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NCT04311489
|
Refractory Ascites in Patients With Liver Cirrhosis, and the Potential Treatment With 48 Hours Infusion of Ularitide.
|
This clinical trial intends to investigate the safety, tolerability and efficacy of ularitide on the renal response in patients with liver cirrhosis and refractory ascites for a maximum exposure duration of 48 hours, through a randomized, placebo-controlled, double-blind, single-center trial.
|
The investigators hypothesize that ularitide infusion is more effective than placebo to induce and maintain clinically meaningful natriuresis and diuresis in patients with liver cirrhosis and refractory ascites.~Participants will be given ularitide or placebo intravenously while hospitalized at Department of Hepatology and Gastroenterology at Aarhus University Hospital. During the hospitalization blood and urine samples are frequently collected.~30 ng/kg/min is the starting dosage for all participants. Depending on effects and/or side effects, ULA04 is designed to individualize treatment doses by up- and/or downtitration of the infusion dose within a predefined dose range. Relevant safety precautions are incorporated in the study design and treatment will be prematurely discontinued if a pre-defined stopping criteria presents.~Patients will be followed up for the appearance of serious adverse events 30 days after the treatment.~If a separate written consent is given by the participants, additional blood and urine samples will be collected and stored in a biobank for future research.
|
Single-center, Randomized, Double-blind, Placebo-controlled Clinical Trial for the Safety, Tolerability and Efficacy of Ularitide in Cirrhosis Patients With Refractory Ascites.
|
Cirrhosis, Liver, Ascites Hepatic
|
* Drug: Ularitide
* Drug: Placebo
|
Inclusion Criteria:~Men and women >18 years~Liver cirrhosis confirmed by fibroscan (>20 kPa), or by imaging with signs of an irregular liver surface with collaterals, or clinically by cirrhosis stigmata~Refractory ascites Definition: failure to respond to or intolerance to high dose diuretics (spironolactone up to 400mg/day and furosemide up to 160mg/day) and early ascites recurrence (reappearance of grade 2 or 3 ascites within 4 weeks of initial mobilization or ≥2 paracentesis within last 3 months)~Urine sodium excretion <60 mmol/24 hour~Serum creatinine <150 µmol/L~Child-Turcotte-Pugh score of B or C (<13)~Bilirubin <150 µmol/L~Prothrombin time (PP) 0.20-0.60 (INR 1.3-2.5)~Systolic blood pressure ≥95 mmHg~Written informed consent to participate in the clinical trial~Exclusion Criteria:~Gastrointestinal bleeding within 2 weeks prior to inclusion~Proteinuria >500 mg/day~Hemoglobin <5.5 mmol/L~Spontaneous bacterial peritonitis within 2 weeks prior to inclusion~Loculated ascites~Hepatic encephalopathy grade 2-4 (West-Haven classification)~Obstructive uropathy~Primary kidney disease~Known diagnosis of congestive heart failure~Known diagnosis of acute-on-chronic liver failure~Known diagnosis of systemic inflammatory response syndrome~Acute infections by known diagnosis and/or antibiotic treatment~Known HIV infection~Known allergy to the investigational drug or other natriuretic peptides~Treatment with dobutamine, levosimendan, milrinone, any phosphodiesterase inhibitor, octreotide, midodrine, vasopressin, dopamine or other vasopressors within 2 weeks prior to inclusion~Nephrotoxic drugs within 1 month prior to inclusion~Fertile women not using contraception, either an intrauterine device or hormonal contraception~Positive pregnancy test in pre-menopausal women or in breast-feeding women~Participation in an interventional clinical drug trial within 1 month prior to inclusion~Legal incapacity or limited legal capacity~Patients who are employees or relatives of the investigator
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled clinical trial
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute and relative change in sodium excretion rate. | | After 24 hours and at termination of treatment (up to 48 hours) |
| Absolute and relative change in urine volume. | | After 24 hours and at termination of treatment (up to 48 hours) |
| Change of absolute body weight. | | At termination of treatment (up to 48 hours) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of responders in the ularitide group versus the placebo group, defined by: | Urine volume increase of ≥100 % versus baseline, urine volume increase ≥50 % versus baseline, natriuresis increase by ≥100 % versus baseline and/or body weight reduction by ≥2 kg versus baseline. | Throughout the treatment period. Latest measure at termination of treatment (up to 48 hours) |
| Absolute and relative change in sodium excretion rate. | | After 2 hours and 4 hours of treatment and at 6 hours post-treatment follow-up |
| Absolute and relative change in urine volume. | | After 2 hours and 4 hours of treatment and at 6 hours post-treatment follow-up |
| Absolute and relative change in plasma cyclic guanosine monophosphate (cGMP) concentration. | | Throughout the treatment period. Latest measure at 6 hours post-treatment follow-up |
| Absolute and relative change in waist circumference. | | After 24 hours and at termination of treatment (up to 48 hours) |
| Absolute and relative change in serum creatinine. | | After 24 hours and at termination of treatment (up to 48 hours) |
| Absolute and relative change in estimated glomerular filtration rate (eGFR). | | After 24 hours and at termination of treatment (up to 48 hours) |
| Absolute and relative change in plasma and urine osmolalities. | | Throughout the treatment period. Latest measure at 6 hours post-treatment follow-up |
| Absolute and relative change in GFR-24h-Crea (Glomerular filtration rate based on 24-hour creatinine clearance). | | After 24 hours and 48 hours of treatment |
| Absolute and relative change in hematocrit. | | After 24 hours and 48 hours of treatment and at 6 hours post-treatment follow-up |
| Absolute and relative change in plasma copeptin concentration. | | After 24 hours and 48 hours of treatment and at 6 hours post-treatment follow-up |
| Absolute and relative change in plasma renin concentration. | | After 24 hours and 48 hours of treatment and at 6 hours post-treatment follow-up |
| Absolute and relative change in plasma angiotensin concentration. | | After 24 hours and 48 hours of treatment and at 6 hours post-treatment follow-up |
| Absolute and relative change in plasma aldosterone concentration. | | After 24 hours and 48 hours of treatment and at 6 hours post-treatment follow-up |
|
Cirrhosis, Ascites, Refractory ascites, Natriuresis, Diuresis, Urodilatin, Ularitide, natriuretic peptide
|
Ularitide, Bronchodilator Agents, Autonomic Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anti-Asthmatic Agents, Respiratory System Agents, Diuretics, Natriuretic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ularitide<br>Test product. Continuous intravenous infusion with 30 ng/kg/min for 48 hours. | Drug: Ularitide<br>* Continuous intravenous infusion for 48 hours at a dose of 30 ng/kg/min. Depending on effect and/or side effects dose can be adjusted to 15 ng/kg/min or 45 ng/kg/min.<br>* Other names: Urodilatin;|
| Placebo Comparator: Placebo<br>Matching placebo. Continuous IV infusion for 48 hours. | Drug: Placebo<br>* Continuous intravenous infusion for 48 hours at a bodyweight-adjusted infusion rate.<br>|
|
Refractory Ascites in Patients With Liver Cirrhosis, and the Potential Treatment With 48 Hours Infusion of Ularitide.
Study Overview
=================
Brief Summary
-----------------
This clinical trial intends to investigate the safety, tolerability and efficacy of ularitide on the renal response in patients with liver cirrhosis and refractory ascites for a maximum exposure duration of 48 hours, through a randomized, placebo-controlled, double-blind, single-center trial.
Detailed Description
-----------------
The investigators hypothesize that ularitide infusion is more effective than placebo to induce and maintain clinically meaningful natriuresis and diuresis in patients with liver cirrhosis and refractory ascites. Participants will be given ularitide or placebo intravenously while hospitalized at Department of Hepatology and Gastroenterology at Aarhus University Hospital. During the hospitalization blood and urine samples are frequently collected. 30 ng/kg/min is the starting dosage for all participants. Depending on effects and/or side effects, ULA04 is designed to individualize treatment doses by up- and/or downtitration of the infusion dose within a predefined dose range. Relevant safety precautions are incorporated in the study design and treatment will be prematurely discontinued if a pre-defined stopping criteria presents. Patients will be followed up for the appearance of serious adverse events 30 days after the treatment. If a separate written consent is given by the participants, additional blood and urine samples will be collected and stored in a biobank for future research.
Official Title
-----------------
Single-center, Randomized, Double-blind, Placebo-controlled Clinical Trial for the Safety, Tolerability and Efficacy of Ularitide in Cirrhosis Patients With Refractory Ascites.
Conditions
-----------------
Cirrhosis, Liver, Ascites Hepatic
Intervention / Treatment
-----------------
* Drug: Ularitide
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women >18 years Liver cirrhosis confirmed by fibroscan (>20 kPa), or by imaging with signs of an irregular liver surface with collaterals, or clinically by cirrhosis stigmata Refractory ascites Definition: failure to respond to or intolerance to high dose diuretics (spironolactone up to 400mg/day and furosemide up to 160mg/day) and early ascites recurrence (reappearance of grade 2 or 3 ascites within 4 weeks of initial mobilization or ≥2 paracentesis within last 3 months) Urine sodium excretion <60 mmol/24 hour Serum creatinine <150 µmol/L Child-Turcotte-Pugh score of B or C (<13) Bilirubin <150 µmol/L Prothrombin time (PP) 0.20-0.60 (INR 1.3-2.5) Systolic blood pressure ≥95 mmHg Written informed consent to participate in the clinical trial Exclusion Criteria: Gastrointestinal bleeding within 2 weeks prior to inclusion Proteinuria >500 mg/day Hemoglobin <5.5 mmol/L Spontaneous bacterial peritonitis within 2 weeks prior to inclusion Loculated ascites Hepatic encephalopathy grade 2-4 (West-Haven classification) Obstructive uropathy Primary kidney disease Known diagnosis of congestive heart failure Known diagnosis of acute-on-chronic liver failure Known diagnosis of systemic inflammatory response syndrome Acute infections by known diagnosis and/or antibiotic treatment Known HIV infection Known allergy to the investigational drug or other natriuretic peptides Treatment with dobutamine, levosimendan, milrinone, any phosphodiesterase inhibitor, octreotide, midodrine, vasopressin, dopamine or other vasopressors within 2 weeks prior to inclusion Nephrotoxic drugs within 1 month prior to inclusion Fertile women not using contraception, either an intrauterine device or hormonal contraception Positive pregnancy test in pre-menopausal women or in breast-feeding women Participation in an interventional clinical drug trial within 1 month prior to inclusion Legal incapacity or limited legal capacity Patients who are employees or relatives of the investigator
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: Randomized, double-blind, placebo-controlled clinical trial
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ularitide<br>Test product. Continuous intravenous infusion with 30 ng/kg/min for 48 hours. | Drug: Ularitide<br>* Continuous intravenous infusion for 48 hours at a dose of 30 ng/kg/min. Depending on effect and/or side effects dose can be adjusted to 15 ng/kg/min or 45 ng/kg/min.<br>* Other names: Urodilatin;|
| Placebo Comparator: Placebo<br>Matching placebo. Continuous IV infusion for 48 hours. | Drug: Placebo<br>* Continuous intravenous infusion for 48 hours at a bodyweight-adjusted infusion rate.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute and relative change in sodium excretion rate. | | After 24 hours and at termination of treatment (up to 48 hours) |
| Absolute and relative change in urine volume. | | After 24 hours and at termination of treatment (up to 48 hours) |
| Change of absolute body weight. | | At termination of treatment (up to 48 hours) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of responders in the ularitide group versus the placebo group, defined by: | Urine volume increase of ≥100 % versus baseline, urine volume increase ≥50 % versus baseline, natriuresis increase by ≥100 % versus baseline and/or body weight reduction by ≥2 kg versus baseline. | Throughout the treatment period. Latest measure at termination of treatment (up to 48 hours) |
| Absolute and relative change in sodium excretion rate. | | After 2 hours and 4 hours of treatment and at 6 hours post-treatment follow-up |
| Absolute and relative change in urine volume. | | After 2 hours and 4 hours of treatment and at 6 hours post-treatment follow-up |
| Absolute and relative change in plasma cyclic guanosine monophosphate (cGMP) concentration. | | Throughout the treatment period. Latest measure at 6 hours post-treatment follow-up |
| Absolute and relative change in waist circumference. | | After 24 hours and at termination of treatment (up to 48 hours) |
| Absolute and relative change in serum creatinine. | | After 24 hours and at termination of treatment (up to 48 hours) |
| Absolute and relative change in estimated glomerular filtration rate (eGFR). | | After 24 hours and at termination of treatment (up to 48 hours) |
| Absolute and relative change in plasma and urine osmolalities. | | Throughout the treatment period. Latest measure at 6 hours post-treatment follow-up |
| Absolute and relative change in GFR-24h-Crea (Glomerular filtration rate based on 24-hour creatinine clearance). | | After 24 hours and 48 hours of treatment |
| Absolute and relative change in hematocrit. | | After 24 hours and 48 hours of treatment and at 6 hours post-treatment follow-up |
| Absolute and relative change in plasma copeptin concentration. | | After 24 hours and 48 hours of treatment and at 6 hours post-treatment follow-up |
| Absolute and relative change in plasma renin concentration. | | After 24 hours and 48 hours of treatment and at 6 hours post-treatment follow-up |
| Absolute and relative change in plasma angiotensin concentration. | | After 24 hours and 48 hours of treatment and at 6 hours post-treatment follow-up |
| Absolute and relative change in plasma aldosterone concentration. | | After 24 hours and 48 hours of treatment and at 6 hours post-treatment follow-up |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cirrhosis, Ascites, Refractory ascites, Natriuresis, Diuresis, Urodilatin, Ularitide, natriuretic peptide
|
NCT01113788
|
Tricuspid Isthmus Imaged by CARTOsound, Patients With Typical Atrial Flutter
|
The investigators propose a third hypothesis based on the anatomic observations made in pathological studies. The investigators hypothesize that the anatomic architecture determines the functional properties of the TV-IVC isthmus. As a result,~• Muscular bundles are preferential routes of conduction through the TV-IVC isthmus. The isthmus acts like a series of discreet conduction routes rather than as a sheet of tissue.~The muscular bundles form selective targets for ablation and therefore the entire anatomic line need not be ablated. This has direct implications for ablation of the isthmus.
|
Patients undergoing atrial flutter ablation will have cartosound imaging done during procedure to determine if this will shorten ablation times.
|
Tricuspid Isthmus Architecture as Imaged by CARTOsound, Determines Ablation Times in Patients With Typical Atrial Flutter
|
Atrial Flutter
|
* Device: tricuspid isthmus imaging with Cartosound
|
Inclusion Criteria:~Patients must be over 18 years of age provided written informed consent documented atrial flutter by ECG , holter monitor or TTM~Exclusion Criteria:~previous atrial flutter ablation non isthmus dependent atrial flutter prior right atrial surgery
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| observational including ablation lesion number, ablation time in minutes, fluoroscopic | | 12 months |
|
atrial flutter, tricuspid isthmus, ablation
|
Atrial Flutter, Arrhythmias, Cardiac, Heart Diseases, Cardiovascular Diseases, Pathologic Processes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| imaging<br>imaging with usual catheter/fluoroscopy, no cartosound | Device: tricuspid isthmus imaging with Cartosound<br>* tricuspid isthmus imaging with Cartosound<br>* Other names: Cartosound;|
|
Tricuspid Isthmus Imaged by CARTOsound, Patients With Typical Atrial Flutter
Study Overview
=================
Brief Summary
-----------------
The investigators propose a third hypothesis based on the anatomic observations made in pathological studies. The investigators hypothesize that the anatomic architecture determines the functional properties of the TV-IVC isthmus. As a result, • Muscular bundles are preferential routes of conduction through the TV-IVC isthmus. The isthmus acts like a series of discreet conduction routes rather than as a sheet of tissue. The muscular bundles form selective targets for ablation and therefore the entire anatomic line need not be ablated. This has direct implications for ablation of the isthmus.
Detailed Description
-----------------
Patients undergoing atrial flutter ablation will have cartosound imaging done during procedure to determine if this will shorten ablation times.
Official Title
-----------------
Tricuspid Isthmus Architecture as Imaged by CARTOsound, Determines Ablation Times in Patients With Typical Atrial Flutter
Conditions
-----------------
Atrial Flutter
Intervention / Treatment
-----------------
* Device: tricuspid isthmus imaging with Cartosound
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must be over 18 years of age provided written informed consent documented atrial flutter by ECG , holter monitor or TTM Exclusion Criteria: previous atrial flutter ablation non isthmus dependent atrial flutter prior right atrial surgery
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| imaging<br>imaging with usual catheter/fluoroscopy, no cartosound | Device: tricuspid isthmus imaging with Cartosound<br>* tricuspid isthmus imaging with Cartosound<br>* Other names: Cartosound;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| observational including ablation lesion number, ablation time in minutes, fluoroscopic | | 12 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
atrial flutter, tricuspid isthmus, ablation
|
||
NCT03445390
|
The Effect of Intravenous Acetaminophen on Post-Operative Pain After Craniotomy
|
The purpose of the study is to determine the efficacy of IV acetaminophen when administered to neurosurgical patients at the beginning and end of their surgery. If the result is improved pain control with less opioid consumption postoperatively, then those patients may also experience less opioid related side effects such as nausea/vomiting, pruritus, and sedation. While numerous other studies have failed to show a benefit of IV acetaminophen after neurosurgical procedures, we are studying the administration of 1 g in two doses over the course of the operation.
|
The Effect of Intravenous Acetaminophen on Post-Operative Pain After Craniotomy: A Randomized Control Trial
|
Pain
|
* Drug: Acetaminophen
* Drug: Placebo
|
Inclusion Criteria:~Patients with a diagnosis of bilateral moyamoya disease scheduled for bilateral external-carotid to internal-carotid bypass surgery to be done in two stages.~Exclusion Criteria:~Allergy or history of reaction to acetaminophen. Patients with liver disease. Anyone not able to provide informed consent.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Patients selected for this study were being treated for Moyamoya disease and required two operations, scheduled 1-2 weeks apart. With random assignment, patients were administered 1 gram of intravenous acetaminophen at the beginning and end of surgery, and placebo during the other operation.
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-operative Opioid Consumption | From nursing records how much opioid was administered to each patient post-operatively. Opioid use was measured in micrograms (ug) of fentanyl. | Up to 24 hours post-operative |
| Post-operative Pain | Patients were asked to rate their pain on a scale of 1 to 10, with 1 being least pain, and 10 being most pain. Pain was assessed continually once per hour during the post-operative period and the average pain score calculated per participant. The average of the participants' average scores is presented for each group. | Up to 24 hours post-operative |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Count of Participants Requiring Anti-emetic Administration | | Up to 24 hours post-operative |
|
Acetaminophen, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Antipyretics
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetaminophen First<br>Patients in this group are presenting for 2 surgeries and will be administered intravenous acetaminophen in one surgery and placebo in the other. Patients in this group will be randomized to receive acetaminophen first. | Drug: Acetaminophen<br>* Acetaminophen 1 g intravenous given at the beginning and end of surgery.<br>* Other names: Tylenol;Drug: Placebo<br>* Placebo to match acetaminophen given at the beginning and end of surgery.<br>|
| Experimental: Placebo First<br>Patients in this group are presenting for 2 surgeries and will be administered intravenous acetaminophen in one surgery and placebo in the other. Patients in this group will be randomized to receive placebo first. | Drug: Acetaminophen<br>* Acetaminophen 1 g intravenous given at the beginning and end of surgery.<br>* Other names: Tylenol;Drug: Placebo<br>* Placebo to match acetaminophen given at the beginning and end of surgery.<br>|
|
The Effect of Intravenous Acetaminophen on Post-Operative Pain After Craniotomy
Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to determine the efficacy of IV acetaminophen when administered to neurosurgical patients at the beginning and end of their surgery. If the result is improved pain control with less opioid consumption postoperatively, then those patients may also experience less opioid related side effects such as nausea/vomiting, pruritus, and sedation. While numerous other studies have failed to show a benefit of IV acetaminophen after neurosurgical procedures, we are studying the administration of 1 g in two doses over the course of the operation.
Official Title
-----------------
The Effect of Intravenous Acetaminophen on Post-Operative Pain After Craniotomy: A Randomized Control Trial
Conditions
-----------------
Pain
Intervention / Treatment
-----------------
* Drug: Acetaminophen
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with a diagnosis of bilateral moyamoya disease scheduled for bilateral external-carotid to internal-carotid bypass surgery to be done in two stages. Exclusion Criteria: Allergy or history of reaction to acetaminophen. Patients with liver disease. Anyone not able to provide 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: Crossover Assignment
Interventional Model Description: Patients selected for this study were being treated for Moyamoya disease and required two operations, scheduled 1-2 weeks apart. With random assignment, patients were administered 1 gram of intravenous acetaminophen at the beginning and end of surgery, and placebo during the other operation.
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetaminophen First<br>Patients in this group are presenting for 2 surgeries and will be administered intravenous acetaminophen in one surgery and placebo in the other. Patients in this group will be randomized to receive acetaminophen first. | Drug: Acetaminophen<br>* Acetaminophen 1 g intravenous given at the beginning and end of surgery.<br>* Other names: Tylenol;Drug: Placebo<br>* Placebo to match acetaminophen given at the beginning and end of surgery.<br>|
| Experimental: Placebo First<br>Patients in this group are presenting for 2 surgeries and will be administered intravenous acetaminophen in one surgery and placebo in the other. Patients in this group will be randomized to receive placebo first. | Drug: Acetaminophen<br>* Acetaminophen 1 g intravenous given at the beginning and end of surgery.<br>* Other names: Tylenol;Drug: Placebo<br>* Placebo to match acetaminophen given at the beginning and end of surgery.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-operative Opioid Consumption | From nursing records how much opioid was administered to each patient post-operatively. Opioid use was measured in micrograms (ug) of fentanyl. | Up to 24 hours post-operative |
| Post-operative Pain | Patients were asked to rate their pain on a scale of 1 to 10, with 1 being least pain, and 10 being most pain. Pain was assessed continually once per hour during the post-operative period and the average pain score calculated per participant. The average of the participants' average scores is presented for each group. | Up to 24 hours post-operative |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Count of Participants Requiring Anti-emetic Administration | | Up to 24 hours post-operative |
|
||
NCT02134340
|
A Safety and Biodistribution Study of [I-124]-CPD-1028 Injection in Solid Tumours
|
The purpose of the study is to evaluate the safety and biodistribution of [I-124]-CPD-1028 Injection in cancer patients with solid tumours.
|
Up to 18 adult participants will be enrolled in this Phase 1a study to evaluate the safety and biodistribution of [I-124]-CPD-1028 Injection in patients with Insulin-like Growth Factor-1R (IGF-1R) upregulated solid tumours. All eligible subjects who have given written informed consent and qualify based on the study's inclusion/exclusion criteria will be enrolled in the study. Each enrolled subject will take part in six visits consisting of a screening visit, an Investigational Product administration visit, 3 assessment visits involving 2-3 Positron Emission Tomography/Computed Tomography (PET/CT) scans, and a follow-up safety telephone call. At Visit 2, subjects will start a course of treatment to protect the thyroid from radioactivity and may receive a pre-targeting dose of an additional investigational agent, CPD-1061.
|
A Phase 1a, Multi-centre, Open-label, Non-randomized Study to Assess the Safety, Biodistribution and Tumour Uptake of [I-124]-CPD-1028 Injection
|
Cancer
|
* Drug: [I-124]-CPD-1028 Injection
* Biological: CPD-1061
|
Inclusion Criteria:~Age ≥18 years old with life expectancy > 12 weeks with confirmed metastatic or unresectable malignancy~Patients must have progressed after at least first-line chemotherapy and have an Eastern Cooperative Oncology Group (ECOG) status of 0, 1 or 2.~All patients must have archival tumour samples available and must have verification of IGF-1R expression.~Patients must have adequate organ and marrow function, vital signs and ECG.~Females of childbearing potential must not be pregnant and both males and females must use adequate forms of contraception.~Signed informed consent form~Subject must be compliant and have a high probability of completing the study.~Exclusion Criteria:~Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from previous treatment.~Patients who have received a therapeutic radiopharmaceutical in the past year or who are currently receiving any other investigational agents.~Previous treatment with IGF-1R inhibitors.~Patients who are currently taking antithyroid medications and lithium or potassium sparing diuretics.~Subjects with known or suspected allergies or contraindications to the investigational agents and iodine~Subjects with uncontrolled intercurrent illness~Female subjects who are pregnant, planning to become pregnant or are lactating and/or breast-feeding.~Patients with diabetes requiring therapy unless controlled through diet or metformin.~Subjects who are undergoing monitoring of occupational ionising radiation exposure.~Subjects with hypothyroidism requiring thyroid supplementation
|
18 Years
| null |
All
|
No
|
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate safety of [I-124]-CPD-1028 Injection | The safety of [I-124]-CPD-1028 Injection will be assessed for up to 30 days post injection by measuring the occurrence of adverse events and changes from baseline in physical examination, clinical laboratory parameters, electrocardiogram recordings, and vital signs (blood pressure, heart rate, body temperature, respiratory rate and oxygen saturation). | Up to 30 days |
| Obtain preliminary biodistribution data for [I-124]-CPD-1028 | Biodistribution data will be assessed by quantitative analysis of imaging scans taken 2-3 days and 5-7 days post injection by (1) measuring tumour uptake and background tissue levels in selected regions of interest on whole body images and (2) determining if suitable quantitative imaging metrics can be identified. | Up to 18 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure blood and plasma clearance of [I-124]-CPD-1028 and levels of free [I-124]-Iodide | Blood and plasma clearance of [I-124]-CPD-1028 and levels of free [I-124]-iodide will be assessed by analysis of blood and plasma samples taken up to 18 days post-injection. | Up to 18 days |
| Compare [I-124]-CPD-1028 uptake in tumours to IGF-1R expression | [I-124]-CPD-1028 PET/CT images taken up to 18 days post-injection will be compared to immunohistochemistry staining scores of IGF-1R on previously obtained tumour samples. | Up to 18 days |
| Compare [I-124]-CPD-1028 PET/CT images to other imaging modalities | [I-124]-CPD-1028 PET/CT images taken up to 18 days post-injection will be visually (qualitatively) compared to previously obtained CT and/or MRI images. | Up to 18 days |
|
IGF1R
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [I-124]-CPD-1028 PET/CT<br>Administration of [I-124]-CPD-1028 Injection followed by a maximum of 3 PET/CT imaging sessions.~A pre-targeting dose of CPD-1061 may be given prior to injection of [I-124]-CPD-1028. | Drug: [I-124]-CPD-1028 Injection<br>* A single intravenous dose of [I-124]-CPD-1028 Injection will be given at Visit 2 (within 21 days of screening Visit 1), and may be followed by whole body PET/CT imaging approximately 3 hours post-injection. PET/CT imaging will occur at Visit 3 (2-3 days after Visit 2) and Visit 4 (5-7 days after Visit 2). PET/CT imaging may also occur at Visit 5 (16-18 days after Visit 2). Visit 6 (28 +/- 2 days after Visit 2) is a follow-up telephone call for a post-treatment safety assessment. At Visits 2-5, whole body biodistribution and tumour uptake will be assessed. At all visits, safety will be assessed.<br>Biological: CPD-1061<br>* [Optional] An intravenous dose of 0.4, 1.4 or 6 mg/kg of body weight of CPD-1061 may be given 1-2 hours prior to injection of [I-124]-CPD-1028 at Visit 2. The decision to use CPD-1061 and the dose amount is based on an adaptive design and is dependent on interim reviews of imaging data.<br>|
|
A Safety and Biodistribution Study of [I-124]-CPD-1028 Injection in Solid Tumours
Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to evaluate the safety and biodistribution of [I-124]-CPD-1028 Injection in cancer patients with solid tumours.
Detailed Description
-----------------
Up to 18 adult participants will be enrolled in this Phase 1a study to evaluate the safety and biodistribution of [I-124]-CPD-1028 Injection in patients with Insulin-like Growth Factor-1R (IGF-1R) upregulated solid tumours. All eligible subjects who have given written informed consent and qualify based on the study's inclusion/exclusion criteria will be enrolled in the study. Each enrolled subject will take part in six visits consisting of a screening visit, an Investigational Product administration visit, 3 assessment visits involving 2-3 Positron Emission Tomography/Computed Tomography (PET/CT) scans, and a follow-up safety telephone call. At Visit 2, subjects will start a course of treatment to protect the thyroid from radioactivity and may receive a pre-targeting dose of an additional investigational agent, CPD-1061.
Official Title
-----------------
A Phase 1a, Multi-centre, Open-label, Non-randomized Study to Assess the Safety, Biodistribution and Tumour Uptake of [I-124]-CPD-1028 Injection
Conditions
-----------------
Cancer
Intervention / Treatment
-----------------
* Drug: [I-124]-CPD-1028 Injection
* Biological: CPD-1061
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥18 years old with life expectancy > 12 weeks with confirmed metastatic or unresectable malignancy Patients must have progressed after at least first-line chemotherapy and have an Eastern Cooperative Oncology Group (ECOG) status of 0, 1 or 2. All patients must have archival tumour samples available and must have verification of IGF-1R expression. Patients must have adequate organ and marrow function, vital signs and ECG. Females of childbearing potential must not be pregnant and both males and females must use adequate forms of contraception. Signed informed consent form Subject must be compliant and have a high probability of completing the study. Exclusion Criteria: Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from previous treatment. Patients who have received a therapeutic radiopharmaceutical in the past year or who are currently receiving any other investigational agents. Previous treatment with IGF-1R inhibitors. Patients who are currently taking antithyroid medications and lithium or potassium sparing diuretics. Subjects with known or suspected allergies or contraindications to the investigational agents and iodine Subjects with uncontrolled intercurrent illness Female subjects who are pregnant, planning to become pregnant or are lactating and/or breast-feeding. Patients with diabetes requiring therapy unless controlled through diet or metformin. Subjects who are undergoing monitoring of occupational ionising radiation exposure. Subjects with hypothyroidism requiring thyroid supplementation
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [I-124]-CPD-1028 PET/CT<br>Administration of [I-124]-CPD-1028 Injection followed by a maximum of 3 PET/CT imaging sessions. A pre-targeting dose of CPD-1061 may be given prior to injection of [I-124]-CPD-1028. | Drug: [I-124]-CPD-1028 Injection<br>* A single intravenous dose of [I-124]-CPD-1028 Injection will be given at Visit 2 (within 21 days of screening Visit 1), and may be followed by whole body PET/CT imaging approximately 3 hours post-injection. PET/CT imaging will occur at Visit 3 (2-3 days after Visit 2) and Visit 4 (5-7 days after Visit 2). PET/CT imaging may also occur at Visit 5 (16-18 days after Visit 2). Visit 6 (28 +/- 2 days after Visit 2) is a follow-up telephone call for a post-treatment safety assessment. At Visits 2-5, whole body biodistribution and tumour uptake will be assessed. At all visits, safety will be assessed.<br>Biological: CPD-1061<br>* [Optional] An intravenous dose of 0.4, 1.4 or 6 mg/kg of body weight of CPD-1061 may be given 1-2 hours prior to injection of [I-124]-CPD-1028 at Visit 2. The decision to use CPD-1061 and the dose amount is based on an adaptive design and is dependent on interim reviews of imaging data.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate safety of [I-124]-CPD-1028 Injection | The safety of [I-124]-CPD-1028 Injection will be assessed for up to 30 days post injection by measuring the occurrence of adverse events and changes from baseline in physical examination, clinical laboratory parameters, electrocardiogram recordings, and vital signs (blood pressure, heart rate, body temperature, respiratory rate and oxygen saturation). | Up to 30 days |
| Obtain preliminary biodistribution data for [I-124]-CPD-1028 | Biodistribution data will be assessed by quantitative analysis of imaging scans taken 2-3 days and 5-7 days post injection by (1) measuring tumour uptake and background tissue levels in selected regions of interest on whole body images and (2) determining if suitable quantitative imaging metrics can be identified. | Up to 18 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure blood and plasma clearance of [I-124]-CPD-1028 and levels of free [I-124]-Iodide | Blood and plasma clearance of [I-124]-CPD-1028 and levels of free [I-124]-iodide will be assessed by analysis of blood and plasma samples taken up to 18 days post-injection. | Up to 18 days |
| Compare [I-124]-CPD-1028 uptake in tumours to IGF-1R expression | [I-124]-CPD-1028 PET/CT images taken up to 18 days post-injection will be compared to immunohistochemistry staining scores of IGF-1R on previously obtained tumour samples. | Up to 18 days |
| Compare [I-124]-CPD-1028 PET/CT images to other imaging modalities | [I-124]-CPD-1028 PET/CT images taken up to 18 days post-injection will be visually (qualitatively) compared to previously obtained CT and/or MRI images. | Up to 18 days |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
IGF1R
|
|
NCT02038816
|
Azacitidine Plus Deferasirox (ICL670) in Higher Risk Myelodysplastic Syndromes (MDS)
|
Myelodysplastic syndromes are common blood disorders that can affect as many as one in 1000 Canadians over the age of 65. They are characterized by low blood counts that require frequent blood transfusions. The development of iron overload in these patients is inevitable. The iron deposits in vital organs such as the heart and the liver and can lead to organ dysfunction. Deferasirox is a well-studied drug that helps remove iron from the body. Most people with this disorder die due to progression of their disease to acute leukemia through multiple mechanisms. Iron overload in patients with myelodysplastic syndromes has been shown to be associated with shorter survival, and potentially a higher chance of leukemia. In a certain sub-group of higher risk patients, the drug azacitidine has been shown to decrease the chance of progression to leukemia and death from it. Thus, it is presently the standard of care for these patients. However, 50% of higher risk patients are still unresponsive to this medication, leaving a large group of patients for which other treatment options are emergently needed. Given that a large proportion of higher risk MDS patients fail to respond to azacitidine, and the evidence that iron deposition may lead to increased leukemic transformation, we would like to study whether iron removal from the body with deferasirox potentiates azacitidine in its effects on overall survival, as well as the chance of leukemia transformation. This question needs to be addressed in a randomized controlled trial, and the first step is a preliminary study to determine if the combination of azacitidine and deferasirox has any biologic effect. This study will determine whether this combination leads to blood count improvement over azacitidine alone. If this drug combination ultimately proves more useful than azacitidine alone with respect to survival, this has the potential to impact the care of a large proportion of patients with myelodysplastic syndromes.
|
Patients with stable disease after 6 cycles of AZA with higher risk MDS will be randomized to either standard of care (continued AZA until progression ) or AZA + defasirox. Primary endpoint is augmented response rate by the addition of deferasirox
|
A PHASE II STUDY OF Azacitidine Plus Deferasirox (ICL670) in Higher Risk Myelodysplastic Syndromes (MDS)
|
Myelodysplastic Syndromes
|
* Drug: Deferasirox + Azacitidine
* Drug: Azacitidine
|
Inclusion Criteria:~Adults >18 yrs of age~WHO defined MDS with Higher risk MDS (IPSS int-2/high)~Azacitidine X at least 6 cycles with no hematologic improvement/no disease progression as per IWG 2006 criteria~Ferritin >500 µg/L~If transfusion independent, must have Hb <110 g/L OR Neutrophils < 1,000/mL OR Platelets < 100,000/mL~ECOG ≤2~CrCl >40 ml/min~Exclusion Criteria:~Increased ALT (>300 U/L)~Uncontrolled infection~HIV+~Pregnant or breast-feeding~Previous and concurrent iron chelation~Concurrent use of hematopoietic growth factors including erythropoietin, darbepoietin and granulocyte colony stimulating factor~Concurrent use of other disease modifying agents including cytotoxic chemotherapy, histone deacetylase inhibitors, other hypomethylating agents or lenalidomide
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in proportion of patients with hematologic improvement as defined by the IWG criteria30 with the addition of deferasirox to azacitidine compared with azacitidine alone in higher risk non-responding MDS patients after 6 cycles of azacitidine. | improvement in blood counts or remission status | 6 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability (defined by the percentage of patients able to remain on deferasirox for 6 cycles concurrent with azacitidine) and safety (type, using CTCAE version 4.0, frequency, severity, and relationship of adverse events to study therapy) | toxicity as defined by compliance | 6 months |
| Percentage and absolute change in serum ferritin and labile plasma iron (LPI) between baseline and end of study | Impact of experimental arm on iron parameters | 6 months |
| Percentage change in CD34 cell intracellular reactive oxygen species (ROS) from baseline to end of study. | Impact of experimental arm on markers of oxidative stress in the bone marrow | 6 months |
| Percentage change in erythroid colony forming units (BFU-E and CFU-E) from baseline to end of study | Impact of experimental arm on erythropoiesis | 6 months |
| Percentage change in markers of DNA damage (lipid peroxidation, GSH content, and gH2AX expression), and activity of NFkappaB and Akt signaling pathways between baseline and end of study. | Impact of experimental arm on markers of DNA damage | 6 months |
|
Iron Chelating Agents, Chelating Agents, Azacitidine, Deferasirox, Antimetabolites, Antineoplastic, Antimetabolites, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents, Enzyme Inhibitors, Sequestering Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deferasirox + Azacitidine<br>Azacitidine 75 mg/m2 daily X 7 days every 28 days for 6 cycles + Deferasirox 10-30 mg/kg/d depending on transfusion needs | Drug: Deferasirox + Azacitidine<br>* Deferasirox:~20 mg/kg/d for < 14ml/kg/mo pRBCs (~ <4U/mo), 30mg/kg/d for ≥14ml/kg/mo pRBCs(≥4U/mo), 10mg/kg/d for transfusion-independent patients<br>* Other names: Vidaza;Drug: Azacitidine<br>* Azacitidine 75mg/m2 sc daily X 7 days (5-2-2 schedule permitted) on a 28 day cycle for 6 cycles<br>* Other names: Vidaza;|
| Active Comparator: Azacitidine<br>Azacitidine 75 mg/m2 daily X 7 days every 28 days for 6 cycles | Drug: Azacitidine<br>* Azacitidine 75mg/m2 sc daily X 7 days (5-2-2 schedule permitted) on a 28 day cycle for 6 cycles<br>* Other names: Vidaza;|
|
Azacitidine Plus Deferasirox (ICL670) in Higher Risk Myelodysplastic Syndromes (MDS)
Study Overview
=================
Brief Summary
-----------------
Myelodysplastic syndromes are common blood disorders that can affect as many as one in 1000 Canadians over the age of 65. They are characterized by low blood counts that require frequent blood transfusions. The development of iron overload in these patients is inevitable. The iron deposits in vital organs such as the heart and the liver and can lead to organ dysfunction. Deferasirox is a well-studied drug that helps remove iron from the body. Most people with this disorder die due to progression of their disease to acute leukemia through multiple mechanisms. Iron overload in patients with myelodysplastic syndromes has been shown to be associated with shorter survival, and potentially a higher chance of leukemia. In a certain sub-group of higher risk patients, the drug azacitidine has been shown to decrease the chance of progression to leukemia and death from it. Thus, it is presently the standard of care for these patients. However, 50% of higher risk patients are still unresponsive to this medication, leaving a large group of patients for which other treatment options are emergently needed. Given that a large proportion of higher risk MDS patients fail to respond to azacitidine, and the evidence that iron deposition may lead to increased leukemic transformation, we would like to study whether iron removal from the body with deferasirox potentiates azacitidine in its effects on overall survival, as well as the chance of leukemia transformation. This question needs to be addressed in a randomized controlled trial, and the first step is a preliminary study to determine if the combination of azacitidine and deferasirox has any biologic effect. This study will determine whether this combination leads to blood count improvement over azacitidine alone. If this drug combination ultimately proves more useful than azacitidine alone with respect to survival, this has the potential to impact the care of a large proportion of patients with myelodysplastic syndromes.
Detailed Description
-----------------
Patients with stable disease after 6 cycles of AZA with higher risk MDS will be randomized to either standard of care (continued AZA until progression ) or AZA + defasirox. Primary endpoint is augmented response rate by the addition of deferasirox
Official Title
-----------------
A PHASE II STUDY OF Azacitidine Plus Deferasirox (ICL670) in Higher Risk Myelodysplastic Syndromes (MDS)
Conditions
-----------------
Myelodysplastic Syndromes
Intervention / Treatment
-----------------
* Drug: Deferasirox + Azacitidine
* Drug: Azacitidine
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults >18 yrs of age WHO defined MDS with Higher risk MDS (IPSS int-2/high) Azacitidine X at least 6 cycles with no hematologic improvement/no disease progression as per IWG 2006 criteria Ferritin >500 µg/L If transfusion independent, must have Hb <110 g/L OR Neutrophils < 1,000/mL OR Platelets < 100,000/mL ECOG ≤2 CrCl >40 ml/min Exclusion Criteria: Increased ALT (>300 U/L) Uncontrolled infection HIV+ Pregnant or breast-feeding Previous and concurrent iron chelation Concurrent use of hematopoietic growth factors including erythropoietin, darbepoietin and granulocyte colony stimulating factor Concurrent use of other disease modifying agents including cytotoxic chemotherapy, histone deacetylase inhibitors, other hypomethylating agents or lenalidomide
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: Deferasirox + Azacitidine<br>Azacitidine 75 mg/m2 daily X 7 days every 28 days for 6 cycles + Deferasirox 10-30 mg/kg/d depending on transfusion needs | Drug: Deferasirox + Azacitidine<br>* Deferasirox: 20 mg/kg/d for < 14ml/kg/mo pRBCs ( <4U/mo), 30mg/kg/d for ≥14ml/kg/mo pRBCs(≥4U/mo), 10mg/kg/d for transfusion-independent patients<br>* Other names: Vidaza;Drug: Azacitidine<br>* Azacitidine 75mg/m2 sc daily X 7 days (5-2-2 schedule permitted) on a 28 day cycle for 6 cycles<br>* Other names: Vidaza;|
| Active Comparator: Azacitidine<br>Azacitidine 75 mg/m2 daily X 7 days every 28 days for 6 cycles | Drug: Azacitidine<br>* Azacitidine 75mg/m2 sc daily X 7 days (5-2-2 schedule permitted) on a 28 day cycle for 6 cycles<br>* Other names: Vidaza;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in proportion of patients with hematologic improvement as defined by the IWG criteria30 with the addition of deferasirox to azacitidine compared with azacitidine alone in higher risk non-responding MDS patients after 6 cycles of azacitidine. | improvement in blood counts or remission status | 6 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability (defined by the percentage of patients able to remain on deferasirox for 6 cycles concurrent with azacitidine) and safety (type, using CTCAE version 4.0, frequency, severity, and relationship of adverse events to study therapy) | toxicity as defined by compliance | 6 months |
| Percentage and absolute change in serum ferritin and labile plasma iron (LPI) between baseline and end of study | Impact of experimental arm on iron parameters | 6 months |
| Percentage change in CD34 cell intracellular reactive oxygen species (ROS) from baseline to end of study. | Impact of experimental arm on markers of oxidative stress in the bone marrow | 6 months |
| Percentage change in erythroid colony forming units (BFU-E and CFU-E) from baseline to end of study | Impact of experimental arm on erythropoiesis | 6 months |
| Percentage change in markers of DNA damage (lipid peroxidation, GSH content, and gH2AX expression), and activity of NFkappaB and Akt signaling pathways between baseline and end of study. | Impact of experimental arm on markers of DNA damage | 6 months |
|
|
NCT04376554
|
Effect of Tebipenem on Normal Human Intestinal Microbiota
|
The overall purpose of this study is to support the development of an oral formulation of TBPM-PI-HBr by assessing the potential ecological effects of tebipenem on the normal intestinal microbiota as compared to the effects of oral amoxicillin-clavulanate.
|
This is a single-center, open-label, randomized, parallel-group, active-control, phase 1 study consisting of 10-day treatment period using TBPM-PI-HBr (600mg) (2× 300mg film coated tablets) or amoxicillin-clavulanate (500mg/125mg) orally every 8 hours (PO q8h [±1 hour]) in healthy volunteers. Participants will be randomized by gender to 1:1 ratio on Day 1. A maximum of 30 participants will be randomly assigned to the study treatment groups (15 in each arm) such that approximately 24 evaluable participants complete the study. Due to the multidimensional nature of data of the study, a power statement on a single endpoint is not appropriate. The main aim of the study is to estimate the effects of treatment on the intestinal microbiota, and to assess the pattern of susceptibility to specific pathogens. Based upon previous studies, a sample size of 12 participants in each group is considered sufficient to demonstrate a clinically significant impact of antibiotics on the microbiota. Total duration of study participation for each participant will be approximately 7 months.Screening visit will be performed between Day -28 to Day -1. Randomization will be performed on Day 1 and with treatment being administered from Day 1 to Day 10. Follow-up of participants will occur on Day 14, 21, 90 and 180 with appropriate visit windows. Adverse events and concomitant medications will be recorded until the end of the study (Day 180).
|
Phase 1 Study to Evaluate the Effect of Oral Administration of Tebipenem Pivoxil Hydrobromide on Normal Human Intestinal Microbiota in Healthy Volunteers
|
Healthy Volunteers
|
* Drug: TBPM-PI-HBr
* Drug: amoxicillin-clavulanate
|
Inclusion Criteria:~Healthy adult males and/or females, ≥18 years of age at the time of screening;~Medically healthy without clinically significant abnormal values for hematology, clinical chemistry, urinalysis, physical examination, vital signs, or ECG as determined by the investigator during the screening period. Discussion is encouraged between the Investigator and the Sponsor Medical Monitor regarding the clinical relevance of any abnormal laboratory value during the pre-dose period;~Willing and able to provide written informed consent;~Willing and able to comply with all study assessments and adhere to the protocol schedule, including all scheduled post-therapy visits;~Have suitable venous access for blood sampling;~Women of childbearing potential (WOCBP*) must use a highly effective form of birth control (confirmed by the Investigator). Rhythm methods will not be considered as highly effective methods of birth control. WOCBP must agree to use a highly effective method of birth control, as defined above, from signing the Informed Consent Form (ICF), throughout the study duration and until 30 days after the last dose of study drug;~Non-vasectomized male volunteers must use an adequate method of contraception (condom or condom with spermicide, depending on local regulations) from the time of signing the ICF, throughout the study duration and until 30 days after the last dose of study drug. Men with a partner who is (are) not of childbearing potential are exempt from these requirements;~Male volunteers must not donate sperm for time of signing the ICF until at least 30 days after the last dose of the study drug~Exclusion Criteria:~History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or surgery within the past 3 months determined by the Investigator to be clinically relevant;~History or presence of known or suspected gastrointestinal disorder, including but not limited to Clostridioides difficile infection, inflammatory bowel disease, recent history of food poisoning or other stomach/intestinal disorders including gastroenteritis (within 6 months);~History of systemic antibiotic treatment during the last three months prior to randomization;~Use of any systemic prescription medication or any systemic over-the-counter medication, including herbal products and vitamins or probiotics within 7 days prior to randomization; except for hormonal contraceptives and the intermittent use of paracetamol, ibuprofen, and antihistamines;~Alanine transaminase (ALT) or aspartate transaminase (AST) >5 × upper limit of normal and CrCl of ≤50 mL/min, as estimated by the Lund-Malmö revised formula;~History of seizure disorders, except for febrile seizures in childhood;~History of substance or alcohol abuse and positive urine drug testing at screening. History of substance or alcohol abuse and negative urine drug testing at screening can be enrolled in study based on the Investigator's discretion;~Positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV);~Documented or suspected hypersensitivity reaction or anaphylaxis to β-lactam antibiotics (e.g., cephalosporins, penicillins, carbapenems), product excipients (Mannitol, microcrystalline cellulose, crospovidone, magnesium stearate, colloidal silicon dioxide, and film coating systems [Opadry]) or any contraindication to the use of amoxicillin- clavulanate;~Participation in another investigational clinical study within 3 months prior to Day 1;~Current or anticipated need for systemic antibiotics, probiotics, or laxatives during the study;~Any other condition or prior therapy, which, in the opinion of the Investigator, would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likely to be non-compliant with any study requirements.
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single-Center, Open-Label, Randomized, Parallel-Group, Active Control, Phase 1 Study
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the number of microorganisms in the intestinal flora of healthy subjects during and after 10 days of oral administration of TBPM-PI-HBr or amoxicillin-clavulanate | Changes in the number of microorganisms identified in feces | Change from baseline (Day-1), at Days 2, 4, 7, 10, 14, 21, 90, and 180 |
| Changes in the types of microorganisms in the intestinal flora of healthy subjects during and after 10 days of oral administration of TBPM-PI-HBr or amoxicillin-clavulanate | Changes in the types of microorganisms identified in feces | Change from baseline (Day-1), at Days 2, 4, 7, 10, 14, 21, 90, and 180 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To explore the potential for development of resistance by measuring the number of new colonizing bacterial isolates | Emergence of resistant strains with increasing minimum inhibitory concentration values during treatment and post-treatment with tebipenem and amoxicillin-clavulanate will be determined from fecal samples. | Change from baseline (Day-1), at Days 2, 4, 7, 10, 14, 21, 90, and 180 |
| To assess the plasma concentrations of tebipenem over 10 days of oral administration of TBPM-PI-HBr. | PK concentration of tebipenem will be measured in plasma. Concentrations of tebipenem will be plotted for each participant. | Day 1 through Day 14 |
| To assess the fecal concentrations of tebipenem over 10 days of oral administration of TBPM-PI-HBr. | PK concentration of tebipenem will be measured in feces.Concentrations of tebipenem will be plotted for each participant. | Day 1 through Day 14 |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | To assess the incidents of treatment-emergent adverse events following 10 days of oral TBPM-PI-HBr administration | Incidents of treatment-emergent adverse events from Day 1 through last follow-up visit (180 days after last dose) |
| Incidence of abnormal safety laboratory assessments [Safety and Tolerability] | To assess the incidents of abnormal hematology, biochemistry, coagulation and urinalysis assessments following 10 days of oral TBPM-PI-HBr administration | Incidents of abnormal safety laboratory assessments from Day 1 through last follow-up visit (180 days after last dose) |
| Incidence of abnormal vital sign assessments [Safety and Tolerability] | To assess the incidents of abnormal heart rate, blood pressure and body temperature assessments following 10 days of oral TBPM-PI-HBr administration | Incidents of abnormal vital sign assessments from Day 1 through last follow-up visit (180 days after last dose) |
| Incidence of abnormal physical exam assessments [Safety and Tolerability] | To assess the incidents of abnormal body system assessments following 10 days of oral TBPM-PI-HBr administration | Incidents of abnormal physical exam assessments from Day 1 through last follow-up visit (180 days after last dose) |
|
intestinal microbiota, safety, pharmacokinetics, TBPM-PI-HBr, tebipenem
|
Amoxicillin, Clavulanic Acid, Clavulanic Acids, Amoxicillin-Potassium Clavulanate Combination, Anti-Bacterial Agents, Anti-Infective Agents, beta-Lactamase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TBPM-PI-HBr<br>Healthy subjects meeting eligibility criteria will be sequentially randomized to receive either 600mg TBPM-PI-HBr every 8 hours (PO q8h [±1 hour]) or 500/125mg amoxicillin-clavulanate PO q8h (±1 hour) for 10 days. | Drug: TBPM-PI-HBr<br>* TBPM-PI-HBr (2 x 300mg tablets) PO q8h [±1 hour] for 10 days<br>* Other names: TBPM-PI-HBr oral tablet;|
| Active Comparator: amoxicillin-clavulanate<br>Healthy subjects meeting eligibility criteria will be sequentially randomized to receive either 500/125mg amoxicillin-clavulanate PO q8h (±1 hour) or 600mg TBPM-PI-HBr every 8 hours (PO q8h [±1 hour]) or for 10 days. | Drug: amoxicillin-clavulanate<br>* amoxicillin-clavulanate (1 × 500mg/125mg tablet) PO q8h [±1 hour] for 10 days<br>* Other names: amoxicillin-clavulanate oral tablets;|
|
Effect of Tebipenem on Normal Human Intestinal Microbiota
Study Overview
=================
Brief Summary
-----------------
The overall purpose of this study is to support the development of an oral formulation of TBPM-PI-HBr by assessing the potential ecological effects of tebipenem on the normal intestinal microbiota as compared to the effects of oral amoxicillin-clavulanate.
Detailed Description
-----------------
This is a single-center, open-label, randomized, parallel-group, active-control, phase 1 study consisting of 10-day treatment period using TBPM-PI-HBr (600mg) (2× 300mg film coated tablets) or amoxicillin-clavulanate (500mg/125mg) orally every 8 hours (PO q8h [±1 hour]) in healthy volunteers. Participants will be randomized by gender to 1:1 ratio on Day 1. A maximum of 30 participants will be randomly assigned to the study treatment groups (15 in each arm) such that approximately 24 evaluable participants complete the study. Due to the multidimensional nature of data of the study, a power statement on a single endpoint is not appropriate. The main aim of the study is to estimate the effects of treatment on the intestinal microbiota, and to assess the pattern of susceptibility to specific pathogens. Based upon previous studies, a sample size of 12 participants in each group is considered sufficient to demonstrate a clinically significant impact of antibiotics on the microbiota. Total duration of study participation for each participant will be approximately 7 months.Screening visit will be performed between Day -28 to Day -1. Randomization will be performed on Day 1 and with treatment being administered from Day 1 to Day 10. Follow-up of participants will occur on Day 14, 21, 90 and 180 with appropriate visit windows. Adverse events and concomitant medications will be recorded until the end of the study (Day 180).
Official Title
-----------------
Phase 1 Study to Evaluate the Effect of Oral Administration of Tebipenem Pivoxil Hydrobromide on Normal Human Intestinal Microbiota in Healthy Volunteers
Conditions
-----------------
Healthy Volunteers
Intervention / Treatment
-----------------
* Drug: TBPM-PI-HBr
* Drug: amoxicillin-clavulanate
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy adult males and/or females, ≥18 years of age at the time of screening; Medically healthy without clinically significant abnormal values for hematology, clinical chemistry, urinalysis, physical examination, vital signs, or ECG as determined by the investigator during the screening period. Discussion is encouraged between the Investigator and the Sponsor Medical Monitor regarding the clinical relevance of any abnormal laboratory value during the pre-dose period; Willing and able to provide written informed consent; Willing and able to comply with all study assessments and adhere to the protocol schedule, including all scheduled post-therapy visits; Have suitable venous access for blood sampling; Women of childbearing potential (WOCBP*) must use a highly effective form of birth control (confirmed by the Investigator). Rhythm methods will not be considered as highly effective methods of birth control. WOCBP must agree to use a highly effective method of birth control, as defined above, from signing the Informed Consent Form (ICF), throughout the study duration and until 30 days after the last dose of study drug; Non-vasectomized male volunteers must use an adequate method of contraception (condom or condom with spermicide, depending on local regulations) from the time of signing the ICF, throughout the study duration and until 30 days after the last dose of study drug. Men with a partner who is (are) not of childbearing potential are exempt from these requirements; Male volunteers must not donate sperm for time of signing the ICF until at least 30 days after the last dose of the study drug Exclusion Criteria: History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or surgery within the past 3 months determined by the Investigator to be clinically relevant; History or presence of known or suspected gastrointestinal disorder, including but not limited to Clostridioides difficile infection, inflammatory bowel disease, recent history of food poisoning or other stomach/intestinal disorders including gastroenteritis (within 6 months); History of systemic antibiotic treatment during the last three months prior to randomization; Use of any systemic prescription medication or any systemic over-the-counter medication, including herbal products and vitamins or probiotics within 7 days prior to randomization; except for hormonal contraceptives and the intermittent use of paracetamol, ibuprofen, and antihistamines; Alanine transaminase (ALT) or aspartate transaminase (AST) >5 × upper limit of normal and CrCl of ≤50 mL/min, as estimated by the Lund-Malmö revised formula; History of seizure disorders, except for febrile seizures in childhood; History of substance or alcohol abuse and positive urine drug testing at screening. History of substance or alcohol abuse and negative urine drug testing at screening can be enrolled in study based on the Investigator's discretion; Positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV); Documented or suspected hypersensitivity reaction or anaphylaxis to β-lactam antibiotics (e.g., cephalosporins, penicillins, carbapenems), product excipients (Mannitol, microcrystalline cellulose, crospovidone, magnesium stearate, colloidal silicon dioxide, and film coating systems [Opadry]) or any contraindication to the use of amoxicillin- clavulanate; Participation in another investigational clinical study within 3 months prior to Day 1; Current or anticipated need for systemic antibiotics, probiotics, or laxatives during the study; Any other condition or prior therapy, which, in the opinion of the Investigator, would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likely to be non-compliant with any study requirements.
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
Interventional Model Description: Single-Center, Open-Label, Randomized, Parallel-Group, Active Control, Phase 1 Study
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TBPM-PI-HBr<br>Healthy subjects meeting eligibility criteria will be sequentially randomized to receive either 600mg TBPM-PI-HBr every 8 hours (PO q8h [±1 hour]) or 500/125mg amoxicillin-clavulanate PO q8h (±1 hour) for 10 days. | Drug: TBPM-PI-HBr<br>* TBPM-PI-HBr (2 x 300mg tablets) PO q8h [±1 hour] for 10 days<br>* Other names: TBPM-PI-HBr oral tablet;|
| Active Comparator: amoxicillin-clavulanate<br>Healthy subjects meeting eligibility criteria will be sequentially randomized to receive either 500/125mg amoxicillin-clavulanate PO q8h (±1 hour) or 600mg TBPM-PI-HBr every 8 hours (PO q8h [±1 hour]) or for 10 days. | Drug: amoxicillin-clavulanate<br>* amoxicillin-clavulanate (1 × 500mg/125mg tablet) PO q8h [±1 hour] for 10 days<br>* Other names: amoxicillin-clavulanate oral tablets;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the number of microorganisms in the intestinal flora of healthy subjects during and after 10 days of oral administration of TBPM-PI-HBr or amoxicillin-clavulanate | Changes in the number of microorganisms identified in feces | Change from baseline (Day-1), at Days 2, 4, 7, 10, 14, 21, 90, and 180 |
| Changes in the types of microorganisms in the intestinal flora of healthy subjects during and after 10 days of oral administration of TBPM-PI-HBr or amoxicillin-clavulanate | Changes in the types of microorganisms identified in feces | Change from baseline (Day-1), at Days 2, 4, 7, 10, 14, 21, 90, and 180 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To explore the potential for development of resistance by measuring the number of new colonizing bacterial isolates | Emergence of resistant strains with increasing minimum inhibitory concentration values during treatment and post-treatment with tebipenem and amoxicillin-clavulanate will be determined from fecal samples. | Change from baseline (Day-1), at Days 2, 4, 7, 10, 14, 21, 90, and 180 |
| To assess the plasma concentrations of tebipenem over 10 days of oral administration of TBPM-PI-HBr. | PK concentration of tebipenem will be measured in plasma. Concentrations of tebipenem will be plotted for each participant. | Day 1 through Day 14 |
| To assess the fecal concentrations of tebipenem over 10 days of oral administration of TBPM-PI-HBr. | PK concentration of tebipenem will be measured in feces.Concentrations of tebipenem will be plotted for each participant. | Day 1 through Day 14 |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | To assess the incidents of treatment-emergent adverse events following 10 days of oral TBPM-PI-HBr administration | Incidents of treatment-emergent adverse events from Day 1 through last follow-up visit (180 days after last dose) |
| Incidence of abnormal safety laboratory assessments [Safety and Tolerability] | To assess the incidents of abnormal hematology, biochemistry, coagulation and urinalysis assessments following 10 days of oral TBPM-PI-HBr administration | Incidents of abnormal safety laboratory assessments from Day 1 through last follow-up visit (180 days after last dose) |
| Incidence of abnormal vital sign assessments [Safety and Tolerability] | To assess the incidents of abnormal heart rate, blood pressure and body temperature assessments following 10 days of oral TBPM-PI-HBr administration | Incidents of abnormal vital sign assessments from Day 1 through last follow-up visit (180 days after last dose) |
| Incidence of abnormal physical exam assessments [Safety and Tolerability] | To assess the incidents of abnormal body system assessments following 10 days of oral TBPM-PI-HBr administration | Incidents of abnormal physical exam assessments from Day 1 through last follow-up visit (180 days after last dose) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
intestinal microbiota, safety, pharmacokinetics, TBPM-PI-HBr, tebipenem
|
NCT01073514
|
Clinical Trial of Bile Etiology ,Proteomics and Metabonomics of Malignant Biliary Obstruction
|
To investigate bile culture and susceptibility test in patients with malignant biliary obstruction (MBO) or relation between bile, portal vein or vein culture and biliary infection. Also to get the information of bile metabonomics to find potential tumor marker .Culture of the organism is recognized as the gold standard for diagnosis of infection. Our research may be one of the first research on culture and susceptibility test in patients with MBO. The results of the trial research will be benefit to experiential therapy of MBO with biliary infection and diagnosis of MBO.
|
We will obtain bile sample for culture and susceptibility ,proteomics metabonomics test after PTBD. Also get the blood and urine samples.
|
Clinical Trial of Bile Etiology,Proteomics and Metabonomics of Malignant Biliary Obstruction
|
Malignant Biliary Obstruction
|
Inclusion Criteria:~Those with MBO who can receive Percutaneous Transhepatic Biliary Drainage(PTBD)~Exclusion Criteria:~Those with MBO who cannot receive Percutaneous Transhepatic Biliary Drainage(PTBD)
|
18 Years
|
70 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
Malignant biliary obstruction (MBO)
|
Clinical Trial of Bile Etiology ,Proteomics and Metabonomics of Malignant Biliary Obstruction
Study Overview
=================
Brief Summary
-----------------
To investigate bile culture and susceptibility test in patients with malignant biliary obstruction (MBO) or relation between bile, portal vein or vein culture and biliary infection. Also to get the information of bile metabonomics to find potential tumor marker .Culture of the organism is recognized as the gold standard for diagnosis of infection. Our research may be one of the first research on culture and susceptibility test in patients with MBO. The results of the trial research will be benefit to experiential therapy of MBO with biliary infection and diagnosis of MBO.
Detailed Description
-----------------
We will obtain bile sample for culture and susceptibility ,proteomics metabonomics test after PTBD. Also get the blood and urine samples.
Official Title
-----------------
Clinical Trial of Bile Etiology,Proteomics and Metabonomics of Malignant Biliary Obstruction
Conditions
-----------------
Malignant Biliary Obstruction
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Those with MBO who can receive Percutaneous Transhepatic Biliary Drainage(PTBD) Exclusion Criteria: Those with MBO who cannot receive Percutaneous Transhepatic Biliary Drainage(PTBD)
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?
-----------------
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
-----------------
Malignant biliary obstruction (MBO)
|
|||||
NCT05477862
|
Neural Mechanisms of Clinically Designed Improvisatory Music for Alzheimer's Disease
|
Clinically Designed Improvisatory Music (CDIM) is a form of improvised music based on calm-inducing sound parameters which brought relief to our cohort of neurology patients. As a direct sound-based approach, CDIM does not rely on autobiographical memory and may have wider applicability and generalizability. We wish to examine if CDIM decreases anxiety in 15 cognitively healthy individuals and 15 Alzheimer Disease patients with anxiety (AD-A).
|
The goal of this study is to identify the neural mechanisms of induced calmness through live clinically designed improvisatory music (CDIM) in cognitively healthy individuals and persons with Alzheimer's dementia suffering from agitation. This study is novel as most music interventions for dementia use familiar music and the underlying neural mechanism of calmness induced by music is not well known. We plan to investigate changes in 3 major large-scale brain networks using functional magnetic resonance imaging (fMRI). The major questions we plan to answer are as follows: 1. How does improvisatory music change the connectivity within brain emotion related networks in neurotypical individuals? 2. Does improvisatory music induce a state of calmness in individuals with Alzheimer's dementia and how? Based on objective evidence provided by this study we can justify further usage of music for patients with Alzheimer's, in particular, in the form of improvisation.
|
Neural Mechanisms of Induced Calmness After Listening to Improvisatory Music: An Investigation for Healthy Individuals and Persons With Alzheimer's Dementia
|
Alzheimer Disease
|
* Behavioral: Clinically Designed Improvisatory Music
|
Inclusion Criteria:~Cognitively healthy individuals~Cognitively healthy control participants evaluated through the Northwestern Mesulam Center. BAI > 8.~Exclusion Criteria: hearing loss~Individuals with mild to moderate Alzheimer's disease~This group will similarly be recruited through the Mesulam Center. All individuals recruited by the research Core at the center are well characterized tests standardized across all NIH funded Alzheimer Centers across the nation. Individuals with mild to moderate neurocognitive disorder due to AD will have an MMSE greater than >15 and Clinical Dementia Rating (CDR) between 0.5 and 2.. They will also have a history of neurocognitive-related agitation/anxiety, and a Beck Anxiety Index (BAI) greater than 8, suggestive of at least a mild level of anxiety.~Exclusion criteria: MMSE<15, CDR>2, hearing loss
|
55 Years
|
85 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 15 individuals with Alzheimer Disease (AD) and 15 cognitively healthy individuals.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Neuropsychiatric Inventory (NPI) [NPI-1: pre-intervention; NPI-2: post-intervention] | Change in NPI (NPI-2 minus NPI-1) | Through study completion (3 years) |
| Change in Beck Anxiety Inventory [BAI-1: pre-intervention; BAI-2: post-intervention] | Change in BAI (BAI-2 minus BAI-1) | Through study completion (3 years) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Systolic Blood Pressure [SBP-1: pre-intervention; SBP-2: post-intervention] | Change in SBP (SBP-2 minus SBP-1) | Through study completion (3 years) |
| Change in Heart rate [HR-1: pre-intervention; HR-2: post-intervention] | Change in HR (HR-2 minus HR-1) | Through study completion (3 years) |
| Change Respiratory Rate [RR-1: pre-intervention; RR-2: post-intervention] | Change in RR (RR-2 minus RR-1) | Through study completion (3 years) |
| Change in Skin conductance [SC-1: pre-intervention; SC-2: post-intervention] | Change in SC (SC-2 minus SC-1) | Through study completion (3 years) |
| Change in Resting state functional connectivity MRI | Functional Connectivity within three resting state networks: Change in Default Network (DN), Change in Salience Network (SN), and Change in Reward Network (RN). | Through study completion (3 years) |
|
Anxiety, Alzheimer, Dementia, Agitation, Irritability, Music Intervention, Music Medicine, Music Improvisation
|
Tauopathies, Alzheimer Disease, Dementia, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Neurodegenerative Diseases, Neurocognitive Disorders, Mental Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alzheimer Disease (AD)<br> | Behavioral: Clinically Designed Improvisatory Music<br>* Clinically Designed Improvisatory Music (CDIM) is a form of improvised music based on calm-inducing sound parameters which brought relief to our cohort of neurology patients.<br>|
| Experimental: Cognitively Healthy (CH)<br> | Behavioral: Clinically Designed Improvisatory Music<br>* Clinically Designed Improvisatory Music (CDIM) is a form of improvised music based on calm-inducing sound parameters which brought relief to our cohort of neurology patients.<br>|
|
Neural Mechanisms of Clinically Designed Improvisatory Music for Alzheimer's Disease
Study Overview
=================
Brief Summary
-----------------
Clinically Designed Improvisatory Music (CDIM) is a form of improvised music based on calm-inducing sound parameters which brought relief to our cohort of neurology patients. As a direct sound-based approach, CDIM does not rely on autobiographical memory and may have wider applicability and generalizability. We wish to examine if CDIM decreases anxiety in 15 cognitively healthy individuals and 15 Alzheimer Disease patients with anxiety (AD-A).
Detailed Description
-----------------
The goal of this study is to identify the neural mechanisms of induced calmness through live clinically designed improvisatory music (CDIM) in cognitively healthy individuals and persons with Alzheimer's dementia suffering from agitation. This study is novel as most music interventions for dementia use familiar music and the underlying neural mechanism of calmness induced by music is not well known. We plan to investigate changes in 3 major large-scale brain networks using functional magnetic resonance imaging (fMRI). The major questions we plan to answer are as follows: 1. How does improvisatory music change the connectivity within brain emotion related networks in neurotypical individuals? 2. Does improvisatory music induce a state of calmness in individuals with Alzheimer's dementia and how? Based on objective evidence provided by this study we can justify further usage of music for patients with Alzheimer's, in particular, in the form of improvisation.
Official Title
-----------------
Neural Mechanisms of Induced Calmness After Listening to Improvisatory Music: An Investigation for Healthy Individuals and Persons With Alzheimer's Dementia
Conditions
-----------------
Alzheimer Disease
Intervention / Treatment
-----------------
* Behavioral: Clinically Designed Improvisatory Music
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Cognitively healthy individuals Cognitively healthy control participants evaluated through the Northwestern Mesulam Center. BAI > 8. Exclusion Criteria: hearing loss Individuals with mild to moderate Alzheimer's disease This group will similarly be recruited through the Mesulam Center. All individuals recruited by the research Core at the center are well characterized tests standardized across all NIH funded Alzheimer Centers across the nation. Individuals with mild to moderate neurocognitive disorder due to AD will have an MMSE greater than >15 and Clinical Dementia Rating (CDR) between 0.5 and 2.. They will also have a history of neurocognitive-related agitation/anxiety, and a Beck Anxiety Index (BAI) greater than 8, suggestive of at least a mild level of anxiety. Exclusion criteria: MMSE<15, CDR>2, hearing loss
Ages Eligible for Study
-----------------
Minimum Age: 55 Years
Maximum Age: 85 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 15 individuals with Alzheimer Disease (AD) and 15 cognitively healthy individuals.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alzheimer Disease (AD)<br> | Behavioral: Clinically Designed Improvisatory Music<br>* Clinically Designed Improvisatory Music (CDIM) is a form of improvised music based on calm-inducing sound parameters which brought relief to our cohort of neurology patients.<br>|
| Experimental: Cognitively Healthy (CH)<br> | Behavioral: Clinically Designed Improvisatory Music<br>* Clinically Designed Improvisatory Music (CDIM) is a form of improvised music based on calm-inducing sound parameters which brought relief to our cohort of neurology patients.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Neuropsychiatric Inventory (NPI) [NPI-1: pre-intervention; NPI-2: post-intervention] | Change in NPI (NPI-2 minus NPI-1) | Through study completion (3 years) |
| Change in Beck Anxiety Inventory [BAI-1: pre-intervention; BAI-2: post-intervention] | Change in BAI (BAI-2 minus BAI-1) | Through study completion (3 years) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Systolic Blood Pressure [SBP-1: pre-intervention; SBP-2: post-intervention] | Change in SBP (SBP-2 minus SBP-1) | Through study completion (3 years) |
| Change in Heart rate [HR-1: pre-intervention; HR-2: post-intervention] | Change in HR (HR-2 minus HR-1) | Through study completion (3 years) |
| Change Respiratory Rate [RR-1: pre-intervention; RR-2: post-intervention] | Change in RR (RR-2 minus RR-1) | Through study completion (3 years) |
| Change in Skin conductance [SC-1: pre-intervention; SC-2: post-intervention] | Change in SC (SC-2 minus SC-1) | Through study completion (3 years) |
| Change in Resting state functional connectivity MRI | Functional Connectivity within three resting state networks: Change in Default Network (DN), Change in Salience Network (SN), and Change in Reward Network (RN). | Through study completion (3 years) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Anxiety, Alzheimer, Dementia, Agitation, Irritability, Music Intervention, Music Medicine, Music Improvisation
|
NCT05571865
|
Diabetic Cardiomyopathy and Heart Failure
|
This study will demonstrate the beneficial effects of ketone bodies in type 1 diabetes (T1D) patients and will have significant translational applications to prevent serious metabolic conditions such as T1D induced diabetic cardiomyopathy (DCM).
|
T1D remains the primary cause of DCM. The long-term goal is to understand the mechanism of T1D leading to DCM. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in degrading the low-density lipoprotein receptors (LDLRs) and that increases the circulating LDL cholesterol (LDL-C). Further, PCSK9 increases duringT1D and that, in turn, decreases mitochondrial bioenergetics, transcription factor- mitochondrial (TFAM), and the mitochondrial numbers thus creates an oxidative stress. These changes lead to oxidation of high-density lipoprotein paraoxonase-1 (HDL-Pon1). Because Pon1 hydrolyzes homocysteine (Hcy), the oxidized Pon1 thus causes accumulation of Hcy (i.e. hyperhomocysteinemia; HHcy). Also, the 'metabolic memory' is associated with epigenetic modification (methylation) of genes encoding proteins such as thioredoxin interacting protein (TXNIP). Since methylation/epigenetics inhibits genes, this phenomenon generates even more amounts of Hcy. Investigators have shown that HHcy decreases G-protein coupled receptor (GPCR) Gαs subunit, protein kinase-B (AKT), focal adhesion kinase (FAK) but increases calpain-1, inflammasome and oxidative stress. The central hypothesis is that an increase in PCSK9 causes oxidative stress and decreases TXNIP thus causing oxidation of HDL-Pon1 and subsequent accumulation of Hcy. These alterations lead to decrease in Gαs, AKT, FAK and concomitant increase in PCSK9 and calpain-1 causing metabolic, diastolic, and systolic cardiac dysfunction. Treatment with ketone bodies (the food for mitochondria) will mitigate these changes.
|
Preventing Diabetic Cardiomyopathy and Heart Failure by Ketone Bodies
|
Diabetic Cardiomyopathies, Heart Failure
|
* Dietary Supplement: Probiotic
|
Inclusion Criteria:~-Diabetic subjects with high blood glucose levels~Exclusion Criteria:~- Comorbidities affecting glucose levels and cardiac function
|
18 Years
|
70 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Diabetic, and non-diabetic subjects.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Outcome Measure-I | Levels of glucose in blood and urine | 4 years |
| Primary Outcome Measure-II | Cardiac function evaluation by electrocardiogram | 4 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Outcome Measure-I | Biochemical estimation of biomarkers from blood samples | 4 years |
|
Diabetic Cardiomyopathy, Metabolic Dysregulation, and Heart Failure.
|
Endocrine System Diseases, Heart Failure, Cardiomyopathies, Diabetic Cardiomyopathies, Heart Diseases, Cardiovascular Diseases, Diabetes Complications, Diabetes Mellitus
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Control subjects (non-diabetic).<br>Control subjects (non-diabetic):~10 subjects: No intervention (placebo). 10 subjects: Intervention (probiotic) | Dietary Supplement: Probiotic<br>* Oral administration of a probiotic<br>|
| Other: Diabetic Subjects<br>Diabetic subjects:~10 subjects: No intervention (placebo). 10 subjects: Intervention (probiotic) | Dietary Supplement: Probiotic<br>* Oral administration of a probiotic<br>|
|
Diabetic Cardiomyopathy and Heart Failure
Study Overview
=================
Brief Summary
-----------------
This study will demonstrate the beneficial effects of ketone bodies in type 1 diabetes (T1D) patients and will have significant translational applications to prevent serious metabolic conditions such as T1D induced diabetic cardiomyopathy (DCM).
Detailed Description
-----------------
T1D remains the primary cause of DCM. The long-term goal is to understand the mechanism of T1D leading to DCM. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in degrading the low-density lipoprotein receptors (LDLRs) and that increases the circulating LDL cholesterol (LDL-C). Further, PCSK9 increases duringT1D and that, in turn, decreases mitochondrial bioenergetics, transcription factor- mitochondrial (TFAM), and the mitochondrial numbers thus creates an oxidative stress. These changes lead to oxidation of high-density lipoprotein paraoxonase-1 (HDL-Pon1). Because Pon1 hydrolyzes homocysteine (Hcy), the oxidized Pon1 thus causes accumulation of Hcy (i.e. hyperhomocysteinemia; HHcy). Also, the 'metabolic memory' is associated with epigenetic modification (methylation) of genes encoding proteins such as thioredoxin interacting protein (TXNIP). Since methylation/epigenetics inhibits genes, this phenomenon generates even more amounts of Hcy. Investigators have shown that HHcy decreases G-protein coupled receptor (GPCR) Gαs subunit, protein kinase-B (AKT), focal adhesion kinase (FAK) but increases calpain-1, inflammasome and oxidative stress. The central hypothesis is that an increase in PCSK9 causes oxidative stress and decreases TXNIP thus causing oxidation of HDL-Pon1 and subsequent accumulation of Hcy. These alterations lead to decrease in Gαs, AKT, FAK and concomitant increase in PCSK9 and calpain-1 causing metabolic, diastolic, and systolic cardiac dysfunction. Treatment with ketone bodies (the food for mitochondria) will mitigate these changes.
Official Title
-----------------
Preventing Diabetic Cardiomyopathy and Heart Failure by Ketone Bodies
Conditions
-----------------
Diabetic Cardiomyopathies, Heart Failure
Intervention / Treatment
-----------------
* Dietary Supplement: Probiotic
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: -Diabetic subjects with high blood glucose levels Exclusion Criteria: - Comorbidities affecting glucose levels and cardiac function
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
Interventional Model Description: Diabetic, and non-diabetic subjects.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Control subjects (non-diabetic).<br>Control subjects (non-diabetic): 10 subjects: No intervention (placebo). 10 subjects: Intervention (probiotic) | Dietary Supplement: Probiotic<br>* Oral administration of a probiotic<br>|
| Other: Diabetic Subjects<br>Diabetic subjects: 10 subjects: No intervention (placebo). 10 subjects: Intervention (probiotic) | Dietary Supplement: Probiotic<br>* Oral administration of a probiotic<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Outcome Measure-I | Levels of glucose in blood and urine | 4 years |
| Primary Outcome Measure-II | Cardiac function evaluation by electrocardiogram | 4 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Outcome Measure-I | Biochemical estimation of biomarkers from blood samples | 4 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diabetic Cardiomyopathy, Metabolic Dysregulation, and Heart Failure.
|
NCT05528640
|
Interventional Study of Mental Health Literacy Educational Program for General Hospital Nurses
|
Mental health literacy is a concept that encompasses knowledge of mental health, mental illnesses, and their management; mental illness-related attitudes/ stigma; and help-seeking efficacy. It impacted care provision by affecting healthcare professionals' ability to recognize, manage and prevent mental illnesses. It was found that physical-mental comorbidity (co-occurrence of physical and mental illnesses) imposed a burden on patients and the healthcare system. However, the referral rate to psychiatric consultation-liaison in general hospitals was low could be attributed to the suboptimal level of mental health literacy of general hospital healthcare professionals. Nurses are the major healthcare workforce in general hospitals for the initial identification of mental illness, help doctors to deal with patients' conditions, and make a contribution to positive patient outcomes in general hospitals. Therefore, there is an urgent need to improve the mental health literacy of nurses working in general hospitals.~An education program had been developed guided by the concept of mental health literacy, and self-efficacy theory. This study aims to examine the effect of an educational program on improving the mental health literacy of general hospital nurses, in terms of knowledge of mental health, mental illnesses, and their treatment; attitude or stigma about mental illnesses; and help-seeking efficacy. It also measures the interventional effect on perceived competency in caring for patients with mental illness and work stress among general hospital nurses, as well as patient satisfaction with nursing care in general hospitals.
|
This study is a prospective 2-arm parallel controlled trial. The study sites will be conducted in the emergency departments and medical wards of two similar regional general hospitals. It is estimated using GPower that a sample size of 64 participants per group is adequate to detect an effect size of 0.5 on the primary outcomes at a post-intervention time point with 80% power at a 5% level of significance. Participants will be assigned to either an intervention group or a control group. Participants in the intervention group will receive a Mental Health Literacy Program consisting of six 30-minutes online educational sessions and one 60-minutes face-to-face session. No active intervention will be given to the control group. Outcome measures will be measured by the Mental Health Literacy Scale, the Behavioral Health Care Competency survey, the Workplace Stress Scale, and Hospital Patient Satisfaction Survey at baseline, immediately after intervention, and one-month after intervention.
|
The Effectiveness of an Educational Program on the Mental Health Literacy of Nurses Working in General Hospitals: a Controlled Trial
|
Mental Health Issue
|
* Other: Mental Health Literacy Program
|
Inclusion Criteria:~Full-time registered nurse (general) or enrolled nurse (general)~Take care for adult patients in emergency departments or medical ward~Exclusion Criteria:~Does not understand Chinese and English~Unable to access or use the internet.
| null | null |
All
|
No
|
Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study is a prospective 2-arm parallel controlled trial.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in level of mental health literacy | The level of participant's mental health literacy will be evaluated using The Mental Health Literacy Scale developed by Connor & Casey (2015). This questionnaire comprised 35 items which consisted of the ability to recognize disorders (8 questions), knowledge of where to seek information (4 questions), knowledge of risk factors and causes (2 questions), knowledge of self-treatment (2 questions), knowledge of professional help available (3 questions), attitudes that promote recognition or appropriate help-seeking behavior (16 questions) (O'Connor & Casey, 2015). Questions with a 4-point scale are rated 1 was very unlikely/unhelpful, 4 was very likely/helpful and for a 5-point scale that 1 strongly disagreed/definitely unwilling, 5 strongly agreed/definitely willing. The higher the total score indicates a higher level of mental health literacy. | Baseline, immediately after intervention, one month after intervention |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in perceived competency in caring for patients with mental illnesses | The Behavioral Health Care Competency survey will be used to assess the perceived competency in caring for patients with mental illnesses. It consists of 23-items to assess the participants' perception of their competency in assessment, intervention, recognition of the need for referral, and dealing with resources issues (Rutledge et al., 2013; Rutledge et al., 2012). Questions with a 5-point Likert-type scale with responses 1= Strongly disagree to 5= Strongly agree The higher the total score, the higher respondent's perceived competency in caring for patients with mental illnesses. | Baseline, immediately after intervention, one month after intervention |
| Change from baseline in level of work stress | The Workplace Stress Scale developed by the Marlin Company will be used to assess participants' work stress levels. This scale consists of eight items that describe the perception of the respondent toward his or her work. Questions with a 5-point scale are rated 1' was never, and 5 was very often. The higher the total score indicates a higher level of work stress. A total score of 15 or lower interpreted as stress is not much of an issue, whilst 31-40 was indicative of a potentially dangerous stress level that may need to seek professional assistance. | Baseline, immediately after intervention, one month after intervention |
| Change from baseline in patient satisfaction with nursing care | Hospital Patient Satisfaction Survey will be used to assess the patient satisfaction with nursing care in general hospitals. There are eight questions on the scale to measure patient satisfaction with nursing care during the hospitalization with a 4-point Likert scale (from 0=never to 4=always). | Baseline, immediately after intervention, one month after intervention |
|
Education, Mental health literacy, Nurses, General hospital
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mental Health Literacy Educational Program<br>An educational program consisting of six 30-minutes online educational sessions and one 60-minutes face-to-face session. | Other: Mental Health Literacy Program<br>* Six educational sessions will be delivered on a private YouTube channel which consists of information about mental health literacy (knowledge about priority mental illnesses, attitude/ stigma related to mental illnesses, and help-seeking efficacy). There will be six-weeks unrestricted access period. Afterwards, the round-up session which consists of problem-based learning and group sharing will be delivered in person. Two vignettes based on the clinical scenarios will be given for discussion. Furthermore, participants are encouraged to share their opinion on mental health literacy, strategies for dealing with difficulties of caring for patients with mental illnesses in general hospitals, way to promote mental health literacy of healthcare professionals in general hospitals<br>|
| No Intervention: Control Group<br>No active intervention | |
|
Interventional Study of Mental Health Literacy Educational Program for General Hospital Nurses
Study Overview
=================
Brief Summary
-----------------
Mental health literacy is a concept that encompasses knowledge of mental health, mental illnesses, and their management; mental illness-related attitudes/ stigma; and help-seeking efficacy. It impacted care provision by affecting healthcare professionals' ability to recognize, manage and prevent mental illnesses. It was found that physical-mental comorbidity (co-occurrence of physical and mental illnesses) imposed a burden on patients and the healthcare system. However, the referral rate to psychiatric consultation-liaison in general hospitals was low could be attributed to the suboptimal level of mental health literacy of general hospital healthcare professionals. Nurses are the major healthcare workforce in general hospitals for the initial identification of mental illness, help doctors to deal with patients' conditions, and make a contribution to positive patient outcomes in general hospitals. Therefore, there is an urgent need to improve the mental health literacy of nurses working in general hospitals. An education program had been developed guided by the concept of mental health literacy, and self-efficacy theory. This study aims to examine the effect of an educational program on improving the mental health literacy of general hospital nurses, in terms of knowledge of mental health, mental illnesses, and their treatment; attitude or stigma about mental illnesses; and help-seeking efficacy. It also measures the interventional effect on perceived competency in caring for patients with mental illness and work stress among general hospital nurses, as well as patient satisfaction with nursing care in general hospitals.
