. Acthar Gel (repository corticotropin injection)
|
Inclusion Criteria:~Adult male or female subjects with MS having a relapse (attack) or exacerbation of MS. Acute symptomatic exacerbation of MS present for > 24 hours and < 14 days at screening with new or worsening symptoms, and with signs referable to the symptoms in the absence of a fever or active infection.~Diagnosis of a relapsing forms of multiple sclerosis before randomization as determined by Poser or McDonald Criteria (standard MS diagnostic criteria).~Expanded disability status scale (EDDS) between 2 and 6.5, inclusive at entry.~Episodes include study neurologist or neuro-ophthalmologist diagnosed: acute optic neuritis, cerebellar, brainstem dysfunction, myelitis, focal cerebral, and/or definitive focal sensory dysfunction.~New objective clinical finding other than the sensory exacerbation or the bowel/bladder signs alone. Sensory deficits alone will not qualify except for optic neuritis.~Subjects may continue on their current immunomodulation therapy such as interferons, glatiramer acetate, gilenya or natalizumab.~Identified patients must be between the ages of 18 and 55 years, inclusive.~Ability to understand and the willingness to sign a written informed consent document.~Exclusion Criteria:~Subjects who are pregnant, or nursing.~Any patients treated with systemic corticosteroid use within one month of the index episode at screening.~Prior use of immunosuppressive treatments within 90 days of index episode (mitoxantrone, azathioprine, Cellcept, IVIg) or plasmapheresis.~Unable to perform timed 25 foot walk (ambulation Index), 9 HPT (9 hole peg test), PASAT (Paced Auditory Serial Addition Test) 3.~Peripheral or cranial neuropathy as sole problem of acute episode.~Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.~History of any significant cardiac, gastrointestinal, hepatic, pulmonary, or renal disease; immune deficiency; or other medical conditions that would preclude corticosteroid therapy.~Subjects with clinical diagnosis of scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, hypertension, or sensitivity to proteins of porcine origin.~Primary Progressive Multiple Sclerosis (PPMS) (MS without attacks). -
|
18 Years
|
55 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of EDSS Mean Recovery between 5-day vs 14-day SQ 80 IU ACTHar Gel therapy groups | To determine whether a standard 14 day course of SQ 80 IU ACTHar Gel therapy might be superior (in twice as many patients) to treatment with 5 day SQ regimen for ACTHar Gel as determined by EDSS mean recovery from Day 0 (time of steroid therapy initiation) to Day 28 (and day 90). | 28 Days (with 90 day follow-up) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of ambulation between the 5-day vs.14-day SQ 80 IU ACTHar Gel therapy groups | The ambulation index (AI) will be used for patients with long track (pyramidal) relapses, i.e. relapses with leg involvement. This is a standardized rating scale developed to assess mobility by evaluating the time and degree of assistance required to walk 25 feet. | 28 Days (with 90 day follow-up) |
| Comparison of upper extremity function between the 5-day vs.14-day SQ 80 IU ACTHar Gel therapy groups | The nine-hole peg test (9HPT) will be used for patients with arm involvement during relapses. The 9-HPT is a brief, standardized, quantitative test of upper extremity function. This is a timed test to determine how long it takes the patient to quickly place nine pegs (one at a time) in a wooden box with 9 empty holes, and them remove them again (one at a time) as quickly as possible. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand. | 28 day (with 90 follow up) |
| Comparison of subjective impressions of effectiveness between the 5-day vs 14-day SQ 80 IU ACTHar Gel therapy groups | The patient global impression of change (PGI-Change) will be used in patients to compare subjective impressions of effectiveness between treatment groups | 28 day (with 90 day follow up) |
| Compare visual function between 5-day vs 14-day SQ 80 IU ACTHar Gel therapy groups | Visual function, as measured by low contrast Sloan sensitivity testing (LCSST) will be performed on each patient at baseline and at the end of treatment | 28 day (with 90 day follow up) |
| Comparison of cognitive function between the 5-day vs 14-day SQ 80 IU ACTHar Gel therapy groups | In patients who report cognitive deficits during relapse, the paced auditory serial addition test (PASAT-3) will be used to assess and measure capacity and rate of information processing, and sustained and divided attention. This is a common neuropsychological test used in MS trials that involves working memory, attention and arithmetic capabilities. Patients will hear a series of recorded single-digit numbers at a rate of 1 per 3 seconds, and asked to add the number they just heard with the number they heard before. | 28 day (with 90 day follow up) |
|
MS, Multiple Sclerosis
|
Adrenocorticotropic Hormone, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acthar Gel 80 IU x 14 days<br>Acthar Gel 80 IU SQ x 14 days | Drug: H.P. Acthar Gel (repository corticotropin injection)<br>* Acthar Gel 80 IU<br>* Other names: ACTH Gel;|
| Experimental: Acthar Gel 80 IU x 5 days<br>Acthar Gel 80 IU SQ x 5 days | Drug: H.P. Acthar Gel (repository corticotropin injection)<br>* Acthar Gel 80 IU<br>* Other names: ACTH Gel;|
|
Pilot Clinical Trial of ACTHar Gel 14 Days Subcutaneous (SQ)Versus ACTHar Gel Five Days SQ for the Treatment of MS Exacerbations
Study Overview
=================
Brief Summary
-----------------
This pilot study is designed as a prospective cohort study to determine whether standard subcutaneous (SQ) Highly-Purified (HP) Acthar Gel 14 days is superior to SQ HP Acthar Gel 5 days in the treatment of relapses or attacks in multiple sclerosis (MS).
Detailed Description
-----------------
Evaluations and treatment will be administered as an outpatient in the Neurology Clinic. Each subject will be seen for MS relapse or exacerbation in the Neurology Clinic during a routine or semi-emergent visit. Patients will be offered an FDA approved treatment (ACTHar Gel) for MS attacks under a standard 14 day SQ protocol (standard 14 day SQ protocol (80 IU x 14 days) or a 5 day SQ protocol - (5 day subcutaneous protocol (80 IU x 5 days). Both protocols are within package insert guidelines. The subjects will be evaluated for Extended Disability Status Scales (EDSS), a standardized measure of clinical status in MS and the initial visit and 28 days later (and 90 days later). We will compare the change in EDSS outcomes between day 0 and day 28 (day 90) to determine if the 14 days is superior to 5 day protocol may be clinically equivalent. Patients will also be evaluated for walking, upper extremity function (9 hole peg test), cognition and vision.
Official Title
-----------------
Pilot Clinical Trial of ACTHar Gel 14 Days Subcutaneous (SQ) Versus ACTHar Gel Five Days SQ for the Treatment of MS Exacerbations
Conditions
-----------------
Multiple Sclerosis (MS)
Intervention / Treatment
-----------------
* Drug: H.P. Acthar Gel (repository corticotropin injection)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult male or female subjects with MS having a relapse (attack) or exacerbation of MS. Acute symptomatic exacerbation of MS present for > 24 hours and < 14 days at screening with new or worsening symptoms, and with signs referable to the symptoms in the absence of a fever or active infection. Diagnosis of a relapsing forms of multiple sclerosis before randomization as determined by Poser or McDonald Criteria (standard MS diagnostic criteria). Expanded disability status scale (EDDS) between 2 and 6.5, inclusive at entry. Episodes include study neurologist or neuro-ophthalmologist diagnosed: acute optic neuritis, cerebellar, brainstem dysfunction, myelitis, focal cerebral, and/or definitive focal sensory dysfunction. New objective clinical finding other than the sensory exacerbation or the bowel/bladder signs alone. Sensory deficits alone will not qualify except for optic neuritis. Subjects may continue on their current immunomodulation therapy such as interferons, glatiramer acetate, gilenya or natalizumab. Identified patients must be between the ages of 18 and 55 years, inclusive. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Subjects who are pregnant, or nursing. Any patients treated with systemic corticosteroid use within one month of the index episode at screening. Prior use of immunosuppressive treatments within 90 days of index episode (mitoxantrone, azathioprine, Cellcept, IVIg) or plasmapheresis. Unable to perform timed 25 foot walk (ambulation Index), 9 HPT (9 hole peg test), PASAT (Paced Auditory Serial Addition Test) 3. Peripheral or cranial neuropathy as sole problem of acute episode. Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements. History of any significant cardiac, gastrointestinal, hepatic, pulmonary, or renal disease; immune deficiency; or other medical conditions that would preclude corticosteroid therapy. Subjects with clinical diagnosis of scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, hypertension, or sensitivity to proteins of porcine origin. Primary Progressive Multiple Sclerosis (PPMS) (MS without attacks). -
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acthar Gel 80 IU x 14 days<br>Acthar Gel 80 IU SQ x 14 days | Drug: H.P. Acthar Gel (repository corticotropin injection)<br>* Acthar Gel 80 IU<br>* Other names: ACTH Gel;|
| Experimental: Acthar Gel 80 IU x 5 days<br>Acthar Gel 80 IU SQ x 5 days | Drug: H.P. Acthar Gel (repository corticotropin injection)<br>* Acthar Gel 80 IU<br>* Other names: ACTH Gel;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of EDSS Mean Recovery between 5-day vs 14-day SQ 80 IU ACTHar Gel therapy groups | To determine whether a standard 14 day course of SQ 80 IU ACTHar Gel therapy might be superior (in twice as many patients) to treatment with 5 day SQ regimen for ACTHar Gel as determined by EDSS mean recovery from Day 0 (time of steroid therapy initiation) to Day 28 (and day 90). | 28 Days (with 90 day follow-up) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of ambulation between the 5-day vs.14-day SQ 80 IU ACTHar Gel therapy groups | The ambulation index (AI) will be used for patients with long track (pyramidal) relapses, i.e. relapses with leg involvement. This is a standardized rating scale developed to assess mobility by evaluating the time and degree of assistance required to walk 25 feet. | 28 Days (with 90 day follow-up) |
| Comparison of upper extremity function between the 5-day vs.14-day SQ 80 IU ACTHar Gel therapy groups | The nine-hole peg test (9HPT) will be used for patients with arm involvement during relapses. The 9-HPT is a brief, standardized, quantitative test of upper extremity function. This is a timed test to determine how long it takes the patient to quickly place nine pegs (one at a time) in a wooden box with 9 empty holes, and them remove them again (one at a time) as quickly as possible. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand. | 28 day (with 90 follow up) |
| Comparison of subjective impressions of effectiveness between the 5-day vs 14-day SQ 80 IU ACTHar Gel therapy groups | The patient global impression of change (PGI-Change) will be used in patients to compare subjective impressions of effectiveness between treatment groups | 28 day (with 90 day follow up) |
| Compare visual function between 5-day vs 14-day SQ 80 IU ACTHar Gel therapy groups | Visual function, as measured by low contrast Sloan sensitivity testing (LCSST) will be performed on each patient at baseline and at the end of treatment | 28 day (with 90 day follow up) |
| Comparison of cognitive function between the 5-day vs 14-day SQ 80 IU ACTHar Gel therapy groups | In patients who report cognitive deficits during relapse, the paced auditory serial addition test (PASAT-3) will be used to assess and measure capacity and rate of information processing, and sustained and divided attention. This is a common neuropsychological test used in MS trials that involves working memory, attention and arithmetic capabilities. Patients will hear a series of recorded single-digit numbers at a rate of 1 per 3 seconds, and asked to add the number they just heard with the number they heard before. | 28 day (with 90 day follow up) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
MS, Multiple Sclerosis
|
NCT03792685
|
Looking for Personalized Nutrition for Obesity/Type 2 Diabetes Mellitus Prevention
|
The objectives of this trial are to assess the effects of interactions between genetic factors and diet with various macronutrient intake on the metabolic disorders, obesity and type 2 diabetes risk, prevention, development and progress.
|
This is a randomized, crossover study that includes 1 screening visit and four meal challenge test visits, separated by a 1-2-weeks washout period. The screening will include 2000 people, males and females, to evaluate the genotype frequencies in studied population, and to find carriers of the rare genetic single nucleotide polymorphisms (SNPs), who will fulfill all the other inclusion criteria. An oral glucose tolerance test (OGTT) will be completed at screening visit. Moreover, the fasting blood samples will be collected for genetic analysis, and measurements of blood glucose and lipid metabolism profile, high-sensitivity C-reactive protein (hs-CRP), hormones/peptides and other factors involved in energy balance regulation. Subjects will be asked to record their daily food intake for 3 days. Assessments of vital signs and body height and weight, waist and hip circumferences, body fat content and body fat distribution, review of concomitant medication/supplement use and inclusion and exclusion criteria, and evaluation of adverse effects will be performed throughout the study. To meal challenge test only men will be included, since the sex hormones may influence the study endpoints. Subjects will be encouraged to maintain their habitual diet during wash-out periods. During the each meal challenge test subjects will consume one of the study meals in random order. The blood will be collected at fasting state and 30, 60, 120, 180 and 240 minutes after meal intake. The energy expenditure and substrate utilization will be measured by indirect calorimetry method at the fasting and postprandially.
|
Analysis of Genetic Aspects of Metabolic Response on Diet With Different Content of Carbohydrate and Fat. Searching for Genetic Markers for Individualized Therapy in Patients With Obesity and Type 2 Diabetes
|
Overweight and Obesity, Diabetes Mellitus, Type 2, Metabolic Syndrome, Genetic Predisposition, Diet Modification
|
* Other: Normo-carbohydrate meal intake
* Other: High-carbohydrate meal intake
* Other: High-fat meal intake
* Other: High-protein meal intake
|
Inclusion Criteria:~healthy men with normal body weight and with overweight/obesity~men with metabolic syndrome, hypertension, type 2 diabetes newly diagnosed, or not treated with any medicines~maintaining the usual diet and lifestyle throughout the study~Exclusion Criteria:~infectious or acute diseases in the last 4 weeks before the study visits~any medicines/dietary supplements consumption in the last 4 weeks before the study visits~high level of daily physical activity~the following any special diet or dietary patterns (vegetarian, high-fat etc.)~the presence of any other significant disease which may affect the results (hormonal disorders, history of any surgeries on gastrointestinal tract, allergies known or suspected, heart failure, history of cancer, any kidney, pancrea and liver diseases, except non-alcoholic fatty liver)~abusive alcohol consumption~abusive coffee or energy drinks consumption~drug consumption
|
18 Years
|
65 Years
|
Male
|
Accepts Healthy Volunteers
|
Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The postprandial change and differences in blood glucose levels associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in blood glucose concentrations (mg/dL) will be evaluated, dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 30, 60, 120, 180, 240 minutes after meal intake. |
| The postprandial change and differences in serum insulin concentrations associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in serum insulin concentrations (IU/mL) will be evaluated, dependently on the meal type, genetic and metabolic (body weight, body fat content) | Fasting (time 0) and 30, 60, 120, 180, 240 minutes after meal intake. |
| The change and differences in postprandial Triglycerides (TGs) concentrations associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in blood TGs (mg/dL) concentrations will be evaluated, dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 30, 60, 120, 180, 240 minutes after meal intake. |
| The change and differences in postprandial Free Fatty Acids (FFAs) concentrations associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in blood FFAs (umol/L) concentrations will be evaluated, dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 30, 60, 120, 180, 240 minutes after meal intake. |
| The change and differences in postprandial energy expenditure levels associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in energy expenditure levels (kcal/min) will be evaluated by indirect calorimetry method, dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 60, 120, 180, 240 minutes after meal intake. |
| The change and differences in postprandial substrates (carbohydrate, fat and protein) utilization levels associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in substrates (carbohydrate, fat and protein) utilization (mg/min) will be evaluated by indirect calorimetry method, dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 60, 120, 180, 240 minutes after meal intake. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change and differences in postprandial ghrelin concentrations associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in blood ghrelin concentrations (pg/mL) will be evaluated dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 30, 60, 120, 180, 240 minutes after meal intake. |
| The change and differences in postprandial leptin concentrations associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in blood leptin concentrations (ng/mL) will be evaluated dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 30, 60, 120, 180, 240 minutes after meal intake. |
| The change and differences in postprandial adiponectin concentrations associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in blood adiponectin concentrations (ng/mL) will be evaluated dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 30, 60, 120, 180, 240 minutes after meal intake. |
| The change and differences in postprandial peptide YY (PYY) concentrations associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in blood PYY (pg/mL) concentrations will be evaluated dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 30, 60, 120, 180 minutes after meal intake. |
| The change and differences in postprandial plasma metabolites profiles associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in plasma metabolites profiles (metabolomic fingerprinting) will be evaluated dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 30, 60, 120, 180 minutes after meal intake. |
|
Diabetes Mellitus, Obesity, Overweight, Metabolic Syndrome, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Overnutrition, Nutrition Disorders, Body Weight, Insulin Resistance, Hyperinsulinism, Disease Susceptibility, Disease Attributes, Pathologic Processes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normal weight<br>Normal weight men. Interventions: normo-carbohydrate meal intake, high-carbohydrate meal intake, high-fat meal intake, high-protein meal intake. | Other: Normo-carbohydrate meal intake<br>* Subjects are going to receive the normo-carbohydrate meal.<br>Other: High-carbohydrate meal intake<br>* Subjects are going to receive the high-carbohydrate meal.<br>Other: High-fat meal intake<br>* Subjects are going to receive the high-fat meal.<br>Other: High-protein meal intake<br>* Subjects are going to receive the high-protein meal.<br>|
| Experimental: Overweight/obesity<br>Men with overweight or obesity. Interventions: normo-carbohydrate meal intake, high-carbohydrate meal intake, high-fat meal intake, high-protein meal intake. | Other: Normo-carbohydrate meal intake<br>* Subjects are going to receive the normo-carbohydrate meal.<br>Other: High-carbohydrate meal intake<br>* Subjects are going to receive the high-carbohydrate meal.<br>Other: High-fat meal intake<br>* Subjects are going to receive the high-fat meal.<br>Other: High-protein meal intake<br>* Subjects are going to receive the high-protein meal.<br>|
| Experimental: Diabetes<br>Men with prediabetes or type 2 diabetes mellitus. Interventions: normo-carbohydrate meal intake, high-carbohydrate meal intake, high-fat meal intake, high-protein meal intake. | Other: Normo-carbohydrate meal intake<br>* Subjects are going to receive the normo-carbohydrate meal.<br>Other: High-carbohydrate meal intake<br>* Subjects are going to receive the high-carbohydrate meal.<br>Other: High-fat meal intake<br>* Subjects are going to receive the high-fat meal.<br>Other: High-protein meal intake<br>* Subjects are going to receive the high-protein meal.<br>|
|
Looking for Personalized Nutrition for Obesity/Type 2 Diabetes Mellitus Prevention
Study Overview
=================
Brief Summary
-----------------
The objectives of this trial are to assess the effects of interactions between genetic factors and diet with various macronutrient intake on the metabolic disorders, obesity and type 2 diabetes risk, prevention, development and progress.
Detailed Description
-----------------
This is a randomized, crossover study that includes 1 screening visit and four meal challenge test visits, separated by a 1-2-weeks washout period. The screening will include 2000 people, males and females, to evaluate the genotype frequencies in studied population, and to find carriers of the rare genetic single nucleotide polymorphisms (SNPs), who will fulfill all the other inclusion criteria. An oral glucose tolerance test (OGTT) will be completed at screening visit. Moreover, the fasting blood samples will be collected for genetic analysis, and measurements of blood glucose and lipid metabolism profile, high-sensitivity C-reactive protein (hs-CRP), hormones/peptides and other factors involved in energy balance regulation. Subjects will be asked to record their daily food intake for 3 days. Assessments of vital signs and body height and weight, waist and hip circumferences, body fat content and body fat distribution, review of concomitant medication/supplement use and inclusion and exclusion criteria, and evaluation of adverse effects will be performed throughout the study. To meal challenge test only men will be included, since the sex hormones may influence the study endpoints. Subjects will be encouraged to maintain their habitual diet during wash-out periods. During the each meal challenge test subjects will consume one of the study meals in random order. The blood will be collected at fasting state and 30, 60, 120, 180 and 240 minutes after meal intake. The energy expenditure and substrate utilization will be measured by indirect calorimetry method at the fasting and postprandially.
Official Title
-----------------
Analysis of Genetic Aspects of Metabolic Response on Diet With Different Content of Carbohydrate and Fat. Searching for Genetic Markers for Individualized Therapy in Patients With Obesity and Type 2 Diabetes
Conditions
-----------------
Overweight and Obesity, Diabetes Mellitus, Type 2, Metabolic Syndrome, Genetic Predisposition, Diet Modification
Intervention / Treatment
-----------------
* Other: Normo-carbohydrate meal intake
* Other: High-carbohydrate meal intake
* Other: High-fat meal intake
* Other: High-protein meal intake
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: healthy men with normal body weight and with overweight/obesity men with metabolic syndrome, hypertension, type 2 diabetes newly diagnosed, or not treated with any medicines maintaining the usual diet and lifestyle throughout the study Exclusion Criteria: infectious or acute diseases in the last 4 weeks before the study visits any medicines/dietary supplements consumption in the last 4 weeks before the study visits high level of daily physical activity the following any special diet or dietary patterns (vegetarian, high-fat etc.) the presence of any other significant disease which may affect the results (hormonal disorders, history of any surgeries on gastrointestinal tract, allergies known or suspected, heart failure, history of cancer, any kidney, pancrea and liver diseases, except non-alcoholic fatty liver) abusive alcohol consumption abusive coffee or energy drinks consumption drug consumption
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years
Sexes Eligible for Study
-----------------
Male
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: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normal weight<br>Normal weight men. Interventions: normo-carbohydrate meal intake, high-carbohydrate meal intake, high-fat meal intake, high-protein meal intake. | Other: Normo-carbohydrate meal intake<br>* Subjects are going to receive the normo-carbohydrate meal.<br>Other: High-carbohydrate meal intake<br>* Subjects are going to receive the high-carbohydrate meal.<br>Other: High-fat meal intake<br>* Subjects are going to receive the high-fat meal.<br>Other: High-protein meal intake<br>* Subjects are going to receive the high-protein meal.<br>|
| Experimental: Overweight/obesity<br>Men with overweight or obesity. Interventions: normo-carbohydrate meal intake, high-carbohydrate meal intake, high-fat meal intake, high-protein meal intake. | Other: Normo-carbohydrate meal intake<br>* Subjects are going to receive the normo-carbohydrate meal.<br>Other: High-carbohydrate meal intake<br>* Subjects are going to receive the high-carbohydrate meal.<br>Other: High-fat meal intake<br>* Subjects are going to receive the high-fat meal.<br>Other: High-protein meal intake<br>* Subjects are going to receive the high-protein meal.<br>|
| Experimental: Diabetes<br>Men with prediabetes or type 2 diabetes mellitus. Interventions: normo-carbohydrate meal intake, high-carbohydrate meal intake, high-fat meal intake, high-protein meal intake. | Other: Normo-carbohydrate meal intake<br>* Subjects are going to receive the normo-carbohydrate meal.<br>Other: High-carbohydrate meal intake<br>* Subjects are going to receive the high-carbohydrate meal.<br>Other: High-fat meal intake<br>* Subjects are going to receive the high-fat meal.<br>Other: High-protein meal intake<br>* Subjects are going to receive the high-protein meal.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The postprandial change and differences in blood glucose levels associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in blood glucose concentrations (mg/dL) will be evaluated, dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 30, 60, 120, 180, 240 minutes after meal intake. |
| The postprandial change and differences in serum insulin concentrations associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in serum insulin concentrations (IU/mL) will be evaluated, dependently on the meal type, genetic and metabolic (body weight, body fat content) | Fasting (time 0) and 30, 60, 120, 180, 240 minutes after meal intake. |
| The change and differences in postprandial Triglycerides (TGs) concentrations associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in blood TGs (mg/dL) concentrations will be evaluated, dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 30, 60, 120, 180, 240 minutes after meal intake. |
| The change and differences in postprandial Free Fatty Acids (FFAs) concentrations associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in blood FFAs (umol/L) concentrations will be evaluated, dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 30, 60, 120, 180, 240 minutes after meal intake. |
| The change and differences in postprandial energy expenditure levels associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in energy expenditure levels (kcal/min) will be evaluated by indirect calorimetry method, dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 60, 120, 180, 240 minutes after meal intake. |
| The change and differences in postprandial substrates (carbohydrate, fat and protein) utilization levels associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in substrates (carbohydrate, fat and protein) utilization (mg/min) will be evaluated by indirect calorimetry method, dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 60, 120, 180, 240 minutes after meal intake. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change and differences in postprandial ghrelin concentrations associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in blood ghrelin concentrations (pg/mL) will be evaluated dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 30, 60, 120, 180, 240 minutes after meal intake. |
| The change and differences in postprandial leptin concentrations associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in blood leptin concentrations (ng/mL) will be evaluated dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 30, 60, 120, 180, 240 minutes after meal intake. |
| The change and differences in postprandial adiponectin concentrations associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in blood adiponectin concentrations (ng/mL) will be evaluated dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 30, 60, 120, 180, 240 minutes after meal intake. |
| The change and differences in postprandial peptide YY (PYY) concentrations associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in blood PYY (pg/mL) concentrations will be evaluated dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 30, 60, 120, 180 minutes after meal intake. |
| The change and differences in postprandial plasma metabolites profiles associated with investigated single nucleotide polymorphisms. | The postprandial change and differences in plasma metabolites profiles (metabolomic fingerprinting) will be evaluated dependently on the meal type, genetic and metabolic (body weight, body fat content) factors. | Fasting (time 0) and 30, 60, 120, 180 minutes after meal intake. |
|
|
NCT01435915
|
Ropinirole PR Pharmacokinetics Study Among Chinese Healthy Subjects
|
The purpose of this study is to investigate the pharmacokinetic profile of ropinirole PR after single and multiple doses of the PR-formulation. It will also investigate the safety and tolerability of ropinirole PR after single and multiple doses of PR-formulation.