Detailed Description
-----------------
This study is a prospective 2-arm parallel controlled trial. The study sites will be conducted in the emergency departments and medical wards of two similar regional general hospitals. It is estimated using GPower that a sample size of 64 participants per group is adequate to detect an effect size of 0.5 on the primary outcomes at a post-intervention time point with 80% power at a 5% level of significance. Participants will be assigned to either an intervention group or a control group. Participants in the intervention group will receive a Mental Health Literacy Program consisting of six 30-minutes online educational sessions and one 60-minutes face-to-face session. No active intervention will be given to the control group. Outcome measures will be measured by the Mental Health Literacy Scale, the Behavioral Health Care Competency survey, the Workplace Stress Scale, and Hospital Patient Satisfaction Survey at baseline, immediately after intervention, and one-month after intervention.
Official Title
-----------------
The Effectiveness of an Educational Program on the Mental Health Literacy of Nurses Working in General Hospitals: a Controlled Trial
Conditions
-----------------
Mental Health Issue
Intervention / Treatment
-----------------
* Other: Mental Health Literacy Program
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Full-time registered nurse (general) or enrolled nurse (general) Take care for adult patients in emergency departments or medical ward Exclusion Criteria: Does not understand Chinese and English Unable to access or use the internet.
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study is a prospective 2-arm parallel controlled trial.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mental Health Literacy Educational Program<br>An educational program consisting of six 30-minutes online educational sessions and one 60-minutes face-to-face session. | Other: Mental Health Literacy Program<br>* Six educational sessions will be delivered on a private YouTube channel which consists of information about mental health literacy (knowledge about priority mental illnesses, attitude/ stigma related to mental illnesses, and help-seeking efficacy). There will be six-weeks unrestricted access period. Afterwards, the round-up session which consists of problem-based learning and group sharing will be delivered in person. Two vignettes based on the clinical scenarios will be given for discussion. Furthermore, participants are encouraged to share their opinion on mental health literacy, strategies for dealing with difficulties of caring for patients with mental illnesses in general hospitals, way to promote mental health literacy of healthcare professionals in general hospitals<br>|
| No Intervention: Control Group<br>No active intervention | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in level of mental health literacy | The level of participant's mental health literacy will be evaluated using The Mental Health Literacy Scale developed by Connor & Casey (2015). This questionnaire comprised 35 items which consisted of the ability to recognize disorders (8 questions), knowledge of where to seek information (4 questions), knowledge of risk factors and causes (2 questions), knowledge of self-treatment (2 questions), knowledge of professional help available (3 questions), attitudes that promote recognition or appropriate help-seeking behavior (16 questions) (O'Connor & Casey, 2015). Questions with a 4-point scale are rated 1 was very unlikely/unhelpful, 4 was very likely/helpful and for a 5-point scale that 1 strongly disagreed/definitely unwilling, 5 strongly agreed/definitely willing. The higher the total score indicates a higher level of mental health literacy. | Baseline, immediately after intervention, one month after intervention |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in perceived competency in caring for patients with mental illnesses | The Behavioral Health Care Competency survey will be used to assess the perceived competency in caring for patients with mental illnesses. It consists of 23-items to assess the participants' perception of their competency in assessment, intervention, recognition of the need for referral, and dealing with resources issues (Rutledge et al., 2013; Rutledge et al., 2012). Questions with a 5-point Likert-type scale with responses 1= Strongly disagree to 5= Strongly agree The higher the total score, the higher respondent's perceived competency in caring for patients with mental illnesses. | Baseline, immediately after intervention, one month after intervention |
| Change from baseline in level of work stress | The Workplace Stress Scale developed by the Marlin Company will be used to assess participants' work stress levels. This scale consists of eight items that describe the perception of the respondent toward his or her work. Questions with a 5-point scale are rated 1' was never, and 5 was very often. The higher the total score indicates a higher level of work stress. A total score of 15 or lower interpreted as stress is not much of an issue, whilst 31-40 was indicative of a potentially dangerous stress level that may need to seek professional assistance. | Baseline, immediately after intervention, one month after intervention |
| Change from baseline in patient satisfaction with nursing care | Hospital Patient Satisfaction Survey will be used to assess the patient satisfaction with nursing care in general hospitals. There are eight questions on the scale to measure patient satisfaction with nursing care during the hospitalization with a 4-point Likert scale (from 0=never to 4=always). | Baseline, immediately after intervention, one month after intervention |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Education, Mental health literacy, Nurses, General hospital
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NCT05578768
|
Prediction of IBD Disease Activity in Individual Patients Based on PROMs and Clinical Data
|
The proposed study will use a PROM (Patient report Outcome Measurement)-tool in combination with clinical and biochemical data to train and validate a Relapse Prediction Model for individual patients.
|
The primary objective is to train and validate a relapse prediction model for individual patients available for daily (remote) care management. Besides that, risk-based care pathways for different prediction outcomes will be evaluated, prediction scores will be correlated to medication type, CRP/Calprotectin and/or endoscopy, and with known IBD clinical risk profiles. Moreover dietary intake will be correlated with the IBD risk profiles.~Study design: Multicentre, retrospective analysis of two prospective cohorts. Study population: Adult IBD patients. Main study parameters/endpoints: The endpoint will be a prediction regarding step-up or step-down in the care pathways. In other words, the percentage of patients in each individual care pathway with agreement between risk score of the individual patient and actual flares during a follow-up time of 24 months. Furthermore insight will be gained in dietary patterns amongst patients with different IBD risk profiles.~No benefits or risks are associated with participating in this study, because only standard of care is given.
|
Prediction of IBD Disease Activity in Individual Patients Based on PROMs and Clinical Data
|
IBD, Inflammatory Bone Disease
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* Other: No intervention
|
Inclusion Criteria:~Adult IBD patients~Subjects willing and able to sign informed consent~Own and are able to use a smart phone (Android or iOS)~Exclusion Criteria:~Unwilling or unable to adhere to the protocol~Unwilling or unable to adhere to the informed consent~Age <18y
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Develop a relapse prediction model for individual patients (agreement between risk score of the individual patient and actual flares) based on both clinical parameters and biochemical parameters in the individual care pathways. | This model will be based on both clinical parameters and biochemical parameters in the individual care pathways. | After 2 years |
| Validate the above mentioned prediction model and make it available for daily (remote) care management. | Based on the information form the validation cohort. The model will be validated retrospectively. | After 2 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evaluate risk-based care pathways for different prediction outcomes in clinical practice e.g. high intensity monitoring care pathway for patients with a high prediction score. | Evaluate whether predefined risk-based care pathways are in line with prediction outcomes of the relapse prediction model. | After 2 years |
| Correlate the prediction scores of the different care pathways to medication type. | See if there is a statistical correlation between medication type and prediction score | After 2 years |
| Correlate prediction scores of the different pathways with biomarkers CRP/Calprotectin and/or endoscopy | See if there is a statistical correlation between prediction score and biomarkers CRP/Calprotectin and/or endoscopy | After 2 years |
| Correlate prediction scores from the algorithm with known IBD clinical risk factors | See if there is a statistical correlation between prediction scores from the model to known clinical risk factors like e.g. operation history, presence of EIM. | After 2 years |
| Correlate dietary intake with the assigned IBD clinical risk profiles | See if there is a statistical correlation between dietary intake and assigned IBD clinical risk profile. | After 2 years |
|
Bone Diseases, Osteitis, Musculoskeletal Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| training phase<br>The study procedures for both cohorts are the same. | Other: No intervention<br>* Patients will receive standard of care.<br>|
| validation phase<br>The study procedures for both cohorts are the same. | Other: No intervention<br>* Patients will receive standard of care.<br>|
|
Prediction of IBD Disease Activity in Individual Patients Based on PROMs and Clinical Data
Study Overview
=================
Brief Summary
-----------------
The proposed study will use a PROM (Patient report Outcome Measurement)-tool in combination with clinical and biochemical data to train and validate a Relapse Prediction Model for individual patients.
Detailed Description
-----------------
The primary objective is to train and validate a relapse prediction model for individual patients available for daily (remote) care management. Besides that, risk-based care pathways for different prediction outcomes will be evaluated, prediction scores will be correlated to medication type, CRP/Calprotectin and/or endoscopy, and with known IBD clinical risk profiles. Moreover dietary intake will be correlated with the IBD risk profiles. Study design: Multicentre, retrospective analysis of two prospective cohorts. Study population: Adult IBD patients. Main study parameters/endpoints: The endpoint will be a prediction regarding step-up or step-down in the care pathways. In other words, the percentage of patients in each individual care pathway with agreement between risk score of the individual patient and actual flares during a follow-up time of 24 months. Furthermore insight will be gained in dietary patterns amongst patients with different IBD risk profiles. No benefits or risks are associated with participating in this study, because only standard of care is given.
Official Title
-----------------
Prediction of IBD Disease Activity in Individual Patients Based on PROMs and Clinical Data
Conditions
-----------------
IBD, Inflammatory Bone Disease
Intervention / Treatment
-----------------
* Other: No intervention
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult IBD patients Subjects willing and able to sign informed consent Own and are able to use a smart phone (Android or iOS) Exclusion Criteria: Unwilling or unable to adhere to the protocol Unwilling or unable to adhere to the informed consent Age <18y
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| training phase<br>The study procedures for both cohorts are the same. | Other: No intervention<br>* Patients will receive standard of care.<br>|
| validation phase<br>The study procedures for both cohorts are the same. | Other: No intervention<br>* Patients will receive standard of care.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Develop a relapse prediction model for individual patients (agreement between risk score of the individual patient and actual flares) based on both clinical parameters and biochemical parameters in the individual care pathways. | This model will be based on both clinical parameters and biochemical parameters in the individual care pathways. | After 2 years |
| Validate the above mentioned prediction model and make it available for daily (remote) care management. | Based on the information form the validation cohort. The model will be validated retrospectively. | After 2 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evaluate risk-based care pathways for different prediction outcomes in clinical practice e.g. high intensity monitoring care pathway for patients with a high prediction score. | Evaluate whether predefined risk-based care pathways are in line with prediction outcomes of the relapse prediction model. | After 2 years |
| Correlate the prediction scores of the different care pathways to medication type. | See if there is a statistical correlation between medication type and prediction score | After 2 years |
| Correlate prediction scores of the different pathways with biomarkers CRP/Calprotectin and/or endoscopy | See if there is a statistical correlation between prediction score and biomarkers CRP/Calprotectin and/or endoscopy | After 2 years |
| Correlate prediction scores from the algorithm with known IBD clinical risk factors | See if there is a statistical correlation between prediction scores from the model to known clinical risk factors like e.g. operation history, presence of EIM. | After 2 years |
| Correlate dietary intake with the assigned IBD clinical risk profiles | See if there is a statistical correlation between dietary intake and assigned IBD clinical risk profile. | After 2 years |
|
||
NCT03727763
|
Cetuximab and Vemurafenib Plus FOLFIRI for BRAF V600E Mutated Advanced Colorectal Cancer (IMPROVEMENT)
|
This clinical trial aims to evaluate the efficacy, safety of FOLFIRI with vemurafenib and cetuximab in Advanced Colorectal Cancer Patients with BRAF V600E mutation.
|
Cetuximab and Vemurafenib Plus FOLFIRI for BRAF V600E Mutated Advanced Colorectal Cancer (IMPROVEMENT): A Single-arm Study
|
Colorectal Cancer
|
* Drug: Vemurafenib
* Drug: Cetuximab
|
Inclusion Criteria:~Patients have histologically or cytologically confirmed advanced or recurrent CRC;~Patients with BRAV V600E mutation/KRAS WT based on the NGS or ARMS-PCR detection of tumor tissue;~Patients have measurable disease as defined by RECIST 1.1 as determined by investigator;~Patient with a history of radiotherapy at least 3 months before on the day of providing consent, but the measurable lesion should not be within the scope of radiotherapy;~Patients without a history of receiving vemurafenib or cetuximab;~Patients with age of 18-75yr;~Patients with a performance status of 0,1or 2 on the Eastern Cooperative Oncology Group.；~Patients with Life expectancy of more than 12 weeks;~Patients must have the ability to understand and sign the written informed consent voluntarily;~Female of childbearing potential who are negative in a pregnancy test within 14 days before enrollment. Both male and female patients should agree to use an adequate method of contraception (total abstinence, an intrauterine device or hormone releasing system, an contraceptive implant and an oral contraceptive) starting with the first dose of study therapy through 120 days after the last dose of study therapy. Duration will be determined when the subject is assigned to treatment.~Exclusion Criteria:~Patients with KRAS/NRAS mutation;~Patients with major surgery or severe trauma within 4 weeks before the first medication;~Patients with hypersensitivity to the components in the study protocol;；~Patients who are ready to give birth or are pregnant.。~Patients with brain metastases 。~Bone marrow, liver and kidney function did not meet the requirements of chemotherapy as follows：~Neutrophil count<1,500/mm3；~Platelet count <80,000/mm3；~Total bilirubin >1.5-times the upper limit of normal；~ALT/AST>2.5-times the upper limit of normal for patients without liver metastases; (5.0-times the upper limit of normal for patients without liver metastases)~Creatinine >1.5-times the upper limit of normal；~Patients with cancers other than advanced colorectal cancer within five years prior to the start of treatment in this study. Cervical carcinoma in situ, cured basal cell carcinoma and bladder epithelial tumor were excluded;；~Patients without legal capacity or limited civil capacity;
|
18 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate(ORR) | Evaluation of tumor burden based on RECIST criteria every 3 cycles(each cycle is 14 days), ORR is the proportion of patients with reduction in tumor burden of a predefined amount, including complete response and partial response. | up to 55 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) | Evaluation of tumor burden based on RECIST criteria every 3 cycles(each cycle is 14 days), and DCR is the proportion of patients with reduction in tumor burden of a predefined amount, including complete response, partial response and stable disease | up to 55 months |
| Progression-free survival | Evaluation of tumor burden based on RECIST criteria until first documented progress through study completion, an average of 6 weeks | Time from treatment beginning until the date of first documented progression, assessed up to 55 months |
| Overall survival | From date of treatment beginning until the date of death from any cause, through study completion, an average of 6 weeks | Time from treatment beginning until date of death from any cause, assessed up to 55 months |
| adverse events | Incidence of Treatment-related adverse Events | Through study completion, an average of 4 weeks |
|
FLOFIRI, vemurafenib, cetuximab, BRAF V600E mutation, Advanced Colorectal Cancer
|
Cetuximab, Vemurafenib, Antineoplastic Agents, Immunological, Antineoplastic Agents, Protein Kinase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FIVC group<br>Irinotecan 180mg/m2 iv gtt (14 days per course) leucovorin 400mg/m2 iv gtt (14 days per course) 5-fluorouracil 400mg/m2 iv (14 days per course) 5-fluorouracil 2400 mg/m2 46h (14 days per course) vemurafenib 960mg po bid cetuximab 500mg/m2 iv gtt (14 days per course) | Drug: Vemurafenib<br>* 960mg po bid<br>* Other names: PLX4032, RG7204;Drug: Cetuximab<br>* 500mg/m2 iv gtt (14 days per course)<br>* Other names: ERBITUX;|
|
Cetuximab and Vemurafenib Plus FOLFIRI for BRAF V600E Mutated Advanced Colorectal Cancer (IMPROVEMENT)
Study Overview
=================
Brief Summary
-----------------
This clinical trial aims to evaluate the efficacy, safety of FOLFIRI with vemurafenib and cetuximab in Advanced Colorectal Cancer Patients with BRAF V600E mutation.
Official Title
-----------------
Cetuximab and Vemurafenib Plus FOLFIRI for BRAF V600E Mutated Advanced Colorectal Cancer (IMPROVEMENT): A Single-arm Study
Conditions
-----------------
Colorectal Cancer
Intervention / Treatment
-----------------
* Drug: Vemurafenib
* Drug: Cetuximab
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients have histologically or cytologically confirmed advanced or recurrent CRC; Patients with BRAV V600E mutation/KRAS WT based on the NGS or ARMS-PCR detection of tumor tissue; Patients have measurable disease as defined by RECIST 1.1 as determined by investigator; Patient with a history of radiotherapy at least 3 months before on the day of providing consent, but the measurable lesion should not be within the scope of radiotherapy; Patients without a history of receiving vemurafenib or cetuximab; Patients with age of 18-75yr; Patients with a performance status of 0,1or 2 on the Eastern Cooperative Oncology Group.； Patients with Life expectancy of more than 12 weeks; Patients must have the ability to understand and sign the written informed consent voluntarily; Female of childbearing potential who are negative in a pregnancy test within 14 days before enrollment. Both male and female patients should agree to use an adequate method of contraception (total abstinence, an intrauterine device or hormone releasing system, an contraceptive implant and an oral contraceptive) starting with the first dose of study therapy through 120 days after the last dose of study therapy. Duration will be determined when the subject is assigned to treatment. Exclusion Criteria: Patients with KRAS/NRAS mutation; Patients with major surgery or severe trauma within 4 weeks before the first medication; Patients with hypersensitivity to the components in the study protocol;； Patients who are ready to give birth or are pregnant.。 Patients with brain metastases 。 Bone marrow, liver and kidney function did not meet the requirements of chemotherapy as follows： Neutrophil count<1,500/mm3； Platelet count <80,000/mm3； Total bilirubin >1.5-times the upper limit of normal； ALT/AST>2.5-times the upper limit of normal for patients without liver metastases; (5.0-times the upper limit of normal for patients without liver metastases) Creatinine >1.5-times the upper limit of normal； Patients with cancers other than advanced colorectal cancer within five years prior to the start of treatment in this study. Cervical carcinoma in situ, cured basal cell carcinoma and bladder epithelial tumor were excluded;； Patients without legal capacity or limited civil capacity;
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FIVC group<br>Irinotecan 180mg/m2 iv gtt (14 days per course) leucovorin 400mg/m2 iv gtt (14 days per course) 5-fluorouracil 400mg/m2 iv (14 days per course) 5-fluorouracil 2400 mg/m2 46h (14 days per course) vemurafenib 960mg po bid cetuximab 500mg/m2 iv gtt (14 days per course) | Drug: Vemurafenib<br>* 960mg po bid<br>* Other names: PLX4032, RG7204;Drug: Cetuximab<br>* 500mg/m2 iv gtt (14 days per course)<br>* Other names: ERBITUX;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate(ORR) | Evaluation of tumor burden based on RECIST criteria every 3 cycles(each cycle is 14 days), ORR is the proportion of patients with reduction in tumor burden of a predefined amount, including complete response and partial response. | up to 55 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) | Evaluation of tumor burden based on RECIST criteria every 3 cycles(each cycle is 14 days), and DCR is the proportion of patients with reduction in tumor burden of a predefined amount, including complete response, partial response and stable disease | up to 55 months |
| Progression-free survival | Evaluation of tumor burden based on RECIST criteria until first documented progress through study completion, an average of 6 weeks | Time from treatment beginning until the date of first documented progression, assessed up to 55 months |
| Overall survival | From date of treatment beginning until the date of death from any cause, through study completion, an average of 6 weeks | Time from treatment beginning until date of death from any cause, assessed up to 55 months |
| adverse events | Incidence of Treatment-related adverse Events | Through study completion, an average of 4 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
FLOFIRI, vemurafenib, cetuximab, BRAF V600E mutation, Advanced Colorectal Cancer
|
|
NCT00270374
|
A Study Comparing Blood Flow and Clinical and Safety Effects of the Addition of Natrecor (Nesiritide), Placebo or Intravenous Nitroglycerin to Standard Care for the Treatment of Worsening Congestive Heart Failure.
|
The purpose of this study is to compare the hemodynamic (blood flow) and clinical effects of the study drug, Natrecor (nesiritide, a recombinant form of the natural human peptide normally secreted by the heart in response to heart failure) to those of intravenous nitroglycerin or placebo, when added to the standard care therapy that is usually administered in the treatment of patients with worsening congestive heart failure.
|
Advanced congestive heart failure (CHF) accounts for over 1 million hospital admissions yearly in the U.S. and is also associated with a high rate of readmission to the hospital within a short turn-around time period following discharge. CHF is associated with a relatively high death rate, up to 40 or 50% in 2 years. The risk of sudden cardiac death in patients with CHF is 6 to 9 times greater than that of the general population. Despite medical advances, some patients are unresponsive to the oral medications used to treat CHF and require added therapy. Such patients are typically New York Heart Association (NYHA) Class III and IV, and require intravenous (IV) therapy with inotropic agents. Inotropic agents are drugs that influence muscular contractility. IV administration with inotropic drugs requires careful patient selection and close monitoring to ensure safe and effective therapy.~There are many medical conditions that lead to worsening CHF and these underlying conditions contribute to a significant and potentially life-threatening loss of cardiac function. Some of these are conditions that lead to abnormal cardiac contraction and/or relaxation (e.g., coronary arterial disease, hypertension, diabetes, drug or alcohol toxicity); conditions that lead to volume or pressure overload (mitral or tricuspid valve regurgitation, hyperthyroidism); and conditions that limit ventricle filling (e.g., mitral or tricuspid valve stenosis). However, many patients have a condition of dilated cardiomyopathy, an abnormality of the heart muscle wall in which the walls of the heart become stretched and weakened, with no easily identifiable cause. Any risk factor may cause CHF, but combinations dramatically increase the risk of developing CHF.~Natriuretic peptides ANP and BNP are small molecules and are the group of naturally-occuring substances that act in the body to oppose the activity of the renin-angiotensin-aldosterone (RAA) system. They serve as counter-regulatory hormones and are secreted in response to the increased atrial and ventricular stretching that occurs in secondary increased blood volume. Natrecor (nesiritide) is the proprietary name for the IV formulation of human B-type natriuretic peptide (hBNP).~In-patient treatment for acutely decompensated CHF with intravenous vasodilator therapy (such as nitroglycerin or nitroprusside) is useful for a number of reasons. Vasodilators reduce ventricular filling pressure and volume, decreasing pulmonary congestion and the resulting symptoms of breathlessness. Intravenous vasodilators may also achieve afterload reduction leading to decreased mitral regurgitation and increased forward stroke volume. IV administration of externally produced hBNP leads to vasodilation, antagonism of the renin-aldosterone system and an increase in diuresis. hBNP may be a potent agent for the treatment of CHF, with a unique combination of desirable blood flow throughout the body, hormones secreted by the sympathetic nervous system, and renal effects not possessed by currently available therapies. In a 6-hour placebo-controlled comparison in patients with acutely decompensated CHF, Natrecor® was associated with significant improvements in the symptoms of CHF (including dyspnea and fatigue), a decrease in aldosterone, and an increase in urine output. (According to LeJemtel et al 1998) The VMAC trial (Vasodilation in the Management of Acute CHF) is a double-blinded, randomized, active-controlled and placebo-controlled study in which the study drug would be added to standard care therapies such as diuretics, dobutamine, or dopamine. This study compares the effects of the addition of Natrecor®, nitroglycerin, or placebo to standard care (diuretics, dobutamine, dopamine, or other long-term cardiac therapies) in patients requiring hospitalization for the treatment of dyspnea at rest due to acutely decompensated CHF. Based on the cumulative experience with Natrecor, the dose of Natrecor was modified for the VMAC trial to a 2-µg/kg bolus followed by a 0.01-µg/kg/min infusion.~The primary objective of the VMAC study is to compare the blood flow and observe treatment and safety effects of the new dose of Natrecor to placebo, when added to standard care, in the treatment of acutely worsening CHF. The primary overall outcome that the study plan is based upon are the changes from the beginning of a study to 3 hours after the start of study drug, in pulmonary capillary wedge pressure (PCWP) (in subjects who have right heart catheters only) and the subject's self-evaluation of their breathing difficulties. The secondary objective is to compare the hemodynamic, (blood flow throughout the body) and clinical effects of Natrecor® with IV nitroglycerin and placebo. Additional objectives include a comparison of the use of other IV vasoactive agents and/or IV diuretics and the effects on other hemodynamic variables. The hypothesis of this study is that using the modified dose of Natrecor, (a 2-µg/kg bolus followed by a 0.01-µg/kg/min infusion) will achieve peak effects sooner than with previously studied doses, to sustain effects for at least 48 hours, and minimize excessive effects on blood pressure. Natrecor or placebo, administered as an intravenous 2-µg/kg bolus, followed by a fixed-dose infusion of 0.01-µg/kg/min.
|
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Hemodynamic and Clinical Effects of Natrecor (Nesiritide) Compared With Nitroglycerin Therapy for Symptomatic Decompensated CHF, The VMAC Trial: Vasodilation in the Management of Acute Congestive Heart Failure
|
Symptomatic Decompensated Congestive Heart Failure, Congestive Heart Failure in Acute Coronary Syndrome
|
* Drug: nesiritide
|
Inclusion Criteria:~Patients with dyspnea (difficulty breathing and shortness of breath) at rest, while supine, or immediately upon minimal activity such as talking, eating, or bathing~having evidence of heart disease, rather than pulmonary disease, as the primary cause for the dyspnea (by demonstrating at least two of the following: jugular venous distension, paroxysmal nocturnal dyspnea or 2-pillow orthopnea within 72 hours before the start of study drug, abdominal discomfort due to hepatosplanchnic congestion, chest x-ray with findings indicative of heart failure)~having elevated cardiac filling pressures either by clinical estimate in non-catheterized patients, or a measured pulmonary capillary wedge pressure (PCWP) >= 20 mm Hg in catheterized patients~requiring hospitalization and intravenous therapy for at least 24 hours for the treatment of acutely decompensated heart failure.~Exclusion Criteria:~NPatients having systolic blood pressure consistently less than 90 mm Hg~having cardiogenic shock (a sudden decrease in blood pressure that results in decreased perfusion of body tissues and organs), volume depletion, or any other clinical condition that would contraindicate the administration of an intravenous agent with potent vasodilating properties~having their most recent pulmonary capillary wedge pressure (PCWP) < 20 mm Hg within 24 hours before randomization~having a clinical status so acutely unstable that the potential subject could not tolerate placement of a right heart catheter or the 3-hour placebo period~unable to have intravenous nitroglycerin withheld (e.g., intravenous nitroglycerin for management of an acute coronary syndrome).
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to 3 hours after the start of study drug in PCWP (pulmonary capillary wedge pressure) in subjects who have right heart catheters; Change from baseline in dyspnea (difficult breathing) 3 hours after the start study drug | | |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on PCWP (pulmonary capillary wedge pressure) and dyspnea (difficult breathing) 1 hour after the start of study drug; Onset of effect on PCWP; Effect on PCWP 24 hours after the start of study drug; Overall safety profile | | |
|
Congestive heart failure, CHF, Left-sided heart failure, Right-sided heart failure, Systolic Heart Failure
|
Natriuretic Peptide, Brain, Natriuretic Agents, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>nesiritide | Drug: nesiritide<br> <br> |
|
A Study Comparing Blood Flow and Clinical and Safety Effects of the Addition of Natrecor (Nesiritide), Placebo or Intravenous Nitroglycerin to Standard Care for the Treatment of Worsening Congestive Heart Failure.
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare the hemodynamic (blood flow) and clinical effects of the study drug, Natrecor (nesiritide, a recombinant form of the natural human peptide normally secreted by the heart in response to heart failure) to those of intravenous nitroglycerin or placebo, when added to the standard care therapy that is usually administered in the treatment of patients with worsening congestive heart failure.
Detailed Description
-----------------
Advanced congestive heart failure (CHF) accounts for over 1 million hospital admissions yearly in the U.S. and is also associated with a high rate of readmission to the hospital within a short turn-around time period following discharge. CHF is associated with a relatively high death rate, up to 40 or 50% in 2 years. The risk of sudden cardiac death in patients with CHF is 6 to 9 times greater than that of the general population. Despite medical advances, some patients are unresponsive to the oral medications used to treat CHF and require added therapy. Such patients are typically New York Heart Association (NYHA) Class III and IV, and require intravenous (IV) therapy with inotropic agents. Inotropic agents are drugs that influence muscular contractility. IV administration with inotropic drugs requires careful patient selection and close monitoring to ensure safe and effective therapy. There are many medical conditions that lead to worsening CHF and these underlying conditions contribute to a significant and potentially life-threatening loss of cardiac function. Some of these are conditions that lead to abnormal cardiac contraction and/or relaxation (e.g., coronary arterial disease, hypertension, diabetes, drug or alcohol toxicity); conditions that lead to volume or pressure overload (mitral or tricuspid valve regurgitation, hyperthyroidism); and conditions that limit ventricle filling (e.g., mitral or tricuspid valve stenosis). However, many patients have a condition of dilated cardiomyopathy, an abnormality of the heart muscle wall in which the walls of the heart become stretched and weakened, with no easily identifiable cause. Any risk factor may cause CHF, but combinations dramatically increase the risk of developing CHF. Natriuretic peptides ANP and BNP are small molecules and are the group of naturally-occuring substances that act in the body to oppose the activity of the renin-angiotensin-aldosterone (RAA) system. They serve as counter-regulatory hormones and are secreted in response to the increased atrial and ventricular stretching that occurs in secondary increased blood volume. Natrecor (nesiritide) is the proprietary name for the IV formulation of human B-type natriuretic peptide (hBNP). In-patient treatment for acutely decompensated CHF with intravenous vasodilator therapy (such as nitroglycerin or nitroprusside) is useful for a number of reasons. Vasodilators reduce ventricular filling pressure and volume, decreasing pulmonary congestion and the resulting symptoms of breathlessness. Intravenous vasodilators may also achieve afterload reduction leading to decreased mitral regurgitation and increased forward stroke volume. IV administration of externally produced hBNP leads to vasodilation, antagonism of the renin-aldosterone system and an increase in diuresis. hBNP may be a potent agent for the treatment of CHF, with a unique combination of desirable blood flow throughout the body, hormones secreted by the sympathetic nervous system, and renal effects not possessed by currently available therapies. In a 6-hour placebo-controlled comparison in patients with acutely decompensated CHF, Natrecor® was associated with significant improvements in the symptoms of CHF (including dyspnea and fatigue), a decrease in aldosterone, and an increase in urine output. (According to LeJemtel et al 1998) The VMAC trial (Vasodilation in the Management of Acute CHF) is a double-blinded, randomized, active-controlled and placebo-controlled study in which the study drug would be added to standard care therapies such as diuretics, dobutamine, or dopamine. This study compares the effects of the addition of Natrecor®, nitroglycerin, or placebo to standard care (diuretics, dobutamine, dopamine, or other long-term cardiac therapies) in patients requiring hospitalization for the treatment of dyspnea at rest due to acutely decompensated CHF. Based on the cumulative experience with Natrecor, the dose of Natrecor was modified for the VMAC trial to a 2-µg/kg bolus followed by a 0.01-µg/kg/min infusion. The primary objective of the VMAC study is to compare the blood flow and observe treatment and safety effects of the new dose of Natrecor to placebo, when added to standard care, in the treatment of acutely worsening CHF. The primary overall outcome that the study plan is based upon are the changes from the beginning of a study to 3 hours after the start of study drug, in pulmonary capillary wedge pressure (PCWP) (in subjects who have right heart catheters only) and the subject's self-evaluation of their breathing difficulties. The secondary objective is to compare the hemodynamic, (blood flow throughout the body) and clinical effects of Natrecor® with IV nitroglycerin and placebo. Additional objectives include a comparison of the use of other IV vasoactive agents and/or IV diuretics and the effects on other hemodynamic variables. The hypothesis of this study is that using the modified dose of Natrecor, (a 2-µg/kg bolus followed by a 0.01-µg/kg/min infusion) will achieve peak effects sooner than with previously studied doses, to sustain effects for at least 48 hours, and minimize excessive effects on blood pressure. Natrecor or placebo, administered as an intravenous 2-µg/kg bolus, followed by a fixed-dose infusion of 0.01-µg/kg/min.
Official Title
-----------------
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Hemodynamic and Clinical Effects of Natrecor (Nesiritide) Compared With Nitroglycerin Therapy for Symptomatic Decompensated CHF, The VMAC Trial: Vasodilation in the Management of Acute Congestive Heart Failure
Conditions
-----------------
Symptomatic Decompensated Congestive Heart Failure, Congestive Heart Failure in Acute Coronary Syndrome
Intervention / Treatment
-----------------
* Drug: nesiritide
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with dyspnea (difficulty breathing and shortness of breath) at rest, while supine, or immediately upon minimal activity such as talking, eating, or bathing having evidence of heart disease, rather than pulmonary disease, as the primary cause for the dyspnea (by demonstrating at least two of the following: jugular venous distension, paroxysmal nocturnal dyspnea or 2-pillow orthopnea within 72 hours before the start of study drug, abdominal discomfort due to hepatosplanchnic congestion, chest x-ray with findings indicative of heart failure) having elevated cardiac filling pressures either by clinical estimate in non-catheterized patients, or a measured pulmonary capillary wedge pressure (PCWP) >= 20 mm Hg in catheterized patients requiring hospitalization and intravenous therapy for at least 24 hours for the treatment of acutely decompensated heart failure. Exclusion Criteria: NPatients having systolic blood pressure consistently less than 90 mm Hg having cardiogenic shock (a sudden decrease in blood pressure that results in decreased perfusion of body tissues and organs), volume depletion, or any other clinical condition that would contraindicate the administration of an intravenous agent with potent vasodilating properties having their most recent pulmonary capillary wedge pressure (PCWP) < 20 mm Hg within 24 hours before randomization having a clinical status so acutely unstable that the potential subject could not tolerate placement of a right heart catheter or the 3-hour placebo period unable to have intravenous nitroglycerin withheld (e.g., intravenous nitroglycerin for management of an acute coronary syndrome).
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>nesiritide | Drug: nesiritide<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to 3 hours after the start of study drug in PCWP (pulmonary capillary wedge pressure) in subjects who have right heart catheters; Change from baseline in dyspnea (difficult breathing) 3 hours after the start study drug | | |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on PCWP (pulmonary capillary wedge pressure) and dyspnea (difficult breathing) 1 hour after the start of study drug; Onset of effect on PCWP; Effect on PCWP 24 hours after the start of study drug; Overall safety profile | | |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Congestive heart failure, CHF, Left-sided heart failure, Right-sided heart failure, Systolic Heart Failure
|
NCT05534139
|
Clinicopathological MRI and CSF Correlates in Huntington's Disease.
|
In this study the investigators will link brain iron levels obtained from quantitative susceptibility maps of HD patients with specific and well-known clinical CSF markers for iron accumulation, neurodegeneration and neuroinflammation. The relationship between iron accumulation and neuroinflammation, and the clinical and genetic characteristics of HD will be investigated. This will provide an important basis for the evaluation of brain iron levels as an imaging biomarker for disease state in HD and their relationship with the salient pathomechanisms of the disease.
|
This investigator-initiated, single-site cross-sectional study looks at iron accumulation using 7T MR-imaging, CSF and blood. This will be achieved in a two-day visit involving clinical assessments, MRI-scanning of the brain, followed by a lumbar puncture the next day, after overnight fasting. Sixty-five volunteers with HD and 25 volunteers without HD will be included. Of these 65 volunteers with HD, 25 will be premanifest, 20 early manifest and 20 moderate manifest, in order to cover the wide-spectrum of Huntington's Disease.
|
Clinicopathological MRI and CSF Correlates of Iron Accumulation, Neurodegeneration and Neuroinflammation in Huntington's Disease.
|
Huntington Disease
|
* Diagnostic Test: 7T MRI-scan
* Diagnostic Test: CSF collection via lumbar puncture
* Diagnostic Test: Blood withdrawal
* Diagnostic Test: Clinical measures
|
Inclusion Criteria:~Native Dutch/Flemish speaker~Ability to undergo MRI scanning;~Written informed consent must be obtained from the participant.~And in addition:~If the participant is a pre-manifest HD gene carrier:~CAG expansion ≥ 40;~UHDRS Total Motor Score (TMS) ≤ 5;~Total Functional Capacity (TFC) = 13;~Diagnostic Confidence Score < 4.~If the participant is an early-manifest HD gene carrier:~CAG expansion ≥ 36;~Diagnostic Confidence Score = 4;~HD stage I: TFC scores between 11 and 13 inclusive.~If the participant is a moderate manifest HD gene carrier:~CAG expansion ≥ 36;~Diagnostic Confidence Score = 4;~HD stage II: TFC scores between 7 and 11 inclusive.~If the participant is a control subject:~Partner/spouse of a patient not at risk of HD OR sibling with genetic test results available that show a normal CAG repeat length for both HTT alleles (<36);~No other known cognitive, neurological or psychiatric disorders.~Exclusion Criteria:~Additional major comorbidities not related to HD (e.g. cardiovascular diseases, coagulopathy, hypertension, diabetes mellitus, and/or other neurological disorders);~History of severe head injury;~Status of the participant after brain surgery;~Past erythrocyte transfusions;~Use of investigational drugs or participation in a clinical drug trial within 30 days prior to study visit;~Current intoxication, drug or alcohol abuse or dependence;~Pregnancy;~Inability to understand the information about the protocol;~Severe physical restrictions (completely wheelchair dependent);~Severe chorea that, in the investigator's judgment, precludes the patient's participation in and completion of the MRI and/or lumbar puncture.~Contra-indication to MRI scanning, such as:~Claustrophobia;~Pacemakers and defibrillators;~Nerve stimulators;~Intracranial clips;~Intraorbital or intraocular metallic fragments;~Cochlear implants;~Ferromagnetic implants;~Hydrocephalus pump;~Intra-utrine device (not all types);~Permanent make-up;~Tattoos above the shoulders (not all).~Contraindications for a lumbar puncture, including:~Screening blood test results outside normal ranges(white cell count, neutrophil count, lymphocyte count, hemoglobin, platelets, Prothrombin time (PT), activated partial thromboplastin time (APTT), C-reactive protein (CRP) and serum ferritin) if only marginally decreased or increased this will be decided by the clinical PI;~Signs and symptoms of increased intracranial pressure which will be confirmed on the 7T MRI (T1 and FLAIR scan) or by a fundoscopy;~Local infections of the skin;~Use of anti-coagulant drugs within the last 14 days prior lumbar puncture.
|
21 Years
|
75 Years
|
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantified Susceptibility Mapping | MRI analysis to quantify iron accumulation | At baseline |
| Iron in CSF | Amount of iron and ferritin measured in CSF | At baseline |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Iron in blood | Amount of iron and ferritin measured in blood | At baseline |
| Clinical motor signs | Motor signs obtained using the Unified Huntington's Disease Rating Scale - Total Motor Score. This is a scale assessing motor symptoms of HD, ranging from a score of 0 to 124, where higher scores mean a worse outcome. | At baseline |
| Neuroinflammation and neurodegeneration biomarkers in CSF | a.o.~NFL: pg/mL~CHIT1: pg/mL~IL-6: pg/mL | Baseline |
| Neuroinflammation and neurodegeneration biomarkers in CSF | - YKL-40: ng/mL | Baseline |
| Cognitive score | Assessment of cognitive tests. | At baseline |
| Neuropsychiatric symptoms | Assessment of short Problem Behaviour Assessment. Each symptom is rated for severity on a 5-point scale : 0 = not at all; 1 = trivial; 2 = mild; 3 = moderate (disrupting everyday activities) and 4 = severe or intolerable. Each symptom is also scored for frequency on a 5-point scale as follows: 0 = symptom absent; 1 = less than once weekly; 2 = at least once a week; 3 = most days (up to and including some part of everyday); and 4 = all day, every day. Severity and frequency scores are multiplied to produce an overall 'PBA score' for each symptom. | At baseline |
|
7T-MRI, Huntington's Disease, Iron accumulation, Quantified susceptibility mapping, QSM, CSF, Neurodegeneration, Neuroinflammation
|
Huntington Disease, Basal Ganglia Diseases, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Dementia, Chorea, Dyskinesias, Movement Disorders, Heredodegenerative Disorders, Nervous System, Neurodegenerative Diseases, Genetic Diseases, Inborn, Cognition Disorders, Neurocognitive Disorders, Mental Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy controls<br>Partner/spouse of a patient not at risk of HD OR sibling with genetic test results available that show a normal CAG repeat length for both HTT alleles (<36); No other known cognitive, neurological or psychiatric disorders. | Diagnostic Test: 7T MRI-scan<br>* MRI-scanning of the brain using a 7T-MRI scanner<br>Diagnostic Test: CSF collection via lumbar puncture<br>* CSF is collected by doing a lumbar puncture<br>Diagnostic Test: Blood withdrawal<br>* Blood is collected by doing a blood withdrawal<br>Diagnostic Test: Clinical measures<br>* UHDRS-Total motor score, UHDRS-short problem behaviour assessment, UHDRS-Cognitive assessments<br>|
| Premanifest HD expanded gene carrier<br>HDGEC before clinical onset: TMS <5, DCL <4, TFC = 13. No other major comorbidity. | Diagnostic Test: 7T MRI-scan<br>* MRI-scanning of the brain using a 7T-MRI scanner<br>Diagnostic Test: CSF collection via lumbar puncture<br>* CSF is collected by doing a lumbar puncture<br>Diagnostic Test: Blood withdrawal<br>* Blood is collected by doing a blood withdrawal<br>Diagnostic Test: Clinical measures<br>* UHDRS-Total motor score, UHDRS-short problem behaviour assessment, UHDRS-Cognitive assessments<br>|
| Early Manifest HD patient<br>HDGEC after clincial onset: TMS >5, DCL = 4. Early stage of disease: TFC 11-13. No other major comorbidity. | Diagnostic Test: 7T MRI-scan<br>* MRI-scanning of the brain using a 7T-MRI scanner<br>Diagnostic Test: CSF collection via lumbar puncture<br>* CSF is collected by doing a lumbar puncture<br>Diagnostic Test: Blood withdrawal<br>* Blood is collected by doing a blood withdrawal<br>Diagnostic Test: Clinical measures<br>* UHDRS-Total motor score, UHDRS-short problem behaviour assessment, UHDRS-Cognitive assessments<br>|
| Moderate Manifest HD patient<br>HDGEC after clincial onset: TMS >5, DCL = 4. Moderate stage of disease: TFC 7-10. No other major comorbidity. | Diagnostic Test: 7T MRI-scan<br>* MRI-scanning of the brain using a 7T-MRI scanner<br>Diagnostic Test: CSF collection via lumbar puncture<br>* CSF is collected by doing a lumbar puncture<br>Diagnostic Test: Blood withdrawal<br>* Blood is collected by doing a blood withdrawal<br>Diagnostic Test: Clinical measures<br>* UHDRS-Total motor score, UHDRS-short problem behaviour assessment, UHDRS-Cognitive assessments<br>|
|
Clinicopathological MRI and CSF Correlates in Huntington's Disease.
Study Overview
=================
Brief Summary
-----------------
In this study the investigators will link brain iron levels obtained from quantitative susceptibility maps of HD patients with specific and well-known clinical CSF markers for iron accumulation, neurodegeneration and neuroinflammation. The relationship between iron accumulation and neuroinflammation, and the clinical and genetic characteristics of HD will be investigated. This will provide an important basis for the evaluation of brain iron levels as an imaging biomarker for disease state in HD and their relationship with the salient pathomechanisms of the disease.
Detailed Description
-----------------
This investigator-initiated, single-site cross-sectional study looks at iron accumulation using 7T MR-imaging, CSF and blood. This will be achieved in a two-day visit involving clinical assessments, MRI-scanning of the brain, followed by a lumbar puncture the next day, after overnight fasting. Sixty-five volunteers with HD and 25 volunteers without HD will be included. Of these 65 volunteers with HD, 25 will be premanifest, 20 early manifest and 20 moderate manifest, in order to cover the wide-spectrum of Huntington's Disease.
Official Title
-----------------
Clinicopathological MRI and CSF Correlates of Iron Accumulation, Neurodegeneration and Neuroinflammation in Huntington's Disease.
Conditions
-----------------
Huntington Disease
Intervention / Treatment
-----------------
* Diagnostic Test: 7T MRI-scan
* Diagnostic Test: CSF collection via lumbar puncture
* Diagnostic Test: Blood withdrawal
* Diagnostic Test: Clinical measures
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Native Dutch/Flemish speaker Ability to undergo MRI scanning; Written informed consent must be obtained from the participant. And in addition: If the participant is a pre-manifest HD gene carrier: CAG expansion ≥ 40; UHDRS Total Motor Score (TMS) ≤ 5; Total Functional Capacity (TFC) = 13; Diagnostic Confidence Score < 4. If the participant is an early-manifest HD gene carrier: CAG expansion ≥ 36; Diagnostic Confidence Score = 4; HD stage I: TFC scores between 11 and 13 inclusive. If the participant is a moderate manifest HD gene carrier: CAG expansion ≥ 36; Diagnostic Confidence Score = 4; HD stage II: TFC scores between 7 and 11 inclusive. If the participant is a control subject: Partner/spouse of a patient not at risk of HD OR sibling with genetic test results available that show a normal CAG repeat length for both HTT alleles (<36); No other known cognitive, neurological or psychiatric disorders. Exclusion Criteria: Additional major comorbidities not related to HD (e.g. cardiovascular diseases, coagulopathy, hypertension, diabetes mellitus, and/or other neurological disorders); History of severe head injury; Status of the participant after brain surgery; Past erythrocyte transfusions; Use of investigational drugs or participation in a clinical drug trial within 30 days prior to study visit; Current intoxication, drug or alcohol abuse or dependence; Pregnancy; Inability to understand the information about the protocol; Severe physical restrictions (completely wheelchair dependent); Severe chorea that, in the investigator's judgment, precludes the patient's participation in and completion of the MRI and/or lumbar puncture. Contra-indication to MRI scanning, such as: Claustrophobia; Pacemakers and defibrillators; Nerve stimulators; Intracranial clips; Intraorbital or intraocular metallic fragments; Cochlear implants; Ferromagnetic implants; Hydrocephalus pump; Intra-utrine device (not all types); Permanent make-up; Tattoos above the shoulders (not all). Contraindications for a lumbar puncture, including: Screening blood test results outside normal ranges(white cell count, neutrophil count, lymphocyte count, hemoglobin, platelets, Prothrombin time (PT), activated partial thromboplastin time (APTT), C-reactive protein (CRP) and serum ferritin) if only marginally decreased or increased this will be decided by the clinical PI; Signs and symptoms of increased intracranial pressure which will be confirmed on the 7T MRI (T1 and FLAIR scan) or by a fundoscopy; Local infections of the skin; Use of anti-coagulant drugs within the last 14 days prior lumbar puncture.
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?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy controls<br>Partner/spouse of a patient not at risk of HD OR sibling with genetic test results available that show a normal CAG repeat length for both HTT alleles (<36); No other known cognitive, neurological or psychiatric disorders. | Diagnostic Test: 7T MRI-scan<br>* MRI-scanning of the brain using a 7T-MRI scanner<br>Diagnostic Test: CSF collection via lumbar puncture<br>* CSF is collected by doing a lumbar puncture<br>Diagnostic Test: Blood withdrawal<br>* Blood is collected by doing a blood withdrawal<br>Diagnostic Test: Clinical measures<br>* UHDRS-Total motor score, UHDRS-short problem behaviour assessment, UHDRS-Cognitive assessments<br>|
| Premanifest HD expanded gene carrier<br>HDGEC before clinical onset: TMS <5, DCL <4, TFC = 13. No other major comorbidity. | Diagnostic Test: 7T MRI-scan<br>* MRI-scanning of the brain using a 7T-MRI scanner<br>Diagnostic Test: CSF collection via lumbar puncture<br>* CSF is collected by doing a lumbar puncture<br>Diagnostic Test: Blood withdrawal<br>* Blood is collected by doing a blood withdrawal<br>Diagnostic Test: Clinical measures<br>* UHDRS-Total motor score, UHDRS-short problem behaviour assessment, UHDRS-Cognitive assessments<br>|
| Early Manifest HD patient<br>HDGEC after clincial onset: TMS >5, DCL = 4. Early stage of disease: TFC 11-13. No other major comorbidity. | Diagnostic Test: 7T MRI-scan<br>* MRI-scanning of the brain using a 7T-MRI scanner<br>Diagnostic Test: CSF collection via lumbar puncture<br>* CSF is collected by doing a lumbar puncture<br>Diagnostic Test: Blood withdrawal<br>* Blood is collected by doing a blood withdrawal<br>Diagnostic Test: Clinical measures<br>* UHDRS-Total motor score, UHDRS-short problem behaviour assessment, UHDRS-Cognitive assessments<br>|
| Moderate Manifest HD patient<br>HDGEC after clincial onset: TMS >5, DCL = 4. Moderate stage of disease: TFC 7-10. No other major comorbidity. | Diagnostic Test: 7T MRI-scan<br>* MRI-scanning of the brain using a 7T-MRI scanner<br>Diagnostic Test: CSF collection via lumbar puncture<br>* CSF is collected by doing a lumbar puncture<br>Diagnostic Test: Blood withdrawal<br>* Blood is collected by doing a blood withdrawal<br>Diagnostic Test: Clinical measures<br>* UHDRS-Total motor score, UHDRS-short problem behaviour assessment, UHDRS-Cognitive assessments<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantified Susceptibility Mapping | MRI analysis to quantify iron accumulation | At baseline |
| Iron in CSF | Amount of iron and ferritin measured in CSF | At baseline |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Iron in blood | Amount of iron and ferritin measured in blood | At baseline |
| Clinical motor signs | Motor signs obtained using the Unified Huntington's Disease Rating Scale - Total Motor Score. This is a scale assessing motor symptoms of HD, ranging from a score of 0 to 124, where higher scores mean a worse outcome. | At baseline |
| Neuroinflammation and neurodegeneration biomarkers in CSF | a.o. NFL: pg/mL CHIT1: pg/mL IL-6: pg/mL | Baseline |
| Neuroinflammation and neurodegeneration biomarkers in CSF | - YKL-40: ng/mL | Baseline |
| Cognitive score | Assessment of cognitive tests. | At baseline |
| Neuropsychiatric symptoms | Assessment of short Problem Behaviour Assessment. Each symptom is rated for severity on a 5-point scale : 0 = not at all; 1 = trivial; 2 = mild; 3 = moderate (disrupting everyday activities) and 4 = severe or intolerable. Each symptom is also scored for frequency on a 5-point scale as follows: 0 = symptom absent; 1 = less than once weekly; 2 = at least once a week; 3 = most days (up to and including some part of everyday); and 4 = all day, every day. Severity and frequency scores are multiplied to produce an overall 'PBA score' for each symptom. | At baseline |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
7T-MRI, Huntington's Disease, Iron accumulation, Quantified susceptibility mapping, QSM, CSF, Neurodegeneration, Neuroinflammation
|
|
NCT04370639
|
A Pilot Study to Assess the Feasibility and Tolerability of the AccuFlow Perfusion Sensor for Intrapartum Hemorrhage
|
Obstetric hemorrhage is one of the leading causes of maternal death worldwide. One of the challenges in management of hemorrhage is that young, healthy women compensate for blood loss via peripheral vasoconstriction, so they maintain their blood pressure and heart rate at normal levels even after experiencing significant blood loss. By the time vital sign abnormalities appear, interventions must be performed extremely rapidly to avoid organ damage and maternal death. Clinical methods of estimating blood loss in real time, such as visual estimation, are notoriously unreliable, and changes in laboratory testing such as hemoglobin levels lag hours behind actual blood loss. A tool which can detect and quantify blood loss in real time, before vital sign changes occur, has the potential to allow for earlier mobilization of resources and intervention in these cases, thus saving lives. This device is meant to detect changes in skin blood flow which reflect vasoconstriction. The investigators believe that this device, therefore, has the potential to be able to detect and quantify blood loss in real-time. However, as this novel device has never been used for this purpose, before undertaking a large clinical trial, the investigators feel it is necessary to perform a pilot study to assess the feasibility and tolerability of this device. The investigators plan to test this by asking 50 patients undergoing planned cesarean section to wear the device during their surgery. The device will collect skin perfusion measurements during the surgery, which will not be available to the operating team. The patients will also be asked to complete a survey regarding their experience wearing the device. The investigators will use this information to ensure that the device is transmitting interpretable data, that patients feel the device is tolerable during surgery, and to ensure that the device can be used in the operating room without any unforeseen logistical challenges which would need to be addressed in planning a larger trial. The investigators will perform a preliminary comparison of sensor readings to laboratory findings, to assist in planning a larger trial.
|
Hemorrhage remains the leading cause of direct pregnancy-related death in both the developing world and the developed world. Young, healthy patients compensate for hemorrhage via peripheral vasoconstriction, delaying the emergence of vital sign abnormalities until 15-30% of total blood volume has been lost (1-2L in a term pregnant patient). A significant drop in blood pressure and marked tachycardia (>120bpm) are not seen until 30-40% of blood volume has been lost. After 40% loss, however, patients may rapidly decompensate, leaving a narrow window between the emergence of vital sign abnormalities and rapid clinical decompensation. In facilities where obstetricians and anesthesiologists are not in-house at all times and blood product availability is limited, this narrow window may prove catastrophic.~Furthermore, management of obstetrical blood loss presents many unique challenges. First, during delivery, when hemorrhage is expected and occurs acutely and visibly, blood is often mixed with amniotic fluid, making it difficult to establish actual blood loss. Second, laboratory measurement of hemoglobin concentrations can be falsely normal during an acute episode of bleeding, as the hemoglobin measured does not reflect actual hemoglobin concentration until several hours after the hemorrhage event, when equilibration occurs. Third, unlike other surgical patients, postpartum women are expected to experience ongoing vaginal bleeding after their delivery. Bleeding which is persistently slightly heavier than average can lead to significant blood loss over a period of several days, without either the patient or the staff caring for her recognizing the hemorrhage until the patient becomes symptomatic or vital sign instability occurs. The postpartum uterus can serve as a reservoir for retained blood and clot, allowing a patient to continue bleeding into her uterus after delivery without any external evidence of bleeding. In a thin patient this is frequently recognized on fundal checks where the size of the uterus is evaluated, but in obese patients the uterine fundus may be difficult to appreciate, and a significant volume of blood can accumulate in the uterus before it is recognized.~Due to the high risk of mortality related to postpartum hemorrhage and the difficulties providers face quantifying blood loss accurately after delivery,, it is imperative to develop a tool that can detect and quantify hemorrhage before vital sign changes occur. This tool should be simple to use, allowing healthcare providers at all levels to identify hemorrhage early and to mobilize appropriate resources. This will facilitate earlier intervention to treat blood loss before clinical decompensation. As stated, vasoconstriction is the earliest physiologic responses to acute hypovolemia6 and, as such, would be an appropriate target for such a tool.~The AccuFlow Sensor is a device that is based on Combined Heat-Flux and Temperature Sensor (CHFT+) technology developed in the heat transfer laboratory at Virginia Tech and produced by ThermanSENSE Corp (Roanoke, VA). The device, which consists of a heat flux sensor, a thin-film thermocouple, and a heater element, makes direct, quantitative measurements of perfusion occurring at the surface of exposed tissue in real-time. The sensor is less than 1mm thick, covers one square inch of skin, and adheres to the patient's skin using a piece of medical-grade silicone adhesive tape. The heater applies a small amount of heat to the skin surface, raising its temperature to approximately 39 degrees C. The heat flux sensor measures the rate at which the heat dissipates into the tissue, and uses this to calculate perfusion using the Pennes Bio-Heat Transfer Equation, which was developed to describe patterns of heat distribution in the human forearm and which has been the standard tool to predict temperature distributions in living human tissue since the 1950s.10 The sensor measures both surface perfusion and deep perfusion (1-2cm below the skin surface).~The primary theoretical source of patient injury or discomfort from the device is thermal injury from the heater element. Under typical circumstances, the device heats up to approximately 39 degrees Celsius (102 Fahrenheit, the temperature of a typical hot tub), and to prevent thermal injury, the device automatically shuts off should it reach a temperature of 45 C (113F, just above the typical hot-shower temperature of 110F). The device has been tested for comfort and tolerability on 20 healthy volunteers, who reported no discomfort while wearing the device or afterwards. Prior studies have shown no evidence of thermal injury in tissues exposed to a temperature of 39C for prolonged periods, and that exposure to temperatures of 45C causes mild thermal injury only after 150 minutes of constant exposure.11 As this device only heats up while it is taking a measurement, and never higher than 45C, the risk of a thermal injury while wearing the device for the duration of a cesarean section as planned during this study is extremely low. However, should the sensor become uncomfortable to the patient, it can easily be removed. To date, the sensor has been used to evaluate viability of organs intended for transplantation, by measuring blood flow at the surface of the organ.7 Currently, the sensor is being used to evaluate differences in tissue perfusion between pediatric patients with sickle cell anemia and healthy controls in an ongoing research study at Virginia Tech. Of note, the device meets FDA criteria for a nonsignificant risk device, and has been determined to be a nonsignificant risk device by the Institutional Review Board at Virginia Tech/Carilion Clinic for use in adult and pediatric patients at Carilion Clinic facilities. As mentioned before, the patent-pending AccuFlow device is provided by ThermaSENSE Corp. (Roanoke, VA) and a number of sensors will be contributed for the purpose of this study. The device has not yet been studied for detection of obstetric hemorrhage.~In order to determine whether the device is able to accurately detect obstetric hemorrhage, it must be tested on a number of patients who can be identified and enrolled in a research study prior to experiencing a significant volume of blood loss, and whose volume of blood loss can be retrospectively calculated with some degree of accuracy and compared to the device's measurements. Patients undergoing planned, scheduled cesarean delivery are an ideal study population, because they undergo routine measurements of height, weight, hemoglobin, and hematocrit before surgery, and a repeat hemoglobin and hematocrit the day after surgery, once physiologic equilibration has occurred. From these hematocrit measurements, the percentage and volume of blood loss can be calculated and compared to the measurements obtained from the Non-Invasive Blood Perfusion Sensor.~The investigators propose to perform a pilot study consisting of 50 patients, with a planned interim analysis after 25 patients. These patients will be asked to wear the sensor during their planned cesarean delivery, and to complete a survey immediately after their surgery regarding their experience wearing the device. The device will be applied preoperatively and removed postoperatively, and a member of the study team will remain in the operating room to monitor the device and to note any significant events which occur during surgery, as well as any potential challenges with the use of the device which must be considered in planning future trials. Additional information will be gathered from the patients' charts including demographics, height, weight, hemoglobin and hematocrit before and after surgery. The investigators will review the sensor readings and the laboratory findings to determine which of a number of different methods of analyzing device readings should be used in a larger trial, as well as which of the measurement sites used by the sensors provides the most relevant data, in order to streamline the device design prior to a larger trial.
|
Non-Invasive Hemorrhage Monitoring: A Pilot Study to Assess the Feasibility and Tolerability of the AccuFlow Perfusion Sensor for the Detection of Intrapartum Hemorrhage
|
Hemorrhage, Postpartum, Hemorrhage, Vasoconstriction
|
* Device: AccuFlow sensor
* Other: Survey
|
Inclusion Criteria:~Age 18 years or older~English speaking~Undergoing planned cesarean section at Women and Infants Hospital~BMI on admission less than or equal to 35 kg/m2~Preoperative hemoglobin greater than or equal to 11.5g/dL on routine labs~Exclusion Criteria:~History of allergy or other adverse reaction to adhesives~Fever at the time of recruitment
|
18 Years
| null |
Female
|
Accepts Healthy Volunteers
|
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improving sensor design and analysis | We will use the sensor readings obtained from this study to determine how best to obtain and analyze sensor readings in a larger trial. This will include comparing different ratios of readings (both different points in time during the case and different measurement sites on the patient) to determine the ideal number and locations of sensors, and ideal method of data analysis, for a larger trial. | 6 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device Tolerability | Patients will be asked to complete a survey after their cesarean rating the tolerability of the device, as well as the tolerability of standard anesthesia monitoring equipment (blood pressure cuff and pulse oximeter), to assess how the tolerability of the novel device compares to equipment already in use. This will be done in this way because although there is a validated scale for tolerability of wearable computer devices, this scale is only validated as a comparison between two options, and no absolute threshold below which a device is considered tolerable has been established. | 6 months. |
| Accuracy | We will compare the available device readings to the available lab measurements of hemorrhage, to determine if a difference is seen between patients with 10% blood volume lost vs 20% blood volume lost. This will assist in planning a larger trial by determining how many patients with higher-volume blood loss would need to be included, and therefore what total enrollment would likely be needed in the larger trial. | 6 months |
|
Postpartum Hemorrhage, Hemorrhage, Pathologic Processes, Obstetric Labor Complications, Pregnancy Complications, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Puerperal Disorders, Uterine Hemorrhage
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AccuFlow Sensor<br>These 50 patients will wear the AccuFlow sensor device during their surgery, and will complete the post-procedural survey. The data will be reviewed after 25 patients, and the pilot study may be stopped at that point if it is felt that the device feasibility and tolerability have been adequately established. | Device: AccuFlow sensor<br>* AccuFlow sensor will be worn and survey completed<br>Other: Survey<br>* Patients will be asked to complete a survey regarding device tolerability after completing their cesarean section.<br>|
|
A Pilot Study to Assess the Feasibility and Tolerability of the AccuFlow Perfusion Sensor for Intrapartum Hemorrhage
Study Overview
=================
Brief Summary
-----------------
Obstetric hemorrhage is one of the leading causes of maternal death worldwide. One of the challenges in management of hemorrhage is that young, healthy women compensate for blood loss via peripheral vasoconstriction, so they maintain their blood pressure and heart rate at normal levels even after experiencing significant blood loss. By the time vital sign abnormalities appear, interventions must be performed extremely rapidly to avoid organ damage and maternal death. Clinical methods of estimating blood loss in real time, such as visual estimation, are notoriously unreliable, and changes in laboratory testing such as hemoglobin levels lag hours behind actual blood loss. A tool which can detect and quantify blood loss in real time, before vital sign changes occur, has the potential to allow for earlier mobilization of resources and intervention in these cases, thus saving lives. This device is meant to detect changes in skin blood flow which reflect vasoconstriction. The investigators believe that this device, therefore, has the potential to be able to detect and quantify blood loss in real-time. However, as this novel device has never been used for this purpose, before undertaking a large clinical trial, the investigators feel it is necessary to perform a pilot study to assess the feasibility and tolerability of this device. The investigators plan to test this by asking 50 patients undergoing planned cesarean section to wear the device during their surgery. The device will collect skin perfusion measurements during the surgery, which will not be available to the operating team. The patients will also be asked to complete a survey regarding their experience wearing the device. The investigators will use this information to ensure that the device is transmitting interpretable data, that patients feel the device is tolerable during surgery, and to ensure that the device can be used in the operating room without any unforeseen logistical challenges which would need to be addressed in planning a larger trial. The investigators will perform a preliminary comparison of sensor readings to laboratory findings, to assist in planning a larger trial.
Detailed Description
-----------------
Hemorrhage remains the leading cause of direct pregnancy-related death in both the developing world and the developed world. Young, healthy patients compensate for hemorrhage via peripheral vasoconstriction, delaying the emergence of vital sign abnormalities until 15-30% of total blood volume has been lost (1-2L in a term pregnant patient). A significant drop in blood pressure and marked tachycardia (>120bpm) are not seen until 30-40% of blood volume has been lost. After 40% loss, however, patients may rapidly decompensate, leaving a narrow window between the emergence of vital sign abnormalities and rapid clinical decompensation. In facilities where obstetricians and anesthesiologists are not in-house at all times and blood product availability is limited, this narrow window may prove catastrophic. Furthermore, management of obstetrical blood loss presents many unique challenges. First, during delivery, when hemorrhage is expected and occurs acutely and visibly, blood is often mixed with amniotic fluid, making it difficult to establish actual blood loss. Second, laboratory measurement of hemoglobin concentrations can be falsely normal during an acute episode of bleeding, as the hemoglobin measured does not reflect actual hemoglobin concentration until several hours after the hemorrhage event, when equilibration occurs. Third, unlike other surgical patients, postpartum women are expected to experience ongoing vaginal bleeding after their delivery. Bleeding which is persistently slightly heavier than average can lead to significant blood loss over a period of several days, without either the patient or the staff caring for her recognizing the hemorrhage until the patient becomes symptomatic or vital sign instability occurs. The postpartum uterus can serve as a reservoir for retained blood and clot, allowing a patient to continue bleeding into her uterus after delivery without any external evidence of bleeding. In a thin patient this is frequently recognized on fundal checks where the size of the uterus is evaluated, but in obese patients the uterine fundus may be difficult to appreciate, and a significant volume of blood can accumulate in the uterus before it is recognized. Due to the high risk of mortality related to postpartum hemorrhage and the difficulties providers face quantifying blood loss accurately after delivery,, it is imperative to develop a tool that can detect and quantify hemorrhage before vital sign changes occur. This tool should be simple to use, allowing healthcare providers at all levels to identify hemorrhage early and to mobilize appropriate resources. This will facilitate earlier intervention to treat blood loss before clinical decompensation. As stated, vasoconstriction is the earliest physiologic responses to acute hypovolemia6 and, as such, would be an appropriate target for such a tool. The AccuFlow Sensor is a device that is based on Combined Heat-Flux and Temperature Sensor (CHFT+) technology developed in the heat transfer laboratory at Virginia Tech and produced by ThermanSENSE Corp (Roanoke, VA). The device, which consists of a heat flux sensor, a thin-film thermocouple, and a heater element, makes direct, quantitative measurements of perfusion occurring at the surface of exposed tissue in real-time. The sensor is less than 1mm thick, covers one square inch of skin, and adheres to the patient's skin using a piece of medical-grade silicone adhesive tape. The heater applies a small amount of heat to the skin surface, raising its temperature to approximately 39 degrees C. The heat flux sensor measures the rate at which the heat dissipates into the tissue, and uses this to calculate perfusion using the Pennes Bio-Heat Transfer Equation, which was developed to describe patterns of heat distribution in the human forearm and which has been the standard tool to predict temperature distributions in living human tissue since the 1950s.10 The sensor measures both surface perfusion and deep perfusion (1-2cm below the skin surface). The primary theoretical source of patient injury or discomfort from the device is thermal injury from the heater element. Under typical circumstances, the device heats up to approximately 39 degrees Celsius (102 Fahrenheit, the temperature of a typical hot tub), and to prevent thermal injury, the device automatically shuts off should it reach a temperature of 45 C (113F, just above the typical hot-shower temperature of 110F). The device has been tested for comfort and tolerability on 20 healthy volunteers, who reported no discomfort while wearing the device or afterwards. Prior studies have shown no evidence of thermal injury in tissues exposed to a temperature of 39C for prolonged periods, and that exposure to temperatures of 45C causes mild thermal injury only after 150 minutes of constant exposure.11 As this device only heats up while it is taking a measurement, and never higher than 45C, the risk of a thermal injury while wearing the device for the duration of a cesarean section as planned during this study is extremely low. However, should the sensor become uncomfortable to the patient, it can easily be removed. To date, the sensor has been used to evaluate viability of organs intended for transplantation, by measuring blood flow at the surface of the organ.7 Currently, the sensor is being used to evaluate differences in tissue perfusion between pediatric patients with sickle cell anemia and healthy controls in an ongoing research study at Virginia Tech. Of note, the device meets FDA criteria for a nonsignificant risk device, and has been determined to be a nonsignificant risk device by the Institutional Review Board at Virginia Tech/Carilion Clinic for use in adult and pediatric patients at Carilion Clinic facilities. As mentioned before, the patent-pending AccuFlow device is provided by ThermaSENSE Corp. (Roanoke, VA) and a number of sensors will be contributed for the purpose of this study. The device has not yet been studied for detection of obstetric hemorrhage. In order to determine whether the device is able to accurately detect obstetric hemorrhage, it must be tested on a number of patients who can be identified and enrolled in a research study prior to experiencing a significant volume of blood loss, and whose volume of blood loss can be retrospectively calculated with some degree of accuracy and compared to the device's measurements. Patients undergoing planned, scheduled cesarean delivery are an ideal study population, because they undergo routine measurements of height, weight, hemoglobin, and hematocrit before surgery, and a repeat hemoglobin and hematocrit the day after surgery, once physiologic equilibration has occurred. From these hematocrit measurements, the percentage and volume of blood loss can be calculated and compared to the measurements obtained from the Non-Invasive Blood Perfusion Sensor. The investigators propose to perform a pilot study consisting of 50 patients, with a planned interim analysis after 25 patients. These patients will be asked to wear the sensor during their planned cesarean delivery, and to complete a survey immediately after their surgery regarding their experience wearing the device. The device will be applied preoperatively and removed postoperatively, and a member of the study team will remain in the operating room to monitor the device and to note any significant events which occur during surgery, as well as any potential challenges with the use of the device which must be considered in planning future trials. Additional information will be gathered from the patients' charts including demographics, height, weight, hemoglobin and hematocrit before and after surgery. The investigators will review the sensor readings and the laboratory findings to determine which of a number of different methods of analyzing device readings should be used in a larger trial, as well as which of the measurement sites used by the sensors provides the most relevant data, in order to streamline the device design prior to a larger trial.
Official Title
-----------------
Non-Invasive Hemorrhage Monitoring: A Pilot Study to Assess the Feasibility and Tolerability of the AccuFlow Perfusion Sensor for the Detection of Intrapartum Hemorrhage
Conditions
-----------------
Hemorrhage, Postpartum, Hemorrhage, Vasoconstriction
Intervention / Treatment
-----------------
* Device: AccuFlow sensor
* Other: Survey
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 years or older English speaking Undergoing planned cesarean section at Women and Infants Hospital BMI on admission less than or equal to 35 kg/m2 Preoperative hemoglobin greater than or equal to 11.5g/dL on routine labs Exclusion Criteria: History of allergy or other adverse reaction to adhesives Fever at the time of recruitment
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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AccuFlow Sensor<br>These 50 patients will wear the AccuFlow sensor device during their surgery, and will complete the post-procedural survey. The data will be reviewed after 25 patients, and the pilot study may be stopped at that point if it is felt that the device feasibility and tolerability have been adequately established. | Device: AccuFlow sensor<br>* AccuFlow sensor will be worn and survey completed<br>Other: Survey<br>* Patients will be asked to complete a survey regarding device tolerability after completing their cesarean section.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improving sensor design and analysis | We will use the sensor readings obtained from this study to determine how best to obtain and analyze sensor readings in a larger trial. This will include comparing different ratios of readings (both different points in time during the case and different measurement sites on the patient) to determine the ideal number and locations of sensors, and ideal method of data analysis, for a larger trial. | 6 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device Tolerability | Patients will be asked to complete a survey after their cesarean rating the tolerability of the device, as well as the tolerability of standard anesthesia monitoring equipment (blood pressure cuff and pulse oximeter), to assess how the tolerability of the novel device compares to equipment already in use. This will be done in this way because although there is a validated scale for tolerability of wearable computer devices, this scale is only validated as a comparison between two options, and no absolute threshold below which a device is considered tolerable has been established. | 6 months. |
| Accuracy | We will compare the available device readings to the available lab measurements of hemorrhage, to determine if a difference is seen between patients with 10% blood volume lost vs 20% blood volume lost. This will assist in planning a larger trial by determining how many patients with higher-volume blood loss would need to be included, and therefore what total enrollment would likely be needed in the larger trial. | 6 months |
|
|
NCT02898935
|
Improvement of the Accuracy of Spatial Representation of Invasive Exploratory Electrodes in Focal Epilepsy
|
Reconstruction software allows visualization of cortical structure in 3 dimensions, showing on a single picture the position of all the electrodes. The EEG signal of each recording plot of the electrode is analyzed and compared with the underlying brain structure reconstructed by the software. It is therefore possible to visualize 1) ictogenic and epileptogenic areas using neurophysiological stereoelectroencephalography (SEEG) data and 2) adjacent functional cortical areas with functional imaging and SEEG. Software makes it possible to determine the links between these areas. This study aims to show that using these software is an asset in surgical decision and in the choice of surgical strategy.~Each patient has presurgical evaluation (usual care), including morphologic and (if necessary) functional MRI, EEG and SEEG. In this study, software will be used to analyze the processed data (FSL software, FMRIB laboratory, Oxford University and BrainVisa/Anatomist. The surgical decision will be taken according to the usual staff procedures, based on the usual examination results. After the decision making process, the staff will be asked to reconsider the surgical decision, according to the analysis provided by the software. The discrepancies between the decisions will be recorded.
| null |
Focal Epilepsy
|
Inclusion Criteria:~children aged 18 months to 17 years old~drug resistant focal epilepsy~scheduled for deep brain electrodes exploration to assess surgical indication~Exclusion Criteria:~contraindication to anesthesia or surgery~refusal (of parents or child) to participate in the study~no health insurance coverage
|
18 Months
|
17 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of patients for whom surgical strategy would change if using the software | change in medical strategy includes surgery indication, resection volume, topography of resection area | 1 day |
|
Epilepsy, Epilepsies, Partial, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases
|
Improvement of the Accuracy of Spatial Representation of Invasive Exploratory Electrodes in Focal Epilepsy
Study Overview
=================
Brief Summary
-----------------
Reconstruction software allows visualization of cortical structure in 3 dimensions, showing on a single picture the position of all the electrodes. The EEG signal of each recording plot of the electrode is analyzed and compared with the underlying brain structure reconstructed by the software. It is therefore possible to visualize 1) ictogenic and epileptogenic areas using neurophysiological stereoelectroencephalography (SEEG) data and 2) adjacent functional cortical areas with functional imaging and SEEG. Software makes it possible to determine the links between these areas. This study aims to show that using these software is an asset in surgical decision and in the choice of surgical strategy. Each patient has presurgical evaluation (usual care), including morphologic and (if necessary) functional MRI, EEG and SEEG. In this study, software will be used to analyze the processed data (FSL software, FMRIB laboratory, Oxford University and BrainVisa/Anatomist. The surgical decision will be taken according to the usual staff procedures, based on the usual examination results. After the decision making process, the staff will be asked to reconsider the surgical decision, according to the analysis provided by the software. The discrepancies between the decisions will be recorded.
Conditions
-----------------
Focal Epilepsy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: children aged 18 months to 17 years old drug resistant focal epilepsy scheduled for deep brain electrodes exploration to assess surgical indication Exclusion Criteria: contraindication to anesthesia or surgery refusal (of parents or child) to participate in the study no health insurance coverage
Ages Eligible for Study
-----------------
Minimum Age: 18 Months
Maximum Age: 17 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 |
| --- | --- | --- |
| number of patients for whom surgical strategy would change if using the software | change in medical strategy includes surgery indication, resection volume, topography of resection area | 1 day |
|
||||||
NCT02927184
|
Safety and Tolerability of VK2809 in Patients With Primary Hypercholesterolemia and Non-Alcoholic Fatty Liver Disease
|
This study will investigate the efficacy, safety, and tolerability of VK2809 in lowering LDL-C and liver fat content in patients with primary hypercholesterolemia and fatty liver disease. The primary efficacy endpoint is percent change from baseline LDL-C at the end of the treatment period (Week 12). Secondary endpoints include effects on liver fat content and other liver and lipid markers, as well as effects on safety and tolerability, and pharmacokinetic (PK) measurements.
|
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess The Efficacy, Safety, and Tolerability of VK2809 Administered for 12 Weeks Followed by a 4-Week Off-Drug Phase in Patients With Primary Hypercholesterolemia and Non-Alcoholic Fatty Liver Disease
|
Hyperlipidemia, NAFLD
|
* Drug: VK2809
* Drug: Placebo
|
Inclusion Criteria:~Minimum of 10% liver fat as assessed by MRI - Proton Density Fat Fraction~Fasting serum LDL-C >130 mg/dL at screening, >110 mg/dL on lipid lowering medications~Any one of the following:~Triglycerides ≥150 mg/dL or receiving prescription medication for elevated triglycerides.~Systolic blood pressure >130 mmHg or diastolic blood pressure ≥85 mmHg or receiving prescription medication for hypertension.~Waist circumference >40 inches (men) or >35 inches (women)~Body mass index (BMI) 18.50 - 40.00 kg/m2 inclusive at screening~Provide a personally-signed and dated informed consent document~Exclusion Criteria:~Females of childbearing potential and males unwilling to use barrier birth control method (condom) throughout the study~Resting 12-lead ECG showing QTc >450 msec, any tachyarrhythmia or morphology change, or any other clinically significant abnormality~Cardiovascular event requiring hospitalization in the past year~History or presence of thyroid disorder~History of malignancy in past 5 years~LDL-C ≥190 mg/dL or familial hypercholesterolemia~Significant hepatic or renal function test abnormalities
|
18 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in LDL-C in patients receiving VK2809 compared to placebo | | 12 weeks |
|
Liver Diseases, Fatty Liver, Non-alcoholic Fatty Liver Disease, Hypercholesterolemia, Hyperlipidemias, Digestive System Diseases, Dyslipidemias, Lipid Metabolism Disorders, Metabolic Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo capsule | Drug: Placebo<br> <br> |
| Experimental: VK2809 (5mg)<br>5mg VK2809 capsule | Drug: VK2809<br> <br> |
| Experimental: VK2809 (10mg)<br>10mg VK2809 capsule | Drug: VK2809<br> <br> |
| Experimental: VK2809 (10mg QOD)<br>10mg VK2809 capsule | Drug: VK2809<br> <br> |
|
Safety and Tolerability of VK2809 in Patients With Primary Hypercholesterolemia and Non-Alcoholic Fatty Liver Disease
Study Overview
=================
Brief Summary
-----------------
This study will investigate the efficacy, safety, and tolerability of VK2809 in lowering LDL-C and liver fat content in patients with primary hypercholesterolemia and fatty liver disease. The primary efficacy endpoint is percent change from baseline LDL-C at the end of the treatment period (Week 12). Secondary endpoints include effects on liver fat content and other liver and lipid markers, as well as effects on safety and tolerability, and pharmacokinetic (PK) measurements.
Official Title
-----------------
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess The Efficacy, Safety, and Tolerability of VK2809 Administered for 12 Weeks Followed by a 4-Week Off-Drug Phase in Patients With Primary Hypercholesterolemia and Non-Alcoholic Fatty Liver Disease
Conditions
-----------------
Hyperlipidemia, NAFLD
Intervention / Treatment
-----------------
* Drug: VK2809
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Minimum of 10% liver fat as assessed by MRI - Proton Density Fat Fraction Fasting serum LDL-C >130 mg/dL at screening, >110 mg/dL on lipid lowering medications Any one of the following: Triglycerides ≥150 mg/dL or receiving prescription medication for elevated triglycerides. Systolic blood pressure >130 mmHg or diastolic blood pressure ≥85 mmHg or receiving prescription medication for hypertension. Waist circumference >40 inches (men) or >35 inches (women) Body mass index (BMI) 18.50 - 40.00 kg/m2 inclusive at screening Provide a personally-signed and dated informed consent document Exclusion Criteria: Females of childbearing potential and males unwilling to use barrier birth control method (condom) throughout the study Resting 12-lead ECG showing QTc >450 msec, any tachyarrhythmia or morphology change, or any other clinically significant abnormality Cardiovascular event requiring hospitalization in the past year History or presence of thyroid disorder History of malignancy in past 5 years LDL-C ≥190 mg/dL or familial hypercholesterolemia Significant hepatic or renal function test abnormalities
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo capsule | Drug: Placebo<br> <br> |
| Experimental: VK2809 (5mg)<br>5mg VK2809 capsule | Drug: VK2809<br> <br> |
| Experimental: VK2809 (10mg)<br>10mg VK2809 capsule | Drug: VK2809<br> <br> |
| Experimental: VK2809 (10mg QOD)<br>10mg VK2809 capsule | Drug: VK2809<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in LDL-C in patients receiving VK2809 compared to placebo | | 12 weeks |
|
|||
NCT05651633
|
Analgesic Ear Drops for Children With Acute Otitis Media
|
This trial aims to investigate whether analgesic ear drops added to usual care provide superior ear pain relief over usual care alone in children presenting to primary care with AOM. Children will be randomly allocated (ratio 1:1) to either 1) lidocaine hydrochloride 5mg/g ear drops (Otalgan) 1-2 drops up to six times daily for a maximum of 7 days in addition to usual care (oral analgesics, with/without antibiotics) or 2) usual care. Parents will complete a symptom diary for 4 weeks as well as generic and disease-specific quality of life questionnaires at baseline and 4 weeks. The primary outcome is the parent-reported ear pain score (0-10) over the first 3 days.~NOTE:~At the time of publication of the study protocol paper, the investigators were unable to make any amendments to the trial registration record in the Netherlands Trial Register (NTR) (NL9500; date of registration: 28 May 2021). The addition of a data sharing plan was required to adhere to the International Committee of Medical Journal Editors (ICMJE) guidelines. The investigators therefore re-registered the trial in ClinicalTrials.gov. This second registration is for modification purposes only and the NTR record (NL9500) should be regarded as the primary trial registration.
|
Effectiveness of Analgesic Ear Drops as add-on Treatment to Oral Analgesics in Children With Acute Otitis Media: a Pragmatic Randomised Controlled Trial
|
Acute Otitis Media, Pain
|
* Drug: lidocaine hydrochloride 5mg/g
|
Inclusion Criteria:~Age 1 to 6 years~Parent-reported ear pain in 24 hours prior to enrolment~GP-diagnosis of (uni- or bilateral) AOM~Exclusion Criteria:~with (suspected) tympanic membrane perforation or ventilation tubes~with ear wax obscuring visualisation of the tympanic membrane~who are systemically very unwell or require hospital admission (e.g. child has signs and symptoms of serious illness and/or complications such as mastoiditis/meningitis)~who are at high risk of serious complications including children with known immunodeficiency other than partial IgA or IgG2 deficiencies, craniofacial malformation including cleft palate, Down syndrome and previous ear surgery (with the exception of ventilation tubes in the past)~who have a known allergy or sensitivity to study medication or similar substances (e.g. other amide-type anaesthetics: bupivacaine, mepivacaine, prilocaine, etc)~who have taken part in any research involving medicines within the last 90 days, or any other AOM-related research within the last 30 days~who suffer from chronic recurrent pain of another origin than the ear~who have participated in this trial during prior AOM episode
|
1 Year
|
6 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: pragmatic, two arm, individually randomised, open, superiority trial
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The parent-reported ear pain score over the first three days | Parents will record their child's ear pain scores during the first three consecutive days using a 0-10 validated numerical rating scale. Higher scores indicate greater severity. | 3 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of children consuming antibiotics | | in the first 7 days |
| proportion of children with oral analgesic use | | in the first 7 days |
| overall symptom burden (crying/distress, disturbed sleep, interference with normal activity, appetite, fever and hearing problems) using a 0-6 Likert scale | higher scores indicate greater severity | in the first 7 days |
| number of days with ear pain | | during follow up (4 weeks) |
| number of GP reconsultations with/without subsequent antibiotic prescribing | | during follow-up (4 weeks) |
| number of participants with adverse events | | during follow-up (4 weeks) |
| number of participants with complications of AOM | | during follow-up (4 weeks) |
| costs | Mean costs per patient will be compared across the randomisation groups | during follow-up (4 weeks) |
| generic quality of life of the child assessed using the 47-item short-form of the Infant Toddler Quality of Life Questionnaire (ITQOL-SF47) | The questionnaire consists of 47 items in the following areas: overall health, physical abilities, growth and development, pain, temperament and moods, behavior, general health, parental emotional impact, parental time impact, and family cohesion. Scale for each area: from 0 (worst health) to 100 (best health) | at baseline and at 4 weeks |
| disease-specific quality of life of the child assessed using the Otitis media-6 (OM-6) questionnaire | The 6 questions measure Physical Suffering, Hearing Loss, Speech Impairment, Emotional Distress, Activity Limitations, and Caregiver Concerns. Responses for each item were scored from 1 to 7 (1=Not present/no problem; 2=Hardly a problem at all; 3=Somewhat of a problem; 4=Moderate problem; 5=Quite a bit of a problem; 6=Very much of a problem; 7=Extreme problem). A mean score of all six items comprises the OM Total Score. Higher mean scores of all six items indicate greater severity and impact of OM on the child's QOL. | at baseline and at 4 weeks |
| incremental cost-effectiveness ratios; calculated by dividing the estimated differences in costs between groups by the differences in effects observed | i.e. the additional cost per additional 1 point reduction in mean ear pain score over the first three days for the analgesic ear drops group versus the usual care group | during follow-up (4 weeks) |
|
Lidocaine, Anesthetics, Local, Anesthetics, Central Nervous System Depressants, Physiological Effects of Drugs, Sensory System Agents, Peripheral Nervous System Agents, Anti-Arrhythmia Agents, Voltage-Gated Sodium Channel Blockers, Sodium Channel Blockers, Membrane Transport Modulators, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lidocaine ear drops with usual care<br>usual care: oral analgesic with/without antibiotics | Drug: lidocaine hydrochloride 5mg/g<br>* 1-2 drops up to six times daily for a maximum of 7 days<br>* Other names: Otalgan;|
| No Intervention: usual care<br>usual care: oral analgesic with/without antibiotics | |
|
Analgesic Ear Drops for Children With Acute Otitis Media
Study Overview
=================
Brief Summary
-----------------
This trial aims to investigate whether analgesic ear drops added to usual care provide superior ear pain relief over usual care alone in children presenting to primary care with AOM. Children will be randomly allocated (ratio 1:1) to either 1) lidocaine hydrochloride 5mg/g ear drops (Otalgan) 1-2 drops up to six times daily for a maximum of 7 days in addition to usual care (oral analgesics, with/without antibiotics) or 2) usual care. Parents will complete a symptom diary for 4 weeks as well as generic and disease-specific quality of life questionnaires at baseline and 4 weeks. The primary outcome is the parent-reported ear pain score (0-10) over the first 3 days. NOTE: At the time of publication of the study protocol paper, the investigators were unable to make any amendments to the trial registration record in the Netherlands Trial Register (NTR) (NL9500; date of registration: 28 May 2021). The addition of a data sharing plan was required to adhere to the International Committee of Medical Journal Editors (ICMJE) guidelines. The investigators therefore re-registered the trial in ClinicalTrials.gov. This second registration is for modification purposes only and the NTR record (NL9500) should be regarded as the primary trial registration.
Official Title
-----------------
Effectiveness of Analgesic Ear Drops as add-on Treatment to Oral Analgesics in Children With Acute Otitis Media: a Pragmatic Randomised Controlled Trial
Conditions
-----------------
Acute Otitis Media, Pain
Intervention / Treatment
-----------------
* Drug: lidocaine hydrochloride 5mg/g
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 1 to 6 years Parent-reported ear pain in 24 hours prior to enrolment GP-diagnosis of (uni- or bilateral) AOM Exclusion Criteria: with (suspected) tympanic membrane perforation or ventilation tubes with ear wax obscuring visualisation of the tympanic membrane who are systemically very unwell or require hospital admission (e.g. child has signs and symptoms of serious illness and/or complications such as mastoiditis/meningitis) who are at high risk of serious complications including children with known immunodeficiency other than partial IgA or IgG2 deficiencies, craniofacial malformation including cleft palate, Down syndrome and previous ear surgery (with the exception of ventilation tubes in the past) who have a known allergy or sensitivity to study medication or similar substances (e.g. other amide-type anaesthetics: bupivacaine, mepivacaine, prilocaine, etc) who have taken part in any research involving medicines within the last 90 days, or any other AOM-related research within the last 30 days who suffer from chronic recurrent pain of another origin than the ear who have participated in this trial during prior AOM episode
Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 6 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: pragmatic, two arm, individually randomised, open, superiority trial
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lidocaine ear drops with usual care<br>usual care: oral analgesic with/without antibiotics | Drug: lidocaine hydrochloride 5mg/g<br>* 1-2 drops up to six times daily for a maximum of 7 days<br>* Other names: Otalgan;|
| No Intervention: usual care<br>usual care: oral analgesic with/without antibiotics | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The parent-reported ear pain score over the first three days | Parents will record their child's ear pain scores during the first three consecutive days using a 0-10 validated numerical rating scale. Higher scores indicate greater severity. | 3 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of children consuming antibiotics | | in the first 7 days |
| proportion of children with oral analgesic use | | in the first 7 days |
| overall symptom burden (crying/distress, disturbed sleep, interference with normal activity, appetite, fever and hearing problems) using a 0-6 Likert scale | higher scores indicate greater severity | in the first 7 days |
| number of days with ear pain | | during follow up (4 weeks) |
| number of GP reconsultations with/without subsequent antibiotic prescribing | | during follow-up (4 weeks) |
| number of participants with adverse events | | during follow-up (4 weeks) |
| number of participants with complications of AOM | | during follow-up (4 weeks) |
| costs | Mean costs per patient will be compared across the randomisation groups | during follow-up (4 weeks) |
| generic quality of life of the child assessed using the 47-item short-form of the Infant Toddler Quality of Life Questionnaire (ITQOL-SF47) | The questionnaire consists of 47 items in the following areas: overall health, physical abilities, growth and development, pain, temperament and moods, behavior, general health, parental emotional impact, parental time impact, and family cohesion. Scale for each area: from 0 (worst health) to 100 (best health) | at baseline and at 4 weeks |
| disease-specific quality of life of the child assessed using the Otitis media-6 (OM-6) questionnaire | The 6 questions measure Physical Suffering, Hearing Loss, Speech Impairment, Emotional Distress, Activity Limitations, and Caregiver Concerns. Responses for each item were scored from 1 to 7 (1=Not present/no problem; 2=Hardly a problem at all; 3=Somewhat of a problem; 4=Moderate problem; 5=Quite a bit of a problem; 6=Very much of a problem; 7=Extreme problem). A mean score of all six items comprises the OM Total Score. Higher mean scores of all six items indicate greater severity and impact of OM on the child's QOL. | at baseline and at 4 weeks |
| incremental cost-effectiveness ratios; calculated by dividing the estimated differences in costs between groups by the differences in effects observed | i.e. the additional cost per additional 1 point reduction in mean ear pain score over the first three days for the analgesic ear drops group versus the usual care group | during follow-up (4 weeks) |
|
||
NCT03147521
|
Accidental Falls Care Bundle
|
Accidental falls represents an elderly very important health problem, both in the community and within the hospital. The aim of this research project is to evaluate the effectiveness of accidental falls prevention care bundle in geriatrics, internal medicine, post acute, and rehabilitation wards, in terms of incidence and outcome reduction. It will be also investigated the cost effectiveness ratio, in terms of falls avoided, care bundle implementation costs, and falls related healthcare costs. The study will permit to evaluate the implementation feasibleness in time, considering the study will last for 20 months.
|
Stepped Wedge Cluster Randomized Controlled Trial for the Evaluation of Effectiveness of a Accidental Falls Care Bundle Implementation in Elderly Hospital Patients.
|
Accidental Falls
|
* Other: Care bundle
|
Inclusion Criteria:~Patients with ≥ 75 years of age with or without documented fall risk and patients with < 75 years of age, but ≥ 18, only at documented fall risk, admitted at participant wards. The risk assessment will be performed with Conley scale and/or on the base of some specific fall risk characteristics (previous falls, cognitive impairment, neuropsychological damage, increased need to go to the bathroom for increased evacuative needs, neuroleptic or cardiovascular drugs assumption);~Patients (or legal guardian for those incapable of giving their consent) that give their consent to the study participation .~Exclusion Criteria:~Patients or legal guardian that don't give their consent to study participation.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Falls Incidence rate | Number of accidental falls respect number of hospital days of stay in elderly hospital patients at the end of a 5 months step. | 5 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Falls outcome | Numbers falls from wich a fractures or a brain haemorrhage has been generated | 5 monts |
| Cost-effectiveness | Cost effectiveness ratio in terms of costs and avoided falls. Cost Implementation costs: costs for education and staff meeting; printed material costs. | 20 months |
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Accidental falls care bundle<br>Care Bundle Implementation Arm | Other: Care bundle<br>* Risk fall assessment at hospital admission with Conley scale or with findings of specific risk characteristics (previous falls, cognitive impairment, neuropsychological damage, increased need to go to the bathroom for increased evacuative needs, neuroleptic or cardiovascular drugs assumption); if risk is found shear the information with the team, writing it in patient chart, and positioning a specific symbol on patient bed. Inform patient and family about fall risk and ask, if possible, a continuous caregiver presence. Universal strategy application for the environmental safety and patient safety. Periodic assessment of drugs therapy, with the aim of reduce those that acts on central nervous system and cardiovascular system. If patient is at risk and alone, verify each 2 hours the need to go to the bathroom, change position or drink.<br>|
| Active Comparator: Accidental falls standard care<br>Standard Care Implementation Arm (Universal strategy application for the environmental and patient) | Other: Care bundle<br>* Risk fall assessment at hospital admission with Conley scale or with findings of specific risk characteristics (previous falls, cognitive impairment, neuropsychological damage, increased need to go to the bathroom for increased evacuative needs, neuroleptic or cardiovascular drugs assumption); if risk is found shear the information with the team, writing it in patient chart, and positioning a specific symbol on patient bed. Inform patient and family about fall risk and ask, if possible, a continuous caregiver presence. Universal strategy application for the environmental safety and patient safety. Periodic assessment of drugs therapy, with the aim of reduce those that acts on central nervous system and cardiovascular system. If patient is at risk and alone, verify each 2 hours the need to go to the bathroom, change position or drink.<br>|
|
Accidental Falls Care Bundle
Study Overview
=================
Brief Summary
-----------------
Accidental falls represents an elderly very important health problem, both in the community and within the hospital. The aim of this research project is to evaluate the effectiveness of accidental falls prevention care bundle in geriatrics, internal medicine, post acute, and rehabilitation wards, in terms of incidence and outcome reduction. It will be also investigated the cost effectiveness ratio, in terms of falls avoided, care bundle implementation costs, and falls related healthcare costs. The study will permit to evaluate the implementation feasibleness in time, considering the study will last for 20 months.
Official Title
-----------------
Stepped Wedge Cluster Randomized Controlled Trial for the Evaluation of Effectiveness of a Accidental Falls Care Bundle Implementation in Elderly Hospital Patients.
Conditions
-----------------
Accidental Falls
Intervention / Treatment
-----------------
* Other: Care bundle
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with ≥ 75 years of age with or without documented fall risk and patients with < 75 years of age, but ≥ 18, only at documented fall risk, admitted at participant wards. The risk assessment will be performed with Conley scale and/or on the base of some specific fall risk characteristics (previous falls, cognitive impairment, neuropsychological damage, increased need to go to the bathroom for increased evacuative needs, neuroleptic or cardiovascular drugs assumption); Patients (or legal guardian for those incapable of giving their consent) that give their consent to the study participation . Exclusion Criteria: Patients or legal guardian that don't give their consent to study participation.
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: Sequential Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Accidental falls care bundle<br>Care Bundle Implementation Arm | Other: Care bundle<br>* Risk fall assessment at hospital admission with Conley scale or with findings of specific risk characteristics (previous falls, cognitive impairment, neuropsychological damage, increased need to go to the bathroom for increased evacuative needs, neuroleptic or cardiovascular drugs assumption); if risk is found shear the information with the team, writing it in patient chart, and positioning a specific symbol on patient bed. Inform patient and family about fall risk and ask, if possible, a continuous caregiver presence. Universal strategy application for the environmental safety and patient safety. Periodic assessment of drugs therapy, with the aim of reduce those that acts on central nervous system and cardiovascular system. If patient is at risk and alone, verify each 2 hours the need to go to the bathroom, change position or drink.<br>|
| Active Comparator: Accidental falls standard care<br>Standard Care Implementation Arm (Universal strategy application for the environmental and patient) | Other: Care bundle<br>* Risk fall assessment at hospital admission with Conley scale or with findings of specific risk characteristics (previous falls, cognitive impairment, neuropsychological damage, increased need to go to the bathroom for increased evacuative needs, neuroleptic or cardiovascular drugs assumption); if risk is found shear the information with the team, writing it in patient chart, and positioning a specific symbol on patient bed. Inform patient and family about fall risk and ask, if possible, a continuous caregiver presence. Universal strategy application for the environmental safety and patient safety. Periodic assessment of drugs therapy, with the aim of reduce those that acts on central nervous system and cardiovascular system. If patient is at risk and alone, verify each 2 hours the need to go to the bathroom, change position or drink.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Falls Incidence rate | Number of accidental falls respect number of hospital days of stay in elderly hospital patients at the end of a 5 months step. | 5 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Falls outcome | Numbers falls from wich a fractures or a brain haemorrhage has been generated | 5 monts |
| Cost-effectiveness | Cost effectiveness ratio in terms of costs and avoided falls. Cost Implementation costs: costs for education and staff meeting; printed material costs. | 20 months |
|
|||
NCT02610270
|
Erythrocyte Omega-3 Fatty Acid Content in Elite Athletes
|
A suitable concentration of omega-3 fatty acids in relation to omega 6 is considered necessary for a good cell function and prevention of various inflammatory processes. Diet and supplementation are the fundamental procedures to achieve the reference values for several years. Athletes are individuals under physical stress and higher tissue restoration, while maintaining adequate diets they show, as the rest of humans, lower than desired levels. In the present study the investigators aims to determine the modification of those levels by the administration of two different doses of a given product, keeping the same model of diet and physical and competition.
|
The study aims to assess concentrations of the different fatty acids in the erythrocyte membrane before and after administration of a compound with high quality omega3 (EPA and DHA) in two different doses, compared with control group . The period of evaluation and management is four months, one month for the proposed renewal of red blood cells. The composition of the diet, the sports calendar, caloric expenditure and level of training is determined. During the study process it is excluded subjects with injuries or disease processes and ensure that no one take any supplement or modify workouts or diet.
|
Erythrocyte Omega-3 Fatty Acid Content in Elite Athletes in Response to Omega-3 Supplementation: A Dose-Response
|
Healthy
|
* Dietary Supplement: 2 Gums
* Dietary Supplement: 3 Gums
|
Inclusion Criteria:~Healthy, young men and women athletes from the Olympic Training Center (OTC) of Sant Cugat del Valles in Barcelona (Spain) (20 to 45 years of age) belonging to different summer sport activities were asked to participate.~Exclusion Criteria:~Any type of inflammatory process, or the use of anti-inflammatory medications, consumption of n-3 Fatty Acids (FA) supplements and n-3 FA-supplemented foods in the past 3 months; planning to change dietary habits, or training schedule.~During the study, any subject that falls under injury or need nonsteroidal antiinflammatory drug or get sick by inflammatory or infectious disease.
| null | null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fatty acid levels at the membrane of the red blood cells | Evaluation will be obtained before and after the experimental period | Four months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impregnation in relation to dosage administrated to the athletes | Evaluate the impregnation level of the membrane of red blood cells, taken into account the two dosages in relation of the subjects characteristics, sex (M,F), omega3 index (EPA/DHA%), weight (kg), age(years), etc. looking for a relationships of better or worse impregnation depending on sex, body weight, body mass index, previous level of omega3, etc. | Four months |
| Different level of impregnation of the red blood cells in relation to dosage and weight of the athletes | Evaluate the impregnation level of the membrane of red blood cells, taken into account the two dosages in relation of the subjects characteristics, weight (kg). | Four months |
| Different level of impregnation of the red blood cells in relation to dosage and different previous omega 3 index of the athletes | Evaluate the impregnation level of the membrane of red blood cells, taken into account the two dosages in relation of the subjects characteristic of previous level of omega3 index (EPA/DHA%) | Four months |
| Different level of impregnation of the red blood cells in relation to dosage and different sex of the athletes | Evaluate the impregnation level of the membrane of red blood cells, taken into account the two dosages in relation of the sex (M,F) of the subjects | Four months |
| Different level of impregnation of the red blood cells in relation to dosage and different age of the athletes | Evaluate the impregnation level of the membrane of red blood cells, taken into account the two dosages in relation of the age(years) of the subjects etc. | Four months |
|
Sport, fatty acid, omega 3
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2 Gums<br>Athletes that continued their usual training and diet, who took 2 gums of omega 3 (DHA 760 mg) during the experimental period. | Dietary Supplement: 2 Gums<br>* 760 mg DHA<br>|
| Experimental: 3 Gums<br>Athletes that continued their usual training and diet, who took 3 gums of omega 3 (DHA 1140 mg) during the experimental period. | Dietary Supplement: 3 Gums<br>* 1140 mg DHA<br>|
| No Intervention: Control<br>Athletes and coaches that continued their usual training and diet, but did not take any supplements during the experimental period. | |
|
Erythrocyte Omega-3 Fatty Acid Content in Elite Athletes
Study Overview
=================
Brief Summary
-----------------
A suitable concentration of omega-3 fatty acids in relation to omega 6 is considered necessary for a good cell function and prevention of various inflammatory processes. Diet and supplementation are the fundamental procedures to achieve the reference values for several years. Athletes are individuals under physical stress and higher tissue restoration, while maintaining adequate diets they show, as the rest of humans, lower than desired levels. In the present study the investigators aims to determine the modification of those levels by the administration of two different doses of a given product, keeping the same model of diet and physical and competition.
Detailed Description
-----------------
The study aims to assess concentrations of the different fatty acids in the erythrocyte membrane before and after administration of a compound with high quality omega3 (EPA and DHA) in two different doses, compared with control group . The period of evaluation and management is four months, one month for the proposed renewal of red blood cells. The composition of the diet, the sports calendar, caloric expenditure and level of training is determined. During the study process it is excluded subjects with injuries or disease processes and ensure that no one take any supplement or modify workouts or diet.
Official Title
-----------------
Erythrocyte Omega-3 Fatty Acid Content in Elite Athletes in Response to Omega-3 Supplementation: A Dose-Response
Conditions
-----------------
Healthy
Intervention / Treatment
-----------------
* Dietary Supplement: 2 Gums
* Dietary Supplement: 3 Gums
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy, young men and women athletes from the Olympic Training Center (OTC) of Sant Cugat del Valles in Barcelona (Spain) (20 to 45 years of age) belonging to different summer sport activities were asked to participate. Exclusion Criteria: Any type of inflammatory process, or the use of anti-inflammatory medications, consumption of n-3 Fatty Acids (FA) supplements and n-3 FA-supplemented foods in the past 3 months; planning to change dietary habits, or training schedule. During the study, any subject that falls under injury or need nonsteroidal antiinflammatory drug or get sick by inflammatory or infectious disease.
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2 Gums<br>Athletes that continued their usual training and diet, who took 2 gums of omega 3 (DHA 760 mg) during the experimental period. | Dietary Supplement: 2 Gums<br>* 760 mg DHA<br>|
| Experimental: 3 Gums<br>Athletes that continued their usual training and diet, who took 3 gums of omega 3 (DHA 1140 mg) during the experimental period. | Dietary Supplement: 3 Gums<br>* 1140 mg DHA<br>|
| No Intervention: Control<br>Athletes and coaches that continued their usual training and diet, but did not take any supplements during the experimental period. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fatty acid levels at the membrane of the red blood cells | Evaluation will be obtained before and after the experimental period | Four months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impregnation in relation to dosage administrated to the athletes | Evaluate the impregnation level of the membrane of red blood cells, taken into account the two dosages in relation of the subjects characteristics, sex (M,F), omega3 index (EPA/DHA%), weight (kg), age(years), etc. looking for a relationships of better or worse impregnation depending on sex, body weight, body mass index, previous level of omega3, etc. | Four months |
| Different level of impregnation of the red blood cells in relation to dosage and weight of the athletes | Evaluate the impregnation level of the membrane of red blood cells, taken into account the two dosages in relation of the subjects characteristics, weight (kg). | Four months |
| Different level of impregnation of the red blood cells in relation to dosage and different previous omega 3 index of the athletes | Evaluate the impregnation level of the membrane of red blood cells, taken into account the two dosages in relation of the subjects characteristic of previous level of omega3 index (EPA/DHA%) | Four months |
| Different level of impregnation of the red blood cells in relation to dosage and different sex of the athletes | Evaluate the impregnation level of the membrane of red blood cells, taken into account the two dosages in relation of the sex (M,F) of the subjects | Four months |
| Different level of impregnation of the red blood cells in relation to dosage and different age of the athletes | Evaluate the impregnation level of the membrane of red blood cells, taken into account the two dosages in relation of the age(years) of the subjects etc. | Four months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Sport, fatty acid, omega 3
|
|
NCT01249404
|
Dysport® Adult Lower Limb Spasticity Study
|
The purpose of this research study is to assess the efficacy of Dysport® compared to placebo in improving muscle tone in hemiparetic subjects with lower limb spasticity due to stroke or traumatic brain injury.
|
A Phase III, Multicentre, Double-blind, Prospective, Randomized, Placebo-controlled Study, Assessing the Efficacy and Safety of Dysport® Used for the Treatment of Lower-limb Spasticity in Adult Subjects With Hemiparesis Due to Stroke or Traumatic Brain Injury
|
Leg Spasticity
|
* Biological: Botulinum toxin type A
* Drug: Placebo
|
Inclusion Criteria:~Subjects aged 18 to 80 years of age~Post stroke or brain injury~Intensity of muscle tone greater than or equal to 2, as measured on the Modified Ashworth Scale~Ambulatory patients~Exclusion Criteria:~Fixed contractures~Physiotherapy initiated less than 4 weeks before entry~Previous surgery or previous treatment with phenol and/or alcohol in lower limb~Neurological/neuromuscular disorders which may interfere with protocol evaluations
|
18 Years
|
80 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Least Squares Mean Change From Baseline to Week 4 in the MAS Score in the Gastrocnemius-soleus Complex (GSC) (Knee Extended) | Muscle tone in the treated limb was assessed by MAS in the GSC (with the knee extended) at baseline, at Weeks 1, 4 and 12, at discretionary visits at Weeks 16, 20 and 24, and at end of study. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion (ROM)), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. The least squares mean change from baseline at Week 4 is reported. | Baseline and Week 4 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physician's Global Assesment (PGA) of Treatment Response at Week 4 | An assessment of overall treatment response was conducted at Weeks 4 and 12, and discretionary visits at Weeks 16, 20 and 24 and at end of study by an investigator who had not assessed the MAS. The investigator rated the response to treatment in the subject's lower limb after injection of Dysport® relative to the status at the baseline. Answers were made on a 9 point rating scale: -4=markedly worse, -3=much worse, -2=worse, -1=slightly worse, 0=no change, +1=slightly improved, +2=improved, +3=much improved, +4=markedly improved. The mean PGA score at Week 4 is reported. | At Week 4 |
| Least Squares Mean Change From Baseline to Week 4 in Comfortable Barefoot Walking Speed | Comfortable walking speed was assessed as a measure of functional ability and gait over 10 metres. Evaluations were made barefoot, without walking aids, at baseline and Weeks 1, 4 and 12 and discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Week 4 is reported. | Baseline and Week 4 |
|
Botulinum Toxins, Botulinum Toxins, Type A, abobotulinumtoxinA, Acetylcholine Release Inhibitors, Membrane Transport Modulators, Molecular Mechanisms of Pharmacological Action, Cholinergic Agents, Neurotransmitter Agents, Physiological Effects of Drugs, Neuromuscular Agents, Peripheral Nervous System Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dysport® 1000 U, IM<br>1000 U, I.M. (in the muscle), on day 1 (single treatment cycle) | Biological: Botulinum toxin type A<br>* I.M. injection on day 1 (single treatment cycle)<br>* Other names: AbobotulinumtoxinA (Dysport®);|
| Experimental: Dysport® 1500 U, IM<br>1500 U, I.M., on day 1 (single treatment cycle) | Biological: Botulinum toxin type A<br>* I.M. injection on day 1 (single treatment cycle)<br>* Other names: AbobotulinumtoxinA (Dysport®);|
| Placebo Comparator: Placebo<br>I.M., on day 1 (single treatment cycle) | Drug: Placebo<br>* I.M. injection on day 1 (single treatment cycle)<br>|
|
Dysport® Adult Lower Limb Spasticity Study
Study Overview
=================
Brief Summary
-----------------
The purpose of this research study is to assess the efficacy of Dysport® compared to placebo in improving muscle tone in hemiparetic subjects with lower limb spasticity due to stroke or traumatic brain injury.
Official Title
-----------------
A Phase III, Multicentre, Double-blind, Prospective, Randomized, Placebo-controlled Study, Assessing the Efficacy and Safety of Dysport® Used for the Treatment of Lower-limb Spasticity in Adult Subjects With Hemiparesis Due to Stroke or Traumatic Brain Injury
Conditions
-----------------
Leg Spasticity
Intervention / Treatment
-----------------
* Biological: Botulinum toxin type A
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects aged 18 to 80 years of age Post stroke or brain injury Intensity of muscle tone greater than or equal to 2, as measured on the Modified Ashworth Scale Ambulatory patients Exclusion Criteria: Fixed contractures Physiotherapy initiated less than 4 weeks before entry Previous surgery or previous treatment with phenol and/or alcohol in lower limb Neurological/neuromuscular disorders which may interfere with protocol evaluations
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dysport® 1000 U, IM<br>1000 U, I.M. (in the muscle), on day 1 (single treatment cycle) | Biological: Botulinum toxin type A<br>* I.M. injection on day 1 (single treatment cycle)<br>* Other names: AbobotulinumtoxinA (Dysport®);|
| Experimental: Dysport® 1500 U, IM<br>1500 U, I.M., on day 1 (single treatment cycle) | Biological: Botulinum toxin type A<br>* I.M. injection on day 1 (single treatment cycle)<br>* Other names: AbobotulinumtoxinA (Dysport®);|
| Placebo Comparator: Placebo<br>I.M., on day 1 (single treatment cycle) | Drug: Placebo<br>* I.M. injection on day 1 (single treatment cycle)<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Least Squares Mean Change From Baseline to Week 4 in the MAS Score in the Gastrocnemius-soleus Complex (GSC) (Knee Extended) | Muscle tone in the treated limb was assessed by MAS in the GSC (with the knee extended) at baseline, at Weeks 1, 4 and 12, at discretionary visits at Weeks 16, 20 and 24, and at end of study. The MAS consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion (ROM)), 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension), and can be applied to muscles of both the upper and lower limbs. The least squares mean change from baseline at Week 4 is reported. | Baseline and Week 4 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physician's Global Assesment (PGA) of Treatment Response at Week 4 | An assessment of overall treatment response was conducted at Weeks 4 and 12, and discretionary visits at Weeks 16, 20 and 24 and at end of study by an investigator who had not assessed the MAS. The investigator rated the response to treatment in the subject's lower limb after injection of Dysport® relative to the status at the baseline. Answers were made on a 9 point rating scale: -4=markedly worse, -3=much worse, -2=worse, -1=slightly worse, 0=no change, +1=slightly improved, +2=improved, +3=much improved, +4=markedly improved. The mean PGA score at Week 4 is reported. | At Week 4 |
| Least Squares Mean Change From Baseline to Week 4 in Comfortable Barefoot Walking Speed | Comfortable walking speed was assessed as a measure of functional ability and gait over 10 metres. Evaluations were made barefoot, without walking aids, at baseline and Weeks 1, 4 and 12 and discretionary visits at Weeks 16, 20 and 24 and at end of study. The least squares mean change from baseline at Week 4 is reported. | Baseline and Week 4 |
|
||
NCT04546594
|
Epidemiological Data on Pain
|
The ALGOBASES project is an observational epidemiological study of pain through the collection of pain evaluation questionnaires and information with the aim of creating a descriptive pain evaluation in all patients who need to benefit from orthopedic, thoracic or gynecological surgery. The painful symptomatology will thus be evaluated in all its dimensions (demographic data, physical, psychological, socio-cultural components) and linked to the pathology justifying the specialized care. It is planned to collect the same data at each subsequent event in order to allow the determination of predictive factors, pain trajectories according to the type of surgery, and the profile of subjects at risk of acute or chronic postoperative pain.
|
Collection of Epidemiological Data on Pain Related to Orthopedic, Thoracic or Gynecological Surgery
|
Orthopedic Disorder, Thoracic, Gynecological; Surgery (Previous), Causing Obstructed Labor, Affecting Fetus, Pain
|
Inclusion Criteria:~Patient over 17 years old Patient needing orthopedic surgery Patient needing gynecological surgery Patient needing thoracic surgery Patient who has given written consent to participate in the trial. Socially insured patient Patient willing to comply with all study procedures and study duration~Exclusion Criteria:~Age under 18 years old~Non-communicating patient~Patient does not understand French~Patient without social protection~Patient refusing to participate
|
17 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Descriptive analysis of the typology of pain in patients needing surgery. | The typology of pain will be analyzed on the basis of responses to questionnaires on the affective and sensory dimension of pain, quality of life, depression, anxiety and catastrophizing | Baseline |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Descriptive analysis of specific symptomatology of pain Description of the general and painful symptomatology in patients needing surgery. | Describe the specific symptomatology of pain separately according to the 3 pathologies: patients needing orthopedic, thoracic and gynecological surgery. | follow-up over a period of five years during post-operative or pain medical consultation |
| Pain Catastrophizing Scale (PCS) according to pain | | Baseline and follow-up over a period of five years during post-operative or pain medical consultation |
| Hospital Anxiety Depression scale (HAD) according to pain | | Baseline and follow-up over a period of five years during post-operative or pain medical consultation |
| EQD5 according to pain | | Baseline and follow-up over a period of five years during post-operative or pain medical consultation |
| Identification of factors predictive of acute or chronic pain. | The presence of pain will be defined by the presence of severe pain and/or the presence of neuropathic pain. | Baseline and at three months, six months, one year |
|
Pain,, perioperative pain, epidemiology, predictive factors
|
Musculoskeletal Diseases, Dystocia, Obstetric Labor Complications, Pregnancy Complications, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Orthopedic surgery<br> | |
| Thoracic surgery<br> | |
| Gynecological surgery<br> | |
|
Epidemiological Data on Pain
Study Overview
=================
Brief Summary
-----------------
The ALGOBASES project is an observational epidemiological study of pain through the collection of pain evaluation questionnaires and information with the aim of creating a descriptive pain evaluation in all patients who need to benefit from orthopedic, thoracic or gynecological surgery. The painful symptomatology will thus be evaluated in all its dimensions (demographic data, physical, psychological, socio-cultural components) and linked to the pathology justifying the specialized care. It is planned to collect the same data at each subsequent event in order to allow the determination of predictive factors, pain trajectories according to the type of surgery, and the profile of subjects at risk of acute or chronic postoperative pain.
Official Title
-----------------
Collection of Epidemiological Data on Pain Related to Orthopedic, Thoracic or Gynecological Surgery
Conditions
-----------------
Orthopedic Disorder, Thoracic, Gynecological; Surgery (Previous), Causing Obstructed Labor, Affecting Fetus, Pain
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient over 17 years old Patient needing orthopedic surgery Patient needing gynecological surgery Patient needing thoracic surgery Patient who has given written consent to participate in the trial. Socially insured patient Patient willing to comply with all study procedures and study duration Exclusion Criteria: Age under 18 years old Non-communicating patient Patient does not understand French Patient without social protection Patient refusing to participate
Ages Eligible for Study
-----------------
Minimum Age: 17 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 |
| --- | --- |
| Orthopedic surgery<br> | |
| Thoracic surgery<br> | |
| Gynecological surgery<br> | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Descriptive analysis of the typology of pain in patients needing surgery. | The typology of pain will be analyzed on the basis of responses to questionnaires on the affective and sensory dimension of pain, quality of life, depression, anxiety and catastrophizing | Baseline |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Descriptive analysis of specific symptomatology of pain Description of the general and painful symptomatology in patients needing surgery. | Describe the specific symptomatology of pain separately according to the 3 pathologies: patients needing orthopedic, thoracic and gynecological surgery. | follow-up over a period of five years during post-operative or pain medical consultation |
| Pain Catastrophizing Scale (PCS) according to pain | | Baseline and follow-up over a period of five years during post-operative or pain medical consultation |
| Hospital Anxiety Depression scale (HAD) according to pain | | Baseline and follow-up over a period of five years during post-operative or pain medical consultation |
| EQD5 according to pain | | Baseline and follow-up over a period of five years during post-operative or pain medical consultation |
| Identification of factors predictive of acute or chronic pain. | The presence of pain will be defined by the presence of severe pain and/or the presence of neuropathic pain. | Baseline and at three months, six months, one year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pain,, perioperative pain, epidemiology, predictive factors
|
|||
NCT04945837
|
Psychologic Impact of COVID-19 Pandemic on the Hospital Staff of the Nouvelle Aquitaine Area
|
Evaluation of the psychological impact of the COVID-19 pandemic on hospital staff in the French Nouvelle Aquitaine area, through a longitudinal study with repeated self-administered psychologic scales
|
Evaluation of the psychological impact of Coronavirus disease 2019 (COVID-19) on hospital personnel in Nouvelle Aquitaine. IMPSY-COV Upon recent outbreaks of new diseases (SARS, MERS-CoV, Ebola) have led to the emergence of psychiatric disorders in healthcare workers , such as post-traumatic stress , anxiety (e.g., panic attacks) or depressive episodes. Observed similarities in between propagation patterns of SARS-CoV-2 and SARS, alow us to expect the occurence of similar psychiatric disorders in COVID-19 context to those described (Vignaud, Prieto, 2020). The study is set up to assess the psychological state of hospital personnel in the working conditions of treating COVID-19 suffering patients.~87000 hospital staff workers from the Nouvelle Aquitaine region will be invited to take part in the study. This includes medical and non-medical professionals from general and psychiatric hospitals exposed to COVID-19.~Study design. The protocol shows two phases and five measurement timepoints. In the initial phase (T0), eligible persons will be contacted via email. Those wishing to participate will then consent, answer socio-demographic questions and a series of psychology questionnaires. In the longitudinal phase, participants will be again invited to answer the same series of questionnaires four times: one month after the initial phase (T1), 3 months after (T2), 6 months after (T3) and 12 months after (T4).~Statistical analysis. In order to identify the consequences generated by COVID-19 in hospital personnel through a longitudinal protocol, several statistical analyses are considered, including logistic and linear regressions as well as ANOVA and MANOVA.~Expected outcomes. The study will assess the occurrence and the evolution of psychological distress and identify vulnerability factors that may trigger psychiatric disorders in these situations. The study will also provide an opportunity to improve the supporting actions of professionals affected by the crisis.
|
Psychologic Impact of COVID-19 Pandemic on the Hospital Staff of the Nouvelle Aquitaine Area : a Prospective Longitudinal Study by Self-administered Questionnaires
|
Covid19, Personnel, Hospital, Work-Related Condition, Work-Related Stress Disorder
|
* Other: self administered questionnaire
|
Inclusion Criteria:~18 years or more~hospital workers exposed to COVID-19~consented to participate to the study~master the french langage~Understanding of type, objectives and study methology~accept an on-line evaluation~Benefit from health insurance~Exclusion Criteria:~refuse to participate~pregnant or breastfeeding woman~Be under measure of legal protection: guardianship, curatorship or safeguard of justice.
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective Longitudinal Study by Self-administered Questionnaires
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in anxiety disorder overcome | GAD-7 score:~> 7 , the anxiety disorder status is supected, [5; 9] corresponds to anxiety evaluation: light [10; 14] corresponds to anxiety evaluation: moderate > 15, corresponds to anxiety evaluation: severe | inclusion, month 1, month 3, month 6, month 12 |
| Changes in anxiety disorder overcome | PDSR verifies that maximum of the panic state is reached within ten minutes | inclusion, month 1, month 3, month 6, month 12 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination and collection of lived traumatic events types | Life Events Checklist for DSM-5 (LEC-5) | inclusion, month 1, month 3, month 6, month 12 |
| Posttraumatic stress disorder symptoms presence and measurment | Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) PCL-5 score > 32 indicate presence of Posttraumatic Stress Trouble (PST) | inclusion, month 1, month 3, month 6, month 12 |
| 2-last-week mood assessment | Beck Depression Inventory - Fast Screen - France (BDI-FS FR) score > 13 indicates presence of a depressive trouble | inclusion, month 1, month 3, month 6, month 12 |
| Identification of coping pattern to stress | Coping Inventory for Stressful Situations (CISS) questionnaire Participant assess from 'little to a lot his tendency to adopt a task, emotion or behaviour based pattern | inclusion, month 1, month 3, month 6, month 12 |
| Burn out diagnosis | MASLACH BURNOUT INVENTORY (MBI questionnaire) assessment of the 3 aspects from low to high~burn out feeling~deshumanisation~accomplishment at work | inclusion, month 1, month 3, month 6, month 12 |
| Self evaluation of state of health | considering the 4-last-weeks the participant will assess 8 under-scales for score 0 to 100 (favourable) | inclusion, month 1, month 3, month 6, month 12 |
| Psycho active drugs intakes and level of intake over the last month | selection of the drug and level of intake will n*be assessed 'none', new, increasing, constant | inclusion, month 1, month 3, month 6, month 12 |
| Evaluation of the CUMP support to health professionnals | answer yes' or no support has been contacted already or since the last study assessement | inclusion, month 1, month 3, month 6, month 12 |
|
COVID-19, Mental health, Anxiety, Hospital personnel, Longitudinal, Pandemic
|
Occupational Stress, Pneumonia, Viral, Pneumonia, Respiratory Tract Infections, Infections, Virus Diseases, Coronavirus Infections, Coronaviridae Infections, Nidovirales Infections, RNA Virus Infections, Lung Diseases, Respiratory Tract Diseases, Occupational Diseases, Stress, Psychological, Behavioral Symptoms, COVID-19
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: unique study arm<br>Initial socio-demographic questionnaire 5 timepoints psychologic and self-administered questionnaires | Other: self administered questionnaire<br>* longitunidal descriptive study<br>|
|
Psychologic Impact of COVID-19 Pandemic on the Hospital Staff of the Nouvelle Aquitaine Area
Study Overview
=================
Brief Summary
-----------------
Evaluation of the psychological impact of the COVID-19 pandemic on hospital staff in the French Nouvelle Aquitaine area, through a longitudinal study with repeated self-administered psychologic scales
Detailed Description
-----------------
Evaluation of the psychological impact of Coronavirus disease 2019 (COVID-19) on hospital personnel in Nouvelle Aquitaine. IMPSY-COV Upon recent outbreaks of new diseases (SARS, MERS-CoV, Ebola) have led to the emergence of psychiatric disorders in healthcare workers , such as post-traumatic stress , anxiety (e.g., panic attacks) or depressive episodes. Observed similarities in between propagation patterns of SARS-CoV-2 and SARS, alow us to expect the occurence of similar psychiatric disorders in COVID-19 context to those described (Vignaud, Prieto, 2020). The study is set up to assess the psychological state of hospital personnel in the working conditions of treating COVID-19 suffering patients. 87000 hospital staff workers from the Nouvelle Aquitaine region will be invited to take part in the study. This includes medical and non-medical professionals from general and psychiatric hospitals exposed to COVID-19. Study design. The protocol shows two phases and five measurement timepoints. In the initial phase (T0), eligible persons will be contacted via email. Those wishing to participate will then consent, answer socio-demographic questions and a series of psychology questionnaires. In the longitudinal phase, participants will be again invited to answer the same series of questionnaires four times: one month after the initial phase (T1), 3 months after (T2), 6 months after (T3) and 12 months after (T4). Statistical analysis. In order to identify the consequences generated by COVID-19 in hospital personnel through a longitudinal protocol, several statistical analyses are considered, including logistic and linear regressions as well as ANOVA and MANOVA. Expected outcomes. The study will assess the occurrence and the evolution of psychological distress and identify vulnerability factors that may trigger psychiatric disorders in these situations. The study will also provide an opportunity to improve the supporting actions of professionals affected by the crisis.
Official Title
-----------------
Psychologic Impact of COVID-19 Pandemic on the Hospital Staff of the Nouvelle Aquitaine Area : a Prospective Longitudinal Study by Self-administered Questionnaires
Conditions
-----------------
Covid19, Personnel, Hospital, Work-Related Condition, Work-Related Stress Disorder
Intervention / Treatment
-----------------
* Other: self administered questionnaire
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years or more hospital workers exposed to COVID-19 consented to participate to the study master the french langage Understanding of type, objectives and study methology accept an on-line evaluation Benefit from health insurance Exclusion Criteria: refuse to participate pregnant or breastfeeding woman Be under measure of legal protection: guardianship, curatorship or safeguard of justice.
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: Prospective Longitudinal Study by Self-administered Questionnaires
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: unique study arm<br>Initial socio-demographic questionnaire 5 timepoints psychologic and self-administered questionnaires | Other: self administered questionnaire<br>* longitunidal descriptive study<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in anxiety disorder overcome | GAD-7 score: > 7 , the anxiety disorder status is supected, [5; 9] corresponds to anxiety evaluation: light [10; 14] corresponds to anxiety evaluation: moderate > 15, corresponds to anxiety evaluation: severe | inclusion, month 1, month 3, month 6, month 12 |
| Changes in anxiety disorder overcome | PDSR verifies that maximum of the panic state is reached within ten minutes | inclusion, month 1, month 3, month 6, month 12 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination and collection of lived traumatic events types | Life Events Checklist for DSM-5 (LEC-5) | inclusion, month 1, month 3, month 6, month 12 |
| Posttraumatic stress disorder symptoms presence and measurment | Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) PCL-5 score > 32 indicate presence of Posttraumatic Stress Trouble (PST) | inclusion, month 1, month 3, month 6, month 12 |
| 2-last-week mood assessment | Beck Depression Inventory - Fast Screen - France (BDI-FS FR) score > 13 indicates presence of a depressive trouble | inclusion, month 1, month 3, month 6, month 12 |
| Identification of coping pattern to stress | Coping Inventory for Stressful Situations (CISS) questionnaire Participant assess from 'little to a lot his tendency to adopt a task, emotion or behaviour based pattern | inclusion, month 1, month 3, month 6, month 12 |
| Burn out diagnosis | MASLACH BURNOUT INVENTORY (MBI questionnaire) assessment of the 3 aspects from low to high burn out feeling deshumanisation accomplishment at work | inclusion, month 1, month 3, month 6, month 12 |
| Self evaluation of state of health | considering the 4-last-weeks the participant will assess 8 under-scales for score 0 to 100 (favourable) | inclusion, month 1, month 3, month 6, month 12 |
| Psycho active drugs intakes and level of intake over the last month | selection of the drug and level of intake will n*be assessed 'none', new, increasing, constant | inclusion, month 1, month 3, month 6, month 12 |
| Evaluation of the CUMP support to health professionnals | answer yes' or no support has been contacted already or since the last study assessement | inclusion, month 1, month 3, month 6, month 12 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COVID-19, Mental health, Anxiety, Hospital personnel, Longitudinal, Pandemic
|
NCT02390739
|
Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing Human Thyroglobulin to People With Thyroglobulin Expressing Thyroid Cancer
|
Background~The NCI Surgery Branch has developed an experimental therapy for treating patient with metastatic thyroid cancer that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with a type of virus (retrovirus) to attack only the tumor cells, and then giving the cells back to the patient. This type of therapy is called gene transfer. In this protocol, we are modifying the patient s white blood cells with a retrovirus that has the gene for anti-thyroglobulin incorporated in the retrovirus.~Objectives:~The purpose of this study is to see if these tumor fighting cells (genetically modified cells) that express the receptor for the thyroglobulin molecule on their surface can cause thyroid tumors to shrink and to see if this treatment is safe.~Eligibility:~<TAB>Adults 18 and older with thyroid cancer that has the thyroglobulin molecule on tumor surfaces~Design:~<TAB>Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed~<TAB>Leukapheresis: If the patients meet all of the requirements for the study they will undergo leukapheresis to obtain white blood cells to make the anti- thyroglobulin cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.}~<TAB>Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the anti-thyroglobulin cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment.~Follow up:~Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2 days.
|
Background:~We generated a murine T-cell receptor (mTCR) that recognizes human thyroglobulin (hTG) in the context of HLA-A0201 and constructed a single retroviral vector that contains its alpha and beta chains and will confer hTG recognition to HLA-A0201+ PBL on transduction.~In co-cultures with HLA-A0201+, hTG+ target cells, anti-TG mTCR transduced T cells secrete significant amounts of IFN- >= with high specificity.~Objectives:~Primary objectives:~To determine the safety of administering PBL transduced with this anti-TG mTCR in concert with preparative lymphodepletion and high dose interleukin-2 (IL-2; aldesleukin).~Determine if these mTCR-transduced PBL can mediate the regression of TG-expressing tumors.~Eligibility:~Patients who are HLA-A*0201 positive and 18 years of age or older must have~-Advanced TG-expressing thyroid cancer (including those with bone-only disease) which has progressed after surgery (if indicated) and radioiodine ablation~Patients may not have:~-Contraindications for high dose aldesleukin administration.~Design:~PBMC obtained by leukapheresis will be cultured in the presence of anti-CD3 (OKT3) and aldesleukin in order to stimulate T-cell growth.~Transduction is initiated by exposure of these cells to retroviral vector supernatant containing replication-incompetent virus encoding the anti-TG mTCR.~All patients will receive a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine.~On day 0 patients will receive their PBL transduced with the anti-TG mTCR and then begin high dose aldesleukin.~A complete evaluation of evaluable lesions will be conducted approximately 4-6 weeks after treatment.~The study will be conducted using a Phase I/II optimal design.~The objective will be to determine if the combination of high dose aldesleukin, lymphocyte depleting chemotherapy, and anti-TG mTCR-gene engineered lymphocytes is able to be associated with a clinical response rate that can rule out 5% (p0=0.05) in favor of a modest 20% PR + CR rate (p1=0.20).~A total of up to 68 patients may be required; approximately 25 patients in the phase I portion of the study and 43 (41, plus an allowance of up to 2 non-evaluable) patients in the phase II portion of the study.
|
Phase I/II Study Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing Human Thyroglobulin to Patients With Thyroglobulin Expressing Thyroid Cancer
|
Metastatic Thyroid Cancer
|
* Drug: Aldesleukin
* Drug: Fludarabine
* Drug: Cyclophosphamide
* Biological: Anti-Thyroglobulin mTCR PBL
|
INCLUSION CRITERIA:~Unresectable thyroid cancer expressing TG as assessed by one of the following methods: RT-PCR on tumor tissue, or by immunohistochemistry of resected tissue.~Recurrent/metastatic radioiodine refractory disease that has progressed within the past 6 months with at least 1 lesion increasing by 0.5cm in diameter or with increasing bone metastases.~Confirmation of diagnosis of thyroid cancer by the Laboratory of Pathology of the NCI.~PET avid disease with SUV >5.~Patients must have previously received standard systemic therapy for advanced thyroid cancer (to include radioactive iodine for iodine-avid tumors and surgery (if indicated)) and have been either non-responders (progressive disease) or have recurred.~Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible.~Greater than or equal to 18 years of age and less than or equal to 70 years of age.~Willing to sign a durable power of attorney~Able to understand and sign the Informed Consent Document~Clinical performance status of ECOG 0 or 1~Life expectancy of greater than three months~Patients must be HLA-A*0201 positive~Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after treatment.~Serology:~Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)~Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.~o. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.~p. Hematology~Absolute neutrophil count greater than 1000/mm3 without the support of filgrastim~WBC less than or equal to 3000/mm3~Platelet count greater than or equal to 100,000/mm3~Hemoglobin greater than 8.0 g/dl~q. Chemistry:~Serum ALT/AST less than or equal to to 2.5 times the upper limit of normal~Serum creatinine less than or equal to to 1.6 mg/dl~Total bilirubin less than or equal to to 1.5 mg/dl, except in patients with Gilbert s Syndrome who must have a total bilirubin less than 3.0 mg/dl.~r. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).~Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less.~EXCLUSION CRITERIA:~Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.~Any form of primary immunodeficiency (such as Severe Combined~Immunodeficiency Disease).~Active systemic infections (e.g. : requiring anti-infective treatment), coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.~Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).~Concurrent systemic steroid therapy.~History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine.~History of coronary revascularization or ischemic symptoms~Documented LVEF of less than or equal to 45%. Testing is required in patients with:~Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block~Age greater than or equal to 60 years old
|
18 Years
|
70 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine a safe dose of administration and determine if this approach will result in an objective tumor regression. | | Approximately 4 years |
|
Immunotherapy, Gene Therapy, Metastatic Cancer
|
Aldesleukin, Cyclophosphamide, Fludarabine, Immunosuppressive Agents, Immunologic Factors, Physiological Effects of Drugs, Antirheumatic Agents, Antineoplastic Agents, Alkylating, Alkylating Agents, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents, Myeloablative Agonists, Anti-HIV Agents, Anti-Retroviral Agents, Antiviral Agents, Anti-Infective Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br>All patients will receive a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine followed by antithyroglobulin mTCR PBL and aldesleukin. | Drug: Aldesleukin<br>* Aldeskeukin 720,000 IU/kg IV over 15 minutes approximately every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 3 days (maximum of 9 doses).<br>Drug: Fludarabine<br>* Day -7 to -3:Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.<br>Drug: Cyclophosphamide<br>* Days -7 and -6:Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hour.<br>Biological: Anti-Thyroglobulin mTCR PBL<br>* On day 0, one to four days after last dose of fludarabine, cells will be infused intravenously (IV) over 20 to 30 minutes.<br>|
|
Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing Human Thyroglobulin to People With Thyroglobulin Expressing Thyroid Cancer
Study Overview
=================
Brief Summary
-----------------
Background The NCI Surgery Branch has developed an experimental therapy for treating patient with metastatic thyroid cancer that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with a type of virus (retrovirus) to attack only the tumor cells, and then giving the cells back to the patient. This type of therapy is called gene transfer. In this protocol, we are modifying the patient s white blood cells with a retrovirus that has the gene for anti-thyroglobulin incorporated in the retrovirus. Objectives: The purpose of this study is to see if these tumor fighting cells (genetically modified cells) that express the receptor for the thyroglobulin molecule on their surface can cause thyroid tumors to shrink and to see if this treatment is safe. Eligibility: <TAB>Adults 18 and older with thyroid cancer that has the thyroglobulin molecule on tumor surfaces Design: <TAB>Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed <TAB>Leukapheresis: If the patients meet all of the requirements for the study they will undergo leukapheresis to obtain white blood cells to make the anti- thyroglobulin cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.} <TAB>Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the anti-thyroglobulin cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment. Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2 days.
Detailed Description
-----------------
Background: We generated a murine T-cell receptor (mTCR) that recognizes human thyroglobulin (hTG) in the context of HLA-A0201 and constructed a single retroviral vector that contains its alpha and beta chains and will confer hTG recognition to HLA-A0201+ PBL on transduction. In co-cultures with HLA-A0201+, hTG+ target cells, anti-TG mTCR transduced T cells secrete significant amounts of IFN- >= with high specificity. Objectives: Primary objectives: To determine the safety of administering PBL transduced with this anti-TG mTCR in concert with preparative lymphodepletion and high dose interleukin-2 (IL-2; aldesleukin). Determine if these mTCR-transduced PBL can mediate the regression of TG-expressing tumors. Eligibility: Patients who are HLA-A*0201 positive and 18 years of age or older must have -Advanced TG-expressing thyroid cancer (including those with bone-only disease) which has progressed after surgery (if indicated) and radioiodine ablation Patients may not have: -Contraindications for high dose aldesleukin administration. Design: PBMC obtained by leukapheresis will be cultured in the presence of anti-CD3 (OKT3) and aldesleukin in order to stimulate T-cell growth. Transduction is initiated by exposure of these cells to retroviral vector supernatant containing replication-incompetent virus encoding the anti-TG mTCR. All patients will receive a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine. On day 0 patients will receive their PBL transduced with the anti-TG mTCR and then begin high dose aldesleukin. A complete evaluation of evaluable lesions will be conducted approximately 4-6 weeks after treatment. The study will be conducted using a Phase I/II optimal design. The objective will be to determine if the combination of high dose aldesleukin, lymphocyte depleting chemotherapy, and anti-TG mTCR-gene engineered lymphocytes is able to be associated with a clinical response rate that can rule out 5% (p0=0.05) in favor of a modest 20% PR + CR rate (p1=0.20). A total of up to 68 patients may be required; approximately 25 patients in the phase I portion of the study and 43 (41, plus an allowance of up to 2 non-evaluable) patients in the phase II portion of the study.
Official Title
-----------------
Phase I/II Study Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing Human Thyroglobulin to Patients With Thyroglobulin Expressing Thyroid Cancer
Conditions
-----------------
Metastatic Thyroid Cancer
Intervention / Treatment
-----------------
* Drug: Aldesleukin
* Drug: Fludarabine
* Drug: Cyclophosphamide
* Biological: Anti-Thyroglobulin mTCR PBL
Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITERIA: Unresectable thyroid cancer expressing TG as assessed by one of the following methods: RT-PCR on tumor tissue, or by immunohistochemistry of resected tissue. Recurrent/metastatic radioiodine refractory disease that has progressed within the past 6 months with at least 1 lesion increasing by 0.5cm in diameter or with increasing bone metastases. Confirmation of diagnosis of thyroid cancer by the Laboratory of Pathology of the NCI. PET avid disease with SUV >5. Patients must have previously received standard systemic therapy for advanced thyroid cancer (to include radioactive iodine for iodine-avid tumors and surgery (if indicated)) and have been either non-responders (progressive disease) or have recurred. Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Greater than or equal to 18 years of age and less than or equal to 70 years of age. Willing to sign a durable power of attorney Able to understand and sign the Informed Consent Document Clinical performance status of ECOG 0 or 1 Life expectancy of greater than three months Patients must be HLA-A*0201 positive Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after treatment. Serology: Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.) Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative. o. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus. p. Hematology Absolute neutrophil count greater than 1000/mm3 without the support of filgrastim WBC less than or equal to 3000/mm3 Platelet count greater than or equal to 100,000/mm3 Hemoglobin greater than 8.0 g/dl q. Chemistry: Serum ALT/AST less than or equal to to 2.5 times the upper limit of normal Serum creatinine less than or equal to to 1.6 mg/dl Total bilirubin less than or equal to to 1.5 mg/dl, except in patients with Gilbert s Syndrome who must have a total bilirubin less than 3.0 mg/dl. r. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo). Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less. EXCLUSION CRITERIA: Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease). Active systemic infections (e.g. : requiring anti-infective treatment), coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease. Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities). Concurrent systemic steroid therapy. History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine. History of coronary revascularization or ischemic symptoms Documented LVEF of less than or equal to 45%. Testing is required in patients with: Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block Age greater than or equal to 60 years old
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br>All patients will receive a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine followed by antithyroglobulin mTCR PBL and aldesleukin. | Drug: Aldesleukin<br>* Aldeskeukin 720,000 IU/kg IV over 15 minutes approximately every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 3 days (maximum of 9 doses).<br>Drug: Fludarabine<br>* Day -7 to -3:Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.<br>Drug: Cyclophosphamide<br>* Days -7 and -6:Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hour.<br>Biological: Anti-Thyroglobulin mTCR PBL<br>* On day 0, one to four days after last dose of fludarabine, cells will be infused intravenously (IV) over 20 to 30 minutes.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine a safe dose of administration and determine if this approach will result in an objective tumor regression. | | Approximately 4 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immunotherapy, Gene Therapy, Metastatic Cancer
|
|
NCT03444012
|
ADHERE-S (NIS Brilique)
|
noninterventional study investigating persistence and adherence on ticagrelor in ACS patients in Serbia
|
Non-interventional Prospective Data Collection on Persistence and Adherence on Ticagrelor in ACS Adult Patients in Serbia
|
ACS (Acute Coronary Syndrome)
|
* Drug: ticagrelor 90 mg
|
Inclusion Criteria:~≥ 18 years of age~diagnosed with ACS - STEMI or NSTEMI or unstable angina, invasively or non-invasively treated~Patients already on treatment with ticagrelor at least for 1 month and no longer than 3 months prior to study initiation. Enrolment in this study must not be trigger for ticagrelor initiation.~read and signed the Informed Consent Form~Exclusion Criteria:~Any contraindications as per approved SmPC of Brilique~• Patients with life-threatening conditions which could disable patients to comply with scheduled visits and/or not able to fill in the patient questionnaires.
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| duration (number of days) on ticagrelor therapy in patients with acute coronary syndrome | | 1 year (12 months) |
|
Physiological Effects of Drugs, Ticagrelor, Platelet Aggregation Inhibitors, Purinergic P2Y Receptor Antagonists, Purinergic P2 Receptor Antagonists, Purinergic Antagonists, Purinergic Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action
|
| Intervention/Treatment |
| --- |
|Drug: ticagrelor 90 mg|persistence and adherence on ticagrelor in ACS patients|
|
ADHERE-S (NIS Brilique)
Study Overview
=================
Brief Summary
-----------------
noninterventional study investigating persistence and adherence on ticagrelor in ACS patients in Serbia
Official Title
-----------------
Non-interventional Prospective Data Collection on Persistence and Adherence on Ticagrelor in ACS Adult Patients in Serbia
Conditions
-----------------
ACS (Acute Coronary Syndrome)
Intervention / Treatment
-----------------
* Drug: ticagrelor 90 mg
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥ 18 years of age diagnosed with ACS - STEMI or NSTEMI or unstable angina, invasively or non-invasively treated Patients already on treatment with ticagrelor at least for 1 month and no longer than 3 months prior to study initiation. Enrolment in this study must not be trigger for ticagrelor initiation. read and signed the Informed Consent Form Exclusion Criteria: Any contraindications as per approved SmPC of Brilique • Patients with life-threatening conditions which could disable patients to comply with scheduled visits and/or not able to fill in the patient questionnaires.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Intervention/Treatment |
| --- |
|Drug: ticagrelor 90 mg|persistence and adherence on ticagrelor in ACS patients|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| duration (number of days) on ticagrelor therapy in patients with acute coronary syndrome | | 1 year (12 months) |
|
||||
NCT03481231
|
In Situ Immune Parameters and Their Prognostic Role on the Survival of Patients With Glioblastoma
|
Glioblastoma (GBM) is the most frequent brain tumor. Currently survival is poor and few treatments are available. Recent data show that there is no immune privilege of the central nervous system (CNS) and that GBM are invaded by effector CD8 T cells, letting us hypothesis that GBM growth is dependent of immunosurveillance.~The aim of this study is to better understand the antitumor immune response against GBM to unravel new effectors and immunosuppressive pathways important for the regulation of anticancer immunity and to discover new immune activating strategies with the objectives to isolate subgroups of GBMs that could benefit from an immunotherapy approach. To achieve this goal, GBM tumor samples and a blood sample will be collected during the initial tumor resection.~The sites involved in the recruitment of the patients will be the neurosurgical teams in Brussel, Dijon, Nantes and Padova.
|
Primary objective :~The primary objective is to determine for each of the 3 molecular subtypes of glioblastoma the predictive performance on 1-year overall survival of in situ immune parameters~Secondary objectives :~To identify the best combination of in vivo immune parameters that is predictive of 1-year overall survival To determine the impact of immune parameters on overall survival Create a collection of biological samples
|
In Situ Immune Parameters and Their Prognostic Role on the Survival of Patients With Glioblastoma
|
Glioblastoma
|
Inclusion Criteria:~Patients with newly diagnosed, brain tumor~Gross or near total resection of the contrast-enhancing tumor mass decides by the neurosurgeron.~Subjects ≥18 and ≤75 years of age at surgery~Patients must be able to understand and sign the informed consent documents indicating that they are aware of the investigational nature of this study.~Confirmation of the diagnosis of grade IV GBM by the local pathologist with an independent neuropathologist who will review this diagnosis~Primary therapy must consist of surgical resection with the intent for a gross or near total resection of the contrast-enhancing tumor mass, followed by conventional external beam radiation therapy and concurrent temozolomide chemotherapy.~Tumor biopsy for biological analysis has to be performed before using ultrasonic surgery~Exclusion Criteria:~Patient with other type of primary brain tumor or metastases~Patients with only biopsy performed for the diagnosis~Subjects under guardianship, curatorship or judicial protection~Female subjects who are pregnant or breast-feeding
|
18 Years
|
75 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | Determination for each of the 3 molecular subtypes of glioblastoma the predictive performance on 1-year overall survival of in situ immune parameters | 24 months |
|
immunotherapy, tumors and blood samples
|
Neoplasms, Neuroepithelial, Neuroectodermal Tumors, Neoplasms, Germ Cell and Embryonal, Neoplasms by Histologic Type, Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms, Nerve Tissue, Glioblastoma, Astrocytoma, Glioma
|
In Situ Immune Parameters and Their Prognostic Role on the Survival of Patients With Glioblastoma
Study Overview
=================
Brief Summary
-----------------
Glioblastoma (GBM) is the most frequent brain tumor. Currently survival is poor and few treatments are available. Recent data show that there is no immune privilege of the central nervous system (CNS) and that GBM are invaded by effector CD8 T cells, letting us hypothesis that GBM growth is dependent of immunosurveillance. The aim of this study is to better understand the antitumor immune response against GBM to unravel new effectors and immunosuppressive pathways important for the regulation of anticancer immunity and to discover new immune activating strategies with the objectives to isolate subgroups of GBMs that could benefit from an immunotherapy approach. To achieve this goal, GBM tumor samples and a blood sample will be collected during the initial tumor resection. The sites involved in the recruitment of the patients will be the neurosurgical teams in Brussel, Dijon, Nantes and Padova.
Detailed Description
-----------------
Primary objective : The primary objective is to determine for each of the 3 molecular subtypes of glioblastoma the predictive performance on 1-year overall survival of in situ immune parameters Secondary objectives : To identify the best combination of in vivo immune parameters that is predictive of 1-year overall survival To determine the impact of immune parameters on overall survival Create a collection of biological samples
Official Title
-----------------
In Situ Immune Parameters and Their Prognostic Role on the Survival of Patients With Glioblastoma
Conditions
-----------------
Glioblastoma
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with newly diagnosed, brain tumor Gross or near total resection of the contrast-enhancing tumor mass decides by the neurosurgeron. Subjects ≥18 and ≤75 years of age at surgery Patients must be able to understand and sign the informed consent documents indicating that they are aware of the investigational nature of this study. Confirmation of the diagnosis of grade IV GBM by the local pathologist with an independent neuropathologist who will review this diagnosis Primary therapy must consist of surgical resection with the intent for a gross or near total resection of the contrast-enhancing tumor mass, followed by conventional external beam radiation therapy and concurrent temozolomide chemotherapy. Tumor biopsy for biological analysis has to be performed before using ultrasonic surgery Exclusion Criteria: Patient with other type of primary brain tumor or metastases Patients with only biopsy performed for the diagnosis Subjects under guardianship, curatorship or judicial protection Female subjects who are pregnant or breast-feeding
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?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | Determination for each of the 3 molecular subtypes of glioblastoma the predictive performance on 1-year overall survival of in situ immune parameters | 24 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
immunotherapy, tumors and blood samples
|
||||
NCT02569255
|
Safe Use of New Oral Anticoagulants in Ablation for Atrial Fibrillation
|
Use of new oral anticoagulants (NOAC) in patients before and after catheter based pulmonary vein isolation (PVI) is still controversial. Experience is reported from consecutive patients ablated with PVI for atrial fibrillation and treated with dabigatran, rivaroxaban, or apixaban from Nov 2011 until Dec 2014. Patients are followed for 3 month after ablation. All complications possible being related to the use of NOAC are registered.
|
Use of new oral anticoagulants (NOAC) in patients before and after radiofrequency ablation with pulmonary vein isolation (PVI) is still controversial. Experience is reported from consecutive patients ablated with PVI for atrial fibrillation and treated with dabigatran, rivaroxaban, or apixaban from Nov 2011 until Dec 2014. Patients paused their NOAC treatment for 24 hours before ablation. Patients were routinely followed up after 3 months with a standard formular focused on possible adverse events (major bleeding complications or thromboembolic events) to NOAC treatment. Adverse events related to the use of NOAC were registered during treatment or during 3 months of follow-up.
|
Safe Use of New Oral Anticoagulants in Patients Treated by Catheter Ablation for Atrial Fibrillation
|
Atrial Fibrillation
|
* Procedure: Pulmonary venous ostia isolation
|
Inclusion Criteria:~Symptomatic atrial fibrillation despite pharmacological treatment.~Exclusion Criteria:~None
| null | null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with bleeding or thromboembolism during PVI and/or three months of follow up | Any bleeding or thromboembolism observed during the PVI procedure and/or during 3 months of follow-up are registered. Also, if any procedure related complication was worsened by treatment with NOAC was registered. | Up to three months after PVI |
|
Atrial Fibrillation, Arrhythmias, Cardiac, Heart Diseases, Cardiovascular Diseases, Pathologic Processes
|
| Intervention/Treatment |
| --- |
|Procedure: Pulmonary venous ostia isolation|Percutaneous, catheterbased, radiofrequency ablation with left atrial access via atrial septal puncture. Helped by 3D-imaging system (Carto(tm)) and electrical signal guidance the PV ostia together with neighbouring atrial tissue is electrically isolated from the rest of the left atrium.|
|
Safe Use of New Oral Anticoagulants in Ablation for Atrial Fibrillation
Study Overview
=================
Brief Summary
-----------------
Use of new oral anticoagulants (NOAC) in patients before and after catheter based pulmonary vein isolation (PVI) is still controversial. Experience is reported from consecutive patients ablated with PVI for atrial fibrillation and treated with dabigatran, rivaroxaban, or apixaban from Nov 2011 until Dec 2014. Patients are followed for 3 month after ablation. All complications possible being related to the use of NOAC are registered.
Detailed Description
-----------------
Use of new oral anticoagulants (NOAC) in patients before and after radiofrequency ablation with pulmonary vein isolation (PVI) is still controversial. Experience is reported from consecutive patients ablated with PVI for atrial fibrillation and treated with dabigatran, rivaroxaban, or apixaban from Nov 2011 until Dec 2014. Patients paused their NOAC treatment for 24 hours before ablation. Patients were routinely followed up after 3 months with a standard formular focused on possible adverse events (major bleeding complications or thromboembolic events) to NOAC treatment. Adverse events related to the use of NOAC were registered during treatment or during 3 months of follow-up.
Official Title
-----------------
Safe Use of New Oral Anticoagulants in Patients Treated by Catheter Ablation for Atrial Fibrillation
Conditions
-----------------
Atrial Fibrillation
Intervention / Treatment
-----------------
* Procedure: Pulmonary venous ostia isolation
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Symptomatic atrial fibrillation despite pharmacological treatment. Exclusion Criteria: None
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Intervention/Treatment |
| --- |
|Procedure: Pulmonary venous ostia isolation|Percutaneous, catheterbased, radiofrequency ablation with left atrial access via atrial septal puncture. Helped by 3D-imaging system (Carto(tm)) and electrical signal guidance the PV ostia together with neighbouring atrial tissue is electrically isolated from the rest of the left atrium.|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with bleeding or thromboembolism during PVI and/or three months of follow up | Any bleeding or thromboembolism observed during the PVI procedure and/or during 3 months of follow-up are registered. Also, if any procedure related complication was worsened by treatment with NOAC was registered. | Up to three months after PVI |
|
|||
NCT00749411
|
Safety and Tolerability of Repeat Dosing of GSK233705/GW642444 in COPD
|
The purpose of this study is the evaluate the safety and tolerability of repeat dosing of the combination of inhaled GSK233705 and GW642444 administered once-daily in subjects with COPD.
|
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, 4-week Study to Evaluate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Repeat Inhaled Doses of the Combination of GSK233705 and GW642444 Administered Once-daily in Subjects With COPD
|
Pulmonary Disease, Chronic Obstructive
|
* Drug: Placebo
* Drug: GSK233705/GW642444
|
Inclusion Criteria:~male and females 40 to 80 years of age (inclusive)~COPD diagnosis~Current or previous smokers with a cigarette smoking history of at least 10 pack-~Post-albuterol FEV1/FVC of 0.70 or less~Post-albuterol FEV1 of 35% to 80% (inclusive)~Exclusion Criteria:~Pregnant or lactating females~current diagnosis of asthma~respiratory disorders other than COPD~clinically significant cardiovascular, neurological, psychiatric, renal, immunological, endocrine, or hematological abnormalities that are uncontrolled~clinically significant sleep apnea~previous lung resection surgery~clinically significant abnormalities confirmed by chest x-ray that are not related to COPD~hospitalization for COPD within 3 months of screening~use of antibiotics for lower respiratory tract infection within 6 months of screening~abnormal and clinically significant 12-lead ECG findings~current malignancy in remission for less that 5 years~medical conditions that would contraindicate the use of anticholinergics~positive hepatitis B or C test~history of alcohol or drug abuse~unable to withhold albuterol for 6 or more hours~use of long term oxygen therapy~conditions that would limit the validity of informed consent~use of GW642444 or GSK233705 in previous studies~use of an investigation drug with 30 days of screening~use of inhaled corticosteroids (ICS) at a dose greater than 1000mcg of fluticasone propionate or equivalent~hypersensitivity to beta-agonists~concurrent use of long-acting beta-agonists (LABA) or long-acting muscaring antagonists, LABA/ICS combination products, cytochrome p450 inhibitors, oral or depot corticosteroids, theophyllines, oral beta agonists, oral leukotrine modulators, inhaled short acting anticholinergics.
|
40 Years
|
80 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Weighted Mean Pulse Rate Over (0-4 Hours) at Day 28. | Baseline was the most recent result taken on or before pre-dose (Day 1). The analysis was performed using a Repeated Measures Model. This model used all available weighted mean pulse rate values recorded. Change from Baseline was calculated as (Change from Baseline = Assessment value - Baseline value). | Baseline (Pre-dose, Day 1) and Day 28 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon 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. | On-treatment; from treatment start until one day after treatment stop (Up to Day 29) |
|
COPD, long-acting beta agonist, Emphysema, Chronic Bronchitis, Chronic Obstructive Pulmonary Disease (COPD), bronchodilator, long acting muscarinic antagonist
|
Lung Diseases, Pulmonary Disease, Chronic Obstructive, Respiratory Tract Diseases, Chronic Disease, Disease Attributes, Pathologic Processes, Lung Diseases, Obstructive
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: GSK233705/GW642444<br>* The combination of the long-acting muscarinic antagonist GSK233705 and the long acting beta agonist GW642444 in a single inhaler.<br>|
| Placebo Comparator: Arm 2<br> | Drug: Placebo<br>* matching placebo<br>|
|
Safety and Tolerability of Repeat Dosing of GSK233705/GW642444 in COPD
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is the evaluate the safety and tolerability of repeat dosing of the combination of inhaled GSK233705 and GW642444 administered once-daily in subjects with COPD.
Official Title
-----------------
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, 4-week Study to Evaluate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Repeat Inhaled Doses of the Combination of GSK233705 and GW642444 Administered Once-daily in Subjects With COPD
Conditions
-----------------
Pulmonary Disease, Chronic Obstructive
Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: GSK233705/GW642444
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: male and females 40 to 80 years of age (inclusive) COPD diagnosis Current or previous smokers with a cigarette smoking history of at least 10 pack- Post-albuterol FEV1/FVC of 0.70 or less Post-albuterol FEV1 of 35% to 80% (inclusive) Exclusion Criteria: Pregnant or lactating females current diagnosis of asthma respiratory disorders other than COPD clinically significant cardiovascular, neurological, psychiatric, renal, immunological, endocrine, or hematological abnormalities that are uncontrolled clinically significant sleep apnea previous lung resection surgery clinically significant abnormalities confirmed by chest x-ray that are not related to COPD hospitalization for COPD within 3 months of screening use of antibiotics for lower respiratory tract infection within 6 months of screening abnormal and clinically significant 12-lead ECG findings current malignancy in remission for less that 5 years medical conditions that would contraindicate the use of anticholinergics positive hepatitis B or C test history of alcohol or drug abuse unable to withhold albuterol for 6 or more hours use of long term oxygen therapy conditions that would limit the validity of informed consent use of GW642444 or GSK233705 in previous studies use of an investigation drug with 30 days of screening use of inhaled corticosteroids (ICS) at a dose greater than 1000mcg of fluticasone propionate or equivalent hypersensitivity to beta-agonists concurrent use of long-acting beta-agonists (LABA) or long-acting muscaring antagonists, LABA/ICS combination products, cytochrome p450 inhibitors, oral or depot corticosteroids, theophyllines, oral beta agonists, oral leukotrine modulators, inhaled short acting anticholinergics.
Ages Eligible for Study
-----------------
Minimum Age: 40 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: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: GSK233705/GW642444<br>* The combination of the long-acting muscarinic antagonist GSK233705 and the long acting beta agonist GW642444 in a single inhaler.<br>|
| Placebo Comparator: Arm 2<br> | Drug: Placebo<br>* matching placebo<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Weighted Mean Pulse Rate Over (0-4 Hours) at Day 28. | Baseline was the most recent result taken on or before pre-dose (Day 1). The analysis was performed using a Repeated Measures Model. This model used all available weighted mean pulse rate values recorded. Change from Baseline was calculated as (Change from Baseline = Assessment value - Baseline value). | Baseline (Pre-dose, Day 1) and Day 28 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon 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. | On-treatment; from treatment start until one day after treatment stop (Up to Day 29) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COPD, long-acting beta agonist, Emphysema, Chronic Bronchitis, Chronic Obstructive Pulmonary Disease (COPD), bronchodilator, long acting muscarinic antagonist
|
|
NCT05514145
|
The Effectiveness of Combined Design Nance/Transpalatal Arch Appliance in Maintaining Arch Dimensions After Premature Extraction of Primary Molars
|
This study will evaluate the effectiveness of N-TPA appliance compared to Nance SM in maintaining the arch dimensions after bilateral premature extraction of primary molars in children.
|
In this randomized controlled clinical trial, 30 healthy children, 8-9 years of age with premature extraction of bilateral maxillary primary molars will be selected. Children will be randomly allocated into two equal groups of 15 children each according to the type of the appliance that will be used. Group I will receive a a Nance SM, and Group II a combined N-TPA appliance . Panoramic X-rays and study casts will be made, and baseline measurements will be recorded including arch circumference, intermolar width and arch depth. The appliances will be fabricated and cemented intra-orally.~The patients will be followed up at 3, 6 and 9 months for re-evaluation of arch circumference, intermolar width, arch depth, and patient acceptance.
|
The Effectiveness of Combined Design Nance/Transpalatal Arch Appliance in Maintaining Arch Dimensions After Premature Extraction of Primary Molars (Randomized Controlled Clinical Trial)
|
Space Maintenance
|
* Device: Nance/Transpalatal arch space maintainer
* Device: Nance space maintainer
|
Inclusion Criteria:~Fully erupted maxillary permanent first molars.~Angle's class I occlusion.(31)~Adequate space for premolar eruption according to Moyer's arch length analysis.(31)~Fair to good oral hygiene according to Silness and Loe plaque index.(32)~No history of allergy to polymethyl methacrylate.~Exclusion Criteria:~Children with congenitally absent permanent successors.~Children with successors not covered by bone with 2/3 of the root formed.(33)
|
8 Years
|
9 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized parallel controlled clinical trial
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy in maintaining arch dimensions | All arch dimensions are measured with a 0.5 mm stainless steel wire on the study casts which was then measured with a digital caliper in millimeters (accuracy up to 0.02mm):~Changes in arch circumference after insertion of both Nance and Nance/transpalatal arch (N-TPA) appliances after 3, 6- and 9-months follow-up.~Changes in intermolar width after insertion of both Nance and Nance/transpalatal arch (N-TPA) appliances after 3, 6- and 9-months follow-up.~Changes in arch depth after insertion of both Nance and Nance/transpalatal arch (N-TPA) appliances after 3, 6- and 9-months follow-up. | 9 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient acceptance by modified faces pain scale | Patient acceptance are measured by the modified faces pain scale of both Nance and N-TPA appliances after 3, 6- and 9-months follow-up.~Patient acceptance is measured as : (a) Satisfied (b) Indifferent (c) Dissatisfied | 9 months |
|
Nance/transpalatal arch, Nance space maintainer, Space maintainer, Space maintenance
|
Premature Birth, Obstetric Labor, Premature, Obstetric Labor Complications, Pregnancy Complications, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nance space maintainer<br>Conventional space maintainer for the maxillary arch as control | Device: Nance space maintainer<br>* Conventional space maintainer for the maxillary arch used in mixed dentition<br>|
| Experimental: Nance/Transpalatal arch space maintainer<br>New design of a space maintainer for the maxillary arch | Device: Nance/Transpalatal arch space maintainer<br>* A combined design of both Nance and Transpalatal arch space maintainers as a space maintainer for the maxillary arch in mixed dentition<br>|
|
The Effectiveness of Combined Design Nance/Transpalatal Arch Appliance in Maintaining Arch Dimensions After Premature Extraction of Primary Molars
Study Overview
=================
Brief Summary
-----------------
This study will evaluate the effectiveness of N-TPA appliance compared to Nance SM in maintaining the arch dimensions after bilateral premature extraction of primary molars in children.
Detailed Description
-----------------
In this randomized controlled clinical trial, 30 healthy children, 8-9 years of age with premature extraction of bilateral maxillary primary molars will be selected. Children will be randomly allocated into two equal groups of 15 children each according to the type of the appliance that will be used. Group I will receive a a Nance SM, and Group II a combined N-TPA appliance . Panoramic X-rays and study casts will be made, and baseline measurements will be recorded including arch circumference, intermolar width and arch depth. The appliances will be fabricated and cemented intra-orally. The patients will be followed up at 3, 6 and 9 months for re-evaluation of arch circumference, intermolar width, arch depth, and patient acceptance.
Official Title
-----------------
The Effectiveness of Combined Design Nance/Transpalatal Arch Appliance in Maintaining Arch Dimensions After Premature Extraction of Primary Molars (Randomized Controlled Clinical Trial)
Conditions
-----------------
Space Maintenance
Intervention / Treatment
-----------------
* Device: Nance/Transpalatal arch space maintainer
* Device: Nance space maintainer
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Fully erupted maxillary permanent first molars. Angle's class I occlusion.(31) Adequate space for premolar eruption according to Moyer's arch length analysis.(31) Fair to good oral hygiene according to Silness and Loe plaque index.(32) No history of allergy to polymethyl methacrylate. Exclusion Criteria: Children with congenitally absent permanent successors. Children with successors not covered by bone with 2/3 of the root formed.(33)
Ages Eligible for Study
-----------------
Minimum Age: 8 Years
Maximum Age: 9 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized parallel controlled clinical trial
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nance space maintainer<br>Conventional space maintainer for the maxillary arch as control | Device: Nance space maintainer<br>* Conventional space maintainer for the maxillary arch used in mixed dentition<br>|
| Experimental: Nance/Transpalatal arch space maintainer<br>New design of a space maintainer for the maxillary arch | Device: Nance/Transpalatal arch space maintainer<br>* A combined design of both Nance and Transpalatal arch space maintainers as a space maintainer for the maxillary arch in mixed dentition<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy in maintaining arch dimensions | All arch dimensions are measured with a 0.5 mm stainless steel wire on the study casts which was then measured with a digital caliper in millimeters (accuracy up to 0.02mm): Changes in arch circumference after insertion of both Nance and Nance/transpalatal arch (N-TPA) appliances after 3, 6- and 9-months follow-up. Changes in intermolar width after insertion of both Nance and Nance/transpalatal arch (N-TPA) appliances after 3, 6- and 9-months follow-up. Changes in arch depth after insertion of both Nance and Nance/transpalatal arch (N-TPA) appliances after 3, 6- and 9-months follow-up. | 9 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient acceptance by modified faces pain scale | Patient acceptance are measured by the modified faces pain scale of both Nance and N-TPA appliances after 3, 6- and 9-months follow-up. Patient acceptance is measured as : (a) Satisfied (b) Indifferent (c) Dissatisfied | 9 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nance/transpalatal arch, Nance space maintainer, Space maintainer, Space maintenance
|
NCT01681615
|
Challenge Test for Acetylsalicylic Acid Hypersensitivity
|
The investigators want to find new challenge test for Acetylsalicylic hypersensitivity / Aspirin hypersensitivity. The investigators suggest that this new test will be as efficient as the already established protocols in terms of sensitivity and specificity.
|
Hypersensitivity to Acetylsalicylic Acid or Aspirin (and other NSAIDS) is a condition that affects up to 2,5% of the population. Most cases are seen in a complex of such hypersensitivity with chronic eosinophilic rhinosinusitis with nasal polyposis and asthma. Despite research in finding a reliable in-vitro-test for the condition, challenge tests are still considered gold standard. So far oral, nasal, inhalation and intravenous routes of administration has been described in literature.
|
Challenge Test for Acetylsalicylic Acid Hypersensitivity
|
Asthma Aspirin-sensitive, ASA Intolerant Asthma, Asthma, Aspirin-Induced, Asthma, Nasal Polyps, and Aspirin Intolerance
|
* Drug: Acetylsalicylate
* Drug: Isotonic NaCl
|
Inclusion Criteria:~Persons between 18 and 60 years of age~Suspected Acetylsalicylic Acid Hypersensitivity~Exclusion Criteria:~History on anaphylactic shock after NSAIDS intake~History on gastric ulcer after NSAIDS intake~Patients previously gone through testing or desensitisation for Aspirin hypersensitivity~Clinical unstable asthma or baseline FEV1<70%~Severe disease of the heart, digestive tract, liver or kidney~Severe chronic urticaria~Present conjunctivitis~Pregnancy
|
18 Years
|
60 Years
|
All
|
No
|
Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inspiratory nasal flow measured by Rhinomanometry | Bilateral flow reduction >40% considered positive test. | Within 45 min from challenge |
| Expiratory nasal flow measured by Rhinomanometry | Bilateral expiratory flow reduction >40% considered positive. | Within 45 min from challenge |
| Pulmonary forced expiratory volume in 1 second (FEV1) | Reduction in FEV1 >20% is considered as positive test. | Within 45 min from challenge |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conjunctival symptoms | 0=no symptoms, 1=limited redness and / or itching, 2=conjunctival redness and /or itching / swelling or bullae within 5 minutes from testing.~Value 1 and 2 is considered positive if unilateral. | Within 45 days from challenge |
| Nasal symptoms | Rhinorrhea, congestion and sneezing is considered as positive test. | Within 45 minutes from challenge |
| Bronchial and laryngeal symptoms | Bronchospasm. tight chest, wheezing or laryngospasm is considered as positive test. | Within 45 minutes from challenge |
|
Challenge test for Aspirin Hypersensitivity, Challenge test for Acetylsalicylic Hypersensitivity
|
Asthma, Nasal Polyps, Asthma, Aspirin-Induced, Hypersensitivity, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive, Lung Diseases, Respiratory Hypersensitivity, Hypersensitivity, Immediate, Immune System Diseases, Nose Diseases, Otorhinolaryngologic Diseases, Polyps, Pathological Conditions, Anatomical, Drug Hypersensitivity, Drug-Related Side Effects and Adverse Reactions, Chemically-Induced Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Acetylsalicylate<br>Acetylsalicylic Acid Eyedrops | Drug: Acetylsalicylate<br>* 1-2 drops<br>|
| Placebo Comparator: isotonic NaCl<br>Saline Eyedrops | Drug: Isotonic NaCl<br>* 1 drop<br>|
|
Challenge Test for Acetylsalicylic Acid Hypersensitivity
Study Overview
=================
Brief Summary
-----------------
The investigators want to find new challenge test for Acetylsalicylic hypersensitivity / Aspirin hypersensitivity. The investigators suggest that this new test will be as efficient as the already established protocols in terms of sensitivity and specificity.
Detailed Description
-----------------
Hypersensitivity to Acetylsalicylic Acid or Aspirin (and other NSAIDS) is a condition that affects up to 2,5% of the population. Most cases are seen in a complex of such hypersensitivity with chronic eosinophilic rhinosinusitis with nasal polyposis and asthma. Despite research in finding a reliable in-vitro-test for the condition, challenge tests are still considered gold standard. So far oral, nasal, inhalation and intravenous routes of administration has been described in literature.