|
A Single Dose and Repeat Dose Study to Investigate the Pharmacokinetics of Ropinirole After Single and Multiple Doses of a PR-formulation in Chinese Healthy Male and Female Subjects
|
Parkinson Disease
|
* Drug: Ropinirole
|
Inclusion Criteria:~Healthy adult men and women between 18 and 45 years of age, inclusive.~Body weight >=50Kg.~Body Mass Index (BMI) 19 - 24 kg/m2.~No abnormality on clinical examination.~No abnormality revealed by the clinical chemistry or haematology examination at the pre-study medical examination.~A normal 12-lead ECG at the pre-study screening.~Normal systolic (100-140mmHg) and diastolic (<90mmHg) blood pressure at pre-study screening.~Written informed consent prior to admission to the study.~Exclusion Criteria:~Any clinically relevant abnormality identified on the screening history and physical or laboratory examination significant cardiovascular, neurological, psychiatric, haematological or renal abnormalities.~Definite or suspected personal history or family history of adverse reactions or hypersensitivity to the study drug or to drugs with a similar chemical structure.~History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.~The subject has received prescribed medication within 7 days prior to the first dosing day, which in the opinion of the principal medical investigator interfered with the study procedures or compromised safety.~The subject has received over-the-counter (OTC) medicine within 48 hours prior to the first study day. Subjects who took OTC medication could still be entered into the study, if, in the opinion of the principal/co-investigator, the medication received did not interfere with the study procedures or compromised safety of the subjects.~Abuse of alcohol, defined as an average weekly intake of greater than 21 units or an average daily intake of greater than three units. One unit is equivalent to half a pint of beer, one measure of spirits or one glass of wine.~Positive screen for addictive drugs and tobacco.~Participation in a trial with any drug within the 1 month before the start of the study.~Either blood donation within the previous 3 months, or donation of a quantity of blood within the previous 12 months that would result in the subject having donated more than 1,500mL blood in a period from 12 months before this study up to and including the end of the study.~Positive pre-study screening result for hepatitis B antigen, hepatitis C antibody and HIV-1/2 antibodies.~Pregnancy and/or lactation;~Female subjects of childbearing potential who are intending to become pregnant and/or are not willing to avoid pregnancy by means of barrier contraception methods (i.e. condoms or IUD) during the study from 5 days prior to screening or in the 3 months following the study.~Female subjects with positive serum hCG test result at screening or on Days 1 of both study phases with positive urine HCG test.
|
18 Years
|
45 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Profile of Pharmacokinetics | Cmax, AUC (0-24), AUC(0-inf) | predose,1,2,3,4,6,8,10,12,14,16,18,20,22,24,36,48,72, 96,120,144,168 hours post-dose |
| Profile of Pharmacokinetics | Css_max, Css_min and AUCss | predose,1,2,3,4,6,8,10,12,14,16,18,20,22,24 hours after last repeated dosing |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Profile of Pharmacokinetics | Tmax, T1/2, Kel | pre-dose,1,2,3,4,6,8,10,12,14,16,18,20,22, 24,36,48,72,96,120,144,168hours post-dose |
| Composition of Pharmacokinetics | Tmax, Css_av, DF，accumulation ratios (Ro and Rs) | predose,1,2,3,4,6,8,10,12,14,16,18,20,22,24 hours after last repeated dosing |
|
Ropinirole, Antiparkinson Agents, Anti-Dyskinesia Agents, Dopamine Agonists, Dopamine Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects receiving ropinirole<br>Eligible subjects will receive single and multiple oral dose of ropinirole prolonged release tablet in sequence over 14 days without dosing on washout period from Day 2 to Day 7. | Drug: Ropinirole<br>* Ropinirole 2 milligrams once daily prolonged release tablet will be given at 24-hour intervals in the morning.~Single and repeat dose treatment periods will be separated by 7 days of washout period.<br>|
|
Ropinirole PR Pharmacokinetics Study Among Chinese Healthy Subjects
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the pharmacokinetic profile of ropinirole PR after single and multiple doses of the PR-formulation. It will also investigate the safety and tolerability of ropinirole PR after single and multiple doses of PR-formulation.
Official Title
-----------------
A Single Dose and Repeat Dose Study to Investigate the Pharmacokinetics of Ropinirole After Single and Multiple Doses of a PR-formulation in Chinese Healthy Male and Female Subjects
Conditions
-----------------
Parkinson Disease
Intervention / Treatment
-----------------
* Drug: Ropinirole
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy adult men and women between 18 and 45 years of age, inclusive. Body weight >=50Kg. Body Mass Index (BMI) 19 - 24 kg/m2. No abnormality on clinical examination. No abnormality revealed by the clinical chemistry or haematology examination at the pre-study medical examination. A normal 12-lead ECG at the pre-study screening. Normal systolic (100-140mmHg) and diastolic (<90mmHg) blood pressure at pre-study screening. Written informed consent prior to admission to the study. Exclusion Criteria: Any clinically relevant abnormality identified on the screening history and physical or laboratory examination significant cardiovascular, neurological, psychiatric, haematological or renal abnormalities. Definite or suspected personal history or family history of adverse reactions or hypersensitivity to the study drug or to drugs with a similar chemical structure. History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs. The subject has received prescribed medication within 7 days prior to the first dosing day, which in the opinion of the principal medical investigator interfered with the study procedures or compromised safety. The subject has received over-the-counter (OTC) medicine within 48 hours prior to the first study day. Subjects who took OTC medication could still be entered into the study, if, in the opinion of the principal/co-investigator, the medication received did not interfere with the study procedures or compromised safety of the subjects. Abuse of alcohol, defined as an average weekly intake of greater than 21 units or an average daily intake of greater than three units. One unit is equivalent to half a pint of beer, one measure of spirits or one glass of wine. Positive screen for addictive drugs and tobacco. Participation in a trial with any drug within the 1 month before the start of the study. Either blood donation within the previous 3 months, or donation of a quantity of blood within the previous 12 months that would result in the subject having donated more than 1,500mL blood in a period from 12 months before this study up to and including the end of the study. Positive pre-study screening result for hepatitis B antigen, hepatitis C antibody and HIV-1/2 antibodies. Pregnancy and/or lactation; Female subjects of childbearing potential who are intending to become pregnant and/or are not willing to avoid pregnancy by means of barrier contraception methods (i.e. condoms or IUD) during the study from 5 days prior to screening or in the 3 months following the study. Female subjects with positive serum hCG test result at screening or on Days 1 of both study phases with positive urine HCG test.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects receiving ropinirole<br>Eligible subjects will receive single and multiple oral dose of ropinirole prolonged release tablet in sequence over 14 days without dosing on washout period from Day 2 to Day 7. | Drug: Ropinirole<br>* Ropinirole 2 milligrams once daily prolonged release tablet will be given at 24-hour intervals in the morning. Single and repeat dose treatment periods will be separated by 7 days of washout period.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Profile of Pharmacokinetics | Cmax, AUC (0-24), AUC(0-inf) | predose,1,2,3,4,6,8,10,12,14,16,18,20,22,24,36,48,72, 96,120,144,168 hours post-dose |
| Profile of Pharmacokinetics | Css_max, Css_min and AUCss | predose,1,2,3,4,6,8,10,12,14,16,18,20,22,24 hours after last repeated dosing |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Profile of Pharmacokinetics | Tmax, T1/2, Kel | pre-dose,1,2,3,4,6,8,10,12,14,16,18,20,22, 24,36,48,72,96,120,144,168hours post-dose |
| Composition of Pharmacokinetics | Tmax, Css_av, DF，accumulation ratios (Ro and Rs) | predose,1,2,3,4,6,8,10,12,14,16,18,20,22,24 hours after last repeated dosing |
|
||
NCT01428271
|
Comparison Between the Expected Site of Sacral Hiatus by Conventional Method and the Real Site by Ultrasonography for Caudal Block in Children
|
Caudal block is one of the most useful and popular regional block in pediatric anesthetic practice. Successful caudal block depends on the proper placement of a needle through sacral hiatus by following anatomical landmarks. The sacrum and the position of sacral hiatus are extreme variable anatomical structure. Generally, the equilateral triangle located between the apex of the sacral hiatus and posterior superior iliac spines is used in determining the location of the sacral hiatus as the conventional method. Previous study demonstrated that the triangle formed between the apex of the sacral hiatus and the posterior superior iliac spines was found to have the features of an equilateral triangle in adult. There is no study about the efficacy of the conventional method using the equilateral triangle in children. In this study, the investigators will compare between the expected site of sacral hiatus by conventional method using the equilateral triangle and the real site of the sacral hiatus confirmed by ultrasonography for caudal block in children.
| null |
Inguinal Herniorraphy
|
* Other: Ultrasonography
|
Inclusion Criteria:~Children aged 0-72 months~patient whho are scheduled to undergo elective inguinal herniorraphy under general anesthesia~Exclusion Criteria:~The history of prematurity~he histories of the infection, tumor, and operation in sacrum 3. The history or suspicion of meningomyelocele
| null |
6 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the expected site of the sacral hiatus by convential method | 1)The distance bewteen the midpoint of posterior superior iliac spines and the expected site of sacral hiatus by conventional method and 2)the distance between the midpoint of posterior superior iliac spines and the real site of sacral hiatus by ultrasonography. | approximately 5 minutes after general anesthesia |
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Herniorrhapy with caudal block<br>Children aged 0-72 months who are scheduled to undergo elective inguinal herniorrhapy under general anesthesia with caudal block | Other: Ultrasonography<br>* The confirmation of the real site of the sacral hiatus by ultrasonography<br>|
|
Comparison Between the Expected Site of Sacral Hiatus by Conventional Method and the Real Site by Ultrasonography for Caudal Block in Children
Study Overview
=================
Brief Summary
-----------------
Caudal block is one of the most useful and popular regional block in pediatric anesthetic practice. Successful caudal block depends on the proper placement of a needle through sacral hiatus by following anatomical landmarks. The sacrum and the position of sacral hiatus are extreme variable anatomical structure. Generally, the equilateral triangle located between the apex of the sacral hiatus and posterior superior iliac spines is used in determining the location of the sacral hiatus as the conventional method. Previous study demonstrated that the triangle formed between the apex of the sacral hiatus and the posterior superior iliac spines was found to have the features of an equilateral triangle in adult. There is no study about the efficacy of the conventional method using the equilateral triangle in children. In this study, the investigators will compare between the expected site of sacral hiatus by conventional method using the equilateral triangle and the real site of the sacral hiatus confirmed by ultrasonography for caudal block in children.
Conditions
-----------------
Inguinal Herniorraphy
Intervention / Treatment
-----------------
* Other: Ultrasonography
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Children aged 0-72 months patient whho are scheduled to undergo elective inguinal herniorraphy under general anesthesia Exclusion Criteria: The history of prematurity he histories of the infection, tumor, and operation in sacrum 3. The history or suspicion of meningomyelocele
Ages Eligible for Study
-----------------
Maximum Age: 6 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 |
| --- | --- |
| Herniorrhapy with caudal block<br>Children aged 0-72 months who are scheduled to undergo elective inguinal herniorrhapy under general anesthesia with caudal block | Other: Ultrasonography<br>* The confirmation of the real site of the sacral hiatus by ultrasonography<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the expected site of the sacral hiatus by convential method | 1)The distance bewteen the midpoint of posterior superior iliac spines and the expected site of sacral hiatus by conventional method and 2)the distance between the midpoint of posterior superior iliac spines and the real site of sacral hiatus by ultrasonography. | approximately 5 minutes after general anesthesia |
|
|||||
NCT01516840
|
Venous Thromboembolism (VTE) Treatment Study in Japanese Deep Vein Thrombosis (DVT) Patients
|
The objective of this study is to evaluate the efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of two different dosages of rivaroxaban in the treatment of deep vein thrombosis (DVT) and the prevention of the occurrence and the recurrence of DVT or pulmonary embolism (PE) in Japanese patients with acute symptomatic DVT without symptomatic PE.
|
The general design of the trial is open label between the Rivaroxaban and the reference arm. However, there are two groups in the Rivaroxaban arm only for the initial 3 weeks. Between these two groups and in this initial period, the study is blinded.
|
Randomized, Open-label (Double Blind Among Rivaroxaban Groups in the Initial 3 Weeks), Parallel-group, Active-controlled Study of Rivaroxaban in Patients With Acute Symptomatic Deep Vein Thrombosis Without Symptomatic Pulmonary Embolism
|
Deep Vein Thrombosis
|
* Drug: Rivaroxaban (Xarelto, BAY59-7939)
* Drug: Rivaroxaban (Xarelto, BAY59-7939)
* Drug: Unfractionated heparin
* Drug: Warfarin
|
Inclusion Criteria:~Men and women >/= 20 years of age in patients with confirmed acute symptomatic proximal deep vein thrombosis (DVT) without symptomatic pulmonary embolism (PE)~Exclusion Criteria:~Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of DVT~More than 48 hours pre-randomization treatment with therapeutic dosages of anti-coagulant treatment or more than a single dose of warfarin from the onset of the current episode of DVT to randomization~Calculated creatinine clearance (CLCR) < 30 mL/min~Subjects with hepatic disease which is associated with coagulopathy leading to a clinically relevant bleeding risk~Active bleeding or high risk for bleeding contraindicating treatment with unfractioned Heparin (UFH) or warfarin~Systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg
|
20 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with newly onset of symptomatic venous thromboembolism (VTE) | | Up to 12 months |
| Number of clinically relevant bleedings | | Up to 2 days after last dose |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with improvement in thrombotic burden | | At week 3 |
| Number of participants with deterioration in thrombotic burden | | Up to 12 months |
| Number of participants with the composite of newly onset of symptomatic VTE or asymptomatic deterioration of thrombus | | Up to 12 months |
|
acute symptomatic deep vein thrombosis
|
Heparin, Calcium heparin, Warfarin, Rivaroxaban, Anticoagulants, Fibrinolytic Agents, Fibrin Modulating Agents, Molecular Mechanisms of Pharmacological Action, Factor Xa Inhibitors, Antithrombins, Serine Proteinase Inhibitors, Protease Inhibitors, Enzyme Inhibitors
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* 10 mg twice daily for 21 days, followed by 15 mg once daily<br>|
| Experimental: Arm 2<br> | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* 15 mg twice daily for 21 days, followed by 15 mg once daily<br>|
| Active Comparator: Arm 3<br> | Drug: Unfractionated heparin<br>* To be adjusted to maintain the activated partial thromboplastin time (aPTT) prolongation (1.5 to 2.5 times the control)<br>|
| Active Comparator: Arm 4<br> | Drug: Warfarin<br>* To be adjusted on the basis of prothrombin time-international normalized ratio (PT-INR) values target range (1.5 to 2.5)<br>|
|
Venous Thromboembolism (VTE) Treatment Study in Japanese Deep Vein Thrombosis (DVT) Patients
Study Overview
=================
Brief Summary
-----------------
The objective of this study is to evaluate the efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of two different dosages of rivaroxaban in the treatment of deep vein thrombosis (DVT) and the prevention of the occurrence and the recurrence of DVT or pulmonary embolism (PE) in Japanese patients with acute symptomatic DVT without symptomatic PE.
Detailed Description
-----------------
The general design of the trial is open label between the Rivaroxaban and the reference arm. However, there are two groups in the Rivaroxaban arm only for the initial 3 weeks. Between these two groups and in this initial period, the study is blinded.
Official Title
-----------------
Randomized, Open-label (Double Blind Among Rivaroxaban Groups in the Initial 3 Weeks), Parallel-group, Active-controlled Study of Rivaroxaban in Patients With Acute Symptomatic Deep Vein Thrombosis Without Symptomatic Pulmonary Embolism
Conditions
-----------------
Deep Vein Thrombosis
Intervention / Treatment
-----------------
* Drug: Rivaroxaban (Xarelto, BAY59-7939)
* Drug: Rivaroxaban (Xarelto, BAY59-7939)
* Drug: Unfractionated heparin
* Drug: Warfarin
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women >/= 20 years of age in patients with confirmed acute symptomatic proximal deep vein thrombosis (DVT) without symptomatic pulmonary embolism (PE) Exclusion Criteria: Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of DVT More than 48 hours pre-randomization treatment with therapeutic dosages of anti-coagulant treatment or more than a single dose of warfarin from the onset of the current episode of DVT to randomization Calculated creatinine clearance (CLCR) < 30 mL/min Subjects with hepatic disease which is associated with coagulopathy leading to a clinically relevant bleeding risk Active bleeding or high risk for bleeding contraindicating treatment with unfractioned Heparin (UFH) or warfarin Systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg
Ages Eligible for Study
-----------------
Minimum Age: 20 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: Arm 1<br> | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* 10 mg twice daily for 21 days, followed by 15 mg once daily<br>|
| Experimental: Arm 2<br> | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* 15 mg twice daily for 21 days, followed by 15 mg once daily<br>|
| Active Comparator: Arm 3<br> | Drug: Unfractionated heparin<br>* To be adjusted to maintain the activated partial thromboplastin time (aPTT) prolongation (1.5 to 2.5 times the control)<br>|
| Active Comparator: Arm 4<br> | Drug: Warfarin<br>* To be adjusted on the basis of prothrombin time-international normalized ratio (PT-INR) values target range (1.5 to 2.5)<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with newly onset of symptomatic venous thromboembolism (VTE) | | Up to 12 months |
| Number of clinically relevant bleedings | | Up to 2 days after last dose |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with improvement in thrombotic burden | | At week 3 |
| Number of participants with deterioration in thrombotic burden | | Up to 12 months |
| Number of participants with the composite of newly onset of symptomatic VTE or asymptomatic deterioration of thrombus | | Up to 12 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
acute symptomatic deep vein thrombosis
|
NCT04448184
|
Platelet Transfusions in Hematopoietic Stem Cell Transplantation (The PATH III Trial)
|
It is hypothesized that a strategy using prophylactic oral and intravenous Tranexamic Acid (TXA) with therapeutic platelet transfusions (if required) is safe and more effective than prophylactic platelet transfusions in patients undergoing an autologous hematopoietic stem cell transplantation (ASCT).
|
In Canada, over 1,500 autologous hematopoietic stem cell transplantations (ASCT) are performed annually for hematologic malignancies. It is currently standard practice to provide a prophylactic transfusion of platelets to prevent bleeding when the daily measured platelet count is less than 10 x 109/L. A patient may require up to six adult platelet doses during the post-transplant period. However, the true benefit of prophylactic platelet transfusions in the ASCT setting is unclear and has been called into question by several recent studies.~Prophylactic platelet transfusions may not only be unnecessary, they may be detrimental to the patient. Among blood products, platelet transfusions are associated with the highest risk of both infectious and non-infectious complications: this would include bacterial infections and allergic /febrile reactions. Moreover, the potential overuse of platelet products places a significant burden on a scarce health care resource that is provided through volunteer donations.~An alternative strategy to prevent bleeding and reduce the need for platelet transfusions involves administering Tranexamic Acid, an antifibrinolytic agent to stabilize blood clots and reduce bleeding. Tranexamic Acid is safe and effective in many clinical scenarios, and may be a reasonable alternative for prophylactic platelet transfusions. In the setting of ASCT, Tranexamic Acid may reduce bleeding and further enhance a strategy of therapeutic platelet transfusions where platelets are administered only in the event of active bleeding symptoms.~The effect of prophylactic platelet transfusions and Tranexamic Acid on clinical, quality of life and economic outcomes in patients receiving ASCT is unknown. The primary aim of this research program is to perform a randomized controlled trial to determine whether a strategy of prophylactic Tranexamic Acid (with therapeutic platelet transfusions) is safe and effective compared to prophylactic platelet transfusions in patients undergoing ASCT.~A pilot trial demonstrated feasibility by successfully recruiting 100 patients and these patients will be rolled over into the phase III study. The treatment assignment and bleeding outcomes for these patients remain blinded.
|
Platelet Transfusions in Hematopoietic Stem Cell Transplantation - The PATH Phase III Trial
|
Hematologic Neoplasms
|
* Drug: Tranexamic Acid
|
Inclusion Criteria:~Adults 18 years or older undergoing ASCT for a hematologic malignancy~Patients providing written informed consent prior to starting transplantation~Exclusion Criteria:~A previous WHO grade 2, 3 or 4 bleeding event within the past year~A previous or current unprovoked thrombotic event defined as a pulmonary embolism, deep vein thrombosis, cerebral thrombosis~A current provoked thrombotic event (e.g. catheter-related thrombosis) within last month and/or still requiring anticoagulant treatment.~A requirement for therapeutic anticoagulant or anti-platelet drugs during ASCT~Active angina (chest pain of presumed cardiac origin either at rest or with activity)~Current or previous (within 2 weeks) urinary tract bleeding~An inherited hemostatic or thrombotic disorder~Coagulopathy defined as a prothrombin time '/International Normalization Ratio (INR) or activated partial thromboplastin time more than 1.5 times the upper limit of normal or fibrinogen less than 2 g/L~Previously documented history of refractoriness to platelet transfusion secondary to HLA antibodies (Refractoriness is defined as 2 consecutive ABO matched platelet transfusions with platelet increment of < 7.5 and the presence of anti-HLA antibodies)~Significant renal impairment (creatinine more than 1.5 times the upper limit of normal or a eGFR less than 0.5 mL/min/1.78m2)~Pregnant or breast-feeding~Unwilling or unable to provide informed consent~Participant has acquired disturbances to his/her colour vision (does not apply to congenital colour blindness)~Participant has known sensitivity or allergy to Tranexamic Acid or any of its ingredients
|
18 Years
| null |
All
|
No
|
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WHO (World Health Organization) bleeding events of Grade 2 or higher | | Daily, up to 30 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WHO bleeding events of Grade 3 or 4 | | Daily, up to 30 days |
| Time from randomization to bleeding of WHO events Grade 2 or higher | | Daily, up to 30 days |
| Number of days with bleeding of WHO bleeding events Grade 2 or higher | | Daily, up to 30 days |
| Bleeding Severity Measurement Scale (BSMS) for bleeding events Grade 2 or higher | The BSMS scale measures bleeding grade and classification from 0-2. 0 indicates no bleeding. Grade 1 bleeding consists of trace bleeding and mild bleeding and is not clinically significant. Grade 2 bleeding consists of serious bleeding, serious bleeding causing significant morbidity, and fatal bleeding. Grade 2 bleeding is clinically significant. | Daily, up to 30 days |
| Number of platelet and/or red blood cell transfusions | | Daily, up to 30 days |
| Adverse reactions related to tranexamic acid | Number and type of reactions will be recorded. | Daily, up to 30 days. |
| Venous thromboembolism grade 2 or higher | | Daily, up to 30 days. |
| Adverse reactions related to platelet transfusion | Number and type of reactions will be recorded. | Daily, up to 30 days. |
| Time to platelet count recovery | | Daily, up to 30 days. |
| Number of days with a platelet count < 10 x 109/L | | Daily, up to 30 days. |
| LOS (Length of hospital stay) | LOS = admission date - discharge date | LOS will be measured as the number of days elapsed between hospital admission and hospital discharge date up to 30 days. |
| Transplant related outcome: Bearman Scoring System for Organ Toxicity following HSCT | This is a validated scoring system to assess toxicity during HSCT. In this system, grade I toxicity is reversible without treatment and grade 2 is not life threatening, but requires treatment. Grade 3 requires life-support intervention and grade 4 is fatal. Regimen-related toxicity in each organ system was scored as the highest grade achieved in that organ system through day 28, except that deaths occurring after day 28 as a result of regimen-related toxicity occurring before day 28 are also scored as grade 4. Adverse events that could be attributed to infection (culture-documented), bleeding or other medications are not scored as regimen-related toxicity. The maximum toxicity is the highest grade recorded in any individual organ system and the cumulative toxicity score is the sum of the highest grades recorded for all eight organ systems. | Day 30 |
| Transplant related outcome: Incidence of infections at Day 30 following ASCT | | Day 30 |
| Transplant related outcome: Mortality at Day 30 and 180 | | Day 30, Day 180 |
| Economic Analyses | Incremental cost effectiveness ratios | 5 years |
| Quality of Life Measure: FACT-Thrombocytopenia 18 | The FACT consists of 5 subscales that measure physical well-being, functional well-being, social/family well-being and emotional well-being. The BMT subscale of the FACT includes additional items specifically designed to test quality of life and symptoms specific to transplant patients. | Weekly, up to 30 days |
| Quality of Life Measure: FACT- BMT | The FACT-BMT scale is valid and sensitive to clinical change in transplant recipients. It is the most consistently used scale amongst the Canadian Bone Marrow Transplant Group (CBMTG). It is the preferred scale in several Canadian multicentre trials in stem cell transplantation. FACT- Thrombocytopenia 18 is valid measure to elicit quality of life due to thrombocytopenia, and will complement the FACT-BMT scale. | Day 30, Day 90, Day 180 |
| Quality of Life Measure: GAD-7 | GAD-7 is a short validated scale that assesses symptoms of generalized anxiety and is commonly used in medical settings. There is no specific validated scale to assess anxiety of patients who are at risk for bleeding. | Weekly, up to 30 days |
| Quality of Life Measure: EQ-5D | EQ-5D is a standardized measure of health status to provide a simple, generic measure of health for clinical and economic appraisal. It is applicable to a wide range of health conditions and treatments; it provides a simple descriptive profile and a single index value for health status that can be used in the clinical and economic evaluation of health care. It is cognitively undemanding, taking only a few minutes to complete. | Weekly, up to 30 days |
|
Tranexamic Acid, Antifibrinolytic Agents, Fibrin Modulating Agents, Molecular Mechanisms of Pharmacological Action, Hemostatics, Coagulants
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Prophylactic Platelet Transfusion<br>Patients allocated to the prophylactic platelet transfusion group will receive a platelet transfusion when the measured platelet count is less than 10 x 109/L. | |
| Experimental: Prophylactic Tranexamic Acid<br>Patients allocated to the prophylactic Tranexamic Acid group will receive a standardized routine oral or intravenous dose of Tranexamic Acid 1 gram three times daily. | Drug: Tranexamic Acid<br>* Patients allocated to the prophylactic Tranexamic Acid group will receive a standardized routine oral or intravenous dose of Tranexamic Acid 1 gram three times daily.~Tranexamic Acid will start when Platelet count is less than 50 x 109/L and continue until platelet engraftment. Patients in this group will not receive routine prophylactic platelet transfusions. Subjects unable to swallow oral Tranexamic Acid pills may have the tablets crushed, administered via nasogastric (NG) tube or the medication will be administered intravenously.<br>* Other names: Cyclokapron®;|
|
Platelet Transfusions in Hematopoietic Stem Cell Transplantation (The PATH III Trial)
Study Overview
=================
Brief Summary
-----------------
It is hypothesized that a strategy using prophylactic oral and intravenous Tranexamic Acid (TXA) with therapeutic platelet transfusions (if required) is safe and more effective than prophylactic platelet transfusions in patients undergoing an autologous hematopoietic stem cell transplantation (ASCT).