Official Title
-----------------
Challenge Test for Acetylsalicylic Acid Hypersensitivity
Conditions
-----------------
Asthma Aspirin-sensitive, ASA Intolerant Asthma, Asthma, Aspirin-Induced, Asthma, Nasal Polyps, and Aspirin Intolerance
Intervention / Treatment
-----------------
* Drug: Acetylsalicylate
* Drug: Isotonic NaCl
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Persons between 18 and 60 years of age Suspected Acetylsalicylic Acid Hypersensitivity Exclusion Criteria: History on anaphylactic shock after NSAIDS intake History on gastric ulcer after NSAIDS intake Patients previously gone through testing or desensitisation for Aspirin hypersensitivity Clinical unstable asthma or baseline FEV1<70% Severe disease of the heart, digestive tract, liver or kidney Severe chronic urticaria Present conjunctivitis Pregnancy
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: Single Group Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Acetylsalicylate<br>Acetylsalicylic Acid Eyedrops | Drug: Acetylsalicylate<br>* 1-2 drops<br>|
| Placebo Comparator: isotonic NaCl<br>Saline Eyedrops | Drug: Isotonic NaCl<br>* 1 drop<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inspiratory nasal flow measured by Rhinomanometry | Bilateral flow reduction >40% considered positive test. | Within 45 min from challenge |
| Expiratory nasal flow measured by Rhinomanometry | Bilateral expiratory flow reduction >40% considered positive. | Within 45 min from challenge |
| Pulmonary forced expiratory volume in 1 second (FEV1) | Reduction in FEV1 >20% is considered as positive test. | Within 45 min from challenge |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conjunctival symptoms | 0=no symptoms, 1=limited redness and / or itching, 2=conjunctival redness and /or itching / swelling or bullae within 5 minutes from testing. Value 1 and 2 is considered positive if unilateral. | Within 45 days from challenge |
| Nasal symptoms | Rhinorrhea, congestion and sneezing is considered as positive test. | Within 45 minutes from challenge |
| Bronchial and laryngeal symptoms | Bronchospasm. tight chest, wheezing or laryngospasm is considered as positive test. | Within 45 minutes from challenge |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Challenge test for Aspirin Hypersensitivity, Challenge test for Acetylsalicylic Hypersensitivity
|
NCT02939781
|
Measuring the Metabolic Cost of Fever
|
Fever is part of the body's immune response, often triggered by infection. Fever is commonly treated with medicines such as paracetamol, mainly because people feel unwell with fever. However fever does have a role in fighting infection: it enables the rest of the immune system to function more efficiently, and may directly stop bacteria and viruses from multiplying. In most cases however treating fever does not matter because the rest of the immune system can cope well enough to fight the infection (with or without additional treatment, like antibiotics).~In critically ill patients however any advantage in the fight against infection may be crucial. In a large observational study of adult patients in the intensive care unit, patients who developed an early fever with temperature between 38.5-39.5 degrees C fared relatively better than patients who were colder. So it is possible that in critical illness fever may be beneficial. However in critical illness the body does have limited energy resources. In order to raise the body temperature energy is required. However the investigators do not know how much energy is required to generate a fever in critically ill children. This study will aim to try and measure the energy required to generate a fever in a critically ill child. The investigators will measure energy expenditure directly in children admitted to the intensive care unit by measuring the levels of oxygen and carbon dioxide they breathe in and out (a method called indirect calorimetry). This will enable the investigators to judge whether the benefits of a fever can be justified by the energy costs in the energy depleted state that is critical illness.
|
Measuring Energy Expenditure Before and After Fever in Critically Ill Children
|
Child, Critical Illness, Fever
|
* Device: Indirect calorimetry
|
Inclusion Criteria:~- all children on the paediatric intensive care unit at Great Ormond Street Hospital who~are likely to or have developed a fever (suspected infection, following trauma, post major surgery)~are over 10kg (approx 1 year of age)~are invasively ventilated~Exclusion Criteria:~- Children who~have a brain injury, where active temperature control may be instituted~patients post cardiac surgery~patient with or at risk of cardiac arrhythmias~patients post cardiac arrest~patient with refractory status epilepticus~children with a greater than 5% leak around the endotracheal tube~children with a fraction of inspired oxygen >0.6
|
0 Years
|
15 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Energy Expenditure Per Degree Celsius During Fever and Defervescence | Children at risk of fever will have energy expenditure measured by indirect calorimetry at baseline, when the develop a fever, and continuously until fever dehisces. Change in energy expenditure during fever to be calculated as difference in energy expenditure at the maximum temperature minus the energy expenditure at baseline, divided by the difference in temperature. Change in energy expenditure during defervescence to be calculated as difference in energy expenditure at the maximum temperature and the lowest temperature following the fall in temperature, divided by the difference in temperature.~Both will also be expressed as a % of the starting energy expenditure (i.e. from baseline for change during fever, from maximum temperature during defervescence) | 6 hours |
|
Fever, Critical Illness, Body Temperature Changes, Disease Attributes, Pathologic Processes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Febrile critically ill children<br>Children above 10kg admitted to the paediatric intensive care unit at Great Ormond Street Hospital who are mechanically ventilated and have a high likelihood of developing a fever. Energy expenditure will be measured using indirect calorimetry at baseline, and continuously during fever, until fever subsides. | Device: Indirect calorimetry<br>* Indirect calorimetry measurement at baseline (stable state), at onset of fever and continued till fever dehiscence<br>|
|
Measuring the Metabolic Cost of Fever
Study Overview
=================
Brief Summary
-----------------
Fever is part of the body's immune response, often triggered by infection. Fever is commonly treated with medicines such as paracetamol, mainly because people feel unwell with fever. However fever does have a role in fighting infection: it enables the rest of the immune system to function more efficiently, and may directly stop bacteria and viruses from multiplying. In most cases however treating fever does not matter because the rest of the immune system can cope well enough to fight the infection (with or without additional treatment, like antibiotics). In critically ill patients however any advantage in the fight against infection may be crucial. In a large observational study of adult patients in the intensive care unit, patients who developed an early fever with temperature between 38.5-39.5 degrees C fared relatively better than patients who were colder. So it is possible that in critical illness fever may be beneficial. However in critical illness the body does have limited energy resources. In order to raise the body temperature energy is required. However the investigators do not know how much energy is required to generate a fever in critically ill children. This study will aim to try and measure the energy required to generate a fever in a critically ill child. The investigators will measure energy expenditure directly in children admitted to the intensive care unit by measuring the levels of oxygen and carbon dioxide they breathe in and out (a method called indirect calorimetry). This will enable the investigators to judge whether the benefits of a fever can be justified by the energy costs in the energy depleted state that is critical illness.
Official Title
-----------------
Measuring Energy Expenditure Before and After Fever in Critically Ill Children
Conditions
-----------------
Child, Critical Illness, Fever
Intervention / Treatment
-----------------
* Device: Indirect calorimetry
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: - all children on the paediatric intensive care unit at Great Ormond Street Hospital who are likely to or have developed a fever (suspected infection, following trauma, post major surgery) are over 10kg (approx 1 year of age) are invasively ventilated Exclusion Criteria: - Children who have a brain injury, where active temperature control may be instituted patients post cardiac surgery patient with or at risk of cardiac arrhythmias patients post cardiac arrest patient with refractory status epilepticus children with a greater than 5% leak around the endotracheal tube children with a fraction of inspired oxygen >0.6
Ages Eligible for Study
-----------------
Minimum Age: 0 Years
Maximum Age: 15 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Febrile critically ill children<br>Children above 10kg admitted to the paediatric intensive care unit at Great Ormond Street Hospital who are mechanically ventilated and have a high likelihood of developing a fever. Energy expenditure will be measured using indirect calorimetry at baseline, and continuously during fever, until fever subsides. | Device: Indirect calorimetry<br>* Indirect calorimetry measurement at baseline (stable state), at onset of fever and continued till fever dehiscence<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Energy Expenditure Per Degree Celsius During Fever and Defervescence | Children at risk of fever will have energy expenditure measured by indirect calorimetry at baseline, when the develop a fever, and continuously until fever dehisces. Change in energy expenditure during fever to be calculated as difference in energy expenditure at the maximum temperature minus the energy expenditure at baseline, divided by the difference in temperature. Change in energy expenditure during defervescence to be calculated as difference in energy expenditure at the maximum temperature and the lowest temperature following the fall in temperature, divided by the difference in temperature. Both will also be expressed as a % of the starting energy expenditure (i.e. from baseline for change during fever, from maximum temperature during defervescence) | 6 hours |
|
||||
NCT01071057
|
Naloxone for the Treatment of Opioid-Induced Pruritus
|
The purpose of this study is to improve how we treat itching, a common side effect associated with the use of morphine pain medication. Itching is a problem experienced by up to 30% of the children treated with pain medications in the morphine family.~Despite studies demonstrating the effectiveness of using naloxone to treat itchiness in adults receiving morphine pain medications, there are not many studies in children. This study is designed to study how well naloxone works for treatment of itching in children
|
Hypothesis: Naloxone co-administered simultaneously with standard Patient Controlled Analgesia (PCA) basal and bolus morphine will significantly reduce the incidence of Opioid Induced Pruritus (OIP) without affecting analgesia or opioid consumption in children.~Specific Objectives:~To determine if naloxone (12 µg/ml) mixed in a single infusion with morphine (1 mg/ml) will be effective in the prevention of opioid induced pruritus (OIP).~To determine if treatment with naloxone will result in attenuation of analgesia or an increase in opioid utilisation.~To determine if treatment with naloxone will reduce other opioid induced side effects such as nausea and vomiting.~Methods: This study is divided into two phases. Phase 1 - Although, there are studies confirming the compatibility of morphine (4 mg/mL) with naloxone (16 µg/mL) in separate infusion pumps run into the same intravenous site, there are no studies confirming the chemical and physical compatibility of morphine and naloxone in the same syringe with the standard concentrations used at BCCH. Therefore, a compatibility and stability study of naloxone and morphine solution in the same syringe will be performed.~Phase 2 - Phase 2 is a blinded clinical trial where 70 subjects will be randomized to receive either morphine mixed with naloxone or morphine mixed with placebo.With institutional review board approval, and written parental/guardian informed consent (and assent if appropriate), we will recruit children, ages 5-16 years, receiving intravenous opioids via PCA for post-operative pain control. Subjects will be evaluated every 4 hr for pain scores, frequency of vomiting, nausea, pruritus, sedation, and respiratory depression. At 24 and 48 hr, the total morphine consumption will be calculated.~Data analysis: Differences in the incidence and intensity of pruritus between the two groups will be compared. We will review side effects using the following control variables: (1) demographic data; and (2) summation of opioid use in each 4 hr period for total opioid consumption. ANOVA and crosstabs will be used where appropriate to analyze data.
|
Naloxone for the Treatment of Opioid-Induced Pruritus: A Double-Blind, Prospective, Randomized, Controlled Study
|
Pruritus
|
* Drug: Naloxone
* Drug: Saline/Morphine
|
Inclusion Criteria:~Children 5-18 years of age undergoing surgery at BCCH~ASA I - II.~Children receiving PCA morphine.~Informed consent/assent provided by child/parent/guardian.~Exclusion Criteria~Children with known abnormal developmental profile.~Children with known opioid allergy.~Inability/failure to obtain informed consent/assent from parent/guardian/child.~Children receiving concurrent opioids.~Children with pre-existing pruritus from non-opioid related cause.~Children receiving PCA hydromorphone or fentanyl.~ASA 3 and above.~Children who require admission to the Pediatric Intensive Care Unit (PICU). - Children involved in any investigational drug trial within the previous one month.~Any child in the study that experiences unmanageable pruritus within the protocol time frame and is converted to hydromorphone will continue to be monitored for 48 hours. However, this will be taken into account during statistical analysis of study results. Appropriate conventional rescue medication for pruritus (diphenhydramine 0.5mg/kg IV 4hrly PRN) will be provided for any child who continues to experience pruritus.
|
5 Years
|
18 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pruritus incidence and intensity | | 2 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-report pain scores | | 2 days |
| Morphine, ondansetron, diphenhydramine utilization | | 2 days |
|
opioid-induced pruritus, naloxone
|
Morphine, Naloxone, Analgesics, Opioid, Narcotics, Central Nervous System Depressants, Physiological Effects of Drugs, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Narcotic Antagonists
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Naloxone/morphine<br>Naloxone (12 µg/ml) mixed in a single infusion with morphine (1 mg/ml). The study solutions will be prepared by a pharmacist and diluted in saline to produce equal volumes to ensure proper blinding. | Drug: Naloxone<br>* Basal infusion of 20µg/kg/hour, bolus dose of 20µg /kg, lockout of 5 minutes with hourly maximum not to exceed 150µg /kg/hr, maximum 6 bolus doses. Subject pain relief will be assessed and documented by nursing staff and supervised by the Acute Pain Service (APS). Morphine will be titrated to subject need according to APS PCA protocol.<br>|
| Placebo Comparator: saline/morphine<br>Patients will be randomly assigned to one of two groups (Naloxone/morphine or saline/morphine) using computer-generated random numbers. On arrival to the PACU patients will be started on IV PCA and randomized study drug | Drug: Saline/Morphine<br>* Basal infusion of 20µg/kg/hour, bolus dose of 20µg /kg, lockout of 5 minutes with hourly maximum not to exceed 150µg /kg/hr, maximum 6 bolus doses. Subject pain relief will be assessed and documented by nursing staff and supervised by the Acute Pain Service (APS). Morphine will be titrated to subject need according to APS PCA protocol.<br>|
|
Naloxone for the Treatment of Opioid-Induced Pruritus
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to improve how we treat itching, a common side effect associated with the use of morphine pain medication. Itching is a problem experienced by up to 30% of the children treated with pain medications in the morphine family. Despite studies demonstrating the effectiveness of using naloxone to treat itchiness in adults receiving morphine pain medications, there are not many studies in children. This study is designed to study how well naloxone works for treatment of itching in children
Detailed Description
-----------------
Hypothesis: Naloxone co-administered simultaneously with standard Patient Controlled Analgesia (PCA) basal and bolus morphine will significantly reduce the incidence of Opioid Induced Pruritus (OIP) without affecting analgesia or opioid consumption in children. Specific Objectives: To determine if naloxone (12 µg/ml) mixed in a single infusion with morphine (1 mg/ml) will be effective in the prevention of opioid induced pruritus (OIP). To determine if treatment with naloxone will result in attenuation of analgesia or an increase in opioid utilisation. To determine if treatment with naloxone will reduce other opioid induced side effects such as nausea and vomiting. Methods: This study is divided into two phases. Phase 1 - Although, there are studies confirming the compatibility of morphine (4 mg/mL) with naloxone (16 µg/mL) in separate infusion pumps run into the same intravenous site, there are no studies confirming the chemical and physical compatibility of morphine and naloxone in the same syringe with the standard concentrations used at BCCH. Therefore, a compatibility and stability study of naloxone and morphine solution in the same syringe will be performed. Phase 2 - Phase 2 is a blinded clinical trial where 70 subjects will be randomized to receive either morphine mixed with naloxone or morphine mixed with placebo.With institutional review board approval, and written parental/guardian informed consent (and assent if appropriate), we will recruit children, ages 5-16 years, receiving intravenous opioids via PCA for post-operative pain control. Subjects will be evaluated every 4 hr for pain scores, frequency of vomiting, nausea, pruritus, sedation, and respiratory depression. At 24 and 48 hr, the total morphine consumption will be calculated. Data analysis: Differences in the incidence and intensity of pruritus between the two groups will be compared. We will review side effects using the following control variables: (1) demographic data; and (2) summation of opioid use in each 4 hr period for total opioid consumption. ANOVA and crosstabs will be used where appropriate to analyze data.
Official Title
-----------------
Naloxone for the Treatment of Opioid-Induced Pruritus: A Double-Blind, Prospective, Randomized, Controlled Study
Conditions
-----------------
Pruritus
Intervention / Treatment
-----------------
* Drug: Naloxone
* Drug: Saline/Morphine
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Children 5-18 years of age undergoing surgery at BCCH ASA I - II. Children receiving PCA morphine. Informed consent/assent provided by child/parent/guardian. Exclusion Criteria Children with known abnormal developmental profile. Children with known opioid allergy. Inability/failure to obtain informed consent/assent from parent/guardian/child. Children receiving concurrent opioids. Children with pre-existing pruritus from non-opioid related cause. Children receiving PCA hydromorphone or fentanyl. ASA 3 and above. Children who require admission to the Pediatric Intensive Care Unit (PICU). - Children involved in any investigational drug trial within the previous one month. Any child in the study that experiences unmanageable pruritus within the protocol time frame and is converted to hydromorphone will continue to be monitored for 48 hours. However, this will be taken into account during statistical analysis of study results. Appropriate conventional rescue medication for pruritus (diphenhydramine 0.5mg/kg IV 4hrly PRN) will be provided for any child who continues to experience pruritus.
Ages Eligible for Study
-----------------
Minimum Age: 5 Years
Maximum 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: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Naloxone/morphine<br>Naloxone (12 µg/ml) mixed in a single infusion with morphine (1 mg/ml). The study solutions will be prepared by a pharmacist and diluted in saline to produce equal volumes to ensure proper blinding. | Drug: Naloxone<br>* Basal infusion of 20µg/kg/hour, bolus dose of 20µg /kg, lockout of 5 minutes with hourly maximum not to exceed 150µg /kg/hr, maximum 6 bolus doses. Subject pain relief will be assessed and documented by nursing staff and supervised by the Acute Pain Service (APS). Morphine will be titrated to subject need according to APS PCA protocol.<br>|
| Placebo Comparator: saline/morphine<br>Patients will be randomly assigned to one of two groups (Naloxone/morphine or saline/morphine) using computer-generated random numbers. On arrival to the PACU patients will be started on IV PCA and randomized study drug | Drug: Saline/Morphine<br>* Basal infusion of 20µg/kg/hour, bolus dose of 20µg /kg, lockout of 5 minutes with hourly maximum not to exceed 150µg /kg/hr, maximum 6 bolus doses. Subject pain relief will be assessed and documented by nursing staff and supervised by the Acute Pain Service (APS). Morphine will be titrated to subject need according to APS PCA protocol.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pruritus incidence and intensity | | 2 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-report pain scores | | 2 days |
| Morphine, ondansetron, diphenhydramine utilization | | 2 days |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
opioid-induced pruritus, naloxone
|
NCT03208634
|
Rehabilitation Multi Sensory Room for Robot Assisted Functional Movements in Upper-limb Rehabilitation in Chronic Stroke
|
Robotic rehabilitation is promising to promote function in stroke patients. The assist as needed training paradigm has shown to stimulate neuroplasticity but often cannot be used because stroke patients are too impaired to actively control the robot against gravity. Aim of this study is to present a novel robotic approach based on fully assisted functional movements and to examine the effect of the intervention in terms of motor function improvement in subjects with chronic stroke in the short term and at 6-month follow up. A preliminary evaluation of the effectiveness of the intervention in improving activity and participation in the short term is also performed. Further, the study aims to verify whether some instrumental measures (using kinematics, EMG and EEG) may help gain insight into the mechanisms leading to improved motor ability following the robotic intervention and can be used to predict functional recovery.
|
Stroke is a leading cause of serious long-term disability in developed countries, and has an enormous emotional and socioeconomic impact on patients, families and, health services. Upper-limb impairments and functional problems are, in fact, very common after a stroke. Impairments commonly include difficulty moving and co-ordinating the arms, hands and fingers, often resulting in difficulty carrying out Activities of Daily Living (ADLs) such as eating, dressing and washing. More than half of people with upper-limb impairment after stroke will still have difficulties in performing ADLs many months to years after their stroke. Robotic rehabilitation systems have the potential to deliver large doses of motor training in a cost-effective manner and, although the debate on the efficacy of robotic therapy is still open, they are emerging as valid solutions to help stroke survivors in the rehabilitation of the upper limb. Recent review of Norouzi-Gheidari shows that the effect of a robotic training is comparable to a conventional therapy training of the same length and intensity. A recent Cochrane systematic review of Mehrholz included 34 trials (involving 1160 participants) showed that electromechanical and robot-assisted arm training improved ADLs scores, arm function, and arm muscle strength, but the quality of the evidence was low to very low. Unfortunately, the mechanisms leading to impairment reduction following the robotic training are still unclear. It is known that neuroplasticity plays an important role in the motor recovery process of stroke patients and, further, that the patient should be engaged during the treatment in order to foster a process similar to motor learning. To promote engagement and maximize neuroplasticity, two main methods have been studied in robotic rehabilitation: i) the assist-as-needed training paradigm, and ii) the Detection of Patient Intent (DPI) method, also called guided force training. The first one, which consists in providing the minimal assistance needed to the subject to complete the task required, has shown promising results in enhancing the participation to the treatment, especially in medium-high functional patients. The DPI method, instead, is based on triggering the movement of the robot using the patient's exerted force or induced velocity. In some cases, the DPI method may even exploit biomedical signals like EMG or EEG to initiate the given task.~Besides the modality of interaction between patient and robot, another important feature that can determining the success of the therapy is the type of movement proposed. It is known that treatments based on purposeful movements show better results in the recovery of the upper-limb function than those based on movements without a goal. Therefore, a proper rehabilitation program should include high repetition task-oriented movements.~Unfortunately, the assist-as-need principle and the DPI method are often of little applicability in training against gravity, especially in the case of low functioning patients with high strength and coordination impairments. In these cases, when the patient is not able to control actively the robot, full assistance, based on a rigidly imposed trajectory (path and motion law), is the only remaining option in robotic rehabilitation.~In this preliminary study, an upper-limb rehabilitation program based on robot fully assisted (rigidly imposed) goal-oriented movements is presented.~Aim of this study is to present a novel robotic approach based on fully assisted functional movements and to examine the effect of the intervention in terms of motor function improvement in subjects with chronic stroke in the short term and at 6-month follow up. A preliminary evaluation of the effectiveness of the intervention in improving activity and participation in the short term is also performed. Further, the study aims to verify whether some instrumental measures (using kinematics, EMG and EEG) may help gain insight into the mechanisms leading to improved motor ability following the robotic intervention and can be used to predict functional recovery.~STUDY POPULATION AND DESIGN In this cohort study, a convenience sample of 20 patients with mild-to-severe upper-limb impairment (upper-limb Fugl-Meyer scores at baseline: 11/66 to 61/66 points) 6 months or more poststroke will be enrolled. The study is in 2 phases. A pilot trial, involving 10 patients, will aim to verifying the short-term efficacy of the robotic intervention in reducing motor impairment. If results will be positive, the study will be continued and the sample size will be calculated on statistical basis from the preliminary results. The second trial aims to improving the number of patients and to verifying whether functional improvements translate into improved activity and participation.~INTERVENTION The intervention is administered by a trained research therapist via an end-effector robot (Pa10-7, Mitsubishi, Japan), which was customized to assist 3D multi-joint functional movements against gravity performed at physiological velocity. The robot enables the execution of both reaching movements, which in everyday life are used to interact with the environment (e.g. reach, grasp, and manipulate objects) and movements taking place in the peripersonal space.~The intervention protocol, identical in the 2 phases of the study, consists in the execution of two functional movements, namely the Reaching Movement (RM) against gravity and the Hand-to-Mouth Movement (HtMM):~starting with the robot handle just above the thigh, the assisted RM consists in compound movements of shoulder flexion and elbow extension getting as far as 90 degrees of shoulder flexion and fully extended elbow are reached;~starting with the robot handle just above the thigh, the assisted HtMM consists in flexing the elbow (and the shoulder) to positioning the robot-handle in front of the mouth. Importantly, the handle is free to rotate and, therefore, the patient has to actively (internal/external wrist rotation) put it in the right position, that is with its extremity pointing towards the mouth.~The robot handle paths and velocities are customized on each patient's anthropometric measures and residual functional abilities.~Each session consists in 20 minutes of robot-assisted RM and 20 minutes of robot-assisted HtMM. Movements are fully assisted (the robot handle moved along the path with a predefined motion law independently of the forces exerted by the patient on the handle) but the patient is explicitly asked to participate by trying to follow (slightly anticipate) the moving handle. Recalling that both movements are against gravity, in order not to get fatigued, the patient is asked to change the level of engagement every 5 movements by alternately relaxing during movement and actively participating.~Rehabilitation consists in a 1-month intervention, 3 sessions a week performed on Monday, Wednesday and Friday, for a total of 12 sessions.~CLINICAL ASSESSMENT Patients are clinically tested at baseline (T0), just after intervention (T1) and at 6 months or more after intervention (T2). One trained physical therapist, the same for all patients, performs all outcome assessments (pretreatment as well as posttreatment and follow up) with the supervision of the patient's referent physician, who can double check the clinical tests results even consulting the videos of the patients. To minimize biases during post-treatment evaluation, he cannot have access and view the results of previous sessions.~The primary outcome measure is the upper-limb motor function subdomain (sections A-D) of the FMA, which comprised 33 items, each scored on a 0, 1, 2 points ordinal scale. The range of this scale score, here forward referred to as Upper-Extremity Fugl-Meyer Assessment (UE-FMA), is from 0 (no function) to 66 (normal function).~The secondary outcome measures are the Wolf Motor Function Test (WMFT) and the (MAL), which are administered to patients only in the final trial. The WMFT consists of 15 tasks (timed single- or multiple-joint motions and functional tasks). The execution of each task is timed (WMFT TIME) and rated using a 6-point functional ability scale (WMFT FAS).~The MAL is a semi-structured interview, which evaluates the Quality of Movement (QOM) and Amount of Use (AOU) the patient makes of the affected limb in 30 activities of daily life.~The following tests are further carried out: 1) The Medical Research Council scale for muscle strength (MRC) is used for evaluating the muscles (joint) strength of three targeted movements: shoulder abduction, elbow extension and fingers extension. MRC is a 15 points scale (5 points for each item); 2) The Modified Ashworth Scale (MAS) is used to assess spasticity. Each tested movement is given a 0 to 5 score (0 no spasticity, 1 slight increase in muscle tone at end movement, 2 slight increase in muscle tone up to half of the ROM, 3 more marked increase in muscle tone through most of the ROM, 4 considerable increase in muscle tone, 5 affected part rigid in flexion or extension. The tested movement were: wrist extension, elbow extension and shoulder abduction, for a total of 15 (negative) points. 3) The Clinical Global Impression Scale of severity and improvement is used to evaluating: (a) severity of psychopathology from 1 to 7 and (b) change from the initiation of treatment on a similar seven-point scale. 4) The Draw a Person Test to assessing the patient's body awareness and, finally, 5) The Nasa-Task Load Index is used to assessing the patient's physical and mental load during intervention.~INSTRUMENTAL ASSESSMENT The instrumental evaluation hereafter listed are performed at baseline (T0), just after intervention (T1) and at 6 months or more after intervention (T2). Acquisitions are carried out during both robot assisted and no-assisted reaching and hand-to-mouth movements performed with the more affected limb and no-assisted movements performed with the less affected limb.~upper-limb kinematics (6 TVcs, Smart-D, BTS Bioengineering, Italy) and dynamic surface EMG (the upper trapezius, the anterior, middle and posterior deltoids, the triceps brachii lateral head, the biceps long head, and the brachioradialisn muscles; FreeEMG 300, BTS Bioengineering, Italy). Range of movements, velocities, normalized jerk and coefficient of periodicity are calculated using the method published by Caimmi in 2008.~EEG signals are recorded using a cap providing 64 electrodes positioned according to the International 10/10 System; EMG activity is simultaneously recorded from pairs of Ag/AgCl surface electrodes placed bilaterally 2-3 cm apart over the deltoid anterior and the triceps muscles during reaching, and biceps and the brachioradialis muscles during the hand-to-mouth movement. The EEG and EMG data are acquired using a Neuroscan system at a sampling frequency of 512 Hz (band-pass filters: 1-200 Hz). Event Related Desynchronization/Synchronization (ERD/ERS) analysis is performed to quantify the movement related power change of the EEG oscillatory activity in alpha and beta bands over the premotor and primary sensorimotor areas.~DATA ANALYSIS Based on the primary outcome measure results of the pilot trial, the sample size of the study will be computed using the freeware G*Power 3.1.9.2, general statistical power analysis program. Comparisons of data between different sessions are performed with the Wilcoxon signed-rank test, considering the value of significance at 0.05. Linear regression and Pearson's correlation are used to evaluate the relationship between the UE-FMA improvement and 1) the age of patients. 2) the time from the stroke, and 3) the calculated kinematic quantities. The statistical analysis is performed using WinSTAT® for Microsoft® ver.2012.1.0.94.
|
La Riabilitazione Robot Assistita Del Paziente Neurologico: l'Elettromiografia Dinamica di Superficie Come Strumento Per la Personalizzazione Del Trattamento
|
Chronic Stroke
|
* Device: Robotic intervention
|
Inclusion Criteria:~hemiplegia after first stroke;~time from the stroke event > 6 months;~absence of severe attentive deficits;~ability to perform active arm movements (shoulder flexion MRC > 1 and AROM > 60°, elbow flexion-extension MRC >1 and AROM > 90°) and able to hold the robot handle,~Modified Ashworth Scale score ≤ 3 (see section outcome)~Exclusion Criteria:~other concurrent upper-limb rehabilitation interventions;~presence of global aphasia and/or cognitive impairments that could interfere with~understanding the instructions during evaluation and treatment.~concomitant progressive central nervous system disorders, peripheral nervous system disorders or myopathies
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Upper-Extremity Fugl-Meyer Assessment | Function domain | Baseline; 4 weeks; 6-month follow up |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Wolf Motor Function Test (WMFT) | Activity domain | Baseline; 4 weeks; 6-month follow up |
| Change in Motor Activity Log | Participation domain | Baseline; 4 weeks; 6-month follow up |
|
robotics, motor performance, stroke patient, upper limb, rehabilitation
|
Stroke, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Vascular Diseases, Cardiovascular Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Robotic intervention<br>Robotic intervention. | Device: Robotic intervention<br>* One-month robotic intervention. Twelve sessions, three sessions a week, 40 minutes each. Twenty minutes of fully assisted reaching + 20 minutes of assisted Hand-to-Mouth<br>|
|
Rehabilitation Multi Sensory Room for Robot Assisted Functional Movements in Upper-limb Rehabilitation in Chronic Stroke
Study Overview
=================
Brief Summary
-----------------
Robotic rehabilitation is promising to promote function in stroke patients. The assist as needed training paradigm has shown to stimulate neuroplasticity but often cannot be used because stroke patients are too impaired to actively control the robot against gravity. Aim of this study is to present a novel robotic approach based on fully assisted functional movements and to examine the effect of the intervention in terms of motor function improvement in subjects with chronic stroke in the short term and at 6-month follow up. A preliminary evaluation of the effectiveness of the intervention in improving activity and participation in the short term is also performed. Further, the study aims to verify whether some instrumental measures (using kinematics, EMG and EEG) may help gain insight into the mechanisms leading to improved motor ability following the robotic intervention and can be used to predict functional recovery.
Detailed Description
-----------------
Stroke is a leading cause of serious long-term disability in developed countries, and has an enormous emotional and socioeconomic impact on patients, families and, health services. Upper-limb impairments and functional problems are, in fact, very common after a stroke. Impairments commonly include difficulty moving and co-ordinating the arms, hands and fingers, often resulting in difficulty carrying out Activities of Daily Living (ADLs) such as eating, dressing and washing. More than half of people with upper-limb impairment after stroke will still have difficulties in performing ADLs many months to years after their stroke. Robotic rehabilitation systems have the potential to deliver large doses of motor training in a cost-effective manner and, although the debate on the efficacy of robotic therapy is still open, they are emerging as valid solutions to help stroke survivors in the rehabilitation of the upper limb. Recent review of Norouzi-Gheidari shows that the effect of a robotic training is comparable to a conventional therapy training of the same length and intensity. A recent Cochrane systematic review of Mehrholz included 34 trials (involving 1160 participants) showed that electromechanical and robot-assisted arm training improved ADLs scores, arm function, and arm muscle strength, but the quality of the evidence was low to very low. Unfortunately, the mechanisms leading to impairment reduction following the robotic training are still unclear. It is known that neuroplasticity plays an important role in the motor recovery process of stroke patients and, further, that the patient should be engaged during the treatment in order to foster a process similar to motor learning. To promote engagement and maximize neuroplasticity, two main methods have been studied in robotic rehabilitation: i) the assist-as-needed training paradigm, and ii) the Detection of Patient Intent (DPI) method, also called guided force training. The first one, which consists in providing the minimal assistance needed to the subject to complete the task required, has shown promising results in enhancing the participation to the treatment, especially in medium-high functional patients. The DPI method, instead, is based on triggering the movement of the robot using the patient's exerted force or induced velocity. In some cases, the DPI method may even exploit biomedical signals like EMG or EEG to initiate the given task. Besides the modality of interaction between patient and robot, another important feature that can determining the success of the therapy is the type of movement proposed. It is known that treatments based on purposeful movements show better results in the recovery of the upper-limb function than those based on movements without a goal. Therefore, a proper rehabilitation program should include high repetition task-oriented movements. Unfortunately, the assist-as-need principle and the DPI method are often of little applicability in training against gravity, especially in the case of low functioning patients with high strength and coordination impairments. In these cases, when the patient is not able to control actively the robot, full assistance, based on a rigidly imposed trajectory (path and motion law), is the only remaining option in robotic rehabilitation. In this preliminary study, an upper-limb rehabilitation program based on robot fully assisted (rigidly imposed) goal-oriented movements is presented. Aim of this study is to present a novel robotic approach based on fully assisted functional movements and to examine the effect of the intervention in terms of motor function improvement in subjects with chronic stroke in the short term and at 6-month follow up. A preliminary evaluation of the effectiveness of the intervention in improving activity and participation in the short term is also performed. Further, the study aims to verify whether some instrumental measures (using kinematics, EMG and EEG) may help gain insight into the mechanisms leading to improved motor ability following the robotic intervention and can be used to predict functional recovery. STUDY POPULATION AND DESIGN In this cohort study, a convenience sample of 20 patients with mild-to-severe upper-limb impairment (upper-limb Fugl-Meyer scores at baseline: 11/66 to 61/66 points) 6 months or more poststroke will be enrolled. The study is in 2 phases. A pilot trial, involving 10 patients, will aim to verifying the short-term efficacy of the robotic intervention in reducing motor impairment. If results will be positive, the study will be continued and the sample size will be calculated on statistical basis from the preliminary results. The second trial aims to improving the number of patients and to verifying whether functional improvements translate into improved activity and participation. INTERVENTION The intervention is administered by a trained research therapist via an end-effector robot (Pa10-7, Mitsubishi, Japan), which was customized to assist 3D multi-joint functional movements against gravity performed at physiological velocity. The robot enables the execution of both reaching movements, which in everyday life are used to interact with the environment (e.g. reach, grasp, and manipulate objects) and movements taking place in the peripersonal space. The intervention protocol, identical in the 2 phases of the study, consists in the execution of two functional movements, namely the Reaching Movement (RM) against gravity and the Hand-to-Mouth Movement (HtMM): starting with the robot handle just above the thigh, the assisted RM consists in compound movements of shoulder flexion and elbow extension getting as far as 90 degrees of shoulder flexion and fully extended elbow are reached; starting with the robot handle just above the thigh, the assisted HtMM consists in flexing the elbow (and the shoulder) to positioning the robot-handle in front of the mouth. Importantly, the handle is free to rotate and, therefore, the patient has to actively (internal/external wrist rotation) put it in the right position, that is with its extremity pointing towards the mouth. The robot handle paths and velocities are customized on each patient's anthropometric measures and residual functional abilities. Each session consists in 20 minutes of robot-assisted RM and 20 minutes of robot-assisted HtMM. Movements are fully assisted (the robot handle moved along the path with a predefined motion law independently of the forces exerted by the patient on the handle) but the patient is explicitly asked to participate by trying to follow (slightly anticipate) the moving handle. Recalling that both movements are against gravity, in order not to get fatigued, the patient is asked to change the level of engagement every 5 movements by alternately relaxing during movement and actively participating. Rehabilitation consists in a 1-month intervention, 3 sessions a week performed on Monday, Wednesday and Friday, for a total of 12 sessions. CLINICAL ASSESSMENT Patients are clinically tested at baseline (T0), just after intervention (T1) and at 6 months or more after intervention (T2). One trained physical therapist, the same for all patients, performs all outcome assessments (pretreatment as well as posttreatment and follow up) with the supervision of the patient's referent physician, who can double check the clinical tests results even consulting the videos of the patients. To minimize biases during post-treatment evaluation, he cannot have access and view the results of previous sessions. The primary outcome measure is the upper-limb motor function subdomain (sections A-D) of the FMA, which comprised 33 items, each scored on a 0, 1, 2 points ordinal scale. The range of this scale score, here forward referred to as Upper-Extremity Fugl-Meyer Assessment (UE-FMA), is from 0 (no function) to 66 (normal function). The secondary outcome measures are the Wolf Motor Function Test (WMFT) and the (MAL), which are administered to patients only in the final trial. The WMFT consists of 15 tasks (timed single- or multiple-joint motions and functional tasks). The execution of each task is timed (WMFT TIME) and rated using a 6-point functional ability scale (WMFT FAS). The MAL is a semi-structured interview, which evaluates the Quality of Movement (QOM) and Amount of Use (AOU) the patient makes of the affected limb in 30 activities of daily life. The following tests are further carried out: 1) The Medical Research Council scale for muscle strength (MRC) is used for evaluating the muscles (joint) strength of three targeted movements: shoulder abduction, elbow extension and fingers extension. MRC is a 15 points scale (5 points for each item); 2) The Modified Ashworth Scale (MAS) is used to assess spasticity. Each tested movement is given a 0 to 5 score (0 no spasticity, 1 slight increase in muscle tone at end movement, 2 slight increase in muscle tone up to half of the ROM, 3 more marked increase in muscle tone through most of the ROM, 4 considerable increase in muscle tone, 5 affected part rigid in flexion or extension. The tested movement were: wrist extension, elbow extension and shoulder abduction, for a total of 15 (negative) points. 3) The Clinical Global Impression Scale of severity and improvement is used to evaluating: (a) severity of psychopathology from 1 to 7 and (b) change from the initiation of treatment on a similar seven-point scale. 4) The Draw a Person Test to assessing the patient's body awareness and, finally, 5) The Nasa-Task Load Index is used to assessing the patient's physical and mental load during intervention. INSTRUMENTAL ASSESSMENT The instrumental evaluation hereafter listed are performed at baseline (T0), just after intervention (T1) and at 6 months or more after intervention (T2). Acquisitions are carried out during both robot assisted and no-assisted reaching and hand-to-mouth movements performed with the more affected limb and no-assisted movements performed with the less affected limb. upper-limb kinematics (6 TVcs, Smart-D, BTS Bioengineering, Italy) and dynamic surface EMG (the upper trapezius, the anterior, middle and posterior deltoids, the triceps brachii lateral head, the biceps long head, and the brachioradialisn muscles; FreeEMG 300, BTS Bioengineering, Italy). Range of movements, velocities, normalized jerk and coefficient of periodicity are calculated using the method published by Caimmi in 2008. EEG signals are recorded using a cap providing 64 electrodes positioned according to the International 10/10 System; EMG activity is simultaneously recorded from pairs of Ag/AgCl surface electrodes placed bilaterally 2-3 cm apart over the deltoid anterior and the triceps muscles during reaching, and biceps and the brachioradialis muscles during the hand-to-mouth movement. The EEG and EMG data are acquired using a Neuroscan system at a sampling frequency of 512 Hz (band-pass filters: 1-200 Hz). Event Related Desynchronization/Synchronization (ERD/ERS) analysis is performed to quantify the movement related power change of the EEG oscillatory activity in alpha and beta bands over the premotor and primary sensorimotor areas. DATA ANALYSIS Based on the primary outcome measure results of the pilot trial, the sample size of the study will be computed using the freeware G*Power 3.1.9.2, general statistical power analysis program. Comparisons of data between different sessions are performed with the Wilcoxon signed-rank test, considering the value of significance at 0.05. Linear regression and Pearson's correlation are used to evaluate the relationship between the UE-FMA improvement and 1) the age of patients. 2) the time from the stroke, and 3) the calculated kinematic quantities. The statistical analysis is performed using WinSTAT® for Microsoft® ver.2012.1.0.94.
Official Title
-----------------
La Riabilitazione Robot Assistita Del Paziente Neurologico: l'Elettromiografia Dinamica di Superficie Come Strumento Per la Personalizzazione Del Trattamento
Conditions
-----------------
Chronic Stroke
Intervention / Treatment
-----------------
* Device: Robotic intervention
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: hemiplegia after first stroke; time from the stroke event > 6 months; absence of severe attentive deficits; ability to perform active arm movements (shoulder flexion MRC > 1 and AROM > 60°, elbow flexion-extension MRC >1 and AROM > 90°) and able to hold the robot handle, Modified Ashworth Scale score ≤ 3 (see section outcome) Exclusion Criteria: other concurrent upper-limb rehabilitation interventions; presence of global aphasia and/or cognitive impairments that could interfere with understanding the instructions during evaluation and treatment. concomitant progressive central nervous system disorders, peripheral nervous system disorders or myopathies
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: Robotic intervention<br>Robotic intervention. | Device: Robotic intervention<br>* One-month robotic intervention. Twelve sessions, three sessions a week, 40 minutes each. Twenty minutes of fully assisted reaching + 20 minutes of assisted Hand-to-Mouth<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Upper-Extremity Fugl-Meyer Assessment | Function domain | Baseline; 4 weeks; 6-month follow up |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Wolf Motor Function Test (WMFT) | Activity domain | Baseline; 4 weeks; 6-month follow up |
| Change in Motor Activity Log | Participation domain | Baseline; 4 weeks; 6-month follow up |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
robotics, motor performance, stroke patient, upper limb, rehabilitation
|
NCT02922283
|
IL2 Imaging in Metastatic Melanoma
|
T cell infiltration of tumor lesions is a known prognostic factor in several tumor types and is used as treatment mechanism in some of these tumor types. In metastatic melanoma, treatment with immune checkpoint inhibitors induces clinical benefit in about 30-50% of the patients. These immune-based therapies are however accompanied by serious immune-related adverse events and high costs.~Tumor infiltrating T cells express the high affinity interleukin-2 (IL2) receptor on their surface. These T cells could therefore be visualized by molecular imaging with a radio-labelled ligand for this receptor. For this purpose, the investigators have developed the PET tracer [18F]FB-IL2.~The study commences with a biodistribution study (phase 1) in 5 subjects. Thereafter the main study (phase 2) starts, in which 25 subjects will receive two [18F]FB-IL2 PET scans at baseline and week 6 of treatment with either ipilimumab, nivolumab, pembrolizumab or the combination of ipilimumab and nivolumab. If [18F]FB-IL2 PET is able to detect a response to treatment, it could serve as a non-invasive early indicator of T cell response to the treatment. Besides, accumulation of the PET tracer in non-target tissue could indicate infiltration of activated T cells in normal organs and thus may predict the development of an immune-related adverse event.
|
[18F]FB-IL2 Imaging of T Cell Response as Biomarker to Guide Treatment Decisions in Metastatic Melanoma Patients
|
Melanoma
|
* Device: IL2-PET scan
* Procedure: Tumor biopsy
* Device: CT scan
* Procedure: Biopsy of non-target tissue
|
Inclusion Criteria:~Has signed informed consent.~≥18 years of age.~Histologically confirmed cutaneous metastatic melanoma (Stage IV).~Evidence of at least one measurable metastatic lesion based on RECIST version 1.1.~At least one easy accessible metastatic melanoma lesion, of which biopsy can be performed.~Eligible for treatment with ipilimumab, nivolumab, pembrolizumab, or the combination of ipilimumab and nivolumab.~No contraindication for performing a CT scan.~Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.~Women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study.~Must have adequate organ function (e.g. liver, kidney) as defined~Exclusion Criteria:~Pre-existing auto-immune disease, which could be exacerbated by ipilimumab (e.g. Crohn, Hashimoto's Thyroiditis).~Presence of malignancy other than the disease under study within 5 years of study enrolment. Subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.~Brain metastases that are symptomatic or not stable for 8 weeks (must be documented by imaging).~The use of corticosteroids (at the start of treatment). Note: Corticosteroids are allowed during the study for immune-related toxicity of immunotherapy, as this will not interfere with activity of immunotherapy.~Evidence of active infection requiring antibiotic therapy at start of treatment.~Current use of a prohibited medication or requirement of any of these medications during treatment with immune-checkpoint inhibitors as mentioned in the summary of product characteristics (SPC) for Yervoy, Opdivo, and Keytruda.~Known immediate or delayed hypersensitivity reaction to ipilimumab, nivolumab or pembrolizumab or excipients.~Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Grade 2 or higher from previous anti-cancer therapy, except alopecia.~A history or evidence of cardiovascular risk including any of the following:~A history or evidence of current clinically significant uncontrolled arrhythmias;~A history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization.~A history or evidence of current ≥Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines.~Abnormal cardiac valve morphology (≥grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study.~Presence of cardiac metastases.~Any serious or unstable pre-existing medical conditions (i.e. diabetes mellitus, hypertension, etc), psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol.~Altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.~Pregnant or nursing females.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biodistribution and kinetics of [18F]FB-IL2. | Biodistribution and kinetics will be assessed in the first five patients that participate in this trial (phase 1). A 60-minute dynamic PET scan of the chest and 2 total-body PET scans at 60 and 120 minutes will be acquired to determine tracer kinetics and residence time of the tracer in major organs. | 2 hours |
| The ability of the [18F]FB-IL2 PET to detect a treatment-induced immune response in tumors. | For detection of a treatment-induced immune response the absolute tracer uptake in tumor lesions will be compared between the scan at baseline and the scan after 6 weeks of treatment with ipilimumab, nivolumab, pembrolizumab or the combination of ipilimumab and nivolumab. | 6 weeks |
| Correlation between tumor uptake of [18F]FB-IL2 with the number of IL2 receptor positive immune cells. | The amount of IL2 receptor positive cells will be scored by immunohistochemical staining of tumor biopsy material and will be correlated to the tumor uptake of [18F]FB-IL2. | 2 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between tumor uptake of [18F]FB-IL2 with response to therapy. | The increase in tumor uptake of [18F]FB-IL2 ofu the tumor lesions on the PET scan at baseline and week 6 of treatment with immunotherapy, will be correlated to radiological response as measured on the CT scans at week 6, 12 and 16 according to the RECIST 1.1 criteria. | 16 weeks |
| To analyze heterogeneity in immune response to treatment between separate lesions, as determined by [18F]FB-IL2 PET. | Both the heterogeneity between separate lesions in one patient and between lesions in different patients will be determined and if possible will be correlated to treatment response (lesion based). | 16 weeks |
| Treatment induced immune cell activation in non-target tissues and if possible the correlation of PET observations with side effects related to the tissue involved. | Treatment induced immune cell activation in non-target tissue will be determined by visually comparing the PET results at baseline and after 6 weeks of treatment. In regions with a higher tracer uptake on the week 6 scan the absolute uptake will be determined and this will be correlated to the development of an immune-related adverse event. In case of immune-related side effects localized to the skin or colon, biopsy samples are optional and tissue infiltration of IL2 receptor positive cells can be correlated to [18F]FB-IL2 uptake on PET. | 16 weeks |
| Adverse events of [18F]FB-IL2 PET. | Adverse events will be recorded. Vital signs and blood parameters will be determined before and after tracer injection and directly after the PET scan for safety reasons. | 16 weeks |
|
T cell response, Interleukin 2, PET scan, Ipilimumab, Pembrolizumab, Nivolumab
|
Physiological Effects of Drugs, Interleukin-2, Antineoplastic Agents, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IL2-PET scan<br>[18F]FB-IL2 PET scan, Tumor biopsy, CT scan, Biopsy of non-target tissue | Device: IL2-PET scan<br>* All patients in this study will undergo a IL2 PET scan at baseline and week 6 of treatment with immunotherapy.<br>* Other names: [18F]FB-IL2 PET scan;Procedure: Tumor biopsy<br>* A procedure to acquire tissue of a predetermined melanoma metastasis will be performed in all patients that participate in phase 2 of this study.<br>Device: CT scan<br>* A CT scan of diagnostic quality will accompany all the PET scans and will additionally been made 12 and 16 weeks after start of immunotherapy to evaluate response to treatment.<br>Procedure: Biopsy of non-target tissue<br>* A biopsy of skin and colon non-target tissue involved in an immune-related side effect is optional in patients that participate in phase 2 of this study.<br>|
|
IL2 Imaging in Metastatic Melanoma
Study Overview
=================
Brief Summary
-----------------
T cell infiltration of tumor lesions is a known prognostic factor in several tumor types and is used as treatment mechanism in some of these tumor types. In metastatic melanoma, treatment with immune checkpoint inhibitors induces clinical benefit in about 30-50% of the patients. These immune-based therapies are however accompanied by serious immune-related adverse events and high costs. Tumor infiltrating T cells express the high affinity interleukin-2 (IL2) receptor on their surface. These T cells could therefore be visualized by molecular imaging with a radio-labelled ligand for this receptor. For this purpose, the investigators have developed the PET tracer [18F]FB-IL2. The study commences with a biodistribution study (phase 1) in 5 subjects. Thereafter the main study (phase 2) starts, in which 25 subjects will receive two [18F]FB-IL2 PET scans at baseline and week 6 of treatment with either ipilimumab, nivolumab, pembrolizumab or the combination of ipilimumab and nivolumab. If [18F]FB-IL2 PET is able to detect a response to treatment, it could serve as a non-invasive early indicator of T cell response to the treatment. Besides, accumulation of the PET tracer in non-target tissue could indicate infiltration of activated T cells in normal organs and thus may predict the development of an immune-related adverse event.
Official Title
-----------------
[18F]FB-IL2 Imaging of T Cell Response as Biomarker to Guide Treatment Decisions in Metastatic Melanoma Patients
Conditions
-----------------
Melanoma
Intervention / Treatment
-----------------
* Device: IL2-PET scan
* Procedure: Tumor biopsy
* Device: CT scan
* Procedure: Biopsy of non-target tissue
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Has signed informed consent. ≥18 years of age. Histologically confirmed cutaneous metastatic melanoma (Stage IV). Evidence of at least one measurable metastatic lesion based on RECIST version 1.1. At least one easy accessible metastatic melanoma lesion, of which biopsy can be performed. Eligible for treatment with ipilimumab, nivolumab, pembrolizumab, or the combination of ipilimumab and nivolumab. No contraindication for performing a CT scan. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. Women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study. Must have adequate organ function (e.g. liver, kidney) as defined Exclusion Criteria: Pre-existing auto-immune disease, which could be exacerbated by ipilimumab (e.g. Crohn, Hashimoto's Thyroiditis). Presence of malignancy other than the disease under study within 5 years of study enrolment. Subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Brain metastases that are symptomatic or not stable for 8 weeks (must be documented by imaging). The use of corticosteroids (at the start of treatment). Note: Corticosteroids are allowed during the study for immune-related toxicity of immunotherapy, as this will not interfere with activity of immunotherapy. Evidence of active infection requiring antibiotic therapy at start of treatment. Current use of a prohibited medication or requirement of any of these medications during treatment with immune-checkpoint inhibitors as mentioned in the summary of product characteristics (SPC) for Yervoy, Opdivo, and Keytruda. Known immediate or delayed hypersensitivity reaction to ipilimumab, nivolumab or pembrolizumab or excipients. Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Grade 2 or higher from previous anti-cancer therapy, except alopecia. A history or evidence of cardiovascular risk including any of the following: A history or evidence of current clinically significant uncontrolled arrhythmias; A history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization. A history or evidence of current ≥Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines. Abnormal cardiac valve morphology (≥grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study. Presence of cardiac metastases. Any serious or unstable pre-existing medical conditions (i.e. diabetes mellitus, hypertension, etc), psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol. Altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent. Pregnant or nursing females.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IL2-PET scan<br>[18F]FB-IL2 PET scan, Tumor biopsy, CT scan, Biopsy of non-target tissue | Device: IL2-PET scan<br>* All patients in this study will undergo a IL2 PET scan at baseline and week 6 of treatment with immunotherapy.<br>* Other names: [18F]FB-IL2 PET scan;Procedure: Tumor biopsy<br>* A procedure to acquire tissue of a predetermined melanoma metastasis will be performed in all patients that participate in phase 2 of this study.<br>Device: CT scan<br>* A CT scan of diagnostic quality will accompany all the PET scans and will additionally been made 12 and 16 weeks after start of immunotherapy to evaluate response to treatment.<br>Procedure: Biopsy of non-target tissue<br>* A biopsy of skin and colon non-target tissue involved in an immune-related side effect is optional in patients that participate in phase 2 of this study.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biodistribution and kinetics of [18F]FB-IL2. | Biodistribution and kinetics will be assessed in the first five patients that participate in this trial (phase 1). A 60-minute dynamic PET scan of the chest and 2 total-body PET scans at 60 and 120 minutes will be acquired to determine tracer kinetics and residence time of the tracer in major organs. | 2 hours |
| The ability of the [18F]FB-IL2 PET to detect a treatment-induced immune response in tumors. | For detection of a treatment-induced immune response the absolute tracer uptake in tumor lesions will be compared between the scan at baseline and the scan after 6 weeks of treatment with ipilimumab, nivolumab, pembrolizumab or the combination of ipilimumab and nivolumab. | 6 weeks |
| Correlation between tumor uptake of [18F]FB-IL2 with the number of IL2 receptor positive immune cells. | The amount of IL2 receptor positive cells will be scored by immunohistochemical staining of tumor biopsy material and will be correlated to the tumor uptake of [18F]FB-IL2. | 2 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between tumor uptake of [18F]FB-IL2 with response to therapy. | The increase in tumor uptake of [18F]FB-IL2 ofu the tumor lesions on the PET scan at baseline and week 6 of treatment with immunotherapy, will be correlated to radiological response as measured on the CT scans at week 6, 12 and 16 according to the RECIST 1.1 criteria. | 16 weeks |
| To analyze heterogeneity in immune response to treatment between separate lesions, as determined by [18F]FB-IL2 PET. | Both the heterogeneity between separate lesions in one patient and between lesions in different patients will be determined and if possible will be correlated to treatment response (lesion based). | 16 weeks |
| Treatment induced immune cell activation in non-target tissues and if possible the correlation of PET observations with side effects related to the tissue involved. | Treatment induced immune cell activation in non-target tissue will be determined by visually comparing the PET results at baseline and after 6 weeks of treatment. In regions with a higher tracer uptake on the week 6 scan the absolute uptake will be determined and this will be correlated to the development of an immune-related adverse event. In case of immune-related side effects localized to the skin or colon, biopsy samples are optional and tissue infiltration of IL2 receptor positive cells can be correlated to [18F]FB-IL2 uptake on PET. | 16 weeks |
| Adverse events of [18F]FB-IL2 PET. | Adverse events will be recorded. Vital signs and blood parameters will be determined before and after tracer injection and directly after the PET scan for safety reasons. | 16 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
T cell response, Interleukin 2, PET scan, Ipilimumab, Pembrolizumab, Nivolumab
|
|
NCT05284643
|
Spectroscopic MRI, Proton Therapy, and Avastin for Recurrent Glioblastoma
|
The purpose of this research is to find hidden cancer with an experimental magnetic resonance imaging (MRI) scan called spectroscopic magnetic resonance imaging (sMRI). That spectroscopic MRI scan will be used to increase the area of the brain receiving radiation and then the dose of radiation in attempt to kill more of the cancer. Proton radiotherapy and bevacizumab (Avastin) are used to minimize the possible side effects of this approach.
|
A common second course of radiation therapy for recurrent glioblastoma uses 35 Gy in 10 fractions to a small area defined by gadolinium enhancement on MRI. This is based in part on a recent cooperative group trial (RTOG 1205, NCT01730950) with concurrent bevacizumab resulting in very low toxicity and borderline progression free survival benefit. We hypothesize that radiation therapy would be more effective for recurrent glioblastoma when delivered to a larger area defined by spectroscopic MRI. The spectroscopic MRI can delineate occult microscopic disease not seen on clinical MRI. Our group was a partner in the multi-institutional spectroscopic MRI guided dose escalation pilot trial in the first line for glioblastoma (NCT03137888) showing safety and efficacy of planning radiation therapy based on spectroscopic MRI Choline to NAA (Cho:NAA) ratio maps. A local Cho:NAA ratio above 2 (Cho:NAA>2) is known to correlate with high local GBM burden on pathology. In this study, we will use the same technique to target radiation therapy to recurrent glioblastoma in a larger area of the brain harboring microscopic tumor. We will start with the conventional radiation dose of 35 Gy in 10 fractions to the larger area defined by the spectroscopic MRI. If this is safe and feasible, we will perform a dose escalation to 40 Gy in 10 fractions to areas of gadolinium enhancement and sMRI Cho:NAA>2 since existing data suggests that those areas harbor the highest risk of future progression. Use of proton radiotherapy to limit brain targeted outside of the treated regions and bevacizumab to prevent radiation toxicity are hypothesized to limit the side effects of this approach.
|
Pilot Trial of Spectroscopic MRI-guided, Dose-Escalated Proton Radiation Therapy and Bevacizumab for Recurrent Glioblastoma
|
Recurrent Glioblastoma
|
* Radiation: Intensity Modulated Proton Therapy (IMPT)
* Drug: Bevacizumab
|
Inclusion Criteria:~A. Recurrent glioblastoma (or variants such as gliosarcoma) based on one of the following criteria:~An area of MRI enhancement consistent with glioblastoma outside of the initial high dose radiation field.~Biopsy or resection proven recurrent glioblastoma.~Progressive glioblastoma based on advanced imaging (brain positron emission tomography (PET), perfusion MRI, or clinical MR Spectroscopy)~B. Pathology diagnosis of glioblastoma, or variants such as gliosarcoma, on initial and/or re-resection by 2016 WHO glioblastoma criteria. Prior pathology reports or specimens can be re-examined and reclassified as glioblastoma based on current criteria.~C. Total area of recurrence on T1 post-contrast MRI (including all nodules of likely tumor) have a linear maximum measurement of 6 cm or less.~D. Patients must have received prior brain radiation therapy for glioma in conventional fractionation (1.8 - 2 Gy per fraction, total dose maximum 63 Gy).~E. Patients must have completed prior brain radiation four to six months or more prior to study treatment for recurrent tumors that are at least half based within the high dose (> 46 Gy) radiation field.~For marginal or out of field radiation failures where at least half of the enhancing disease is outside of the prior high dose radiation field but there is field overlap, patients must have completed prior radiation at least four months or more prior to study treatment.~For in field radiation failures where at least half of the enhancing disease is within the prior high dose radiation field, patients must have completed prior radiation at least six months or more prior to study treatment.~F. A minimum time must be elapsed from the administration of any prior anti-tumor or investigational agents to initiation of study treatments on this protocol as follows:~28 days or 5 half-lives, whichever is shorter, elapsed from the administration of any experimental agent prior to initiation of study treatment.~28 days elapsed from the administration of any prior cytotoxic agents except~i. 14 days from vincristine and ≥ 21 days from procarbazine and Temozolomide (TMZ) prior to initiation of study treatment.~G. Age at least 18.~H. Patients must be able to have MRI scans.~I. Karnofsky performance status 60-100.~J. Life expectancy greater than 12 weeks at the discretion of the enrolling investigator.qa~K. Female subjects should have a negative serum pregnancy test unless they confirm their menopausal status and/or have undergone previous hysterectomy and/or oophorectomy.~L. Both men and women with childbearing potential should agree to use effective contraception for the duration of the treatment and for at least 6 months after the last treatment since medications that will be used can be harmful for the embryo. See contraception requirements, protocol section 4.16.~M. Complete blood count (CBC)/differential within 21 days prior to registration with absolute neutrophil count at least 1500 cells/mm2, platelets at least 75,000 cells/mm2, and hemoglobin at least 9.0 g/dl (transfusion or other intervention to achieve Hgb of 9.0 or greater is acceptable).~N. Liver function tests must demonstrate total bilirubin 2 mg/dL or less, serum glutamic-oxaloacetic transaminase (SGOT) or aspartate aminotransferase (AST) 2.5 times the upper limit of normal or less within 21 days prior to registration.~O. Kidney function tests must indicate serum creatinine 1.8 mg/dL or less within 21 days prior to registration and the following:~a. Urine protein: creatinine (UPC) ratio < 1.0 within 14 days prior to registration OR urine dipstick for proteinuria ≤ 2+ (patients discovered to have > 2+ proteinuria on dipstick urinalysis at baseline must have a UPC ratio done that is <1.0 to be eligible. If the UPC ratio is ≥ 1.0 then the patients should undergo a 24-hour urine collection and must demonstrate ≤1g of protein in 24 hours to be eligible).~i. Note: UPC ratio of spot urine is an estimation of the 24-hour urine protein excretion; a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm. UPC ratio is calculated using one of the following formulas:~[urine protein]/[urine creatinine]: if both protein and creatinine are reported in mg/dL~[(urine protein) x0.088]/[urine creatinine]: if urine creatinine is reported in mmol/L~P. Patients on full-dose anticoagulants must meet both of the following criteria:~No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)~In-range international normalized ratio (INR) (typically 2-3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin, within 21 days prior to registration~Exclusion Criteria:~A. Brain tumors other than glioblastoma (or variants such as gliosarcoma) by World Health Organization (WHO) criteria.~B. Glioma that has not previously undergone standard first line therapies including a first course of radiation therapy.~C. Glioma that has already undergone a second course of radiation therapy.~D. Multi-focal disease (separate enhancing nodules across multiple brain lobes). Note: Multiple nodules in the same region are allowed as long as the total linear diameter is 6 cm or less.~E. Patients who have had treatment with Bevacizumab in the past.~F. Patients who will receive chemotherapy concurrent with study therapy other than bevacizumab.~G. Patients with recurrent Glioblastoma (rGBM) based in the following anatomical regions known to have magnetic susceptibility or poor signal will be excluded: temporal lobe below the level of the floor of the third ventricle, orbitofrontal cortex, prefrontal cortex, medial frontal gyrus, brainstem, and cerebellum (these regions have known sMRI artifact).~H. Pregnant or breastfeeding patients.~I. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1 year. Non-invasive tumors are permissible (e.g., carcinoma in situ).~J. Severe active co-morbidities as follows:~Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to registration.~Transmural myocardial infarction within the last 6 months prior to registration.~History of stroke or transient ischemic attack within 6 months prior to registration.~Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease.~Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.~Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.~Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function other than screening panel (Section 3.1) and coagulation parameters are not required for entry into this protocol.~Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.~K. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.~L. Prior allergic reaction to the study drug (Bevacizumab)~M. Prior history of hypertensive crisis or hypertensive encephalopathy.~N. History of a non-healing wound, ulcer, or bone fracture within 90 days (3 months) prior to registration~O. Gastrointestinal bleeding or any other hemorrhage/bleeding event Common Terminology Criteria for Adverse Events (CTCAE), v. 4 grade 3 or greater within 30 days prior to registration~P. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration (with the exception of craniotomy)~Q. Concurrent receipt of any other investigational agents
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients for whom sMRI-guided therapy is technically successful | The percentage of participants for whom sMRI-guided therapy is successful will be reported as the percentage of participants who show no significant residual tumor after protocol therapy. | About 60 days |
| Incidence of Grade 3 irreversible or any Grade 4/5 neurologic toxicity. | The incidence of irreversible Grade 3 or any Grade 4/5 neurologic adverse events (AEs) or serious adverse events (SAEs) in study participants will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion. Incidence of these toxicities will be reported for both cohorts, Cohort A (sMRI-Guided RT at 35 Gy in 10 fractions) and Cohort B (sMRI-Guided RT at 40 Gy in 10 fractions). | Up to 6 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | Progression-free Survival (PFS) is defined as the time from the start of radiation therapy to any documented progression or death from any cause, whichever occurs first. Surviving patients without progression will be censored at the date of last contact. | Up to 2 years |
| Overall Survival (OS) | Overall Survival (OS) is defined as the time from the start of radiation therapy to date of death from any cause. Surviving patients will be censored at the date of last contact. | Up to 2 years |
| Comparison of Cerebral Blood Volumes (CBV) among MRI techniques | Comparison of the cerebral blood volumes (CBV) in participants measured by Spectroscopic MRI (sMRI) versus by conventional MRI and multiparametric MRI (mpMRI). CBV is defined as the volume of blood in a given amount of brain tissue, most commonly milliliters of blood per 100 g of brain tissue. | About 3 months |
| Comparison of Apparent Diffusion Coefficients (ADC) among MRI techniques | Comparison of the apparent diffusion coefficients (ADC) in participants measured by Spectroscopic MRI (sMRI) versus by conventional MRI and multiparametric MRI (mpMRI). ADC is a measure of the magnitude of diffusion (of water molecules) within tissue, and is commonly clinically calculated using MRI with diffusion-weighted imaging (DWI). ADC of tissue is expressed in units of mm2/s. | About 3 months |
| Volume of enhancing disease at first progression compared to MRI volumes. | Assessed by evaluating the patterns of failure after sMRI-guided radiotherapy and correlating with sMRI and other mpMRI markers. | About 3 months |
| Health-Related Quality of Life (HRQOL) Scores: FACT-Br Questionnaire | Health-Related Quality of Life will be assessed using scores from the Functional Assessment of Cancer Therapy - Brain (FACT-Br) questionnaire version 4. The FACT-Br will be used to evaluate patient function and satisfaction after protocol treatment. The questionnaire has 5 subscales (Physical Well-being, Social/Family Well-being, Emotional Well-being, Function Well-being and Brain Cancer). Response options for each item form a 5-point Likert scale, ranging from 0 (Not al all) to 4 (Very Much). The questionnaire has a total score ranging from 0 - 200, with higher scores representing better HRQOL. | Up to 2 years |
|
Brain Cancer
|
Bevacizumab, Antineoplastic Agents, Immunological, Antineoplastic Agents, Angiogenesis Inhibitors, Angiogenesis Modulating Agents, Growth Substances, Physiological Effects of Drugs, Growth Inhibitors
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: sMRI-Guided RT at 35 Gy in 10 fractions<br>Participants will receive a total dose of 3500 centigrays (cGY) (35Gy) of Spectroscopic Magnetic Resonance Imaging (sMRI)-guided radiation therapy delivered in 10 fractions, 350 cGy (3.5 Gy) to the Clinical Target Volume (CTV) by Intensity Modulated Proton Therapy (IMPT) simultaneous integrated boost technique.~Participants will also receive Bevacizumab per standard of care, at treating physician's discretion. Initial dose will begin prior to first dose of radiation therapy (RT). | Radiation: Intensity Modulated Proton Therapy (IMPT)<br>* Participants will receive radiation therapy delivered via intensity modulated proton therapy (IMPT) simultaneous integrated boost technique over a period of 10 days, 5 days per week for approximately 2 weeks.<br>Drug: Bevacizumab<br>* Bevacizumab will be administered intravenously (IV), beginning at a dose of 10 mg/kg every 2-3 weeks until disease progression.<br>* Other names: Avastin;|
| Experimental: Cohort B: sMRI-Guided RT at 40 Gy in 10 fractions<br>Participants will receive a total dose of 4000 cGY (40Gy) of Spectroscopic Magnetic Resonance Imaging (sMRI)-guided radiation therapy delivered in 10 fractions, 400 cGy (4 Gy) to the Clinical Target Volume (CTV) by Intensity Modulated Proton Therapy (IMPT) simultaneous integrated boost technique.~Participants will also receive Bevacizumab per standard of care, at treating physician's discretion. Initial dose will begin prior to first dose of radiation therapy (RT). | Radiation: Intensity Modulated Proton Therapy (IMPT)<br>* Participants will receive radiation therapy delivered via intensity modulated proton therapy (IMPT) simultaneous integrated boost technique over a period of 10 days, 5 days per week for approximately 2 weeks.<br>Drug: Bevacizumab<br>* Bevacizumab will be administered intravenously (IV), beginning at a dose of 10 mg/kg every 2-3 weeks until disease progression.<br>* Other names: Avastin;|
|
Spectroscopic MRI, Proton Therapy, and Avastin for Recurrent Glioblastoma
Study Overview
=================
Brief Summary
-----------------
The purpose of this research is to find hidden cancer with an experimental magnetic resonance imaging (MRI) scan called spectroscopic magnetic resonance imaging (sMRI). That spectroscopic MRI scan will be used to increase the area of the brain receiving radiation and then the dose of radiation in attempt to kill more of the cancer. Proton radiotherapy and bevacizumab (Avastin) are used to minimize the possible side effects of this approach.
Detailed Description
-----------------
A common second course of radiation therapy for recurrent glioblastoma uses 35 Gy in 10 fractions to a small area defined by gadolinium enhancement on MRI. This is based in part on a recent cooperative group trial (RTOG 1205, NCT01730950) with concurrent bevacizumab resulting in very low toxicity and borderline progression free survival benefit. We hypothesize that radiation therapy would be more effective for recurrent glioblastoma when delivered to a larger area defined by spectroscopic MRI. The spectroscopic MRI can delineate occult microscopic disease not seen on clinical MRI. Our group was a partner in the multi-institutional spectroscopic MRI guided dose escalation pilot trial in the first line for glioblastoma (NCT03137888) showing safety and efficacy of planning radiation therapy based on spectroscopic MRI Choline to NAA (Cho:NAA) ratio maps. A local Cho:NAA ratio above 2 (Cho:NAA>2) is known to correlate with high local GBM burden on pathology. In this study, we will use the same technique to target radiation therapy to recurrent glioblastoma in a larger area of the brain harboring microscopic tumor. We will start with the conventional radiation dose of 35 Gy in 10 fractions to the larger area defined by the spectroscopic MRI. If this is safe and feasible, we will perform a dose escalation to 40 Gy in 10 fractions to areas of gadolinium enhancement and sMRI Cho:NAA>2 since existing data suggests that those areas harbor the highest risk of future progression. Use of proton radiotherapy to limit brain targeted outside of the treated regions and bevacizumab to prevent radiation toxicity are hypothesized to limit the side effects of this approach.
Official Title
-----------------
Pilot Trial of Spectroscopic MRI-guided, Dose-Escalated Proton Radiation Therapy and Bevacizumab for Recurrent Glioblastoma
Conditions
-----------------
Recurrent Glioblastoma
Intervention / Treatment
-----------------
* Radiation: Intensity Modulated Proton Therapy (IMPT)
* Drug: Bevacizumab
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A. Recurrent glioblastoma (or variants such as gliosarcoma) based on one of the following criteria: An area of MRI enhancement consistent with glioblastoma outside of the initial high dose radiation field. Biopsy or resection proven recurrent glioblastoma. Progressive glioblastoma based on advanced imaging (brain positron emission tomography (PET), perfusion MRI, or clinical MR Spectroscopy) B. Pathology diagnosis of glioblastoma, or variants such as gliosarcoma, on initial and/or re-resection by 2016 WHO glioblastoma criteria. Prior pathology reports or specimens can be re-examined and reclassified as glioblastoma based on current criteria. C. Total area of recurrence on T1 post-contrast MRI (including all nodules of likely tumor) have a linear maximum measurement of 6 cm or less. D. Patients must have received prior brain radiation therapy for glioma in conventional fractionation (1.8 - 2 Gy per fraction, total dose maximum 63 Gy). E. Patients must have completed prior brain radiation four to six months or more prior to study treatment for recurrent tumors that are at least half based within the high dose (> 46 Gy) radiation field. For marginal or out of field radiation failures where at least half of the enhancing disease is outside of the prior high dose radiation field but there is field overlap, patients must have completed prior radiation at least four months or more prior to study treatment. For in field radiation failures where at least half of the enhancing disease is within the prior high dose radiation field, patients must have completed prior radiation at least six months or more prior to study treatment. F. A minimum time must be elapsed from the administration of any prior anti-tumor or investigational agents to initiation of study treatments on this protocol as follows: 28 days or 5 half-lives, whichever is shorter, elapsed from the administration of any experimental agent prior to initiation of study treatment. 28 days elapsed from the administration of any prior cytotoxic agents except i. 14 days from vincristine and ≥ 21 days from procarbazine and Temozolomide (TMZ) prior to initiation of study treatment. G. Age at least 18. H. Patients must be able to have MRI scans. I. Karnofsky performance status 60-100. J. Life expectancy greater than 12 weeks at the discretion of the enrolling investigator.qa K. Female subjects should have a negative serum pregnancy test unless they confirm their menopausal status and/or have undergone previous hysterectomy and/or oophorectomy. L. Both men and women with childbearing potential should agree to use effective contraception for the duration of the treatment and for at least 6 months after the last treatment since medications that will be used can be harmful for the embryo. See contraception requirements, protocol section 4.16. M. Complete blood count (CBC)/differential within 21 days prior to registration with absolute neutrophil count at least 1500 cells/mm2, platelets at least 75,000 cells/mm2, and hemoglobin at least 9.0 g/dl (transfusion or other intervention to achieve Hgb of 9.0 or greater is acceptable). N. Liver function tests must demonstrate total bilirubin 2 mg/dL or less, serum glutamic-oxaloacetic transaminase (SGOT) or aspartate aminotransferase (AST) 2.5 times the upper limit of normal or less within 21 days prior to registration. O. Kidney function tests must indicate serum creatinine 1.8 mg/dL or less within 21 days prior to registration and the following: a. Urine protein: creatinine (UPC) ratio < 1.0 within 14 days prior to registration OR urine dipstick for proteinuria ≤ 2+ (patients discovered to have > 2+ proteinuria on dipstick urinalysis at baseline must have a UPC ratio done that is <1.0 to be eligible. If the UPC ratio is ≥ 1.0 then the patients should undergo a 24-hour urine collection and must demonstrate ≤1g of protein in 24 hours to be eligible). i. Note: UPC ratio of spot urine is an estimation of the 24-hour urine protein excretion; a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm. UPC ratio is calculated using one of the following formulas: [urine protein]/[urine creatinine]: if both protein and creatinine are reported in mg/dL [(urine protein) x0.088]/[urine creatinine]: if urine creatinine is reported in mmol/L P. Patients on full-dose anticoagulants must meet both of the following criteria: No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices) In-range international normalized ratio (INR) (typically 2-3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin, within 21 days prior to registration Exclusion Criteria: A. Brain tumors other than glioblastoma (or variants such as gliosarcoma) by World Health Organization (WHO) criteria. B. Glioma that has not previously undergone standard first line therapies including a first course of radiation therapy. C. Glioma that has already undergone a second course of radiation therapy. D. Multi-focal disease (separate enhancing nodules across multiple brain lobes). Note: Multiple nodules in the same region are allowed as long as the total linear diameter is 6 cm or less. E. Patients who have had treatment with Bevacizumab in the past. F. Patients who will receive chemotherapy concurrent with study therapy other than bevacizumab. G. Patients with recurrent Glioblastoma (rGBM) based in the following anatomical regions known to have magnetic susceptibility or poor signal will be excluded: temporal lobe below the level of the floor of the third ventricle, orbitofrontal cortex, prefrontal cortex, medial frontal gyrus, brainstem, and cerebellum (these regions have known sMRI artifact). H. Pregnant or breastfeeding patients. I. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1 year. Non-invasive tumors are permissible (e.g., carcinoma in situ). J. Severe active co-morbidities as follows: Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to registration. Transmural myocardial infarction within the last 6 months prior to registration. History of stroke or transient ischemic attack within 6 months prior to registration. Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration. Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function other than screening panel (Section 3.1) and coagulation parameters are not required for entry into this protocol. Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. K. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic. L. Prior allergic reaction to the study drug (Bevacizumab) M. Prior history of hypertensive crisis or hypertensive encephalopathy. N. History of a non-healing wound, ulcer, or bone fracture within 90 days (3 months) prior to registration O. Gastrointestinal bleeding or any other hemorrhage/bleeding event Common Terminology Criteria for Adverse Events (CTCAE), v. 4 grade 3 or greater within 30 days prior to registration P. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration (with the exception of craniotomy) Q. Concurrent receipt of any other investigational agents
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: sMRI-Guided RT at 35 Gy in 10 fractions<br>Participants will receive a total dose of 3500 centigrays (cGY) (35Gy) of Spectroscopic Magnetic Resonance Imaging (sMRI)-guided radiation therapy delivered in 10 fractions, 350 cGy (3.5 Gy) to the Clinical Target Volume (CTV) by Intensity Modulated Proton Therapy (IMPT) simultaneous integrated boost technique. Participants will also receive Bevacizumab per standard of care, at treating physician's discretion. Initial dose will begin prior to first dose of radiation therapy (RT). | Radiation: Intensity Modulated Proton Therapy (IMPT)<br>* Participants will receive radiation therapy delivered via intensity modulated proton therapy (IMPT) simultaneous integrated boost technique over a period of 10 days, 5 days per week for approximately 2 weeks.<br>Drug: Bevacizumab<br>* Bevacizumab will be administered intravenously (IV), beginning at a dose of 10 mg/kg every 2-3 weeks until disease progression.<br>* Other names: Avastin;|
| Experimental: Cohort B: sMRI-Guided RT at 40 Gy in 10 fractions<br>Participants will receive a total dose of 4000 cGY (40Gy) of Spectroscopic Magnetic Resonance Imaging (sMRI)-guided radiation therapy delivered in 10 fractions, 400 cGy (4 Gy) to the Clinical Target Volume (CTV) by Intensity Modulated Proton Therapy (IMPT) simultaneous integrated boost technique. Participants will also receive Bevacizumab per standard of care, at treating physician's discretion. Initial dose will begin prior to first dose of radiation therapy (RT). | Radiation: Intensity Modulated Proton Therapy (IMPT)<br>* Participants will receive radiation therapy delivered via intensity modulated proton therapy (IMPT) simultaneous integrated boost technique over a period of 10 days, 5 days per week for approximately 2 weeks.<br>Drug: Bevacizumab<br>* Bevacizumab will be administered intravenously (IV), beginning at a dose of 10 mg/kg every 2-3 weeks until disease progression.<br>* Other names: Avastin;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients for whom sMRI-guided therapy is technically successful | The percentage of participants for whom sMRI-guided therapy is successful will be reported as the percentage of participants who show no significant residual tumor after protocol therapy. | About 60 days |
| Incidence of Grade 3 irreversible or any Grade 4/5 neurologic toxicity. | The incidence of irreversible Grade 3 or any Grade 4/5 neurologic adverse events (AEs) or serious adverse events (SAEs) in study participants will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion. Incidence of these toxicities will be reported for both cohorts, Cohort A (sMRI-Guided RT at 35 Gy in 10 fractions) and Cohort B (sMRI-Guided RT at 40 Gy in 10 fractions). | Up to 6 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | Progression-free Survival (PFS) is defined as the time from the start of radiation therapy to any documented progression or death from any cause, whichever occurs first. Surviving patients without progression will be censored at the date of last contact. | Up to 2 years |
| Overall Survival (OS) | Overall Survival (OS) is defined as the time from the start of radiation therapy to date of death from any cause. Surviving patients will be censored at the date of last contact. | Up to 2 years |
| Comparison of Cerebral Blood Volumes (CBV) among MRI techniques | Comparison of the cerebral blood volumes (CBV) in participants measured by Spectroscopic MRI (sMRI) versus by conventional MRI and multiparametric MRI (mpMRI). CBV is defined as the volume of blood in a given amount of brain tissue, most commonly milliliters of blood per 100 g of brain tissue. | About 3 months |
| Comparison of Apparent Diffusion Coefficients (ADC) among MRI techniques | Comparison of the apparent diffusion coefficients (ADC) in participants measured by Spectroscopic MRI (sMRI) versus by conventional MRI and multiparametric MRI (mpMRI). ADC is a measure of the magnitude of diffusion (of water molecules) within tissue, and is commonly clinically calculated using MRI with diffusion-weighted imaging (DWI). ADC of tissue is expressed in units of mm2/s. | About 3 months |
| Volume of enhancing disease at first progression compared to MRI volumes. | Assessed by evaluating the patterns of failure after sMRI-guided radiotherapy and correlating with sMRI and other mpMRI markers. | About 3 months |
| Health-Related Quality of Life (HRQOL) Scores: FACT-Br Questionnaire | Health-Related Quality of Life will be assessed using scores from the Functional Assessment of Cancer Therapy - Brain (FACT-Br) questionnaire version 4. The FACT-Br will be used to evaluate patient function and satisfaction after protocol treatment. The questionnaire has 5 subscales (Physical Well-being, Social/Family Well-being, Emotional Well-being, Function Well-being and Brain Cancer). Response options for each item form a 5-point Likert scale, ranging from 0 (Not al all) to 4 (Very Much). The questionnaire has a total score ranging from 0 - 200, with higher scores representing better HRQOL. | Up to 2 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Brain Cancer
|
NCT01467024
|
Evaluation of the MP Diagnostics HTLV Blot 2.4
|
The purpose of this study is:~To assess the validity and reproducibility of the MP Diagnostics HTLV Blot 2.4.~To conduct a sensitivity analysis of the HTLV Blot 2.4 using a known positive population.
|
This is a retrospective study designed to assess the validity and reproducibility of the MP Diagnostics IVD device, the HTLV Blot 2.4 (MP Blot), in various populations. The study will be conducted at three geographical distinct locations.~The validity of the MP Blot will be assessed by calculating the following:~Percent negative agreement with CDPHL Algorithm on 200 EIA negative specimens~Percent positive agreement with CDPHL Algorithm on 200 EIA repeat reactive specimens~The sensitivity of the MP Blot will be evaluated by testing 200 known positive specimens. The study will be performed using three product lots at three clinical sites.~The reproducibility of the MP Blot will be assessed by testing two replicates of a three member panel at three clinical testing sites with each of three lots of product over multiple days by three operators.
|
Evaluation of the MP Diagnostics HTLV Blot 2.4
|
HTLV I Associated Myelopathies, HTLV-I Infections, HTLV-II Infections, Human T-lymphotropic Virus 1, Human T-lymphotropic Virus 2, HTLV I Associated T Cell Leukemia Lymphoma
|
* Other: CDPHL Algorithm
|
Inclusion Criteria:~EIA Negative Population~Male or female~Completion of a health history evaluation for routine donor screening~Willing and able to provide informed consent~Negative screening assay results for all ARC screening assays~EIA Repeat Reactive Population~Male or female~Completion of a health history evaluation for routine donor screening~Willing and able to provide informed consent~Previous RR result by bioMerieux ELISA, Abbott EIA, and / or Abbott ChLIA PRISM~Known Positive Population~Male or female~Willing and able to provide informed consent~Previous reactive screening test using either the bioMerieux ELISA, the Abbott EIA or the Abbott ChLIA PRISM, followed by supplemental testing~Exclusion Criteria:~EIA Negative Population~Inadequate sample volume for testing~Unable to provide samples that meet the sample suitability requirements for testing~Positive screening result for any infectious disease tested by ARC~EIA Repeat Reactive Population~Inadequate sample volume for testing~Unable to provide samples that meet the sample suitability requirements for testing~Positive result for HIV, HBV, HCV, or any other infectious disease~Known Positive Population~Unwilling or unable to provide informed consent~Unable to provide adequate sample volume for testing~Unable to provide samples that meet the sample suitability requirements for testing~Positive result for HIV
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
HTLV, Confirmatory, Supplemental, Blot, HTLV-I, HTLV-II
|
Infections, Communicable Diseases, HTLV-I Infections, Paraparesis, Tropical Spastic, HTLV-II Infections, Leukemia, T-Cell, Leukemia-Lymphoma, Adult T-Cell, Spinal Cord Diseases, Disease Attributes, Pathologic Processes, Virus Diseases, Leukemia, Lymphoid, Leukemia, Neoplasms by Histologic Type, Neoplasms, Lymphoproliferative Disorders, Lymphatic Diseases, Immunoproliferative Disorders, Immune System Diseases, Central Nervous System Diseases, Nervous System Diseases, Deltaretrovirus Infections, Retroviridae Infections, RNA Virus Infections, Immunologic Deficiency Syndromes, Myelitis, Central Nervous System Infections, Neuroinflammatory Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| EIA Negative<br>Blood donor specimens that tested non-reactive by previously licensed HTLV screening assay. | Other: CDPHL Algorithm<br>* Supplemental testing algorithm performed by the CDPHL.<br>|
| EIA Repeat Reactive<br>Blood donor specimens that tested repeat reactive by previously licensed HTLV screening assay, but are unconfirmed. | Other: CDPHL Algorithm<br>* Supplemental testing algorithm performed by the CDPHL.<br>|
| Known Positive<br>Blood donor specimens that tested repeat reactive with a licensed HTLV screening assay and have been confirmed through additional, unlicensed supplemental testing. | Other: CDPHL Algorithm<br>* Supplemental testing algorithm performed by the CDPHL.<br>|
|
Evaluation of the MP Diagnostics HTLV Blot 2.4
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is: To assess the validity and reproducibility of the MP Diagnostics HTLV Blot 2.4. To conduct a sensitivity analysis of the HTLV Blot 2.4 using a known positive population.
Detailed Description
-----------------
This is a retrospective study designed to assess the validity and reproducibility of the MP Diagnostics IVD device, the HTLV Blot 2.4 (MP Blot), in various populations. The study will be conducted at three geographical distinct locations. The validity of the MP Blot will be assessed by calculating the following: Percent negative agreement with CDPHL Algorithm on 200 EIA negative specimens Percent positive agreement with CDPHL Algorithm on 200 EIA repeat reactive specimens The sensitivity of the MP Blot will be evaluated by testing 200 known positive specimens. The study will be performed using three product lots at three clinical sites. The reproducibility of the MP Blot will be assessed by testing two replicates of a three member panel at three clinical testing sites with each of three lots of product over multiple days by three operators.