Detailed Description
-----------------
In Canada, over 1,500 autologous hematopoietic stem cell transplantations (ASCT) are performed annually for hematologic malignancies. It is currently standard practice to provide a prophylactic transfusion of platelets to prevent bleeding when the daily measured platelet count is less than 10 x 109/L. A patient may require up to six adult platelet doses during the post-transplant period. However, the true benefit of prophylactic platelet transfusions in the ASCT setting is unclear and has been called into question by several recent studies. Prophylactic platelet transfusions may not only be unnecessary, they may be detrimental to the patient. Among blood products, platelet transfusions are associated with the highest risk of both infectious and non-infectious complications: this would include bacterial infections and allergic /febrile reactions. Moreover, the potential overuse of platelet products places a significant burden on a scarce health care resource that is provided through volunteer donations. An alternative strategy to prevent bleeding and reduce the need for platelet transfusions involves administering Tranexamic Acid, an antifibrinolytic agent to stabilize blood clots and reduce bleeding. Tranexamic Acid is safe and effective in many clinical scenarios, and may be a reasonable alternative for prophylactic platelet transfusions. In the setting of ASCT, Tranexamic Acid may reduce bleeding and further enhance a strategy of therapeutic platelet transfusions where platelets are administered only in the event of active bleeding symptoms. The effect of prophylactic platelet transfusions and Tranexamic Acid on clinical, quality of life and economic outcomes in patients receiving ASCT is unknown. The primary aim of this research program is to perform a randomized controlled trial to determine whether a strategy of prophylactic Tranexamic Acid (with therapeutic platelet transfusions) is safe and effective compared to prophylactic platelet transfusions in patients undergoing ASCT. A pilot trial demonstrated feasibility by successfully recruiting 100 patients and these patients will be rolled over into the phase III study. The treatment assignment and bleeding outcomes for these patients remain blinded.
Official Title
-----------------
Platelet Transfusions in Hematopoietic Stem Cell Transplantation - The PATH Phase III Trial
Conditions
-----------------
Hematologic Neoplasms
Intervention / Treatment
-----------------
* Drug: Tranexamic Acid
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults 18 years or older undergoing ASCT for a hematologic malignancy Patients providing written informed consent prior to starting transplantation Exclusion Criteria: A previous WHO grade 2, 3 or 4 bleeding event within the past year A previous or current unprovoked thrombotic event defined as a pulmonary embolism, deep vein thrombosis, cerebral thrombosis A current provoked thrombotic event (e.g. catheter-related thrombosis) within last month and/or still requiring anticoagulant treatment. A requirement for therapeutic anticoagulant or anti-platelet drugs during ASCT Active angina (chest pain of presumed cardiac origin either at rest or with activity) Current or previous (within 2 weeks) urinary tract bleeding An inherited hemostatic or thrombotic disorder Coagulopathy defined as a prothrombin time '/International Normalization Ratio (INR) or activated partial thromboplastin time more than 1.5 times the upper limit of normal or fibrinogen less than 2 g/L Previously documented history of refractoriness to platelet transfusion secondary to HLA antibodies (Refractoriness is defined as 2 consecutive ABO matched platelet transfusions with platelet increment of < 7.5 and the presence of anti-HLA antibodies) Significant renal impairment (creatinine more than 1.5 times the upper limit of normal or a eGFR less than 0.5 mL/min/1.78m2) Pregnant or breast-feeding Unwilling or unable to provide informed consent Participant has acquired disturbances to his/her colour vision (does not apply to congenital colour blindness) Participant has known sensitivity or allergy to Tranexamic Acid or any of its ingredients
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Prophylactic Platelet Transfusion<br>Patients allocated to the prophylactic platelet transfusion group will receive a platelet transfusion when the measured platelet count is less than 10 x 109/L. | |
| Experimental: Prophylactic Tranexamic Acid<br>Patients allocated to the prophylactic Tranexamic Acid group will receive a standardized routine oral or intravenous dose of Tranexamic Acid 1 gram three times daily. | Drug: Tranexamic Acid<br>* Patients allocated to the prophylactic Tranexamic Acid group will receive a standardized routine oral or intravenous dose of Tranexamic Acid 1 gram three times daily. Tranexamic Acid will start when Platelet count is less than 50 x 109/L and continue until platelet engraftment. Patients in this group will not receive routine prophylactic platelet transfusions. Subjects unable to swallow oral Tranexamic Acid pills may have the tablets crushed, administered via nasogastric (NG) tube or the medication will be administered intravenously.<br>* Other names: Cyclokapron®;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WHO (World Health Organization) bleeding events of Grade 2 or higher | | Daily, up to 30 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WHO bleeding events of Grade 3 or 4 | | Daily, up to 30 days |
| Time from randomization to bleeding of WHO events Grade 2 or higher | | Daily, up to 30 days |
| Number of days with bleeding of WHO bleeding events Grade 2 or higher | | Daily, up to 30 days |
| Bleeding Severity Measurement Scale (BSMS) for bleeding events Grade 2 or higher | The BSMS scale measures bleeding grade and classification from 0-2. 0 indicates no bleeding. Grade 1 bleeding consists of trace bleeding and mild bleeding and is not clinically significant. Grade 2 bleeding consists of serious bleeding, serious bleeding causing significant morbidity, and fatal bleeding. Grade 2 bleeding is clinically significant. | Daily, up to 30 days |
| Number of platelet and/or red blood cell transfusions | | Daily, up to 30 days |
| Adverse reactions related to tranexamic acid | Number and type of reactions will be recorded. | Daily, up to 30 days. |
| Venous thromboembolism grade 2 or higher | | Daily, up to 30 days. |
| Adverse reactions related to platelet transfusion | Number and type of reactions will be recorded. | Daily, up to 30 days. |
| Time to platelet count recovery | | Daily, up to 30 days. |
| Number of days with a platelet count < 10 x 109/L | | Daily, up to 30 days. |
| LOS (Length of hospital stay) | LOS = admission date - discharge date | LOS will be measured as the number of days elapsed between hospital admission and hospital discharge date up to 30 days. |
| Transplant related outcome: Bearman Scoring System for Organ Toxicity following HSCT | This is a validated scoring system to assess toxicity during HSCT. In this system, grade I toxicity is reversible without treatment and grade 2 is not life threatening, but requires treatment. Grade 3 requires life-support intervention and grade 4 is fatal. Regimen-related toxicity in each organ system was scored as the highest grade achieved in that organ system through day 28, except that deaths occurring after day 28 as a result of regimen-related toxicity occurring before day 28 are also scored as grade 4. Adverse events that could be attributed to infection (culture-documented), bleeding or other medications are not scored as regimen-related toxicity. The maximum toxicity is the highest grade recorded in any individual organ system and the cumulative toxicity score is the sum of the highest grades recorded for all eight organ systems. | Day 30 |
| Transplant related outcome: Incidence of infections at Day 30 following ASCT | | Day 30 |
| Transplant related outcome: Mortality at Day 30 and 180 | | Day 30, Day 180 |
| Economic Analyses | Incremental cost effectiveness ratios | 5 years |
| Quality of Life Measure: FACT-Thrombocytopenia 18 | The FACT consists of 5 subscales that measure physical well-being, functional well-being, social/family well-being and emotional well-being. The BMT subscale of the FACT includes additional items specifically designed to test quality of life and symptoms specific to transplant patients. | Weekly, up to 30 days |
| Quality of Life Measure: FACT- BMT | The FACT-BMT scale is valid and sensitive to clinical change in transplant recipients. It is the most consistently used scale amongst the Canadian Bone Marrow Transplant Group (CBMTG). It is the preferred scale in several Canadian multicentre trials in stem cell transplantation. FACT- Thrombocytopenia 18 is valid measure to elicit quality of life due to thrombocytopenia, and will complement the FACT-BMT scale. | Day 30, Day 90, Day 180 |
| Quality of Life Measure: GAD-7 | GAD-7 is a short validated scale that assesses symptoms of generalized anxiety and is commonly used in medical settings. There is no specific validated scale to assess anxiety of patients who are at risk for bleeding. | Weekly, up to 30 days |
| Quality of Life Measure: EQ-5D | EQ-5D is a standardized measure of health status to provide a simple, generic measure of health for clinical and economic appraisal. It is applicable to a wide range of health conditions and treatments; it provides a simple descriptive profile and a single index value for health status that can be used in the clinical and economic evaluation of health care. It is cognitively undemanding, taking only a few minutes to complete. | Weekly, up to 30 days |
|
|
NCT01676662
|
Solace European Confirmatory Trial
|
The Solace European Confirmatory (SOLECT) Trial is designed to determine whether the Solace Bladder Control System is safe and effective for the treatment of Stress Urinary Incontinence (SUI) in adult females.
|
Subject will undergo treatment with the Solace Bladder Control System or a sham procedure, with the results being compared at 3 months.~All patients undergoing sham treatment are treated at 3 months.
|
An Evaluation of the Solace Bladder Control System in the Treatment of Female Subjects With Stress Urinary Incontinence
|
Stress Urinary Incontinence
|
* Device: Solace Bladder Control System
* Device: Solace Sham Treatment
|
Inclusion Criteria:~Female 18 years of age or older with stress urinary incontinence (SUI)~Experienced SUI for at least 12 months and attempted and failed prior noninvasive treatment~Willing to undergo cystoscopic procedures required and 36 month follow-up~On stable medication for a minimum of 3 months~Free of local genital skin infection~Positive Pad Weight Test~Free of impassable urethral strictures, trauma or necrosis~Exclusion Criteria (must answer NO):~Pregnant or planning to become pregnant during the study period~Non-ambulatory or bedridden or physically unable to complete test exercises~Morbidly obese (defined as BMI ≥ 40 kg/m2)~Bladder infection (including bladder inflammation or edema) or UTI within 3 months~History of recurrent urinary tract infections~Prior surgical procedure for incontinence within the past 6 months~Is taking medications for urinary incontinence other than anticholinergics~History of kidney stones~Has a prosthetic heart valve~Unable to tolerate any form of antibiotic~Taking anticoagulation therapy, other than aspirin~Has urinary incontinence due to Intrinsic Sphincter Deficiency (ISD)
|
18 Years
| null |
Female
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in quality of life as assessed by pad weight tests assessments and questionnaires | Comparison of increases in pad weight test and patient reported outcomes on questionnaires. | 3 Months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-related adverse events | Site-reported adverse events designated as related to the treatment. | 3 Months |
| Severity of treatment-related adverse events | Site-reported adverse events designated as related to the treatment. | 3 Months |
|
Urinary Incontinence, Urinary Incontinence, Stress, Urination Disorders, Urologic Diseases, Urological Manifestations, Signs and Symptoms
|
Enuresis, Urinary Incontinence, Urinary Incontinence, Stress, Urination Disorders, Urologic Diseases, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Male Urogenital Diseases, Lower Urinary Tract Symptoms, Urological Manifestations, Behavioral Symptoms, Elimination Disorders, Mental Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment on Day 0<br>Subjects who are treated with the Solace Bladder Control System upon entry into the trial. | Device: Solace Bladder Control System<br>* Subjects may undergo treatment every 12 months until study completion.<br>|
| Sham Comparator: Sham Treatment on Day 0<br>Patients who undergo a sham procedure upon entry into the trial, with treatment with the Solace Bladder Control System at 3 months after the sham procedure. | Device: Solace Bladder Control System<br>* Subjects may undergo treatment every 12 months until study completion.<br>Device: Solace Sham Treatment<br>* Sham procedure that resembles treatment with the Solace Bladder Control System<br>|
|
Solace European Confirmatory Trial
Study Overview
=================
Brief Summary
-----------------
The Solace European Confirmatory (SOLECT) Trial is designed to determine whether the Solace Bladder Control System is safe and effective for the treatment of Stress Urinary Incontinence (SUI) in adult females.
Detailed Description
-----------------
Subject will undergo treatment with the Solace Bladder Control System or a sham procedure, with the results being compared at 3 months. All patients undergoing sham treatment are treated at 3 months.
Official Title
-----------------
An Evaluation of the Solace Bladder Control System in the Treatment of Female Subjects With Stress Urinary Incontinence
Conditions
-----------------
Stress Urinary Incontinence
Intervention / Treatment
-----------------
* Device: Solace Bladder Control System
* Device: Solace Sham Treatment
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female 18 years of age or older with stress urinary incontinence (SUI) Experienced SUI for at least 12 months and attempted and failed prior noninvasive treatment Willing to undergo cystoscopic procedures required and 36 month follow-up On stable medication for a minimum of 3 months Free of local genital skin infection Positive Pad Weight Test Free of impassable urethral strictures, trauma or necrosis Exclusion Criteria (must answer NO): Pregnant or planning to become pregnant during the study period Non-ambulatory or bedridden or physically unable to complete test exercises Morbidly obese (defined as BMI ≥ 40 kg/m2) Bladder infection (including bladder inflammation or edema) or UTI within 3 months History of recurrent urinary tract infections Prior surgical procedure for incontinence within the past 6 months Is taking medications for urinary incontinence other than anticholinergics History of kidney stones Has a prosthetic heart valve Unable to tolerate any form of antibiotic Taking anticoagulation therapy, other than aspirin Has urinary incontinence due to Intrinsic Sphincter Deficiency (ISD)
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment on Day 0<br>Subjects who are treated with the Solace Bladder Control System upon entry into the trial. | Device: Solace Bladder Control System<br>* Subjects may undergo treatment every 12 months until study completion.<br>|
| Sham Comparator: Sham Treatment on Day 0<br>Patients who undergo a sham procedure upon entry into the trial, with treatment with the Solace Bladder Control System at 3 months after the sham procedure. | Device: Solace Bladder Control System<br>* Subjects may undergo treatment every 12 months until study completion.<br>Device: Solace Sham Treatment<br>* Sham procedure that resembles treatment with the Solace Bladder Control System<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in quality of life as assessed by pad weight tests assessments and questionnaires | Comparison of increases in pad weight test and patient reported outcomes on questionnaires. | 3 Months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-related adverse events | Site-reported adverse events designated as related to the treatment. | 3 Months |
| Severity of treatment-related adverse events | Site-reported adverse events designated as related to the treatment. | 3 Months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Urinary Incontinence, Urinary Incontinence, Stress, Urination Disorders, Urologic Diseases, Urological Manifestations, Signs and Symptoms
|
NCT04600687
|
B/F/TAF Ease of Swallowability Trial
|
The trial will assess the tolerability and swallowability of a STR placebo of B/F/TAF as compared to DTG/ABC/3TC placebo STR in healthy individuals and HIV antiretroviral naïve patients. The study team will evaluate the ease of swallow and patient's tolerance of the medication formulation, an important, yet often overlooked aspect of ART adherence, with the potential for significant impact on patient's outcomes.
|
The study will plan to recruit 50 volunteers who will be randomized to receive Placebo A (B/F/TAF) or Placebo B (DTG/ABC/3TC). Randomization will ensure that the patients will have equal opportunity to try either placebo tablet first to avoid bias. Randomization will be done by an investigator not evaluating or providing the questionnaires to the patient. Participants will complete a questionnaire regarding what medications they take and what factors they consider affect their ease to swallow pills or tablets. The participants will be administered one of the placebo tablet with the research investigator present and will complete a questionnaire immediately following the first placebo dose. A study timeout for 15-30 minutes will be done following completion of the questionnaires. After which, participants will take the second placebo tablet and complete the final questionnaires.~The primary comparison will be between the placebo tablets A and B for tolerability, ease of swallow and participant preference. The investigators estimate that the sample size needed to detect a difference of at least 1 point in a 5 point Likert scale will be 50 patients with a standard deviation of 2 points, with >90% power.
|
Comparison of the Ease of Swallowability of B/F/TAF Placebo Compared to DTG/ABC/3TC Placebo
|
HIV Infections
|
* Other: Placebo tablets
|
Inclusion Criteria:~HIV seronegative or seropositive treatment naïve adult over 18 years of age, currently in stable condition, ambulatory and able to swallow tablets or pills.~Patients able to provide informed consent and remain in clinic for at least 2 hours.~Study participants able to complete the study questionnaires.~No known history of allergies to any of the placebo components.~Exclusion Criteria:~Patients with known dysphagia or motility disorders leading to difficulty swallowing liquids, food or medications.~Patients allergic to any component of the placebo tablets.~Children under the age of 18 years.~Adults unable to provide informed consent.~Female patients known to be pregnant.~HIV seropositive patients on antiretroviral therapy or with prior history of antiretroviral therapy.
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Participants will be randomized to take the first placebo tablet and within 30 minutes then take the second placebo tablet. The participants will complete questionnaires prior to taking any placebo pill and after each dose.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the ease of swallowability and tolerability of two antiretroviral placebo tablets | To evaluate the ease and tolerability of swallowing and tolerability of two antiretroviral placebo tablet representing Bictegravir/Emtricitabine/TAF (B/F/TAF) single tablet as compared to a placebo tablet representing Dolutegravir/Abacavir/Lamivudine (DTG/ABC/3TC) by Likert scale questionnaire assessment. | One hour |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of pill/tablet size of two antiretroviral placebo tablets on acceptability for patients for adherence. | To assess whether a smaller pill/tablet size is associated with better acceptance by patients by questionnaire. | One hour |
| Tablet characteristics that matter to patients for ease of swallow and for adherence | To determine which particular tablet characteristic is more important as indicated by patients that affects their acceptance of a particular tablet or medication by questionnaire. | One hour |
| Patient's ease of swallow and medication preferences impact on medication adherence | To assess patients' view on how pill/tablet size and ease of swallow impacts their medication adherence by questionnaire using a Likert scale. | One hour |
| How patient's cultural differences affect acceptability of pill/tablet size | To determine if there are any cultural or ethnic differences in pill/tablet acceptance or ease of swallow. | One hour |
|
HIV, adherence, tolerability
|
HIV Infections, Blood-Borne Infections, Communicable Diseases, Infections, Sexually Transmitted Diseases, Viral, Sexually Transmitted Diseases, Lentivirus Infections, Retroviridae Infections, RNA Virus Infections, Virus Diseases, Genital Diseases, Urogenital Diseases, Immunologic Deficiency Syndromes, Immune System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Arm<br>Participants will be enrolled in a single arm with a cross over design. Each participant will receive both placebo tablets about 30 minutes apart. Questionnaires will be completed prior to and after each placebo tablet is swallowed. | Other: Placebo tablets<br>* Participants will take placebo tablets identical to the commercial versions of the two combination antiretroviral single tablet regimens of bictegravir/emtricitabine/tenofovir alanfenamide and dolutegravir/abacavir/lamivudine.<br>|
|
B/F/TAF Ease of Swallowability Trial
Study Overview
=================
Brief Summary
-----------------
The trial will assess the tolerability and swallowability of a STR placebo of B/F/TAF as compared to DTG/ABC/3TC placebo STR in healthy individuals and HIV antiretroviral naïve patients. The study team will evaluate the ease of swallow and patient's tolerance of the medication formulation, an important, yet often overlooked aspect of ART adherence, with the potential for significant impact on patient's outcomes.
Detailed Description
-----------------
The study will plan to recruit 50 volunteers who will be randomized to receive Placebo A (B/F/TAF) or Placebo B (DTG/ABC/3TC). Randomization will ensure that the patients will have equal opportunity to try either placebo tablet first to avoid bias. Randomization will be done by an investigator not evaluating or providing the questionnaires to the patient. Participants will complete a questionnaire regarding what medications they take and what factors they consider affect their ease to swallow pills or tablets. The participants will be administered one of the placebo tablet with the research investigator present and will complete a questionnaire immediately following the first placebo dose. A study timeout for 15-30 minutes will be done following completion of the questionnaires. After which, participants will take the second placebo tablet and complete the final questionnaires. The primary comparison will be between the placebo tablets A and B for tolerability, ease of swallow and participant preference. The investigators estimate that the sample size needed to detect a difference of at least 1 point in a 5 point Likert scale will be 50 patients with a standard deviation of 2 points, with >90% power.
Official Title
-----------------
Comparison of the Ease of Swallowability of B/F/TAF Placebo Compared to DTG/ABC/3TC Placebo
Conditions
-----------------
HIV Infections
Intervention / Treatment
-----------------
* Other: Placebo tablets
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: HIV seronegative or seropositive treatment naïve adult over 18 years of age, currently in stable condition, ambulatory and able to swallow tablets or pills. Patients able to provide informed consent and remain in clinic for at least 2 hours. Study participants able to complete the study questionnaires. No known history of allergies to any of the placebo components. Exclusion Criteria: Patients with known dysphagia or motility disorders leading to difficulty swallowing liquids, food or medications. Patients allergic to any component of the placebo tablets. Children under the age of 18 years. Adults unable to provide informed consent. Female patients known to be pregnant. HIV seropositive patients on antiretroviral therapy or with prior history of antiretroviral therapy.