Official Title
-----------------
Evaluation of the MP Diagnostics HTLV Blot 2.4
Conditions
-----------------
HTLV I Associated Myelopathies, HTLV-I Infections, HTLV-II Infections, Human T-lymphotropic Virus 1, Human T-lymphotropic Virus 2, HTLV I Associated T Cell Leukemia Lymphoma
Intervention / Treatment
-----------------
* Other: CDPHL Algorithm
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: EIA Negative Population Male or female Completion of a health history evaluation for routine donor screening Willing and able to provide informed consent Negative screening assay results for all ARC screening assays EIA Repeat Reactive Population Male or female Completion of a health history evaluation for routine donor screening Willing and able to provide informed consent Previous RR result by bioMerieux ELISA, Abbott EIA, and / or Abbott ChLIA PRISM Known Positive Population Male or female Willing and able to provide informed consent Previous reactive screening test using either the bioMerieux ELISA, the Abbott EIA or the Abbott ChLIA PRISM, followed by supplemental testing Exclusion Criteria: EIA Negative Population Inadequate sample volume for testing Unable to provide samples that meet the sample suitability requirements for testing Positive screening result for any infectious disease tested by ARC EIA Repeat Reactive Population Inadequate sample volume for testing Unable to provide samples that meet the sample suitability requirements for testing Positive result for HIV, HBV, HCV, or any other infectious disease Known Positive Population Unwilling or unable to provide informed consent Unable to provide adequate sample volume for testing Unable to provide samples that meet the sample suitability requirements for testing Positive result for HIV
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 |
| --- | --- |
| EIA Negative<br>Blood donor specimens that tested non-reactive by previously licensed HTLV screening assay. | Other: CDPHL Algorithm<br>* Supplemental testing algorithm performed by the CDPHL.<br>|
| EIA Repeat Reactive<br>Blood donor specimens that tested repeat reactive by previously licensed HTLV screening assay, but are unconfirmed. | Other: CDPHL Algorithm<br>* Supplemental testing algorithm performed by the CDPHL.<br>|
| Known Positive<br>Blood donor specimens that tested repeat reactive with a licensed HTLV screening assay and have been confirmed through additional, unlicensed supplemental testing. | Other: CDPHL Algorithm<br>* Supplemental testing algorithm performed by the CDPHL.<br>|
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
-----------------
HTLV, Confirmatory, Supplemental, Blot, HTLV-I, HTLV-II
|
||
NCT02409719
|
Home Rehabilitation in Patients After Primary Total Knee Arthroplasty
|
The investigators include patients attending the outpatient clinic in the area of Orthopedics and Traumatology of the investigators hospital with a diagnosis of knee osteoarthritis, which treatment requires surgery. Patients will be divided into two groups. In both groups, they will be given verbal, clear and detailed information on the approach to follow, the exercises given in brochures, and in the study group a schedule will be given in order to record rehabilitation exercises in patients after total knee replacement (TKA). Both groups will be assessed before and after surgery, together with outpatient follow-up by, WOMAC, Visual Analogue Scale and OKS (Oxford Knee Score).
|
Osteoarthritis (OA) is the most common rheumatic disease worldwide. OA cause joint pain and occupational disability in the adult population. In Mexico, OA is one of the top ten reasons of consultation in primary attention care.~Joint arthroplasty is a major advance in the treatment of chronic joint pain. It is indicated in patients in whose conservative medical therapy has failed. Total knee arthroplasty (TKA) is a surgery that reduces pain and improves function and quality of life in patients with knee disorders, actually is one of the most successful medical procedures. However, a critical consideration in patients with TKA is the successful control of postoperative pain. An adequate pain control allows faster rehabilitation, reduces complications and is highly correlated with patient satisfaction. A multimodal pain management decreases the use of narcotics, improve pain scores, increase patient satisfaction and allows early recovery.~Regarding postoperative rehabilitation, its suggested that rehabilitation programs are based on a biopsychosocial philosophy and integrate exercises and self-management interventions are effective in the treatment of osteoarthritis. Rehabilitation therapy an important area that should be considered. It helps people recover faster from their illness, injury or medical procedures and make possible to get back to their daily activities.~The World Health Organization describes rehabilitation as a process that aims to enable people to maintain and achieve their physical, sensory, intellectual, functional, psychological and social level in an optimal way. It is known that rehabilitation involves contributions from various health disciplines, including physical therapy and occupational therapy and offered in inpatient, outpatient and community patients.~In patients with total knee replacement, rehabilitation interventions may involve education and exercise before surgery, early mobilization while being in the hospital and a postoperative program, along with an adequate pain management.~Perioperative care has shown an improvement in the recovery, it reduces hospital day stay, convalescent and risk of postoperative medical complications.~It has been shown that early initiation of rehabilitation within 24 hours after total knee arthroplasty reduces in-hospital time and decreases the number of sessions required to achieve autonomy, balance and normal gait. Madsen et al. demonstrated that rehabilitation exercises at home have the same effect as those made in rehabilitation group within six months postoperatively, based on a study of 80 patients randomly divided into a control- study group.~Optimal pain management is vital seeking to achieve the goal of recovery called fast track. It involves early therapy with specialized protocols, early discharge and quick recovery. Lamplot et al. demonstrated in a prospective randomized study of 36 patients, using this method, a decrease in opioid consumption and its adverse effects, a decreased pain score, a shortening time for physical therapy and an increase in patient satisfaction.~Postoperative analgesia can be achieved by a variety of techniques. These include: intravenous analgesia, epidural analgesia, techniques for peripheral nerve block and periarticular injections. All aim to control pain in patients and provide the better satisfaction.~Integrating these interventions in a clinical pathway, better functional results are obtained, hospital stay is reduced and there is an improvement in the patient's recovery, mainly in short-term.
|
Home Rehabilitation in Patients After Primary Total Knee Arthroplasty
|
Osteoarthritis, Rehabilitation
|
* Other: Schedule
* Other: Verbal Information and Booklet
|
Inclusion Criteria:~Age between 18 and 90 years~Patients with Knee osteoarthritis (OA) grade 4 ( Kellgren-Lawrence based on radiographic findings)~Total Knee Arthroplasty (TKA) for primary OA~Rapid rehabilitation desire~Exclusion Criteria:~Age <18 and > 90 years~Patients with Knee osteoarthritis grade 1-2 ( Kellgren-Lawrence based on radiographic findings)~Patients with asociated Rheumatic syndromes~Patients with anticoagulant therapy~Patients with hepatic problems, Diabetes Mellitus, Coagulopathy, hearth conditions, immunodepressed, or infections~Drugs abuse history~Physiatric disease~Pregnant patients~Patients with hemoglobin values < 11g/dl , platelets < 150,000/ μL
|
18 Years
|
90 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total WOMAC Score | The total score is provided for Western Ontario and McMaster Universities Arthritis Index (WOMAC).~It is a widely score used in the evaluation of Hip and Knee Osteoarthritis. Consists of a self-administered questionnaire consisting of 24 items divided into 3 subscales:~pain (5 items), stiffness (2 items), and physical functioning (17 items) of the joints.~Scale Range: 5 items of pain (score range 0-20), 2 items for stiffness (score range 0-8), and 17 items for functional limitation (score range 0-68). The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). Total WOMAC score range 0-96.~For each subscale higher values represent worse outcomes.~Subscales are summed for a total WOMAC score. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.~WOMAC Index was developed in 1982 at Western Ontario and McMaster Universities. | up to 12 months (O, 2, 4, 6 weeks, 3,6 and 12 months) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scale (Measure of Pain Intensity) | The pain Visual Analog Scale is a unidimensional measure of pain intensity. The scale is most commonly anchored by no pain (score of 0) and pain as bad as it could be or worst imaginable pain (scale of 10). | up to 12 months (O, 2, 4, 6 weeks, 3,6 and 12 months) |
|
Arthritis, Degenerative, Recovery of function
|
Osteoarthritis, Arthritis, Joint Diseases, Musculoskeletal Diseases, Rheumatic Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control - Verbal information and Booklet<br>Verbal information will be provided in order to explain how the patient should perform physical rehabilitation exercises. Furthermore, an illustrative booklet with representative exercises will be given. | Other: Verbal Information and Booklet<br>* Verbal information will be provided in order to explain how the patient should perform physical rehabilitation exercises. Furthermore, an illustrative booklet with representative exercises will be given. Also, an illustrative daily schedule to mark on the exact day in which the exercise was performed<br>* Other names: Verbal and Booklet Physical Rehabilitation information;|
| Experimental: Study - Verbal information, Booklet & Schedule.<br>Verbal information will be provided in order to explain how the patient should perform physical rehabilitation exercises. Furthermore, an illustrative booklet with representative exercises will be given. Also, an illustrative daily schedule to mark on the exact day in which the exercise was performed | Other: Schedule<br>* Illustrative daily planner to point the day that the exercise was performed<br>* Other names: Planner;Other: Verbal Information and Booklet<br>* Verbal information will be provided in order to explain how the patient should perform physical rehabilitation exercises. Furthermore, an illustrative booklet with representative exercises will be given. Also, an illustrative daily schedule to mark on the exact day in which the exercise was performed<br>* Other names: Verbal and Booklet Physical Rehabilitation information;|
|
Home Rehabilitation in Patients After Primary Total Knee Arthroplasty
Study Overview
=================
Brief Summary
-----------------
The investigators include patients attending the outpatient clinic in the area of Orthopedics and Traumatology of the investigators hospital with a diagnosis of knee osteoarthritis, which treatment requires surgery. Patients will be divided into two groups. In both groups, they will be given verbal, clear and detailed information on the approach to follow, the exercises given in brochures, and in the study group a schedule will be given in order to record rehabilitation exercises in patients after total knee replacement (TKA). Both groups will be assessed before and after surgery, together with outpatient follow-up by, WOMAC, Visual Analogue Scale and OKS (Oxford Knee Score).
Detailed Description
-----------------
Osteoarthritis (OA) is the most common rheumatic disease worldwide. OA cause joint pain and occupational disability in the adult population. In Mexico, OA is one of the top ten reasons of consultation in primary attention care. Joint arthroplasty is a major advance in the treatment of chronic joint pain. It is indicated in patients in whose conservative medical therapy has failed. Total knee arthroplasty (TKA) is a surgery that reduces pain and improves function and quality of life in patients with knee disorders, actually is one of the most successful medical procedures. However, a critical consideration in patients with TKA is the successful control of postoperative pain. An adequate pain control allows faster rehabilitation, reduces complications and is highly correlated with patient satisfaction. A multimodal pain management decreases the use of narcotics, improve pain scores, increase patient satisfaction and allows early recovery. Regarding postoperative rehabilitation, its suggested that rehabilitation programs are based on a biopsychosocial philosophy and integrate exercises and self-management interventions are effective in the treatment of osteoarthritis. Rehabilitation therapy an important area that should be considered. It helps people recover faster from their illness, injury or medical procedures and make possible to get back to their daily activities. The World Health Organization describes rehabilitation as a process that aims to enable people to maintain and achieve their physical, sensory, intellectual, functional, psychological and social level in an optimal way. It is known that rehabilitation involves contributions from various health disciplines, including physical therapy and occupational therapy and offered in inpatient, outpatient and community patients. In patients with total knee replacement, rehabilitation interventions may involve education and exercise before surgery, early mobilization while being in the hospital and a postoperative program, along with an adequate pain management. Perioperative care has shown an improvement in the recovery, it reduces hospital day stay, convalescent and risk of postoperative medical complications. It has been shown that early initiation of rehabilitation within 24 hours after total knee arthroplasty reduces in-hospital time and decreases the number of sessions required to achieve autonomy, balance and normal gait. Madsen et al. demonstrated that rehabilitation exercises at home have the same effect as those made in rehabilitation group within six months postoperatively, based on a study of 80 patients randomly divided into a control- study group. Optimal pain management is vital seeking to achieve the goal of recovery called fast track. It involves early therapy with specialized protocols, early discharge and quick recovery. Lamplot et al. demonstrated in a prospective randomized study of 36 patients, using this method, a decrease in opioid consumption and its adverse effects, a decreased pain score, a shortening time for physical therapy and an increase in patient satisfaction. Postoperative analgesia can be achieved by a variety of techniques. These include: intravenous analgesia, epidural analgesia, techniques for peripheral nerve block and periarticular injections. All aim to control pain in patients and provide the better satisfaction. Integrating these interventions in a clinical pathway, better functional results are obtained, hospital stay is reduced and there is an improvement in the patient's recovery, mainly in short-term.
Official Title
-----------------
Home Rehabilitation in Patients After Primary Total Knee Arthroplasty
Conditions
-----------------
Osteoarthritis, Rehabilitation
Intervention / Treatment
-----------------
* Other: Schedule
* Other: Verbal Information and Booklet
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 18 and 90 years Patients with Knee osteoarthritis (OA) grade 4 ( Kellgren-Lawrence based on radiographic findings) Total Knee Arthroplasty (TKA) for primary OA Rapid rehabilitation desire Exclusion Criteria: Age <18 and > 90 years Patients with Knee osteoarthritis grade 1-2 ( Kellgren-Lawrence based on radiographic findings) Patients with asociated Rheumatic syndromes Patients with anticoagulant therapy Patients with hepatic problems, Diabetes Mellitus, Coagulopathy, hearth conditions, immunodepressed, or infections Drugs abuse history Physiatric disease Pregnant patients Patients with hemoglobin values < 11g/dl , platelets < 150,000/ μL
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control - Verbal information and Booklet<br>Verbal information will be provided in order to explain how the patient should perform physical rehabilitation exercises. Furthermore, an illustrative booklet with representative exercises will be given. | Other: Verbal Information and Booklet<br>* Verbal information will be provided in order to explain how the patient should perform physical rehabilitation exercises. Furthermore, an illustrative booklet with representative exercises will be given. Also, an illustrative daily schedule to mark on the exact day in which the exercise was performed<br>* Other names: Verbal and Booklet Physical Rehabilitation information;|
| Experimental: Study - Verbal information, Booklet & Schedule.<br>Verbal information will be provided in order to explain how the patient should perform physical rehabilitation exercises. Furthermore, an illustrative booklet with representative exercises will be given. Also, an illustrative daily schedule to mark on the exact day in which the exercise was performed | Other: Schedule<br>* Illustrative daily planner to point the day that the exercise was performed<br>* Other names: Planner;Other: Verbal Information and Booklet<br>* Verbal information will be provided in order to explain how the patient should perform physical rehabilitation exercises. Furthermore, an illustrative booklet with representative exercises will be given. Also, an illustrative daily schedule to mark on the exact day in which the exercise was performed<br>* Other names: Verbal and Booklet Physical Rehabilitation information;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total WOMAC Score | The total score is provided for Western Ontario and McMaster Universities Arthritis Index (WOMAC). It is a widely score used in the evaluation of Hip and Knee Osteoarthritis. Consists of a self-administered questionnaire consisting of 24 items divided into 3 subscales: pain (5 items), stiffness (2 items), and physical functioning (17 items) of the joints. Scale Range: 5 items of pain (score range 0-20), 2 items for stiffness (score range 0-8), and 17 items for functional limitation (score range 0-68). The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). Total WOMAC score range 0-96. For each subscale higher values represent worse outcomes. Subscales are summed for a total WOMAC score. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. WOMAC Index was developed in 1982 at Western Ontario and McMaster Universities. | up to 12 months (O, 2, 4, 6 weeks, 3,6 and 12 months) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scale (Measure of Pain Intensity) | The pain Visual Analog Scale is a unidimensional measure of pain intensity. The scale is most commonly anchored by no pain (score of 0) and pain as bad as it could be or worst imaginable pain (scale of 10). | up to 12 months (O, 2, 4, 6 weeks, 3,6 and 12 months) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Arthritis, Degenerative, Recovery of function
|
NCT04165629
|
Platelet Reactivity in PAD Undergoing Percutaneous Angioplasty
|
Dual antiplatelet therapy has a key role in a prevention of thrombosis of treated artery in patients undergoing percutaneous transluminal angioplasty (PTA). Weak therapeutic response and presence of residual platelet activity is related to high risk for stent thrombosis and it is well in known in coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). However there are few data on the association between a different entity of platelet inhibition on antiplatelet treatment and clinical outcomes in patients with peripheral artery disease (PAD). The aim of this study was to evaluate the degree of on-treatment platelet reactivity, and its association with ischemic and hemorrhagic adverse events at follow up in PAD patients undergoing PTA.
|
This is a single-center observational cohort study. All together 450 patients undergoing and elective PTA (both with and without stenting) who are going to be refereed to the Clinic for Vascular and Endovascular Surgery (based on the previous experience) during the two year period (January 1st 2020 and January 1st 2022) are planned to be involved in this study. All interventions will be performed according to the current standards and the type of the endovascular procedure will be at the discretion of operator. All patients will receive at the day of treatment 300mg of Aspirin and 300mg of Clopidogrel. The day after the procedure platelet function will be assessed by point-of-care impedance aggregometry test using the Multiplate analyzer. According to the manufacturer proposition, resistancy on Aspirin will be defined as arachidonic acid receptor (ASPI) value < 600 and ASPI/thrombin receptor activating peptide (TRAP) < 0.5, and for Clopidogrel adenosine diphosphate (ADP) < 500 and ADP/TRAP < 0.5 . After that patients will receive dual antiplatelet therapy (Aspirin 100mg and Clopidogrel 75mg) in the six months period. Follow-up examinations will be scheduled on 1, 6 and 12 months after the intervention. Adherence to antiplatelet treatment will assessed during scheduled or unscheduled examinations. Statistical analysis will be performed using the software package SPSS 20 (SPSS Inc., Chicago, Il, USA). Categorical data will be represented as numbers and percentages. Chi-square test or Fisher exact test as appropriate will be used to compare categorical data. Continuous variables will be represented as mean ± standard deviation and as median and interquartile range, depending on the normality of data. Student's t test or Mann-Whitney U test as appropriate will be used to compare two population groups. We will then assess the ability of ASPI and ADP values to distinguish between patients with and without clinical event at 6 months follow up by receiver-operating characteristic (ROC) curve analysis and the optimal cut-off ASPI and ADP values will be determined by estimating the value resulting in the maximum sum of sensitivity and specificity (area under the curve - AUC). Kaplan-Meier curves with log-rank test will be used to assess difference in the time-to-event end-points. A multivariable Cox proportional hazard model adjusted for clinical and laboratory variables will be performed to evaluate the independent contribution of platelet hyper- or hypo-reactivity to the outcomes. A P-values <0.05 will be considered statistically significant.
|
Influence of Platelet Reactivity in Peripheral Arterial Disease Patients Undergoing Percutaneous Angioplasty on Mid-term Outcomes
|
Peripheral Artery Disease, Critical Limb Ischemia, Claudication, Intermittent
|
* Drug: Aspirin 300mg and Clopidogrel 300mg
|
Inclusion Criteria:~- all patients treated due to PAD with PTA with/without stenting of aorto-iliac, femoro-popliteal and crural disease at the mentioned time period with critical limb ischemia (CLI) or intermittent claudication (IC)~Exclusion Criteria:~younger that 18 and older than 85~contraindications for Aspirin and Clopidogrel use~thrombocytopenia (<100 x 10⁹/l)~thrombocytosis (>450 x 10⁹/l)~kidney insufficiency (stage 4 and 5)~more severe anemia (Hgb < 100 g/l)~severe hepatic disorder~congestive heart failure~known hemorrhagic disorder~known malignant disease~previous use of drugs with known anti-thrombocyte mechanism of action (dipyridamole, NSAID)~use oral anticoagulant therapy~use of corticosteroids~use of drugs that are metabolized threw CYP3A4 (like erythromycin and rifampicin)
|
18 Years
|
85 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Adverse Limb Event (MALE) | It includes major amputation, reintervention which could be surgical or repeat angioplasty. Major amputation is defined as amputation above the ankle. | 6 months |
| Mortality | All-cause mortality | 6 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Adverse Cardio- and Cerebrovascular Events (MACCE) | Nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death | 6 months |
| Bleeding complications | Major and minor bleeding | 6 months |
|
Aspirin, Clopidogrel, Anti-Inflammatory Agents, Non-Steroidal, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anti-Inflammatory Agents, Antirheumatic Agents, Fibrinolytic Agents, Fibrin Modulating Agents, Molecular Mechanisms of Pharmacological Action, Platelet Aggregation Inhibitors, Cyclooxygenase Inhibitors, Enzyme Inhibitors, Antipyretics, Purinergic P2Y Receptor Antagonists, Purinergic P2 Receptor Antagonists, Purinergic Antagonists, Purinergic Agents, Neurotransmitter Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Aspirin responders<br>On impedance aggregometry- Multiplate analyzer, if ASPI < 600 or ASPI/TRAP < 0.5 | Drug: Aspirin 300mg and Clopidogrel 300mg<br>* Aspirin 300mg and Clopidogrel 300mg on the day of the PTA<br>|
| Aspirin non-responders<br>On impedance aggregometry- Multiplate analyzer, if ASPI > 600 or ASPI/TRAP > 0.5 | Drug: Aspirin 300mg and Clopidogrel 300mg<br>* Aspirin 300mg and Clopidogrel 300mg on the day of the PTA<br>|
| Clopidogrel responders<br>On impedance aggregometry- Multiplate analyzer, if ADP < 500 or ADP/TRAP < 0.5 | Drug: Aspirin 300mg and Clopidogrel 300mg<br>* Aspirin 300mg and Clopidogrel 300mg on the day of the PTA<br>|
| Clopidogrel non-responders<br>On impedance aggregometry- Multiplate analyzer, if ADP > 500 or ADP/TRAP > 0.5 | Drug: Aspirin 300mg and Clopidogrel 300mg<br>* Aspirin 300mg and Clopidogrel 300mg on the day of the PTA<br>|
|
Platelet Reactivity in PAD Undergoing Percutaneous Angioplasty
Study Overview
=================
Brief Summary
-----------------
Dual antiplatelet therapy has a key role in a prevention of thrombosis of treated artery in patients undergoing percutaneous transluminal angioplasty (PTA). Weak therapeutic response and presence of residual platelet activity is related to high risk for stent thrombosis and it is well in known in coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). However there are few data on the association between a different entity of platelet inhibition on antiplatelet treatment and clinical outcomes in patients with peripheral artery disease (PAD). The aim of this study was to evaluate the degree of on-treatment platelet reactivity, and its association with ischemic and hemorrhagic adverse events at follow up in PAD patients undergoing PTA.
Detailed Description
-----------------
This is a single-center observational cohort study. All together 450 patients undergoing and elective PTA (both with and without stenting) who are going to be refereed to the Clinic for Vascular and Endovascular Surgery (based on the previous experience) during the two year period (January 1st 2020 and January 1st 2022) are planned to be involved in this study. All interventions will be performed according to the current standards and the type of the endovascular procedure will be at the discretion of operator. All patients will receive at the day of treatment 300mg of Aspirin and 300mg of Clopidogrel. The day after the procedure platelet function will be assessed by point-of-care impedance aggregometry test using the Multiplate analyzer. According to the manufacturer proposition, resistancy on Aspirin will be defined as arachidonic acid receptor (ASPI) value < 600 and ASPI/thrombin receptor activating peptide (TRAP) < 0.5, and for Clopidogrel adenosine diphosphate (ADP) < 500 and ADP/TRAP < 0.5 . After that patients will receive dual antiplatelet therapy (Aspirin 100mg and Clopidogrel 75mg) in the six months period. Follow-up examinations will be scheduled on 1, 6 and 12 months after the intervention. Adherence to antiplatelet treatment will assessed during scheduled or unscheduled examinations. Statistical analysis will be performed using the software package SPSS 20 (SPSS Inc., Chicago, Il, USA). Categorical data will be represented as numbers and percentages. Chi-square test or Fisher exact test as appropriate will be used to compare categorical data. Continuous variables will be represented as mean ± standard deviation and as median and interquartile range, depending on the normality of data. Student's t test or Mann-Whitney U test as appropriate will be used to compare two population groups. We will then assess the ability of ASPI and ADP values to distinguish between patients with and without clinical event at 6 months follow up by receiver-operating characteristic (ROC) curve analysis and the optimal cut-off ASPI and ADP values will be determined by estimating the value resulting in the maximum sum of sensitivity and specificity (area under the curve - AUC). Kaplan-Meier curves with log-rank test will be used to assess difference in the time-to-event end-points. A multivariable Cox proportional hazard model adjusted for clinical and laboratory variables will be performed to evaluate the independent contribution of platelet hyper- or hypo-reactivity to the outcomes. A P-values <0.05 will be considered statistically significant.
Official Title
-----------------
Influence of Platelet Reactivity in Peripheral Arterial Disease Patients Undergoing Percutaneous Angioplasty on Mid-term Outcomes
Conditions
-----------------
Peripheral Artery Disease, Critical Limb Ischemia, Claudication, Intermittent
Intervention / Treatment
-----------------
* Drug: Aspirin 300mg and Clopidogrel 300mg
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: - all patients treated due to PAD with PTA with/without stenting of aorto-iliac, femoro-popliteal and crural disease at the mentioned time period with critical limb ischemia (CLI) or intermittent claudication (IC) Exclusion Criteria: younger that 18 and older than 85 contraindications for Aspirin and Clopidogrel use thrombocytopenia (<100 x 10⁹/l) thrombocytosis (>450 x 10⁹/l) kidney insufficiency (stage 4 and 5) more severe anemia (Hgb < 100 g/l) severe hepatic disorder congestive heart failure known hemorrhagic disorder known malignant disease previous use of drugs with known anti-thrombocyte mechanism of action (dipyridamole, NSAID) use oral anticoagulant therapy use of corticosteroids use of drugs that are metabolized threw CYP3A4 (like erythromycin and rifampicin)
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Aspirin responders<br>On impedance aggregometry- Multiplate analyzer, if ASPI < 600 or ASPI/TRAP < 0.5 | Drug: Aspirin 300mg and Clopidogrel 300mg<br>* Aspirin 300mg and Clopidogrel 300mg on the day of the PTA<br>|
| Aspirin non-responders<br>On impedance aggregometry- Multiplate analyzer, if ASPI > 600 or ASPI/TRAP > 0.5 | Drug: Aspirin 300mg and Clopidogrel 300mg<br>* Aspirin 300mg and Clopidogrel 300mg on the day of the PTA<br>|
| Clopidogrel responders<br>On impedance aggregometry- Multiplate analyzer, if ADP < 500 or ADP/TRAP < 0.5 | Drug: Aspirin 300mg and Clopidogrel 300mg<br>* Aspirin 300mg and Clopidogrel 300mg on the day of the PTA<br>|
| Clopidogrel non-responders<br>On impedance aggregometry- Multiplate analyzer, if ADP > 500 or ADP/TRAP > 0.5 | Drug: Aspirin 300mg and Clopidogrel 300mg<br>* Aspirin 300mg and Clopidogrel 300mg on the day of the PTA<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Adverse Limb Event (MALE) | It includes major amputation, reintervention which could be surgical or repeat angioplasty. Major amputation is defined as amputation above the ankle. | 6 months |
| Mortality | All-cause mortality | 6 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Adverse Cardio- and Cerebrovascular Events (MACCE) | Nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death | 6 months |
| Bleeding complications | Major and minor bleeding | 6 months |
|
||
NCT04602728
|
Building Adaptive Coping and Knowledge to Improve Daily Life
|
The purpose of this study is to find out how teenagers with chronic pain and sickle cell disease respond to a new training program called Back2Life and get their feedback about how to modify the program to best fit their needs. The Back2Life training program focuses on teaching pain coping skills (also known as cognitive-behavioral therapy). The program teaches skills and strategies that may help teens improve chronic pain management and get back into their everyday activities.
|
Sickle cell disease (SCD) is a genetic disorder of the hemoglobin in which the course of acute pain from vaso-occlusion and its sequelae vary widely across genotypes and individual patients. SCD pain often begins during childhood and can progress to chronic pain for approximately 23% of children and adolescents. Youth with chronic SCD pain, that is pain that is present on most days per month and persists for at least 6 months, report high levels of functional disability, elevated depressive and anxiety symptoms, and reduced quality of life relative to youth with SCD without chronic pain. The complex, multifactorial nature of chronic SCD pain can also contribute to increased healthcare utilization for pain. The most effective management and treatment of chronic SCD pain likely requires individualized, multimodal, multidisciplinary treatments that go beyond pharmacological management alone. A range of evidence-based non-pharmacological treatments, such as behavioral health, complementary, and integrative health approaches, are recommended for chronic pain management and are gaining greater awareness and integration into comprehensive chronic pain care.~Behavioral health treatment, such as cognitive-behavioral therapy (CBT) for pain, focuses on improved daily functioning and coping through several core treatment components such as psychoeducation about how the body processes pain, relaxation skills training, and cognitive strategies. Youth with chronic SCD pain need an evidence-based, culturally informed, adaptive treatment. Behavioral treatments that are tailored to patient and family needs are beneficial when patients may require different levels of care. Adaptive designs are more effective in improving health outcomes, satisfaction with treatment, and reducing healthcare use than standard protocols where patients receive a fixed one size fits all treatment that is not personalized to their needs; adaptive designs are also recommended for tailoring evidence-based interventions with culturally diverse populations. Adaptive treatments can integrate evidence-based strategies to address common co-morbid problems associated with chronic pain, such as elevated anxiety or depressive symptoms or sleep disturbance. Teaching parents problem-solving skills can reduce caregiver stress among families managing chronic pain and illness.~This study will utilize an adaptive behavioral treatment to target psychosocial risk factors for youth with chronic SCD pain as a first step towards developing a stepped care model for SCD pain.
|
Building Adaptive Coping and Knowledge to Improve Daily Life (Back2Life): A Pilot Feasibility Clinical Trial for Youth With Chronic Sickle Cell Pain
|
Sickle Cell Disease
|
* Behavioral: Back2Life
|
Inclusion Criteria for Youth:~diagnosed with SCD (any genotype)~report chronic pain~speak and read English~have not initiated new disease modifying-treatments (e.g, hydroxyurea, Endari, voxelotor, crizanlizumab, chronic transfusions) or significantly increased dosages of any disease-modifying treatments in the past 3 months~Inclusion Criteria for Parents or Caregivers:~speak and read English~Exclusion Criteria for Youth:~have comorbid medical conditions typically associated with pain but unrelated to SCD (e.g., rheumatologic disorders or inflammatory bowel disease)~are receiving chronic transfusion indicated for central nervous system risks and/or complications, previous overt strokes, or significant cognitive or developmental limitations, as per their healthcare provider or parent, that would impair completion of self-report measures or engagement in treatment sessions~received ≥ 3 sessions of outpatient psychological therapy for pain management in the 6 months prior to screening~Exclusion Criteria for Parents or Caregivers:~have significant cognitive limitations or severe psychiatric conditions, as per the child's healthcare team or history, that would impair completion of self-report measures or engagement in treatment sessions
|
10 Years
|
18 Years
|
All
|
No
|
Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Interventional Model Description: Youth and parent/caregiver dyads will participate in the same intervention.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Patient Reported Outcomes Measurement Information System (PROMIS) Pediatric Short Form Pain Interference Score | The PROMIS Pediatric Short Form for Pain Interference, Self- and Parent-Proxy Report, is an 8-item self-report measure assessing functional interference due to pain in the past 7 days. Total scores are standardized to a T-score with a mean of 50 and a standard deviation of 10, where higher scores indicate increased hindrance of life activities due to pain. | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Change in Sickle Cell Disease Pain Burden Interview-Youth (SCPBI-Y) Score | The Sickle Cell Pain Burden Interview for Youth, Self- and Caregiver-Proxy Report is a 7-item, validated measure of pain burden in 7-21 year olds. Responses are given on a 5-point Likert scale where 0 = none and 4 = every. Both the patient self-report and parent-proxy ask respondents to report the amount of days in the past month where pain occurred or pain impacted daily life. Total scores range from 0 to 28 and higher scores indicate a greater pain burden. | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Change in PROMIS Pediatric Short Form Pain Behaviors Score | The PROMIS Pediatric Short Form Pain Behaviors, Parent-Proxy Report is an 8-item measure completed by parents that assesses pain behaviors displayed by their child in the past 7 days. Total scores are standardized to a T-score with a mean of 50 and a standard deviation of 10, where higher scores indicate increased behaviors due to pain. | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Change in Child Self-Efficacy Scale Score | Child Self-Efficacy Scale, Self- and Parent-Proxy Report is a well-established, 7-item measure of self-efficacy for functioning despite pain for 8-19 year olds. Respondents report how sure about their (or their child's) ability to perform certain daily tasks when they have pain, on a scale from 1 to 5 where 1 = very sure and 5 = very unsure. Total scores range from 7 to 35 and lower scores indicate greater self-efficacy. | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Number of Dyads Completing the Study | Treatment feasibility will be assessed by the number of participant dyads who complete the study. | Month 6 |
| Percent of Study Assignments Completed | Treatment feasibility will be assessed by completion of study assignments. | Month 6 |
| Participant Evaluation of the Intervention | Treatment feasibility will be assessed via a qualitative interview where participants are asked open ended questions. Participants will be asked if they thought the Back2Life program is a reasonable approach for chronic pain management, if the program was helpful, and if it could be integrated into their lifestyle. Participants will also be asked to describe barriers in implementing the program. | Immediately Post-Treatment |
| Treatment Evaluation Inventory-Short Form (TEI-SF) Score | The Treatment Evaluation Inventory-Short Form will be completed at the end of treatment. It includes 9 items adapted to be specific to pediatric pain. Items are rated on a 5-point Likert scale ranging from 1 to 5. Total scores range from 9 to 45. Higher scores indicate increased acceptability with the study treatment. | Immediately Post-Treatment |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Emergency Department Visits | Healthcare utilization will be extracted from the medical record to document the total number of emergency department (ED) visits for pain for 6-months and 12-months pre- and post-treatment. | 12 months prior to Baseline to 12 months post-treatment |
| Number of Hospital Admissions | Healthcare utilization will be extracted from the medical record to document the total number of hospital admissions for pain for 6-months and 12-months pre- and post-treatment. | 12 months prior to Baseline to 12 months post-treatment |
| Change in Daily Opioid Use | Daily use of opioid pain medication will be determined based on participant completion of daily diaries for 1-week at each assessment visit. Participants will record opioid use daily (presence/absence). | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Change in Pediatric Inventory for Parents (PIP) Score | The Pediatric Inventory for Parents is a 42-item parent-reported measure of caregiver stress related to child chronic illness. Responses are given on a 5-point Likert scale where 1 = not at all and 5 = extremely. Total scores range from 42 to 210 and higher scores indicate greater caregiver stress. | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Change in Adolescent Sleep Wake Scale (ASWS) Score | The Adolescent Sleep Wake Scale (ASWS) is a 28-item patient-reported describing the occurrence and frequency of various behavioral sleep characteristics over the past month. Responses are given on a 6-point Likert scale where 1 = always and 6 = never. Total scores range from 28 to 168 and higher scores indicate better sleep quality. | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Change in PROMIS Pediatric Short Form Depressive Symptoms Score | The PROMIS Pediatric Short Form Depressive Symptoms questionnaire, Self- and Parent-Proxy Report is an 8-item measure designed for youth to assess self-reported symptoms of depression. Total scores are standardized to a T-score with a mean of 50 and a standard deviation of 10, where higher scores indicate increased depression. | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Change in Pain Catastrophizing Scale Score | The Pain Catastrophizing Scale, Child and Parent Report, is a 13-item well-validated self-report and parent-report measure of worried thoughts about pain. Items are answered on a 5-point scale where 0 = not true at all and 4 = very true. Total scores range from 0 to 52 and higher scores indicate increased catastrophic thinking. | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Change in Pain Stages of Change Questionnaire (PSOCQ) Score | The Pain Stages of Change Questionnaire, Adolescent and Parent Report is a 30-item measure designed to evaluate parent and adolescent perceptions of readiness to adopt a self-management approach to pain. Responses to items are given on a 5-point scale where 1 = strongly disagree and 5 = strongly agree. Average scores are obtained for categories of precontemplation, contemplation, action, and maintenance and the category with the highest score indicates where the youth participant is in terms of stages of change related to pain management. | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Change in Interleukin -1β (IL-1β), Concentration | Plasma concentration of the inflammatory biomarker IL-1β will be assessed. IL-1β increases in response to inflammation, pain, and autoimmune diseases. | Baseline, Month 3, Month 6 |
| Change in Interleukin 6 (IL-6) Concentration | Plasma concentration of the inflammatory biomarker IL-6 will be assessed. IL-6 is increased during injury or illness. | Baseline, Month 3, Month 6 |
| Change in Interleukin 8 (IL-8) Concentration | Plasma concentration of the inflammatory biomarker IL-8 will be assessed. IL-8 is produced when inflammation is present. | Baseline, Month 3, Month 6 |
| Change in Tumor Necrosis Factor - Alpha (TNF-α) Concentration | Plasma concentration of the inflammatory biomarker TNF-α will be assessed. TNF-α is a pro-inflammatory cytokine that regulates the inflammatory response and it is elevated during illness or injury. | Baseline, Month 3, Month 6 |
| Change in C-Reactive Protein (CRP) Concentration | Plasma concentration of the inflammatory biomarker CRP will be assessed. CRP increases in response to bodily inflammation. | Baseline, Month 3, Month 6 |
| Change in Brain-Derived Neurotrophic Factor (BDNP) Concentration | Plasma concentration of the inflammatory biomarker BDNP will be assessed. BDNP expression is reduced when high bodily inflammation is present. | Baseline, Month 3, Month 6 |
| Change in Interferon Gamma (IFN-y) Concentration | Plasma concentration of the inflammatory biomarker IFN-y will be assessed. IFN-y is involved with regulating immune and inflammatory responses. IFN-y concentration is elevated during illness. | Baseline, Month 3, Month 6 |
|
Pediatrics, Cognitive behavioral therapy, Behavioral intervention
|
Anemia, Anemia, Sickle Cell, Anemia, Hemolytic, Congenital, Anemia, Hemolytic, Hematologic Diseases, Hemoglobinopathies, Genetic Diseases, Inborn
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Back2Life Program<br>Youth with chronic SCD pain and their parents or caregivers receiving an adaptive cognitive behavioral treatment program for pain coping skills. | Behavioral: Back2Life<br>* The Back2Life intervention uses an adaptive treatment approach with module-based treatment sessions selected on the basis of baseline assessment (rather than a fixed treatment approach) to allow flexibility in tailoring treatment components to meet individual family needs. All youth participants will receive the standard 6-session pain coping skills training program, consisting of learning ways to cope with and manage chronic sickle cell pain. The standard program includes topics that were identified by young people with chronic sickle cell pain and their parents as important skills for all youth with chronic pain and sickle cell disease. In addition to the standard 6-session program, youth participants may receive an additional 1 to 4 sessions that may help with specific problems and/or co-morbidities related to pain. At least one parent or guardian is required to attend the sessions with their child.<br>|
|
Building Adaptive Coping and Knowledge to Improve Daily Life
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to find out how teenagers with chronic pain and sickle cell disease respond to a new training program called Back2Life and get their feedback about how to modify the program to best fit their needs. The Back2Life training program focuses on teaching pain coping skills (also known as cognitive-behavioral therapy). The program teaches skills and strategies that may help teens improve chronic pain management and get back into their everyday activities.
Detailed Description
-----------------
Sickle cell disease (SCD) is a genetic disorder of the hemoglobin in which the course of acute pain from vaso-occlusion and its sequelae vary widely across genotypes and individual patients. SCD pain often begins during childhood and can progress to chronic pain for approximately 23% of children and adolescents. Youth with chronic SCD pain, that is pain that is present on most days per month and persists for at least 6 months, report high levels of functional disability, elevated depressive and anxiety symptoms, and reduced quality of life relative to youth with SCD without chronic pain. The complex, multifactorial nature of chronic SCD pain can also contribute to increased healthcare utilization for pain. The most effective management and treatment of chronic SCD pain likely requires individualized, multimodal, multidisciplinary treatments that go beyond pharmacological management alone. A range of evidence-based non-pharmacological treatments, such as behavioral health, complementary, and integrative health approaches, are recommended for chronic pain management and are gaining greater awareness and integration into comprehensive chronic pain care. Behavioral health treatment, such as cognitive-behavioral therapy (CBT) for pain, focuses on improved daily functioning and coping through several core treatment components such as psychoeducation about how the body processes pain, relaxation skills training, and cognitive strategies. Youth with chronic SCD pain need an evidence-based, culturally informed, adaptive treatment. Behavioral treatments that are tailored to patient and family needs are beneficial when patients may require different levels of care. Adaptive designs are more effective in improving health outcomes, satisfaction with treatment, and reducing healthcare use than standard protocols where patients receive a fixed one size fits all treatment that is not personalized to their needs; adaptive designs are also recommended for tailoring evidence-based interventions with culturally diverse populations. Adaptive treatments can integrate evidence-based strategies to address common co-morbid problems associated with chronic pain, such as elevated anxiety or depressive symptoms or sleep disturbance. Teaching parents problem-solving skills can reduce caregiver stress among families managing chronic pain and illness. This study will utilize an adaptive behavioral treatment to target psychosocial risk factors for youth with chronic SCD pain as a first step towards developing a stepped care model for SCD pain.
Official Title
-----------------
Building Adaptive Coping and Knowledge to Improve Daily Life (Back2Life): A Pilot Feasibility Clinical Trial for Youth With Chronic Sickle Cell Pain
Conditions
-----------------
Sickle Cell Disease
Intervention / Treatment
-----------------
* Behavioral: Back2Life
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria for Youth: diagnosed with SCD (any genotype) report chronic pain speak and read English have not initiated new disease modifying-treatments (e.g, hydroxyurea, Endari, voxelotor, crizanlizumab, chronic transfusions) or significantly increased dosages of any disease-modifying treatments in the past 3 months Inclusion Criteria for Parents or Caregivers: speak and read English Exclusion Criteria for Youth: have comorbid medical conditions typically associated with pain but unrelated to SCD (e.g., rheumatologic disorders or inflammatory bowel disease) are receiving chronic transfusion indicated for central nervous system risks and/or complications, previous overt strokes, or significant cognitive or developmental limitations, as per their healthcare provider or parent, that would impair completion of self-report measures or engagement in treatment sessions received ≥ 3 sessions of outpatient psychological therapy for pain management in the 6 months prior to screening Exclusion Criteria for Parents or Caregivers: have significant cognitive limitations or severe psychiatric conditions, as per the child's healthcare team or history, that would impair completion of self-report measures or engagement in treatment sessions
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?
-----------------
Design Details
Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Interventional Model Description: Youth and parent/caregiver dyads will participate in the same intervention.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Back2Life Program<br>Youth with chronic SCD pain and their parents or caregivers receiving an adaptive cognitive behavioral treatment program for pain coping skills. | Behavioral: Back2Life<br>* The Back2Life intervention uses an adaptive treatment approach with module-based treatment sessions selected on the basis of baseline assessment (rather than a fixed treatment approach) to allow flexibility in tailoring treatment components to meet individual family needs. All youth participants will receive the standard 6-session pain coping skills training program, consisting of learning ways to cope with and manage chronic sickle cell pain. The standard program includes topics that were identified by young people with chronic sickle cell pain and their parents as important skills for all youth with chronic pain and sickle cell disease. In addition to the standard 6-session program, youth participants may receive an additional 1 to 4 sessions that may help with specific problems and/or co-morbidities related to pain. At least one parent or guardian is required to attend the sessions with their child.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Patient Reported Outcomes Measurement Information System (PROMIS) Pediatric Short Form Pain Interference Score | The PROMIS Pediatric Short Form for Pain Interference, Self- and Parent-Proxy Report, is an 8-item self-report measure assessing functional interference due to pain in the past 7 days. Total scores are standardized to a T-score with a mean of 50 and a standard deviation of 10, where higher scores indicate increased hindrance of life activities due to pain. | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Change in Sickle Cell Disease Pain Burden Interview-Youth (SCPBI-Y) Score | The Sickle Cell Pain Burden Interview for Youth, Self- and Caregiver-Proxy Report is a 7-item, validated measure of pain burden in 7-21 year olds. Responses are given on a 5-point Likert scale where 0 = none and 4 = every. Both the patient self-report and parent-proxy ask respondents to report the amount of days in the past month where pain occurred or pain impacted daily life. Total scores range from 0 to 28 and higher scores indicate a greater pain burden. | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Change in PROMIS Pediatric Short Form Pain Behaviors Score | The PROMIS Pediatric Short Form Pain Behaviors, Parent-Proxy Report is an 8-item measure completed by parents that assesses pain behaviors displayed by their child in the past 7 days. Total scores are standardized to a T-score with a mean of 50 and a standard deviation of 10, where higher scores indicate increased behaviors due to pain. | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Change in Child Self-Efficacy Scale Score | Child Self-Efficacy Scale, Self- and Parent-Proxy Report is a well-established, 7-item measure of self-efficacy for functioning despite pain for 8-19 year olds. Respondents report how sure about their (or their child's) ability to perform certain daily tasks when they have pain, on a scale from 1 to 5 where 1 = very sure and 5 = very unsure. Total scores range from 7 to 35 and lower scores indicate greater self-efficacy. | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Number of Dyads Completing the Study | Treatment feasibility will be assessed by the number of participant dyads who complete the study. | Month 6 |
| Percent of Study Assignments Completed | Treatment feasibility will be assessed by completion of study assignments. | Month 6 |
| Participant Evaluation of the Intervention | Treatment feasibility will be assessed via a qualitative interview where participants are asked open ended questions. Participants will be asked if they thought the Back2Life program is a reasonable approach for chronic pain management, if the program was helpful, and if it could be integrated into their lifestyle. Participants will also be asked to describe barriers in implementing the program. | Immediately Post-Treatment |
| Treatment Evaluation Inventory-Short Form (TEI-SF) Score | The Treatment Evaluation Inventory-Short Form will be completed at the end of treatment. It includes 9 items adapted to be specific to pediatric pain. Items are rated on a 5-point Likert scale ranging from 1 to 5. Total scores range from 9 to 45. Higher scores indicate increased acceptability with the study treatment. | Immediately Post-Treatment |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Emergency Department Visits | Healthcare utilization will be extracted from the medical record to document the total number of emergency department (ED) visits for pain for 6-months and 12-months pre- and post-treatment. | 12 months prior to Baseline to 12 months post-treatment |
| Number of Hospital Admissions | Healthcare utilization will be extracted from the medical record to document the total number of hospital admissions for pain for 6-months and 12-months pre- and post-treatment. | 12 months prior to Baseline to 12 months post-treatment |
| Change in Daily Opioid Use | Daily use of opioid pain medication will be determined based on participant completion of daily diaries for 1-week at each assessment visit. Participants will record opioid use daily (presence/absence). | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Change in Pediatric Inventory for Parents (PIP) Score | The Pediatric Inventory for Parents is a 42-item parent-reported measure of caregiver stress related to child chronic illness. Responses are given on a 5-point Likert scale where 1 = not at all and 5 = extremely. Total scores range from 42 to 210 and higher scores indicate greater caregiver stress. | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Change in Adolescent Sleep Wake Scale (ASWS) Score | The Adolescent Sleep Wake Scale (ASWS) is a 28-item patient-reported describing the occurrence and frequency of various behavioral sleep characteristics over the past month. Responses are given on a 6-point Likert scale where 1 = always and 6 = never. Total scores range from 28 to 168 and higher scores indicate better sleep quality. | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Change in PROMIS Pediatric Short Form Depressive Symptoms Score | The PROMIS Pediatric Short Form Depressive Symptoms questionnaire, Self- and Parent-Proxy Report is an 8-item measure designed for youth to assess self-reported symptoms of depression. Total scores are standardized to a T-score with a mean of 50 and a standard deviation of 10, where higher scores indicate increased depression. | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Change in Pain Catastrophizing Scale Score | The Pain Catastrophizing Scale, Child and Parent Report, is a 13-item well-validated self-report and parent-report measure of worried thoughts about pain. Items are answered on a 5-point scale where 0 = not true at all and 4 = very true. Total scores range from 0 to 52 and higher scores indicate increased catastrophic thinking. | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Change in Pain Stages of Change Questionnaire (PSOCQ) Score | The Pain Stages of Change Questionnaire, Adolescent and Parent Report is a 30-item measure designed to evaluate parent and adolescent perceptions of readiness to adopt a self-management approach to pain. Responses to items are given on a 5-point scale where 1 = strongly disagree and 5 = strongly agree. Average scores are obtained for categories of precontemplation, contemplation, action, and maintenance and the category with the highest score indicates where the youth participant is in terms of stages of change related to pain management. | Baseline, Immediately Post-Treatment, Month 3, Month 6 |
| Change in Interleukin -1β (IL-1β), Concentration | Plasma concentration of the inflammatory biomarker IL-1β will be assessed. IL-1β increases in response to inflammation, pain, and autoimmune diseases. | Baseline, Month 3, Month 6 |
| Change in Interleukin 6 (IL-6) Concentration | Plasma concentration of the inflammatory biomarker IL-6 will be assessed. IL-6 is increased during injury or illness. | Baseline, Month 3, Month 6 |
| Change in Interleukin 8 (IL-8) Concentration | Plasma concentration of the inflammatory biomarker IL-8 will be assessed. IL-8 is produced when inflammation is present. | Baseline, Month 3, Month 6 |
| Change in Tumor Necrosis Factor - Alpha (TNF-α) Concentration | Plasma concentration of the inflammatory biomarker TNF-α will be assessed. TNF-α is a pro-inflammatory cytokine that regulates the inflammatory response and it is elevated during illness or injury. | Baseline, Month 3, Month 6 |
| Change in C-Reactive Protein (CRP) Concentration | Plasma concentration of the inflammatory biomarker CRP will be assessed. CRP increases in response to bodily inflammation. | Baseline, Month 3, Month 6 |
| Change in Brain-Derived Neurotrophic Factor (BDNP) Concentration | Plasma concentration of the inflammatory biomarker BDNP will be assessed. BDNP expression is reduced when high bodily inflammation is present. | Baseline, Month 3, Month 6 |
| Change in Interferon Gamma (IFN-y) Concentration | Plasma concentration of the inflammatory biomarker IFN-y will be assessed. IFN-y is involved with regulating immune and inflammatory responses. IFN-y concentration is elevated during illness. | Baseline, Month 3, Month 6 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pediatrics, Cognitive behavioral therapy, Behavioral intervention
|
NCT03222310
|
A Study to Evaluate the Effect of a Potent Cytochrome P450 (CYP) 3A Inhibitor on Ipatasertib
|
This study will be a single center, open-label, 2-period, fixed-sequence, Phase 1 drug-drug interaction study in healthy subjects. The primary purpose of this study is to evaluate the effect of itraconazole on the PK of ipatasertib and its primary metabolite (G-037720).
|
Effect of a Potent CYP3A and P-gp Inhibitor (Itraconazole) on Ipatasertib Pharmacokinetics in Healthy Subjects
|
Healthy Volunteers
|
* Drug: Ipatasertib
* Drug: Itraconazole
|
Inclusion Criteria:~Within body mass index (BMI) range 18.5 to 32.0 kg/m2, inclusive~In good health, determined by no clinically significant findings from medical history, 12-lead ECG, and vital signs~Clinical laboratory evaluations (including chemistry panel [fasted at least 8 hours], hematology, and urinalysis [UA] with complete microscopic analysis within the reference range for the test laboratory, unless deemed not clinically significant by the Investigator)~Negative test for selected drugs of abuse at Screening (does not include alcohol) and at Check-in (Day -2)~Negative hepatitis panel (hepatitis B surface antigen and hepatitis C virus antibody) and negative human immunodeficiency virus (HIV) antibody screens~Exclusion Criteria:~Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, GI, neurological, or psychiatric disorder (as determined by the Investigator)~History of diabetes requiring insulin or fasting glucose ≥160 mg/dL~History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator~history of stomach or intestinal surgery or resection, or other GI disorder that would potentially alter absorption and/or excretion of orally administered drugs, except that appendectomy, hernia repair, and/or cholecystectomy will be allowed~history or presence of an abnormal ECG, which, in the Investigator's opinion, is clinically significant
|
18 Years
|
55 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of ipatasertib and its Metabolite (G-037720) | Cmax is the maximum observed concentration. | Pre-dose, 0.167, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1 and 19; 168, 192 hours post dose on Day 19 |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Ipatasertib and its Metabolite (G-037720) | AUC(0-inf) is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of a drug over time. | Pre-dose, 0.167, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1 and 19; 168, 192 hours post dose on Day 19 |
| Area Under the Plasma Concentration-Time Curve From Hour 0 to the Last Measureable Concentration (AUC0-t) of Ipatasertib and its Metabolite (G-037720) | Area Under the Plasma Concentration-Time Curve From Hour 0 to the Last Measureable Concentration (AUC0-t) will be reported. | Pre-dose, 0.167, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1 and 19; 168, 192 hours post dose on Day 19 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced at Least 1 Adverse Event | An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. | Up to 28 days after the last dose of the study drug (approximately up to 51 days) |
|
Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs, Antineoplastic Agents, Hormone Antagonists, Itraconazole, Ipatasertib, Antifungal Agents, Anti-Infective Agents, 14-alpha Demethylase Inhibitors, Cytochrome P-450 Enzyme Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Steroid Synthesis Inhibitors, Cytochrome P-450 CYP3A Inhibitors, Protein Kinase Inhibitors
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ipatasertib<br>Participants will receive one 100 milligram (mg) ipatasertib tablet orally on Day 1 of treatment in treatment period 1 followed by two 100 mg itraconazole capsules orally on Days 15 to 23 along with one 100 mg of ipatasertib on Day 19 in treatment period 2. Both the treatment period will be separated by a washout period of 14 days. | Drug: Ipatasertib<br>* Ipatasertib 100 mg tablet orally once daily.<br>Drug: Itraconazole<br>* Itraconazole 100 mg capsules orally once daily.<br>|
|
A Study to Evaluate the Effect of a Potent Cytochrome P450 (CYP) 3A Inhibitor on Ipatasertib
Study Overview
=================
Brief Summary
-----------------
This study will be a single center, open-label, 2-period, fixed-sequence, Phase 1 drug-drug interaction study in healthy subjects. The primary purpose of this study is to evaluate the effect of itraconazole on the PK of ipatasertib and its primary metabolite (G-037720).
Official Title
-----------------
Effect of a Potent CYP3A and P-gp Inhibitor (Itraconazole) on Ipatasertib Pharmacokinetics in Healthy Subjects
Conditions
-----------------
Healthy Volunteers
Intervention / Treatment
-----------------
* Drug: Ipatasertib
* Drug: Itraconazole
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Within body mass index (BMI) range 18.5 to 32.0 kg/m2, inclusive In good health, determined by no clinically significant findings from medical history, 12-lead ECG, and vital signs Clinical laboratory evaluations (including chemistry panel [fasted at least 8 hours], hematology, and urinalysis [UA] with complete microscopic analysis within the reference range for the test laboratory, unless deemed not clinically significant by the Investigator) Negative test for selected drugs of abuse at Screening (does not include alcohol) and at Check-in (Day -2) Negative hepatitis panel (hepatitis B surface antigen and hepatitis C virus antibody) and negative human immunodeficiency virus (HIV) antibody screens Exclusion Criteria: Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, GI, neurological, or psychiatric disorder (as determined by the Investigator) History of diabetes requiring insulin or fasting glucose ≥160 mg/dL History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator history of stomach or intestinal surgery or resection, or other GI disorder that would potentially alter absorption and/or excretion of orally administered drugs, except that appendectomy, hernia repair, and/or cholecystectomy will be allowed history or presence of an abnormal ECG, which, in the Investigator's opinion, is clinically significant
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
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ipatasertib<br>Participants will receive one 100 milligram (mg) ipatasertib tablet orally on Day 1 of treatment in treatment period 1 followed by two 100 mg itraconazole capsules orally on Days 15 to 23 along with one 100 mg of ipatasertib on Day 19 in treatment period 2. Both the treatment period will be separated by a washout period of 14 days. | Drug: Ipatasertib<br>* Ipatasertib 100 mg tablet orally once daily.<br>Drug: Itraconazole<br>* Itraconazole 100 mg capsules orally once daily.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of ipatasertib and its Metabolite (G-037720) | Cmax is the maximum observed concentration. | Pre-dose, 0.167, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1 and 19; 168, 192 hours post dose on Day 19 |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Ipatasertib and its Metabolite (G-037720) | AUC(0-inf) is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of a drug over time. | Pre-dose, 0.167, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1 and 19; 168, 192 hours post dose on Day 19 |
| Area Under the Plasma Concentration-Time Curve From Hour 0 to the Last Measureable Concentration (AUC0-t) of Ipatasertib and its Metabolite (G-037720) | Area Under the Plasma Concentration-Time Curve From Hour 0 to the Last Measureable Concentration (AUC0-t) will be reported. | Pre-dose, 0.167, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1 and 19; 168, 192 hours post dose on Day 19 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced at Least 1 Adverse Event | An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. | Up to 28 days after the last dose of the study drug (approximately up to 51 days) |
|
||
NCT02445508
|
Effect of Bile Acid Secretion and Sequestration on GLP-1 Secretion
|
Accumulating evidence suggests that bile acids in our intestines may constitute essential components in the complex mechanisms regulating gut hormone secretion and glucose homeostasis. Thus, it is likely that modification of the enterohepatic circulation of bile acids can lead to changes in gut hormone secretion and consequently affect glucose homeostasis.~The current study is a human interventional randomized controlled cross-over study including four study days for each participant. As a tool to sequester bile acids we will use sevelamer, a phosphate binding resin used in the treatment of hyperphosphataemia in adult patients with chronic kidney disease. Surprisingly, sevelamer has been shown to improve glycaemic control in patients with chronic kidney disease and type 2 diabetes. Intravenous infusion of cholecystokinin will be used to elicit gallbladder contraction and emptying. The aim is to examine how (and if) bile acid sequestration can influence postprandial glucagon-like peptide-1 (GLP-1) secretion and glucose homeostasis in patients with type 2 diabetes.~The investigators hypothesize that higher luminal concentrations of bile acids in the distal gut will elicit changes in gut hormone secretion. The current study will help to clarify this hypothesis and improve our general understanding of the association between bile acid circulation and signalling, gut hormone secretion and glucose metabolism.
|
Effect of Bile Acid Secretion and Sequestration on GLP-1 Secretion
|
Diabetes Mellitus, Type 2
|
* Drug: Sevelamer
* Drug: Cholecystokinin
* Drug: Sevelamer placebo
* Drug: Isotonic saline
|
Inclusion Criteria:~Type 2 diabetes for at least 3 months (diagnosed according to the criteria of the World Health Organization (WHO))~Men and postmenopausal women~Metformin applied as the only anti-diabetic drug~Caucasian ethnicity~Normal haemoglobin~Age above 40 years and below 70 years~BMI >23 kg/m2 and <35 kg/m2~Informed and written consent~Exclusion Criteria:~Liver disease (alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary disorder~Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major intra-abdominal surgery~Nephropathy (serum creatinine >150 µM and/or albuminuria)~Hypo- and hyperthyroidism~Hypo- and hypercalcaemia~Hypo- and hyperphosphataemia~Active or recent malignant disease~Treatment with medicine that cannot be paused for 12 hours~Treatment with oral anticoagulants~Any treatment or condition requiring acute or sub-acute medical or surgical intervention~Any condition considered incompatible with participation by the investigators
|
40 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucagon-like peptide-1 (GLP-1): Incremental and total area under the Concentration-Time Curve | Incremental and total area under the Concentration-Time Curve (AUC 0-240 min) | -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responses of various other gut hormones: Incremental and total area under the Concentration-Time Curve | Incremental and total area under the Concentration-Time Curve (AUC 0-240 min) | -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4 |
| Blood analysis of paracetamol as an assessment of gastric emptying | Assessment of gastric emptying | -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4 |
| Indirect calorimetry: Basal metabolic rate | Basal metabolic rate | -30 min to 240 min |
| Gallbladder volume as assessed by Ultrasound measurements | Gallbladder volume | -30 min to 240 min |
| Appetite as assessed by Visual analog scale score | Appetite | -30 min to 240 min |
|
Sequestering Agents, Molecular Mechanisms of Pharmacological Action, Cholecystokinin, Sevelamer, Chelating Agents, Cholagogues and Choleretics, Gastrointestinal Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo+Placebo<br>Oral ingestion of sevelamer placebo powder combined with intravenous infusion of isotonic saline. | Drug: Sevelamer placebo<br> <br> Drug: Isotonic saline<br> <br> |
| Active Comparator: Placebo+Cholecystokinin<br>Oral ingestion of sevelamer placebo powder combined with intravenous infusion of cholecystokinin. | Drug: Cholecystokinin<br> <br> Drug: Sevelamer placebo<br> <br> |
| Active Comparator: Sevelamer+Placebo<br>Oral ingestion of sevelamer powder combined with intravenous infusion of isotonic saline. | Drug: Sevelamer<br> <br> Drug: Isotonic saline<br> <br> |
| Active Comparator: Sevelamer+Cholecystokinin<br>Oral ingestion of sevelamer powder combined with intravenous infusion of cholecystokinin. | Drug: Sevelamer<br> <br> Drug: Cholecystokinin<br> <br> |
|
Effect of Bile Acid Secretion and Sequestration on GLP-1 Secretion
Study Overview
=================
Brief Summary
-----------------
Accumulating evidence suggests that bile acids in our intestines may constitute essential components in the complex mechanisms regulating gut hormone secretion and glucose homeostasis. Thus, it is likely that modification of the enterohepatic circulation of bile acids can lead to changes in gut hormone secretion and consequently affect glucose homeostasis. The current study is a human interventional randomized controlled cross-over study including four study days for each participant. As a tool to sequester bile acids we will use sevelamer, a phosphate binding resin used in the treatment of hyperphosphataemia in adult patients with chronic kidney disease. Surprisingly, sevelamer has been shown to improve glycaemic control in patients with chronic kidney disease and type 2 diabetes. Intravenous infusion of cholecystokinin will be used to elicit gallbladder contraction and emptying. The aim is to examine how (and if) bile acid sequestration can influence postprandial glucagon-like peptide-1 (GLP-1) secretion and glucose homeostasis in patients with type 2 diabetes. The investigators hypothesize that higher luminal concentrations of bile acids in the distal gut will elicit changes in gut hormone secretion. The current study will help to clarify this hypothesis and improve our general understanding of the association between bile acid circulation and signalling, gut hormone secretion and glucose metabolism.
Official Title
-----------------
Effect of Bile Acid Secretion and Sequestration on GLP-1 Secretion
Conditions
-----------------
Diabetes Mellitus, Type 2
Intervention / Treatment
-----------------
* Drug: Sevelamer
* Drug: Cholecystokinin
* Drug: Sevelamer placebo
* Drug: Isotonic saline
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Type 2 diabetes for at least 3 months (diagnosed according to the criteria of the World Health Organization (WHO)) Men and postmenopausal women Metformin applied as the only anti-diabetic drug Caucasian ethnicity Normal haemoglobin Age above 40 years and below 70 years BMI >23 kg/m2 and <35 kg/m2 Informed and written consent Exclusion Criteria: Liver disease (alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary disorder Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major intra-abdominal surgery Nephropathy (serum creatinine >150 µM and/or albuminuria) Hypo- and hyperthyroidism Hypo- and hypercalcaemia Hypo- and hyperphosphataemia Active or recent malignant disease Treatment with medicine that cannot be paused for 12 hours Treatment with oral anticoagulants Any treatment or condition requiring acute or sub-acute medical or surgical intervention Any condition considered incompatible with participation by the investigators
Ages Eligible for Study
-----------------
Minimum Age: 40 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo+Placebo<br>Oral ingestion of sevelamer placebo powder combined with intravenous infusion of isotonic saline. | Drug: Sevelamer placebo<br> <br> Drug: Isotonic saline<br> <br> |
| Active Comparator: Placebo+Cholecystokinin<br>Oral ingestion of sevelamer placebo powder combined with intravenous infusion of cholecystokinin. | Drug: Cholecystokinin<br> <br> Drug: Sevelamer placebo<br> <br> |
| Active Comparator: Sevelamer+Placebo<br>Oral ingestion of sevelamer powder combined with intravenous infusion of isotonic saline. | Drug: Sevelamer<br> <br> Drug: Isotonic saline<br> <br> |
| Active Comparator: Sevelamer+Cholecystokinin<br>Oral ingestion of sevelamer powder combined with intravenous infusion of cholecystokinin. | Drug: Sevelamer<br> <br> Drug: Cholecystokinin<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucagon-like peptide-1 (GLP-1): Incremental and total area under the Concentration-Time Curve | Incremental and total area under the Concentration-Time Curve (AUC 0-240 min) | -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responses of various other gut hormones: Incremental and total area under the Concentration-Time Curve | Incremental and total area under the Concentration-Time Curve (AUC 0-240 min) | -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4 |
| Blood analysis of paracetamol as an assessment of gastric emptying | Assessment of gastric emptying | -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1-4 |
| Indirect calorimetry: Basal metabolic rate | Basal metabolic rate | -30 min to 240 min |
| Gallbladder volume as assessed by Ultrasound measurements | Gallbladder volume | -30 min to 240 min |
| Appetite as assessed by Visual analog scale score | Appetite | -30 min to 240 min |
|
||
NCT04663438
|
Real World Study of Efficacy and Safety of Atezolizumab Plus Chemotherapy in Chinese Patients With ES-SCLC
|
The study is a prospective,multi-center,single arm,real world study to evaluate safety and performance of Atezolizumab plus chemotherapy in patients with extensive-stage small-cell lung cancer,and also to explore potential biomarkers for Immune-related Adverse Events.
|
In 2018,the results of IMpower 133 were reported on WCLC.Meanwhile,the data was published in NEJM.Atezolizumab combined with carboplatin and etoposide for extensive stage small cell lung cancer was recommended as the first by NCCN guidelines quickly.~Atezolizumab plus chemotherapy was approved by NMPA on Feb 13,2020,making Atezolizumab for 1L ES-SCLC in China.~Real world study can reflect the efficacy and safety of treatment in clinical practice.Based on the research of public database,the prospective cohort study had been reported,but the study based on Chinese patients still left weak point.
|
First-line Atezolizumab Plus Chemotherapy in Patients With Extensive-stage Small-cell Lung Cancer:a Real World,Single Arm,Multicenter,Prospective Study in China
|
Extensive-stage Small Cell Lung Cancer
|
* Drug: Chemotherapy Drugs, Cancer
|
Inclusion Criteria:~Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group [VALG] staging system)~No prior systemic treatment for ES-SCLC~18-80 years old, or more than 10 months of expected natural survival;~Eastern Cooperative Oncology Group performance status of 0 or 1 or 2~Measurable disease, as defined by RECIST v1.1 Adequate hematologic and end organ function~Treatment-free for at least 6 months since last chemo/radiotherapy, among those treated (with curative intent) with prior chemo/radiotherapy for limited-stage SCLC~The subject must be willing and able to participate in the study procedures and to understand and sign the informed consent~Exclusion Criteria:~Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab or 6 months after the final dose chemotherapy. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.~Patients or family members cannot understand the conditions and goals of this study.~The subject has an estimated life expectancy of less than 10 months The subject is unable or unwilling to comply with the study requirements or follow-up schedule
|
18 Years
|
80 Years
|
All
| null |
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Duration of overall survival | Baseline until death from any cause(up to approximately 23 months) |
| irAE | Percentage of participants with Immune-related | Baseline until up to 90 days after end of treatment(up to approximately 46 months) and related biomarkers |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Duration of Progression-Free Survival as assessed by the Investigator using Recist v1.1 | Baseline until PD or death,whichever occurs first(up to approximately 23months)] |
| Treatment related biomarkers | Biomarkers:CD 4+,CD28+,PD L1,TMB etc. | Baseline until PD or death,whichever occurs during this period(up to approximately 23months)] |
| Quality of Life (QL) | QL as assessed by using EORTC | Baseline until PD or death,whichever occurs during this period(up to approximately 23months)] |
| ) Score | QLQ C30 Score and EORTC QLQ Lung cancer module (LC13)Score | Baseline until PD or death,whichever occurs during this period(up to approximately 23months)] |
|
1L ES-SCLC
|
Antineoplastic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Arm A<br>200/Atezolizumab combined with EC regimen Atezolizumab:1200 mg Q3w | Drug: Chemotherapy Drugs, Cancer<br>* Other chemotherapy:Irinotecan;topotecan;Enrotinib;Bevacil<br>|
| Arm B<br>100/Atezolizumab combined with chemotherapy Atezolizumab:1200mg Q3w | Drug: Chemotherapy Drugs, Cancer<br>* Other chemotherapy:Irinotecan;topotecan;Enrotinib;Bevacil<br>|
|
Real World Study of Efficacy and Safety of Atezolizumab Plus Chemotherapy in Chinese Patients With ES-SCLC
Study Overview
=================
Brief Summary
-----------------
The study is a prospective,multi-center,single arm,real world study to evaluate safety and performance of Atezolizumab plus chemotherapy in patients with extensive-stage small-cell lung cancer,and also to explore potential biomarkers for Immune-related Adverse Events.
Detailed Description
-----------------
In 2018,the results of IMpower 133 were reported on WCLC.Meanwhile,the data was published in NEJM.Atezolizumab combined with carboplatin and etoposide for extensive stage small cell lung cancer was recommended as the first by NCCN guidelines quickly. Atezolizumab plus chemotherapy was approved by NMPA on Feb 13,2020,making Atezolizumab for 1L ES-SCLC in China. Real world study can reflect the efficacy and safety of treatment in clinical practice.Based on the research of public database,the prospective cohort study had been reported,but the study based on Chinese patients still left weak point.
Official Title
-----------------
First-line Atezolizumab Plus Chemotherapy in Patients With Extensive-stage Small-cell Lung Cancer:a Real World,Single Arm,Multicenter,Prospective Study in China
Conditions
-----------------
Extensive-stage Small Cell Lung Cancer
Intervention / Treatment
-----------------
* Drug: Chemotherapy Drugs, Cancer
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group [VALG] staging system) No prior systemic treatment for ES-SCLC 18-80 years old, or more than 10 months of expected natural survival; Eastern Cooperative Oncology Group performance status of 0 or 1 or 2 Measurable disease, as defined by RECIST v1.1 Adequate hematologic and end organ function Treatment-free for at least 6 months since last chemo/radiotherapy, among those treated (with curative intent) with prior chemo/radiotherapy for limited-stage SCLC The subject must be willing and able to participate in the study procedures and to understand and sign the informed consent Exclusion Criteria: Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab or 6 months after the final dose chemotherapy. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment. Patients or family members cannot understand the conditions and goals of this study. The subject has an estimated life expectancy of less than 10 months The subject is unable or unwilling to comply with the study requirements or follow-up schedule
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years
Sexes Eligible for Study
-----------------
All
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Arm A<br>200/Atezolizumab combined with EC regimen Atezolizumab:1200 mg Q3w | Drug: Chemotherapy Drugs, Cancer<br>* Other chemotherapy:Irinotecan;topotecan;Enrotinib;Bevacil<br>|
| Arm B<br>100/Atezolizumab combined with chemotherapy Atezolizumab:1200mg Q3w | Drug: Chemotherapy Drugs, Cancer<br>* Other chemotherapy:Irinotecan;topotecan;Enrotinib;Bevacil<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Duration of overall survival | Baseline until death from any cause(up to approximately 23 months) |
| irAE | Percentage of participants with Immune-related | Baseline until up to 90 days after end of treatment(up to approximately 46 months) and related biomarkers |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Duration of Progression-Free Survival as assessed by the Investigator using Recist v1.1 | Baseline until PD or death,whichever occurs first(up to approximately 23months)] |
| Treatment related biomarkers | Biomarkers:CD 4+,CD28+,PD L1,TMB etc. | Baseline until PD or death,whichever occurs during this period(up to approximately 23months)] |
| Quality of Life (QL) | QL as assessed by using EORTC | Baseline until PD or death,whichever occurs during this period(up to approximately 23months)] |
| ) Score | QLQ C30 Score and EORTC QLQ Lung cancer module (LC13)Score | Baseline until PD or death,whichever occurs during this period(up to approximately 23months)] |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
1L ES-SCLC
|
|
NCT02738749
|
Sodium Channel Splicing in Heart Failure Trial (SOCS-HEFT) Prospective Study
|
Congestive heart failure (CHF) represents a major health care concern in the United States. Currently, risk stratification of sudden cardiac death and the need for implantable cardioverter-defibrillator (ICD) placement are essentially dependent upon assessment of left ventricular ejection fraction (LVEF). Nevertheless, the predictive value of LVEF is suboptimal, alternative testing for risk assessment for the development of sudden cardiac death in the heart failure population is desirable.~At the genome level, the investigator has focused on the role of SCN5A gene mutations in arrhythmogenesis. Lymphocyte SCN5A mRNA processing may serve as a surrogate marker to assess SCN5A function at the cardiac level and may correlated with arrhythmic risk in high risk populations. This study will determine if SCN5A variant levels are predictive of appropriate ICD therapies in patients with a newly implanted ICD.
|
Scientific Background and Significance Introduction~Congestive heart failure (CHF) represents a major health care concern in the United States. It has been estimated that approximately 5 million patients in the U.S. have CHF, and nearly 550,000 people are diagnosed with this disease annually. It is known that sudden cardiac death occurs more frequently in the setting of structural heart disease. Moreover, the risk for sudden cardiac death is 6 to 9 times greater in the heart failure population, and cardiac arrhythmias are perhaps the leading cause of death in CHF patients. Currently, both the American College of Cardiology and the American Heart Association endorse the placement of implantable cardioverter-defibrillators (ICDs) in patients with ischemic cardiomyopathy, reasonable life expectancy, and reduced ejection fraction below 40% (class I, level of evidence A). Additionally, placement of ICDs is recommended in non-ischemic cardiomyopathy patients who meet similar requirements with an ejection fraction of less than 35% (class I, level of evidence B). Despite these recommendations for primary prevention of sudden death by way of ICD implantation, more than half of the patients receiving a device are likely to not experience an arrhythmic event that necessitates ICD therapy delivery. ICD devices, on average, cost $20,000-50,000 exclusive of operative and follow up costs. Currently, risk stratification of sudden cardiac death and the need for ICD placement are essentially dependent upon assessment of left ventricular ejection fraction. Other methods employed for risk stratification are signal averaged electrocardiogram (ECG) and another electrocardiographic technique known as T-wave alternans. Although these methods are FDA approved for risk prediction of cardiac death, such techniques are not widely employed in the U.S. given equipment and personnel costs to implement them. Thus, alternative testing for risk assessment for the development of sudden cardiac death in the heart failure population is desirable.~Role of Sodium Channels and the SCN5A Gene~The cardiac voltage-gated sodium (Na+) channel, SCN5A, is the main channel generating current for electrical propagation in heart muscle and is the target of many antiarrhythmic drugs. Defective expression of the cardiac Na+ channel results in increased arrhythmic risk as evidenced by sudden death in the Brugada Syndrome. SCN5A mutations have also been implicated in the inherited long-QT syndrome, which can result in the development of the fatal dysrhythmias like ventricular fibrillation and torsades de pointes. Additionally, mutations in the SCN5A gene have also been proposed to exist and enhance risk for drug-induced dysrhythmias.~Many studies have been done to shed light on the role of this tetrodotoxin-insensitive sodium channel in disease states. It has been demonstrated that mutated sodium channels in dilated cardiomyopathy may function differently depending upon the specific mutation type of the principal Na+ channel. Specifically, Nguyen et al have demonstrated that these mutations may lead to changes in physiological function such as slower action potential rise time, enhanced late sodium current during steady state, or impaired inactivation. Additional mutations in the SCN5A gene have been linked to shifts in voltage dependence of Na+ channel inactivation in patients with idiopathic ventricular fibrillation. Prior research has suggested that decreased inactivation of late sodium currents may contribute to action potential prolongation. A different SCN5A gene abnormality has been shown to lead to decreased sodium current density and an positive shift in the cell membrane half-maximal activation potential. Therefore, mutations of the Na+ channel can cause altered channel behavior and arrhythmias.~Previous study showed that disruptions in sodium handling may result in change in calcium homeostasis via action of the Na+/Ca2+ exchanger. Overall, such changes in sodium current (INa) are likely to significantly contribute to arrhythmia in the setting of failing myocardium.~At the genome level, research has focused on the role of SCN5A gene mutations in arrhythmogenesis. Nevertheless, the investigators have recently described acquired defects in Na+ channel messenger RNA (mRNA) that result in reduced Na+ current and occur only in failing hearts. Three 3'-terminal SCN5A mRNA splicing variants were identified and characterized in failing human heart ventricles. Additional measurements suggested that the truncation mutants could cause electrical abnormalities severe enough to contribute to arrhythmic risk. Also, the investigators showed that lymphocytes process sodium channels similarly to cardiomyocytes. Thus, lymphocyte SCN5A mRNA processing may serve as a surrogate marker to assess SCN5A function at the cardiac level and may correlated with arrhythmic risk in high risk populations. This study will determine if SCN5A variant levels are predictive of appropriate ICD therapies in patients with a newly implanted ICD.
|
Sodium Channel Splicing in Heart Failure Trial (SOCS-HEFT) Prospective Study
|
Death, Sudden, Cardiac
|
* Device: Implantable cardioverter-defibrillator (ICD)
|
Inclusion Criteria:~All patients must be greater than 18 years of age.~All patients must be able to give informed consent.~Patients must receive an ICD within 10 days for primary prevention.~Exclusion Criteria:~Patients less than 18 years of age.~History of congenital heart disease.~History of congenital electrophysiological disorders like the long-QT syndrome or Brugada disease.~Patients have an ICD implanted for secondary prevention.~Patients taking immunosuppressive medications, have chronic infection, or have an acute or chronic inflammatory illness that might alter white cell mRNA expression.~Patients with any illness expected to result in death within 18 months of enrollment.~Patients with white blood cell dyscrasia or cancers.~Patients with end-stage renal disease (ESRD) on hemodialysis or peritoneal dialysis~Current illicit drug use.~Inability to give informed consent.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The levels of sodium channel splicing variants measured by gene expression that are related to arrhythmic events, change every 3 months from baseline to one 1 year after ICD therapy. | | baseline, 3-month, 6-month, 9-month, and 12-month after ICD therapy |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The levels of sodium channel splicing variants measured by gene expression that are related to the type of ICD implanted, change every 3 months from baseline to one 1 year after ICD therapy. | | baseline, 3-month, 6-month, 9-month, and 12-month after ICD therapy |
|
sudden cardiac death, sodium channel splicing variant
|
Heart Failure, Death, Sudden, Cardiac, Death, Sudden, Heart Diseases, Cardiovascular Diseases, Death, Pathologic Processes, Heart Arrest
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: ICD group<br>Adult patients with newly implanted ICD devices for primary prevention will be enrolled. At baseline, 3-, 6-, 9-, and 12-month followup visit, the medial information and blood samples will be collected. | Device: Implantable cardioverter-defibrillator (ICD)<br>* Patients with newly implanted implantable cardioverter-defibrillators (ICDs) for primary prevention will be enrolled.<br>|
|
Sodium Channel Splicing in Heart Failure Trial (SOCS-HEFT) Prospective Study
Study Overview
=================
Brief Summary
-----------------
Congestive heart failure (CHF) represents a major health care concern in the United States. Currently, risk stratification of sudden cardiac death and the need for implantable cardioverter-defibrillator (ICD) placement are essentially dependent upon assessment of left ventricular ejection fraction (LVEF). Nevertheless, the predictive value of LVEF is suboptimal, alternative testing for risk assessment for the development of sudden cardiac death in the heart failure population is desirable. At the genome level, the investigator has focused on the role of SCN5A gene mutations in arrhythmogenesis. Lymphocyte SCN5A mRNA processing may serve as a surrogate marker to assess SCN5A function at the cardiac level and may correlated with arrhythmic risk in high risk populations. This study will determine if SCN5A variant levels are predictive of appropriate ICD therapies in patients with a newly implanted ICD.
Detailed Description
-----------------
Scientific Background and Significance Introduction Congestive heart failure (CHF) represents a major health care concern in the United States. It has been estimated that approximately 5 million patients in the U.S. have CHF, and nearly 550,000 people are diagnosed with this disease annually. It is known that sudden cardiac death occurs more frequently in the setting of structural heart disease. Moreover, the risk for sudden cardiac death is 6 to 9 times greater in the heart failure population, and cardiac arrhythmias are perhaps the leading cause of death in CHF patients. Currently, both the American College of Cardiology and the American Heart Association endorse the placement of implantable cardioverter-defibrillators (ICDs) in patients with ischemic cardiomyopathy, reasonable life expectancy, and reduced ejection fraction below 40% (class I, level of evidence A). Additionally, placement of ICDs is recommended in non-ischemic cardiomyopathy patients who meet similar requirements with an ejection fraction of less than 35% (class I, level of evidence B). Despite these recommendations for primary prevention of sudden death by way of ICD implantation, more than half of the patients receiving a device are likely to not experience an arrhythmic event that necessitates ICD therapy delivery. ICD devices, on average, cost $20,000-50,000 exclusive of operative and follow up costs. Currently, risk stratification of sudden cardiac death and the need for ICD placement are essentially dependent upon assessment of left ventricular ejection fraction. Other methods employed for risk stratification are signal averaged electrocardiogram (ECG) and another electrocardiographic technique known as T-wave alternans. Although these methods are FDA approved for risk prediction of cardiac death, such techniques are not widely employed in the U.S. given equipment and personnel costs to implement them. Thus, alternative testing for risk assessment for the development of sudden cardiac death in the heart failure population is desirable. Role of Sodium Channels and the SCN5A Gene The cardiac voltage-gated sodium (Na+) channel, SCN5A, is the main channel generating current for electrical propagation in heart muscle and is the target of many antiarrhythmic drugs. Defective expression of the cardiac Na+ channel results in increased arrhythmic risk as evidenced by sudden death in the Brugada Syndrome. SCN5A mutations have also been implicated in the inherited long-QT syndrome, which can result in the development of the fatal dysrhythmias like ventricular fibrillation and torsades de pointes. Additionally, mutations in the SCN5A gene have also been proposed to exist and enhance risk for drug-induced dysrhythmias. Many studies have been done to shed light on the role of this tetrodotoxin-insensitive sodium channel in disease states. It has been demonstrated that mutated sodium channels in dilated cardiomyopathy may function differently depending upon the specific mutation type of the principal Na+ channel. Specifically, Nguyen et al have demonstrated that these mutations may lead to changes in physiological function such as slower action potential rise time, enhanced late sodium current during steady state, or impaired inactivation. Additional mutations in the SCN5A gene have been linked to shifts in voltage dependence of Na+ channel inactivation in patients with idiopathic ventricular fibrillation. Prior research has suggested that decreased inactivation of late sodium currents may contribute to action potential prolongation. A different SCN5A gene abnormality has been shown to lead to decreased sodium current density and an positive shift in the cell membrane half-maximal activation potential. Therefore, mutations of the Na+ channel can cause altered channel behavior and arrhythmias. Previous study showed that disruptions in sodium handling may result in change in calcium homeostasis via action of the Na+/Ca2+ exchanger. Overall, such changes in sodium current (INa) are likely to significantly contribute to arrhythmia in the setting of failing myocardium. At the genome level, research has focused on the role of SCN5A gene mutations in arrhythmogenesis. Nevertheless, the investigators have recently described acquired defects in Na+ channel messenger RNA (mRNA) that result in reduced Na+ current and occur only in failing hearts. Three 3'-terminal SCN5A mRNA splicing variants were identified and characterized in failing human heart ventricles. Additional measurements suggested that the truncation mutants could cause electrical abnormalities severe enough to contribute to arrhythmic risk. Also, the investigators showed that lymphocytes process sodium channels similarly to cardiomyocytes. Thus, lymphocyte SCN5A mRNA processing may serve as a surrogate marker to assess SCN5A function at the cardiac level and may correlated with arrhythmic risk in high risk populations. This study will determine if SCN5A variant levels are predictive of appropriate ICD therapies in patients with a newly implanted ICD.