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: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Participants will be randomized to take the first placebo tablet and within 30 minutes then take the second placebo tablet. The participants will complete questionnaires prior to taking any placebo pill and after each dose.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Arm<br>Participants will be enrolled in a single arm with a cross over design. Each participant will receive both placebo tablets about 30 minutes apart. Questionnaires will be completed prior to and after each placebo tablet is swallowed. | Other: Placebo tablets<br>* Participants will take placebo tablets identical to the commercial versions of the two combination antiretroviral single tablet regimens of bictegravir/emtricitabine/tenofovir alanfenamide and dolutegravir/abacavir/lamivudine.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the ease of swallowability and tolerability of two antiretroviral placebo tablets | To evaluate the ease and tolerability of swallowing and tolerability of two antiretroviral placebo tablet representing Bictegravir/Emtricitabine/TAF (B/F/TAF) single tablet as compared to a placebo tablet representing Dolutegravir/Abacavir/Lamivudine (DTG/ABC/3TC) by Likert scale questionnaire assessment. | One hour |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of pill/tablet size of two antiretroviral placebo tablets on acceptability for patients for adherence. | To assess whether a smaller pill/tablet size is associated with better acceptance by patients by questionnaire. | One hour |
| Tablet characteristics that matter to patients for ease of swallow and for adherence | To determine which particular tablet characteristic is more important as indicated by patients that affects their acceptance of a particular tablet or medication by questionnaire. | One hour |
| Patient's ease of swallow and medication preferences impact on medication adherence | To assess patients' view on how pill/tablet size and ease of swallow impacts their medication adherence by questionnaire using a Likert scale. | One hour |
| How patient's cultural differences affect acceptability of pill/tablet size | To determine if there are any cultural or ethnic differences in pill/tablet acceptance or ease of swallow. | One hour |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV, adherence, tolerability
|
NCT03100370
|
Effects of Combined Spinal Direct Current Stimulation on Upper Limb Recovery in Acquired Brain Injury
|
This study will compare different polarities of transcutaneous spinal direct current stimulation combined with robotic-assisted arm training (RAT) in adults with acquired brain injury (ABI). Participants will receive 20 minutes of 2.5 milliamps (mA) anodal, cathodal, and sham transpinal direct current stimulation (tsDCS) over cervical spine combined with high intensity robotic-assisted arm training, five days a week, for 2 consecutive weeks.
|
Acquired brain injury (ABI) is the leading cause of neurological disability in the United States and accounts for the poor physical health and the social dysfunction evident in survivors. Hemiparesis due to acquired brain injury is the primary cause of disability and arm paresis is perceived as the primary cause of disability by individuals who have suffered ABI because of the limitations it creates in performing activities of daily living (ADL). Rehabilitation of the impaired limb is essential for improving motor function after ABI, yet only 31% of ABI survivors receive outpatient rehabilitation. Therefore, effective therapy for upper-limb paresis must be addressed. Approximately 80% of all ABI survivors suffer from upper limb paresis and only 18% of these individuals gain full motor recovery with conventional treatments in the year following ABI.~The study will use cross-over, randomized, sham controlled, double-blinded design. Participants with subacute or chronic ABI will each be assigned to receive active anodal spinal stimulation, active cathodal spinal stimulation, and sham spinal stimulation for the same duration, and the order that each participant will receive anodal, cathodal, and sham stimulation will be randomized. In all the experiments participants will receive robotic assisted training for duration of 1.5 hours. The first 20 minutes of training will be coupled with spinal stimulation. Treatment will be administered at an intensity of 5 sessions per week for 2 weeks.
|
Effects of Combined Spinal Direct Current Stimulation on Upper Limb Recovery in Acquired Brain Injury (ABI)
|
Acquired Brain Injury
|
* Device: tsDCS-Anodal Stimulation
* Device: tsDCS-Cathodal Stimulation
* Device: tsDCS-Sham Stimulation
* Device: Robotic-assisted training of arm and hand functions
|
Inclusion Criteria:~Providing written informed consent prior to any study related procedures;~Age above 18;~Diagnosis of acquired brain injury at least for 6 month~No neuropsychiatric comorbidities~Not being involved in any specific exercise program (e.g., neuromuscular electrical stimulation (NMES), functional electrical stimulation (FES)) within the previous 3 months;~No planned alteration in upper-extremity therapy or medication for muscle tone during the course of the study;~Eligibility for standard upper-extremity rehabilitation at the time of enrollment (i.e., absence medical comorbidities that would prevent standard rehabilitation);~No condition (e.g., severe arthritis, extreme shoulder pain) that would interfere with valid administration of the measures or with interpreting motor testing;~No contraindications to tsDCS:~metal in the head between stimulation area~metal in the spine between stimulation area~implanted brain medical devices~No pregnancy;~No contraindications for Transcranial Magnetic Stimulation (TMS) and magnetic resonance imaging (MRI) based on TMS and MRI screening forms~Exclusion Criteria:~Uncontrolled epilepsy;~Any joint contracture or severe spasticity in the affected upper extremity, as measured by a Modified Ashworth Score > than 3 out of 4;~History of substance abuse;~Subject who cannot provide self-transportation to the study location
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Each participant will receive active anodal spinal stimulation, active cathodal spinal stimulation, and sham spinal stimulation. The order that each participant receives anodal, cathodal, and sham stimulation will be randomized.
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fugl-Meyer Arm (FMA) Motor Score | FMA is a stroke-specific, performance based impairment index. It quantitatively measures impairment based on Twitchell and Brunnstrom's concept of sequential stages of motor return in hemiplegic stroke patients. It uses an ordinal scale for scoring of 33 items for the upper limb component of the F-M scale (0:can not perform; 1:can perform partially; 2:can perform fully). Total range is 0-66, 0 being poor and 66 normal. | baseline |
| Fugl-Meyer Arm (FMA) Motor Score | FMA is a stroke-specific, performance based impairment index. It quantitatively measures impairment based on Twitchell and Brunnstrom's concept of sequential stages of motor return in hemiplegic stroke patients. It uses an ordinal scale for scoring of 33 items for the upper limb component of the F-M scale (0:can not perform; 1:can perform partially; 2:can perform fully). Total range is 0-66, 0 being poor and 66 normal. | 2 weeks |
| Fugl-Meyer Arm (FMA) Motor Score | FMA is a stroke-specific, performance based impairment index. It quantitatively measures impairment based on Twitchell and Brunnstrom's concept of sequential stages of motor return in hemiplegic stroke patients. It uses an ordinal scale for scoring of 33 items for the upper limb component of the F-M scale (0:can not perform; 1:can perform partially; 2:can perform fully). Total range is 0-66, 0 being poor and 66 normal. | 1 month |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Jebsen Taylor Hand Function Test (JTHFT) | The JTHFT is a motor performance test and assesses the time needed to perform 7 everyday activities (for example, flipping cards and feeding). Score is reported as items completed per second. | Baseline |
| Action Research Arm Test (ARAT) | The ARAT is used to assess subject's ability to manipulate-lift-release objects horizontally and vertically, which differs in size, weight and shape. The test consists of 19 items divided into 4 sub-tests (grasp, grip, pinch, gross arm movement) and each item is rated on a 4-point scale. The possible total score ranges between 0-57. Higher scores indicate better performance. | Baseline |
| Motor Activity Log (MAL) | The MAL ranges from 0 to 5, with a higher score indicating greater ability to use the affected arm. | Baseline |
| Pinch Strength | A pinch gauge will be used to measure maximum pinch force. | Baseline |
| Quantitative Movement Measurement | Robotic movement data will be used to quantitatively measure changes in movement smoothness | Change from baseline at 2 weeks and at 1 month |
| Number of Participants With Adverse Effects Related to tsDCS | Safety will be measured by questioning and observing participants at each treatment session. Adverse effects, such as skin redness etc. will be recorded. | Baseline |
| Jebsen Taylor Hand Function Test (JTHFT) | The JTHFT is a motor performance test and assesses the time needed to perform 7 everyday activities (for example, flipping cards and feeding). Score is reported as items completed per second. | 2 weeks |
| Jebsen Taylor Hand Function Test (JTHFT) | The JTHFT is a motor performance test and assesses the time needed to perform 7 everyday activities (for example, flipping cards and feeding). Score is reported as items completed per second. | 1 month |
| Action Research Arm Test (ARAT) | The ARAT is used to assess subject's ability to manipulate-lift-release objects horizontally and vertically, which differs in size, weight and shape. The test consists of 19 items divided into 4 sub-tests (grasp, grip, pinch, gross arm movement) and each item is rated on a 4-point scale. The possible total score ranges between 0-57. Higher scores indicate better performance. | 2 weeks |
| Action Research Arm Test (ARAT) | The ARAT is used to assess subject's ability to manipulate-lift-release objects horizontally and vertically, which differs in size, weight and shape. The test consists of 19 items divided into 4 sub-tests (grasp, grip, pinch, gross arm movement) and each item is rated on a 4-point scale. The possible total score ranges between 0-57. Higher scores indicate better performance. | 1 month |
| Motor Activity Log (MAL) | The MAL ranges from 0 to 5, with a higher score indicating greater ability to use the affected arm. | 2 weeks |
| Motor Activity Log (MAL) | The MAL ranges from 0 to 5, with a higher score indicating greater ability to use the affected arm. | 1 month |
| Number of Participants With Adverse Effects Related to tsDCS | Safety will be measured by questioning and observing participants at each treatment session. Adverse effects, such as skin redness etc. will be recorded. | 2 weeks |
| Number of Participants With Adverse Effects Related to tsDCS | Safety will be measured by questioning and observing participants at each treatment session. Adverse effects, such as skin redness etc. will be recorded. | 1 month |
| Pinch Strength | A pinch gauge will be used to measure maximum pinch force. | 2 weeks |
| Pinch Strength | A pinch gauge will be used to measure maximum pinch force. | 1 month |
| Grip Strength | A grip dynamometer will be used to measure maximum gross grasp force. | baseline |
| Grip Strength | A grip dynamometer will be used to measure maximum gross grasp force. | 2 weeks |
| Grip Strength | A grip dynamometer will be used to measure maximum gross grasp force. | 1 month |
| Spasticity as Assessed by the Modified Ashworth Scale (MAS) | This test measures spasticity in patients with lesions of the Central Nervous System by testing resistance to passive movement about a joint with varying degrees of velocity. Scores range from 0-4, with 0 indicating normal muscle tone and 4 indicating very high spasticity. The investigators will measure spasticity in the trained upper limb. | baseline |
| Spasticity as Assessed by the Modified Ashworth Scale (MAS) | This test measures spasticity in patients with lesions of the Central Nervous System by testing resistance to passive movement about a joint with varying degrees of velocity. Scores range from 0-4, with 0 indicating normal muscle tone and 4 indicating very high spasticity. The investigators will measure spasticity in the trained upper limb. | 2 weeks |
| Spasticity as Assessed by the Modified Ashworth Scale (MAS) | This test measures spasticity in patients with lesions of the Central Nervous System by testing resistance to passive movement about a joint with varying degrees of velocity. Scores range from 0-4, with 0 indicating normal muscle tone and 4 indicating very high spasticity. The investigators will measure spasticity in the trained upper limb. | 1 month |
| Spinal Reflexes | | Change from baseline at 2 weeks and at 1 month |
| Change in Strength of Selective Muscle Groups | | Change from baseline at 2 weeks and at 1 month |
| Neurophysiologic Testing for Spinal Conductivity (SSEP) | | Change from baseline at 2 weeks and at 1 month |
|
Brain Injuries, Wounds and Injuries, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Craniocerebral Trauma, Trauma, Nervous System
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tsDCS-Anodal & robotic arm training (RAT), then tsDCS-Cathodal & RAT, then tsDCS-Sham & RAT<br>anodal tsDCS over cervical spine, 2.5mA for 20 minutes | Device: tsDCS-Anodal Stimulation<br>* 2.5mA anodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Cathodal Stimulation<br>* 2.5mA cathodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Sham Stimulation<br>* 2.5mA sham tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: Robotic-assisted training of arm and hand functions<br>* 70 minutes of robotic-assisted training (RAT) of arm and hand functions will follow each of the tsDCS sessions, five days a week, for two weeks. Robotic-assisted training will be provided by using the MAHI Exo-II device.<br>|
| Experimental: tsDCS-Anodal & robotic arm training (RAT), then tsDCS-Sham & RAT, then tsDCS-Cathodal & RAT<br>cathodal tsDCS over cervical spine, 2.5mA for 20 minutes | Device: tsDCS-Anodal Stimulation<br>* 2.5mA anodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Cathodal Stimulation<br>* 2.5mA cathodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Sham Stimulation<br>* 2.5mA sham tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: Robotic-assisted training of arm and hand functions<br>* 70 minutes of robotic-assisted training (RAT) of arm and hand functions will follow each of the tsDCS sessions, five days a week, for two weeks. Robotic-assisted training will be provided by using the MAHI Exo-II device.<br>|
| Experimental: tsDCS-Cathodal & robotic arm training (RAT), then tsDCS-Anodal & RAT, then tsDCS-Sham & RAT<br>sham tsDCS over cervical spine, 2.5mA for 20 minutes | Device: tsDCS-Anodal Stimulation<br>* 2.5mA anodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Cathodal Stimulation<br>* 2.5mA cathodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Sham Stimulation<br>* 2.5mA sham tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: Robotic-assisted training of arm and hand functions<br>* 70 minutes of robotic-assisted training (RAT) of arm and hand functions will follow each of the tsDCS sessions, five days a week, for two weeks. Robotic-assisted training will be provided by using the MAHI Exo-II device.<br>|
| Experimental: tsDCS-Cathodal & robotic arm training (RAT), then tsDCS-Sham & RAT, then tsDCS-Anodal & RAT<br> | Device: tsDCS-Anodal Stimulation<br>* 2.5mA anodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Cathodal Stimulation<br>* 2.5mA cathodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Sham Stimulation<br>* 2.5mA sham tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: Robotic-assisted training of arm and hand functions<br>* 70 minutes of robotic-assisted training (RAT) of arm and hand functions will follow each of the tsDCS sessions, five days a week, for two weeks. Robotic-assisted training will be provided by using the MAHI Exo-II device.<br>|
| Experimental: tsDCS-Sham & robotic arm training (RAT), then tsDCS-Anodal & RAT, then tsDCS- Cathodal & RAT<br> | Device: tsDCS-Anodal Stimulation<br>* 2.5mA anodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Cathodal Stimulation<br>* 2.5mA cathodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Sham Stimulation<br>* 2.5mA sham tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: Robotic-assisted training of arm and hand functions<br>* 70 minutes of robotic-assisted training (RAT) of arm and hand functions will follow each of the tsDCS sessions, five days a week, for two weeks. Robotic-assisted training will be provided by using the MAHI Exo-II device.<br>|
| Experimental: tsDCS-Sham & robotic arm training (RAT), then tsDCS-Cathodal & RAT, then tsDCS-Anodal & RAT<br> | Device: tsDCS-Anodal Stimulation<br>* 2.5mA anodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Cathodal Stimulation<br>* 2.5mA cathodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Sham Stimulation<br>* 2.5mA sham tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: Robotic-assisted training of arm and hand functions<br>* 70 minutes of robotic-assisted training (RAT) of arm and hand functions will follow each of the tsDCS sessions, five days a week, for two weeks. Robotic-assisted training will be provided by using the MAHI Exo-II device.<br>|
|
Effects of Combined Spinal Direct Current Stimulation on Upper Limb Recovery in Acquired Brain Injury
Study Overview
=================
Brief Summary
-----------------
This study will compare different polarities of transcutaneous spinal direct current stimulation combined with robotic-assisted arm training (RAT) in adults with acquired brain injury (ABI). Participants will receive 20 minutes of 2.5 milliamps (mA) anodal, cathodal, and sham transpinal direct current stimulation (tsDCS) over cervical spine combined with high intensity robotic-assisted arm training, five days a week, for 2 consecutive weeks.
Detailed Description
-----------------
Acquired brain injury (ABI) is the leading cause of neurological disability in the United States and accounts for the poor physical health and the social dysfunction evident in survivors. Hemiparesis due to acquired brain injury is the primary cause of disability and arm paresis is perceived as the primary cause of disability by individuals who have suffered ABI because of the limitations it creates in performing activities of daily living (ADL). Rehabilitation of the impaired limb is essential for improving motor function after ABI, yet only 31% of ABI survivors receive outpatient rehabilitation. Therefore, effective therapy for upper-limb paresis must be addressed. Approximately 80% of all ABI survivors suffer from upper limb paresis and only 18% of these individuals gain full motor recovery with conventional treatments in the year following ABI. The study will use cross-over, randomized, sham controlled, double-blinded design. Participants with subacute or chronic ABI will each be assigned to receive active anodal spinal stimulation, active cathodal spinal stimulation, and sham spinal stimulation for the same duration, and the order that each participant will receive anodal, cathodal, and sham stimulation will be randomized. In all the experiments participants will receive robotic assisted training for duration of 1.5 hours. The first 20 minutes of training will be coupled with spinal stimulation. Treatment will be administered at an intensity of 5 sessions per week for 2 weeks.
Official Title
-----------------
Effects of Combined Spinal Direct Current Stimulation on Upper Limb Recovery in Acquired Brain Injury (ABI)
Conditions
-----------------
Acquired Brain Injury
Intervention / Treatment
-----------------
* Device: tsDCS-Anodal Stimulation
* Device: tsDCS-Cathodal Stimulation
* Device: tsDCS-Sham Stimulation
* Device: Robotic-assisted training of arm and hand functions
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Providing written informed consent prior to any study related procedures; Age above 18; Diagnosis of acquired brain injury at least for 6 month No neuropsychiatric comorbidities Not being involved in any specific exercise program (e.g., neuromuscular electrical stimulation (NMES), functional electrical stimulation (FES)) within the previous 3 months; No planned alteration in upper-extremity therapy or medication for muscle tone during the course of the study; Eligibility for standard upper-extremity rehabilitation at the time of enrollment (i.e., absence medical comorbidities that would prevent standard rehabilitation); No condition (e.g., severe arthritis, extreme shoulder pain) that would interfere with valid administration of the measures or with interpreting motor testing; No contraindications to tsDCS: metal in the head between stimulation area metal in the spine between stimulation area implanted brain medical devices No pregnancy; No contraindications for Transcranial Magnetic Stimulation (TMS) and magnetic resonance imaging (MRI) based on TMS and MRI screening forms Exclusion Criteria: Uncontrolled epilepsy; Any joint contracture or severe spasticity in the affected upper extremity, as measured by a Modified Ashworth Score > than 3 out of 4; History of substance abuse; Subject who cannot provide self-transportation to the study location
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
Interventional Model Description: Each participant will receive active anodal spinal stimulation, active cathodal spinal stimulation, and sham spinal stimulation. The order that each participant receives anodal, cathodal, and sham stimulation will be randomized.
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tsDCS-Anodal & robotic arm training (RAT), then tsDCS-Cathodal & RAT, then tsDCS-Sham & RAT<br>anodal tsDCS over cervical spine, 2.5mA for 20 minutes | Device: tsDCS-Anodal Stimulation<br>* 2.5mA anodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Cathodal Stimulation<br>* 2.5mA cathodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Sham Stimulation<br>* 2.5mA sham tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: Robotic-assisted training of arm and hand functions<br>* 70 minutes of robotic-assisted training (RAT) of arm and hand functions will follow each of the tsDCS sessions, five days a week, for two weeks. Robotic-assisted training will be provided by using the MAHI Exo-II device.<br>|
| Experimental: tsDCS-Anodal & robotic arm training (RAT), then tsDCS-Sham & RAT, then tsDCS-Cathodal & RAT<br>cathodal tsDCS over cervical spine, 2.5mA for 20 minutes | Device: tsDCS-Anodal Stimulation<br>* 2.5mA anodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Cathodal Stimulation<br>* 2.5mA cathodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Sham Stimulation<br>* 2.5mA sham tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: Robotic-assisted training of arm and hand functions<br>* 70 minutes of robotic-assisted training (RAT) of arm and hand functions will follow each of the tsDCS sessions, five days a week, for two weeks. Robotic-assisted training will be provided by using the MAHI Exo-II device.<br>|
| Experimental: tsDCS-Cathodal & robotic arm training (RAT), then tsDCS-Anodal & RAT, then tsDCS-Sham & RAT<br>sham tsDCS over cervical spine, 2.5mA for 20 minutes | Device: tsDCS-Anodal Stimulation<br>* 2.5mA anodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Cathodal Stimulation<br>* 2.5mA cathodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Sham Stimulation<br>* 2.5mA sham tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: Robotic-assisted training of arm and hand functions<br>* 70 minutes of robotic-assisted training (RAT) of arm and hand functions will follow each of the tsDCS sessions, five days a week, for two weeks. Robotic-assisted training will be provided by using the MAHI Exo-II device.<br>|
| Experimental: tsDCS-Cathodal & robotic arm training (RAT), then tsDCS-Sham & RAT, then tsDCS-Anodal & RAT<br> | Device: tsDCS-Anodal Stimulation<br>* 2.5mA anodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Cathodal Stimulation<br>* 2.5mA cathodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Sham Stimulation<br>* 2.5mA sham tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: Robotic-assisted training of arm and hand functions<br>* 70 minutes of robotic-assisted training (RAT) of arm and hand functions will follow each of the tsDCS sessions, five days a week, for two weeks. Robotic-assisted training will be provided by using the MAHI Exo-II device.<br>|
| Experimental: tsDCS-Sham & robotic arm training (RAT), then tsDCS-Anodal & RAT, then tsDCS- Cathodal & RAT<br> | Device: tsDCS-Anodal Stimulation<br>* 2.5mA anodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Cathodal Stimulation<br>* 2.5mA cathodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Sham Stimulation<br>* 2.5mA sham tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: Robotic-assisted training of arm and hand functions<br>* 70 minutes of robotic-assisted training (RAT) of arm and hand functions will follow each of the tsDCS sessions, five days a week, for two weeks. Robotic-assisted training will be provided by using the MAHI Exo-II device.<br>|
| Experimental: tsDCS-Sham & robotic arm training (RAT), then tsDCS-Cathodal & RAT, then tsDCS-Anodal & RAT<br> | Device: tsDCS-Anodal Stimulation<br>* 2.5mA anodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Cathodal Stimulation<br>* 2.5mA cathodal tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: tsDCS-Sham Stimulation<br>* 2.5mA sham tsDCS over cervical spine for 20 minutes, five days a week, for two weeks. tsDCS electrodes will be placed over cervical spine and shoulder.<br>* Other names: Transcutaneous Spinal Direct Current Stimulation;Device: Robotic-assisted training of arm and hand functions<br>* 70 minutes of robotic-assisted training (RAT) of arm and hand functions will follow each of the tsDCS sessions, five days a week, for two weeks. Robotic-assisted training will be provided by using the MAHI Exo-II device.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fugl-Meyer Arm (FMA) Motor Score | FMA is a stroke-specific, performance based impairment index. It quantitatively measures impairment based on Twitchell and Brunnstrom's concept of sequential stages of motor return in hemiplegic stroke patients. It uses an ordinal scale for scoring of 33 items for the upper limb component of the F-M scale (0:can not perform; 1:can perform partially; 2:can perform fully). Total range is 0-66, 0 being poor and 66 normal. | baseline |
| Fugl-Meyer Arm (FMA) Motor Score | FMA is a stroke-specific, performance based impairment index. It quantitatively measures impairment based on Twitchell and Brunnstrom's concept of sequential stages of motor return in hemiplegic stroke patients. It uses an ordinal scale for scoring of 33 items for the upper limb component of the F-M scale (0:can not perform; 1:can perform partially; 2:can perform fully). Total range is 0-66, 0 being poor and 66 normal. | 2 weeks |
| Fugl-Meyer Arm (FMA) Motor Score | FMA is a stroke-specific, performance based impairment index. It quantitatively measures impairment based on Twitchell and Brunnstrom's concept of sequential stages of motor return in hemiplegic stroke patients. It uses an ordinal scale for scoring of 33 items for the upper limb component of the F-M scale (0:can not perform; 1:can perform partially; 2:can perform fully). Total range is 0-66, 0 being poor and 66 normal. | 1 month |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Jebsen Taylor Hand Function Test (JTHFT) | The JTHFT is a motor performance test and assesses the time needed to perform 7 everyday activities (for example, flipping cards and feeding). Score is reported as items completed per second. | Baseline |
| Action Research Arm Test (ARAT) | The ARAT is used to assess subject's ability to manipulate-lift-release objects horizontally and vertically, which differs in size, weight and shape. The test consists of 19 items divided into 4 sub-tests (grasp, grip, pinch, gross arm movement) and each item is rated on a 4-point scale. The possible total score ranges between 0-57. Higher scores indicate better performance. | Baseline |
| Motor Activity Log (MAL) | The MAL ranges from 0 to 5, with a higher score indicating greater ability to use the affected arm. | Baseline |
| Pinch Strength | A pinch gauge will be used to measure maximum pinch force. | Baseline |
| Quantitative Movement Measurement | Robotic movement data will be used to quantitatively measure changes in movement smoothness | Change from baseline at 2 weeks and at 1 month |
| Number of Participants With Adverse Effects Related to tsDCS | Safety will be measured by questioning and observing participants at each treatment session. Adverse effects, such as skin redness etc. will be recorded. | Baseline |
| Jebsen Taylor Hand Function Test (JTHFT) | The JTHFT is a motor performance test and assesses the time needed to perform 7 everyday activities (for example, flipping cards and feeding). Score is reported as items completed per second. | 2 weeks |
| Jebsen Taylor Hand Function Test (JTHFT) | The JTHFT is a motor performance test and assesses the time needed to perform 7 everyday activities (for example, flipping cards and feeding). Score is reported as items completed per second. | 1 month |
| Action Research Arm Test (ARAT) | The ARAT is used to assess subject's ability to manipulate-lift-release objects horizontally and vertically, which differs in size, weight and shape. The test consists of 19 items divided into 4 sub-tests (grasp, grip, pinch, gross arm movement) and each item is rated on a 4-point scale. The possible total score ranges between 0-57. Higher scores indicate better performance. | 2 weeks |
| Action Research Arm Test (ARAT) | The ARAT is used to assess subject's ability to manipulate-lift-release objects horizontally and vertically, which differs in size, weight and shape. The test consists of 19 items divided into 4 sub-tests (grasp, grip, pinch, gross arm movement) and each item is rated on a 4-point scale. The possible total score ranges between 0-57. Higher scores indicate better performance. | 1 month |
| Motor Activity Log (MAL) | The MAL ranges from 0 to 5, with a higher score indicating greater ability to use the affected arm. | 2 weeks |
| Motor Activity Log (MAL) | The MAL ranges from 0 to 5, with a higher score indicating greater ability to use the affected arm. | 1 month |
| Number of Participants With Adverse Effects Related to tsDCS | Safety will be measured by questioning and observing participants at each treatment session. Adverse effects, such as skin redness etc. will be recorded. | 2 weeks |
| Number of Participants With Adverse Effects Related to tsDCS | Safety will be measured by questioning and observing participants at each treatment session. Adverse effects, such as skin redness etc. will be recorded. | 1 month |
| Pinch Strength | A pinch gauge will be used to measure maximum pinch force. | 2 weeks |
| Pinch Strength | A pinch gauge will be used to measure maximum pinch force. | 1 month |
| Grip Strength | A grip dynamometer will be used to measure maximum gross grasp force. | baseline |
| Grip Strength | A grip dynamometer will be used to measure maximum gross grasp force. | 2 weeks |
| Grip Strength | A grip dynamometer will be used to measure maximum gross grasp force. | 1 month |
| Spasticity as Assessed by the Modified Ashworth Scale (MAS) | This test measures spasticity in patients with lesions of the Central Nervous System by testing resistance to passive movement about a joint with varying degrees of velocity. Scores range from 0-4, with 0 indicating normal muscle tone and 4 indicating very high spasticity. The investigators will measure spasticity in the trained upper limb. | baseline |
| Spasticity as Assessed by the Modified Ashworth Scale (MAS) | This test measures spasticity in patients with lesions of the Central Nervous System by testing resistance to passive movement about a joint with varying degrees of velocity. Scores range from 0-4, with 0 indicating normal muscle tone and 4 indicating very high spasticity. The investigators will measure spasticity in the trained upper limb. | 2 weeks |
| Spasticity as Assessed by the Modified Ashworth Scale (MAS) | This test measures spasticity in patients with lesions of the Central Nervous System by testing resistance to passive movement about a joint with varying degrees of velocity. Scores range from 0-4, with 0 indicating normal muscle tone and 4 indicating very high spasticity. The investigators will measure spasticity in the trained upper limb. | 1 month |
| Spinal Reflexes | | Change from baseline at 2 weeks and at 1 month |
| Change in Strength of Selective Muscle Groups | | Change from baseline at 2 weeks and at 1 month |
| Neurophysiologic Testing for Spinal Conductivity (SSEP) | | Change from baseline at 2 weeks and at 1 month |
|
|
NCT01799993
|
Inhaled Amikacin Solution BAY41-6551 as Adjunctive Therapy in the Treatment of Gram-Negative Pneumonia
|
To demonstrate that as adjunctive therapy to intravenous (IV) antibiotics, BAY 41-6551 400 mg (amikacin as free base) administered as an aerosol by the Pulmonary Drug Delivery System (PDDS) Clinical every 12 hours is safe and more effective than placebo (aerosolized normal saline) administered as an aerosol by the PDDS Clinical every 12 hours, in intubated and mechanically-ventilated patients with Gram-negative Pneumonia. The secondary endpoint objectives are to evaluate the superiority of aerosolized BAY 41-6551 versus aerosolized placebo in pneumonia-related mortality, the Early Clinical Response at Day 10, the days on ventilation, and the days in the intensive care unit (ICU).