Official Title
-----------------
Sodium Channel Splicing in Heart Failure Trial (SOCS-HEFT) Prospective Study
Conditions
-----------------
Death, Sudden, Cardiac
Intervention / Treatment
-----------------
* Device: Implantable cardioverter-defibrillator (ICD)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All patients must be greater than 18 years of age. All patients must be able to give informed consent. Patients must receive an ICD within 10 days for primary prevention. Exclusion Criteria: Patients less than 18 years of age. History of congenital heart disease. History of congenital electrophysiological disorders like the long-QT syndrome or Brugada disease. Patients have an ICD implanted for secondary prevention. Patients taking immunosuppressive medications, have chronic infection, or have an acute or chronic inflammatory illness that might alter white cell mRNA expression. Patients with any illness expected to result in death within 18 months of enrollment. Patients with white blood cell dyscrasia or cancers. Patients with end-stage renal disease (ESRD) on hemodialysis or peritoneal dialysis Current illicit drug use. Inability to give informed consent.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: ICD group<br>Adult patients with newly implanted ICD devices for primary prevention will be enrolled. At baseline, 3-, 6-, 9-, and 12-month followup visit, the medial information and blood samples will be collected. | Device: Implantable cardioverter-defibrillator (ICD)<br>* Patients with newly implanted implantable cardioverter-defibrillators (ICDs) for primary prevention will be enrolled.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The levels of sodium channel splicing variants measured by gene expression that are related to arrhythmic events, change every 3 months from baseline to one 1 year after ICD therapy. | | baseline, 3-month, 6-month, 9-month, and 12-month after ICD therapy |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The levels of sodium channel splicing variants measured by gene expression that are related to the type of ICD implanted, change every 3 months from baseline to one 1 year after ICD therapy. | | baseline, 3-month, 6-month, 9-month, and 12-month after ICD therapy |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
sudden cardiac death, sodium channel splicing variant
|
NCT01766375
|
the Effects and Safety of Idarubicin-strengthened Pretreatment Program and Conventional Busulfan Cyclophosphamide Pretreatment Program on High-risk Acute Myeloid Leukemia Patient
|
This study was a multi-center, open, randomized-control study on the effects and safety of idarubicin 60mg/M2 combined with BUCY pretreatment program or BUCY pretreatment program on the overall survival rate and disease-free survival rate of acute myeloid leukemia patient in high-risk group over a period of 2 years.
|
This study was a multi-center, open, randomized-control study. It evaluates the effects and safety of idarubicin 60mg/M2 combined with BUCY pretreatment program or BUCY pretreatment program on acute myeloid leukemia patient in high-risk group. 200 patients were studied with 100 patients in each group.~Patients enrolled were randomly divided into group A (idarubicin 60mg/M2 combined with BUCY group) and group B (BUCY group). SAS randomization software was used to obtain randomization numbers. Patients were recommend to start pretreatment within 7 days after randomization.~Main objective: 2-year overall survival (OS) and disease-free survival (DFS) rates.~Secondary objective: safety evaluation (early complications of transplantation, liver, kidney and heart toxicity, treatment-related mortality, blood recovery time), the median period of disease-free survival.~Test drugs Idarubicin (Zavedos ®, Pfizer), busulfan, cyclophosphamide.~Pretreatment plan Drug Group A (IDA 60mg/M2 + BUCY) Group B (BUCY) IDA: 20mg/m2 a day, d-12 ~d-10, intravenous infusion for 1 hour. BU: 4mg/Kg a day, oral administration, d-7 ~d-4, or 3.2mg/Kg a day, intravenous infusion, d-7~d-4.~CY: 60mg/Kg a day, intravenous infusion, d-3~d-2. GVHD prevention plan GVHD is prevented by CSA+MMF+MTX in sibling allogeneic hematopoietic stem cell transplantation (starting from day -1, 3mg/kg of CSA was infused by continuous intravenous drip until gastrointestinal function returned normal when method of administration was changed to oral administration. 5mg/kg was divided into twice oral intakes, maintaining cyclosporine concentration at 200-300ug / L; MTX 15mg/m2 at day +1, 10mg/m2 at day +3, +6 and day +11 (based on actual situations day 11 can be omitted); MMF 0.25g BID starting from day 0 and continued for a month ). Unrelated allogeneic hematopoietic stem cell transplantation used CSA MMF MTX ATG for the prevention of GVHD. 3mg/kg CSA was infused through continuous intravenous drip since day -1 until gastrointestinal function returned to normal when the administration method was changed to oral. 5mg/kg was divided to twice oral intakes maintaining cyclosporine concentrations at 200-300ug/L; MTX 15mg/m2, at day +1, 10mg/m2 at day +3, day +6 and day +11 (based on actual situations day 11 can be omitted); MMF 0.5g BID starting from day 0 and continued for 3 months (a month later, dose can be reduced according to the hemogram); the total ATG was 6mg/kg and was taken in three days, from day -4 to day -2.~Relapse intervention Routine preventive DLI is not recommended, however, if tendency of recurrence found during monitor, chemotherapy, immunotherapy, targeted therapy, secondary transplantation, etc. can be used, and intervention treatment start time should be recorded as the end time.~The efficacy evaluation time point~1-3, 6, 12, 18, 24 months after transplantation.~Follow-up evaluation: indicators such as blood routines and bone marrow detection, and minimal residual disease detection after the end of treatment should be done regularly.
|
A Multi-center, Open, Randomized-control Study to Compare the Effects and Safety of Idarubicin-strengthened Pretreatment Program and Conventional Busulfan Cyclophosphamide Pretreatment Program on High-risk Acute Myeloid Leukemia Patient
|
Acute Myeloid Leukemia
|
* Drug: Cyclosporin A,mycophenolate mofetil,Methotrexate
|
Inclusion Criteria:~Age: 18～50;~Received peripheral blood hematopoietic stem cell transplantation from siblings or unrelated allogeneic donors with identical matching of HLA or 1 alleles mismatched.~Diagnosis: refer to 2011 edition of AML China Guideline for the diagnosis and treatment and diagnosis standards of high-risk acute myeloid leukemia developed through literatures (see Appendix B);~Under general condition, ECOG score ≤ 1;~Normal cardiac functions;~Normal liver and renal function: blood bilirubin≤35 μ mol\/L, AST/ALT lower than twice in the upper limit of normal value, serum creatinine≤ 150 μ mol\/L;~Subjects have signed the informed consent form.~Exclusion Criteria:~Severe uncontrolled infection before transplantation;~With contraindications of idarubicin;~Reached the maximum cumulative dose of anthracyclines, for instance, DNR≥ 450mg/m2, mitoxantrone≥140mg/m2, the total cumulative dose of idarubicin≥ 300mg/m2;~The other conditions that do not meet the inclusion criteria.~Withdrawal criteria:~Those do not meet the inclusion criteria or meet the exclusion criteria after reviewing;~Patient withdraws the informed consent form;~Patient violates the clinical study protocol;~Patient experiences severe adverse events that treatment has to be terminated;~Patient that considered no longer fit to complete clinical trials by researchers.
|
18 Years
|
50 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year disease-free survival (DFS) rates | The purpose of this study is to evaluates the effects of idarubicin 60mg/M2 combined with BUCY pretreatment program or BUCY pretreatment program on acute myeloid leukemia patient in high-risk group. | 4 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year overall survival (OS) rates | It evaluates the effects of idarubicin 60mg/M2 combined with BUCY pretreatment program or BUCY pretreatment program on acute myeloid leukemia patient in high-risk group. 200 patients were studied with 100 patients in each group | 4 years |
|
idarubicin, busulfan, cyclophosphamide, pretreatment, high-risk acute myeloid leukemia patient
|
Antimetabolites, Cyclosporine, Mycophenolic Acid, Methotrexate, Cyclosporins, Abortifacient Agents, Nonsteroidal, Abortifacient Agents, Reproductive Control Agents, Physiological Effects of Drugs, Antimetabolites, Antineoplastic, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents, Dermatologic Agents, Enzyme Inhibitors, Folic Acid Antagonists, Immunosuppressive Agents, Immunologic Factors, Antirheumatic Agents, Nucleic Acid Synthesis Inhibitors, Antifungal Agents, Anti-Infective Agents, Calcineurin Inhibitors, Antibiotics, Antineoplastic, Antibiotics, Antitubercular, Antitubercular Agents, Anti-Bacterial Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IDBUCY<br>Idarubicin: 20mg/m2 a day, d-12 ~d-10, intravenous infusion for 1 hour. Busulfan: 4mg/Kg a day, oral administration, d-7 ~d-4, or 3.2mg/Kg a day, intravenous infusion, d-7~d-4.~cyclophosphamide: 60mg/Kg a day, intravenous infusion, d-3~d-2. | Drug: Cyclosporin A,mycophenolate mofetil,Methotrexate<br>* GVHD is prevented by CSA+MMF+MTX in sibling allogeneic hematopoietic stem cell transplantation (starting from day -1, 3mg/kg of CSA was infused by continuous intravenous drip until gastrointestinal function returned normal when method of administration was changed to oral administration.<br>|
| Active Comparator: BUCY<br>Busulfan: 4mg/Kg a day, oral administration, d-7 ~d-4, or 3.2mg/Kg a day, intravenous infusion, d-7~d-4.~Cyclophosphamide: 60mg/Kg a day, intravenous infusion, d-3~d-2. | Drug: Cyclosporin A,mycophenolate mofetil,Methotrexate<br>* GVHD is prevented by CSA+MMF+MTX in sibling allogeneic hematopoietic stem cell transplantation (starting from day -1, 3mg/kg of CSA was infused by continuous intravenous drip until gastrointestinal function returned normal when method of administration was changed to oral administration.<br>|
|
the Effects and Safety of Idarubicin-strengthened Pretreatment Program and Conventional Busulfan Cyclophosphamide Pretreatment Program on High-risk Acute Myeloid Leukemia Patient
Study Overview
=================
Brief Summary
-----------------
This study was a multi-center, open, randomized-control study on the effects and safety of idarubicin 60mg/M2 combined with BUCY pretreatment program or BUCY pretreatment program on the overall survival rate and disease-free survival rate of acute myeloid leukemia patient in high-risk group over a period of 2 years.
Detailed Description
-----------------
This study was a multi-center, open, randomized-control study. It evaluates the effects and safety of idarubicin 60mg/M2 combined with BUCY pretreatment program or BUCY pretreatment program on acute myeloid leukemia patient in high-risk group. 200 patients were studied with 100 patients in each group. Patients enrolled were randomly divided into group A (idarubicin 60mg/M2 combined with BUCY group) and group B (BUCY group). SAS randomization software was used to obtain randomization numbers. Patients were recommend to start pretreatment within 7 days after randomization. Main objective: 2-year overall survival (OS) and disease-free survival (DFS) rates. Secondary objective: safety evaluation (early complications of transplantation, liver, kidney and heart toxicity, treatment-related mortality, blood recovery time), the median period of disease-free survival. Test drugs Idarubicin (Zavedos ®, Pfizer), busulfan, cyclophosphamide. Pretreatment plan Drug Group A (IDA 60mg/M2 + BUCY) Group B (BUCY) IDA: 20mg/m2 a day, d-12 d-10, intravenous infusion for 1 hour. BU: 4mg/Kg a day, oral administration, d-7 d-4, or 3.2mg/Kg a day, intravenous infusion, d-7 d-4. CY: 60mg/Kg a day, intravenous infusion, d-3 d-2. GVHD prevention plan GVHD is prevented by CSA+MMF+MTX in sibling allogeneic hematopoietic stem cell transplantation (starting from day -1, 3mg/kg of CSA was infused by continuous intravenous drip until gastrointestinal function returned normal when method of administration was changed to oral administration. 5mg/kg was divided into twice oral intakes, maintaining cyclosporine concentration at 200-300ug / L; MTX 15mg/m2 at day +1, 10mg/m2 at day +3, +6 and day +11 (based on actual situations day 11 can be omitted); MMF 0.25g BID starting from day 0 and continued for a month ). Unrelated allogeneic hematopoietic stem cell transplantation used CSA MMF MTX ATG for the prevention of GVHD. 3mg/kg CSA was infused through continuous intravenous drip since day -1 until gastrointestinal function returned to normal when the administration method was changed to oral. 5mg/kg was divided to twice oral intakes maintaining cyclosporine concentrations at 200-300ug/L; MTX 15mg/m2, at day +1, 10mg/m2 at day +3, day +6 and day +11 (based on actual situations day 11 can be omitted); MMF 0.5g BID starting from day 0 and continued for 3 months (a month later, dose can be reduced according to the hemogram); the total ATG was 6mg/kg and was taken in three days, from day -4 to day -2. Relapse intervention Routine preventive DLI is not recommended, however, if tendency of recurrence found during monitor, chemotherapy, immunotherapy, targeted therapy, secondary transplantation, etc. can be used, and intervention treatment start time should be recorded as the end time. The efficacy evaluation time point 1-3, 6, 12, 18, 24 months after transplantation. Follow-up evaluation: indicators such as blood routines and bone marrow detection, and minimal residual disease detection after the end of treatment should be done regularly.
Official Title
-----------------
A Multi-center, Open, Randomized-control Study to Compare the Effects and Safety of Idarubicin-strengthened Pretreatment Program and Conventional Busulfan Cyclophosphamide Pretreatment Program on High-risk Acute Myeloid Leukemia Patient
Conditions
-----------------
Acute Myeloid Leukemia
Intervention / Treatment
-----------------
* Drug: Cyclosporin A,mycophenolate mofetil,Methotrexate
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age: 18～50; Received peripheral blood hematopoietic stem cell transplantation from siblings or unrelated allogeneic donors with identical matching of HLA or 1 alleles mismatched. Diagnosis: refer to 2011 edition of AML China Guideline for the diagnosis and treatment and diagnosis standards of high-risk acute myeloid leukemia developed through literatures (see Appendix B); Under general condition, ECOG score ≤ 1; Normal cardiac functions; Normal liver and renal function: blood bilirubin≤35 μ mol\/L, AST/ALT lower than twice in the upper limit of normal value, serum creatinine≤ 150 μ mol\/L; Subjects have signed the informed consent form. Exclusion Criteria: Severe uncontrolled infection before transplantation; With contraindications of idarubicin; Reached the maximum cumulative dose of anthracyclines, for instance, DNR≥ 450mg/m2, mitoxantrone≥140mg/m2, the total cumulative dose of idarubicin≥ 300mg/m2; The other conditions that do not meet the inclusion criteria. Withdrawal criteria: Those do not meet the inclusion criteria or meet the exclusion criteria after reviewing; Patient withdraws the informed consent form; Patient violates the clinical study protocol; Patient experiences severe adverse events that treatment has to be terminated; Patient that considered no longer fit to complete clinical trials by researchers.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IDBUCY<br>Idarubicin: 20mg/m2 a day, d-12 d-10, intravenous infusion for 1 hour. Busulfan: 4mg/Kg a day, oral administration, d-7 d-4, or 3.2mg/Kg a day, intravenous infusion, d-7 d-4. cyclophosphamide: 60mg/Kg a day, intravenous infusion, d-3 d-2. | Drug: Cyclosporin A,mycophenolate mofetil,Methotrexate<br>* GVHD is prevented by CSA+MMF+MTX in sibling allogeneic hematopoietic stem cell transplantation (starting from day -1, 3mg/kg of CSA was infused by continuous intravenous drip until gastrointestinal function returned normal when method of administration was changed to oral administration.<br>|
| Active Comparator: BUCY<br>Busulfan: 4mg/Kg a day, oral administration, d-7 d-4, or 3.2mg/Kg a day, intravenous infusion, d-7 d-4. Cyclophosphamide: 60mg/Kg a day, intravenous infusion, d-3 d-2. | Drug: Cyclosporin A,mycophenolate mofetil,Methotrexate<br>* GVHD is prevented by CSA+MMF+MTX in sibling allogeneic hematopoietic stem cell transplantation (starting from day -1, 3mg/kg of CSA was infused by continuous intravenous drip until gastrointestinal function returned normal when method of administration was changed to oral administration.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year disease-free survival (DFS) rates | The purpose of this study is to evaluates the effects of idarubicin 60mg/M2 combined with BUCY pretreatment program or BUCY pretreatment program on acute myeloid leukemia patient in high-risk group. | 4 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year overall survival (OS) rates | It evaluates the effects of idarubicin 60mg/M2 combined with BUCY pretreatment program or BUCY pretreatment program on acute myeloid leukemia patient in high-risk group. 200 patients were studied with 100 patients in each group | 4 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
idarubicin, busulfan, cyclophosphamide, pretreatment, high-risk acute myeloid leukemia patient
|
NCT05202002
|
Decrease Type II Diabetes in Gestational Diabetes Population
|
The goal of the study is to examine the impact of an educational video on the rate of breastfeeding in mothers who had gestational diabetes mellitus, and the rate of type-II diabetes mellitus diagnosed postpartum.
|
Decreasing the Incidence of Post-partum Type II Diabetes Mellitus in Gestational Diabetes Population- Prospective Randomized Controlled Trial
|
Gestational Diabetes, Diabetes Mellitus, Type 2, Breastfeeding, Diabetes Mellitus, Type 1, Impaired Glucose Tolerance
|
* Behavioral: Video clip
* Behavioral: No video clip
|
Inclusion Criteria:~Pregnant individuals aged over 18 years old~Diagnosed with Gestational Diabetes Mellitus (GDM) by 100gm oral glucose tolerance test (OGTT) done between week 24-28 of gestation, or by other criteria (50gm glucose challenge test (GCT) >200 mg/dl22 or having one abnormal value in OGTT )~Having pregestational diabetes (DM-I or DM-II)~Can read and understand Hebrew~Exclusion Criteria:~Delivery of a non-viable fetus
|
18 Years
| null |
Female
|
Accepts Healthy Volunteers
|
Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of type II Diabetes Mellitus (DM) diagnosis, as diagnosed by the 75gm oral glucose tolerance test (OGTT) | Participants are requested to perform 75gm oral glucose tolerance test (OGTT) postpartum, as a screening test for type I diabetes mellitus. We will record the results and compare between groups | A phone call at 6 weeks postpartum. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of OGTT performance | Determination the actual performance of the test | A phone call at 6 weeks postpartum. |
| Rate of impaired glucose tolerance (IGT) | Similar to primary outcome | A phone call at 6 weeks postpartum. |
| Rate of exclusive breastfeeding | Participants will be asked by a phone cell, about feeding habits, including exclusive, partial and no breastfeeding of the infant | A phone call at 6 weeks postpartum. |
|
beta-Endorphin, Adrenocorticotropic Hormone, Melanocyte-Stimulating Hormones, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Educational video<br>Participants will receive an online video clip, explaining the benefits of breastfeeding. | Behavioral: Video clip<br>* After obtaining written informed consent, participants received a sealed envelope containing a preprinted paper referral to an online website, with a unique identifier.~After entering the online website, participants will be asked to enter the unique identifier they have received into a text box. Only those whose identifiers were predetermined to be associated with the intervention group will receive the intervention.~The intervention is twenty minutes long educational video clip, in which a brief discussion was presented, by an obstetrician, pediatrician, dietitian, and a breastfeeding consultant, each presenting the benefits of breastfeeding for mother and newborn.<br>* Other names: Intervention group;|
| Sham Comparator: Control group<br>Participants will not receive the video clip | Behavioral: No video clip<br>* Participants in this group will receive a unique identifier that belongs to the control group, thus no video clip will be displayed.<br>* Other names: Control group;|
|
Decrease Type II Diabetes in Gestational Diabetes Population
Study Overview
=================
Brief Summary
-----------------
The goal of the study is to examine the impact of an educational video on the rate of breastfeeding in mothers who had gestational diabetes mellitus, and the rate of type-II diabetes mellitus diagnosed postpartum.
Official Title
-----------------
Decreasing the Incidence of Post-partum Type II Diabetes Mellitus in Gestational Diabetes Population- Prospective Randomized Controlled Trial
Conditions
-----------------
Gestational Diabetes, Diabetes Mellitus, Type 2, Breastfeeding, Diabetes Mellitus, Type 1, Impaired Glucose Tolerance
Intervention / Treatment
-----------------
* Behavioral: Video clip
* Behavioral: No video clip
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pregnant individuals aged over 18 years old Diagnosed with Gestational Diabetes Mellitus (GDM) by 100gm oral glucose tolerance test (OGTT) done between week 24-28 of gestation, or by other criteria (50gm glucose challenge test (GCT) >200 mg/dl22 or having one abnormal value in OGTT ) Having pregestational diabetes (DM-I or DM-II) Can read and understand Hebrew Exclusion Criteria: Delivery of a non-viable fetus
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: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Educational video<br>Participants will receive an online video clip, explaining the benefits of breastfeeding. | Behavioral: Video clip<br>* After obtaining written informed consent, participants received a sealed envelope containing a preprinted paper referral to an online website, with a unique identifier. After entering the online website, participants will be asked to enter the unique identifier they have received into a text box. Only those whose identifiers were predetermined to be associated with the intervention group will receive the intervention. The intervention is twenty minutes long educational video clip, in which a brief discussion was presented, by an obstetrician, pediatrician, dietitian, and a breastfeeding consultant, each presenting the benefits of breastfeeding for mother and newborn.<br>* Other names: Intervention group;|
| Sham Comparator: Control group<br>Participants will not receive the video clip | Behavioral: No video clip<br>* Participants in this group will receive a unique identifier that belongs to the control group, thus no video clip will be displayed.<br>* Other names: Control group;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of type II Diabetes Mellitus (DM) diagnosis, as diagnosed by the 75gm oral glucose tolerance test (OGTT) | Participants are requested to perform 75gm oral glucose tolerance test (OGTT) postpartum, as a screening test for type I diabetes mellitus. We will record the results and compare between groups | A phone call at 6 weeks postpartum. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of OGTT performance | Determination the actual performance of the test | A phone call at 6 weeks postpartum. |
| Rate of impaired glucose tolerance (IGT) | Similar to primary outcome | A phone call at 6 weeks postpartum. |
| Rate of exclusive breastfeeding | Participants will be asked by a phone cell, about feeding habits, including exclusive, partial and no breastfeeding of the infant | A phone call at 6 weeks postpartum. |
|
||
NCT00310414
|
fMRI Studies of Task Specificity in Focal Hand Dystonia
|
This study will examine how the brain makes involuntary spasms and contractions in patients with focal hand dystonia (FHD). Patients with dystonia have muscle spasms that cause uncontrolled twisting and repetitive movement or abnormal postures. In FHD, only the hand is involved. The study will use functional magnetic resonance imaging (fMRI, see below) to study which areas of the brain are primarily affected in FHD and better understand how brain changes produce dystonia symptoms.~Normal right-handed volunteers and patients with FHD who are 18-65 years of age may be eligible for this study. Candidates are screened with a medical history and physical and neurological examinations. Women who can become pregnant have a urine pregnancy test.~All participants undergo fMRI. This test uses a strong magnetic field and radio waves to obtain images of body organs and tissues. The subject lies on a table that is moved into the scanner (a metal cylinder), wearing earplugs to muffle loud knocking and thumping sounds that occur during the scanning process. The procedure lasts about 90 minutes, during which time the patient is asked to lie still for 10-15 minutes at a time. During the procedure, subjects are asked to perform some tasks, including writing, tapping with their hand, and drawing in a zigzag motion. Each task is performed using the right hand, left hand and right foot.
|
Objective:~Writer's cramp, a form of focal hand dystonia, is the most frequently observed task specific dystonia. Symptoms of writer's cramp often appear as soon as the pen is picked up, or after a few words of writing. Patients with simple writer's cramp have difficulties writing, but carry out other tasks with the affected hand without spasms. Little is known about why the hand spasms when writing, while performing other tasks normally.~The purpose of this study is to identify brain areas of activation associated specifically with the task of handwriting with the dystonic hand, in patients with simple writer's cramp. Simple writer's cramp can be defined by a patient exhibiting the symptoms only when writing and symptoms are not present in any other task performance. Specifically for this study, patients should be able to write for 20 seconds consecutively in a run. We plan to use functional magnetic resonance imaging (fMRI) to identify the pattern of blood oxygenation level-dependent (BOLD) activation in the brain when different tasks are performed by different limbs in healthy volunteers and patients with focal hand dystonia.~Study Population:~This research will be conducted using 22 patients diagnosed with simple writer's cramp and 32 healthy volunteers matched for age and gender.~Design:~Using a block design in functional magnetic resonance imaging (fMRI), we will examine the brain activity of patients and healthy volunteers while they execute three tasks: writing, tapping and a zigzagging motion, with three separate limbs: the dystonic hand, the opposite hand, and the right foot.~Outcome Measures:~The changes in signal intensity of the brain activity correlated with the motor program (task of handwriting) and effector (dystonic hand) will be collected and analyzed.~The findings we expect to obtain with this experiment may contribute to basic knowledge of the linkage between task specificity and the dystonic hand, and may provide a better understanding of the pathophysiology of writer's cramp.
|
fMRI Studies of Task Specificity in Focal Hand Dystonia
|
Focal Dystonia
|
INCLUSION CRITERIA:~Focal Dystonia Subjects must be:~Right hand dominant~Between 18 and 65 years old~Diagnosed with mild, simple focal hand dystonia. For this study mild, simple focal hand dystonia suggests that the patient does not present symptoms when performing tasks other than writing. Additionally, the patient should be able to write for 20 seconds consecutively~Willing to abstain from alcohol 48 hours prior to the study~Volunteers must be:~Healthy right-handed dominant individuals~Between 18 and 65 years old~Willing to abstain from alcohol 48 hours prior to the study~EXCLUSION CRITERIA:~Subjects with implanted devices such as pacemakers, medication pumps or defibrillators, metal in the cranium except mouth, intracardiac lines, history of shrapnel injury or any other condition/device that may be contraindicated or prevent the acquisition of MRI~Subjects with any finding on the MRI safety questionnaire which prevents them from safely undergoing an MRI scan~Subjects who are pregnant.~Subjects with claustrophobia or other restrictions which prevent them from undergoing a scan in a confined space for up to 60 minutes~Subjects with any visual, motor, or hearing difficulties~Subjects with severe focal hand dystonia i.e., subjects who experience dystonic spasms in tasks other than/in addition to writing~Subjects with mirror dystonia~Subjects without the capacity to give consent~Subjects with any history of a severe medical condition, such as cardiovascular disease, which will prevent them from lying flat for up to 60 minutes.~Subjects with any history of brain tumor, stroke, head trauma or vascular malformation as obtained by history or from imaging studies.~Subjects who have had recent (within 3 months) Botulinum Toxin (Botox) injections.~Subjects who are on anti-parkinsonian drugs
|
18 Years
|
65 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
Imaging Studies, Botulinum Toxin, Writer's Cramp, Focal Hand Dystonia, FHD, Writer Cramp, Healthy Volunteer, HV
|
Dystonia, Dystonic Disorders, Dyskinesias, Neurologic Manifestations, Nervous System Diseases, Movement Disorders, Central Nervous System Diseases
|
fMRI Studies of Task Specificity in Focal Hand Dystonia
Study Overview
=================
Brief Summary
-----------------
This study will examine how the brain makes involuntary spasms and contractions in patients with focal hand dystonia (FHD). Patients with dystonia have muscle spasms that cause uncontrolled twisting and repetitive movement or abnormal postures. In FHD, only the hand is involved. The study will use functional magnetic resonance imaging (fMRI, see below) to study which areas of the brain are primarily affected in FHD and better understand how brain changes produce dystonia symptoms. Normal right-handed volunteers and patients with FHD who are 18-65 years of age may be eligible for this study. Candidates are screened with a medical history and physical and neurological examinations. Women who can become pregnant have a urine pregnancy test. All participants undergo fMRI. This test uses a strong magnetic field and radio waves to obtain images of body organs and tissues. The subject lies on a table that is moved into the scanner (a metal cylinder), wearing earplugs to muffle loud knocking and thumping sounds that occur during the scanning process. The procedure lasts about 90 minutes, during which time the patient is asked to lie still for 10-15 minutes at a time. During the procedure, subjects are asked to perform some tasks, including writing, tapping with their hand, and drawing in a zigzag motion. Each task is performed using the right hand, left hand and right foot.
Detailed Description
-----------------
Objective: Writer's cramp, a form of focal hand dystonia, is the most frequently observed task specific dystonia. Symptoms of writer's cramp often appear as soon as the pen is picked up, or after a few words of writing. Patients with simple writer's cramp have difficulties writing, but carry out other tasks with the affected hand without spasms. Little is known about why the hand spasms when writing, while performing other tasks normally. The purpose of this study is to identify brain areas of activation associated specifically with the task of handwriting with the dystonic hand, in patients with simple writer's cramp. Simple writer's cramp can be defined by a patient exhibiting the symptoms only when writing and symptoms are not present in any other task performance. Specifically for this study, patients should be able to write for 20 seconds consecutively in a run. We plan to use functional magnetic resonance imaging (fMRI) to identify the pattern of blood oxygenation level-dependent (BOLD) activation in the brain when different tasks are performed by different limbs in healthy volunteers and patients with focal hand dystonia. Study Population: This research will be conducted using 22 patients diagnosed with simple writer's cramp and 32 healthy volunteers matched for age and gender. Design: Using a block design in functional magnetic resonance imaging (fMRI), we will examine the brain activity of patients and healthy volunteers while they execute three tasks: writing, tapping and a zigzagging motion, with three separate limbs: the dystonic hand, the opposite hand, and the right foot. Outcome Measures: The changes in signal intensity of the brain activity correlated with the motor program (task of handwriting) and effector (dystonic hand) will be collected and analyzed. The findings we expect to obtain with this experiment may contribute to basic knowledge of the linkage between task specificity and the dystonic hand, and may provide a better understanding of the pathophysiology of writer's cramp.
Official Title
-----------------
fMRI Studies of Task Specificity in Focal Hand Dystonia
Conditions
-----------------
Focal Dystonia
Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITERIA: Focal Dystonia Subjects must be: Right hand dominant Between 18 and 65 years old Diagnosed with mild, simple focal hand dystonia. For this study mild, simple focal hand dystonia suggests that the patient does not present symptoms when performing tasks other than writing. Additionally, the patient should be able to write for 20 seconds consecutively Willing to abstain from alcohol 48 hours prior to the study Volunteers must be: Healthy right-handed dominant individuals Between 18 and 65 years old Willing to abstain from alcohol 48 hours prior to the study EXCLUSION CRITERIA: Subjects with implanted devices such as pacemakers, medication pumps or defibrillators, metal in the cranium except mouth, intracardiac lines, history of shrapnel injury or any other condition/device that may be contraindicated or prevent the acquisition of MRI Subjects with any finding on the MRI safety questionnaire which prevents them from safely undergoing an MRI scan Subjects who are pregnant. Subjects with claustrophobia or other restrictions which prevent them from undergoing a scan in a confined space for up to 60 minutes Subjects with any visual, motor, or hearing difficulties Subjects with severe focal hand dystonia i.e., subjects who experience dystonic spasms in tasks other than/in addition to writing Subjects with mirror dystonia Subjects without the capacity to give consent Subjects with any history of a severe medical condition, such as cardiovascular disease, which will prevent them from lying flat for up to 60 minutes. Subjects with any history of brain tumor, stroke, head trauma or vascular malformation as obtained by history or from imaging studies. Subjects who have had recent (within 3 months) Botulinum Toxin (Botox) injections. Subjects who are on anti-parkinsonian drugs
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?
-----------------
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
-----------------
Imaging Studies, Botulinum Toxin, Writer's Cramp, Focal Hand Dystonia, FHD, Writer Cramp, Healthy Volunteer, HV
|
||||
NCT00590239
|
Barrett's Esophagus Related Neoplasia (BERN) Project
|
The use of high resolution endoscopy (HRE), narrow band imaging (NBI) and chromoendoscopy increases the detection rates of Barrett's esophagus (BE) and early neoplasia.~Endoscopic mucosal resection (EMR) will improve the accuracy for detection of dysplasia/early neoplasia.~Specific Aim 1 - To create a video-atlas of non-dysplastic and dysplastic/early neoplastic lesions in patients with BE. This will be used for training purposes and to assess learning curve associated with these new technologies.~Specific Aim 2 - To create a standardized classification system for the mucosal and vascular patterns observed in patients with BE.~Specific Aim 3 - To determine the interobserver agreement using the video-atlas for the mucosal and vascular patterns classification agreed upon.~Specific Aim 4 - To determine the endoscopic detection rate of esophageal cancer or precancerous lesions removed during endoscopy.~Specific Aim 5 - To determine the pathologic and clinical outcomes of patients undergoing EMR/ablation; including morbidity, mortality and complications of the procedure.~Results to date (June 2008) : this study is active and open to enrollment. Currently 26 patients have enrolled in this study at the Kansas City VA medical center. In order to participate, patients must be eligible for care at the KCVA hospital.
|
B. BACKGROUND AND SIGNIFICANCE Burden of disease Barrett's esophagus (BE) is an acquired condition resulting from chronic gastroesophageal reflux disease and is a well recognized pre-malignant condition for the development of esophageal adenocarcinoma (EAC) (1, 2). BE is defined as the displacement of the squamocolumnar junction proximal to the gastroesophageal junction with the presence of intestinal metaplasia (15). This condition entails a 30 to 50 fold greater risk for the development of EAC and has an incidence of development of EAC that approaches 0.5% annually (3, 4). EAC is a highly lethal cancer and is the most rapidly increasing cancer in the United States and Western Europe with an incremental increase of 4-10% per year. Although survival rates have improved during the recent years in some countries, the overall 5-year survival rate is still a dismal 10% in most Western populations (5-7). Clinical strategies for preventing deaths from this cancer focus on techniques for identification of esophageal neoplasms in an asymptomatic, early, and curable stage. Therefore, endoscopic screening of subjects with chronic reflux symptoms has been recommended as a method of detecting BE and early cancer (8). Patients with BE are then routinely enrolled in surveillance programs in an attempt to identify those who might benefit from treatment at a pre-invasive stage of EAC with an ultimate aim of reducing cancer related deaths (8).~Limitations of current Barrett's surveillance protocol Current guidelines for surveillance include taking biopsy specimens from endoscopically visible mucosal abnormality followed by random 4-quadrant biopsies every 2 cm throughout the entire length of BE (15). Unfortunately, the effectiveness of this strategy is hampered by numerous factors. Apart from being labor intensive and time consuming for the patient; the accuracy of this protocol is limited by sampling errors. Biopsy specimens from short segments or tongues of columnar mucosa generally reveal intestinal metaplasia in only 40-60% of patients (16). In a study of 570 patients undergoing upper endoscopy, BE was suspected in 146 patients; however, only 60 patients had diagnosis confirmed by biopsy. Short segment BE (SSBE) was more frequently suspected than long segment BE (LSBE) but was correctly diagnosed only 25% of the time compared with 55% for LSBE (17). Similar to the distribution of the metaplastic tissue, the presence of dysplasia or early adenocarcinoma within a Barrett's segment is patchy and focal. Standard endoscopy and random biopsies might fail to detect these lesions. Early neoplastic lesions are not visible to the eye of the endoscopist at standard endoscopy and random biopsies sample only a small proportion of the epithelium at risk. Also, this hit and miss nature of biopsy increases the cost of the procedure and limits the reliability of histologic interpretation of dysplasia. The increasing use of endoscopy has led to more and more patients being diagnosed with BE and offered surveillance. Also, the number of patients being followed up, and to whom potentially curative therapy can be offered, have increased. The advent of newer methods of endoscopic treatment of high-grade dysplasia (HGD) and early EAC in the form of ablative therapy and EMR makes it highly desirable to diagnose dysplasia and EAC early in the disease process. This may help in alleviating the morbidity and mortality associated with esophagectomy for EAC. These compelling reasons coupled with the limitations of current surveillance protocols make the development of new approaches aimed at improving efficacy of Barrett's surveillance mandatory.~Novel imaging techniques and endoscopic therapies Significant effort has been expended on development of new GI techniques in order to provide a precise and even a real time endoscopic diagnosis. Chromoendoscopy is a technique that involves the application of agents to improve characterization of the mucosa resulting in selective uptake or enhancement of mucosal surface pattern (11). HRE units are equipped with charge-coupled devices with up to a million pixels that allow clear visualization of fine mucosal details which may facilitate the detection of early neoplastic lesions (9). NBI is a novel endoscopic technique that is based on the optical phenomenon that the depth of light penetration into tissues is dependent on the wavelength; the shorter the wavelength, the more superficial the penetration. Use of blue light with narrow band filters enables detailed imaging of the mucosal and vascular surface patterns within the BE segment with a high level of resolution and contrast without the need for chromoendoscopy. The main chromophore in esophageal tissues in the visible wavelength is hemoglobin, which has a maximum absorptive wavelength near 415 nm. This is within the wavelength for NBI and responsible for revealing the superficial vasculature (10).~Esophagectomy was considered as the criterion standard for treatment of patients with early EAC. However, it is associated with significant morbidity and mortality, even in experienced surgical hands and high-volume surgical centers. EMR has been used increasingly to replace surgery as a curative treatment modality for early EAC in patients with BE (12, 13). It allows effective local treatment of early cancer, histological analysis of all resected specimens and thus confirmation of diagnosis and complete resection of the lesion. Ablative therapies in BE patients have provided promising results as well (18, 19).~C. PRELIMINARY DATA Our group recently assessed the potential of NBI for the prediction of histology during screening and surveillance endoscopy in BE patients (10). Images obtained by this system were classified according to the mucosal (ridge/villous, circular, irregular/distorted) and vascular (normal, abnormal) patterns and correlated with histology in a prospective and blinded fashion. The sensitivity, specificity, and positive predictive value of the ridge/villous pattern for the diagnosis of intestinal metaplasia without high-grade dysplasia (HGD) were 93.5%, 87%, and 95% respectively. The sensitivity, specificity, and positive predictive value of the irregular/distorted patterns for HGD were 100%, 99%, and 95% respectively. These promising results have been validated by other investigators. Similarly, Dr. Sharma has published several studies involving the use of chromoendoscopy in patients with BE. In a study of 80 patients with columnar lined esophagus using indigo carmine dye and 115x magnification endoscopy, three mucosal patterns as stated above were identified. The presence of ridge/villous pattern for detecting intestinal metaplasia had high sensitivity, specificity, and positive predictive value (97%, 76%, and 92% respectively). Six patients had an irregular/distorted pattern and biopsies revealed HGD in all these patients (11). Our group has been active in evaluating the role of ablative therapies in patients with BE.~We recently assessed the long-term efficacy of achieving complete reversal (endoscopic and histologic) between multipolar electrocoagulation and argon plasma coagulation in patients with BE and assessed factors influencing successful ablation. A total of 35 BE patients were followed for at least 2 years following ablative therapy and complete reversal of BE was achieved in 70% of the patients, regardless of the ablative technique (19). The International Working Group on the Classification of Oesophagitis has been at the forefront for the classification and grading of acid-peptic related esophageal diseases such as erosive esophagitis and BE. Sharma et al developed and validated an endoscopic grading system for BE (Prague C & M criteria). The criteria includes assessment of the circumferential (C) and maximal (M) extent of the endoscopically visualized BE segment along with endoscopic landmarks. This grading system demonstrated a high validity for the endoscopic assessment of visualized BE lengths (20).~D. RESEARCH DESIGN AND METHODS Overview Patients with known / suspected BE Pre-registration, informed consent~Standard endoscopy followed by HRE, NBI and chromoendoscopy~Digital video-recording of endoscopy findings (Subsequent de-identification of all patient information)~Target biopsies of suspected lesions~Removal of abnormal lesions with EMR / mucosal ablation~Pathologist for histologic interpretation~This is a part of a multicenter study initiated at Kansas City. Patients will be recruited from Amsterdam, Mainz, Wiesbaden and Kansas City.~Methods Physical examination and questionnaire All patients will complete a validated GERD questionnaire (GERQ) (21) that records duration, severity, and frequency of heartburn and regurgitation with supplemental information on medications such as acid suppressive therapy, aspirin, NSAIDs, etc. Demographic information and clinical findings such as height, weight and waist circumference will be recorded .~Endoscopic procedure The endoscopic procedures will be performed with a high-resolution endoscope (Olympus GIF-Q240Z, GIF-Q160Z, or more recent versions) that has the capability of performing NBI with the push of a switch. Standard methods of conscious sedation and cardiopulmonary monitoring will be used during each procedure. The distal esophagus will be carefully inspected for the presence of erosions, nodules and plaques. The presence and size of hiatal hernia will be recorded. A plastic disposable distal attachment cap (e.g. Olympus D-201-11802) with a free distal distance of 2-3 mm will be attached to the endoscope in order to fix mucosal areas of interest until images and biopsies have been taken. The endoscopist will be blinded to the previous BE histology of the patient. The classification of mucosal and vascular patterns will be performed in a standardized manner into groups as described above. Details of endoscopy findings and digital video recordings will be entered into an endoscopy form .
|
Endoscopic Detection of Early Neoplasia in Patients With Barrett's Esophagus
|
Barrett's Esophagus, Neoplasms, Gastroesophageal Reflux
|
Inclusion Criteria:~18-80 years~Patients must be able to provide written informed consent~Patients referred for endoscopy for screening/surveillance of BE or for endoscopic treatment of BE with early mucosal neoplasia~Exclusion Criteria:~Current use of aspirin, non-steroidal anti-inflammatory agents(NSAIDs),or chronic anticoagulants that cannot be discontinued prior to the procedure.~Inability to provide written informed consent~Significant thrombocytopenia or coagulopathy~Any significant co-morbid condition that would prevent the safe administration of conscious sedation
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Video-atlas creation | To create a video-atlas of early neoplastic lesions in patients with BE. This will be used for training purposes and to assess learning curve associated with these new technologies. | March 2007 - June 2016 |
| Pathologic and Clinical Outcomes | To determine the pathologic and clinical outcomes of patients undergoing EMR / ablation; including morbidity, mortality and complications of the procedure. | 2007 - 2016 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interobserver agreement for the detection of early neoplasia | To determine the interobserver agreement using the video-atlas for the detection of early neoplasia. | 2015 - 2016 |
| Efficacy of endoscopic detection of early esophageal lesions | To determine the endoscopic detection rate of early neoplastic lesions by expert endoscopists, experienced endoscopists, and trainees. The endoscopist will be graded as 1.) Trainees (in fellowship training); 2.) Experienced endoscopist (<5 yrs of experience in esophageal diseases); 3.) Expert endoscopist (>5 yrs of experience in esophageal diseases). | 2007-2016 |
|
Barrett's Esophagus, Neoplasia, Endoscopic mucosal resection, High resolution endoscopy, Chromoendoscopy
|
Neoplasms, Barrett Esophagus, Gastroesophageal Reflux, Esophageal Motility Disorders, Deglutition Disorders, Esophageal Diseases, Gastrointestinal Diseases, Digestive System Diseases, Precancerous Conditions
|
Barrett's Esophagus Related Neoplasia (BERN) Project
Study Overview
=================
Brief Summary
-----------------
The use of high resolution endoscopy (HRE), narrow band imaging (NBI) and chromoendoscopy increases the detection rates of Barrett's esophagus (BE) and early neoplasia. Endoscopic mucosal resection (EMR) will improve the accuracy for detection of dysplasia/early neoplasia. Specific Aim 1 - To create a video-atlas of non-dysplastic and dysplastic/early neoplastic lesions in patients with BE. This will be used for training purposes and to assess learning curve associated with these new technologies. Specific Aim 2 - To create a standardized classification system for the mucosal and vascular patterns observed in patients with BE. Specific Aim 3 - To determine the interobserver agreement using the video-atlas for the mucosal and vascular patterns classification agreed upon. Specific Aim 4 - To determine the endoscopic detection rate of esophageal cancer or precancerous lesions removed during endoscopy. Specific Aim 5 - To determine the pathologic and clinical outcomes of patients undergoing EMR/ablation; including morbidity, mortality and complications of the procedure. Results to date (June 2008) : this study is active and open to enrollment. Currently 26 patients have enrolled in this study at the Kansas City VA medical center. In order to participate, patients must be eligible for care at the KCVA hospital.
Detailed Description
-----------------
B. BACKGROUND AND SIGNIFICANCE Burden of disease Barrett's esophagus (BE) is an acquired condition resulting from chronic gastroesophageal reflux disease and is a well recognized pre-malignant condition for the development of esophageal adenocarcinoma (EAC) (1, 2). BE is defined as the displacement of the squamocolumnar junction proximal to the gastroesophageal junction with the presence of intestinal metaplasia (15). This condition entails a 30 to 50 fold greater risk for the development of EAC and has an incidence of development of EAC that approaches 0.5% annually (3, 4). EAC is a highly lethal cancer and is the most rapidly increasing cancer in the United States and Western Europe with an incremental increase of 4-10% per year. Although survival rates have improved during the recent years in some countries, the overall 5-year survival rate is still a dismal 10% in most Western populations (5-7). Clinical strategies for preventing deaths from this cancer focus on techniques for identification of esophageal neoplasms in an asymptomatic, early, and curable stage. Therefore, endoscopic screening of subjects with chronic reflux symptoms has been recommended as a method of detecting BE and early cancer (8). Patients with BE are then routinely enrolled in surveillance programs in an attempt to identify those who might benefit from treatment at a pre-invasive stage of EAC with an ultimate aim of reducing cancer related deaths (8). Limitations of current Barrett's surveillance protocol Current guidelines for surveillance include taking biopsy specimens from endoscopically visible mucosal abnormality followed by random 4-quadrant biopsies every 2 cm throughout the entire length of BE (15). Unfortunately, the effectiveness of this strategy is hampered by numerous factors. Apart from being labor intensive and time consuming for the patient; the accuracy of this protocol is limited by sampling errors. Biopsy specimens from short segments or tongues of columnar mucosa generally reveal intestinal metaplasia in only 40-60% of patients (16). In a study of 570 patients undergoing upper endoscopy, BE was suspected in 146 patients; however, only 60 patients had diagnosis confirmed by biopsy. Short segment BE (SSBE) was more frequently suspected than long segment BE (LSBE) but was correctly diagnosed only 25% of the time compared with 55% for LSBE (17). Similar to the distribution of the metaplastic tissue, the presence of dysplasia or early adenocarcinoma within a Barrett's segment is patchy and focal. Standard endoscopy and random biopsies might fail to detect these lesions. Early neoplastic lesions are not visible to the eye of the endoscopist at standard endoscopy and random biopsies sample only a small proportion of the epithelium at risk. Also, this hit and miss nature of biopsy increases the cost of the procedure and limits the reliability of histologic interpretation of dysplasia. The increasing use of endoscopy has led to more and more patients being diagnosed with BE and offered surveillance. Also, the number of patients being followed up, and to whom potentially curative therapy can be offered, have increased. The advent of newer methods of endoscopic treatment of high-grade dysplasia (HGD) and early EAC in the form of ablative therapy and EMR makes it highly desirable to diagnose dysplasia and EAC early in the disease process. This may help in alleviating the morbidity and mortality associated with esophagectomy for EAC. These compelling reasons coupled with the limitations of current surveillance protocols make the development of new approaches aimed at improving efficacy of Barrett's surveillance mandatory. Novel imaging techniques and endoscopic therapies Significant effort has been expended on development of new GI techniques in order to provide a precise and even a real time endoscopic diagnosis. Chromoendoscopy is a technique that involves the application of agents to improve characterization of the mucosa resulting in selective uptake or enhancement of mucosal surface pattern (11). HRE units are equipped with charge-coupled devices with up to a million pixels that allow clear visualization of fine mucosal details which may facilitate the detection of early neoplastic lesions (9). NBI is a novel endoscopic technique that is based on the optical phenomenon that the depth of light penetration into tissues is dependent on the wavelength; the shorter the wavelength, the more superficial the penetration. Use of blue light with narrow band filters enables detailed imaging of the mucosal and vascular surface patterns within the BE segment with a high level of resolution and contrast without the need for chromoendoscopy. The main chromophore in esophageal tissues in the visible wavelength is hemoglobin, which has a maximum absorptive wavelength near 415 nm. This is within the wavelength for NBI and responsible for revealing the superficial vasculature (10). Esophagectomy was considered as the criterion standard for treatment of patients with early EAC. However, it is associated with significant morbidity and mortality, even in experienced surgical hands and high-volume surgical centers. EMR has been used increasingly to replace surgery as a curative treatment modality for early EAC in patients with BE (12, 13). It allows effective local treatment of early cancer, histological analysis of all resected specimens and thus confirmation of diagnosis and complete resection of the lesion. Ablative therapies in BE patients have provided promising results as well (18, 19). C. PRELIMINARY DATA Our group recently assessed the potential of NBI for the prediction of histology during screening and surveillance endoscopy in BE patients (10). Images obtained by this system were classified according to the mucosal (ridge/villous, circular, irregular/distorted) and vascular (normal, abnormal) patterns and correlated with histology in a prospective and blinded fashion. The sensitivity, specificity, and positive predictive value of the ridge/villous pattern for the diagnosis of intestinal metaplasia without high-grade dysplasia (HGD) were 93.5%, 87%, and 95% respectively. The sensitivity, specificity, and positive predictive value of the irregular/distorted patterns for HGD were 100%, 99%, and 95% respectively. These promising results have been validated by other investigators. Similarly, Dr. Sharma has published several studies involving the use of chromoendoscopy in patients with BE. In a study of 80 patients with columnar lined esophagus using indigo carmine dye and 115x magnification endoscopy, three mucosal patterns as stated above were identified. The presence of ridge/villous pattern for detecting intestinal metaplasia had high sensitivity, specificity, and positive predictive value (97%, 76%, and 92% respectively). Six patients had an irregular/distorted pattern and biopsies revealed HGD in all these patients (11). Our group has been active in evaluating the role of ablative therapies in patients with BE. We recently assessed the long-term efficacy of achieving complete reversal (endoscopic and histologic) between multipolar electrocoagulation and argon plasma coagulation in patients with BE and assessed factors influencing successful ablation. A total of 35 BE patients were followed for at least 2 years following ablative therapy and complete reversal of BE was achieved in 70% of the patients, regardless of the ablative technique (19). The International Working Group on the Classification of Oesophagitis has been at the forefront for the classification and grading of acid-peptic related esophageal diseases such as erosive esophagitis and BE. Sharma et al developed and validated an endoscopic grading system for BE (Prague C & M criteria). The criteria includes assessment of the circumferential (C) and maximal (M) extent of the endoscopically visualized BE segment along with endoscopic landmarks. This grading system demonstrated a high validity for the endoscopic assessment of visualized BE lengths (20). D. RESEARCH DESIGN AND METHODS Overview Patients with known / suspected BE Pre-registration, informed consent Standard endoscopy followed by HRE, NBI and chromoendoscopy Digital video-recording of endoscopy findings (Subsequent de-identification of all patient information) Target biopsies of suspected lesions Removal of abnormal lesions with EMR / mucosal ablation Pathologist for histologic interpretation This is a part of a multicenter study initiated at Kansas City. Patients will be recruited from Amsterdam, Mainz, Wiesbaden and Kansas City. Methods Physical examination and questionnaire All patients will complete a validated GERD questionnaire (GERQ) (21) that records duration, severity, and frequency of heartburn and regurgitation with supplemental information on medications such as acid suppressive therapy, aspirin, NSAIDs, etc. Demographic information and clinical findings such as height, weight and waist circumference will be recorded . Endoscopic procedure The endoscopic procedures will be performed with a high-resolution endoscope (Olympus GIF-Q240Z, GIF-Q160Z, or more recent versions) that has the capability of performing NBI with the push of a switch. Standard methods of conscious sedation and cardiopulmonary monitoring will be used during each procedure. The distal esophagus will be carefully inspected for the presence of erosions, nodules and plaques. The presence and size of hiatal hernia will be recorded. A plastic disposable distal attachment cap (e.g. Olympus D-201-11802) with a free distal distance of 2-3 mm will be attached to the endoscope in order to fix mucosal areas of interest until images and biopsies have been taken. The endoscopist will be blinded to the previous BE histology of the patient. The classification of mucosal and vascular patterns will be performed in a standardized manner into groups as described above. Details of endoscopy findings and digital video recordings will be entered into an endoscopy form .
Official Title
-----------------
Endoscopic Detection of Early Neoplasia in Patients With Barrett's Esophagus
Conditions
-----------------
Barrett's Esophagus, Neoplasms, Gastroesophageal Reflux
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18-80 years Patients must be able to provide written informed consent Patients referred for endoscopy for screening/surveillance of BE or for endoscopic treatment of BE with early mucosal neoplasia Exclusion Criteria: Current use of aspirin, non-steroidal anti-inflammatory agents(NSAIDs),or chronic anticoagulants that cannot be discontinued prior to the procedure. Inability to provide written informed consent Significant thrombocytopenia or coagulopathy Any significant co-morbid condition that would prevent the safe administration of conscious sedation
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Video-atlas creation | To create a video-atlas of early neoplastic lesions in patients with BE. This will be used for training purposes and to assess learning curve associated with these new technologies. | March 2007 - June 2016 |
| Pathologic and Clinical Outcomes | To determine the pathologic and clinical outcomes of patients undergoing EMR / ablation; including morbidity, mortality and complications of the procedure. | 2007 - 2016 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interobserver agreement for the detection of early neoplasia | To determine the interobserver agreement using the video-atlas for the detection of early neoplasia. | 2015 - 2016 |
| Efficacy of endoscopic detection of early esophageal lesions | To determine the endoscopic detection rate of early neoplastic lesions by expert endoscopists, experienced endoscopists, and trainees. The endoscopist will be graded as 1.) Trainees (in fellowship training); 2.) Experienced endoscopist (<5 yrs of experience in esophageal diseases); 3.) Expert endoscopist (>5 yrs of experience in esophageal diseases). | 2007-2016 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Barrett's Esophagus, Neoplasia, Endoscopic mucosal resection, High resolution endoscopy, Chromoendoscopy
|
|||
NCT04411329
|
Caudal Epidural With Non Opioid Adjuvants in Lumbosacral Spine Surgery
|
Lumbosacral spine surgeries are accompanied with severe postoperative pain which has a negative effect on patients' recovery. Preemptive analgesia before lumbosacral spine surgeries should be implemented to prevent CNS plasticity and to provide effective pain relief.~The most common way to provide pain management after spine surgery is the intravenous analgesia. Caudal epidural analgesia can be a highly effective method for postoperative pain relief.~The most common way to provide pain management after spine surgery is the intravenous analgesia. Caudal epidural analgesia can be a highly effective method for postoperative pain relief. acting drugs last from 4-8 hours,But this can be prolonged by adding non opioid adjuvants like steroid( dexamethazone,betamethasone), alpha2 agonists (clonidine, dexmedetomidine), or their combination. This study will compare adding different non opioid adjuvants to bupivacaine in caudal epidural for preventive analgesia in lumbosacral spine surgery which can be a part of multimodal analgesia protocol.~.
|
60 patient will be enrolled in the study. They will be allocated randomly into 3 groups. after induction of general anesthesia and changing the patient into prone position injection of the study cocktail through caudal epidural route.(20 ml before skin incision and 10 ml of the same mixture at the end of surgery) in all patients.~In the first group patients will receive 0.125% bupivacaine with 8 mg dexamethasone In the second group we will add 50µg dexmedetomidine to the previous mixture given to the first group.~In the third group we will add 1500 IU hyalurodinase to the mixture given to the first group~During the operation adjustment of sevoflurane concentration and fentanyl incremental doses (0.5 μg/kg) will be according to hemodynamic measurements.~Clinical signs of inadequate analgesia is defined as an increase in blood pressure and heart rate more than 20% from baseline. Efficacy of the caudal epidural block will be tested at beginning of skin incision (15-20 minutes after block). If signs of inadequate analgesia are observed, fentanyl 0.5 µg/kg will be given and those patients will be excluded from the study.~In case of decrease in Blood Pressure greater than 20% from baseline, the patient will be infused by 500 ml ringer lactate and if blood pressure is not responding, administration of increments of 3 mg ephedrine will be given. Also If heart rate decreased to 45 beats/min, atropine sulfate 0.01 mg/kg will be given. Muscle paralysis will be antagonized by sugmmadex 2mg/kg at the end of surgery after switching the patient to the supine position.
|
Caudal Epidural With Non Opioid Adjuvants in Lumbosacral Spine Surgery
|
Caudal Analgesia for Lumosacral Spine Surgeries
|
* Drug: Bupivacaine
* Drug: Dexamethasone
* Drug: Dexmedetomidine
* Drug: Hyalouridinase
|
Inclusion Criteria:~Patients are aged from 18-65 years , ASA I and II, scheduled for lumbar spine surgery (laminectomy, discectomy, foraminotomy, fenestration or fusion) in a virgin back.~Exclusion Criteria:~Patients with multiple level fixation, revision surgery, complicated spinal canal stenosis, traumatic lumbar surgeries were excluded, patients with addiction, allergy to local anesthetics or to any drug used in the study and those with coagulation abnormality are also excluded from the study.
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The duration of analgesia | time from second dose caudal epidural block to first analgesic requirement | postoerative 24 hours. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| postoperative pain | VAS score from zero for (no pain) till 10 for ( the most severe intractable pain) | postoperative 24 hours |
|
Analgesics, Glucocorticoids, Dexamethasone, Dexmedetomidine, Bupivacaine, Anti-Inflammatory Agents, Antiemetics, Autonomic Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Gastrointestinal Agents, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Antineoplastic Agents, Hormonal, Antineoplastic Agents, Anesthetics, Local, Anesthetics, Central Nervous System Depressants, Sensory System Agents, Hypnotics and Sedatives, Analgesics, Non-Narcotic, Adrenergic alpha-2 Receptor Agonists, Adrenergic alpha-Agonists, Adrenergic Agonists, Adrenergic Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: group A<br>patients will receive 30 ml of 0.125% bupivacaine with 8 mg dexamethasone (20 ml before skin incision and 10 ml at end of surgery | Drug: Bupivacaine<br>* local anesthetics, steriod, alpha 2 blockers<br>Drug: Dexamethasone<br>* dexamethazone<br>|
| Active Comparator: group B<br>we will add 50µg dexmedetomidine to the previous mixture given to group A (20 ml before skin incision and 10 ml at end of surgery | Drug: Bupivacaine<br>* local anesthetics, steriod, alpha 2 blockers<br>Drug: Dexamethasone<br>* dexamethazone<br>Drug: Dexmedetomidine<br>* dexmedetomidine<br>|
| Active Comparator: group c<br>we will add 1500 IU hyalurodinase to the mixture given to group A. (20 ml before skin incision and 10 ml at end of surgery | Drug: Bupivacaine<br>* local anesthetics, steriod, alpha 2 blockers<br>Drug: Dexamethasone<br>* dexamethazone<br>Drug: Hyalouridinase<br>* hyalouridinase<br>|
|
Caudal Epidural With Non Opioid Adjuvants in Lumbosacral Spine Surgery
Study Overview
=================
Brief Summary
-----------------
Lumbosacral spine surgeries are accompanied with severe postoperative pain which has a negative effect on patients' recovery. Preemptive analgesia before lumbosacral spine surgeries should be implemented to prevent CNS plasticity and to provide effective pain relief. The most common way to provide pain management after spine surgery is the intravenous analgesia. Caudal epidural analgesia can be a highly effective method for postoperative pain relief. The most common way to provide pain management after spine surgery is the intravenous analgesia. Caudal epidural analgesia can be a highly effective method for postoperative pain relief. acting drugs last from 4-8 hours,But this can be prolonged by adding non opioid adjuvants like steroid( dexamethazone,betamethasone), alpha2 agonists (clonidine, dexmedetomidine), or their combination. This study will compare adding different non opioid adjuvants to bupivacaine in caudal epidural for preventive analgesia in lumbosacral spine surgery which can be a part of multimodal analgesia protocol. .
Detailed Description
-----------------
60 patient will be enrolled in the study. They will be allocated randomly into 3 groups. after induction of general anesthesia and changing the patient into prone position injection of the study cocktail through caudal epidural route.(20 ml before skin incision and 10 ml of the same mixture at the end of surgery) in all patients. In the first group patients will receive 0.125% bupivacaine with 8 mg dexamethasone In the second group we will add 50µg dexmedetomidine to the previous mixture given to the first group. In the third group we will add 1500 IU hyalurodinase to the mixture given to the first group During the operation adjustment of sevoflurane concentration and fentanyl incremental doses (0.5 μg/kg) will be according to hemodynamic measurements. Clinical signs of inadequate analgesia is defined as an increase in blood pressure and heart rate more than 20% from baseline. Efficacy of the caudal epidural block will be tested at beginning of skin incision (15-20 minutes after block). If signs of inadequate analgesia are observed, fentanyl 0.5 µg/kg will be given and those patients will be excluded from the study. In case of decrease in Blood Pressure greater than 20% from baseline, the patient will be infused by 500 ml ringer lactate and if blood pressure is not responding, administration of increments of 3 mg ephedrine will be given. Also If heart rate decreased to 45 beats/min, atropine sulfate 0.01 mg/kg will be given. Muscle paralysis will be antagonized by sugmmadex 2mg/kg at the end of surgery after switching the patient to the supine position.
Official Title
-----------------
Caudal Epidural With Non Opioid Adjuvants in Lumbosacral Spine Surgery
Conditions
-----------------
Caudal Analgesia for Lumosacral Spine Surgeries
Intervention / Treatment
-----------------
* Drug: Bupivacaine
* Drug: Dexamethasone
* Drug: Dexmedetomidine
* Drug: Hyalouridinase
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients are aged from 18-65 years , ASA I and II, scheduled for lumbar spine surgery (laminectomy, discectomy, foraminotomy, fenestration or fusion) in a virgin back. Exclusion Criteria: Patients with multiple level fixation, revision surgery, complicated spinal canal stenosis, traumatic lumbar surgeries were excluded, patients with addiction, allergy to local anesthetics or to any drug used in the study and those with coagulation abnormality are also excluded from the study.
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: group A<br>patients will receive 30 ml of 0.125% bupivacaine with 8 mg dexamethasone (20 ml before skin incision and 10 ml at end of surgery | Drug: Bupivacaine<br>* local anesthetics, steriod, alpha 2 blockers<br>Drug: Dexamethasone<br>* dexamethazone<br>|
| Active Comparator: group B<br>we will add 50µg dexmedetomidine to the previous mixture given to group A (20 ml before skin incision and 10 ml at end of surgery | Drug: Bupivacaine<br>* local anesthetics, steriod, alpha 2 blockers<br>Drug: Dexamethasone<br>* dexamethazone<br>Drug: Dexmedetomidine<br>* dexmedetomidine<br>|
| Active Comparator: group c<br>we will add 1500 IU hyalurodinase to the mixture given to group A. (20 ml before skin incision and 10 ml at end of surgery | Drug: Bupivacaine<br>* local anesthetics, steriod, alpha 2 blockers<br>Drug: Dexamethasone<br>* dexamethazone<br>Drug: Hyalouridinase<br>* hyalouridinase<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The duration of analgesia | time from second dose caudal epidural block to first analgesic requirement | postoerative 24 hours. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| postoperative pain | VAS score from zero for (no pain) till 10 for ( the most severe intractable pain) | postoperative 24 hours |
|
|
NCT05427786
|
A Study to Evaluate the Impact of Pre-procedural Intracoronary Nicorandil Injection to PREVENT reductioN Of decREased TIMI FLOW in Patients Who Undergoing Percutaneous Coronary Intervention for the Coronary Artery Disease
|
The aim of this study was to determine the effect of intra-coronary administration of nicorandil on the prevention of lowering of coronary blood flow for high-risk plaque lesions defined as the high value of lipid core burden index in patients with coronary artery disease who require stent treatment.
|
A Randomized, Open Label, Parallel-group Study to Evaluate the Impact of Pre-procedural Intracoronary Nicorandil Injection to PREVENT reductioN Of decREased TIMI FLOW in Patients Who Undergoing Percutaneous Coronary Intervention for the Coronary Artery Disease
|
No-Reflow Phenomenon, Coronary Artery Disease, Percutaneous Coronary Intervention
|
* Drug: Nicorandil
|
Inclusion Criteria:~Over 19 years old~Patients who agree to the study plan and clinical follow-up plan, voluntarily decide to participate in this study, and consent in writing to the consent to use information~Patients who underwent NIRS-IVUS guided coronary stent surgery for coronary artery disease~Exclusion Criteria:~Patients with TIMI ≤ 2 before coronary intervention~Subjects with known hypersensitivity or contraindications to the following drugs or substances: heparin, aspirin, clopidogrel, ticagrelor, prasugrel, rosuvastatin, ezetimibe, evolocumab, lansoprazole, cobalt chromium, stainless steel nickel And contrast agents (however, even a subject who is hypersensitive to contrast agents can register if they can be controlled by steroids and pheniramine, except for known anaphylaxis.)~Pregnant women, lactating women, or women of childbearing age who plan to become pregnant during this study~Subjects who plan to have surgery to stop antiplatelet drugs within 6 months from registration~Those whose surviving life is expected to be less than 1 year~Subjects who visited the hospital due to cardiogenic shock and are predicted to have low survival probability based on medical judgment
|
19 Years
| null |
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of decreased TIMI flow | occurrence of decreased TIMI flow (0,1,2) during the index procedure~Grade 0-No perfusion~Grade 1-Penetration without perfusion~Grade 2-Partial perfusion but not reach complete perfusion~Grade 3-Complete perfusion;; antegrade flow into the bed distal to the obstruction occurs as promptly as antegrade flow into the bed proximal to the obstruction, and clearance of contrast material from the involved bed is as rapid as clearance from an uninvolved bed in the same vessel or the opposite artery. | during procedure |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of cardiac biomarker level after intervention | level change of CPK | 1 month |
| Change of cardiac biomarker level after intervention | level change of CK-MB | 1 month |
| Change of cardiac biomarker level after intervention | level change of Troponin T | 1 month |
| Change of cardiac biomarker level after intervention | level change of Troponin I | 1 month |
| patient-oriented composite end point | composite of all cause mortality, any myocardial infarction, and any revascularization | 1 year |
| Percentage of All cause mortality | | 1 year |
| Percentage of cardiac death | | 1 year |
| Percentage of myocardial infarction | | 1 year |
| Percentage of revascularization | | 1 year |
|
Nicorandil, No-reflow phenomenon, lipid core burden index, near-infrared spectroscopy
|
Nicorandil, Anti-Arrhythmia Agents, Antihypertensive Agents, Vasodilator Agents, Vitamin B Complex, Vitamins, Micronutrients, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pre-PCI IC Nicorandil<br>If the lipid core burden index at the main lesion site on vascular ultrasound exceeds 353, randomization was performed.~Nicorandil group will be administrated 8cc or more of the prescribed drug (Nicroandil) according to randomization into the coronary artery before starting balloon therapy. | Drug: Nicorandil<br>* Administer 8cc or more of the prescribed drug according to randomization into the coronary artery before starting balloon therapy. The stent treatment method follows the standard treatment method.<br>|
| No Intervention: Standard PCI<br>If the lipid core burden index at the main lesion site on vascular ultrasound exceeds 353, randomization was performed.~Standard PCI group will be performed coronary intervention including starting balloon therapy without pre-administrated nicorandil. | |
|
A Study to Evaluate the Impact of Pre-procedural Intracoronary Nicorandil Injection to PREVENT reductioN Of decREased TIMI FLOW in Patients Who Undergoing Percutaneous Coronary Intervention for the Coronary Artery Disease
Study Overview
=================
Brief Summary
-----------------
The aim of this study was to determine the effect of intra-coronary administration of nicorandil on the prevention of lowering of coronary blood flow for high-risk plaque lesions defined as the high value of lipid core burden index in patients with coronary artery disease who require stent treatment.
Official Title
-----------------
A Randomized, Open Label, Parallel-group Study to Evaluate the Impact of Pre-procedural Intracoronary Nicorandil Injection to PREVENT reductioN Of decREased TIMI FLOW in Patients Who Undergoing Percutaneous Coronary Intervention for the Coronary Artery Disease
Conditions
-----------------
No-Reflow Phenomenon, Coronary Artery Disease, Percutaneous Coronary Intervention
Intervention / Treatment
-----------------
* Drug: Nicorandil
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Over 19 years old Patients who agree to the study plan and clinical follow-up plan, voluntarily decide to participate in this study, and consent in writing to the consent to use information Patients who underwent NIRS-IVUS guided coronary stent surgery for coronary artery disease Exclusion Criteria: Patients with TIMI ≤ 2 before coronary intervention Subjects with known hypersensitivity or contraindications to the following drugs or substances: heparin, aspirin, clopidogrel, ticagrelor, prasugrel, rosuvastatin, ezetimibe, evolocumab, lansoprazole, cobalt chromium, stainless steel nickel And contrast agents (however, even a subject who is hypersensitive to contrast agents can register if they can be controlled by steroids and pheniramine, except for known anaphylaxis.) Pregnant women, lactating women, or women of childbearing age who plan to become pregnant during this study Subjects who plan to have surgery to stop antiplatelet drugs within 6 months from registration Those whose surviving life is expected to be less than 1 year Subjects who visited the hospital due to cardiogenic shock and are predicted to have low survival probability based on medical judgment
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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pre-PCI IC Nicorandil<br>If the lipid core burden index at the main lesion site on vascular ultrasound exceeds 353, randomization was performed. Nicorandil group will be administrated 8cc or more of the prescribed drug (Nicroandil) according to randomization into the coronary artery before starting balloon therapy. | Drug: Nicorandil<br>* Administer 8cc or more of the prescribed drug according to randomization into the coronary artery before starting balloon therapy. The stent treatment method follows the standard treatment method.<br>|
| No Intervention: Standard PCI<br>If the lipid core burden index at the main lesion site on vascular ultrasound exceeds 353, randomization was performed. Standard PCI group will be performed coronary intervention including starting balloon therapy without pre-administrated nicorandil. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of decreased TIMI flow | occurrence of decreased TIMI flow (0,1,2) during the index procedure Grade 0-No perfusion Grade 1-Penetration without perfusion Grade 2-Partial perfusion but not reach complete perfusion Grade 3-Complete perfusion;; antegrade flow into the bed distal to the obstruction occurs as promptly as antegrade flow into the bed proximal to the obstruction, and clearance of contrast material from the involved bed is as rapid as clearance from an uninvolved bed in the same vessel or the opposite artery. | during procedure |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of cardiac biomarker level after intervention | level change of CPK | 1 month |
| Change of cardiac biomarker level after intervention | level change of CK-MB | 1 month |
| Change of cardiac biomarker level after intervention | level change of Troponin T | 1 month |
| Change of cardiac biomarker level after intervention | level change of Troponin I | 1 month |
| patient-oriented composite end point | composite of all cause mortality, any myocardial infarction, and any revascularization | 1 year |
| Percentage of All cause mortality | | 1 year |
| Percentage of cardiac death | | 1 year |
| Percentage of myocardial infarction | | 1 year |
| Percentage of revascularization | | 1 year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nicorandil, No-reflow phenomenon, lipid core burden index, near-infrared spectroscopy
|
|
NCT00660231
|
Gemcitabine and Bexarotene in Treating Patients With Progressive or Refractory Stage IB, Stage II, Stage III, or Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
|
RATIONALE: Drugs used in chemotherapy, such as gemcitabine and bexarotene, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.~PURPOSE: This phase II trial is studying giving gemcitabine together with bexarotene to see how well it works in treating patients with progressive or refractory stage IB, stage II, stage III, or stage IV cutaneous T-cell non-Hodgkin lymphoma.
|
OBJECTIVES:~Primary~Confirm the feasibility and efficacy of the combination of gemcitabine hydrochloride and bexarotene in patients with cutaneous T-cell lymphoma whose disease is no longer controlled by skin-directed therapy and who have had at least one prior systemic therapy.~Secondary~Determine the rate of objective disease control as defined by complete response (CR), clinical complete response (CCR), partial response (PR), and stable disease (SD) for 6 months as determined by the Objective Primary Disease Response Evaluation Criteria (OPDREC).~Evaluate the duration and durability of objective disease response (CR, CCR and PR) as determined by OPDREC criteria.~Evaluate time to objective disease response.~Determine the safety of this combination in terms of adverse events, clinical laboratory data, physical examinations, rate of neutropenic fever and sepsis, blood transfusions, and treatment compliance.~Determine the time to objective disease progression.~Determine the time to treatment failure.~Determine change from baseline in Severity-Weighted Assessment Tool (SWAT) value, Erythroderma SWAT value, Pruritus Visual Analogue Scale, and ECOG performance status.~Determine proportion of disease control, response, and progression as determined by RECIST criteria.~Evaluate the proportion of patients with clearing of Sézary cells from the blood and bone marrow.~Measure changes in patient assessed Quality of Life using Skindex 29 and EORTC QLQ-30.~OUTLINE: This is a multicenter study.~Patients receive gemcitabine hydrochloride IV on days 1 and 8 and oral bexarotene daily on days 1-21. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. After 4 courses of study therapy, patients with responding disease receive oral bexarotene alone daily until disease progression or treatment no longer tolerated.~Patients complete a quality of life questionnaire at baseline, during study therapy, and after completion of study treatment.~After completion of study treatment, patients are followed every 2 months for up to 5 years.~Peer Reviewed and Funded or Endorsed by Cancer Research UK
|
A Phase II Study of Gemcitabine and Bexarotene (Gembex) in the Treatment of Cutaneous T-cell Lymphoma
|
Lymphoma
|
* Drug: bexarotene
* Drug: gemcitabine hydrochloride
|
DISEASE CHARACTERISTICS:~Histologically confirmed cutaneous T-cell lymphoma (CTCL) including its variants (e.g., mycosis fungoides and Sézary syndrome)~CTCL stage IB, IIA, IIB, III or IVA disease~No visceral involvement (i.e., stage IVB disease)~Lymphadenopathy is allowed~Patients must have developed progressive disease after receiving or have been refractory to at least 1 course of prior standard, systemic, skin-directed therapy (e.g., interferon, chemotherapy, or denileukin diftitox [Ontak®])~No CD30 + (Ki1+ve) anaplastic large cell lymphoma~PATIENT CHARACTERISTICS:~ECOG performance status 0-1~Life expectancy > 6 months~Hemoglobin ≥ 9.0 g/dL (transfusions and/or erythropoietin are allowed)~ANC > 1.5 x 10^9/L~Platelet count ≥ 100 x 10^9/L~Total bilirubin ≤ 1.25 times upper limit of normal (ULN)~AST and ALT ≤ 2 times ULN~Serum creatinine ≤ 2 times ULN~No clinically significant active infection~No uncontrolled diabetes mellitus~No excessive alcohol consumption~No biliary tract disease~No history of pancreatitis~HIV negative~Hepatitis B and C negative~Not pregnant or nursing~Negative pregnancy test~Fertile patients must use effective contraception during and for 1 month after study participation~No other malignancy within the past 5 years except curatively treated basal or squamous cell skin cancer, cervical epithelial neoplasm CIN1, or carcinoma in situ~No other significant medical or psychiatric condition that would preclude study compliance~PRIOR CONCURRENT THERAPY:~See Disease Characteristics~More than 4 weeks since any prior investigational agent~More than 2 weeks since prior topical steroids or more than 4 weeks since prior systemic steroids~Local radiotherapy may be given to isolated symptomatic tumour nodules that require immediate treatment for up to 2 weeks prior to study drugs~No prior treatment with bexarotene (Targretin®)~No concurrent anticancer therapy~No concurrent investigational agent~No concurrent drug therapy with other medications that can elevate triglycerides or cause pancreatic toxicity (e.g., gemfibrozil)~No concurrent warfarin
|
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 |
| --- | --- | --- |
| Rate of objective response | | at 24 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration and durability of objective disease response | Time from first date of treatment to the first date of diagnosis of progressive disease | up to 5 years after treatment start |
| Assessment of quality of life | | up to 5 years after treatment start |
|
recurrent mycosis fungoides/Sezary syndrome, stage IB mycosis fungoides/Sezary syndrome, stage II mycosis fungoides/Sezary syndrome, stage III mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome, recurrent cutaneous T-cell non-Hodgkin lymphoma, stage IB cutaneous T-cell non-Hodgkin lymphoma, stage II cutaneous T-cell non-Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma
|
Gemcitabine, Bexarotene, Antimetabolites, Antineoplastic, Antimetabolites, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GemBex<br>Gemcitabine days 1 and 8 of a 3 week cycle (4 cycles total - 12 weeks) Bexarotene daily: in combination with Gemcitabine during first 12 weeks, then Bexarotene maintenance until disease progression. | Drug: bexarotene<br>* Bexarotene daily p.o. 150mg/sq m during week 1 and 2, then 300mg/sq m if tolerated.<br>* Other names: Targretin;Drug: gemcitabine hydrochloride<br>* Gemcitabine i.v. 1000mg/sq m day 1 and day 8 of four 21 day cycles.<br>|
|
Gemcitabine and Bexarotene in Treating Patients With Progressive or Refractory Stage IB, Stage II, Stage III, or Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as gemcitabine and bexarotene, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. PURPOSE: This phase II trial is studying giving gemcitabine together with bexarotene to see how well it works in treating patients with progressive or refractory stage IB, stage II, stage III, or stage IV cutaneous T-cell non-Hodgkin lymphoma.
Detailed Description
-----------------
OBJECTIVES: Primary Confirm the feasibility and efficacy of the combination of gemcitabine hydrochloride and bexarotene in patients with cutaneous T-cell lymphoma whose disease is no longer controlled by skin-directed therapy and who have had at least one prior systemic therapy. Secondary Determine the rate of objective disease control as defined by complete response (CR), clinical complete response (CCR), partial response (PR), and stable disease (SD) for 6 months as determined by the Objective Primary Disease Response Evaluation Criteria (OPDREC). Evaluate the duration and durability of objective disease response (CR, CCR and PR) as determined by OPDREC criteria. Evaluate time to objective disease response. Determine the safety of this combination in terms of adverse events, clinical laboratory data, physical examinations, rate of neutropenic fever and sepsis, blood transfusions, and treatment compliance. Determine the time to objective disease progression. Determine the time to treatment failure. Determine change from baseline in Severity-Weighted Assessment Tool (SWAT) value, Erythroderma SWAT value, Pruritus Visual Analogue Scale, and ECOG performance status. Determine proportion of disease control, response, and progression as determined by RECIST criteria. Evaluate the proportion of patients with clearing of Sézary cells from the blood and bone marrow. Measure changes in patient assessed Quality of Life using Skindex 29 and EORTC QLQ-30. OUTLINE: This is a multicenter study. Patients receive gemcitabine hydrochloride IV on days 1 and 8 and oral bexarotene daily on days 1-21. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. After 4 courses of study therapy, patients with responding disease receive oral bexarotene alone daily until disease progression or treatment no longer tolerated. Patients complete a quality of life questionnaire at baseline, during study therapy, and after completion of study treatment. After completion of study treatment, patients are followed every 2 months for up to 5 years. Peer Reviewed and Funded or Endorsed by Cancer Research UK
Official Title
-----------------
A Phase II Study of Gemcitabine and Bexarotene (Gembex) in the Treatment of Cutaneous T-cell Lymphoma
Conditions
-----------------
Lymphoma
Intervention / Treatment
-----------------
* Drug: bexarotene
* Drug: gemcitabine hydrochloride
Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed cutaneous T-cell lymphoma (CTCL) including its variants (e.g., mycosis fungoides and Sézary syndrome) CTCL stage IB, IIA, IIB, III or IVA disease No visceral involvement (i.e., stage IVB disease) Lymphadenopathy is allowed Patients must have developed progressive disease after receiving or have been refractory to at least 1 course of prior standard, systemic, skin-directed therapy (e.g., interferon, chemotherapy, or denileukin diftitox [Ontak®]) No CD30 + (Ki1+ve) anaplastic large cell lymphoma PATIENT CHARACTERISTICS: ECOG performance status 0-1 Life expectancy > 6 months Hemoglobin ≥ 9.0 g/dL (transfusions and/or erythropoietin are allowed) ANC > 1.5 x 10^9/L Platelet count ≥ 100 x 10^9/L Total bilirubin ≤ 1.25 times upper limit of normal (ULN) AST and ALT ≤ 2 times ULN Serum creatinine ≤ 2 times ULN No clinically significant active infection No uncontrolled diabetes mellitus No excessive alcohol consumption No biliary tract disease No history of pancreatitis HIV negative Hepatitis B and C negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 1 month after study participation No other malignancy within the past 5 years except curatively treated basal or squamous cell skin cancer, cervical epithelial neoplasm CIN1, or carcinoma in situ No other significant medical or psychiatric condition that would preclude study compliance PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 4 weeks since any prior investigational agent More than 2 weeks since prior topical steroids or more than 4 weeks since prior systemic steroids Local radiotherapy may be given to isolated symptomatic tumour nodules that require immediate treatment for up to 2 weeks prior to study drugs No prior treatment with bexarotene (Targretin®) No concurrent anticancer therapy No concurrent investigational agent No concurrent drug therapy with other medications that can elevate triglycerides or cause pancreatic toxicity (e.g., gemfibrozil) No concurrent warfarin
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: GemBex<br>Gemcitabine days 1 and 8 of a 3 week cycle (4 cycles total - 12 weeks) Bexarotene daily: in combination with Gemcitabine during first 12 weeks, then Bexarotene maintenance until disease progression. | Drug: bexarotene<br>* Bexarotene daily p.o. 150mg/sq m during week 1 and 2, then 300mg/sq m if tolerated.<br>* Other names: Targretin;Drug: gemcitabine hydrochloride<br>* Gemcitabine i.v. 1000mg/sq m day 1 and day 8 of four 21 day cycles.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of objective response | | at 24 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration and durability of objective disease response | Time from first date of treatment to the first date of diagnosis of progressive disease | up to 5 years after treatment start |
| Assessment of quality of life | | up to 5 years after treatment start |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent mycosis fungoides/Sezary syndrome, stage IB mycosis fungoides/Sezary syndrome, stage II mycosis fungoides/Sezary syndrome, stage III mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome, recurrent cutaneous T-cell non-Hodgkin lymphoma, stage IB cutaneous T-cell non-Hodgkin lymphoma, stage II cutaneous T-cell non-Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma
|
NCT05547256
|
A Preliminary Exploratory Cohort Study of COVID-19 mRNA Vaccine, Bivalent in Participants Aged 18 Years and Over in China
|
This is a preliminary exploratory cohort study to evaluate safety, tolerability and immunogenicity of COVID-19 mRNA Vaccine, Bivalent (LVRNA021) in participants Aged 18 years and over in China
|
A Preliminary Exploratory Cohort Study to Evaluate Safety, Tolerability and Immunogenicity of COVID-19 mRNA Vaccine, Bivalent (LVRNA021) in Participants Aged 18 Years and Over in China
|
SARS-CoV-2
|
* Biological: COVID-19 Variant (Omicron BA.5) mRNA Vaccine Low dose
* Biological: COVID-19 Variant (Omicron BA.5) mRNA Vaccine High dose
* Drug: Placebo
|
Inclusion Criteria:~Age at the time of first dose of vaccine: adults aged 18-59 years (including boundary values), elderly ≥60 years, both sexes;~Armpit temperature <37.3℃ on the day of enrollment;~Based on the medical history and relevant physical examination and laboratory examination results, the investigator clinically determined that the patient was in good health;~Subjects have independent judgment ability, can read, understand and complete vaccination diary cards, and they participate voluntarily and sign an informed consent form.~Exclusion Criteria:~The subject has a history of SARS-CoV-2 or SARS infection, or has a history of contact with SARS-CoV-2 infected persons (nucleic acid test positive) or suspected infected persons within 30 days before screening, or living abroad within 30 days before screening history, or a positive SARS-CoV-2 nucleic acid test or a positive SARS-CoV-2 IgM or IgG test before the first dose of vaccine;~History of allergy to any component of the study vaccine or a history of a severe allergic reaction to the vaccine or drug (including but not limited to anaphylactic shock, anaphylactic laryngeal edema, anaphylactic purpura, thrombocytopenic purpura, or local anaphylactic necrosis [Arthus reaction]);~Upon questioning, have a history of COVID-19 vaccination, or have received other inactivated vaccines within 14 days before screening, and received live attenuated vaccines within 28 days;~Patients have a medical history or family history of epilepsy, convulsions, neurological diseases and mental diseases;~There are contraindications for intramuscular injection, such as: thrombocytopenia that has been diagnosed, any coagulation disorder or receiving anticoagulant treatment, etc.;~The investigator judges that he is known or suspected of having more serious diseases at the same time, including but not limited to: respiratory diseases (tuberculosis, lung failure, etc.), liver and kidney diseases, cardiovascular diseases (heart failure, severe hypertension, etc.), Malignant tumor, infection or allergic skin disease, HIV infection (test report can be provided), or during the active period of acute infection or chronic disease (within 3 days before vaccination);~Congenital malformations, developmental disorders, or chronic diseases that the investigator judges are not suitable for participating in this study (such as Downs syndrome, sickle cell anemia or neurological disorders, Guillain-Barre syndrome, etc.), excluding stable diabetes/hypertension );~Patients with known immunological impairment or low immunological function diagnosed by the hospital before enrollment, or functional asplenia or splenectomy caused by any situation;~Smokers (≥20 cigarettes per day on average in the past 30 days), alcoholics (≥61 grams of pure alcohol per day on average for men and ≥41 grams of pure alcohol per day for women in the past 30 days) and drug abuse;~Female: those who have a positive blood pregnancy test, are pregnant, breastfeeding, or have a pregnancy plan within one year; men: whose spouse has a pregnancy plan within one year;~Patients have participated in other clinical trials (drugs, biological products or devices) within 3 months before the first dose of vaccine, or plan to participate in other clinical trials during the research period;~Patients received immune enhancement or immunosuppressive therapy within 6 months before the first dose of vaccine (continuous oral or instillation for more than 14 days);~Patients donated blood ≥400 ml within 28 days before screening, or received whole blood, plasma and immunoglobulin therapy within 6 months before screening;~Currently receiving research drug treatment to prevent COVID-19;~Patients are taking antipyretic, analgesic and anti-allergic drugs within 3 days before enrollment;~The investigator judges that the subjects cannot follow the research procedures, comply with the agreement, or plan to permanently relocate from the area before the end of the research, or plan to leave the local area for a long time during the scheduled visit period;~The relevant staff involved in this study or their immediate family members (such as spouses, parents, siblings or children);~According to the investigator's judgment, there are other situations that are not suitable for participating in this clinical trial.