|
A Prospective, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of BAY 41-6551 as Adjunctive Therapy in Intubated and Mechanically-Ventilated Patients With Gram-Negative Pneumonia
|
Pneumonia, Bacterial
|
* Drug: Amikacin Inhalation Solution (BAY41-6551)
* Drug: Aerosolized Placebo
|
Inclusion Criteria:~Males and non-pregnant, non-lactating females, 18 years of age or older~Intubated and mechanically-ventilated~Diagnosis of pneumonia defined as presence of a new or progressive infiltrate(s) on chest radiograph~Presence of Gram-negative organism(s) by either Gram stain or culture of respiratory secretions, or suspected Gram-negative pathogen~Impaired oxygenation~Clinical Pulmonary Infection Score (CPIS) of at least 6~Presence of a multi-drug resistant (MDR) organism in a pre-therapy respiratory specimen OR at least two risk factors for MDR organisms~Exclusion Criteria:~History of hypersensitivity to amikacin or other aminoglycosides~Has received antibiotic therapy for Gram-negative pneumonia for greater than 48 hours at the time of randomization~Known or suspected bacteremia secondary to Staphylococcus aureus~A positive urine and/or serum beta-human Chorionic Gonadotropin pregnancy test~Patients with a serum creatinine > 2 mg/dL (177 µmol/L) [Exception: Patients with a serum creatinine > 2 mg/dL (177 µmol/L) and being treated with continuous renal replacement therapy (Continuous Veno-Venous Hemodialysis and CVVHemoDiafiltration) or daily hemodialysis will receive the aerosol study drug treatment]~Has been on mechanical ventilation for > 28 days~Is participating in or has participated in other investigational interventional studies within the last 28 days prior to study treatment~The risk of rapidly fatal illness and death within 72 hrs, or any concomitant condition not related to ventilator-associated pneumonia that, in the opinion of the investigator, precludes completion of study evaluations and the course of therapy~Has an Acute Physiology and Chronic Health Evaluation (APACHE) II score < 10~Patients receiving veno-venous extracorporeal circulation membrane oxygenation (V-V ECMO)
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Surviving Through LFU Visit | The primary efficacy variable is Survival through the late follow-up (LFU) visit. Survival is achieved when the participant is alive through the LFU visit. No other factors are considered in the evaluation of survival. | Up to 28-32 days after start of study treatment |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adjudicated Pneumonia-Related Death Through LFU Visit | Death through LFU visit was adjudicated as pneumonia-related or pneumonia-unrelated for participants in the amikacin inhale group and participants in the placebo group. | Up to 28-32 days after start of study treatment |
| Number of Participants With Early Clinical Response | Early Clinical Response was determined by the following: 1. CPIS scoring at Days 3, 5, and 10 compared to baseline (a. On Day 3, CPIS increase from baseline by at least 2 points was considered a failure. b. On Day 5, CPIS decrease from baseline of at least 1 point was not a failure. CPIS of no change from baseline was considered a failure. Any CPIS increase from baseline was a failure. c. On Day 10, CPIS decrease from baseline of at least 2 points was not a failure. CPIS decrease of only 1 point is a failure. Clinical Pulmonary Infection Score of no change was considered a failure. Any CPIS increase from baseline was a failure). 2. All-cause mortality through EOT visit was a failure. 3. The development of empyema or lung abscess through the EOT visit was a failure. | Up to 10 days after start of study treatment |
| Number of Days on Mechanical Ventilation Through LFU Visit | Number of days on mechanical ventilator was summarized by descriptive statistics. Duration was defined as the number of days from the date of first study drug through the LFU visit. For participants who lived through the LFU visit, the ventilation days were actual days on ventilation with a maximum value of 28 days. For participants who died after Day 28 but on or before their LFU visit, the days on ventilator was censored at 28 days. For participants who died or discontinued off ventilation, the number of days on ventilation was actual days on ventilation with a maximum value of 28 days. For participants who died or discontinued on ventilation, the number of days on ventilation was 28 days. Further analysis of the number of days on mechanical ventilator was to be performed with censoring at Day 28 for subset of participants on ventilation without censoring. | Up to 28-32 days after start of study treatment |
| Number of Days in the ICU Through LFU Visit | Number of days in ICU was summarized by descriptive statistics. Duration was defined as the number of days from the date of first study drug through the LFU visit. For participants who lived in ICU through the LFU visit, the ICU days were actual days in ICU with a maximum value of 28 days. For participants who died after Day 28 but on or before their LFU visit, the days in ICU was censored at 28 days. For participants who died or discontinued in ICU, the number of days in ICU was 28 days. Further analysis of the number of days in ICU was to be performed with censoring at Day 28 for subset of participants on ventilation and without censoring. | Up to 28-32 days after start of study treatment |
|
Gram-negative pneumonia, Intubation, Mechanical ventilation, Amikacin
|
Amikacin, Anti-Bacterial Agents, Anti-Infective Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amikacin inhale (BAY41-6551)<br>Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10. | Drug: Amikacin Inhalation Solution (BAY41-6551)<br>* 400 mg of aerosolized amikacin every 12 hours for 10 days to be administered using the Pulmonary Drug Delivery System (PDDS Clinical)<br>|
| Placebo Comparator: Placebo<br>Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10. | Drug: Aerosolized Placebo<br>* Aerosolized placebo every 12 hours for 10 days to be administered using the Pulmonary Drug Delivery System (PDDS Clinical)<br>|
|
Inhaled Amikacin Solution BAY41-6551 as Adjunctive Therapy in the Treatment of Gram-Negative Pneumonia
Study Overview
=================
Brief Summary
-----------------
To demonstrate that as adjunctive therapy to intravenous (IV) antibiotics, BAY 41-6551 400 mg (amikacin as free base) administered as an aerosol by the Pulmonary Drug Delivery System (PDDS) Clinical every 12 hours is safe and more effective than placebo (aerosolized normal saline) administered as an aerosol by the PDDS Clinical every 12 hours, in intubated and mechanically-ventilated patients with Gram-negative Pneumonia. The secondary endpoint objectives are to evaluate the superiority of aerosolized BAY 41-6551 versus aerosolized placebo in pneumonia-related mortality, the Early Clinical Response at Day 10, the days on ventilation, and the days in the intensive care unit (ICU).
Official Title
-----------------
A Prospective, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of BAY 41-6551 as Adjunctive Therapy in Intubated and Mechanically-Ventilated Patients With Gram-Negative Pneumonia
Conditions
-----------------
Pneumonia, Bacterial
Intervention / Treatment
-----------------
* Drug: Amikacin Inhalation Solution (BAY41-6551)
* Drug: Aerosolized Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males and non-pregnant, non-lactating females, 18 years of age or older Intubated and mechanically-ventilated Diagnosis of pneumonia defined as presence of a new or progressive infiltrate(s) on chest radiograph Presence of Gram-negative organism(s) by either Gram stain or culture of respiratory secretions, or suspected Gram-negative pathogen Impaired oxygenation Clinical Pulmonary Infection Score (CPIS) of at least 6 Presence of a multi-drug resistant (MDR) organism in a pre-therapy respiratory specimen OR at least two risk factors for MDR organisms Exclusion Criteria: History of hypersensitivity to amikacin or other aminoglycosides Has received antibiotic therapy for Gram-negative pneumonia for greater than 48 hours at the time of randomization Known or suspected bacteremia secondary to Staphylococcus aureus A positive urine and/or serum beta-human Chorionic Gonadotropin pregnancy test Patients with a serum creatinine > 2 mg/dL (177 µmol/L) [Exception: Patients with a serum creatinine > 2 mg/dL (177 µmol/L) and being treated with continuous renal replacement therapy (Continuous Veno-Venous Hemodialysis and CVVHemoDiafiltration) or daily hemodialysis will receive the aerosol study drug treatment] Has been on mechanical ventilation for > 28 days Is participating in or has participated in other investigational interventional studies within the last 28 days prior to study treatment The risk of rapidly fatal illness and death within 72 hrs, or any concomitant condition not related to ventilator-associated pneumonia that, in the opinion of the investigator, precludes completion of study evaluations and the course of therapy Has an Acute Physiology and Chronic Health Evaluation (APACHE) II score < 10 Patients receiving veno-venous extracorporeal circulation membrane oxygenation (V-V ECMO)
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: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amikacin inhale (BAY41-6551)<br>Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10. | Drug: Amikacin Inhalation Solution (BAY41-6551)<br>* 400 mg of aerosolized amikacin every 12 hours for 10 days to be administered using the Pulmonary Drug Delivery System (PDDS Clinical)<br>|
| Placebo Comparator: Placebo<br>Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10. | Drug: Aerosolized Placebo<br>* Aerosolized placebo every 12 hours for 10 days to be administered using the Pulmonary Drug Delivery System (PDDS Clinical)<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Surviving Through LFU Visit | The primary efficacy variable is Survival through the late follow-up (LFU) visit. Survival is achieved when the participant is alive through the LFU visit. No other factors are considered in the evaluation of survival. | Up to 28-32 days after start of study treatment |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adjudicated Pneumonia-Related Death Through LFU Visit | Death through LFU visit was adjudicated as pneumonia-related or pneumonia-unrelated for participants in the amikacin inhale group and participants in the placebo group. | Up to 28-32 days after start of study treatment |
| Number of Participants With Early Clinical Response | Early Clinical Response was determined by the following: 1. CPIS scoring at Days 3, 5, and 10 compared to baseline (a. On Day 3, CPIS increase from baseline by at least 2 points was considered a failure. b. On Day 5, CPIS decrease from baseline of at least 1 point was not a failure. CPIS of no change from baseline was considered a failure. Any CPIS increase from baseline was a failure. c. On Day 10, CPIS decrease from baseline of at least 2 points was not a failure. CPIS decrease of only 1 point is a failure. Clinical Pulmonary Infection Score of no change was considered a failure. Any CPIS increase from baseline was a failure). 2. All-cause mortality through EOT visit was a failure. 3. The development of empyema or lung abscess through the EOT visit was a failure. | Up to 10 days after start of study treatment |
| Number of Days on Mechanical Ventilation Through LFU Visit | Number of days on mechanical ventilator was summarized by descriptive statistics. Duration was defined as the number of days from the date of first study drug through the LFU visit. For participants who lived through the LFU visit, the ventilation days were actual days on ventilation with a maximum value of 28 days. For participants who died after Day 28 but on or before their LFU visit, the days on ventilator was censored at 28 days. For participants who died or discontinued off ventilation, the number of days on ventilation was actual days on ventilation with a maximum value of 28 days. For participants who died or discontinued on ventilation, the number of days on ventilation was 28 days. Further analysis of the number of days on mechanical ventilator was to be performed with censoring at Day 28 for subset of participants on ventilation without censoring. | Up to 28-32 days after start of study treatment |
| Number of Days in the ICU Through LFU Visit | Number of days in ICU was summarized by descriptive statistics. Duration was defined as the number of days from the date of first study drug through the LFU visit. For participants who lived in ICU through the LFU visit, the ICU days were actual days in ICU with a maximum value of 28 days. For participants who died after Day 28 but on or before their LFU visit, the days in ICU was censored at 28 days. For participants who died or discontinued in ICU, the number of days in ICU was 28 days. Further analysis of the number of days in ICU was to be performed with censoring at Day 28 for subset of participants on ventilation and without censoring. | Up to 28-32 days after start of study treatment |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Gram-negative pneumonia, Intubation, Mechanical ventilation, Amikacin
|
|
NCT02796404
|
Homebased Monitoring Cardiac Rehabilitation Program
|
The current state of mobile communication and technology is a tool to support home programs for chronic disease management, useful to facilitate access to these types of programs, because the investigators could obtain telematics information about the parameters, reducing cardiovascular risk factors and cardiovascular morbidity and mortality.
|
The current state of mobile communication and technology is a tool to support home programs for chronic disease management, useful to facilitate access to these types of programs, because the investigators could obtain telematics information about the parameters, reducing cardiovascular risk factors and cardiovascular morbidity and mortality.~Once the patient qualifies for inclusion in the study and has signed informed consent it is included in a list where randomized 7 patients in the experimental group (home-based cardiac rehabilitation Nuubo monitoring vest) and 7 patients are assigned to traditional cardiac rehabilitation group.
|
Effectiveness of a Homebased Cardiac Rehabilitation Program of Mixed Surveillance Using NUUBO Monitoring Vest in Patients With Ischemic Heart Disease at Moderate Cardiovascular Risk
|
Homebased Cardiac Rehabilitation Program After Ischemic Heart Disease
|
* Device: Homebased cardiac rehabilitation program
* Other: Traditional cardiac rehabilitation program
|
Inclusion Criteria:~All of them:~Age ≤ 80 years.~Stable Ischemic heart disease, revascularized by angioplasty or underwent surgery by coronary bypass <= one year from the acute episode.~Good cognitive level.~Ability to perform aerobic exercise tape or cycle ergometer.~Understand the use of a mobile Smartphone or Tablet.~Signature of informed consent.~And at least one of the following:~Ventricular dysfunction by Ejection Fraction (FE) 40 - 50%.~Functional capacity 5-7 metabolic equivalents (METS).~Raising the blood pressure with the effort.~Exclusion Criteria:~Presence of malignant arrhythmias such as ventricular fibrillation outside the acute phase of Acute myocardial infarction (AMI) (> 24 h after AMI), ventricular tachycardia, Atrioventricular block of 2nd degree and 3rd degree, Atrial fibrilation (FA) in patients with Wolf Parkinson White, fibrillation or paroxysmal atrial flutter with response ventricular quickly and hemodynamic deterioration, premature ventricular contractions increases during exertion, paroxysmal supraventricular tachycardia uncontrolled.~Previous infarcts.~Hypotensive response to exercise.~Myocardial Ischemia valued at exercise test.~Unstable Angina.~Nonrevascularizable disease.~Poorly controlled hypertension baseline.~Killip III and IV Killip.~No collaborator.~Valvular heart disease associated.~Pacemaker or Implantable Cardioverter Defibrillator.~Pathology of musculoskeletal, neurological or breathing that impair the ability of prolonged ambulation.
| null |
80 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness measured by exercise testing and control of cardiovascular risk factors | functional capacity obtained by exercise testing and control of cardiovascular risk factors. | During 12 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Results of homebased cardiac rehabilitation monitoring a traditional cardiac rehabilitation program | comparing the results of functional capacity measured by exercise testing and control of cardiovascular risk factors between the two groups | During 12 months |
| Adherence to these programs | see adherence to these program at 3, 6 months and a year depending on the habit of exercise and control of cardiovascular risk factors. | 3, 6 and 12 months |
| Safety to these program | See the safety of home cardiac rehabilitation program of mixed surveillance compared to traditional cardiac rehabilitation program to checking the existence of adverse cardiac events. | During 12 months |
|
home monitoring, cardiac monitoring
|
Heart Diseases, Myocardial Ischemia, Coronary Artery Disease, Cardiovascular Diseases, Vascular Diseases, Coronary Disease, Arteriosclerosis, Arterial Occlusive Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Homebased cardiac rehabilitation program<br>Homebased Cardiac rehabilitation program with monitoring vest and mixed surveillance. | Device: Homebased cardiac rehabilitation program<br>* homebased cardiac rehabilitation program with monitoring vest Nuubo<br>Other: Traditional cardiac rehabilitation program<br>* multidisciplinary intervention in cardiac rehabilitation gym<br>|
| Other: Traditional cardiac rehabilitation<br>Multidisciplinary program in a cardiac rehabilitation gym. Routine clinical practice | Other: Traditional cardiac rehabilitation program<br>* multidisciplinary intervention in cardiac rehabilitation gym<br>|
|
Homebased Monitoring Cardiac Rehabilitation Program
Study Overview
=================
Brief Summary
-----------------
The current state of mobile communication and technology is a tool to support home programs for chronic disease management, useful to facilitate access to these types of programs, because the investigators could obtain telematics information about the parameters, reducing cardiovascular risk factors and cardiovascular morbidity and mortality.
Detailed Description
-----------------
The current state of mobile communication and technology is a tool to support home programs for chronic disease management, useful to facilitate access to these types of programs, because the investigators could obtain telematics information about the parameters, reducing cardiovascular risk factors and cardiovascular morbidity and mortality. Once the patient qualifies for inclusion in the study and has signed informed consent it is included in a list where randomized 7 patients in the experimental group (home-based cardiac rehabilitation Nuubo monitoring vest) and 7 patients are assigned to traditional cardiac rehabilitation group.
Official Title
-----------------
Effectiveness of a Homebased Cardiac Rehabilitation Program of Mixed Surveillance Using NUUBO Monitoring Vest in Patients With Ischemic Heart Disease at Moderate Cardiovascular Risk
Conditions
-----------------
Homebased Cardiac Rehabilitation Program After Ischemic Heart Disease
Intervention / Treatment
-----------------
* Device: Homebased cardiac rehabilitation program
* Other: Traditional cardiac rehabilitation program
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All of them: Age ≤ 80 years. Stable Ischemic heart disease, revascularized by angioplasty or underwent surgery by coronary bypass <= one year from the acute episode. Good cognitive level. Ability to perform aerobic exercise tape or cycle ergometer. Understand the use of a mobile Smartphone or Tablet. Signature of informed consent. And at least one of the following: Ventricular dysfunction by Ejection Fraction (FE) 40 - 50%. Functional capacity 5-7 metabolic equivalents (METS). Raising the blood pressure with the effort. Exclusion Criteria: Presence of malignant arrhythmias such as ventricular fibrillation outside the acute phase of Acute myocardial infarction (AMI) (> 24 h after AMI), ventricular tachycardia, Atrioventricular block of 2nd degree and 3rd degree, Atrial fibrilation (FA) in patients with Wolf Parkinson White, fibrillation or paroxysmal atrial flutter with response ventricular quickly and hemodynamic deterioration, premature ventricular contractions increases during exertion, paroxysmal supraventricular tachycardia uncontrolled. Previous infarcts. Hypotensive response to exercise. Myocardial Ischemia valued at exercise test. Unstable Angina. Nonrevascularizable disease. Poorly controlled hypertension baseline. Killip III and IV Killip. No collaborator. Valvular heart disease associated. Pacemaker or Implantable Cardioverter Defibrillator. Pathology of musculoskeletal, neurological or breathing that impair the ability of prolonged ambulation.
Ages Eligible for Study
-----------------
Maximum Age: 80 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Homebased cardiac rehabilitation program<br>Homebased Cardiac rehabilitation program with monitoring vest and mixed surveillance. | Device: Homebased cardiac rehabilitation program<br>* homebased cardiac rehabilitation program with monitoring vest Nuubo<br>Other: Traditional cardiac rehabilitation program<br>* multidisciplinary intervention in cardiac rehabilitation gym<br>|
| Other: Traditional cardiac rehabilitation<br>Multidisciplinary program in a cardiac rehabilitation gym. Routine clinical practice | Other: Traditional cardiac rehabilitation program<br>* multidisciplinary intervention in cardiac rehabilitation gym<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness measured by exercise testing and control of cardiovascular risk factors | functional capacity obtained by exercise testing and control of cardiovascular risk factors. | During 12 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Results of homebased cardiac rehabilitation monitoring a traditional cardiac rehabilitation program | comparing the results of functional capacity measured by exercise testing and control of cardiovascular risk factors between the two groups | During 12 months |
| Adherence to these programs | see adherence to these program at 3, 6 months and a year depending on the habit of exercise and control of cardiovascular risk factors. | 3, 6 and 12 months |
| Safety to these program | See the safety of home cardiac rehabilitation program of mixed surveillance compared to traditional cardiac rehabilitation program to checking the existence of adverse cardiac events. | During 12 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
home monitoring, cardiac monitoring
|
NCT05620381
|
Health and Sleep Assessment After the Strasbourg Attacks of December 11, 2018
|
Evaluation of the prevalence of post-traumatic stress disorder (PTSD), associated risk factors, health care consumption, and sleep disorders in a civilian population exposed to the December 11, 2018, attacks in Strasbourg. Terrorist attacks have unfortunately become all too frequent on our territory in recent years. A better knowledge of the psychological and psychiatric repercussions on exposed populations is essential in order to better prevent and treat disorders that can have a major functional impact on the lives of exposed individuals and to adapt care during future similar events
|
Health and Sleep Assessment After the Strasbourg Attacks of December 11, 2018
|
Stress Disorders, Post-Traumatic
|
Inclusion criteria:~Major subject (≥ 18 years old),~Having been exposed to the attacks of December 11, 2018 in Strasbourg directly or indirectly (presence at the scene or close relative present at the scene)~Subject who has not expressed his opposition, after information, to the reuse of his data for the purpose of this research~Exclusion Criteria:~Subject who has expressed opposition to participating in the study~Subject under guardianship, curatorship or legal protection
|
18 Years
| null |
All
| null |
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retrospective evaluation of the prevalence of post-traumatic stress disorder (PTSD) in a population exposed to the attacks of December 11, 2018 in Strasbourg | | Files analysed retrospectively from February 11, 2018 to November 30, 2019 will be examined |
|
Stress Disorders, Disorders Post-Traumatic
|
Stress Disorders, Traumatic, Stress Disorders, Post-Traumatic, Trauma and Stressor Related Disorders, Mental Disorders
|
Health and Sleep Assessment After the Strasbourg Attacks of December 11, 2018
Study Overview
=================
Brief Summary
-----------------
Evaluation of the prevalence of post-traumatic stress disorder (PTSD), associated risk factors, health care consumption, and sleep disorders in a civilian population exposed to the December 11, 2018, attacks in Strasbourg. Terrorist attacks have unfortunately become all too frequent on our territory in recent years. A better knowledge of the psychological and psychiatric repercussions on exposed populations is essential in order to better prevent and treat disorders that can have a major functional impact on the lives of exposed individuals and to adapt care during future similar events
Official Title
-----------------
Health and Sleep Assessment After the Strasbourg Attacks of December 11, 2018
Conditions
-----------------
Stress Disorders, Post-Traumatic
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Major subject (≥ 18 years old), Having been exposed to the attacks of December 11, 2018 in Strasbourg directly or indirectly (presence at the scene or close relative present at the scene) Subject who has not expressed his opposition, after information, to the reuse of his data for the purpose of this research Exclusion Criteria: Subject who has expressed opposition to participating in the study Subject under guardianship, curatorship or legal protection
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retrospective evaluation of the prevalence of post-traumatic stress disorder (PTSD) in a population exposed to the attacks of December 11, 2018 in Strasbourg | | Files analysed retrospectively from February 11, 2018 to November 30, 2019 will be examined |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Stress Disorders, Disorders Post-Traumatic
|
|||||
NCT05054218
|
COVID-19 Immunogenicity of a Third Dose of mRNA-1273 Vaccine Among Cancer Patients
|
Investigators will evaluate the immunogenicity of a third dose of mRNA-1273 SARS-CoV-2 vaccine among cancer patients receiving the recommended third vaccine dose
|
Immunogenicity of a Third Dose of mRNA-1273 Vaccine (Moderna) Among Cancer Patients
|
Covid19, SARS-CoV2 Infection
|
* Biological: mRNA-1273
|
Inclusion Criteria:~At least 18 years of age~Is a cancer patient enrolled in the Cancer Patient Immune Response to COVID-19 Vaccine study (a basic science study) MCC 21138 or who has completed the two mRNA-1273 vaccine series prior to March 31, 2021.~Understands, agrees and is able to comply with the study procedures and provides written informed consent.~Has no known or suspected allergy or history of anaphylaxis, urticaria, or other significant adverse reactions to the vaccine or its excipients.~Has not received more or less than 2 doses of mRNA-1273 vaccine~Exclusion Criteria:~Participants who will not return for the third vaccine dose
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. The level of anti-SARS-CoV-2 Spike (S)-specific neutralizing antibody (nAb) 28 days post-dose 3 | The level of anti-SARS-CoV-2 Spike (S)-specific neutralizing antibody (nAb) up to study day 28 will be measured by specific neutralizing antibody and serum assays | 28 days |
| Anti-SARS-CoV-2 Spike (S)-specific neutralizing antibody (nAb) 6 months post-dose 3 | The level of anti-SARS-CoV-2 Spike (S)-specific neutralizing antibody (nAb) up to study month 6 will be measured by specific neutralizing antibody and serum assays | 6 months |
| Anti-SARS-CoV-2 Spike (S)-GMT Ab 28 days post-dose 3 | The level of anti-SARS-CoV-2 Spike (S)-GMT Ab up to study day 28 will be measured by specific neutralizing antibody and serum assays | 28 days |
| Anti-SARS-CoV-2 Spike (S)-GMT Ab 6 months post-dose 3 | The level of anti-SARS-CoV-2 Spike (S)-GMT Ab up to study month 6 will be measured by specific neutralizing antibody and serum assays | 6 months |
| Level antibodies that block the binding of ACE2 to RBD antigens from 10 SARS-CoV-2 variants of concern 28 days post-dose 3 | The level antibodies that block the binding of ACE2 to RBD antigens from 10 SARS-CoV-2 variants of concern up to study day 28 will be measured by specific neutralizing antibody and serum assays | 28 days |
| Level antibodies that block the binding of ACE2 to RBD antigens from 10 SARS-CoV-2 variants of concern 6 months post-dose 3 | The level antibodies that block the binding of ACE2 to RBD antigens from 10 SARS-CoV-2 variants of concern up to study month 6 will be measured by specific neutralizing antibody and serum assays | 6 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Solicited local and systemic adverse reactions (ARs) post-dose 3 up to study day 20 | Investigators will measure solicited local and systemic adverse reactions (ARs) at day 14 (+/- 5 days) post 3rd dose of vaccine | Up to 20 days |
| Solicited local and systemic adverse reactions (ARs) post-dose 3 up to study day 40 | Investigators will measure solicited local and systemic adverse reactions (ARs) at day 28 (+ 14 days) post 3rd dose of vaccine | Up to 42 days |
| Number of participants who experienced Serious Adverse Events and Adverse Events | Participants able to safely tolerate a 3rd dose of mRNA-1273 vaccine as measured by adverse events and serious adverse events. | Baseline thru up to 6 months |
|
Immunogenicity, Antibodies, Vaccine Adverse Events
|
COVID-19, Pneumonia, Viral, Pneumonia, 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 |
| --- | --- |
| Participants who receive 3rd dose of mRNA-1273 SARS-CoV-2 vaccine<br>Cancer patients who have already received their 1st and 2nd doses of mRNA-1273 SARS-CoV-2 vaccine will receive a 3rd dose of the vaccine. The volume of vaccine injected will be 0.5 mL, containing a 100-μg dose of mRNA-1273. | Biological: mRNA-1273<br>* Participants will receive a 0.5 mL injection of the vaccine that contains a 100-μg dose of mRNA1273. The vaccine will be administered into the deltoid muscle.<br>|
|
COVID-19 Immunogenicity of a Third Dose of mRNA-1273 Vaccine Among Cancer Patients
Study Overview
=================
Brief Summary
-----------------
Investigators will evaluate the immunogenicity of a third dose of mRNA-1273 SARS-CoV-2 vaccine among cancer patients receiving the recommended third vaccine dose
Official Title
-----------------
Immunogenicity of a Third Dose of mRNA-1273 Vaccine (Moderna) Among Cancer Patients
Conditions
-----------------
Covid19, SARS-CoV2 Infection
Intervention / Treatment
-----------------
* Biological: mRNA-1273
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: At least 18 years of age Is a cancer patient enrolled in the Cancer Patient Immune Response to COVID-19 Vaccine study (a basic science study) MCC 21138 or who has completed the two mRNA-1273 vaccine series prior to March 31, 2021. Understands, agrees and is able to comply with the study procedures and provides written informed consent. Has no known or suspected allergy or history of anaphylaxis, urticaria, or other significant adverse reactions to the vaccine or its excipients. Has not received more or less than 2 doses of mRNA-1273 vaccine Exclusion Criteria: Participants who will not return for the third vaccine dose
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 |
| --- | --- |
| Participants who receive 3rd dose of mRNA-1273 SARS-CoV-2 vaccine<br>Cancer patients who have already received their 1st and 2nd doses of mRNA-1273 SARS-CoV-2 vaccine will receive a 3rd dose of the vaccine. The volume of vaccine injected will be 0.5 mL, containing a 100-μg dose of mRNA-1273. | Biological: mRNA-1273<br>* Participants will receive a 0.5 mL injection of the vaccine that contains a 100-μg dose of mRNA1273. The vaccine will be administered into the deltoid muscle.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. The level of anti-SARS-CoV-2 Spike (S)-specific neutralizing antibody (nAb) 28 days post-dose 3 | The level of anti-SARS-CoV-2 Spike (S)-specific neutralizing antibody (nAb) up to study day 28 will be measured by specific neutralizing antibody and serum assays | 28 days |
| Anti-SARS-CoV-2 Spike (S)-specific neutralizing antibody (nAb) 6 months post-dose 3 | The level of anti-SARS-CoV-2 Spike (S)-specific neutralizing antibody (nAb) up to study month 6 will be measured by specific neutralizing antibody and serum assays | 6 months |
| Anti-SARS-CoV-2 Spike (S)-GMT Ab 28 days post-dose 3 | The level of anti-SARS-CoV-2 Spike (S)-GMT Ab up to study day 28 will be measured by specific neutralizing antibody and serum assays | 28 days |
| Anti-SARS-CoV-2 Spike (S)-GMT Ab 6 months post-dose 3 | The level of anti-SARS-CoV-2 Spike (S)-GMT Ab up to study month 6 will be measured by specific neutralizing antibody and serum assays | 6 months |
| Level antibodies that block the binding of ACE2 to RBD antigens from 10 SARS-CoV-2 variants of concern 28 days post-dose 3 | The level antibodies that block the binding of ACE2 to RBD antigens from 10 SARS-CoV-2 variants of concern up to study day 28 will be measured by specific neutralizing antibody and serum assays | 28 days |
| Level antibodies that block the binding of ACE2 to RBD antigens from 10 SARS-CoV-2 variants of concern 6 months post-dose 3 | The level antibodies that block the binding of ACE2 to RBD antigens from 10 SARS-CoV-2 variants of concern up to study month 6 will be measured by specific neutralizing antibody and serum assays | 6 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Solicited local and systemic adverse reactions (ARs) post-dose 3 up to study day 20 | Investigators will measure solicited local and systemic adverse reactions (ARs) at day 14 (+/- 5 days) post 3rd dose of vaccine | Up to 20 days |
| Solicited local and systemic adverse reactions (ARs) post-dose 3 up to study day 40 | Investigators will measure solicited local and systemic adverse reactions (ARs) at day 28 (+ 14 days) post 3rd dose of vaccine | Up to 42 days |
| Number of participants who experienced Serious Adverse Events and Adverse Events | Participants able to safely tolerate a 3rd dose of mRNA-1273 vaccine as measured by adverse events and serious adverse events. | Baseline thru up to 6 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immunogenicity, Antibodies, Vaccine Adverse Events
|
||
NCT02120911
|
Feasibility Study of Chemoradiation, TRAstuzumab and Pertuzumab in Resectable HER2+ Esophageal Carcinoma
|
Despite neoadjuvant chemoradiation regimens esophageal cancer remains a disease with poor outcome. The clinical benefit of HER2 targeting with trastuzumab has been shown in the setting of advanced disease and disease and safety of combining trastuzumab with chemoradiation in the curative setting has been established. In breast cancer, the added value of pertuzumab to standard treatment with trastuzumab has been shown both in the neoadjuvant and the metastastic setting. Taken together, there is a sound rationale to explore the combination of radiotherapy plus chemotherapy with trastuzumab and pertuzumab in HER2+resectable esophageal cancer. However, since the number of HER2+ patients in this setting is limited, and no data are available on the safety of this combination prior to major surgery, we propose to first conduct a feasibility study with this treatment stratgy. When the results of this study show that this treatment strategy is feasible, we will subsequently design a prospective study with efficacy as primary endpoint.
|
Objective of the study:~Assess the feasibility of preoperative treatment with pertuzumab and trastuzumab combined with preoperative chemoradiation (carboplatin, paclitaxel and radiation) in terms of withdrawal rate from surgery.~Study design:~This is a non-randomized feasibility study with Paclitaxel (T), Carboplatin (C), Pertuzumab (P). Trastuzumab (H), and radiation (RT) followed by surgical resection of the oesophagus.~Study population:~Patients (male/female) with histologically proven adenocarcinoma of the intrathoracic esophagus or gastro esophageal junction, age >18 and <75 years.~Intervention (if applicable):~Paclitaxel 50 mg/m2 and Carboplatin AUC = 2 will be given by intravenous infusion on days 1, 8, 15, 22 and 29.~Trastuzumab will be administered at a dose of 4 mg/kg on day 1, followed by 2 mg/kg at wk 2-6. From wk 7 onwards trastuzumab is administered at a dose of 6 mg/kg every 3 weeks. Pertuzumab will be given 840 mg intravenously at each administration.~Thus, trastuzumab and pertuzumab will be continued during eight weeks after the end of chemoradiation. Surgery will be planned in or around week 14, approximately eight weeks after the end of chemoradiation.
|
Feasibility Study of Chemoradiation, TRAstuzumab and Pertuzumab in Resectable HER2+Esophageal Carcinoma: the TRAP Study
|
Esophageal Carcinoma
|
* Drug: Pertuzumab, trastuzumab
|
Inclusion Criteria:~Histologically proven adenocarcinoma of the intrathoracic esophagus or gastro esophageal junction.~HER2-positive tumor defined as either IHC 3+ or IHC 2+, the latter in combination with ISH+, as assessed by the sponsor-designated central laboratory (pathology AMC) on a primary tumor biopsy.~Surgical resectable (T2-3, N0-1, M0), as determined by Endoscopic Ultra Sound (EUS) and CT scan of neck, thorax and abdomen.~T1N1 tumors are eligible, T1N0 tumors and in situ carcinoma are not eligible.~Tumor length longitudinal ≤ 10 cm and radial ≤ 5 cm.~If tumor extends below the gastroesophageal (GE) junction into the proximal stomach, the bulk of the tumor must involve the esophagus or GE junction. The tumor must not extend more than 2 cm into the stomach.~No invasion of the tracheobronchial tree or presence of tracheoesophageal fistula.~Age ≥ 18 and ≤ 75 years.~ECOG performance status 0 or 1.~Adequate hematological, renal and hepatic functions defined as:~neutrophiles ≥ 1.5 x 109/L~platelets ≥ 100 x 109/L~hemoglobin ≥ 5.6 mmol~total bilirubin ≤ 1.5 x upper normal limit~creatinine clearance (Cockroft) > 60 ml/min~Adequate left ventricular ejection fraction defined as an LVEF of ≥55%.~Written, voluntary informed consent.~Patients must be accessible to follow up and management in the treatment center.~Exclusion Criteria:~A tumour the epicenter of which in the stomach is greater than 5 cm of the GE junction or those within 5 cm of the GE junction without extension in the oesophagus are classified as gastric cancer.~Past or current history of malignancy other than entry diagnosis except for non-melanomatous skin cancer, or curatively treated in situ carcinoma of the cervix, or malignancy more than 5 years prior to enrollment.~Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation.~Patient (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment.~Previous chemotherapy, radiotherapy, treatment with an anti-HER2 antibody or with small molecule HER2 inhibitors.~Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before randomization.~Pulmonary fibrosis and/or severely impaired lung function.~Pre-existing motor or sensory neurotoxicity greater than WHO grade 1.~Active infection or other serious underlying medical condition which would impair the ability of the patient to receive the planned treatment, including prior allergic reactions to drugs containing Cremophor, such as teniposide or cyclosporine.~Dementia or altered mental status that would prohibit the understanding and giving of informed consent~Inadequate caloric- and/or fluid intake.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % of patients completing trastuzumab and pertuzumab treatment. | See title | up to 14 weeks after start of treatment |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity of pertuzumab and trastuzumab alone and in combination with chemoradiation | See title | up to 14 weeks after start of treatment |
| Number of post-operative complications | See title | up to 3 months after surgery |
| Pathological response | See title | up to 2 weeks after surgery |
| R0 resection rate | See title | up to 2 weeks after surgery |
| Pharmacokinetics of pertuzumab and trastuzumab | See title | up to 14 weeks after start of treatment |
|
Her2+, Resectable esophageal carcinoma, Pertuzumab, Trastuzumab
|
Trastuzumab, Pertuzumab, Antineoplastic Agents, Immunological, Antineoplastic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pertuzumab, trastuzumab<br>Pertuzumab, trastuzumab | Drug: Pertuzumab, trastuzumab<br>* Pertuzumab and trastuzumab will be combined with standard chemoradiation with carboplatin and paclitaxel.<br>* Other names: Herceptin;|
|
Feasibility Study of Chemoradiation, TRAstuzumab and Pertuzumab in Resectable HER2+ Esophageal Carcinoma
Study Overview
=================
Brief Summary
-----------------
Despite neoadjuvant chemoradiation regimens esophageal cancer remains a disease with poor outcome. The clinical benefit of HER2 targeting with trastuzumab has been shown in the setting of advanced disease and disease and safety of combining trastuzumab with chemoradiation in the curative setting has been established. In breast cancer, the added value of pertuzumab to standard treatment with trastuzumab has been shown both in the neoadjuvant and the metastastic setting. Taken together, there is a sound rationale to explore the combination of radiotherapy plus chemotherapy with trastuzumab and pertuzumab in HER2+resectable esophageal cancer. However, since the number of HER2+ patients in this setting is limited, and no data are available on the safety of this combination prior to major surgery, we propose to first conduct a feasibility study with this treatment stratgy. When the results of this study show that this treatment strategy is feasible, we will subsequently design a prospective study with efficacy as primary endpoint.
Detailed Description
-----------------
Objective of the study: Assess the feasibility of preoperative treatment with pertuzumab and trastuzumab combined with preoperative chemoradiation (carboplatin, paclitaxel and radiation) in terms of withdrawal rate from surgery. Study design: This is a non-randomized feasibility study with Paclitaxel (T), Carboplatin (C), Pertuzumab (P). Trastuzumab (H), and radiation (RT) followed by surgical resection of the oesophagus. Study population: Patients (male/female) with histologically proven adenocarcinoma of the intrathoracic esophagus or gastro esophageal junction, age >18 and <75 years. Intervention (if applicable): Paclitaxel 50 mg/m2 and Carboplatin AUC = 2 will be given by intravenous infusion on days 1, 8, 15, 22 and 29. Trastuzumab will be administered at a dose of 4 mg/kg on day 1, followed by 2 mg/kg at wk 2-6. From wk 7 onwards trastuzumab is administered at a dose of 6 mg/kg every 3 weeks. Pertuzumab will be given 840 mg intravenously at each administration. Thus, trastuzumab and pertuzumab will be continued during eight weeks after the end of chemoradiation. Surgery will be planned in or around week 14, approximately eight weeks after the end of chemoradiation.
Official Title
-----------------
Feasibility Study of Chemoradiation, TRAstuzumab and Pertuzumab in Resectable HER2+Esophageal Carcinoma: the TRAP Study
Conditions
-----------------
Esophageal Carcinoma
Intervention / Treatment
-----------------
* Drug: Pertuzumab, trastuzumab
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically proven adenocarcinoma of the intrathoracic esophagus or gastro esophageal junction. HER2-positive tumor defined as either IHC 3+ or IHC 2+, the latter in combination with ISH+, as assessed by the sponsor-designated central laboratory (pathology AMC) on a primary tumor biopsy. Surgical resectable (T2-3, N0-1, M0), as determined by Endoscopic Ultra Sound (EUS) and CT scan of neck, thorax and abdomen. T1N1 tumors are eligible, T1N0 tumors and in situ carcinoma are not eligible. Tumor length longitudinal ≤ 10 cm and radial ≤ 5 cm. If tumor extends below the gastroesophageal (GE) junction into the proximal stomach, the bulk of the tumor must involve the esophagus or GE junction. The tumor must not extend more than 2 cm into the stomach. No invasion of the tracheobronchial tree or presence of tracheoesophageal fistula. Age ≥ 18 and ≤ 75 years. ECOG performance status 0 or 1. Adequate hematological, renal and hepatic functions defined as: neutrophiles ≥ 1.5 x 109/L platelets ≥ 100 x 109/L hemoglobin ≥ 5.6 mmol total bilirubin ≤ 1.5 x upper normal limit creatinine clearance (Cockroft) > 60 ml/min Adequate left ventricular ejection fraction defined as an LVEF of ≥55%. Written, voluntary informed consent. Patients must be accessible to follow up and management in the treatment center. Exclusion Criteria: A tumour the epicenter of which in the stomach is greater than 5 cm of the GE junction or those within 5 cm of the GE junction without extension in the oesophagus are classified as gastric cancer. Past or current history of malignancy other than entry diagnosis except for non-melanomatous skin cancer, or curatively treated in situ carcinoma of the cervix, or malignancy more than 5 years prior to enrollment. Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation. Patient (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment. Previous chemotherapy, radiotherapy, treatment with an anti-HER2 antibody or with small molecule HER2 inhibitors. Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before randomization. Pulmonary fibrosis and/or severely impaired lung function. Pre-existing motor or sensory neurotoxicity greater than WHO grade 1. Active infection or other serious underlying medical condition which would impair the ability of the patient to receive the planned treatment, including prior allergic reactions to drugs containing Cremophor, such as teniposide or cyclosporine. Dementia or altered mental status that would prohibit the understanding and giving of informed consent Inadequate caloric- and/or fluid intake.
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: Pertuzumab, trastuzumab<br>Pertuzumab, trastuzumab | Drug: Pertuzumab, trastuzumab<br>* Pertuzumab and trastuzumab will be combined with standard chemoradiation with carboplatin and paclitaxel.<br>* Other names: Herceptin;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % of patients completing trastuzumab and pertuzumab treatment. | See title | up to 14 weeks after start of treatment |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity of pertuzumab and trastuzumab alone and in combination with chemoradiation | See title | up to 14 weeks after start of treatment |
| Number of post-operative complications | See title | up to 3 months after surgery |
| Pathological response | See title | up to 2 weeks after surgery |
| R0 resection rate | See title | up to 2 weeks after surgery |
| Pharmacokinetics of pertuzumab and trastuzumab | See title | up to 14 weeks after start of treatment |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Her2+, Resectable esophageal carcinoma, Pertuzumab, Trastuzumab
|
NCT02094391
|
Trial of Ipilimumab After Isolated Limb Perfusion, in Patients With Metastases Melanoma
|
Isolated limb perfusion (ILP) results in good response rates for locally advanced melanoma (stage IIIB and IIIC, AJCC 2009). Outcome is influenced by stage of disease, reflecting the aggressiveness of the melanoma. Our objective is to demonstrate at least a doubling of the progression free survival for the patients having an adjuvant treatment by Ipilimumab in this patient population with unfavourable characteristics. PFS ranges from 10-12 months. So at least a doubling of this period would be a clinically highly significant result.
|
A Randomized, Open Label, Multicenter, Comparative Phase II Trial of Ipilimumab After Isolated Limb Perfusion (ILP), in Patients With In-transit Metastases Melanoma Stage IIIB and IIIC
|
In-transit Metastases Melanoma Stage IIIB and IIIC
|
* Drug: Ipilimumab
|
Inclusion Criteria:~Patients with melanoma IT-metastases localized on limb not accessible to a surgical treatment associated or not with regional node metastases (stage IIIB or IIIC: TxN2c or N3) ;~Age above 18 years, no upper limit ;~Evaluable disease according to the RECIST 1.1 criteria ;~ECOG performance status 0-1 ;~Previous specific treatments (chemotherapy, immunotherapy) for the melanoma must be stopped before the inclusion with a wash out period of 3 weeks at least ;~Adequate hematologic, renal and liver function as defined by laboratory values below performed within 4-6 weeks from enrolment :~White blood count (WBC) greater than or equal to 2.5x109/L~Absolute neutrophil count (ANC) greater than or equal to 1x109/L~Platelet count greater than or equal to 75x109/L~Hemoglobin greater than or equal to 9 g/dL (5.6 mmol/L)~Serum creatinine less or equal to 2.5 times upper limit of laboratory normal (ULN)~ASAT and ALAT < 2 ULN~Calcaemia < 12 mg/dl (2.99 mmol/l)~Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug. Both men and women enrolled in this trial must use adequate contraception during the treatment phase of the study and for 1 months afterwards ;~Information of the patient and signature of the informed consent.~Exclusion Criteria:~Surgical resectable tumor and metastatic patients (stage IV) ;~Significant cardiovascular disease, e.g congestive heart failure (NYHA Class II, III or IV), severe angina pectoris, cardiac arrhythmias not controlled, myocardial infarction within a 3 months period prior to inclusion, venous thrombosis, occlusive peripheral arterial disease, recent pulmonary embolism ;~Severe lymphoedema of the limb ;~Patients with contraindications to limb hyperthermia ;~Contraindication for the use of vasopressin, anticoagulants, radioactive tracer monitoring ;~Prior hypersensibility to melphalan and/or tasonermin ;~Prior treatment by Ipilimumab or anti PD1 and PDL1 therapies ;~Severe pulmonary dysfunction ;~Recent history or active peptic ulcer, severe ascites ;~Simultaneous treatment with cardiotoxic substances (e.g anthracyclines) ;~Uncontrolled deep sepsis ;~Pregnancy or breast-feeding ;~Person deprived of his rights or under guardianship ;~Impossibility to submit to the medical follow-up of the trial for geographical, social or psychic reasons ;~History of autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids or patients with history of significant and symptomatic autoimmune disease ;~Chronic steroids > 10 mg/day or chronic immunosuppressive treatment ;~Uncontrolled infectious disease including positive testing for HIV, HBV, HCV ;~No second malignancies in the past 5 years with the exception of surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin.~Patients in whom the blood supply to the extremity distal to the tumour is suspected to be highly dependent on tumour associated blood vessels. This should be clarified by a Doppler ultrasound.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression, local progression or distant progression | | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 9 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | patients who are alive at the time of an analysis will be censored for survival at the time of their last contact | from randomization to documentation of death due to any cause or the last known alive date up to 24 months |
|
Ipilimumab, Antineoplastic Agents, Immunological, Antineoplastic Agents, Immune Checkpoint Inhibitors, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ipilimumab<br> | Drug: Ipilimumab<br>* Ipilimumab is to be administered as an IV infusion with a 1.2μm in-line filter (see current version of Investigator's Brochure), using a volumetric pump, at the 3 mg/kg dose, at the ratio and rate specified in the pharmacy manual, to complete the infusion in 90 minutes with a 100 cc normal saline flush at the end. The total dose needed should be diluted to a total volume of 250 mL in 0.9% sodium chloride injection, USP or 5% Dextrose Injection, USP.. The total dose must be calculated using the most recent subject weight (obtained on the same day of, and prior to, the infusion). If the patient weighs more than 125,0 kg, the Coordinating Investigator needs to be contacted to discuss the total infusion volume, infusion rate and duration. Ipilimumab 3 mg/kg will be administered as a single dose intravenously over 90 minutes every 3 weeks for 4 cycles (Weeks W1, W4, W7, W10). A time interval of +/- 3 days is allowed for Ipilimumab administration.<br>|
| No Intervention: No Ipilimumab<br> | |
|
Trial of Ipilimumab After Isolated Limb Perfusion, in Patients With Metastases Melanoma
Study Overview
=================
Brief Summary
-----------------
Isolated limb perfusion (ILP) results in good response rates for locally advanced melanoma (stage IIIB and IIIC, AJCC 2009). Outcome is influenced by stage of disease, reflecting the aggressiveness of the melanoma. Our objective is to demonstrate at least a doubling of the progression free survival for the patients having an adjuvant treatment by Ipilimumab in this patient population with unfavourable characteristics. PFS ranges from 10-12 months. So at least a doubling of this period would be a clinically highly significant result.