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of solicited adverse events | | Within 28 days after each dose/full dose |
| Incidence of unsolicited adverse events | | Within 28 days after each dose/full dose |
| Incidence of adverse events associated with the study vaccine | | Within 28 days after each dose/full dose |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of grade ≥3 adverse events | | Within 28 days after each dose/full dose |
| Incidence of grade ≥3 adverse events associated with the study vaccine | | Within 28 days after each dose/full dose |
| Statistics of withdrawal from the study due to adverse events | | Within 28 days after each dose/full dose |
| Incidence of SAE | | Within 28 days, 3 months, 6 months, and 12 months after the first dose of immunization to full immunization |
| Incidence of AESI | | Within 28 days, 3 months, 6 months, and 12 months after the first dose of immunization to full immunization |
| Incidence of SAE associated with the study vaccine | | Within 28 days, 3 months, 6 months, and 12 months after the first dose of immunization to full immunization |
| Incidence of AESI associated with the study vaccine | | Within 28 days, 3 months, 6 months, and 12 months after the first dose of immunization to full immunization |
| Incidence of clinically significant abnormalities in laboratory measures | | After vaccination |
|
Immunologic Factors, Physiological Effects of Drugs, Vaccines
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Two doses were administered by intramuscular injection, 28 days apart | Biological: COVID-19 Variant (Omicron BA.5) mRNA Vaccine Low dose<br>* 50μg/dose<br>Drug: Placebo<br>* Saline solution<br>|
| Experimental: Group B<br>Two doses were administered by intramuscular injection, 28 days apart | Biological: COVID-19 Variant (Omicron BA.5) mRNA Vaccine High dose<br>* 100μg/dose<br>Drug: Placebo<br>* Saline solution<br>|
|
A Preliminary Exploratory Cohort Study of COVID-19 mRNA Vaccine, Bivalent in Participants Aged 18 Years and Over in China
Study Overview
=================
Brief Summary
-----------------
This is a preliminary exploratory cohort study to evaluate safety, tolerability and immunogenicity of COVID-19 mRNA Vaccine, Bivalent (LVRNA021) in participants Aged 18 years and over in China
Official Title
-----------------
A Preliminary Exploratory Cohort Study to Evaluate Safety, Tolerability and Immunogenicity of COVID-19 mRNA Vaccine, Bivalent (LVRNA021) in Participants Aged 18 Years and Over in China
Conditions
-----------------
SARS-CoV-2
Intervention / Treatment
-----------------
* Biological: COVID-19 Variant (Omicron BA.5) mRNA Vaccine Low dose
* Biological: COVID-19 Variant (Omicron BA.5) mRNA Vaccine High dose
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age at the time of first dose of vaccine: adults aged 18-59 years (including boundary values), elderly ≥60 years, both sexes; Armpit temperature <37.3℃ on the day of enrollment; Based on the medical history and relevant physical examination and laboratory examination results, the investigator clinically determined that the patient was in good health; Subjects have independent judgment ability, can read, understand and complete vaccination diary cards, and they participate voluntarily and sign an informed consent form. Exclusion Criteria: The subject has a history of SARS-CoV-2 or SARS infection, or has a history of contact with SARS-CoV-2 infected persons (nucleic acid test positive) or suspected infected persons within 30 days before screening, or living abroad within 30 days before screening history, or a positive SARS-CoV-2 nucleic acid test or a positive SARS-CoV-2 IgM or IgG test before the first dose of vaccine; History of allergy to any component of the study vaccine or a history of a severe allergic reaction to the vaccine or drug (including but not limited to anaphylactic shock, anaphylactic laryngeal edema, anaphylactic purpura, thrombocytopenic purpura, or local anaphylactic necrosis [Arthus reaction]); Upon questioning, have a history of COVID-19 vaccination, or have received other inactivated vaccines within 14 days before screening, and received live attenuated vaccines within 28 days; Patients have a medical history or family history of epilepsy, convulsions, neurological diseases and mental diseases; There are contraindications for intramuscular injection, such as: thrombocytopenia that has been diagnosed, any coagulation disorder or receiving anticoagulant treatment, etc.; The investigator judges that he is known or suspected of having more serious diseases at the same time, including but not limited to: respiratory diseases (tuberculosis, lung failure, etc.), liver and kidney diseases, cardiovascular diseases (heart failure, severe hypertension, etc.), Malignant tumor, infection or allergic skin disease, HIV infection (test report can be provided), or during the active period of acute infection or chronic disease (within 3 days before vaccination); Congenital malformations, developmental disorders, or chronic diseases that the investigator judges are not suitable for participating in this study (such as Downs syndrome, sickle cell anemia or neurological disorders, Guillain-Barre syndrome, etc.), excluding stable diabetes/hypertension ); Patients with known immunological impairment or low immunological function diagnosed by the hospital before enrollment, or functional asplenia or splenectomy caused by any situation; Smokers (≥20 cigarettes per day on average in the past 30 days), alcoholics (≥61 grams of pure alcohol per day on average for men and ≥41 grams of pure alcohol per day for women in the past 30 days) and drug abuse; Female: those who have a positive blood pregnancy test, are pregnant, breastfeeding, or have a pregnancy plan within one year; men: whose spouse has a pregnancy plan within one year; Patients have participated in other clinical trials (drugs, biological products or devices) within 3 months before the first dose of vaccine, or plan to participate in other clinical trials during the research period; Patients received immune enhancement or immunosuppressive therapy within 6 months before the first dose of vaccine (continuous oral or instillation for more than 14 days); Patients donated blood ≥400 ml within 28 days before screening, or received whole blood, plasma and immunoglobulin therapy within 6 months before screening; Currently receiving research drug treatment to prevent COVID-19; Patients are taking antipyretic, analgesic and anti-allergic drugs within 3 days before enrollment; The investigator judges that the subjects cannot follow the research procedures, comply with the agreement, or plan to permanently relocate from the area before the end of the research, or plan to leave the local area for a long time during the scheduled visit period; The relevant staff involved in this study or their immediate family members (such as spouses, parents, siblings or children); According to the investigator's judgment, there are other situations that are not suitable for participating in this clinical trial.
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: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Two doses were administered by intramuscular injection, 28 days apart | Biological: COVID-19 Variant (Omicron BA.5) mRNA Vaccine Low dose<br>* 50μg/dose<br>Drug: Placebo<br>* Saline solution<br>|
| Experimental: Group B<br>Two doses were administered by intramuscular injection, 28 days apart | Biological: COVID-19 Variant (Omicron BA.5) mRNA Vaccine High dose<br>* 100μg/dose<br>Drug: Placebo<br>* Saline solution<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of solicited adverse events | | Within 28 days after each dose/full dose |
| Incidence of unsolicited adverse events | | Within 28 days after each dose/full dose |
| Incidence of adverse events associated with the study vaccine | | Within 28 days after each dose/full dose |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of grade ≥3 adverse events | | Within 28 days after each dose/full dose |
| Incidence of grade ≥3 adverse events associated with the study vaccine | | Within 28 days after each dose/full dose |
| Statistics of withdrawal from the study due to adverse events | | Within 28 days after each dose/full dose |
| Incidence of SAE | | Within 28 days, 3 months, 6 months, and 12 months after the first dose of immunization to full immunization |
| Incidence of AESI | | Within 28 days, 3 months, 6 months, and 12 months after the first dose of immunization to full immunization |
| Incidence of SAE associated with the study vaccine | | Within 28 days, 3 months, 6 months, and 12 months after the first dose of immunization to full immunization |
| Incidence of AESI associated with the study vaccine | | Within 28 days, 3 months, 6 months, and 12 months after the first dose of immunization to full immunization |
| Incidence of clinically significant abnormalities in laboratory measures | | After vaccination |
|
||
NCT00932503
|
Antiseptic Sutures and Wound Infection
|
The aim of this study was to ascertain if the use of Vicryl plus® reduced the number of wound infections after transverse laparotomy comparing to polydioxanon suture.
|
All patients are treated using clinical pathways (CP) to standardise surgical procedures in our high volume centre. Part of the clinical process management was the standardisation of wound incision and abdominal wall closure.~Wound closure is achieved by a two-layer technique using continuous absorbable loop suture. The suture length to incision length ratio is at least 4:1. The running sutures are 1 cm apart and at least 1.5 cm from the wound edge 14. In the first timeperiod (TP1), the CP step for fascia closure foresees a PDS loop suture (PDS II®, 150 cm, Ethicon GmbH, Norderstedt, Germany). After the recruitment of 400 patients, that CP step is altered to the use of a triclosan-coated polyglactin 910 loop suture (Vicryl plus®, 150 cm, Ethicon GmbH, Norderstedt, Germany). The primary outcome is the number of wound infections. Patients demographic and disease as well as procedure related data are collected in a clinical information system (ISHmed on SAP platform, GSD, Berlin, Germany) prospectively. Risk factors for poor wound healing, such as operation time, patients age, sex, body mass index, blood loss, peritonitis, antibiotics, and performance level classified according to the American Society of Anesthesiologists (ASA), are collected prospectively to compare the two groups.
|
Do Triclosan Coated Sutures Reduce Wound Infections After Hepatobiliary Surgery? A Prospective Non Randomized Clinical Pathway Driven Study.
|
Wound Infection
|
* Device: Vicryl plus
|
Inclusion Criteria:~surgical pathologies accessed via transverse abdominal incision~primary fascial closure~Exclusion Criteria:~pregnancy~age under 18 years~open abdominal treatment~known hypersensitivity agains PDS/Vicryl/Triclosan
|
18 Years
| null |
All
|
No
|
Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome was the number of wound infections. | | 10 days after demission of patient from hospital |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary outcome was the number of incisional hernia | long time follow up analyzing the number of incisional hernia after laparotomy comparing Vicryl plus and PDS II | follow up points: 6 month, 1 year, 2 years and 3 years |
|
Vicryl plus, wound infection, coated suture material, open abdominal surgery, transverse laparotomy
|
Infections, Communicable Diseases, Wound Infection, Wounds and Injuries, Disease Attributes, Pathologic Processes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: PDS II<br>PDS II® loop suture was used for abdominal wall closure | |
| Active Comparator: Vicryl plus<br>antiseptic coated Vicryl plus was used for abdominal wall closure | Device: Vicryl plus<br>* triclosan-coated polyglactin 910 suture materials with antiseptic activity (Vicryl plus®, Ethicon GmbH, Norderstedt, Germany)<br>* Other names: Vicryl plus®;|
|
Antiseptic Sutures and Wound Infection
Study Overview
=================
Brief Summary
-----------------
The aim of this study was to ascertain if the use of Vicryl plus® reduced the number of wound infections after transverse laparotomy comparing to polydioxanon suture.
Detailed Description
-----------------
All patients are treated using clinical pathways (CP) to standardise surgical procedures in our high volume centre. Part of the clinical process management was the standardisation of wound incision and abdominal wall closure. Wound closure is achieved by a two-layer technique using continuous absorbable loop suture. The suture length to incision length ratio is at least 4:1. The running sutures are 1 cm apart and at least 1.5 cm from the wound edge 14. In the first timeperiod (TP1), the CP step for fascia closure foresees a PDS loop suture (PDS II®, 150 cm, Ethicon GmbH, Norderstedt, Germany). After the recruitment of 400 patients, that CP step is altered to the use of a triclosan-coated polyglactin 910 loop suture (Vicryl plus®, 150 cm, Ethicon GmbH, Norderstedt, Germany). The primary outcome is the number of wound infections. Patients demographic and disease as well as procedure related data are collected in a clinical information system (ISHmed on SAP platform, GSD, Berlin, Germany) prospectively. Risk factors for poor wound healing, such as operation time, patients age, sex, body mass index, blood loss, peritonitis, antibiotics, and performance level classified according to the American Society of Anesthesiologists (ASA), are collected prospectively to compare the two groups.
Official Title
-----------------
Do Triclosan Coated Sutures Reduce Wound Infections After Hepatobiliary Surgery? A Prospective Non Randomized Clinical Pathway Driven Study.
Conditions
-----------------
Wound Infection
Intervention / Treatment
-----------------
* Device: Vicryl plus
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: surgical pathologies accessed via transverse abdominal incision primary fascial closure Exclusion Criteria: pregnancy age under 18 years open abdominal treatment known hypersensitivity agains PDS/Vicryl/Triclosan
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: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: PDS II<br>PDS II® loop suture was used for abdominal wall closure | |
| Active Comparator: Vicryl plus<br>antiseptic coated Vicryl plus was used for abdominal wall closure | Device: Vicryl plus<br>* triclosan-coated polyglactin 910 suture materials with antiseptic activity (Vicryl plus®, Ethicon GmbH, Norderstedt, Germany)<br>* Other names: Vicryl plus®;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome was the number of wound infections. | | 10 days after demission of patient from hospital |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary outcome was the number of incisional hernia | long time follow up analyzing the number of incisional hernia after laparotomy comparing Vicryl plus and PDS II | follow up points: 6 month, 1 year, 2 years and 3 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vicryl plus, wound infection, coated suture material, open abdominal surgery, transverse laparotomy
|
NCT04604509
|
Nicotine Replacement Therapy, Counseling, Varenicline, and Bupropion for Smoking Cessation, the PISCES I Trial
|
This phase IV trial investigates how to personalize treatments (such as medications and/or counseling) for quitting smoking based on the unique character traits of participants. Nicotine replacement therapy, counseling, and/or drugs such as varenicline and bupropion may help participants quit smoking or change smoking behavior. This trial may also help doctors individualize smoking cessation treatment for participants who do not quit smoking after the first course of treatment.
|
PRIMARY OBJECTIVES:~I. Production of precise, unbiased estimates of treatment effects for the constituent therapies and rescue treatment pathways.~II. Development of the predictive algorithm, using the same machine learning techniques described in the preliminary data, to estimate the probabilities that an individual with a given pattern of baseline covariates will successfully quit smoking at the six and twelve week time points.~OUTLINE:~STAGE I: Participants are randomized to 1 of 2 groups.~GROUP I: Participants receive varenicline orally (PO) daily or twice daily (BID) for 6 weeks in the absence of unacceptable toxicity. Participants who quit smoking continue treatment for 6 additional weeks in the absence of unacceptable toxicity. Participants also receive behavioral smoking cessation counseling.~GROUP II: Participants receive nicotine replacement therapy (NRT) consisting of a patch, lozenges, or gum daily for 6 weeks in the absence of unacceptable toxicity. Participants who quit smoking continue treatment for 6 additional weeks in the absence of unacceptable toxicity. Participants also receive behavioral smoking cessation counseling.~STAGE II: After 6 weeks, participants from Stage I who do not quit smoking are randomized to 1 of 5 groups.~GROUP III: Participants continue to receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive behavioral smoking cessation counseling.~GROUP IV: Participants switch to a different therapy and receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive behavioral smoking cessation counseling.~GROUP V: Participants receive a higher dose and continue to receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive behavioral smoking cessation counseling.~GROUP VI: Participants continue to receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive bupropion hydrochloride (bupropion) PO daily for 6 weeks and behavioral smoking cessation counseling.~GROUP VII: Participants receive varenicline as in Group I and NRT as in Group II for 6 weeks. Participants also receive behavioral smoking cessation counseling.~After starting study treatment, patients are followed up at 3 and 6 months.
|
PISCES I: Precision Implemented Smoking Cessation Evaluation Study
|
Cigarette Smoking-Related Carcinoma
|
* Drug: Bupropion Hydrochloride Controlled-release
* Drug: Nicotine Replacement
* Other: Questionnaire Administration
* Other: Tobacco Cessation Counseling
* Drug: Varenicline
|
Inclusion Criteria:~Smoking 5 or more cigarettes, little cigars and/or cigarillos per day, on average, within the past 30 days preceding the screening visit and expired carbon monoxide (CO) >= 5 ppm and/or a urine Nic Check test > 0~Interested in treatment that might change smoking behavior or help them quit smoking~Able to follow verbal and written instructions in English and complete all aspects of the study~Provide informed consent and agree to all assessments and study procedures~Have an address and telephone number where they may be reached~Subjects must report current stable residence in the state of Texas. Stable residence is a domicile in which an individual can operate as if it were his or her own homestead and does not include shelters, halfway houses, treatment centers, or group homes~Be the only participant in their household currently receiving treatment on this protocol~Agree to be treated via telehealth (live audio-video conference and phone) and to be contacted via text and/or email~Willing to refrain from the use of other nicotine/tobacco products for the duration of the study~Exclusion Criteria:~Current enrollment or plans to enroll in another smoking cessation program during the study time frame, including plans to use other smoking cessation medications (i.e., over the counter [OTC] or prescription medication for smoking cessation) or smoking cessation treatments~Serious or unstable medical or psychiatric disorder within the past 3 months, as determined by the study physician~Being pregnant, engaging in breast-feeding, or being of childbearing potential and engaging in sexual activity that could lead to pregnancy and is not protected by a medically acceptable, effective method of birth control while enrolled in the study, as determined by self-report. Medically acceptable contraceptives include: (1) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (2) barrier methods (such as a condom or diaphragm) used with a spermicide, or (3) an intrauterine device (IUD). Contraceptive measures sold for emergency use after unprotected sex are not acceptable methods for routine use~Current use of certain medications:~Smoking cessation meds (last 7 days; e.g., bupropion, NRT, varenicline). Episodic use of NRT in the last 7 days may be considered if the participant agrees to only use study medication once randomized~Certain medications may be exclusionary and others are precautionary, to be evaluated on a case-by-case basis by study physician~Daily use of opioids for 30 days or more on phone screen or at screening is exclusionary, however as needed (PRN) use is allowed (i.e., 3 out of 7 days per week or less or if more frequent use in less than a month's duration)~History of hypersensitivity or allergic reaction to varenicline, NRT, or any component of these formulations as determined by the medical team~Self-report of a history or current diagnosis of schizophrenia or bipolar disorder~Current substance use disorder (Drug Abuse Screening Test [DAST] score > 3; Alcohol Use Disorders Identification Test [USAUDIT] score > 24)~Individuals who report depressive symptoms in the moderately severe or severe range on the Patient Health Questionnaire - Mood Module (PHQ-9) (scores of 15 or above); or who report current suicidal ideation on the PHQ-9~Individuals who report anxiety symptoms in the severe range on the Generalized Anxiety Disorder Scale (GAD-7) (scores of 15 or above); or meet criteria for panic syndrome on the PHQ Panic module~Psychiatric hospitalization within 1 year of screening date~Any otherwise not specified medical or psychiatric condition, illness, disorder, or concomitant medication that could compromise participant safety or treatment, as determined by the principal investigator and/or study physician~Participant considered by the investigator as unsuitable candidate for full participation in both the treatment and follow-up phases of the study
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| End of treatment seven-day point prevalence | Will use Bayesian statistical methods to estimate these effects and their accompanying posterior probabilities. | Up to 6 months |
| Expired carbon monoxide value | Will use Bayesian statistical methods to estimate these effects and their accompanying posterior probabilities. | Up to 6 months |
| Abstinence | Will evaluate utilizing a logistic regression model. | At 12 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days to relapse | Will analyze using Cox proportional hazards regression. | Up to 6 months |
|
Bupropion, Nicotine, Varenicline, Ganglionic Stimulants, Autonomic Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Nicotinic Agonists, Cholinergic Agonists, Cholinergic Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Antidepressive Agents, Second-Generation, Antidepressive Agents, Psychotropic Drugs, Dopamine Uptake Inhibitors, Neurotransmitter Uptake Inhibitors, Membrane Transport Modulators, Dopamine Agents, Cytochrome P-450 CYP2D6 Inhibitors, Cytochrome P-450 Enzyme Inhibitors, Enzyme Inhibitors
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I (varenicline, counseling)<br>Participants receive varenicline PO daily or BID for 6 weeks in the absence of unacceptable toxicity. Participants who quit smoking continue treatment for 6 additional weeks in the absence of unacceptable toxicity. Participants also receive behavioral smoking cessation counseling. | Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Tobacco Cessation Counseling<br>* Receive behavioral smoking cessation counseling<br>Drug: Varenicline<br>* Given PO<br>* Other names: CP-526555;|
| Experimental: Group II (NRT, counseling)<br>Participants receive NRT consisting of a patch, lozenges, or gum daily for 6 weeks in the absence of unacceptable toxicity. Participants who quit smoking continue treatment for 6 additional weeks in the absence of unacceptable toxicity. Participants also receive behavioral smoking cessation counseling. | Drug: Nicotine Replacement<br>* Given via nicotine patch, lozenges, or gum<br>* Other names: NRT;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Tobacco Cessation Counseling<br>* Receive behavioral smoking cessation counseling<br>|
| Experimental: Group III (varenicline or NRT, counseling)<br>Participants continue to receive varenicline as in Group I or NRT as in Group II for 6 additional weeks depending on which group they were assigned to. Participants also receive behavioral smoking cessation counseling. | Drug: Nicotine Replacement<br>* Given via nicotine patch, lozenges, or gum<br>* Other names: NRT;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Tobacco Cessation Counseling<br>* Receive behavioral smoking cessation counseling<br>Drug: Varenicline<br>* Given PO<br>* Other names: CP-526555;|
| Experimental: Group IV (varenicline or NRT, counseling)<br>Participants switch to a different therapy and receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive behavioral smoking cessation counseling. | Drug: Nicotine Replacement<br>* Given via nicotine patch, lozenges, or gum<br>* Other names: NRT;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Tobacco Cessation Counseling<br>* Receive behavioral smoking cessation counseling<br>Drug: Varenicline<br>* Given PO<br>* Other names: CP-526555;|
| Experimental: Group V (higher dose varenicline or NRT, counseling)<br>Participants receive a higher dose and continue to receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive behavioral smoking cessation counseling. | Drug: Nicotine Replacement<br>* Given via nicotine patch, lozenges, or gum<br>* Other names: NRT;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Tobacco Cessation Counseling<br>* Receive behavioral smoking cessation counseling<br>Drug: Varenicline<br>* Given PO<br>* Other names: CP-526555;|
| Experimental: Group VI (varenicline or NRT, bupropion, counseling)<br>Participants continue to receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive bupropion PO daily for 6 weeks and behavioral smoking cessation counseling. | Drug: Bupropion Hydrochloride Controlled-release<br>* Given PO<br>* Other names: Zyban;Drug: Nicotine Replacement<br>* Given via nicotine patch, lozenges, or gum<br>* Other names: NRT;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Tobacco Cessation Counseling<br>* Receive behavioral smoking cessation counseling<br>Drug: Varenicline<br>* Given PO<br>* Other names: CP-526555;|
| Experimental: Group VII (varenicline and NRT, counseling)<br>Participants receive varenicline as in Group I and NRT as in Group II for 6 weeks. Participants also receive behavioral smoking cessation counseling. | Drug: Nicotine Replacement<br>* Given via nicotine patch, lozenges, or gum<br>* Other names: NRT;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Tobacco Cessation Counseling<br>* Receive behavioral smoking cessation counseling<br>Drug: Varenicline<br>* Given PO<br>* Other names: CP-526555;|
|
Nicotine Replacement Therapy, Counseling, Varenicline, and Bupropion for Smoking Cessation, the PISCES I Trial
Study Overview
=================
Brief Summary
-----------------
This phase IV trial investigates how to personalize treatments (such as medications and/or counseling) for quitting smoking based on the unique character traits of participants. Nicotine replacement therapy, counseling, and/or drugs such as varenicline and bupropion may help participants quit smoking or change smoking behavior. This trial may also help doctors individualize smoking cessation treatment for participants who do not quit smoking after the first course of treatment.
Detailed Description
-----------------
PRIMARY OBJECTIVES: I. Production of precise, unbiased estimates of treatment effects for the constituent therapies and rescue treatment pathways. II. Development of the predictive algorithm, using the same machine learning techniques described in the preliminary data, to estimate the probabilities that an individual with a given pattern of baseline covariates will successfully quit smoking at the six and twelve week time points. OUTLINE: STAGE I: Participants are randomized to 1 of 2 groups. GROUP I: Participants receive varenicline orally (PO) daily or twice daily (BID) for 6 weeks in the absence of unacceptable toxicity. Participants who quit smoking continue treatment for 6 additional weeks in the absence of unacceptable toxicity. Participants also receive behavioral smoking cessation counseling. GROUP II: Participants receive nicotine replacement therapy (NRT) consisting of a patch, lozenges, or gum daily for 6 weeks in the absence of unacceptable toxicity. Participants who quit smoking continue treatment for 6 additional weeks in the absence of unacceptable toxicity. Participants also receive behavioral smoking cessation counseling. STAGE II: After 6 weeks, participants from Stage I who do not quit smoking are randomized to 1 of 5 groups. GROUP III: Participants continue to receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive behavioral smoking cessation counseling. GROUP IV: Participants switch to a different therapy and receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive behavioral smoking cessation counseling. GROUP V: Participants receive a higher dose and continue to receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive behavioral smoking cessation counseling. GROUP VI: Participants continue to receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive bupropion hydrochloride (bupropion) PO daily for 6 weeks and behavioral smoking cessation counseling. GROUP VII: Participants receive varenicline as in Group I and NRT as in Group II for 6 weeks. Participants also receive behavioral smoking cessation counseling. After starting study treatment, patients are followed up at 3 and 6 months.
Official Title
-----------------
PISCES I: Precision Implemented Smoking Cessation Evaluation Study
Conditions
-----------------
Cigarette Smoking-Related Carcinoma
Intervention / Treatment
-----------------
* Drug: Bupropion Hydrochloride Controlled-release
* Drug: Nicotine Replacement
* Other: Questionnaire Administration
* Other: Tobacco Cessation Counseling
* Drug: Varenicline
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Smoking 5 or more cigarettes, little cigars and/or cigarillos per day, on average, within the past 30 days preceding the screening visit and expired carbon monoxide (CO) >= 5 ppm and/or a urine Nic Check test > 0 Interested in treatment that might change smoking behavior or help them quit smoking Able to follow verbal and written instructions in English and complete all aspects of the study Provide informed consent and agree to all assessments and study procedures Have an address and telephone number where they may be reached Subjects must report current stable residence in the state of Texas. Stable residence is a domicile in which an individual can operate as if it were his or her own homestead and does not include shelters, halfway houses, treatment centers, or group homes Be the only participant in their household currently receiving treatment on this protocol Agree to be treated via telehealth (live audio-video conference and phone) and to be contacted via text and/or email Willing to refrain from the use of other nicotine/tobacco products for the duration of the study Exclusion Criteria: Current enrollment or plans to enroll in another smoking cessation program during the study time frame, including plans to use other smoking cessation medications (i.e., over the counter [OTC] or prescription medication for smoking cessation) or smoking cessation treatments Serious or unstable medical or psychiatric disorder within the past 3 months, as determined by the study physician Being pregnant, engaging in breast-feeding, or being of childbearing potential and engaging in sexual activity that could lead to pregnancy and is not protected by a medically acceptable, effective method of birth control while enrolled in the study, as determined by self-report. Medically acceptable contraceptives include: (1) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (2) barrier methods (such as a condom or diaphragm) used with a spermicide, or (3) an intrauterine device (IUD). Contraceptive measures sold for emergency use after unprotected sex are not acceptable methods for routine use Current use of certain medications: Smoking cessation meds (last 7 days; e.g., bupropion, NRT, varenicline). Episodic use of NRT in the last 7 days may be considered if the participant agrees to only use study medication once randomized Certain medications may be exclusionary and others are precautionary, to be evaluated on a case-by-case basis by study physician Daily use of opioids for 30 days or more on phone screen or at screening is exclusionary, however as needed (PRN) use is allowed (i.e., 3 out of 7 days per week or less or if more frequent use in less than a month's duration) History of hypersensitivity or allergic reaction to varenicline, NRT, or any component of these formulations as determined by the medical team Self-report of a history or current diagnosis of schizophrenia or bipolar disorder Current substance use disorder (Drug Abuse Screening Test [DAST] score > 3; Alcohol Use Disorders Identification Test [USAUDIT] score > 24) Individuals who report depressive symptoms in the moderately severe or severe range on the Patient Health Questionnaire - Mood Module (PHQ-9) (scores of 15 or above); or who report current suicidal ideation on the PHQ-9 Individuals who report anxiety symptoms in the severe range on the Generalized Anxiety Disorder Scale (GAD-7) (scores of 15 or above); or meet criteria for panic syndrome on the PHQ Panic module Psychiatric hospitalization within 1 year of screening date Any otherwise not specified medical or psychiatric condition, illness, disorder, or concomitant medication that could compromise participant safety or treatment, as determined by the principal investigator and/or study physician Participant considered by the investigator as unsuitable candidate for full participation in both the treatment and follow-up phases of the study
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I (varenicline, counseling)<br>Participants receive varenicline PO daily or BID for 6 weeks in the absence of unacceptable toxicity. Participants who quit smoking continue treatment for 6 additional weeks in the absence of unacceptable toxicity. Participants also receive behavioral smoking cessation counseling. | Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Tobacco Cessation Counseling<br>* Receive behavioral smoking cessation counseling<br>Drug: Varenicline<br>* Given PO<br>* Other names: CP-526555;|
| Experimental: Group II (NRT, counseling)<br>Participants receive NRT consisting of a patch, lozenges, or gum daily for 6 weeks in the absence of unacceptable toxicity. Participants who quit smoking continue treatment for 6 additional weeks in the absence of unacceptable toxicity. Participants also receive behavioral smoking cessation counseling. | Drug: Nicotine Replacement<br>* Given via nicotine patch, lozenges, or gum<br>* Other names: NRT;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Tobacco Cessation Counseling<br>* Receive behavioral smoking cessation counseling<br>|
| Experimental: Group III (varenicline or NRT, counseling)<br>Participants continue to receive varenicline as in Group I or NRT as in Group II for 6 additional weeks depending on which group they were assigned to. Participants also receive behavioral smoking cessation counseling. | Drug: Nicotine Replacement<br>* Given via nicotine patch, lozenges, or gum<br>* Other names: NRT;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Tobacco Cessation Counseling<br>* Receive behavioral smoking cessation counseling<br>Drug: Varenicline<br>* Given PO<br>* Other names: CP-526555;|
| Experimental: Group IV (varenicline or NRT, counseling)<br>Participants switch to a different therapy and receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive behavioral smoking cessation counseling. | Drug: Nicotine Replacement<br>* Given via nicotine patch, lozenges, or gum<br>* Other names: NRT;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Tobacco Cessation Counseling<br>* Receive behavioral smoking cessation counseling<br>Drug: Varenicline<br>* Given PO<br>* Other names: CP-526555;|
| Experimental: Group V (higher dose varenicline or NRT, counseling)<br>Participants receive a higher dose and continue to receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive behavioral smoking cessation counseling. | Drug: Nicotine Replacement<br>* Given via nicotine patch, lozenges, or gum<br>* Other names: NRT;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Tobacco Cessation Counseling<br>* Receive behavioral smoking cessation counseling<br>Drug: Varenicline<br>* Given PO<br>* Other names: CP-526555;|
| Experimental: Group VI (varenicline or NRT, bupropion, counseling)<br>Participants continue to receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive bupropion PO daily for 6 weeks and behavioral smoking cessation counseling. | Drug: Bupropion Hydrochloride Controlled-release<br>* Given PO<br>* Other names: Zyban;Drug: Nicotine Replacement<br>* Given via nicotine patch, lozenges, or gum<br>* Other names: NRT;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Tobacco Cessation Counseling<br>* Receive behavioral smoking cessation counseling<br>Drug: Varenicline<br>* Given PO<br>* Other names: CP-526555;|
| Experimental: Group VII (varenicline and NRT, counseling)<br>Participants receive varenicline as in Group I and NRT as in Group II for 6 weeks. Participants also receive behavioral smoking cessation counseling. | Drug: Nicotine Replacement<br>* Given via nicotine patch, lozenges, or gum<br>* Other names: NRT;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Tobacco Cessation Counseling<br>* Receive behavioral smoking cessation counseling<br>Drug: Varenicline<br>* Given PO<br>* Other names: CP-526555;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| End of treatment seven-day point prevalence | Will use Bayesian statistical methods to estimate these effects and their accompanying posterior probabilities. | Up to 6 months |
| Expired carbon monoxide value | Will use Bayesian statistical methods to estimate these effects and their accompanying posterior probabilities. | Up to 6 months |
| Abstinence | Will evaluate utilizing a logistic regression model. | At 12 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days to relapse | Will analyze using Cox proportional hazards regression. | Up to 6 months |
|
|
NCT01045564
|
Safety and Immunogenicity of Vaccine in Adults at Occupational Risk for Influenza A (H5N1) Exposure
|
The purpose of this study is to characterize the immunogenicity and safety of 3 doses of GSK's avian flu vaccine GSK 1557484A given at different time intervals to adults aged 18 years or greater who are at increased occupational risk of H5N1 exposure.
|
Safety and Immunogenicity of GSK 15574484A Vaccine in Adults at Occupational Risk for Influenza A (H5N1) Exposure
|
Influenza
|
* Biological: GSK influenza virus H5N1 vaccine 1557484A
|
Inclusion Criteria:~A male or female 18 years of age or greater at the time of the first vaccination.~At increased risk of occupational exposure to H5N1 influenza viruses based on:~Exposure to diseased poultry or wild birds,~Exposure, or potential exposure, to human cases of unidentified respiratory disease or known avian influenza,~Handling of human or avian microbiological specimens,~Handling of H5N1 viral isolates,~Or status critical to the implementation of emergency response measures in the event of an influenza pandemic declaration.~Written informed consent obtained from the subject.~Stable health status as defined by absence of a health event satisfying the definition of a serious adverse event, or a change in an ongoing drug therapy due to therapeutic failure or symptoms of drug toxicity, within one (1) month prior to enrollment.~Comprehension of the study requirements, ability to comprehend and comply with procedures for collection of safety data, expressed availability for the required study period, and ability and willingness to attend scheduled visits.~Exclusion Criteria:~Presence of evidence of substance abuse or of neurological or psychiatric diagnoses which, although stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports.~Presence of an oral temperature >= 37.8ºC, or acute symptoms greater than mild severity on the scheduled date of first vaccination.~Diagnosed with cancer, or treatment for cancer, within 3 years.~Persons with a history of cancer who are disease-free without treatment for 3 years or more are eligible.~Persons with a history of histologically-confirmed basal cell carcinoma of the skin successfully treated with local excision only are excepted and may enroll within 3 years of diagnosis, but other histologic types of skin cancer require a 3 year untreated and disease-free window as above.~Women who are disease-free 3 years or more after treatment for breast cancer and receiving long-term prophylactic tamoxifen are excepted and may enroll.~Any confirmed or suspected immunosuppressive or immunodeficient condition including history of human immunodeficiency virus (HIV) infection.~Receipt of systemic glucocorticoids within 1 month prior to study enrollment, or any other cytotoxic or immunosuppressive drug within 6 months of study enrollment.~Receipt of any immunoglobulins and/or any blood products within 3 months of study enrollment or planned administration of any of these products during the study period.~Any significant disorder of coagulation or treatment with warfarin derivatives or heparin. Persons receiving individual doses of low molecular weight heparin outside of 24 hours prior to vaccination, are eligible. Persons receiving prophylactic antiplatelet medications, e.g., low-dose aspirin, and without a clinically-apparent bleeding tendency, are eligible.~An acute evolving neurological disorder or history of Guillain-Barré syndrome within 6 weeks of receipt of seasonal influenza vaccine.~Administration of any vaccines within 30 days before any study vaccination.~Exposure to any investigational or non-registered product (drug or vaccine) during this trial, or within 30 days prior to study enrollment. Potential subjects in the follow-up (i.e., no treatment) phase of a prior investigational study may be enrolled if the investigator's judgment is that it will have no effect on safety, reactogenicity, or immunogenicity endpoints in this study; and that it does not violate the protocol requirements of the prior trial.~Any known or suspected allergy to any constituent of influenza vaccines (including egg proteins or mercurial preservatives); a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine.~Receipt of analgesic or antipyretic medication with the specific intent of prophylaxis of vaccine reactogenicity on the day of treatment constitutes a contraindication to administration of study vaccine at that point in time;~Known pregnancy or a positive urine beta-human chorionic gonadotropin (β-hCG) test result prior to any vaccination.~Lactating or nursing.~Women of child bearing potential who lack a history of reliable contraceptive practices. The provision of this history does NOT replace the requirement to perform, and obtain negative results in pregnancy urine tests prior to treatments.~Reliable contraceptive practices include:~consistent abstinence from heterosexual activity,~consistent use of combined or progestogen oral contraceptives,~injectable progestogen,~implants of levonorgestrel,~estrogen or estrogen/ progestogen vaginal ring,~percutaneous contraceptive patches or intrauterine device (IUD) or intrauterine system (IUS),~vasectomy with documented azoospermia of >= 6 months of the sole male partner, or~double barrier method (condom or occlusive cap plus spermicidal agent).
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Booster humoral immune response in terms of Hemagglutination Inhibition (HI) antibodies (after second vaccination). | | Day 0 and 21 days after the second vaccination |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Booster humoral immune response in terms of Hemagglutination Inhibition (HI) antibodies.on secondary readouts (after second vaccination) | | Days 0 and 21 days after second vaccination |
| Primary humoral immune response in terms of Hemagglutination Inhibition (HI) antibodies (after first vaccination) | | Days 0, 21 and 42 after first vaccination (depending on vaccination schedule) |
| Humoral immune response in terms of Hemagglutination Inhibition (HI) antibodies (after third vaccination) | | Days 364, 385, and 546 |
| Humoral immune response in terms of microneutralization titers and cellular T-cell immune response | | Days 0, 21, 21 days after second vaccination, 364, 385, and 546 (depending on vaccination schedule) |
| Occurrence of specifically-solicited local and general signs and symptoms | | During a 7-day follow up period after each vaccine dose |
| Occurrence of all unsolicited adverse events | | During a 21-day follow up period after each vaccine dose |
| Occurrence of serious adverse events and adverse events of special interest | | From day 0 through day 546 |
|
Immunogenicity, Vaccines, H5N1, Influenza, Pandemic, Human, Avian, Safety
|
Influenza, Human, Influenza in Birds, Respiratory Tract Infections, Infections, Orthomyxoviridae Infections, RNA Virus Infections, Virus Diseases, Respiratory Tract Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>One dose of study vaccine (GSK 1557484A) on Day 0, Day 182, and Day 364 | Biological: GSK influenza virus H5N1 vaccine 1557484A<br>* Three doses of GSK 1557484A administered intramuscularly (IM), the first and third in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm<br>|
| Experimental: B<br>One dose of study vaccine (GSK 1557484A) on Day 0, Day 91, and Day 364 | Biological: GSK influenza virus H5N1 vaccine 1557484A<br>* Three doses of GSK 1557484A administered intramuscularly (IM), the first and third in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm<br>|
| Experimental: C<br>One dose of study vaccine (GSK 1557484A) on Day 0, Day 21, and Day 364 | Biological: GSK influenza virus H5N1 vaccine 1557484A<br>* Three doses of GSK 1557484A administered intramuscularly (IM), the first and third in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm<br>|
| Experimental: D<br>One dose of study vaccine (GSK 1557484A) on Day 0, Day 21, and Day 364 | Biological: GSK influenza virus H5N1 vaccine 1557484A<br>* Three doses of GSK 1557484A administered intramuscularly (IM), the first and third in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm<br>|
| Experimental: E<br>One dose of study vaccine (GSK 1557484A) on Day 0, Day 21, and Day 364 | Biological: GSK influenza virus H5N1 vaccine 1557484A<br>* Three doses of GSK 1557484A administered intramuscularly (IM), the first and third in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm<br>|
|
Safety and Immunogenicity of Vaccine in Adults at Occupational Risk for Influenza A (H5N1) Exposure
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to characterize the immunogenicity and safety of 3 doses of GSK's avian flu vaccine GSK 1557484A given at different time intervals to adults aged 18 years or greater who are at increased occupational risk of H5N1 exposure.
Official Title
-----------------
Safety and Immunogenicity of GSK 15574484A Vaccine in Adults at Occupational Risk for Influenza A (H5N1) Exposure
Conditions
-----------------
Influenza
Intervention / Treatment
-----------------
* Biological: GSK influenza virus H5N1 vaccine 1557484A
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A male or female 18 years of age or greater at the time of the first vaccination. At increased risk of occupational exposure to H5N1 influenza viruses based on: Exposure to diseased poultry or wild birds, Exposure, or potential exposure, to human cases of unidentified respiratory disease or known avian influenza, Handling of human or avian microbiological specimens, Handling of H5N1 viral isolates, Or status critical to the implementation of emergency response measures in the event of an influenza pandemic declaration. Written informed consent obtained from the subject. Stable health status as defined by absence of a health event satisfying the definition of a serious adverse event, or a change in an ongoing drug therapy due to therapeutic failure or symptoms of drug toxicity, within one (1) month prior to enrollment. Comprehension of the study requirements, ability to comprehend and comply with procedures for collection of safety data, expressed availability for the required study period, and ability and willingness to attend scheduled visits. Exclusion Criteria: Presence of evidence of substance abuse or of neurological or psychiatric diagnoses which, although stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports. Presence of an oral temperature >= 37.8ºC, or acute symptoms greater than mild severity on the scheduled date of first vaccination. Diagnosed with cancer, or treatment for cancer, within 3 years. Persons with a history of cancer who are disease-free without treatment for 3 years or more are eligible. Persons with a history of histologically-confirmed basal cell carcinoma of the skin successfully treated with local excision only are excepted and may enroll within 3 years of diagnosis, but other histologic types of skin cancer require a 3 year untreated and disease-free window as above. Women who are disease-free 3 years or more after treatment for breast cancer and receiving long-term prophylactic tamoxifen are excepted and may enroll. Any confirmed or suspected immunosuppressive or immunodeficient condition including history of human immunodeficiency virus (HIV) infection. Receipt of systemic glucocorticoids within 1 month prior to study enrollment, or any other cytotoxic or immunosuppressive drug within 6 months of study enrollment. Receipt of any immunoglobulins and/or any blood products within 3 months of study enrollment or planned administration of any of these products during the study period. Any significant disorder of coagulation or treatment with warfarin derivatives or heparin. Persons receiving individual doses of low molecular weight heparin outside of 24 hours prior to vaccination, are eligible. Persons receiving prophylactic antiplatelet medications, e.g., low-dose aspirin, and without a clinically-apparent bleeding tendency, are eligible. An acute evolving neurological disorder or history of Guillain-Barré syndrome within 6 weeks of receipt of seasonal influenza vaccine. Administration of any vaccines within 30 days before any study vaccination. Exposure to any investigational or non-registered product (drug or vaccine) during this trial, or within 30 days prior to study enrollment. Potential subjects in the follow-up (i.e., no treatment) phase of a prior investigational study may be enrolled if the investigator's judgment is that it will have no effect on safety, reactogenicity, or immunogenicity endpoints in this study; and that it does not violate the protocol requirements of the prior trial. Any known or suspected allergy to any constituent of influenza vaccines (including egg proteins or mercurial preservatives); a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine. Receipt of analgesic or antipyretic medication with the specific intent of prophylaxis of vaccine reactogenicity on the day of treatment constitutes a contraindication to administration of study vaccine at that point in time; Known pregnancy or a positive urine beta-human chorionic gonadotropin (β-hCG) test result prior to any vaccination. Lactating or nursing. Women of child bearing potential who lack a history of reliable contraceptive practices. The provision of this history does NOT replace the requirement to perform, and obtain negative results in pregnancy urine tests prior to treatments. Reliable contraceptive practices include: consistent abstinence from heterosexual activity, consistent use of combined or progestogen oral contraceptives, injectable progestogen, implants of levonorgestrel, estrogen or estrogen/ progestogen vaginal ring, percutaneous contraceptive patches or intrauterine device (IUD) or intrauterine system (IUS), vasectomy with documented azoospermia of >= 6 months of the sole male partner, or double barrier method (condom or occlusive cap plus spermicidal agent).
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: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>One dose of study vaccine (GSK 1557484A) on Day 0, Day 182, and Day 364 | Biological: GSK influenza virus H5N1 vaccine 1557484A<br>* Three doses of GSK 1557484A administered intramuscularly (IM), the first and third in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm<br>|
| Experimental: B<br>One dose of study vaccine (GSK 1557484A) on Day 0, Day 91, and Day 364 | Biological: GSK influenza virus H5N1 vaccine 1557484A<br>* Three doses of GSK 1557484A administered intramuscularly (IM), the first and third in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm<br>|
| Experimental: C<br>One dose of study vaccine (GSK 1557484A) on Day 0, Day 21, and Day 364 | Biological: GSK influenza virus H5N1 vaccine 1557484A<br>* Three doses of GSK 1557484A administered intramuscularly (IM), the first and third in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm<br>|
| Experimental: D<br>One dose of study vaccine (GSK 1557484A) on Day 0, Day 21, and Day 364 | Biological: GSK influenza virus H5N1 vaccine 1557484A<br>* Three doses of GSK 1557484A administered intramuscularly (IM), the first and third in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm<br>|
| Experimental: E<br>One dose of study vaccine (GSK 1557484A) on Day 0, Day 21, and Day 364 | Biological: GSK influenza virus H5N1 vaccine 1557484A<br>* Three doses of GSK 1557484A administered intramuscularly (IM), the first and third in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Booster humoral immune response in terms of Hemagglutination Inhibition (HI) antibodies (after second vaccination). | | Day 0 and 21 days after the second vaccination |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Booster humoral immune response in terms of Hemagglutination Inhibition (HI) antibodies.on secondary readouts (after second vaccination) | | Days 0 and 21 days after second vaccination |
| Primary humoral immune response in terms of Hemagglutination Inhibition (HI) antibodies (after first vaccination) | | Days 0, 21 and 42 after first vaccination (depending on vaccination schedule) |
| Humoral immune response in terms of Hemagglutination Inhibition (HI) antibodies (after third vaccination) | | Days 364, 385, and 546 |
| Humoral immune response in terms of microneutralization titers and cellular T-cell immune response | | Days 0, 21, 21 days after second vaccination, 364, 385, and 546 (depending on vaccination schedule) |
| Occurrence of specifically-solicited local and general signs and symptoms | | During a 7-day follow up period after each vaccine dose |
| Occurrence of all unsolicited adverse events | | During a 21-day follow up period after each vaccine dose |
| Occurrence of serious adverse events and adverse events of special interest | | From day 0 through day 546 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immunogenicity, Vaccines, H5N1, Influenza, Pandemic, Human, Avian, Safety
|
|
NCT03070691
|
Efficacy, Safety and Tolerability of Topically Applied LDE225 Cream (Hedgehog Pathway Inhibitor) in Adult Patients With Nevoid Basal Cell Carcinoma Syndrome (NBCCS)
|
This 22 week study will assess the efficacy, safety, and tolerability of LDE225 versus vehicle when applied topically to basal cell carcinoma (BCC) in patients with NBCCS. Patients will treat multiple BCCs for up to 12 weeks. Treatment success is defined as complete clinical clearance and complete histological clearance in BCCs.
|
A Randomized, Double-blind, Vehicle-controlled, Multicenter Trial of Topically Administered LDE225 Cream (0.75% Bid) to Evaluate Clearance of Basal Cell Carcinoma in Adult Patients With Nevoid Basal Cell Carcinoma Syndrome
|
Basal Cell Carcinoma
|
* Drug: LDE225B
* Drug: Vehicle
|
Inclusion Criteria:~Adult greater than 18 years old, male or female.~Patient must be able to understand and communicate with the investigator and comply with the requirements of the study.~Typical presentation of NBCCS in the opinion of the investigator~At least one of the major clinical criteria of NBCCS.~Multiple BCCs during the screening period~Exclusion Criteria:~Any concomitant dermatological disease that could confound the evaluations, based on the discretion of the investigator.~Prior exposure to LDE225.~Use of systemic treatment for BCC in the 4 weeks prior to Baseline.~Use of topical treatment or photodynamic therapy (PDT) in the 12 weeks prior to Baseline.~Use of other investigational drugs at Baseline, or within 30 days or 5 half-lives prior to Baseline, whichever is longer.~Clinically significant medical condition, as per judgment of the investigator.~History of hypersensitivity to any of the ingredient of the study drug.~Pregnant or nursing (lactating) women~Women of child-bearing potential and fertile males, UNLESS they are using two birth control methods~Other protocol-defined inclusion/exclusion criteria may apply
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To demonstrate superiority of topical LDE225 versus vehicle in terms of treatment success in patients with NBCCs. Measure: Complete clinical clearance and complete histological clearance of BCCs | | 4 weeks after LDE225 treatment |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety of topical treatment with LDE225, compared to vehicle. Measure: Reported systemic adverse events in patients with NBCCS | | Treatment phase and up to 4 weeks after LDE225 treatment |
| To evaluate the local tolerability of topical treatment with LDE225, compared to vehicle. Measure:Reported local adverse events in patients with NBCCS | | Treatment phase and up to 4 weeks after LDE225 treatment |
| To assess the rate of complete clinical clearance of BCCs in patients with NBCCS. Measure: No clinical residual signs of carcinoma | | 4 weeks after LDE225 treatment |
| To assess the rate of complete histological clearance of BCCs in patients with NBCCS. Measure: No residual tumor tissue | | 4 weeks after LDE225 treatment |
|
Basal Cell Nevus Syndrome, BCNS, Hedgehog pathway inhibitor, topical, Smoothened, Basal cell carcinoma, Nevoid Basal Cell Carcinoma Syndrome, NBCCS, Gorlin syndrome, Gorlin-Goltz Syndrome
|
Carcinoma, Carcinoma, Basal Cell, Basal Cell Nevus Syndrome, Syndrome, Disease, Pathologic Processes, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Neoplasms, Neoplasms, Basal Cell, Odontogenic Cysts, Jaw Cysts, Bone Cysts, Cysts, Neoplastic Syndromes, Hereditary, Bone Diseases, Developmental, Bone Diseases, Musculoskeletal Diseases, Jaw Diseases, Stomatognathic Diseases, Abnormalities, Multiple, Congenital Abnormalities, Genetic Diseases, Inborn
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LDE225 0.75% cream<br> | Drug: LDE225B<br>* Cream, 2x daily<br>|
| Placebo Comparator: Vehicle<br> | Drug: Vehicle<br>* cream, 2x daily<br>|
|
Efficacy, Safety and Tolerability of Topically Applied LDE225 Cream (Hedgehog Pathway Inhibitor) in Adult Patients With Nevoid Basal Cell Carcinoma Syndrome (NBCCS)
Study Overview
=================
Brief Summary
-----------------
This 22 week study will assess the efficacy, safety, and tolerability of LDE225 versus vehicle when applied topically to basal cell carcinoma (BCC) in patients with NBCCS. Patients will treat multiple BCCs for up to 12 weeks. Treatment success is defined as complete clinical clearance and complete histological clearance in BCCs.
Official Title
-----------------
A Randomized, Double-blind, Vehicle-controlled, Multicenter Trial of Topically Administered LDE225 Cream (0.75% Bid) to Evaluate Clearance of Basal Cell Carcinoma in Adult Patients With Nevoid Basal Cell Carcinoma Syndrome
Conditions
-----------------
Basal Cell Carcinoma
Intervention / Treatment
-----------------
* Drug: LDE225B
* Drug: Vehicle
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult greater than 18 years old, male or female. Patient must be able to understand and communicate with the investigator and comply with the requirements of the study. Typical presentation of NBCCS in the opinion of the investigator At least one of the major clinical criteria of NBCCS. Multiple BCCs during the screening period Exclusion Criteria: Any concomitant dermatological disease that could confound the evaluations, based on the discretion of the investigator. Prior exposure to LDE225. Use of systemic treatment for BCC in the 4 weeks prior to Baseline. Use of topical treatment or photodynamic therapy (PDT) in the 12 weeks prior to Baseline. Use of other investigational drugs at Baseline, or within 30 days or 5 half-lives prior to Baseline, whichever is longer. Clinically significant medical condition, as per judgment of the investigator. History of hypersensitivity to any of the ingredient of the study drug. Pregnant or nursing (lactating) women Women of child-bearing potential and fertile males, UNLESS they are using two birth control methods 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: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LDE225 0.75% cream<br> | Drug: LDE225B<br>* Cream, 2x daily<br>|
| Placebo Comparator: Vehicle<br> | Drug: Vehicle<br>* cream, 2x daily<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To demonstrate superiority of topical LDE225 versus vehicle in terms of treatment success in patients with NBCCs. Measure: Complete clinical clearance and complete histological clearance of BCCs | | 4 weeks after LDE225 treatment |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety of topical treatment with LDE225, compared to vehicle. Measure: Reported systemic adverse events in patients with NBCCS | | Treatment phase and up to 4 weeks after LDE225 treatment |
| To evaluate the local tolerability of topical treatment with LDE225, compared to vehicle. Measure:Reported local adverse events in patients with NBCCS | | Treatment phase and up to 4 weeks after LDE225 treatment |
| To assess the rate of complete clinical clearance of BCCs in patients with NBCCS. Measure: No clinical residual signs of carcinoma | | 4 weeks after LDE225 treatment |
| To assess the rate of complete histological clearance of BCCs in patients with NBCCS. Measure: No residual tumor tissue | | 4 weeks after LDE225 treatment |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Basal Cell Nevus Syndrome, BCNS, Hedgehog pathway inhibitor, topical, Smoothened, Basal cell carcinoma, Nevoid Basal Cell Carcinoma Syndrome, NBCCS, Gorlin syndrome, Gorlin-Goltz Syndrome
|
|
NCT05392855
|
Symptom Based Performance of Airway Clearance After Starting Highly Effective Modulators for Cystic Fibrosis (SPACE-CF)
|
Cystic Fibrosis (CF) is an autosomal recessive disease cause by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) manifesting in multiple organs, the most common cause of morbidity and mortality continues to be the pulmonary manifestation. CFTR dysfunction leads to reduced mucociliary clearance, impaired innate immune system function in the lungs (within the airway surface liquid [ASL] lining the epithelial barrier of the lungs) and reduced ASL hydration (stickier mucus). To try and help correct this underlying defect patients have been performing airway clearance for decades using different techniques (Percussion and postural drainage [P&PD], Positive expiratory pressure [PEP], Oscillatory positive expiratory pressure [OPEP], High-frequency chest compression [HFCC], exercise), inhaled mucolytics (Hypertonic Saline, Pulmozyme) and inhaled antibiotics. However, performing daily airway clearance can be a large burden on patients and their families with a median number of daily therapies around 7 and average time spent on therapies at almost 2 hours daily. This high treatment burden leads many patients to have reduced adherence to their regimens and multiple studies have shown around 20% of patients performing no daily airway clearance. Since the release of highly effective CFTR modulator therapy patients have experienced improvements in lung function measurements and imaging-based ventilation measurements, reduction in pulmonary exacerbations, and improvement in daily symptom scores. Over 80% of patients and their families and over 95% of clinicians in the United States support the idea of trials looking into the simplification of airway clearance regimens. Combining the inability of most patients to complete their daily regimens, patient and clinician interest in treatment simplification research, and the overwhelming cost of most inhaled medications in cystic fibrosis with the improvement in mucociliary transport and symptoms with highly effective modulator therapy suggests a research program aimed at reducing the treatment burden of daily airway clearance should be considered. The investigators propose the following: determine if there is additional benefit in continuous airway clearance regimens after starting Elexacaftor-Tezacaftor-Ivacaftor (ETI) and if so, is this benefit noticeable on pulmonary function testing and imaging.
|
This will be a randomized controlled trial design with 2:1 randomization (2 to symptom driven to 1 in continuous) for this pilot study to determine if symptom-driven airway clearance after starting Elexacaftor-Tezacaftor-Ivacaftor (ETI) therapy is feasible and can eventually determine if it is non-inferior to continuing airway clearance therapies. The study will be performed as an intention to treat protocol. All participants who are eligible and enrolled will be asked to perform airway clearance twice daily for 12 weeks prior to randomization and then will be followed for 12 weeks including study visits at week 0, week 4, week 8, and week 12. The study will require no change in current use of inhaled antibiotics nor adjust the frequency of the medication during the study. Airway clearance methods to be recorded include aerobika or flutter valve, high frequency chest oscillation therapy (vest), intrapulmonary percussive ventilator, or exercise performed specially for airway clearance. The medications to be monitored included nebulized Albuterol, nebulized hypertonic saline, nebulized Pulmozyme, and nebulized mannitol. The continuous arm (control arm) will be asked to perform airway clearance twice daily for the entirety of the study and record all therapies performed daily. The symptom driven arm will perform airway clearance on their own discretion, whether this be from steady decline in baseline respiratory status or acute flair of symptoms related to infectious etiology. At baseline participants will undergo pulmonary function testing, sputum/throat culture and Cystic Fibrosis Questionnaire Revise (CFQ-R). On week 0, week 4, week 8 and week 12 visits the participants will undergo pulmonary function testing and CFQ-R with addition of sputum/throat cultures on week 12. Between each study visit participants will be asked to perform home spirometry once weekly for the 12-week trial period. For participants enrolled in the continuous group the investigators will ask for participants to perform home spirometry after either twice daily airway clearance routine or for the symptom-based group to perform at roughly the same time of day for each test. Participants will also be asked to keep a daily cystic fibrosis diary during the run-in period and study period in which participants will record if, and how frequent, participants use any airway clearance medications or devices during the day. A reduction in percent predicted forced expiratory volume in 1 second (ppFEV1%) or percent predicted forced vital capacity (ppFVC%) of more than 10% in laboratory PFT testing for 2 consecutive weeks will be deemed an adverse event and lead to the participant in the symptom driven arm being instructed to perform daily airway clearance therapy. A reduction in ppFEV1% and/or ppFVC% in home spirometry by more than 10% will trigger a need for in lab PFT testing to determine if participants have developed an adverse event leading to performing daily airway clearance therapy or if participants are to continue symptom-based airway clearance. Other criteria for participants to be evaluate in-person between study visits include use of daily airway clearance for more than 7 consecutive days in the symptom-based arm or signs and symptoms of a possible acute pulmonary exacerbation. If participants develop an exacerbation from an identifiable cause other than their primary CF lung disease (viral infection, asthma exacerbation, pulmonary embolism, etc.) participants will undergo appropriate treatment, and while the event will be deemed an adverse event, participants will continue with their current treatment protocol. Participants who are treated for an acute severe pulmonary exacerbation requiring IV antibiotics and/or hospitalization will either continue in the continuous treatment arm or if in the symptom driven arm be instructed to perform daily airway clearance for the duration of the study. In participants with concurrent asthma diagnoses, the investigators will not require any discontinuation of additional inhaler/nebulized therapies that are asthma specific, but no bronchodilators will be started specifically for the study.
|
Symptom Based Performance of Airway Clearance Therapy After Starting Highly Effective CFTR Modulator Therapy for Cystic Fibrosis
|
Cystic Fibrosis, Mucociliary Clearance Defect
|
* Other: Symptom driven performance of airway clearance
* Other: Continuous daily performance of airway clearance
|
Inclusion Criteria:~age > 18 years at the time of recruitment~treatment with Elexacaftor-Tezacaftor-Ivacaftor for > 90 days prior to enrollment~willing to continue twice daily airway clearance for a minimum of 90 days and up to180 days if enrolled in the continuing treatment arm~no exacerbations in the last 28 days~Exclusion Criteria:~active smoking or vaping (tobacco, marijuana, recreational drugs)~recent change in chronic airway clearance regimen with the last 28 days~inability to tolerate airway clearance or intolerance to either/or hypertonic saline and Pulmozyme~current treatment for an acute pulmonary exacerbation~ongoing therapy for Nontuberculous Mycobacterium (NTM)~investigational drug use
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial design with 2:1 randomization (2 to symptom driven to 1 in continuous) for this pilot study to determine if intermittent and symptom-driven airway clearance after starting Elexacaftor-Tezacaftor-Ivacaftor (ETI) therapy can be determined to be non-inferior to continuing airway clearance therapies.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change in percent predicted FEV1 (ppFEV1) from week 0 to week 12 in symptom driven airway clearance arm | Difference between symptom driven airway clearance arm and continue daily airway clearance arm in the absolute change in ppFEV1 from Week 0 to Week 12 | 12 weeks |
| Absolute change in percent predicted FVC (ppFVC) from week 0 to week 12 in symptom driven airway clearance arm | Difference between symptom driven airway clearance arm and continue daily airway clearance arm in the absolute change in ppFVC from Week 0 to Week 12 | 12 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change in respiratory symptoms based upon Cystic Fibrosis Questionnaire Revise score | Difference between symptom driven airway clearance arm and continue daily airway clearance arm in the absolute change in respiratory symptoms based upon Cystic Fibrosis Questionnaire Revise score (CFQ-R). Scores for the CFQ-R range from 0-100 with higher scores analogous to better outcomes. | 12 weeks |
| Incidence of adverse events (AE) in the symptom driven airway clearance arm | Difference between symptom driven airway clearance arm and continue daily airway clearance arm in the proportion of participants with at least one event per week | 12 weeks |
| Frequency of performance of airway clearance in symptom driven airway clearance arm | Difference between symptom driven airway clearance arm and continue daily airway clearance arm in the absolute difference of performance of airway clearance | 12 weeks |
| Change in airway colonization with S. aureus or P. aeruginosa | Difference between symptom based airway clearance arm and continue daily airway clearance arm in the absolute difference in sputum/throat cultures positive for S. aureus or P. aeruginosa | 12 weeks |
|
Cystic Fibrosis, Mucociliary clearance, Highly Effective CFTR Modulator Therapy
|
Cystic Fibrosis, Fibrosis, Pathologic Processes, Pancreatic Diseases, Digestive System Diseases, Lung Diseases, Respiratory Tract Diseases, Genetic Diseases, Inborn, Infant, Newborn, Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Symptom driven<br>Symptom driven performance of airway clearance regimen | Other: Symptom driven performance of airway clearance<br>* Perform symptom driven/intermittent airway clearance therapy with frequency based off of patient's daily symptoms including mobilization therapy (high-frequency chest compression or vest device, intrapulmonary percussive ventilator, positive expiratory pressure device) and inhaled/nebulized therapies of albuterol, hypertonic saline and dornase alfa for the 12 week study period.<br>|
| Active Comparator: Continuous<br>Continuous performance of baseline daily airway clearance regimen | Other: Continuous daily performance of airway clearance<br>* Continue run-in protocol of twice daily airway clearance using twice daily mobilization therapy (high-frequency chest compression or vest device, intrapulmonary percussive ventilator, positive expiratory pressure device) and inhaled/nebulized therapies of albuterol, hypertonic saline and dornase alfa for the 12 week study period.<br>|
|
Symptom Based Performance of Airway Clearance After Starting Highly Effective Modulators for Cystic Fibrosis (SPACE-CF)
Study Overview
=================
Brief Summary
-----------------
Cystic Fibrosis (CF) is an autosomal recessive disease cause by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) manifesting in multiple organs, the most common cause of morbidity and mortality continues to be the pulmonary manifestation. CFTR dysfunction leads to reduced mucociliary clearance, impaired innate immune system function in the lungs (within the airway surface liquid [ASL] lining the epithelial barrier of the lungs) and reduced ASL hydration (stickier mucus). To try and help correct this underlying defect patients have been performing airway clearance for decades using different techniques (Percussion and postural drainage [P&PD], Positive expiratory pressure [PEP], Oscillatory positive expiratory pressure [OPEP], High-frequency chest compression [HFCC], exercise), inhaled mucolytics (Hypertonic Saline, Pulmozyme) and inhaled antibiotics. However, performing daily airway clearance can be a large burden on patients and their families with a median number of daily therapies around 7 and average time spent on therapies at almost 2 hours daily. This high treatment burden leads many patients to have reduced adherence to their regimens and multiple studies have shown around 20% of patients performing no daily airway clearance. Since the release of highly effective CFTR modulator therapy patients have experienced improvements in lung function measurements and imaging-based ventilation measurements, reduction in pulmonary exacerbations, and improvement in daily symptom scores. Over 80% of patients and their families and over 95% of clinicians in the United States support the idea of trials looking into the simplification of airway clearance regimens. Combining the inability of most patients to complete their daily regimens, patient and clinician interest in treatment simplification research, and the overwhelming cost of most inhaled medications in cystic fibrosis with the improvement in mucociliary transport and symptoms with highly effective modulator therapy suggests a research program aimed at reducing the treatment burden of daily airway clearance should be considered. The investigators propose the following: determine if there is additional benefit in continuous airway clearance regimens after starting Elexacaftor-Tezacaftor-Ivacaftor (ETI) and if so, is this benefit noticeable on pulmonary function testing and imaging.
Detailed Description
-----------------
This will be a randomized controlled trial design with 2:1 randomization (2 to symptom driven to 1 in continuous) for this pilot study to determine if symptom-driven airway clearance after starting Elexacaftor-Tezacaftor-Ivacaftor (ETI) therapy is feasible and can eventually determine if it is non-inferior to continuing airway clearance therapies. The study will be performed as an intention to treat protocol. All participants who are eligible and enrolled will be asked to perform airway clearance twice daily for 12 weeks prior to randomization and then will be followed for 12 weeks including study visits at week 0, week 4, week 8, and week 12. The study will require no change in current use of inhaled antibiotics nor adjust the frequency of the medication during the study. Airway clearance methods to be recorded include aerobika or flutter valve, high frequency chest oscillation therapy (vest), intrapulmonary percussive ventilator, or exercise performed specially for airway clearance. The medications to be monitored included nebulized Albuterol, nebulized hypertonic saline, nebulized Pulmozyme, and nebulized mannitol. The continuous arm (control arm) will be asked to perform airway clearance twice daily for the entirety of the study and record all therapies performed daily. The symptom driven arm will perform airway clearance on their own discretion, whether this be from steady decline in baseline respiratory status or acute flair of symptoms related to infectious etiology. At baseline participants will undergo pulmonary function testing, sputum/throat culture and Cystic Fibrosis Questionnaire Revise (CFQ-R). On week 0, week 4, week 8 and week 12 visits the participants will undergo pulmonary function testing and CFQ-R with addition of sputum/throat cultures on week 12. Between each study visit participants will be asked to perform home spirometry once weekly for the 12-week trial period. For participants enrolled in the continuous group the investigators will ask for participants to perform home spirometry after either twice daily airway clearance routine or for the symptom-based group to perform at roughly the same time of day for each test. Participants will also be asked to keep a daily cystic fibrosis diary during the run-in period and study period in which participants will record if, and how frequent, participants use any airway clearance medications or devices during the day. A reduction in percent predicted forced expiratory volume in 1 second (ppFEV1%) or percent predicted forced vital capacity (ppFVC%) of more than 10% in laboratory PFT testing for 2 consecutive weeks will be deemed an adverse event and lead to the participant in the symptom driven arm being instructed to perform daily airway clearance therapy. A reduction in ppFEV1% and/or ppFVC% in home spirometry by more than 10% will trigger a need for in lab PFT testing to determine if participants have developed an adverse event leading to performing daily airway clearance therapy or if participants are to continue symptom-based airway clearance. Other criteria for participants to be evaluate in-person between study visits include use of daily airway clearance for more than 7 consecutive days in the symptom-based arm or signs and symptoms of a possible acute pulmonary exacerbation. If participants develop an exacerbation from an identifiable cause other than their primary CF lung disease (viral infection, asthma exacerbation, pulmonary embolism, etc.) participants will undergo appropriate treatment, and while the event will be deemed an adverse event, participants will continue with their current treatment protocol. Participants who are treated for an acute severe pulmonary exacerbation requiring IV antibiotics and/or hospitalization will either continue in the continuous treatment arm or if in the symptom driven arm be instructed to perform daily airway clearance for the duration of the study. In participants with concurrent asthma diagnoses, the investigators will not require any discontinuation of additional inhaler/nebulized therapies that are asthma specific, but no bronchodilators will be started specifically for the study.
Official Title
-----------------
Symptom Based Performance of Airway Clearance Therapy After Starting Highly Effective CFTR Modulator Therapy for Cystic Fibrosis
Conditions
-----------------
Cystic Fibrosis, Mucociliary Clearance Defect
Intervention / Treatment
-----------------
* Other: Symptom driven performance of airway clearance
* Other: Continuous daily performance of airway clearance
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: age > 18 years at the time of recruitment treatment with Elexacaftor-Tezacaftor-Ivacaftor for > 90 days prior to enrollment willing to continue twice daily airway clearance for a minimum of 90 days and up to180 days if enrolled in the continuing treatment arm no exacerbations in the last 28 days Exclusion Criteria: active smoking or vaping (tobacco, marijuana, recreational drugs) recent change in chronic airway clearance regimen with the last 28 days inability to tolerate airway clearance or intolerance to either/or hypertonic saline and Pulmozyme current treatment for an acute pulmonary exacerbation ongoing therapy for Nontuberculous Mycobacterium (NTM) investigational drug 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial design with 2:1 randomization (2 to symptom driven to 1 in continuous) for this pilot study to determine if intermittent and symptom-driven airway clearance after starting Elexacaftor-Tezacaftor-Ivacaftor (ETI) therapy can be determined to be non-inferior to continuing airway clearance therapies.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Symptom driven<br>Symptom driven performance of airway clearance regimen | Other: Symptom driven performance of airway clearance<br>* Perform symptom driven/intermittent airway clearance therapy with frequency based off of patient's daily symptoms including mobilization therapy (high-frequency chest compression or vest device, intrapulmonary percussive ventilator, positive expiratory pressure device) and inhaled/nebulized therapies of albuterol, hypertonic saline and dornase alfa for the 12 week study period.<br>|
| Active Comparator: Continuous<br>Continuous performance of baseline daily airway clearance regimen | Other: Continuous daily performance of airway clearance<br>* Continue run-in protocol of twice daily airway clearance using twice daily mobilization therapy (high-frequency chest compression or vest device, intrapulmonary percussive ventilator, positive expiratory pressure device) and inhaled/nebulized therapies of albuterol, hypertonic saline and dornase alfa for the 12 week study period.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change in percent predicted FEV1 (ppFEV1) from week 0 to week 12 in symptom driven airway clearance arm | Difference between symptom driven airway clearance arm and continue daily airway clearance arm in the absolute change in ppFEV1 from Week 0 to Week 12 | 12 weeks |
| Absolute change in percent predicted FVC (ppFVC) from week 0 to week 12 in symptom driven airway clearance arm | Difference between symptom driven airway clearance arm and continue daily airway clearance arm in the absolute change in ppFVC from Week 0 to Week 12 | 12 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change in respiratory symptoms based upon Cystic Fibrosis Questionnaire Revise score | Difference between symptom driven airway clearance arm and continue daily airway clearance arm in the absolute change in respiratory symptoms based upon Cystic Fibrosis Questionnaire Revise score (CFQ-R). Scores for the CFQ-R range from 0-100 with higher scores analogous to better outcomes. | 12 weeks |
| Incidence of adverse events (AE) in the symptom driven airway clearance arm | Difference between symptom driven airway clearance arm and continue daily airway clearance arm in the proportion of participants with at least one event per week | 12 weeks |
| Frequency of performance of airway clearance in symptom driven airway clearance arm | Difference between symptom driven airway clearance arm and continue daily airway clearance arm in the absolute difference of performance of airway clearance | 12 weeks |
| Change in airway colonization with S. aureus or P. aeruginosa | Difference between symptom based airway clearance arm and continue daily airway clearance arm in the absolute difference in sputum/throat cultures positive for S. aureus or P. aeruginosa | 12 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cystic Fibrosis, Mucociliary clearance, Highly Effective CFTR Modulator Therapy
|
NCT02082990
|
Primary Care-based Facilitated Access to a Web Based Brief Intervention to Reduce Alcohol Consumption
|
Brief Interventions (BIs) for risky drinkers are an effective tool in primary care. Lack of time in daily practice has been identified as a barrier for the wide implementation of BI. There is growing evidence that e-health tools such as web based BIs can be an efficient alternative to standard face-to-face BIs and save time to general practitioners (GP).~The main aim of this study is to test non-inferiority of a web based BI for risky drinkers against a traditional face to face BI delivered by a general practitioner. We have designed a randomised controlled non-inferiority trial comparing both interventions, to be performed in primary care health centres in Catalonia, Spain.~Adults attending in primary care centres and willing to participate, will be invited to fill the short Alcohol Use Disorders Identification Test (AUDIT-C) in a specific website. Those screening positive and who accept to share the baseline data with their GP will be invited to an online assessment of their drinking and randomized to a standard BI with their GP or to the online BI.~Follow-up assessment will be conducted online at months 3 and 12, using the full Alcohol Use Disorder Identification Test (AUDIT) and the quality of life questionnaire (D5-EQD5). The main outcome will be the proportion of risky drinkers according to the AUDIT. Assuming a 30% reduction in the proportion of risky drinkers in the control group (classroom), allowing for an overall attrition of 10% of patients in the trial and non-inferiority assessed against a specified margin of 10%, it is estimated that 500 patients would be required in each group to give the test a 90% power (1-β) to reject the null hypothesis.
|
Trial design: A randomised non-inferiority controlled trial in primary care comparing facilitated access to a website for risky drinkers against a standard face-to-face BI. With the exception of the non-experimental intervention, all components of the study will be administered online to patients. Patients will be actively encouraged by their PHCP to access the application, which is available on the website of the programme 'Alcohol y Salud' (http:// www.alcoholysalud.cat), and will be provided with a unique registration code. The trial website is a Spanish adaptation of the English version of http://www.DownYourDrink.org.uk (DYD) developed in the UK, which includes modules for all the key trial components including screening, consent, assessment, randomisation and follow-up. It also incorporates the alcohol reduction website for the patients in the experimental group. The site has been adapted from the http://www.DownYourDrink.org.uk website developed for the DYD-RCT (randomised controlled trial).14 Details of DYD and the psychological theory that underpinned its development have been reported elsewhere. 21 Country-specific information such as recommended guidelines for alcohol intake, definitions of standard drinks and alcohol-related laws will be included. The website also incorporates a menu-driven facility to enable PHCP to customise automated messages to patients, for example, by adding photographs and pre-recorded messages. The personalised messages will appear to each patient using the log-in code provided by that practitioner.~Practitioner recruitment, training and incentives:~Recruitment will be based on the XaROH network. A 3 h seminar on new technologies, and EI and BI, introducing the trial, will be offered to all members of the XaROH, and those attending will be invited to sign up for the trial. In addition, several advertisements will be posted on the 'Beveu Menys' platform offering participation in the trial. In selecting practices, preference will be given to those with at least 5000 registered patients. Those practices that are selected as participants will be required to undergo a 1-day training programme. The training has four steps: (1) introduction to trial; (2) familiarisation with website; (3) update about EI and BI; and (4) practice in EI and BI (role-playing). Finally, participants will be encouraged to use the website and to tailor-make patient messages. Participating PHCPs will receive a financial incentive of €20 per patient recruited to the trial.
|
A Randomised Controlled Non-inferiority Trial of Primary Care-based Facilitated Access to a Web Based Brief Intervention to Reduce Alcohol Consumption (EFAR-Spain)
|
Hazardous Drinking
|
* Behavioral: Face-to-Face Brief Intervention
* Behavioral: Online Brief Intervention
|
Inclusion Criteria:~Patients aged 18 years old or over attended in primary care during the study period~AUDIT-C 4 or above for women and 5 or above for men (in online screening)~Exclusion Criteria:~Severe psychiatric disorders~Serious visual impairment~Terminal illness~To have inadequate command of the Spanish or Catalan language~AUDIT ≥ 18 in baseline assessment.~Excluded patients will be referred to GPs to consider other interventions.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of risky drinkers according to the Alcohol Use Disorder Identification Test (AUDIT) | % of patients with > 7 scoring in AUDIT (month 3) | At month 3 after the randomisation |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of risky drinkers according to the Alcohol Use Disorder Identification Test (AUDIT) | % of patients with > 7 scoring in AUDIT (month 12) | at month 12 after the randomisation |
| Quality of life EQ-5D-3L questionnaire | Increasing of QoL according to EQ5D53L | at month 3 and 12 after the randomisation |
|
Alcohol-related disorders, Alcohol Drinking, e-health, Alcohol Use Disorder Test, Quality of Life
|
Alcohol Drinking, Drinking Behavior
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Face-to-Face Brief Intervention Group<br>One face-to-face Brief Intervention which is provided by General Practitioner or Nurse | Behavioral: Face-to-Face Brief Intervention<br>* One face-to-face Brief Intervention which is provided by General Practitioner or Nurse<br>|
| Experimental: Online Brief Intervention Group<br>Primary care-based facilitated access to an alcohol reduction website (Brief Intervention) | Behavioral: Online Brief Intervention<br>* Primary care-based facilitated access to an alcohol reduction website (Brief Intervention)<br>|
|
Primary Care-based Facilitated Access to a Web Based Brief Intervention to Reduce Alcohol Consumption
Study Overview
=================
Brief Summary
-----------------
Brief Interventions (BIs) for risky drinkers are an effective tool in primary care. Lack of time in daily practice has been identified as a barrier for the wide implementation of BI. There is growing evidence that e-health tools such as web based BIs can be an efficient alternative to standard face-to-face BIs and save time to general practitioners (GP). The main aim of this study is to test non-inferiority of a web based BI for risky drinkers against a traditional face to face BI delivered by a general practitioner. We have designed a randomised controlled non-inferiority trial comparing both interventions, to be performed in primary care health centres in Catalonia, Spain. Adults attending in primary care centres and willing to participate, will be invited to fill the short Alcohol Use Disorders Identification Test (AUDIT-C) in a specific website. Those screening positive and who accept to share the baseline data with their GP will be invited to an online assessment of their drinking and randomized to a standard BI with their GP or to the online BI. Follow-up assessment will be conducted online at months 3 and 12, using the full Alcohol Use Disorder Identification Test (AUDIT) and the quality of life questionnaire (D5-EQD5). The main outcome will be the proportion of risky drinkers according to the AUDIT. Assuming a 30% reduction in the proportion of risky drinkers in the control group (classroom), allowing for an overall attrition of 10% of patients in the trial and non-inferiority assessed against a specified margin of 10%, it is estimated that 500 patients would be required in each group to give the test a 90% power (1-β) to reject the null hypothesis.
Detailed Description
-----------------
Trial design: A randomised non-inferiority controlled trial in primary care comparing facilitated access to a website for risky drinkers against a standard face-to-face BI. With the exception of the non-experimental intervention, all components of the study will be administered online to patients. Patients will be actively encouraged by their PHCP to access the application, which is available on the website of the programme 'Alcohol y Salud' (http:// www.alcoholysalud.cat), and will be provided with a unique registration code. The trial website is a Spanish adaptation of the English version of http://www.DownYourDrink.org.uk (DYD) developed in the UK, which includes modules for all the key trial components including screening, consent, assessment, randomisation and follow-up. It also incorporates the alcohol reduction website for the patients in the experimental group. The site has been adapted from the http://www.DownYourDrink.org.uk website developed for the DYD-RCT (randomised controlled trial).14 Details of DYD and the psychological theory that underpinned its development have been reported elsewhere. 21 Country-specific information such as recommended guidelines for alcohol intake, definitions of standard drinks and alcohol-related laws will be included. The website also incorporates a menu-driven facility to enable PHCP to customise automated messages to patients, for example, by adding photographs and pre-recorded messages. The personalised messages will appear to each patient using the log-in code provided by that practitioner. Practitioner recruitment, training and incentives: Recruitment will be based on the XaROH network. A 3 h seminar on new technologies, and EI and BI, introducing the trial, will be offered to all members of the XaROH, and those attending will be invited to sign up for the trial. In addition, several advertisements will be posted on the 'Beveu Menys' platform offering participation in the trial. In selecting practices, preference will be given to those with at least 5000 registered patients. Those practices that are selected as participants will be required to undergo a 1-day training programme. The training has four steps: (1) introduction to trial; (2) familiarisation with website; (3) update about EI and BI; and (4) practice in EI and BI (role-playing). Finally, participants will be encouraged to use the website and to tailor-make patient messages. Participating PHCPs will receive a financial incentive of €20 per patient recruited to the trial.
Official Title
-----------------
A Randomised Controlled Non-inferiority Trial of Primary Care-based Facilitated Access to a Web Based Brief Intervention to Reduce Alcohol Consumption (EFAR-Spain)
Conditions
-----------------
Hazardous Drinking
Intervention / Treatment
-----------------
* Behavioral: Face-to-Face Brief Intervention
* Behavioral: Online Brief Intervention
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients aged 18 years old or over attended in primary care during the study period AUDIT-C 4 or above for women and 5 or above for men (in online screening) Exclusion Criteria: Severe psychiatric disorders Serious visual impairment Terminal illness To have inadequate command of the Spanish or Catalan language AUDIT ≥ 18 in baseline assessment. Excluded patients will be referred to GPs to consider other interventions.