Official Title
-----------------
A Randomized, Open Label, Multicenter, Comparative Phase II Trial of Ipilimumab After Isolated Limb Perfusion (ILP), in Patients With In-transit Metastases Melanoma Stage IIIB and IIIC
Conditions
-----------------
In-transit Metastases Melanoma Stage IIIB and IIIC
Intervention / Treatment
-----------------
* Drug: Ipilimumab
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with melanoma IT-metastases localized on limb not accessible to a surgical treatment associated or not with regional node metastases (stage IIIB or IIIC: TxN2c or N3) ; Age above 18 years, no upper limit ; Evaluable disease according to the RECIST 1.1 criteria ; ECOG performance status 0-1 ; Previous specific treatments (chemotherapy, immunotherapy) for the melanoma must be stopped before the inclusion with a wash out period of 3 weeks at least ; Adequate hematologic, renal and liver function as defined by laboratory values below performed within 4-6 weeks from enrolment : White blood count (WBC) greater than or equal to 2.5x109/L Absolute neutrophil count (ANC) greater than or equal to 1x109/L Platelet count greater than or equal to 75x109/L Hemoglobin greater than or equal to 9 g/dL (5.6 mmol/L) Serum creatinine less or equal to 2.5 times upper limit of laboratory normal (ULN) ASAT and ALAT < 2 ULN Calcaemia < 12 mg/dl (2.99 mmol/l) Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug. Both men and women enrolled in this trial must use adequate contraception during the treatment phase of the study and for 1 months afterwards ; Information of the patient and signature of the informed consent. Exclusion Criteria: Surgical resectable tumor and metastatic patients (stage IV) ; Significant cardiovascular disease, e.g congestive heart failure (NYHA Class II, III or IV), severe angina pectoris, cardiac arrhythmias not controlled, myocardial infarction within a 3 months period prior to inclusion, venous thrombosis, occlusive peripheral arterial disease, recent pulmonary embolism ; Severe lymphoedema of the limb ; Patients with contraindications to limb hyperthermia ; Contraindication for the use of vasopressin, anticoagulants, radioactive tracer monitoring ; Prior hypersensibility to melphalan and/or tasonermin ; Prior treatment by Ipilimumab or anti PD1 and PDL1 therapies ; Severe pulmonary dysfunction ; Recent history or active peptic ulcer, severe ascites ; Simultaneous treatment with cardiotoxic substances (e.g anthracyclines) ; Uncontrolled deep sepsis ; Pregnancy or breast-feeding ; Person deprived of his rights or under guardianship ; Impossibility to submit to the medical follow-up of the trial for geographical, social or psychic reasons ; History of autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids or patients with history of significant and symptomatic autoimmune disease ; Chronic steroids > 10 mg/day or chronic immunosuppressive treatment ; Uncontrolled infectious disease including positive testing for HIV, HBV, HCV ; No second malignancies in the past 5 years with the exception of surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin. Patients in whom the blood supply to the extremity distal to the tumour is suspected to be highly dependent on tumour associated blood vessels. This should be clarified by a Doppler ultrasound.
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: Ipilimumab<br> | Drug: Ipilimumab<br>* Ipilimumab is to be administered as an IV infusion with a 1.2μm in-line filter (see current version of Investigator's Brochure), using a volumetric pump, at the 3 mg/kg dose, at the ratio and rate specified in the pharmacy manual, to complete the infusion in 90 minutes with a 100 cc normal saline flush at the end. The total dose needed should be diluted to a total volume of 250 mL in 0.9% sodium chloride injection, USP or 5% Dextrose Injection, USP.. The total dose must be calculated using the most recent subject weight (obtained on the same day of, and prior to, the infusion). If the patient weighs more than 125,0 kg, the Coordinating Investigator needs to be contacted to discuss the total infusion volume, infusion rate and duration. Ipilimumab 3 mg/kg will be administered as a single dose intravenously over 90 minutes every 3 weeks for 4 cycles (Weeks W1, W4, W7, W10). A time interval of +/- 3 days is allowed for Ipilimumab administration.<br>|
| No Intervention: No Ipilimumab<br> | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression, local progression or distant progression | | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 9 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | patients who are alive at the time of an analysis will be censored for survival at the time of their last contact | from randomization to documentation of death due to any cause or the last known alive date up to 24 months |
|
||
NCT00424996
|
Utility of Heidelberg Retina Tomograph in Monitoring Glaucoma Progression
|
Glaucoma is a chronic disease defined by characteristic changes in the optic nerve associated initially with loss of peripheral vision and is treated by lowering intraocular (inside the eye) pressure. It has been reported that noticeable changes to the optic nerve caused by glaucoma may occur several years before changes in vision are noticed. Since changes to the optic nerve and other eye structures due to glaucoma are irreversible, it is important to develop tools for the earliest possible detection of changes due to glaucoma.~The Heidelberg Retina Tomograph (HRT) is a device that is used to produce a three-dimensional map of the optic nerve and retina, and can be used to detect changes in the optic nerve and retina over time. In previous studies, it has been shown to be useful for the detection of changes due to glaucoma. However, the HRT when compared to other techniques to evaluate the optic nerve such as stereophotography, was found to only somewhat agree.~The current study will compare HRT to stereophotography to determine how good each one is at looking and documenting changes in the optic nerve over time due to glaucoma. Using HRT to initiate early topical medication or to change management requires knowing how well HRT results predict the development of visual loss. Accordingly, the results of this study may affect the management of glaucoma patients by optimizing the follow-up of people with this condition and by initiating appropriate and more individualized treatments. Early treatment is crucial for preventing further visual loss in patients with glaucoma or ocular hypertension (high pressure inside the eye).
|
In glaucoma, treatment decisions depend on the development of morphologic and functional damage. Therefore, damage serves as an indicator of management. Commonly, progression is determined by various perimetric techniques.~However, it has been reported that clinically detectable glaucomatous structural alteration of the ONH may precede the development of reproducible white on white and blue on yellow visual field defects by up to several years.~The HRT is a confocal scanning laser tomography device that creates a three-dimensional topographic analysis of the ONH and the peripapillary retina and includes a statistical analysis to evaluate structural change over time.~This technique showed good sensitivity and high specificity in detecting glaucoma progression when tested using computer simulation. The same good results were obtained by the same authors, in another study, in a small subgroup of 16 patients who were monitored for glaucomatous progression by both HRT and ONH stereophotographs for approximately 5.5 years.~However, in our recent retrospective study, our results demonstrated only fair agreement between HRT and clinical judgment of ONH stereophotographs for progression in glaucoma, for a mean follow-up time with HRT of 2.62 years. Although, the evaluation of the ONH stereophotographs is necessarily subjective, it is widely accepted and has been shown to be effective for evaluating change. Using the stereophotographs assessments as the reference standard, the HRT sensitivity was 78% and the specificity to 70%. The positive predictive value of the HRT was 47.8%, while the negative predictive value was 90.3%.~According to the results of this study if the frequency of true positives and false positives does not change with longer follow-up, treatment decisions would be based on a test that may be in error 52.2% of the time.~Accordingly, our previous - and other studies - study demonstrated only fair agreement between HRT and clinical judgment of ONH stereophotographs for progression in glaucoma. At present, the available evidence does not appear to be sufficient to show that the addition of HRT improves the ability to predict the development of clinical optic disc change and/or visual field loss.~Therefore the aim of the current study is to investigate the clinical significance of the HRT in monitoring glaucoma progression. In other words we will investigate how well HRT results for glaucomatous progression are able to predict the future development of optic disc and/or visual field changes in patients with OHT and glaucoma.
|
Utility of Heidelberg Retina Tomograph in Monitoring Glaucoma Progression
|
Glaucoma, Ocular Hypertension
|
Inclusion Criteria:~Best-corrected visual acuity of 20/40 or better~Subjects determined to have OHT or glaucoma~Spherical refraction within 6.0 D with plus or minus sphere, and cylinder within 3.0 D with plus or minus cylinder~Subjects that show progression on the HRT~subjects stable on ONH stereophotographs~subjects with stable and reliable visual fields~Subjects willing to make the required visits for the study~Subjects tolerant to dilating drops~Exclusion Criteria:~A suspicion or actual defect in the visual field of the eye being tested that is explained by the patient's ocular status or history, other than glaucoma~Any history of disease or use of medication that may affect visual field reliability~Past history of stroke or diabetic retinopathy~Inability of the pupils to be dilated to at least 4 mm for the screening visit~Inability to undergo either perimetry test or the ophthalmic examination~Inability to undergo adequate or better quality stereophotographs
|
20 Years
|
80 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retinal tomography | Journal of OphthalmologyVolume 2014 (2014), Article ID 987389, 12 pageshttp://dx.doi.org/10.1155/2014/987389 Clinical Significance of Optic Disc Progression by Topographic Change Analysis Maps in Glaucoma: An 8-Year Follow-Up Study D. Kourkoutas,1 Y. M. Buys,2 J. G. Flanagan,2 N. Karamaounas,1 G. Georgopoulos,3 E. Iliakis,3 M. M. Moschos,3 and G. E. Trope2 | 8 year study |
|
Glaucoma, Ocular Hypertension, Eye Diseases
|
Utility of Heidelberg Retina Tomograph in Monitoring Glaucoma Progression
Study Overview
=================
Brief Summary
-----------------
Glaucoma is a chronic disease defined by characteristic changes in the optic nerve associated initially with loss of peripheral vision and is treated by lowering intraocular (inside the eye) pressure. It has been reported that noticeable changes to the optic nerve caused by glaucoma may occur several years before changes in vision are noticed. Since changes to the optic nerve and other eye structures due to glaucoma are irreversible, it is important to develop tools for the earliest possible detection of changes due to glaucoma. The Heidelberg Retina Tomograph (HRT) is a device that is used to produce a three-dimensional map of the optic nerve and retina, and can be used to detect changes in the optic nerve and retina over time. In previous studies, it has been shown to be useful for the detection of changes due to glaucoma. However, the HRT when compared to other techniques to evaluate the optic nerve such as stereophotography, was found to only somewhat agree. The current study will compare HRT to stereophotography to determine how good each one is at looking and documenting changes in the optic nerve over time due to glaucoma. Using HRT to initiate early topical medication or to change management requires knowing how well HRT results predict the development of visual loss. Accordingly, the results of this study may affect the management of glaucoma patients by optimizing the follow-up of people with this condition and by initiating appropriate and more individualized treatments. Early treatment is crucial for preventing further visual loss in patients with glaucoma or ocular hypertension (high pressure inside the eye).
Detailed Description
-----------------
In glaucoma, treatment decisions depend on the development of morphologic and functional damage. Therefore, damage serves as an indicator of management. Commonly, progression is determined by various perimetric techniques. However, it has been reported that clinically detectable glaucomatous structural alteration of the ONH may precede the development of reproducible white on white and blue on yellow visual field defects by up to several years. The HRT is a confocal scanning laser tomography device that creates a three-dimensional topographic analysis of the ONH and the peripapillary retina and includes a statistical analysis to evaluate structural change over time. This technique showed good sensitivity and high specificity in detecting glaucoma progression when tested using computer simulation. The same good results were obtained by the same authors, in another study, in a small subgroup of 16 patients who were monitored for glaucomatous progression by both HRT and ONH stereophotographs for approximately 5.5 years. However, in our recent retrospective study, our results demonstrated only fair agreement between HRT and clinical judgment of ONH stereophotographs for progression in glaucoma, for a mean follow-up time with HRT of 2.62 years. Although, the evaluation of the ONH stereophotographs is necessarily subjective, it is widely accepted and has been shown to be effective for evaluating change. Using the stereophotographs assessments as the reference standard, the HRT sensitivity was 78% and the specificity to 70%. The positive predictive value of the HRT was 47.8%, while the negative predictive value was 90.3%. According to the results of this study if the frequency of true positives and false positives does not change with longer follow-up, treatment decisions would be based on a test that may be in error 52.2% of the time. Accordingly, our previous - and other studies - study demonstrated only fair agreement between HRT and clinical judgment of ONH stereophotographs for progression in glaucoma. At present, the available evidence does not appear to be sufficient to show that the addition of HRT improves the ability to predict the development of clinical optic disc change and/or visual field loss. Therefore the aim of the current study is to investigate the clinical significance of the HRT in monitoring glaucoma progression. In other words we will investigate how well HRT results for glaucomatous progression are able to predict the future development of optic disc and/or visual field changes in patients with OHT and glaucoma.
Official Title
-----------------
Utility of Heidelberg Retina Tomograph in Monitoring Glaucoma Progression
Conditions
-----------------
Glaucoma, Ocular Hypertension
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Best-corrected visual acuity of 20/40 or better Subjects determined to have OHT or glaucoma Spherical refraction within 6.0 D with plus or minus sphere, and cylinder within 3.0 D with plus or minus cylinder Subjects that show progression on the HRT subjects stable on ONH stereophotographs subjects with stable and reliable visual fields Subjects willing to make the required visits for the study Subjects tolerant to dilating drops Exclusion Criteria: A suspicion or actual defect in the visual field of the eye being tested that is explained by the patient's ocular status or history, other than glaucoma Any history of disease or use of medication that may affect visual field reliability Past history of stroke or diabetic retinopathy Inability of the pupils to be dilated to at least 4 mm for the screening visit Inability to undergo either perimetry test or the ophthalmic examination Inability to undergo adequate or better quality stereophotographs
Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 80 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retinal tomography | Journal of OphthalmologyVolume 2014 (2014), Article ID 987389, 12 pageshttp://dx.doi.org/10.1155/2014/987389 Clinical Significance of Optic Disc Progression by Topographic Change Analysis Maps in Glaucoma: An 8-Year Follow-Up Study D. Kourkoutas,1 Y. M. Buys,2 J. G. Flanagan,2 N. Karamaounas,1 G. Georgopoulos,3 E. Iliakis,3 M. M. Moschos,3 and G. E. Trope2 | 8 year study |
|
|||||
NCT03372382
|
Ibuprofen and Acetaminophen Versus Ibuprofen and Acetaminophen Plus Hydrocodone for Analgesia After Cesarean Section
|
Postpartum patients delivered by cesarean section will be randomized to NSAIDS Vs NSAIDS plus opioid
|
Women will be approached priors to discharge from the hospital, if they meet inclusion criteria and consent for the study, they will be randomized to one of two possible analgesic regimens. They will be followed at 1-2 weeks and 4-6 weeks after discharge to assess pain level.
|
Ibuprofen and Acetaminophen Versus Ibuprofen and Acetaminophen Plus Hydrocodone for Analgesia After Cesarean Section: A Prospective, Randomized Control Trial
|
Opioid Use, Pain, Postoperative
|
* Drug: Ibuprofen
* Drug: Acetaminophen
* Drug: Norco
|
Inclusion Criteria:~English or Spanish speaker women who had a cesarean section~Exclusion Criteria:~Inability or refusal to provide informed consent.~Reported current or prior opioid or benzodiazepine use disorder, including urine drug screen positive for a non prescribed opioid or benzodiazepine upon admission or during prenatal care.~Current treatment with methadone, buprenorphine or buprenorphine plus naloxone.~Known alcoholism disorder.~Severe renal or hepatic impairment.~Known creatinine > 1.5 at the time of delivery or severe proteinuria leading to diagnosis of renal disease prior to delivery.~Severe peptic ulcer disease~Severe asthma (if patient has asthma but has previously tolerated NSAIDS, she will be allowed to participate)~Known CYP450/CY92D6 mutation conferring opioid ultra-rapid metabolizer status.~Allergy to any of the study drugs (anaphylaxis).~Incarcerated or institutionalized patients.~Inability to follow up as outpatient in our outpatient clinic.~wound dehiscence or infection diagnosed prior to discharge from the hospital~wound vac placed prior to discharge from the hospital
|
18 Years
|
50 Years
|
Female
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: two parallel groups included, randomized to control analgesic regimen versus alternative analgesic regimen and followed prospectively.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Level | pain level measured by objective and subjective scales.~1- Objective scale: visual analogue pain score (VAS). It is a 100 mm line, patients will be instructed to mark a point in the line that represents their pain level. A point towards the left will mean less pain and a point towards the right will mean more pain. After the patient makes a selection, the research team will measure where the selected point is (in cm). minimum measurement =0mm = no pain. maximum measurement=100mm=worst pain. | 2-4 weeks postpartum |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Satisfaction | patient satisfaction as measured by the following scale: 1(very dissatisfied) 2(somewhat dissatisfied) 3(neutral) 4(satisfied) 5(very satisfied) | 2-4 weeks postpartum |
|
postpartum
|
Antipyretics, Acetaminophen, Ibuprofen, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anti-Inflammatory Agents, Non-Steroidal, Anti-Inflammatory Agents, Antirheumatic Agents, Cyclooxygenase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ibuprofen plus acetaminophen<br>women that had a C-section will be discharged home with prescriptions for ibuprofen and acetaminophen | Drug: Ibuprofen<br>* NSAID<br>Drug: Acetaminophen<br>* analgesic<br>|
| Experimental: ibuprofen plus acetaminophen/hydrocodone<br>women that had a C-section will be discharged home with prescriptions for ibuprofen and acetaminophen/hydrocodone (Norco) | Drug: Ibuprofen<br>* NSAID<br>Drug: Norco<br>* acetaminophen plus opioid<br>|
|
Ibuprofen and Acetaminophen Versus Ibuprofen and Acetaminophen Plus Hydrocodone for Analgesia After Cesarean Section
Study Overview
=================
Brief Summary
-----------------
Postpartum patients delivered by cesarean section will be randomized to NSAIDS Vs NSAIDS plus opioid
Detailed Description
-----------------
Women will be approached priors to discharge from the hospital, if they meet inclusion criteria and consent for the study, they will be randomized to one of two possible analgesic regimens. They will be followed at 1-2 weeks and 4-6 weeks after discharge to assess pain level.
Official Title
-----------------
Ibuprofen and Acetaminophen Versus Ibuprofen and Acetaminophen Plus Hydrocodone for Analgesia After Cesarean Section: A Prospective, Randomized Control Trial
Conditions
-----------------
Opioid Use, Pain, Postoperative
Intervention / Treatment
-----------------
* Drug: Ibuprofen
* Drug: Acetaminophen
* Drug: Norco
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: English or Spanish speaker women who had a cesarean section Exclusion Criteria: Inability or refusal to provide informed consent. Reported current or prior opioid or benzodiazepine use disorder, including urine drug screen positive for a non prescribed opioid or benzodiazepine upon admission or during prenatal care. Current treatment with methadone, buprenorphine or buprenorphine plus naloxone. Known alcoholism disorder. Severe renal or hepatic impairment. Known creatinine > 1.5 at the time of delivery or severe proteinuria leading to diagnosis of renal disease prior to delivery. Severe peptic ulcer disease Severe asthma (if patient has asthma but has previously tolerated NSAIDS, she will be allowed to participate) Known CYP450/CY92D6 mutation conferring opioid ultra-rapid metabolizer status. Allergy to any of the study drugs (anaphylaxis). Incarcerated or institutionalized patients. Inability to follow up as outpatient in our outpatient clinic. wound dehiscence or infection diagnosed prior to discharge from the hospital wound vac placed prior to discharge from the hospital
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: two parallel groups included, randomized to control analgesic regimen versus alternative analgesic regimen and followed prospectively.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ibuprofen plus acetaminophen<br>women that had a C-section will be discharged home with prescriptions for ibuprofen and acetaminophen | Drug: Ibuprofen<br>* NSAID<br>Drug: Acetaminophen<br>* analgesic<br>|
| Experimental: ibuprofen plus acetaminophen/hydrocodone<br>women that had a C-section will be discharged home with prescriptions for ibuprofen and acetaminophen/hydrocodone (Norco) | Drug: Ibuprofen<br>* NSAID<br>Drug: Norco<br>* acetaminophen plus opioid<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Level | pain level measured by objective and subjective scales. 1- Objective scale: visual analogue pain score (VAS). It is a 100 mm line, patients will be instructed to mark a point in the line that represents their pain level. A point towards the left will mean less pain and a point towards the right will mean more pain. After the patient makes a selection, the research team will measure where the selected point is (in cm). minimum measurement =0mm = no pain. maximum measurement=100mm=worst pain. | 2-4 weeks postpartum |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Satisfaction | patient satisfaction as measured by the following scale: 1(very dissatisfied) 2(somewhat dissatisfied) 3(neutral) 4(satisfied) 5(very satisfied) | 2-4 weeks postpartum |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
postpartum
|
NCT02111057
|
Perioperative Flare in RA: Characterization of Clinical and Biological Features
|
Researchers at the Hospital for Special Surgery are trying to learn more about post-operative rheumatoid arthritis flare (RA). This study hopes to understand RA flare after total joint replacement surgery and what the result of flaring is for patients over the 6 weeks post operation.~Through this study we aim to describe rates, characteristics, and risk factors of RA flare within 6 weeks of total hip arthroplasty (THA) and total knee arthroplasty (TKA)
|
The condition to be studied is worsening (flare) of rheumatoid arthritis (RA) in patients who have undergone arthroplasty. RA patients were recruited prior to elective THA and TKA and prospectively followed. Clinicians evaluated RA clinical characteristics 0-2 weeks before and 6 weeks post surgery. Patients answered questions regarding disease activity including self-reported joint counts and flare status weekly for 6 weeks.
|
Perioperative Flare in RA: Characterization of Clinical and Biological Features
|
Rheumatoid Arthritis
|
Inclusion Criteria:~Age >18~Patients with Rheumatoid Arthritis undergoing total joint replacement surgery~Satisfy American College of Rheumatology(ACR)/European League Against Rheumatism(EULAR) 2010 classification criteria and/or the 1987 RA criteria (see below) and be diagnosed with RA~For control subjects: Have OA(Osteoarthritis), SLE(Systemic lupus erythematosus) or other inflammatory arthritis.~Exclusion Criteria:~Diagnosis of any other systemic rheumatic disease~Diagnosis of or crystalline arthropathy.~Unable to understand or read English.~Unable to follow the study protocol in a reliable manner.~Age < 18 or >75.~EXPLANATION OF CRITERIA:~Rheumatoid arthritis 1987 criteria:~morning stiffness in and around joints lasting at least 1 hour before maximal improvement;~soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician;~swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints;~symmetric swelling (arthritis);~rheumatoid nodules;~the presence of rheumatoid factor; and~radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints.~Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required.~ACR/EULAR 2010 criteria for the classification of RA:~Table 3. The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis~Target population (Who should be tested?): Patients who~have at least 1 joint with definite clinical synovitis (swelling)*~with the synovitis not better explained by another disease~Classification criteria for RA (score-based algorithm: add score of categories A-D;~a score of ≥6/10 is needed for classification of a patient as having definite RA~Score~A. Joint involvement~1 large joint 0~2-10 large joints 1~1-3 small joints (with or without involvement of large joints) 2~4-10 small joints (with or without involvement of large joints) 3~>10 joints (at least 1 small joint) 5~B. Serology (at least 1 test result is needed for classification)~Negative RF and negative ACPA 0~Low-positive RF or low-positive ACPA 2~High-positive RF or high-positive ACPA 3~C. Acute-phase reactants (at least 1 test result is needed for classification)~Normal CRP and normal ESR 0~Abnormal CRP or abnormal ESR 1~D. Duration of symptoms~< 6 weeks 0~6 weeks 1~The criteria are aimed at classification of newly presenting patients. In addition, patients with erosive disease typical of rheumatoid arthritis (RA) with a history compatible with prior fulfillment of the 2010 criteria should be classified as having RA. Patients with longstanding disease, including those whose disease is inactive (with or without treatment) who, based on retrospectively available data, have previously fulfilled the 2010 criteria should be classified as having RA.
|
18 Years
|
90 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of RA Flare at 6 week post surgery | The primary outcome is the rate of RA flare within 6 weeks of surgery as measured by the Outcome Measures in Rheumatoid Arthritis Clinical Trials(OMERACT) flare questionnaire. For comparison, the rate of RA flare at 1 week post surgery is measured. | 6 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity and impact of flares 6 weeks and one year post arthroplasty, using the OMERACT PFQs | The OMERACT PFQs include flare intensity, duration of flare, worsening of domains associated with flare (pain, fatigue, stiffness, patient reported tender and swollen joint count, difficulties with coping and participation). | 6 weeks and one year |
|
Perioperative Outcomes, Rheumatoid Arthritis, Total Hip Replacement, Flare
|
Arthritis, Arthritis, Rheumatoid, Joint Diseases, Musculoskeletal Diseases, Rheumatic Diseases, Connective Tissue Diseases, Autoimmune Diseases, Immune System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Perioperative RA<br>Patients with Rheumatoid Arthritis undergoing a primary or secondary total hip replacement, between the ages of 18 and 90. | |
|
Perioperative Flare in RA: Characterization of Clinical and Biological Features
Study Overview
=================
Brief Summary
-----------------
Researchers at the Hospital for Special Surgery are trying to learn more about post-operative rheumatoid arthritis flare (RA). This study hopes to understand RA flare after total joint replacement surgery and what the result of flaring is for patients over the 6 weeks post operation. Through this study we aim to describe rates, characteristics, and risk factors of RA flare within 6 weeks of total hip arthroplasty (THA) and total knee arthroplasty (TKA)
Detailed Description
-----------------
The condition to be studied is worsening (flare) of rheumatoid arthritis (RA) in patients who have undergone arthroplasty. RA patients were recruited prior to elective THA and TKA and prospectively followed. Clinicians evaluated RA clinical characteristics 0-2 weeks before and 6 weeks post surgery. Patients answered questions regarding disease activity including self-reported joint counts and flare status weekly for 6 weeks.
Official Title
-----------------
Perioperative Flare in RA: Characterization of Clinical and Biological Features
Conditions
-----------------
Rheumatoid Arthritis
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age >18 Patients with Rheumatoid Arthritis undergoing total joint replacement surgery Satisfy American College of Rheumatology(ACR)/European League Against Rheumatism(EULAR) 2010 classification criteria and/or the 1987 RA criteria (see below) and be diagnosed with RA For control subjects: Have OA(Osteoarthritis), SLE(Systemic lupus erythematosus) or other inflammatory arthritis. Exclusion Criteria: Diagnosis of any other systemic rheumatic disease Diagnosis of or crystalline arthropathy. Unable to understand or read English. Unable to follow the study protocol in a reliable manner. Age < 18 or >75. EXPLANATION OF CRITERIA: Rheumatoid arthritis 1987 criteria: morning stiffness in and around joints lasting at least 1 hour before maximal improvement; soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; symmetric swelling (arthritis); rheumatoid nodules; the presence of rheumatoid factor; and radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. ACR/EULAR 2010 criteria for the classification of RA: Table 3. The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis Target population (Who should be tested?): Patients who have at least 1 joint with definite clinical synovitis (swelling)* with the synovitis not better explained by another disease Classification criteria for RA (score-based algorithm: add score of categories A-D; a score of ≥6/10 is needed for classification of a patient as having definite RA Score A. Joint involvement 1 large joint 0 2-10 large joints 1 1-3 small joints (with or without involvement of large joints) 2 4-10 small joints (with or without involvement of large joints) 3 >10 joints (at least 1 small joint) 5 B. Serology (at least 1 test result is needed for classification) Negative RF and negative ACPA 0 Low-positive RF or low-positive ACPA 2 High-positive RF or high-positive ACPA 3 C. Acute-phase reactants (at least 1 test result is needed for classification) Normal CRP and normal ESR 0 Abnormal CRP or abnormal ESR 1 D. Duration of symptoms < 6 weeks 0 6 weeks 1 The criteria are aimed at classification of newly presenting patients. In addition, patients with erosive disease typical of rheumatoid arthritis (RA) with a history compatible with prior fulfillment of the 2010 criteria should be classified as having RA. Patients with longstanding disease, including those whose disease is inactive (with or without treatment) who, based on retrospectively available data, have previously fulfilled the 2010 criteria should be classified as having RA.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Perioperative RA<br>Patients with Rheumatoid Arthritis undergoing a primary or secondary total hip replacement, between the ages of 18 and 90. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of RA Flare at 6 week post surgery | The primary outcome is the rate of RA flare within 6 weeks of surgery as measured by the Outcome Measures in Rheumatoid Arthritis Clinical Trials(OMERACT) flare questionnaire. For comparison, the rate of RA flare at 1 week post surgery is measured. | 6 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity and impact of flares 6 weeks and one year post arthroplasty, using the OMERACT PFQs | The OMERACT PFQs include flare intensity, duration of flare, worsening of domains associated with flare (pain, fatigue, stiffness, patient reported tender and swollen joint count, difficulties with coping and participation). | 6 weeks and one year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Perioperative Outcomes, Rheumatoid Arthritis, Total Hip Replacement, Flare
|
||
NCT04791410
|
Clinical Study on the Efficacy of Microvascular Decompression in the Treatment of Neurogenic Hypertension
|
Hypertension has always been a threat to human health, so the prevention and treatment is of great significance. At present, the treatment of primary hypertension is mainly drug treatment, but many patients can not control their blood pressure in the normal range. Therefore, it is urgent to explore new and effective treatment methods.~Microvascular compression type of neurogenic hypertension is mainly due to abnormal tortuous vascular pulsatile compression of blood pressure center - rostral ventrolateral medulla (RVLM), resulting in the release of sympathetic active substances, leading to hypertension. The purpose of this study is to explore the efficacy and safety of microvascular decompression for hypertension in patients of hemifacial spasm complicated with hypertension, and to explore the common characteristics of patients with effective decompression.~The type of study design was prospective cohort study. According to certain inclusion and exclusion criteria, patients with RVLM compression were treated with RVLM decompression at the same time of facial nerve decompression. Patients who were followed up for 3 months were taken as control group, and the blood pressure of the two groups were measured after 3 months. The main outcome measure was 24-hour ambulatory systolic blood pressure change from baseline to 3 months.
|
Research steps: If the patients with hemifacial spasm are complicated with hypertension and have the intention of surgical treatment, researchers would introduce the process, possible benefits and possible complications of the clinical trial in detail. Patients who agree to be enrolled and meet the inclusion conditions will sign the informed consent form.~The history of hypertension, the relationship between hypertension and hemifacial spasm, the highest blood pressure, oral medication, blood pressure maintenance, whether complicated with dyslipidemia, diabetes, smoking history, etc. Before operation, 24-hour ambulatory blood pressure monitoring was performed to record preoperative systolic blood pressure, diastolic blood pressure and heart rate. The measurement interval is automatically measured every 20 minutes in the daytime (8:00am ~ 10:00pm) and every 30 minutes at night (10:00pm ~ 8:00am). CBP was recorded in the morning (8:00-10:00 AM) before taking medication, and completed in the morning of 8:00-9:00 am the next day. The cuff was placed on the left upper arm. During the monitoring period, the patient was required to reduce the movement of the left upper arm as much as possible to avoid the cuff loosening or falling off, which would affect the measurement results. The record of effective monitoring times must be more than 80% and the covering time must be more than 20h, otherwise the measurement should be repeated. Patients should rest for at least 5 minutes before blood pressure measurement. The upper arm was placed at the heart level. Using OMRON electronic sphygmomanometer, the size of the cuff is suitable for the patient's upper arm circumference, covering at least 2 / 3 of the upper arm circumference. The blood pressure of both upper arms was measured, and the blood pressure of the higher side was taken as the criterion. Repeat the measurement at an interval of 1-2 min, and record the average value of the two readings. If the difference between the two readings of systolic or diastolic blood pressure is more than 5 mmHg, it should be measured again, and the average of the three readings should be taken as the baseline blood pressure measurement result.~Both the experimental group and the control group need to continue to take antihypertensive drugs orally, and the type and dose of drugs remain unchanged.~The experimental group was hospitalized and completed the corresponding hematology and imaging examination. The control group was followed up for 3 months, after the end of the follow-up can be hospitalized and improve the corresponding hematology and imaging examination. If the control group matched with the experimental group is excluded, the control group needs to be rematched. The experimental group received RVLM and (or) IX / X rez decompression at the same time of facial nerve decompression, while the control group received no operation.~Follow up: Patients should be followed up at 3 months. The following items were evaluated and recorded in CRF during follow-up~Physical examination;~Laboratory examination;~Vital signs (heart rate, respiration);~Ambulatory blood pressure examination~Office blood pressure~Antihypertensive medication: the patient's blood pressure and the use of antihypertensive drugs were closely monitored after the operation, and the adjustment time, the type and dosage of antihypertensive drugs after the adjustment were recorded when making adjustments according to the blood pressure and the cardiologist's suggestions.~Postoperative adverse reactions and duration / remission time: adverse reactions such as dizziness, headache, nausea and vomiting, tinnitus, hearing loss, diplopia, facial paralysis, drinking water cough and hoarseness. The above adverse reactions can be recovered in a few days after the operation. The duration of adverse reactions should be recorded and relieved in a few days after the operation.~Postoperative adverse events: such as patient death, acute cardiovascular events (such as cardiac arrest, ventricular fibrillation, myocardial infarction and hypertensive crisis), severe anesthesia or surgical complications (such as long-term mechanical ventilation due to inability to remove endotracheal intubation, pulmonary embolism, postoperative cerebral hemorrhage, severe intracranial infection), etc.~Statistical analysis: SPSS software was used to analyze the follow-up results of the intervention group and the control group. The general statistical test uses the two-sided test, and the one-sided test needs to be explained. P value less than or equal to 0.05 was used to judge whether the difference was statistically significant. The description of quantitative indicators will calculate the mean, standard deviation, median, quartile, minimum and maximum. The classification index is described by the number and percentage of cases. The demographic characteristics, general situation and baseline (before treatment) of the three groups were compared. Among them, t test was used for measurement data and chi square test was used for grade data. Binary logistic regression was used to further verify the influence of age, gender, side, BMI, family history of hypertension and changes of serum catecholamine on the effect of microvascular decompression in the treatment of neurogenic hypertension.
|
Clinical Study on the Efficacy of Microvascular Decompression in the Treatment of Neurogenic Hypertension
|
Neurogenic Hypertension, Hypertension, Surgery
|
* Procedure: microvascular decompression
|
Inclusion Criteria:~Age ≥ 18 years old;~Preoperative MRI showed RVLM compression;~Primary hemifacial spasm without other secondary factors;~The office systolic blood pressure is higher than 140mmHg and the systolic blood pressure of ambulatory blood pressure is higher than 130mmHg;~Sign informed consent.~Exclusion Criteria:~Secondary hypertension, such as renal hypertension, vascular hypertension, etc;~No antihypertensive drugs were taken after admission and ambulatory blood pressure monitoring showed that the blood pressure was within the normal range;~Pregnancy plan or lactation period during pregnancy or within 2 years;~Patients with congestive heart failure (NYHA grade II-IV), myocardial infarction and unstable angina pectoris within 6 months before enrollment; patients with severe heart diseases, such as cardiogenic shock, arrhythmia requiring treatment, heart valve disease, etc;~Severe cerebrovascular diseases (hypertensive encephalopathy, cerebrovascular injury, stroke, transient ischemic attack, etc.) within 6 months before admission;~Patients with severe liver disease or dysfunction (ALT or AST > 2 times the upper limit of normal reference value);~Patients with renal impairment (male serum creatinine > 2.0mg/dl (176 μ mol / L), female serum creatinine > 1.8mg/dl (159 μ mol / L));~Other surgical contraindications, such as coagulation disorders, severe anemia, severe pulmonary infection, persistent state of asthma, upper respiratory tract infection, uncorrected respiratory failure, diabetic ketoacidosis, hepatic encephalopathy, hepatic coma, acute cerebral infarction, etc;~Type I diabetic patients; diabetic patients with poor glycemic control (FBG > 11.1 mmol / L) or type 2 diabetic patients with microalbuminuria;~Had Cushing's syndrome, coarctation of aorta, hyperthyroidism and other diseases in the past;~Patients can not cooperate with the test and follow-up, such as mental disorders, dementia, advanced tumor, etc;~If the antihypertensive drugs were adjusted within 2 weeks before admission, the patients were excluded or re enrolled after the blood pressure was stable for 2 weeks;~Preoperative anesthesia score ≥ grade III;~To screen those who participated in other clinical studies and used research drugs within 3 months before the trial, or planned to participate in other clinical studies during the trial period.
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decreased systolic blood pressure | After 3 months of treatment, 24 h ambulatory blood pressure was measured, systolic blood pressure was compared with baseline level, and the difference was calculated. | 3 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decreased diastolic blood pressure | After 3 months of treatment, 24 h ambulatory blood pressure was measured, diastolic blood pressure was compared with baseline level, and the difference was calculated. | 3 months |
| Decreased office systolic blood pressure | After 3 months of treatment, office blood pressure was measured, systolic blood pressure was compared with baseline level, and the difference was calculated. | 3 months |
| Decreased office diastolic blood pressure | After 3 months of treatment, office blood pressure was measured, diastolic blood pressure was compared with baseline level, and the difference was calculated. | 3 months |
| The cure rate of hypertension 3 months after treatment | | 3 months |
| effective rate of hypertension 3 months after treatment | | 3 months |
|
neurogenic hypertension, microvascular decompression, hemifacial spasm
|
Hypertension, Vascular Diseases, Cardiovascular Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental group<br>patients who met the inclusion criteria were treated with RVLM decompression at the same time of facial nerve decompression. | Procedure: microvascular decompression<br>* Microvascular decompression of rostral ventrolateral medulla<br>|
| control group<br>Patients who met the inclusion criteria were followed up for 3 months before surgery | |
|
Clinical Study on the Efficacy of Microvascular Decompression in the Treatment of Neurogenic Hypertension
Study Overview
=================
Brief Summary
-----------------
Hypertension has always been a threat to human health, so the prevention and treatment is of great significance. At present, the treatment of primary hypertension is mainly drug treatment, but many patients can not control their blood pressure in the normal range. Therefore, it is urgent to explore new and effective treatment methods. Microvascular compression type of neurogenic hypertension is mainly due to abnormal tortuous vascular pulsatile compression of blood pressure center - rostral ventrolateral medulla (RVLM), resulting in the release of sympathetic active substances, leading to hypertension. The purpose of this study is to explore the efficacy and safety of microvascular decompression for hypertension in patients of hemifacial spasm complicated with hypertension, and to explore the common characteristics of patients with effective decompression. The type of study design was prospective cohort study. According to certain inclusion and exclusion criteria, patients with RVLM compression were treated with RVLM decompression at the same time of facial nerve decompression. Patients who were followed up for 3 months were taken as control group, and the blood pressure of the two groups were measured after 3 months. The main outcome measure was 24-hour ambulatory systolic blood pressure change from baseline to 3 months.
Detailed Description
-----------------
Research steps: If the patients with hemifacial spasm are complicated with hypertension and have the intention of surgical treatment, researchers would introduce the process, possible benefits and possible complications of the clinical trial in detail. Patients who agree to be enrolled and meet the inclusion conditions will sign the informed consent form. The history of hypertension, the relationship between hypertension and hemifacial spasm, the highest blood pressure, oral medication, blood pressure maintenance, whether complicated with dyslipidemia, diabetes, smoking history, etc. Before operation, 24-hour ambulatory blood pressure monitoring was performed to record preoperative systolic blood pressure, diastolic blood pressure and heart rate. The measurement interval is automatically measured every 20 minutes in the daytime (8:00am 10:00pm) and every 30 minutes at night (10:00pm 8:00am). CBP was recorded in the morning (8:00-10:00 AM) before taking medication, and completed in the morning of 8:00-9:00 am the next day. The cuff was placed on the left upper arm. During the monitoring period, the patient was required to reduce the movement of the left upper arm as much as possible to avoid the cuff loosening or falling off, which would affect the measurement results. The record of effective monitoring times must be more than 80% and the covering time must be more than 20h, otherwise the measurement should be repeated. Patients should rest for at least 5 minutes before blood pressure measurement. The upper arm was placed at the heart level. Using OMRON electronic sphygmomanometer, the size of the cuff is suitable for the patient's upper arm circumference, covering at least 2 / 3 of the upper arm circumference. The blood pressure of both upper arms was measured, and the blood pressure of the higher side was taken as the criterion. Repeat the measurement at an interval of 1-2 min, and record the average value of the two readings. If the difference between the two readings of systolic or diastolic blood pressure is more than 5 mmHg, it should be measured again, and the average of the three readings should be taken as the baseline blood pressure measurement result. Both the experimental group and the control group need to continue to take antihypertensive drugs orally, and the type and dose of drugs remain unchanged. The experimental group was hospitalized and completed the corresponding hematology and imaging examination. The control group was followed up for 3 months, after the end of the follow-up can be hospitalized and improve the corresponding hematology and imaging examination. If the control group matched with the experimental group is excluded, the control group needs to be rematched. The experimental group received RVLM and (or) IX / X rez decompression at the same time of facial nerve decompression, while the control group received no operation. Follow up: Patients should be followed up at 3 months. The following items were evaluated and recorded in CRF during follow-up Physical examination; Laboratory examination; Vital signs (heart rate, respiration); Ambulatory blood pressure examination Office blood pressure Antihypertensive medication: the patient's blood pressure and the use of antihypertensive drugs were closely monitored after the operation, and the adjustment time, the type and dosage of antihypertensive drugs after the adjustment were recorded when making adjustments according to the blood pressure and the cardiologist's suggestions. Postoperative adverse reactions and duration / remission time: adverse reactions such as dizziness, headache, nausea and vomiting, tinnitus, hearing loss, diplopia, facial paralysis, drinking water cough and hoarseness. The above adverse reactions can be recovered in a few days after the operation. The duration of adverse reactions should be recorded and relieved in a few days after the operation. Postoperative adverse events: such as patient death, acute cardiovascular events (such as cardiac arrest, ventricular fibrillation, myocardial infarction and hypertensive crisis), severe anesthesia or surgical complications (such as long-term mechanical ventilation due to inability to remove endotracheal intubation, pulmonary embolism, postoperative cerebral hemorrhage, severe intracranial infection), etc. Statistical analysis: SPSS software was used to analyze the follow-up results of the intervention group and the control group. The general statistical test uses the two-sided test, and the one-sided test needs to be explained. P value less than or equal to 0.05 was used to judge whether the difference was statistically significant. The description of quantitative indicators will calculate the mean, standard deviation, median, quartile, minimum and maximum. The classification index is described by the number and percentage of cases. The demographic characteristics, general situation and baseline (before treatment) of the three groups were compared. Among them, t test was used for measurement data and chi square test was used for grade data. Binary logistic regression was used to further verify the influence of age, gender, side, BMI, family history of hypertension and changes of serum catecholamine on the effect of microvascular decompression in the treatment of neurogenic hypertension.
Official Title
-----------------
Clinical Study on the Efficacy of Microvascular Decompression in the Treatment of Neurogenic Hypertension
Conditions
-----------------
Neurogenic Hypertension, Hypertension, Surgery
Intervention / Treatment
-----------------
* Procedure: microvascular decompression
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years old; Preoperative MRI showed RVLM compression; Primary hemifacial spasm without other secondary factors; The office systolic blood pressure is higher than 140mmHg and the systolic blood pressure of ambulatory blood pressure is higher than 130mmHg; Sign informed consent. Exclusion Criteria: Secondary hypertension, such as renal hypertension, vascular hypertension, etc; No antihypertensive drugs were taken after admission and ambulatory blood pressure monitoring showed that the blood pressure was within the normal range; Pregnancy plan or lactation period during pregnancy or within 2 years; Patients with congestive heart failure (NYHA grade II-IV), myocardial infarction and unstable angina pectoris within 6 months before enrollment; patients with severe heart diseases, such as cardiogenic shock, arrhythmia requiring treatment, heart valve disease, etc; Severe cerebrovascular diseases (hypertensive encephalopathy, cerebrovascular injury, stroke, transient ischemic attack, etc.) within 6 months before admission; Patients with severe liver disease or dysfunction (ALT or AST > 2 times the upper limit of normal reference value); Patients with renal impairment (male serum creatinine > 2.0mg/dl (176 μ mol / L), female serum creatinine > 1.8mg/dl (159 μ mol / L)); Other surgical contraindications, such as coagulation disorders, severe anemia, severe pulmonary infection, persistent state of asthma, upper respiratory tract infection, uncorrected respiratory failure, diabetic ketoacidosis, hepatic encephalopathy, hepatic coma, acute cerebral infarction, etc; Type I diabetic patients; diabetic patients with poor glycemic control (FBG > 11.1 mmol / L) or type 2 diabetic patients with microalbuminuria; Had Cushing's syndrome, coarctation of aorta, hyperthyroidism and other diseases in the past; Patients can not cooperate with the test and follow-up, such as mental disorders, dementia, advanced tumor, etc; If the antihypertensive drugs were adjusted within 2 weeks before admission, the patients were excluded or re enrolled after the blood pressure was stable for 2 weeks; Preoperative anesthesia score ≥ grade III; To screen those who participated in other clinical studies and used research drugs within 3 months before the trial, or planned to participate in other clinical studies during the trial period.
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 |
| --- | --- |
| Experimental group<br>patients who met the inclusion criteria were treated with RVLM decompression at the same time of facial nerve decompression. | Procedure: microvascular decompression<br>* Microvascular decompression of rostral ventrolateral medulla<br>|
| control group<br>Patients who met the inclusion criteria were followed up for 3 months before surgery | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decreased systolic blood pressure | After 3 months of treatment, 24 h ambulatory blood pressure was measured, systolic blood pressure was compared with baseline level, and the difference was calculated. | 3 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decreased diastolic blood pressure | After 3 months of treatment, 24 h ambulatory blood pressure was measured, diastolic blood pressure was compared with baseline level, and the difference was calculated. | 3 months |
| Decreased office systolic blood pressure | After 3 months of treatment, office blood pressure was measured, systolic blood pressure was compared with baseline level, and the difference was calculated. | 3 months |
| Decreased office diastolic blood pressure | After 3 months of treatment, office blood pressure was measured, diastolic blood pressure was compared with baseline level, and the difference was calculated. | 3 months |
| The cure rate of hypertension 3 months after treatment | | 3 months |
| effective rate of hypertension 3 months after treatment | | 3 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
neurogenic hypertension, microvascular decompression, hemifacial spasm
|
|
NCT00409084
|
Beta Blockers Versus Variceal Band Ligation and Beta Blockers for Primary Prophylaxis of Variceal Bleeding
|
Patients with scarring of the liver (cirrhosis) and portal hypertension (elevated blood pressure in the liver vasculature) can develop esophageal varices (dilated veins). These have an increased risk of bleeding each year. Current recommendations are to prevent bleeding of medium or large varices (when there is no history of bleeding) by starting a blood pressure lowering agent known as a non-selective beta-blocker. Alternatively, rubber bands can be placed on medium to large varices to prevent bleeding (endoscopic variceal band ligation). Using both therapies at the same time has not been studied. In this study, we hope to determine if the use of combination therapy with endoscopic variceal band ligation and beta blockers is more effective than using beta blockers alone to prevent the first bleeding episode from the varices (dilated veins). The efficacy, ability to tolerate, and cost-effectiveness of these two treatment strategies will be compared.
|
Beta Blockers Versus Variceal Band Ligation and Beta Blockers for Primary Prophylaxis of Variceal Bleeding
|
Esophageal Varices
|
* Procedure: endoscopic variceal band ligation
|
Inclusion Criteria:~cirrhosis~medium to large varices~Exclusion Criteria:~contraindications to beta blockers~refusal to give consent~prior history of variceal hemorrhage~creatinine > 1.5 mg/dl
|
18 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| first variceal bleed | | 2 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| survival | | 2 years |
| liver function | | 1 year |
| encephalopathy | | 1 year |
| quality of life | | 1 year |
| frequency of other complications of cirrhosis | | 2 years |
| cost utility | | 1 year |
| patient preference | | 1 year |
|
varices, band ligation, portal hypertension, primary prophylaxis, cirrhosis, beta blockers
|
Esophageal and Gastric Varices, Esophageal Diseases, Gastrointestinal Diseases, Digestive System Diseases, Hypertension, Portal, Liver Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>endoscopic variceal band ligation | Procedure: endoscopic variceal band ligation<br>* endoscopic variceal band ligation<br>|
| Active Comparator: 2<br>subjects will receive nadolol (beta blocker) at 20mg/day with dose titration | Procedure: endoscopic variceal band ligation<br>* endoscopic variceal band ligation<br>|
|
Beta Blockers Versus Variceal Band Ligation and Beta Blockers for Primary Prophylaxis of Variceal Bleeding
Study Overview
=================
Brief Summary
-----------------
Patients with scarring of the liver (cirrhosis) and portal hypertension (elevated blood pressure in the liver vasculature) can develop esophageal varices (dilated veins). These have an increased risk of bleeding each year. Current recommendations are to prevent bleeding of medium or large varices (when there is no history of bleeding) by starting a blood pressure lowering agent known as a non-selective beta-blocker. Alternatively, rubber bands can be placed on medium to large varices to prevent bleeding (endoscopic variceal band ligation). Using both therapies at the same time has not been studied. In this study, we hope to determine if the use of combination therapy with endoscopic variceal band ligation and beta blockers is more effective than using beta blockers alone to prevent the first bleeding episode from the varices (dilated veins). The efficacy, ability to tolerate, and cost-effectiveness of these two treatment strategies will be compared.
Official Title
-----------------
Beta Blockers Versus Variceal Band Ligation and Beta Blockers for Primary Prophylaxis of Variceal Bleeding
Conditions
-----------------
Esophageal Varices
Intervention / Treatment
-----------------
* Procedure: endoscopic variceal band ligation
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: cirrhosis medium to large varices Exclusion Criteria: contraindications to beta blockers refusal to give consent prior history of variceal hemorrhage creatinine > 1.5 mg/dl
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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>endoscopic variceal band ligation | Procedure: endoscopic variceal band ligation<br>* endoscopic variceal band ligation<br>|
| Active Comparator: 2<br>subjects will receive nadolol (beta blocker) at 20mg/day with dose titration | Procedure: endoscopic variceal band ligation<br>* endoscopic variceal band ligation<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| first variceal bleed | | 2 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| survival | | 2 years |
| liver function | | 1 year |
| encephalopathy | | 1 year |
| quality of life | | 1 year |
| frequency of other complications of cirrhosis | | 2 years |
| cost utility | | 1 year |
| patient preference | | 1 year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
varices, band ligation, portal hypertension, primary prophylaxis, cirrhosis, beta blockers
|
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