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: Face-to-Face Brief Intervention Group<br>One face-to-face Brief Intervention which is provided by General Practitioner or Nurse | Behavioral: Face-to-Face Brief Intervention<br>* One face-to-face Brief Intervention which is provided by General Practitioner or Nurse<br>|
| Experimental: Online Brief Intervention Group<br>Primary care-based facilitated access to an alcohol reduction website (Brief Intervention) | Behavioral: Online Brief Intervention<br>* Primary care-based facilitated access to an alcohol reduction website (Brief Intervention)<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of risky drinkers according to the Alcohol Use Disorder Identification Test (AUDIT) | % of patients with > 7 scoring in AUDIT (month 3) | At month 3 after the randomisation |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of risky drinkers according to the Alcohol Use Disorder Identification Test (AUDIT) | % of patients with > 7 scoring in AUDIT (month 12) | at month 12 after the randomisation |
| Quality of life EQ-5D-3L questionnaire | Increasing of QoL according to EQ5D53L | at month 3 and 12 after the randomisation |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alcohol-related disorders, Alcohol Drinking, e-health, Alcohol Use Disorder Test, Quality of Life
|
NCT05222997
|
Therapy of Age-related Macular Degeneration
|
People with the disease age-related macular degeneration (AMD) are treated with the Medical Eye Trainer (MET) system to improve their vision. The training is carried out over 2 months.
|
Age-related macular degeneration (AMD) is a widespread eye disease worldwide. According to the Gutenberg Health Study, about 7000000 people in Germany suffer from it. The numbers for Austria are to be assumed with 700000 due to the smaller population. There are two different forms of AMD, the wet form with 15% and the dry form with 85%. Both types have a high risk of rapid development of significant visual impairment. For the dry form of the disease there are currently only a few therapeutic options. The main one is the nutritional supplement therapy. This treatment can only reduce the progression of deterioration in 10% of affected individuals, but there is a significant side effect profile. Thus, the question arose for completely different treatment approaches. For this reason, the Medical Eye Trainer (MET) was developed. This is a training device which can easily be used in self application. The purpose of this new therapy is not to try to cure AMD. Instead, the eye and brain are trained to better cope with the disease. In a first study on 17 eyes, 11 cases even showed an improvement of the visual performance, the remaining 6 cases showed a stable situation. In no case did a deterioration occur. Thus, for the first time, it was possible not only to slow down this disease, but even to achieve an improvement. In a second study with a planned number of 150 persons, this positive effect will be further investigated. A calculation with G*Power, based on the results of the first study, results in an optimal number of 150 examinations.~The participants will be examined in the hospital Ried im Innkreis and treated by MET. No additional measures are required for the study besides the usual eye examinations in AMD.~The study is open to individuals with dry AMD, regardless of age. Exclusion criteria are wet AMD, epilepsy and double vision. Other eye diseases are not a problem.~The diagnosis is additionally confirmed by an examination of the ocular fundus with an Optical Coherence Tomography (OCT). As an essential factor of the severity of the disease, the visual performance for distance (5-6m) and for near (40cm) is determined.~Participants need a mobile electronic device with the operating system Apple IOS® or Android®. The MET training system in the form of software will be provided for the duration of the study. The therapy is performed daily by the patient him/herself and lasts 90 seconds per eye. A success control is planned after two months. The above mentioned examinations will be repeated.~The MET has a CE-approval in the sense of MPG class 1. This study will be performed according to the Helsinki criteria.
|
Therapy of Age-related Macular Degeneration Through Training With the Medical Eye Trainer
|
Age-Related Macular Degeneration
|
Inclusion Criteria:~Age-related macular degeneration~Exclusion Criteria:~Epilepsy~Double vision
| null | null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in visual acuity | | 2 months |
|
Age-related macular degeneration, AMD, Medical Eye Trainer
|
Eye Diseases, Macular Degeneration, Retinal Degeneration, Retinal Diseases
|
Therapy of Age-related Macular Degeneration
Study Overview
=================
Brief Summary
-----------------
People with the disease age-related macular degeneration (AMD) are treated with the Medical Eye Trainer (MET) system to improve their vision. The training is carried out over 2 months.
Detailed Description
-----------------
Age-related macular degeneration (AMD) is a widespread eye disease worldwide. According to the Gutenberg Health Study, about 7000000 people in Germany suffer from it. The numbers for Austria are to be assumed with 700000 due to the smaller population. There are two different forms of AMD, the wet form with 15% and the dry form with 85%. Both types have a high risk of rapid development of significant visual impairment. For the dry form of the disease there are currently only a few therapeutic options. The main one is the nutritional supplement therapy. This treatment can only reduce the progression of deterioration in 10% of affected individuals, but there is a significant side effect profile. Thus, the question arose for completely different treatment approaches. For this reason, the Medical Eye Trainer (MET) was developed. This is a training device which can easily be used in self application. The purpose of this new therapy is not to try to cure AMD. Instead, the eye and brain are trained to better cope with the disease. In a first study on 17 eyes, 11 cases even showed an improvement of the visual performance, the remaining 6 cases showed a stable situation. In no case did a deterioration occur. Thus, for the first time, it was possible not only to slow down this disease, but even to achieve an improvement. In a second study with a planned number of 150 persons, this positive effect will be further investigated. A calculation with G*Power, based on the results of the first study, results in an optimal number of 150 examinations. The participants will be examined in the hospital Ried im Innkreis and treated by MET. No additional measures are required for the study besides the usual eye examinations in AMD. The study is open to individuals with dry AMD, regardless of age. Exclusion criteria are wet AMD, epilepsy and double vision. Other eye diseases are not a problem. The diagnosis is additionally confirmed by an examination of the ocular fundus with an Optical Coherence Tomography (OCT). As an essential factor of the severity of the disease, the visual performance for distance (5-6m) and for near (40cm) is determined. Participants need a mobile electronic device with the operating system Apple IOS® or Android®. The MET training system in the form of software will be provided for the duration of the study. The therapy is performed daily by the patient him/herself and lasts 90 seconds per eye. A success control is planned after two months. The above mentioned examinations will be repeated. The MET has a CE-approval in the sense of MPG class 1. This study will be performed according to the Helsinki criteria.
Official Title
-----------------
Therapy of Age-related Macular Degeneration Through Training With the Medical Eye Trainer
Conditions
-----------------
Age-Related Macular Degeneration
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age-related macular degeneration Exclusion Criteria: Epilepsy Double vision
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 |
| --- | --- | --- |
| Change in visual acuity | | 2 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Age-related macular degeneration, AMD, Medical Eye Trainer
|
||||
NCT03545854
|
Dispersion of Local Anesthetic on the Erector Spinae Plane Block in Cadavers
|
This study aims to better understand the dispersion of local anesthetic on the Erector Spinae Block, a new technique developed for analgesia. It consists on injection of local anesthetic around the posterior muscles of the Spine. In this study, the investigators will make the injection with coloring solution on cadavers and by dissection will note the dispersion of the solution according to injectate volume. The investigators hypothesize more volume allows bigger spread and will allow new indications of this technique in perioperative analgesia and treatment of chronic Pain
|
The study's methodology will include performing ultrasound guided erector spinae block in cadavers included in the study according to eligibility criteria. After signing of written consent form, the participants will be randomized on the height of the block (vertebral level - T3, T12 and L4) and the volume to be injected (10, 20 and 30ml). The block will be performed by experienced physicians on the technique by ultrasound guidance and fixed pressure measured with an in-line pressure monitor (15 psi) with the cadaver in the lateral position. The cadavers will be submitted to autopsy by standard thoracoabdominal midline incision, with the viscera removed for analysis. The cadavers will have their paraspinal muscles removed (quadratus lumborum and psoas major), the medial parietal pleura opened and the number of levels with colored solution registered, noting the spread to ventral rami of spinal nerves and to the paravertebral space.
|
Determination of Relationship Between Volume and Dispersion of Local Anesthetic on Ultrasound-guided Erector Spinae Plane Block in Cadavers
|
Nerve Block
|
* Procedure: Erector Spinae Plane Block
|
Inclusion Criteria:~Fresh Cadavers (not subject to formaldehyde fixation process or frozen > 24h)~Age > 18 years~Written informed consent signed by responsible party~Height > 150cm and < 190cm~Exclusion Criteria:~Previous spinal surgery~Severe spinal deformity~BMI > 35 kg/m2~Absence of a responsible party to sign the written informed consent
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The cadavers will be randomized to receive the intervention (Erector Spinae Plane Block) on different levels (Vertebral level - T3, T12 and L4) and different volumes (10, 20 and 30ml)
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spread of Coloring Solution secondary to volume injected and vertebral level of injection | Observation of coloring solution around the spinal nerves as they exit the vertebral foramen. Comparison of number of spinal nerves colored according to the volume injected and injection site. | 3 hours |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spread of coloring solution to paravertebral space | Observation of coloring solution on the paravertebral space. Comparison of number of levels of the paravertebral space colored according to volume injected and injection site. | 3 hours |
|
Cadaver, Death, Pathologic Processes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T3 10ml<br>The cadaver will receive an ultrasound-guided Erector Spinae Plane Block with 10ml of coloring solution at the T3 vertebral level | Procedure: Erector Spinae Plane Block<br>* Ultrasound guided injection of coloring solution (methylene blue diluted in water) with a 18G echogenic tuohy needle deep to the plane of the erector spinae muscles.<br>|
| Experimental: T3 20ml<br>The cadaver will receive an ultrasound-guided Erector Spinae Plane Block with 20ml of coloring solution at the T3 vertebral level | Procedure: Erector Spinae Plane Block<br>* Ultrasound guided injection of coloring solution (methylene blue diluted in water) with a 18G echogenic tuohy needle deep to the plane of the erector spinae muscles.<br>|
| Experimental: T3 30ml<br>The cadaver will receive an ultrasound-guided Erector Spinae Plane Block with 30ml of coloring solution at the T3 vertebral level | Procedure: Erector Spinae Plane Block<br>* Ultrasound guided injection of coloring solution (methylene blue diluted in water) with a 18G echogenic tuohy needle deep to the plane of the erector spinae muscles.<br>|
| Experimental: T12 10ml<br>The cadaver will receive an ultrasound-guided Erector Spinae Plane Block with 10ml of coloring solution at the T12 vertebral level | Procedure: Erector Spinae Plane Block<br>* Ultrasound guided injection of coloring solution (methylene blue diluted in water) with a 18G echogenic tuohy needle deep to the plane of the erector spinae muscles.<br>|
| Experimental: T12 20ml<br>The cadaver will receive an ultrasound-guided Erector Spinae Plane Block with 20ml of coloring solution at the T12 vertebral level | Procedure: Erector Spinae Plane Block<br>* Ultrasound guided injection of coloring solution (methylene blue diluted in water) with a 18G echogenic tuohy needle deep to the plane of the erector spinae muscles.<br>|
| Experimental: T12 30ml<br>The cadaver will receive an ultrasound-guided Erector Spinae Plane Block with 30ml of coloring solution at the T12 vertebral level | Procedure: Erector Spinae Plane Block<br>* Ultrasound guided injection of coloring solution (methylene blue diluted in water) with a 18G echogenic tuohy needle deep to the plane of the erector spinae muscles.<br>|
| Experimental: L4 10ml<br>The cadaver will receive an ultrasound-guided Erector Spinae Plane Block with 10ml of coloring solution at the L4 vertebral level | Procedure: Erector Spinae Plane Block<br>* Ultrasound guided injection of coloring solution (methylene blue diluted in water) with a 18G echogenic tuohy needle deep to the plane of the erector spinae muscles.<br>|
| Experimental: L4 20ml<br>The cadaver will receive an ultrasound-guided Erector Spinae Plane Block with 20ml of coloring solution at the L4 vertebral level | Procedure: Erector Spinae Plane Block<br>* Ultrasound guided injection of coloring solution (methylene blue diluted in water) with a 18G echogenic tuohy needle deep to the plane of the erector spinae muscles.<br>|
| Experimental: L4 30ml<br>The cadaver will receive an ultrasound-guided Erector Spinae Plane Block with 30ml of coloring solution at the L4 vertebral level | Procedure: Erector Spinae Plane Block<br>* Ultrasound guided injection of coloring solution (methylene blue diluted in water) with a 18G echogenic tuohy needle deep to the plane of the erector spinae muscles.<br>|
|
Dispersion of Local Anesthetic on the Erector Spinae Plane Block in Cadavers
Study Overview
=================
Brief Summary
-----------------
This study aims to better understand the dispersion of local anesthetic on the Erector Spinae Block, a new technique developed for analgesia. It consists on injection of local anesthetic around the posterior muscles of the Spine. In this study, the investigators will make the injection with coloring solution on cadavers and by dissection will note the dispersion of the solution according to injectate volume. The investigators hypothesize more volume allows bigger spread and will allow new indications of this technique in perioperative analgesia and treatment of chronic Pain
Detailed Description
-----------------
The study's methodology will include performing ultrasound guided erector spinae block in cadavers included in the study according to eligibility criteria. After signing of written consent form, the participants will be randomized on the height of the block (vertebral level - T3, T12 and L4) and the volume to be injected (10, 20 and 30ml). The block will be performed by experienced physicians on the technique by ultrasound guidance and fixed pressure measured with an in-line pressure monitor (15 psi) with the cadaver in the lateral position. The cadavers will be submitted to autopsy by standard thoracoabdominal midline incision, with the viscera removed for analysis. The cadavers will have their paraspinal muscles removed (quadratus lumborum and psoas major), the medial parietal pleura opened and the number of levels with colored solution registered, noting the spread to ventral rami of spinal nerves and to the paravertebral space.
Official Title
-----------------
Determination of Relationship Between Volume and Dispersion of Local Anesthetic on Ultrasound-guided Erector Spinae Plane Block in Cadavers
Conditions
-----------------
Nerve Block
Intervention / Treatment
-----------------
* Procedure: Erector Spinae Plane Block
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Fresh Cadavers (not subject to formaldehyde fixation process or frozen > 24h) Age > 18 years Written informed consent signed by responsible party Height > 150cm and < 190cm Exclusion Criteria: Previous spinal surgery Severe spinal deformity BMI > 35 kg/m2 Absence of a responsible party to sign the written informed consent
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The cadavers will be randomized to receive the intervention (Erector Spinae Plane Block) on different levels (Vertebral level - T3, T12 and L4) and different volumes (10, 20 and 30ml)
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T3 10ml<br>The cadaver will receive an ultrasound-guided Erector Spinae Plane Block with 10ml of coloring solution at the T3 vertebral level | Procedure: Erector Spinae Plane Block<br>* Ultrasound guided injection of coloring solution (methylene blue diluted in water) with a 18G echogenic tuohy needle deep to the plane of the erector spinae muscles.<br>|
| Experimental: T3 20ml<br>The cadaver will receive an ultrasound-guided Erector Spinae Plane Block with 20ml of coloring solution at the T3 vertebral level | Procedure: Erector Spinae Plane Block<br>* Ultrasound guided injection of coloring solution (methylene blue diluted in water) with a 18G echogenic tuohy needle deep to the plane of the erector spinae muscles.<br>|
| Experimental: T3 30ml<br>The cadaver will receive an ultrasound-guided Erector Spinae Plane Block with 30ml of coloring solution at the T3 vertebral level | Procedure: Erector Spinae Plane Block<br>* Ultrasound guided injection of coloring solution (methylene blue diluted in water) with a 18G echogenic tuohy needle deep to the plane of the erector spinae muscles.<br>|
| Experimental: T12 10ml<br>The cadaver will receive an ultrasound-guided Erector Spinae Plane Block with 10ml of coloring solution at the T12 vertebral level | Procedure: Erector Spinae Plane Block<br>* Ultrasound guided injection of coloring solution (methylene blue diluted in water) with a 18G echogenic tuohy needle deep to the plane of the erector spinae muscles.<br>|
| Experimental: T12 20ml<br>The cadaver will receive an ultrasound-guided Erector Spinae Plane Block with 20ml of coloring solution at the T12 vertebral level | Procedure: Erector Spinae Plane Block<br>* Ultrasound guided injection of coloring solution (methylene blue diluted in water) with a 18G echogenic tuohy needle deep to the plane of the erector spinae muscles.<br>|
| Experimental: T12 30ml<br>The cadaver will receive an ultrasound-guided Erector Spinae Plane Block with 30ml of coloring solution at the T12 vertebral level | Procedure: Erector Spinae Plane Block<br>* Ultrasound guided injection of coloring solution (methylene blue diluted in water) with a 18G echogenic tuohy needle deep to the plane of the erector spinae muscles.<br>|
| Experimental: L4 10ml<br>The cadaver will receive an ultrasound-guided Erector Spinae Plane Block with 10ml of coloring solution at the L4 vertebral level | Procedure: Erector Spinae Plane Block<br>* Ultrasound guided injection of coloring solution (methylene blue diluted in water) with a 18G echogenic tuohy needle deep to the plane of the erector spinae muscles.<br>|
| Experimental: L4 20ml<br>The cadaver will receive an ultrasound-guided Erector Spinae Plane Block with 20ml of coloring solution at the L4 vertebral level | Procedure: Erector Spinae Plane Block<br>* Ultrasound guided injection of coloring solution (methylene blue diluted in water) with a 18G echogenic tuohy needle deep to the plane of the erector spinae muscles.<br>|
| Experimental: L4 30ml<br>The cadaver will receive an ultrasound-guided Erector Spinae Plane Block with 30ml of coloring solution at the L4 vertebral level | Procedure: Erector Spinae Plane Block<br>* Ultrasound guided injection of coloring solution (methylene blue diluted in water) with a 18G echogenic tuohy needle deep to the plane of the erector spinae muscles.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spread of Coloring Solution secondary to volume injected and vertebral level of injection | Observation of coloring solution around the spinal nerves as they exit the vertebral foramen. Comparison of number of spinal nerves colored according to the volume injected and injection site. | 3 hours |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spread of coloring solution to paravertebral space | Observation of coloring solution on the paravertebral space. Comparison of number of levels of the paravertebral space colored according to volume injected and injection site. | 3 hours |
|
|
NCT02253381
|
Effect of Position During Spinal Anesthesia on Hemodynamic Change in Cesarean Section
|
Hypotension is the most common complications after spinal anesthesia especially in pregnant patients who undergoing cesarean section. Position during spinal anesthesia may be altering the hemodynamic. For right lateral decubitus, the enlarged uterus compresses inferior vena cava that may decrease venous return and cardiac output. This leads to hypotension.The hypothesis is the right lateral position during spinal anesthesia in pregnant women will be had hemodynamic changing more than the left lateral position. This objective is to compare hemodynamic change between left and right lateral position during spinal anesthesia in pregnant women undergoing cesarean section.
|
Study design: A randomized controlled trial~Study setting:~The study will be conducted in the operating rooms at Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand~Study period:~The total duration of participation in the randomized study is up to the operative day.~Study population:~Pregnant patients undergoing cesarean section receiving spinal anesthesia with 0.5% bupivacaine and 0.2 mg morphine total volume 2.2 ml.~Study sample:~Inclusion criteria~Signed informed consent~Pregnancy~Spinal anesthesia with 0.5% bupivacaine and 0.2 mg morphine total volume 2.2 ml~Elective and emergency surgery~Exclusion criteria~Contraindication for spinal anesthesia~Complicated pregnancy such as maternal heart disease, eclampsia, severe fetal distress, abruption placenta, twin pregnancy, and placenta previa totalis~Maternal height < 150 cm.
|
Effect of Position During Spinal Anesthesia on Hemodynamic Change in Pregnant Women Undergoing Cesarean Section: Randomized Trial
|
Hypotension
|
* Procedure: Right
* Procedure: Left
|
Inclusion Criteria:~Signed informed consent~Term pregnancy~Spinal anesthesia with 0.5% bupivacaine and 0.2 mg morphine total volume 2.2 ml~Exclusion Criteria:~Contraindication for spinal anesthesia~Height < 150 cm.~Complicated pregnancy e.g. heart disease, preclampsia, eclampsia, diabetes millitus, twin, abrupt placenta, placenta pre via, and fetal distress~Failed spinal anesthesia
| null | null |
Female
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypotension | Systolic blood pressure lower than 90 mmHg or decrease more than 20% of baseline | after bupivacaine injection until 15 minutes after spinal anesthesia |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ephedrine consumption | Total amount of ephedrine receiving | intraoperative |
| Apgar score at first minute and fifth minute | | Child delivery at first minute and fifth minute |
|
lateral decubitus position, hypotension, cesarean section
|
Hypotension, Vascular Diseases, Cardiovascular Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Right lateral decubitus position<br>Right lateral decubitus position during spinal anesthesia | Procedure: Right<br>* Right lateral decubitus position during spinal anesthesia<br>|
| Active Comparator: Left lateral decubitus position<br>Left lateral decubitus position during spinal anesthesia | Procedure: Left<br>* Left lateral decubitus position during spinal anesthesia<br>|
|
Effect of Position During Spinal Anesthesia on Hemodynamic Change in Cesarean Section
Study Overview
=================
Brief Summary
-----------------
Hypotension is the most common complications after spinal anesthesia especially in pregnant patients who undergoing cesarean section. Position during spinal anesthesia may be altering the hemodynamic. For right lateral decubitus, the enlarged uterus compresses inferior vena cava that may decrease venous return and cardiac output. This leads to hypotension.The hypothesis is the right lateral position during spinal anesthesia in pregnant women will be had hemodynamic changing more than the left lateral position. This objective is to compare hemodynamic change between left and right lateral position during spinal anesthesia in pregnant women undergoing cesarean section.
Detailed Description
-----------------
Study design: A randomized controlled trial Study setting: The study will be conducted in the operating rooms at Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand Study period: The total duration of participation in the randomized study is up to the operative day. Study population: Pregnant patients undergoing cesarean section receiving spinal anesthesia with 0.5% bupivacaine and 0.2 mg morphine total volume 2.2 ml. Study sample: Inclusion criteria Signed informed consent Pregnancy Spinal anesthesia with 0.5% bupivacaine and 0.2 mg morphine total volume 2.2 ml Elective and emergency surgery Exclusion criteria Contraindication for spinal anesthesia Complicated pregnancy such as maternal heart disease, eclampsia, severe fetal distress, abruption placenta, twin pregnancy, and placenta previa totalis Maternal height < 150 cm.
Official Title
-----------------
Effect of Position During Spinal Anesthesia on Hemodynamic Change in Pregnant Women Undergoing Cesarean Section: Randomized Trial
Conditions
-----------------
Hypotension
Intervention / Treatment
-----------------
* Procedure: Right
* Procedure: Left
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent Term pregnancy Spinal anesthesia with 0.5% bupivacaine and 0.2 mg morphine total volume 2.2 ml Exclusion Criteria: Contraindication for spinal anesthesia Height < 150 cm. Complicated pregnancy e.g. heart disease, preclampsia, eclampsia, diabetes millitus, twin, abrupt placenta, placenta pre via, and fetal distress Failed spinal anesthesia
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Right lateral decubitus position<br>Right lateral decubitus position during spinal anesthesia | Procedure: Right<br>* Right lateral decubitus position during spinal anesthesia<br>|
| Active Comparator: Left lateral decubitus position<br>Left lateral decubitus position during spinal anesthesia | Procedure: Left<br>* Left lateral decubitus position during spinal anesthesia<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypotension | Systolic blood pressure lower than 90 mmHg or decrease more than 20% of baseline | after bupivacaine injection until 15 minutes after spinal anesthesia |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ephedrine consumption | Total amount of ephedrine receiving | intraoperative |
| Apgar score at first minute and fifth minute | | Child delivery at first minute and fifth minute |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
lateral decubitus position, hypotension, cesarean section
|
NCT01742351
|
Internet-based Cognitive Behaviour Therapy (CBT) for Persons Diagnosed With Bipolar II
|
The aim of the study is to test the feasibility and acceptability of internet-based Cognitive Behaviour Therapy (CBT) for persons diagnosed with bipolar disorder, type II. The idea is to treat residual depressive symptoms as well as using psychoeducation to improve their prognosis. Each participant will have a personal therapist that will provide guidance and support throughout the treatment.
|
Internet-based Cognitive Behaviour Therapy for Persons Diagnosed With Bipolar II - a Pilot Study
|
Bipolar Disorder, Type II
|
* Behavioral: Guided internet-based cognitive behavior therapy
|
Inclusion Criteria:~A diagnosis of bipolar disorder type II~Mild to moderate depressive symptoms~18 years of age~Stable medication with a mood stabiliser~Access to the internet~Exclusion Criteria:~Diagnosis of psychosis~Having received psychiatric in-patient care during the past year~Ongoing psychotherapy~Previous manic episode~Previous suicide attempt~Previous parasuicidal behavior documented in patient record (e.g. self-injury)
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in score on the Montgomery-Åsberg Depression Rating Scale - Self rated (MADRS-S) between baseline and post treatment | A nine item questionnaire of depressive symptoms | 9 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the score on the Affective Self Rating Scale (AS-18-M) between baseline and post treatment | A nine item subscale of the AS-18 measuring symptoms of mania/hypomania. | 9 weeks |
|
Bipolar Disorder, Bipolar and Related Disorders, Mood Disorders, Mental Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Guided internet-based cognitive behavior therapy (CBT)<br> | Behavioral: Guided internet-based cognitive behavior therapy<br> <br> |
|
Internet-based Cognitive Behaviour Therapy (CBT) for Persons Diagnosed With Bipolar II
Study Overview
=================
Brief Summary
-----------------
The aim of the study is to test the feasibility and acceptability of internet-based Cognitive Behaviour Therapy (CBT) for persons diagnosed with bipolar disorder, type II. The idea is to treat residual depressive symptoms as well as using psychoeducation to improve their prognosis. Each participant will have a personal therapist that will provide guidance and support throughout the treatment.
Official Title
-----------------
Internet-based Cognitive Behaviour Therapy for Persons Diagnosed With Bipolar II - a Pilot Study
Conditions
-----------------
Bipolar Disorder, Type II
Intervention / Treatment
-----------------
* Behavioral: Guided internet-based cognitive behavior therapy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A diagnosis of bipolar disorder type II Mild to moderate depressive symptoms 18 years of age Stable medication with a mood stabiliser Access to the internet Exclusion Criteria: Diagnosis of psychosis Having received psychiatric in-patient care during the past year Ongoing psychotherapy Previous manic episode Previous suicide attempt Previous parasuicidal behavior documented in patient record (e.g. self-injury)
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: Guided internet-based cognitive behavior therapy (CBT)<br> | Behavioral: Guided internet-based cognitive behavior therapy<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in score on the Montgomery-Åsberg Depression Rating Scale - Self rated (MADRS-S) between baseline and post treatment | A nine item questionnaire of depressive symptoms | 9 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the score on the Affective Self Rating Scale (AS-18-M) between baseline and post treatment | A nine item subscale of the AS-18 measuring symptoms of mania/hypomania. | 9 weeks |
|
||
NCT01675609
|
Study Evaluating the Safety and Efficacy of Brimonidine Tartrate Ophthalmic Solution in Adult and Geriatric Subjects
|
The purpose of this study is to evaluate the safety and efficacy of brimonidine tartrate 0.025% ophthalmic solution used four times daily in a population of adult and geriatric subjects
|
A Single-Center, Double-Masked, Randomized, Vehicle-Controlled, Parallel-Group Study Evaluating the Safety and Efficacy of Brimonidine Tartrate Ophthalmic Solution in Adult and Geriatric Subjects
|
Ocular Redness
|
* Drug: Placebo
* Drug: Brimonidine tartrate 0.025%
|
Inclusion Criteria:~Be at least 40 years of age~Must have normal ocular health~Must have history of redness relief drop use or desire to use~Exclusion Criteria:~Must not have any ocular/systemic health problems~Must agree to avoid disallowed medications
|
40 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular redness | redness evaluated by investigator prior to study medication instillation and redness evaluated by the subject as captured in dosing diary | at specified timepoints for up to 180 minutes |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular Redness | evaluated prior to study medication instillation and at 5 minutes post instillation | up to 5 minutes post study medication instillation |
|
Physiological Effects of Drugs, Brimonidine Tartrate, Antihypertensive Agents, Adrenergic alpha-2 Receptor Agonists, Adrenergic alpha-Agonists, Adrenergic Agonists, Adrenergic Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 1 drop in each eye daily for up to 35 days<br>|
| Experimental: Brimonidine Tartrate 0.025%<br> | Drug: Brimonidine tartrate 0.025%<br>* 1 drop in each eye for up to 35 days<br>|
|
Study Evaluating the Safety and Efficacy of Brimonidine Tartrate Ophthalmic Solution in Adult and Geriatric Subjects
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety and efficacy of brimonidine tartrate 0.025% ophthalmic solution used four times daily in a population of adult and geriatric subjects
Official Title
-----------------
A Single-Center, Double-Masked, Randomized, Vehicle-Controlled, Parallel-Group Study Evaluating the Safety and Efficacy of Brimonidine Tartrate Ophthalmic Solution in Adult and Geriatric Subjects
Conditions
-----------------
Ocular Redness
Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: Brimonidine tartrate 0.025%
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Be at least 40 years of age Must have normal ocular health Must have history of redness relief drop use or desire to use Exclusion Criteria: Must not have any ocular/systemic health problems Must agree to avoid disallowed medications
Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 1 drop in each eye daily for up to 35 days<br>|
| Experimental: Brimonidine Tartrate 0.025%<br> | Drug: Brimonidine tartrate 0.025%<br>* 1 drop in each eye for up to 35 days<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular redness | redness evaluated by investigator prior to study medication instillation and redness evaluated by the subject as captured in dosing diary | at specified timepoints for up to 180 minutes |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular Redness | evaluated prior to study medication instillation and at 5 minutes post instillation | up to 5 minutes post study medication instillation |
|
||
NCT00541645
|
Transient Osteoporosis of Pregnancy: A Possible Peptide Mediator
|
Transient osteoporosis of pregnancy (TOoP) is uncommonly encountered in orthopedic and obstetric practice, with most reports consisting of single cases.~This rare condition consists of significant osteoporosis affecting the hips and spine, causing significant morbidity, and putting young female patients at risk for vertebral and femoral neck fractures.~The pathogenesis of transient osteoporosis of pregnancy is unknown, with various theories as to its etiology.~Recently, a number of reports have described elevated levels of PTHrP in patients with transient osteoporosis in pregnancy and of the postpartum period Our goal in this study is to assess the role of PTHrP in transient osteoporosis of pregnancy
| null |
Transient Osteperosis
|
Inclusion Criteria:~Signed Informed consent
|
18 Years
|
45 Years
|
Female
| null |
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
Transient Osteoporosis of Pregnancy: A Possible Peptide Mediator
Study Overview
=================
Brief Summary
-----------------
Transient osteoporosis of pregnancy (TOoP) is uncommonly encountered in orthopedic and obstetric practice, with most reports consisting of single cases. This rare condition consists of significant osteoporosis affecting the hips and spine, causing significant morbidity, and putting young female patients at risk for vertebral and femoral neck fractures. The pathogenesis of transient osteoporosis of pregnancy is unknown, with various theories as to its etiology. Recently, a number of reports have described elevated levels of PTHrP in patients with transient osteoporosis in pregnancy and of the postpartum period Our goal in this study is to assess the role of PTHrP in transient osteoporosis of pregnancy
Conditions
-----------------
Transient Osteperosis
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed Informed consent
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years
Sexes Eligible for Study
-----------------
Female
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
|||||||
NCT01609881
|
The Role of Prostaglandins in the Progression of Diabetic Retinopathy
|
Objective of the research study:~To measure anterior chamber and vitreous ketorolac (Acuvail®) concentrations after topical administration in patients undergoing routine vitrectomy to determine the ability of the medication to penetrate into the anterior chamber and vitreous cavity, and to compare these levels to the IC50 for the cyclooxygenase-1 and -2 enzymes (COX-1 and COX-2)~To measure vitreous concentrations of prostaglandin subtypes (PGE, PGD, PGF) and other inflammatory mediators (Interleukin-1β [IL-1β], IL-6, IL-8, tumor necrosis factor [TNF]-α, VEGF) in both diabetic and nondiabetic patients undergoing vitrectomy~To determine if topical ketorolac (Acuvail®) can penetrate the anterior chamber and vitreous cavity sufficiently to decrease levels of intraocular inflammatory mediators that have been shown to be elevated in diabetic patients~To serve as a precursor to a 5-year longitudinal clinical trial to determine if chronically administered topical ketorolac (Acuvail®) can prevent, delay or slow diabetic retinopathy.~Research hypothesis~Ketorolac (Acuvail®) will penetrate the anterior chamber and vitreous cavity sufficiently to achieve levels above the IC50 for COX-1 and COX-2~Prostaglandin and other inflammatory mediator levels in the anterior chamber and vitreous cavity will be significantly higher among diabetic patients than nondiabetic controls~Acuvail® can significantly lower anterior chamber and vitreous cavity levels of prostaglandins and other inflammatory mediators in diabetic patients
|
Patients who require vitrectomy for any indication and those meeting the inclusion/exclusion criteria will be included. Patients will be consented to participate in the study and for surgery.~Nondiabetic patients will be included in one of two groups. Twenty will receive topical ketorolac (Acuvail®) preoperatively for 3 days and then samples will be taken at the time of surgery. Twenty other patients will serve as controls for intraocular prostaglandin and cytokine levels (to be compared to diabetic patients). This group will not receive preoperative ketorolac (Acuvail®).~Diabetic patients will be included in one of two groups. Twenty patients will have intraocular prostaglandin and cytokine levels measured. Twenty other patients will be in the interventional group to determine if topical ketorolac (Acuvail®) can successfully lower intraocular prostaglandin and inflammatory cytokine levels.~In all cases, patients are undergoing vitreoretinal surgery as the surgical treatment of choice for their condition. For this study, undiluted samples will be drawn from the vitreous cavity and anterior chamber at the beginning of the vitrectomy. These samples will be stored, analyzed and frozen.~Samples will be tested for prostaglandin levels, in addition to other inflammatory cytokines, and ketorolac levels.~Three days of Acuvail® given four times per day was chosen, as previous studies have shown that one dose of ketorolac 0.4% achieves a peak aqueous concentration of 57.5 ng/mL,1 and that 12 doses over two days achieves an aqueous concentration of 1079 ng/mL.2 Both values are well above the IC50 for COX-1 (5.3 to 7.5 ng/mL) and COX-2 (33.9-45.2 ng/mL). The upper end of this dosing spectrum was chosen, as more doses and a longer duration of therapy is likely required to achieve sufficient vitreous levels to inhibit COX-1 and COX-2. This dosing regimen was also used in another clinical study that assessed ketorolac levels and prostaglandin levels in the vitreous cavity after topical administration four times a day for three days preoperatively.3
|
The Role of Prostaglandins in the Progression of Diabetic Retinopathy and the Therapeutic Efficacy of Topical Ketorolac (Acuvail)
|
Inflammation
|
* Drug: Acuvail
* Other: Placebo
|
Inclusion Criteria:~Adult patients aged 18 years or older who present for vitrectomy surgery for any indication.~Diabetic and non-diabetic patients will be included.~Exclusion criteria:~Patients under the age of 18 years of age.~Pregnant women.~Patients with a history of vitrectomy surgery.~Current topical, periocular, intraocular or systemic corticosteroid use~Co-existent macular, retinovascular or ocular inflammatory disease (age-related macular degeneration, retinal venous occlusive disease, uveitis, etc.)
|
18 Years
|
90 Years
|
All
|
No
|
Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vitreous and anterior chamber levels of prostaglandins, other cytokines, and Acuvail | Vitreous and anterior chamber levels of prostaglandins, other cytokines, and Acuvail | 3 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Outcome | The primary outcomes include drug and prostaglandin concentrations on the anterior chamber and vitreous. | 7 days |
| Secondary Outcome | The secondary outcome will include cytokine levels in the vitreous. | 14 days |
|
Inflammation
|
Ketorolac, Anti-Inflammatory Agents, Non-Steroidal, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anti-Inflammatory Agents, Antirheumatic Agents, Cyclooxygenase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Acuvail<br>Acuvail as preventive for inflammation and possible decrease or prevent diabetic retinopathy. The study has four arms - diabetic ketorolac, diabetic control, normal eyes ketorolac, normal eyes control. patients are randomized to ketorolac or control. | Drug: Acuvail<br>* Dosing of drug 3 days prior to surgery<br>* Other names: Ketorolac 0.45%;|
| Placebo Comparator: Placebo<br>Placebo using artificial tear drops | Other: Placebo<br>* Artificial tears qid for 3 days preoperatively<br>* Other names: tears;|
|
The Role of Prostaglandins in the Progression of Diabetic Retinopathy
Study Overview
=================
Brief Summary
-----------------
Objective of the research study: To measure anterior chamber and vitreous ketorolac (Acuvail®) concentrations after topical administration in patients undergoing routine vitrectomy to determine the ability of the medication to penetrate into the anterior chamber and vitreous cavity, and to compare these levels to the IC50 for the cyclooxygenase-1 and -2 enzymes (COX-1 and COX-2) To measure vitreous concentrations of prostaglandin subtypes (PGE, PGD, PGF) and other inflammatory mediators (Interleukin-1β [IL-1β], IL-6, IL-8, tumor necrosis factor [TNF]-α, VEGF) in both diabetic and nondiabetic patients undergoing vitrectomy To determine if topical ketorolac (Acuvail®) can penetrate the anterior chamber and vitreous cavity sufficiently to decrease levels of intraocular inflammatory mediators that have been shown to be elevated in diabetic patients To serve as a precursor to a 5-year longitudinal clinical trial to determine if chronically administered topical ketorolac (Acuvail®) can prevent, delay or slow diabetic retinopathy. Research hypothesis Ketorolac (Acuvail®) will penetrate the anterior chamber and vitreous cavity sufficiently to achieve levels above the IC50 for COX-1 and COX-2 Prostaglandin and other inflammatory mediator levels in the anterior chamber and vitreous cavity will be significantly higher among diabetic patients than nondiabetic controls Acuvail® can significantly lower anterior chamber and vitreous cavity levels of prostaglandins and other inflammatory mediators in diabetic patients
Detailed Description
-----------------
Patients who require vitrectomy for any indication and those meeting the inclusion/exclusion criteria will be included. Patients will be consented to participate in the study and for surgery. Nondiabetic patients will be included in one of two groups. Twenty will receive topical ketorolac (Acuvail®) preoperatively for 3 days and then samples will be taken at the time of surgery. Twenty other patients will serve as controls for intraocular prostaglandin and cytokine levels (to be compared to diabetic patients). This group will not receive preoperative ketorolac (Acuvail®). Diabetic patients will be included in one of two groups. Twenty patients will have intraocular prostaglandin and cytokine levels measured. Twenty other patients will be in the interventional group to determine if topical ketorolac (Acuvail®) can successfully lower intraocular prostaglandin and inflammatory cytokine levels. In all cases, patients are undergoing vitreoretinal surgery as the surgical treatment of choice for their condition. For this study, undiluted samples will be drawn from the vitreous cavity and anterior chamber at the beginning of the vitrectomy. These samples will be stored, analyzed and frozen. Samples will be tested for prostaglandin levels, in addition to other inflammatory cytokines, and ketorolac levels. Three days of Acuvail® given four times per day was chosen, as previous studies have shown that one dose of ketorolac 0.4% achieves a peak aqueous concentration of 57.5 ng/mL,1 and that 12 doses over two days achieves an aqueous concentration of 1079 ng/mL.2 Both values are well above the IC50 for COX-1 (5.3 to 7.5 ng/mL) and COX-2 (33.9-45.2 ng/mL). The upper end of this dosing spectrum was chosen, as more doses and a longer duration of therapy is likely required to achieve sufficient vitreous levels to inhibit COX-1 and COX-2. This dosing regimen was also used in another clinical study that assessed ketorolac levels and prostaglandin levels in the vitreous cavity after topical administration four times a day for three days preoperatively.3
Official Title
-----------------
The Role of Prostaglandins in the Progression of Diabetic Retinopathy and the Therapeutic Efficacy of Topical Ketorolac (Acuvail)
Conditions
-----------------
Inflammation
Intervention / Treatment
-----------------
* Drug: Acuvail
* Other: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult patients aged 18 years or older who present for vitrectomy surgery for any indication. Diabetic and non-diabetic patients will be included. Exclusion criteria: Patients under the age of 18 years of age. Pregnant women. Patients with a history of vitrectomy surgery. Current topical, periocular, intraocular or systemic corticosteroid use Co-existent macular, retinovascular or ocular inflammatory disease (age-related macular degeneration, retinal venous occlusive disease, uveitis, etc.)
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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Acuvail<br>Acuvail as preventive for inflammation and possible decrease or prevent diabetic retinopathy. The study has four arms - diabetic ketorolac, diabetic control, normal eyes ketorolac, normal eyes control. patients are randomized to ketorolac or control. | Drug: Acuvail<br>* Dosing of drug 3 days prior to surgery<br>* Other names: Ketorolac 0.45%;|
| Placebo Comparator: Placebo<br>Placebo using artificial tear drops | Other: Placebo<br>* Artificial tears qid for 3 days preoperatively<br>* Other names: tears;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vitreous and anterior chamber levels of prostaglandins, other cytokines, and Acuvail | Vitreous and anterior chamber levels of prostaglandins, other cytokines, and Acuvail | 3 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Outcome | The primary outcomes include drug and prostaglandin concentrations on the anterior chamber and vitreous. | 7 days |
| Secondary Outcome | The secondary outcome will include cytokine levels in the vitreous. | 14 days |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Inflammation
|
NCT00976040
|
Optimal Time to Start Antiretroviral Therapy in HIV-infected Adults With Cryptococcal Meningitis
|
The goal of this randomized clinical trial is to compare early versus standard timing of initiation of antiretroviral therapy (ART) with respect to clearance of Cryptococcus neoformans from cerebrospinal fluid (CSF) among HIV-infected adults with Cryptococcal Meningitis.~The investigators hypothesize that early ART mediates more rapid clearance of C. neoformans from CSF, as manifested by a greater rate of decrease in C. neoformans colony forming units (CFUs) during the first 28 days after initiating antifungal treatment.~Secondary hypotheses are that recovery of pathogen specific cellular immunity directed at C. neoformans, as manifested by increases in the number and function of C. neoformans-specific peripheral blood mononuclear cells is associated with 1) ART and 2) pathogen clearance. In addition, patients randomized to the intervention arm will have more rapid clearance of antigen levels in CSF and serum and will have a lower incidence of grade 3 and 4 Adverse events.
|
A Randomized Clinical Trial of Immediate Versus Standard Antiretroviral Therapy for HIV-infected Adults Presenting With Cryptococcal Meningitis
|
Cryptococcal Meningitis, HIV Infections
|
* Other: Early antiretroviral therapy
|
Inclusion Criteria:~HIV 1 infection confirmed by licensed ELISA kit and/or detectable Viral load.~Confirmed Cryptococcal meningitis on the current admission by India ink or CSF cryptococcal antigen~ART naive at the time of enrollment~21 years old and above~Ability and willingness to give written informed consent to participate in the study~Able (as assessed by the patient's medical team)to initiate amphotericin B for cryptococcal meningitis~Initiated amphotericin B 72 hours or less prior to assessment for enrollment or not on amphotericin B at the time of assessment for enrollment~Agrees to obtain outpatient care after discharge within 50 kilometers from Princess Marina Hospital,Scottish Livingstone Hospital and Bamalete Lutheran Hospital~Exclusion Criteria:~Recent (within the past 4 weeks) antifungal use~Pregnant or breastfeeding~Initiated anti-tubercular therapy 2 weeks or less prior to assessment for enrollment.~Bacterial meningitis at the time of assessment for enrollment.~Recent (within the past 1 month) use of the following:systemic cancer chemotherapy,oral or intravenous corticosteroids or other immunomodulators.~Judged by study coordinator to be likely to initiate chemotherapy or any other immunomodulatory therapy prior to the 4 week LP.~Imprisoned.
|
21 Years
|
80 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the CSF CFUs between the immediate and standard ART initiation groups | | 4 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade 3 or 4 adverse events | each participant is followed up for 6 months after the initiation of HAART | 6 months |
| Clearance of C. neoformans antigen from CSF and blood. | | 6 months |
| Change in the number of peripheral blood mononuclear cells responding to C. neoformans | | 4 weeks |
|
HIV-1, Africa, Botswana, Highly active antiretroviral therapy, treatment naive
|
Anti-Retroviral Agents, Antiviral Agents, Anti-Infective Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early antiretroviral therapy<br>Subjects randomized to this arm will initiate antiretroviral therapy within 7 days of enrollment. | Other: Early antiretroviral therapy<br>* The intervention is early initiation of antiretroviral therapy after diagnosis of Cryptococcal meningitis.~In the intervention/experimental arm, triple-drug highly active antiretroviral therapy regimens will be initiated within 7 days of diagnosis of Cryptococcal meningitis.<br>|
| No Intervention: Standard antiretroviral therapy<br>Subjects randomized to this arm will initiate antiretroviral therapy approximately 4 weeks after enrollment. | |
|
Optimal Time to Start Antiretroviral Therapy in HIV-infected Adults With Cryptococcal Meningitis
Study Overview
=================
Brief Summary
-----------------
The goal of this randomized clinical trial is to compare early versus standard timing of initiation of antiretroviral therapy (ART) with respect to clearance of Cryptococcus neoformans from cerebrospinal fluid (CSF) among HIV-infected adults with Cryptococcal Meningitis. The investigators hypothesize that early ART mediates more rapid clearance of C. neoformans from CSF, as manifested by a greater rate of decrease in C. neoformans colony forming units (CFUs) during the first 28 days after initiating antifungal treatment. Secondary hypotheses are that recovery of pathogen specific cellular immunity directed at C. neoformans, as manifested by increases in the number and function of C. neoformans-specific peripheral blood mononuclear cells is associated with 1) ART and 2) pathogen clearance. In addition, patients randomized to the intervention arm will have more rapid clearance of antigen levels in CSF and serum and will have a lower incidence of grade 3 and 4 Adverse events.
Official Title
-----------------
A Randomized Clinical Trial of Immediate Versus Standard Antiretroviral Therapy for HIV-infected Adults Presenting With Cryptococcal Meningitis
Conditions
-----------------
Cryptococcal Meningitis, HIV Infections
Intervention / Treatment
-----------------
* Other: Early antiretroviral therapy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: HIV 1 infection confirmed by licensed ELISA kit and/or detectable Viral load. Confirmed Cryptococcal meningitis on the current admission by India ink or CSF cryptococcal antigen ART naive at the time of enrollment 21 years old and above Ability and willingness to give written informed consent to participate in the study Able (as assessed by the patient's medical team)to initiate amphotericin B for cryptococcal meningitis Initiated amphotericin B 72 hours or less prior to assessment for enrollment or not on amphotericin B at the time of assessment for enrollment Agrees to obtain outpatient care after discharge within 50 kilometers from Princess Marina Hospital,Scottish Livingstone Hospital and Bamalete Lutheran Hospital Exclusion Criteria: Recent (within the past 4 weeks) antifungal use Pregnant or breastfeeding Initiated anti-tubercular therapy 2 weeks or less prior to assessment for enrollment. Bacterial meningitis at the time of assessment for enrollment. Recent (within the past 1 month) use of the following:systemic cancer chemotherapy,oral or intravenous corticosteroids or other immunomodulators. Judged by study coordinator to be likely to initiate chemotherapy or any other immunomodulatory therapy prior to the 4 week LP. Imprisoned.
Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 80 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early antiretroviral therapy<br>Subjects randomized to this arm will initiate antiretroviral therapy within 7 days of enrollment. | Other: Early antiretroviral therapy<br>* The intervention is early initiation of antiretroviral therapy after diagnosis of Cryptococcal meningitis. In the intervention/experimental arm, triple-drug highly active antiretroviral therapy regimens will be initiated within 7 days of diagnosis of Cryptococcal meningitis.<br>|
| No Intervention: Standard antiretroviral therapy<br>Subjects randomized to this arm will initiate antiretroviral therapy approximately 4 weeks after enrollment. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the CSF CFUs between the immediate and standard ART initiation groups | | 4 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade 3 or 4 adverse events | each participant is followed up for 6 months after the initiation of HAART | 6 months |
| Clearance of C. neoformans antigen from CSF and blood. | | 6 months |
| Change in the number of peripheral blood mononuclear cells responding to C. neoformans | | 4 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV-1, Africa, Botswana, Highly active antiretroviral therapy, treatment naive
|
|
NCT01547052
|
Adapting Dialectical Behavior Therapy for Children in Residential Care
|
I: Conduct Pilot Randomized Clinical Trial of Dialectical Behavior Therapy for children (DBT-C) in residential as compared with Treatment-As-Usual (TAU) (60 children in DBT-C and 60 children in the comparison condition).~II: Finalize therapist training manuals and educational materials to guide selection, training, and supervision of treatment providers.
|
Specific Aim 1: Examine feasibility of DBT-C by evaluating response rate in treatment attendance, treatment satisfaction, and any differences in these rates by groups.~Hypothesis 1: DBT-C will be equivalent to TAU in attendance rate and will have significantly greater treatment satisfaction rating by subjects, as well as by therapists and milieu staff.~Specific Aim 2: Examine efficacy of DBT-C as compared to TAU in reducing internalizing and externalizing symptoms.~Hypothesis 2: Children in DBT-C condition as compared to TAU will have significantly fewer internalizing and externalizing symptoms.~Specific Aim 3: Examine efficacy of DBT-C in improving adaptive coping, emotion regulation, risk taking, and social skills, and reducing depression.~Hypothesis 3: Children in DBT-C Training condition as compared to TAU will have significantly greater improvement in adaptive coping skills, emotion regulation, risk taking and impulsivity and social skills, and reducing depressive symptoms.~Specific Aim 4: Examine efficacy of DBT-C in reducing the frequency of critical incidents.~Hypothesis 4: Children in DBT-C condition as compared to TAU will have significantly fewer critical incidents, including psychiatric hospitalization, emergency room visits, total number of days inpatient, suicidal ideations and attempts, self-harm behaviors, sexual acting out, running away, stealing, police involvement, etc.
|
Adapting Dialectical Behavior Therapy for Children in Residential Care: Pilot Randomized Clinical Trial With Children With Severe Emotional and Behavioral Dysregulation
|
Childhood Aggression
|
* Behavioral: DBT for children
* Behavioral: Enhanced Supportive-Educational therapy
|
Inclusion Criteria:~age between 6 years 0 months and 12 years 11 months;~male;~in residential care at Green Chimneys;~projected length of stay is at least 8 months.~Exclusion Criteria:~pervasive developmental disorder;~psychotic disorder;~mental retardation; (all as per psychiatric evaluation at Green Chimneys);~in care or custody of the Department of Social Services (DSS);~caregivers do not speak English.
|
6 Years
|
12 Years
|
Male
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Attendance Form | | post-treatment at 30 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Balloon Analog Risk Task | | pre-treatment, week 6, 12, 18, 24, 30 of treatment and at 3 and 6 months follow-up |
| Mood and Feelings Questionnaire | | pre-treatment, weeks 6, 12, 18, 24 and 30 of treatment at at 3 and 6 months follow-up |
| Emotion Regulation Checklist | | pre-treatment, weeks 12, 24 and 30 of treatment at at 3 and 6 months follow-up |
| Children's Coping Strategies Checklist | | pre-treatment, weeks 12, 24 and 30 of treatment at at 3 and 6 months follow-up |
| Pleasure Scale for Children | | pre-treatment, weeks 12, 24 and 30 of treatment at at 3 and 6 months follow-up |
| Social Skills Rating Scale | | pre-treatment, weeks 12, 24 and 30 of treatment at at 3 and 6 months follow-up |
| Therapy Satisfaction Questionnaire | | week 30 |
| Therapist Satisfaction Scale | | week 30 |
| Milieu Staff Satisfaction Questionnaire | | every 6 months |
| Incident Report | | pre-treatment, weeks 6, 12, 18, 24 and 30 of treatment at at 3 and 6 months follow-up |
| Psychosocial Treatment Compliance Scale | | week 30 |
| Child Behavior Checklist | | at pre-treatment, 6, 12, 18, 24, 30 weeks of treatment, and at 3 and 6 months follow-up |
| Difficulty with Emotion Regulation Scale | | pre-treatment |
|
DBT, child, emotion regulation, behavior problems
|
Aggression, Behavioral Symptoms
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DBT for children<br>Dialectical Behavior Therapy adapted for children | Behavioral: DBT for children<br>* intervention consists of weekly individual 45 min. sessions, twice per week 60 min. group sessions, and every other week 90 min. sessions with parents<br>* Other names: Dialectical Behavior Therapy adapted for Children;|
| Active Comparator: Enhanced Supportive-Educational Therapy<br>Enhanced Treatment-As-Usual, including supportive-educational model, cognitive-behavioral skills and parent management training | Behavioral: Enhanced Supportive-Educational therapy<br>* weekly individual 45 min sessions, twice per week 60 min. group sessions and every other week parent sessions.<br>* Other names: Enhansed TAU;|
|
Adapting Dialectical Behavior Therapy for Children in Residential Care
Study Overview
=================
Brief Summary
-----------------
I: Conduct Pilot Randomized Clinical Trial of Dialectical Behavior Therapy for children (DBT-C) in residential as compared with Treatment-As-Usual (TAU) (60 children in DBT-C and 60 children in the comparison condition). II: Finalize therapist training manuals and educational materials to guide selection, training, and supervision of treatment providers.
Detailed Description
-----------------
Specific Aim 1: Examine feasibility of DBT-C by evaluating response rate in treatment attendance, treatment satisfaction, and any differences in these rates by groups. Hypothesis 1: DBT-C will be equivalent to TAU in attendance rate and will have significantly greater treatment satisfaction rating by subjects, as well as by therapists and milieu staff. Specific Aim 2: Examine efficacy of DBT-C as compared to TAU in reducing internalizing and externalizing symptoms. Hypothesis 2: Children in DBT-C condition as compared to TAU will have significantly fewer internalizing and externalizing symptoms. Specific Aim 3: Examine efficacy of DBT-C in improving adaptive coping, emotion regulation, risk taking, and social skills, and reducing depression. Hypothesis 3: Children in DBT-C Training condition as compared to TAU will have significantly greater improvement in adaptive coping skills, emotion regulation, risk taking and impulsivity and social skills, and reducing depressive symptoms. Specific Aim 4: Examine efficacy of DBT-C in reducing the frequency of critical incidents. Hypothesis 4: Children in DBT-C condition as compared to TAU will have significantly fewer critical incidents, including psychiatric hospitalization, emergency room visits, total number of days inpatient, suicidal ideations and attempts, self-harm behaviors, sexual acting out, running away, stealing, police involvement, etc.
Official Title
-----------------
Adapting Dialectical Behavior Therapy for Children in Residential Care: Pilot Randomized Clinical Trial With Children With Severe Emotional and Behavioral Dysregulation
Conditions
-----------------
Childhood Aggression
Intervention / Treatment
-----------------
* Behavioral: DBT for children
* Behavioral: Enhanced Supportive-Educational therapy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: age between 6 years 0 months and 12 years 11 months; male; in residential care at Green Chimneys; projected length of stay is at least 8 months. Exclusion Criteria: pervasive developmental disorder; psychotic disorder; mental retardation; (all as per psychiatric evaluation at Green Chimneys); in care or custody of the Department of Social Services (DSS); caregivers do not speak English.
Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 12 Years
Sexes Eligible for Study
-----------------
Male
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: DBT for children<br>Dialectical Behavior Therapy adapted for children | Behavioral: DBT for children<br>* intervention consists of weekly individual 45 min. sessions, twice per week 60 min. group sessions, and every other week 90 min. sessions with parents<br>* Other names: Dialectical Behavior Therapy adapted for Children;|
| Active Comparator: Enhanced Supportive-Educational Therapy<br>Enhanced Treatment-As-Usual, including supportive-educational model, cognitive-behavioral skills and parent management training | Behavioral: Enhanced Supportive-Educational therapy<br>* weekly individual 45 min sessions, twice per week 60 min. group sessions and every other week parent sessions.<br>* Other names: Enhansed TAU;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Attendance Form | | post-treatment at 30 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Balloon Analog Risk Task | | pre-treatment, week 6, 12, 18, 24, 30 of treatment and at 3 and 6 months follow-up |
| Mood and Feelings Questionnaire | | pre-treatment, weeks 6, 12, 18, 24 and 30 of treatment at at 3 and 6 months follow-up |
| Emotion Regulation Checklist | | pre-treatment, weeks 12, 24 and 30 of treatment at at 3 and 6 months follow-up |
| Children's Coping Strategies Checklist | | pre-treatment, weeks 12, 24 and 30 of treatment at at 3 and 6 months follow-up |
| Pleasure Scale for Children | | pre-treatment, weeks 12, 24 and 30 of treatment at at 3 and 6 months follow-up |
| Social Skills Rating Scale | | pre-treatment, weeks 12, 24 and 30 of treatment at at 3 and 6 months follow-up |
| Therapy Satisfaction Questionnaire | | week 30 |
| Therapist Satisfaction Scale | | week 30 |
| Milieu Staff Satisfaction Questionnaire | | every 6 months |
| Incident Report | | pre-treatment, weeks 6, 12, 18, 24 and 30 of treatment at at 3 and 6 months follow-up |
| Psychosocial Treatment Compliance Scale | | week 30 |
| Child Behavior Checklist | | at pre-treatment, 6, 12, 18, 24, 30 weeks of treatment, and at 3 and 6 months follow-up |
| Difficulty with Emotion Regulation Scale | | pre-treatment |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
DBT, child, emotion regulation, behavior problems
|
NCT00371995
|
Short Course of Miltefosine and Liposomal Amphotericin B for Kala-azar
|
Miltefosine and liposomal amphotericin B (AmBisome) are approved drugs for visceral leishmaniasis. In this study both drugs will be given in a sequential manner. AmBisome will be given on day 1, followed by Miltefosine for 14 days. Final Cure will be evaluated at six months.
|
Methodology Multicenter trial, eligible patients will be treated with Liposomal amphotericin B (5 mg/kg) on day 1 and then with miltefosine capsules for 14 days (days 2-15).~At two weeks after the end of treatment the initial cure (clinical and parasitological cure) and the clinical response will be determined. If initial cure is observed, a patient will be evaluated after a 6 months (after end of treatment) follow up period for final clinical cure.~Number of patients planned Total number of patients planned: 150 patients at both centers combined. 75 pediatric (2-11 years); 75 adult (12-65 years).~Lack of suitability for the trial:~Post Kala-azar Dermal Leishmaniasis (PKDL)~Concomitant treatment with other anti-leishmanial drugs~Any condition which compromises ability to comply with the study procedures~Administrative reasons:~Any condition or situation that compromises compliance with study procedures including follow-up visit Study medication, dose and mode of administration Liposomal amphotericin B administered intravenously as single dose on day 1, Dosage: 5 mg/kg.~Miltefosine administered orally (50 mg capsules) for 14 days (on days 2-15)~Dosage:~weighing ≥ 25 kg: 100 mg miltefosine daily as one capsule (50 mg) in the morning and one capsule in the evening, after meals for 14 days.~weighing < 25 kg: 50 mg miltefosine daily as one capsule (50 mg) in the morning, after meals for 14 days. Parameter for evaluation~Final cure rate (initial parasite cure and clinical assessment at six month EOT)~Initial parasitological cure rate (based on splenic aspirates or Bone marrow aspirate)~Clinical response at end of treatment (clinical assessment)~Adverse events~Statistical methods~Calculation of cure rate with 95% and 90% lower confidence limit according to Clopper Pearson~Calculation of overall incidence of adverse events
|
The Efficacy and Safety of a Short Course of Miltefosine and Liposomal Amphotericin B for Visceral Leishmaniasis in India
|
Visceral Leishmaniasis
|
* Drug: Liposomal amphotericin B and Miltefosine
|
Inclusion Criteria:~Male and female age between 2 and 65 years (inclusive)~Parasites visualized on splenic aspiration~Signs and symptoms compatible with visceral leishmaniasis (e.g. fever, splenomegaly, anaemia, weight loss, leucopenia, thrombocytopenia)~Confirmed diagnosis of VL by visualization of parasites on splenic/bone marrow aspirate~Fever for at least 2 weeks~Written informed consent from the patient/or from parent or guardian if under 18 years old~Exclusion Criteria:~Hemoglobin < 6 g/dl~White blood cell count < 1000/mm3~Platelets <50,000~Prothrombin time > 5 sec above control~ASAT > 3 times the upper limit of normal~Serum creatinine or BUN > 1.5 times the upper limit of normal~Malaria~Tuberculosis~HIV positive serology~Lactation, pregnancy~Refusing contraception method during treatment period plus 3 months~Any medical condition(s) that upon judgment of physician may affect the safety of the patient when treated with study drugs~Any concomitant drug that is nephrotoxic
|
2 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Final Cure six months after the end of treatment | | 1 year |
|
Visceral leishmaniasis, kala-azar, miltefosine, AmBisome
|
Amphotericin B, Liposomal amphotericin B, Miltefosine, Amebicides, Antiprotozoal Agents, Antiparasitic Agents, Anti-Infective Agents, Anti-Bacterial Agents, Antifungal Agents, Antineoplastic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Liposomal amphotericin B administered intravenously as single dose on day 1, Dosage: 5 mg/kg.~Miltefosine administered orally (50 mg capsules) for 14 days (on days 2-15) | Drug: Liposomal amphotericin B and Miltefosine<br>* Liposomal amphotericin B administered intravenously as single dose on day 1, Dosage: 5 mg/kg.~Miltefosine administered orally (50 mg capsules) for 14 days (on days 2-15)<br>* Other names: AmBisome and Impavido;|
|
Short Course of Miltefosine and Liposomal Amphotericin B for Kala-azar
Study Overview
=================
Brief Summary
-----------------
Miltefosine and liposomal amphotericin B (AmBisome) are approved drugs for visceral leishmaniasis. In this study both drugs will be given in a sequential manner. AmBisome will be given on day 1, followed by Miltefosine for 14 days. Final Cure will be evaluated at six months.
Detailed Description
-----------------
Methodology Multicenter trial, eligible patients will be treated with Liposomal amphotericin B (5 mg/kg) on day 1 and then with miltefosine capsules for 14 days (days 2-15). At two weeks after the end of treatment the initial cure (clinical and parasitological cure) and the clinical response will be determined. If initial cure is observed, a patient will be evaluated after a 6 months (after end of treatment) follow up period for final clinical cure. Number of patients planned Total number of patients planned: 150 patients at both centers combined. 75 pediatric (2-11 years); 75 adult (12-65 years). Lack of suitability for the trial: Post Kala-azar Dermal Leishmaniasis (PKDL) Concomitant treatment with other anti-leishmanial drugs Any condition which compromises ability to comply with the study procedures Administrative reasons: Any condition or situation that compromises compliance with study procedures including follow-up visit Study medication, dose and mode of administration Liposomal amphotericin B administered intravenously as single dose on day 1, Dosage: 5 mg/kg. Miltefosine administered orally (50 mg capsules) for 14 days (on days 2-15) Dosage: weighing ≥ 25 kg: 100 mg miltefosine daily as one capsule (50 mg) in the morning and one capsule in the evening, after meals for 14 days. weighing < 25 kg: 50 mg miltefosine daily as one capsule (50 mg) in the morning, after meals for 14 days. Parameter for evaluation Final cure rate (initial parasite cure and clinical assessment at six month EOT) Initial parasitological cure rate (based on splenic aspirates or Bone marrow aspirate) Clinical response at end of treatment (clinical assessment) Adverse events Statistical methods Calculation of cure rate with 95% and 90% lower confidence limit according to Clopper Pearson Calculation of overall incidence of adverse events
Official Title
-----------------
The Efficacy and Safety of a Short Course of Miltefosine and Liposomal Amphotericin B for Visceral Leishmaniasis in India
Conditions
-----------------
Visceral Leishmaniasis
Intervention / Treatment
-----------------
* Drug: Liposomal amphotericin B and Miltefosine
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female age between 2 and 65 years (inclusive) Parasites visualized on splenic aspiration Signs and symptoms compatible with visceral leishmaniasis (e.g. fever, splenomegaly, anaemia, weight loss, leucopenia, thrombocytopenia) Confirmed diagnosis of VL by visualization of parasites on splenic/bone marrow aspirate Fever for at least 2 weeks Written informed consent from the patient/or from parent or guardian if under 18 years old Exclusion Criteria: Hemoglobin < 6 g/dl White blood cell count < 1000/mm3 Platelets <50,000 Prothrombin time > 5 sec above control ASAT > 3 times the upper limit of normal Serum creatinine or BUN > 1.5 times the upper limit of normal Malaria Tuberculosis HIV positive serology Lactation, pregnancy Refusing contraception method during treatment period plus 3 months Any medical condition(s) that upon judgment of physician may affect the safety of the patient when treated with study drugs Any concomitant drug that is nephrotoxic
Ages Eligible for Study
-----------------
Minimum Age: 2 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Liposomal amphotericin B administered intravenously as single dose on day 1, Dosage: 5 mg/kg. Miltefosine administered orally (50 mg capsules) for 14 days (on days 2-15) | Drug: Liposomal amphotericin B and Miltefosine<br>* Liposomal amphotericin B administered intravenously as single dose on day 1, Dosage: 5 mg/kg. Miltefosine administered orally (50 mg capsules) for 14 days (on days 2-15)<br>* Other names: AmBisome and Impavido;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Final Cure six months after the end of treatment | | 1 year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Visceral leishmaniasis, kala-azar, miltefosine, AmBisome
|
|
NCT05281835
|
Follow-up of Elderly Subjects With Falls Recruited in the Geriatric Departments of Several French Hospitals
|
Falls are the leading cause of accidental death among the elderly, with nearly 8,000 deaths per year in France, including more than 950 deaths on average per year in the Northwest interregion between 2006 and 2013. The incidence of falls increases with age. Falls are often the consequence of multiple factors: extrinsic and intrinsic. The WHO classifies these risk factors into 4 groups: environmental, socio-economic, behavioral and biological.~The best way to act to reduce falls is to identify the risk and severity factors (risk of fracture, risk of loss of autonomy, risk of death) in order to correct those that are modifiable.~On a national scale, the prevention of falls has been considered for many years as a major issue in health prevention [INPES 2005]. The management of elderly patients who fall has been the subject of recommendations for good practice by the French National Authority for Health (HAS) in 2009. These recommendations include the need to look for signs of geriatric severity of falls.~The SNDS National System of healthcare data brings together and links the main national health databases in France. Linking data from the PMSI (Programme de Médicalisation des Systèmes d'Information) and the National Inter-regime Information System of the French National Health Insurance with data from death certificates via the SNDS opens up unique perspectives for improving the quality of follow-up of these patients. Crossing data from the Fall assessment clinic (clinical data) and SNDS data will allow data completeness and will improve our knowledge of the care consumption of elderly fallers. In particular, we wish to determine the risk factors for unplanned hospitalizations of patients with falls.~This project aims to set up a common multicenter cohort of patients assessed during the day hospital for multidisciplinary fall assessment in 12 geriatric services: the university hospitals of Lille, Amiens-Picardie, Rouen, Caen, Tours, Strasbourg, Angers, Dijon, the GHICL and the hospitals of St Quentin, Valenciennes and Beauvais Data collection is currently being harmonized in all participating clinical departments. The databases of the SNDS and that of the fall day hospital assessment will be crossed. This will allow us to improve our knowledge of the follow-up of elderly fallers, the impact of risk factors (clinical, psychosocial, organizational, etc.) and their interactions, the effectiveness of specific management on the occurrence of falls, serious falls as well as the use of care. 1,000 elderly patients admitted in 12 French geriatric departements for a fall assessment will participate in the study.
|
Follow-up of Elderly Subjects With Falls Recruited in the Geriatric Departments of Several French Hospitals
|
Falls in the Elderly
|
Inclusion Criteria:~Male or female, 65 years of age or older~Patients admitted at a day hospital for multidisciplinary falls assessment in one of the 12 geriatric department participating in the study~Patient or, if applicable, his or her trusted person or guardian, having given his or her oral non-opposition~Patient affiliated to a social health insurance scheme (beneficiaries or beneficiaries' dependents)~Exclusion Criteria:~Expressed objection to the collection of data by the subject, his or her guardian, curator, trusted person or family member.~Admission at the day hospital for multidisciplinary falls assessment is not indicated (despite the referral of the patient and the realization of the initial consultation).~Refusal to participate in the study
|
65 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of the first unplanned hospitalization within 1 year after the day hospital for multidisciplinary falls assessment | | 1 year of follow up |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time between initial consultation (HDJ fall) and 1st unscheduled hospitalization occurring within 12 months of follow-up (dependent variable) and potential predictive factors | Time between initial consultation (HDJ fall) and 1st unscheduled hospitalization occurring within 12 months of follow-up (dependent variable) and potential predictive factors (independent variables): behavioral, environmental, medical-biological and socioeconomic factors. | within 12 months |
| Number of unplanned hospitalizations during the 12 months of follow-up or until the patient's death (expressed as number of hospitalizations per 100 patient years). | | within 12 months |
| Time from initial consultation (HDJ fall) to occurrence of death within 12 months of follow-up. | | within 12 months |
| Time between the initial consultation (HDJ fall) and the first hospitalization for fracture during the 12 months of follow-up. | | within 12 months |
| Time from initial consultation (HDJ fall) to occurrence of 1st unplanned hospitalization or death within 12 months of follow-up. | | within 12 months |
|
Elderly, Fallers, Falls, Risk factors, Cohort, National Health Data System
|
Follow-up of Elderly Subjects With Falls Recruited in the Geriatric Departments of Several French Hospitals
Study Overview
=================
Brief Summary
-----------------
Falls are the leading cause of accidental death among the elderly, with nearly 8,000 deaths per year in France, including more than 950 deaths on average per year in the Northwest interregion between 2006 and 2013. The incidence of falls increases with age. Falls are often the consequence of multiple factors: extrinsic and intrinsic. The WHO classifies these risk factors into 4 groups: environmental, socio-economic, behavioral and biological. The best way to act to reduce falls is to identify the risk and severity factors (risk of fracture, risk of loss of autonomy, risk of death) in order to correct those that are modifiable. On a national scale, the prevention of falls has been considered for many years as a major issue in health prevention [INPES 2005]. The management of elderly patients who fall has been the subject of recommendations for good practice by the French National Authority for Health (HAS) in 2009. These recommendations include the need to look for signs of geriatric severity of falls. The SNDS National System of healthcare data brings together and links the main national health databases in France. Linking data from the PMSI (Programme de Médicalisation des Systèmes d'Information) and the National Inter-regime Information System of the French National Health Insurance with data from death certificates via the SNDS opens up unique perspectives for improving the quality of follow-up of these patients. Crossing data from the Fall assessment clinic (clinical data) and SNDS data will allow data completeness and will improve our knowledge of the care consumption of elderly fallers. In particular, we wish to determine the risk factors for unplanned hospitalizations of patients with falls. This project aims to set up a common multicenter cohort of patients assessed during the day hospital for multidisciplinary fall assessment in 12 geriatric services: the university hospitals of Lille, Amiens-Picardie, Rouen, Caen, Tours, Strasbourg, Angers, Dijon, the GHICL and the hospitals of St Quentin, Valenciennes and Beauvais Data collection is currently being harmonized in all participating clinical departments. The databases of the SNDS and that of the fall day hospital assessment will be crossed. This will allow us to improve our knowledge of the follow-up of elderly fallers, the impact of risk factors (clinical, psychosocial, organizational, etc.) and their interactions, the effectiveness of specific management on the occurrence of falls, serious falls as well as the use of care. 1,000 elderly patients admitted in 12 French geriatric departements for a fall assessment will participate in the study.
Official Title
-----------------
Follow-up of Elderly Subjects With Falls Recruited in the Geriatric Departments of Several French Hospitals
Conditions
-----------------
Falls in the Elderly
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, 65 years of age or older Patients admitted at a day hospital for multidisciplinary falls assessment in one of the 12 geriatric department participating in the study Patient or, if applicable, his or her trusted person or guardian, having given his or her oral non-opposition Patient affiliated to a social health insurance scheme (beneficiaries or beneficiaries' dependents) Exclusion Criteria: Expressed objection to the collection of data by the subject, his or her guardian, curator, trusted person or family member. Admission at the day hospital for multidisciplinary falls assessment is not indicated (despite the referral of the patient and the realization of the initial consultation). Refusal to participate in the study
Ages Eligible for Study
-----------------
Minimum Age: 65 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of the first unplanned hospitalization within 1 year after the day hospital for multidisciplinary falls assessment | | 1 year of follow up |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time between initial consultation (HDJ fall) and 1st unscheduled hospitalization occurring within 12 months of follow-up (dependent variable) and potential predictive factors | Time between initial consultation (HDJ fall) and 1st unscheduled hospitalization occurring within 12 months of follow-up (dependent variable) and potential predictive factors (independent variables): behavioral, environmental, medical-biological and socioeconomic factors. | within 12 months |
| Number of unplanned hospitalizations during the 12 months of follow-up or until the patient's death (expressed as number of hospitalizations per 100 patient years). | | within 12 months |
| Time from initial consultation (HDJ fall) to occurrence of death within 12 months of follow-up. | | within 12 months |
| Time between the initial consultation (HDJ fall) and the first hospitalization for fracture during the 12 months of follow-up. | | within 12 months |
| Time from initial consultation (HDJ fall) to occurrence of 1st unplanned hospitalization or death within 12 months of follow-up. | | within 12 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Elderly, Fallers, Falls, Risk factors, Cohort, National Health Data System
|
|||||
NCT00368290
|
Modafinil Treatment for Cocaine Dependence and HIV High-Risk Behavior
|
The purpose of study is to determine if modafinil promotes cocaine abstinence and reduces high risk behavior in cocaine dependent subjects.
|
The purpose of study is to determine if modafinil promotes cocaine abstinence and reduces HRB in cocaine dependent subjects. Modafinil (300 mg/day) or placebo will be administered in an 8-week double-blind trial to patients meeting diagnostic criteria for cocaine dependence in conjunction with Cognitive Behavioral Therapy (CBT).
|
Modafinil Treatment for Cocaine Dependence and HIV-High Risk Behavior
|
Cocaine Dependence
|
* Drug: Modafinil
* Drug: placebo
* Behavioral: Cognitive Behavioral Therapy (CBT)
|
Inclusion Criteria:~18 - 60 years;~Current DSM-IV diagnosis of cocaine dependence;~Using cocaine at least 8 days in a consecutive 30 day period over the 60 day period immediately preceding study entry (If subject was receiving inpatient substance abuse treatment within 30 days prior to screening, subject must have been using cocaine at least 8 days in a consecutive 30 day period over the 60 day period immediately preceding admission to inpatient treatment); 4.)Having a negative urine toxicology (BE) test during screening (no less than 5 days prior to randomization) and a negative urine toxicology (BE) test on the day of randomization. Repeat testing allowed until required negative BE results are obtained;~Able to provide written informed consent and to comply with all study procedures;~Women must be surgically sterile, at least two years postmenopausal, or, if of childbearing potential, be using a medically accepted method of birth control and agree to continue use of this method for at least 30 days after the last dose of study drug (i.e. barrier method with spermicide, steroidal contraceptive [oral and implanted, including Depo-Provera, contraceptives must be used in conjunction with a barrier method], or intrauterine device [IUD]).~Exclusion Criteria:~Currently dependent on any substance other than cocaine or nicotine;~Current Neurological or psychiatric disorders, such as psychosis, bipolar illness, organic brain disease, dementia, or any diseases that require psychotropic medications;~Serious medical illnesses, including but not limited to; uncontrolled hypertension, significant heart disease (including a history of myocardial infarction, angina, mitral valve prolapse, left ventricular hypertrophy, palpitations, and arrhythmia), hepatic disease, renal disease, or any serious, potentially life-threatening or progressive medical illness that may compromise patient safety or study conduct;~Received a drug with known potential for toxicity to a major organ system within the month prior to entering treatment including, but not limited to: chemotherapeutic agents for neoplastic disease (i.e. methotrexate, vincristine, vinblastine, fluorouracil), agents used for parasitic infections, isoniazid, chlorambucil, dactinomycin, chloramphenicol, immunosuppressive and cytotoxic agents (i.e. cyclosporine, tacrolimus), indomethacin, protease inhibitors, amphotericin B, cephalosporins, aminoglycosides, interferon, and sulfonamides;~Clinically significant abnormal laboratory values (see Appendix A);~Has any disease of the gastrointestinal system, liver, or kidneys which could result in altered metabolism or excretion of the study medication (history of major gastrointestinal tract surgery, gastrectomy, gastrostomy, bowel resection, etc.) or history of chronic gastrointestinal disorders (ulcerative colitis, regional enteritis, or gastrointestinal bleeding);~Known hypersensitivity or allergy to modafinil, or receiving chronic therapy with any medication that could interact adversely with modafinil, including propranolol, phenytoin, warfarin and diazepam;~Took monoamine oxidase inhibitors (MAOI) within 30 days prior to randomization;~Taking or has taken an investigational drug within 60 days prior to randomization;~If female and of child-bearing capacity, tests positive on a urine pregnancy test, is lactating, has had three or more days of amenorrhea beyond expected menses at the time of the first dose of study medication, is contemplating pregnancy in the next 6 months, or is not using an effective contraceptive method;~Received therapy with any opiate-substitute (methadone, LAAM, buprenorphine) within 60 days of study enrollment.
|
18 Years
|
60 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants Reporting no Cocaine Craving | Percent of participants reporting no cocaine craving based on Brief Substance Craving Scale (BSCS) - a 4 point likert scale. | 8 weeks |
| Cocaine Use as Measured by Urine Drug Screen | The primary outcome measure was cocaine use measured by self-report, and confirmed by twice weekly urine drug screens. The percentage of participants shows the percentage who were abstinent from cocaine during the last 3 weeks of the trial. | 8 weeks |
|
cocaine dependence, hiv prevention
|
Modafinil, Central Nervous System Stimulants, Physiological Effects of Drugs, Wakefulness-Promoting Agents, Cytochrome P-450 CYP3A Inducers, Cytochrome P-450 Enzyme Inducers, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>modafinil plus CBT | Drug: Modafinil<br>* 300mg a day for 8 weeks<br>* Other names: Provigil;Behavioral: Cognitive Behavioral Therapy (CBT)<br>* Weekly cognitive behavioral therapy sessions for a period of 8 weeks.<br>|
| Placebo Comparator: 2<br>placebo plus CBT | Drug: placebo<br>* placebo pills for 8 weeks<br>Behavioral: Cognitive Behavioral Therapy (CBT)<br>* Weekly cognitive behavioral therapy sessions for a period of 8 weeks.<br>|
|
Modafinil Treatment for Cocaine Dependence and HIV High-Risk Behavior
Study Overview
=================
Brief Summary
-----------------
The purpose of study is to determine if modafinil promotes cocaine abstinence and reduces high risk behavior in cocaine dependent subjects.
Detailed Description
-----------------
The purpose of study is to determine if modafinil promotes cocaine abstinence and reduces HRB in cocaine dependent subjects. Modafinil (300 mg/day) or placebo will be administered in an 8-week double-blind trial to patients meeting diagnostic criteria for cocaine dependence in conjunction with Cognitive Behavioral Therapy (CBT).
Official Title
-----------------
Modafinil Treatment for Cocaine Dependence and HIV-High Risk Behavior
Conditions
-----------------
Cocaine Dependence
Intervention / Treatment
-----------------
* Drug: Modafinil
* Drug: placebo
* Behavioral: Cognitive Behavioral Therapy (CBT)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 - 60 years; Current DSM-IV diagnosis of cocaine dependence; Using cocaine at least 8 days in a consecutive 30 day period over the 60 day period immediately preceding study entry (If subject was receiving inpatient substance abuse treatment within 30 days prior to screening, subject must have been using cocaine at least 8 days in a consecutive 30 day period over the 60 day period immediately preceding admission to inpatient treatment); 4.)Having a negative urine toxicology (BE) test during screening (no less than 5 days prior to randomization) and a negative urine toxicology (BE) test on the day of randomization. Repeat testing allowed until required negative BE results are obtained; Able to provide written informed consent and to comply with all study procedures; Women must be surgically sterile, at least two years postmenopausal, or, if of childbearing potential, be using a medically accepted method of birth control and agree to continue use of this method for at least 30 days after the last dose of study drug (i.e. barrier method with spermicide, steroidal contraceptive [oral and implanted, including Depo-Provera, contraceptives must be used in conjunction with a barrier method], or intrauterine device [IUD]). Exclusion Criteria: Currently dependent on any substance other than cocaine or nicotine; Current Neurological or psychiatric disorders, such as psychosis, bipolar illness, organic brain disease, dementia, or any diseases that require psychotropic medications; Serious medical illnesses, including but not limited to; uncontrolled hypertension, significant heart disease (including a history of myocardial infarction, angina, mitral valve prolapse, left ventricular hypertrophy, palpitations, and arrhythmia), hepatic disease, renal disease, or any serious, potentially life-threatening or progressive medical illness that may compromise patient safety or study conduct; Received a drug with known potential for toxicity to a major organ system within the month prior to entering treatment including, but not limited to: chemotherapeutic agents for neoplastic disease (i.e. methotrexate, vincristine, vinblastine, fluorouracil), agents used for parasitic infections, isoniazid, chlorambucil, dactinomycin, chloramphenicol, immunosuppressive and cytotoxic agents (i.e. cyclosporine, tacrolimus), indomethacin, protease inhibitors, amphotericin B, cephalosporins, aminoglycosides, interferon, and sulfonamides; Clinically significant abnormal laboratory values (see Appendix A); Has any disease of the gastrointestinal system, liver, or kidneys which could result in altered metabolism or excretion of the study medication (history of major gastrointestinal tract surgery, gastrectomy, gastrostomy, bowel resection, etc.) or history of chronic gastrointestinal disorders (ulcerative colitis, regional enteritis, or gastrointestinal bleeding); Known hypersensitivity or allergy to modafinil, or receiving chronic therapy with any medication that could interact adversely with modafinil, including propranolol, phenytoin, warfarin and diazepam; Took monoamine oxidase inhibitors (MAOI) within 30 days prior to randomization; Taking or has taken an investigational drug within 60 days prior to randomization; If female and of child-bearing capacity, tests positive on a urine pregnancy test, is lactating, has had three or more days of amenorrhea beyond expected menses at the time of the first dose of study medication, is contemplating pregnancy in the next 6 months, or is not using an effective contraceptive method; Received therapy with any opiate-substitute (methadone, LAAM, buprenorphine) within 60 days of study enrollment.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>modafinil plus CBT | Drug: Modafinil<br>* 300mg a day for 8 weeks<br>* Other names: Provigil;Behavioral: Cognitive Behavioral Therapy (CBT)<br>* Weekly cognitive behavioral therapy sessions for a period of 8 weeks.<br>|
| Placebo Comparator: 2<br>placebo plus CBT | Drug: placebo<br>* placebo pills for 8 weeks<br>Behavioral: Cognitive Behavioral Therapy (CBT)<br>* Weekly cognitive behavioral therapy sessions for a period of 8 weeks.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants Reporting no Cocaine Craving | Percent of participants reporting no cocaine craving based on Brief Substance Craving Scale (BSCS) - a 4 point likert scale. | 8 weeks |
| Cocaine Use as Measured by Urine Drug Screen | The primary outcome measure was cocaine use measured by self-report, and confirmed by twice weekly urine drug screens. The percentage of participants shows the percentage who were abstinent from cocaine during the last 3 weeks of the trial. | 8 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cocaine dependence, hiv prevention
|
|
NCT02300129
|
Effect of CD07805/47 Gel in Rosacea Flushing
|
Phase 2a study to assess the efficacy and safety of CD07805/47 0.5% gel in the prevention of the flush of rosacea.
|
The objectives of this study in rosacea patients (type I&II) are:~to demonstrate objectively that CD07805/47 0.5% gel is able to prevent a flush induced by a specific trigger (hot water) in controlled condition;~to demonstrate that CD07805/47 0.5% gel is able to prevent a flush whatever the trigger in everyday life condition;~to investigate if reduction in redness is associated with a decrease in skin sensations such as heat, stinging/burning, skin tension and sweating;~to demonstrate that such efficacy on transient redness and sensations takes place in both populations (rosacea type I and rosacea type II).~This is a single-centre, randomized, Investigator masked, placebo controlled study comprising the following periods:~A screening period of maximum 4 weeks~A one-week treatment phase (Period 1) with 3 sessions using the flush model, every other day.~This Period 1 includes a cross-over design (first and third sessions) and a split face design (second session). During this period, thirty six (36) subjects will receive on site the study drugs as follows (the order of each session being randomized):~CD07805/47 placebo gel on both sides of the face,~one side of the face treated with CD07805/47 0.5% gel, the other side treated with the CD07805/47 placebo gel (the allocation of treatment on each half-face will be determined according to a randomization list),~CD07805/47 0.5% gel on both sides of the face;~A 2-days wash-out period (between Period 1 and Period 2) with no treatment on either side of the face~A 4-week treatment phase (Period 2) corresponding to a cross-over design during which the subjects will apply themselves the study drugs at home on the whole face, once daily 7 days per week.~The subjects will be divided in 2 groups of eighteen (18) subjects and will receive either the CD07805/47 0.5% gel the first 2 weeks and then the CD07805/47 placebo gel or the CD07805/47 placebo gel the first 2 weeks and then the CD07805/47 0.5% gel, according to randomization.~All the subjects taking part into the study will not be randomized separately in the two periods but to the full sequence at the beginning of the clinical trial (same randomization number during all the study), explaining the arms/groups detailed in the section Arms and Interventions.~Only primary efficacy endpoint: total number of flushes for each 2-week period will be detailed in the outcome measures section.~The other endpoints are secondary or exploratory.~The purpose of Period 1 is to assess whether simpler and shorter designs based on flush induced by a trigger could be as efficient to detect prevention of flush than the more classical and longer design of Period 2.
|
Effect of CD07805/47 Gel in Subjects Presenting With Flushing Related to Erythematotelangiectatic or Papulopustular Rosacea
|
Rosacea
|
* Drug: CD07805/47, CD07805/47+Placebo, Placebo, CD07805/47, Placebo
* Drug: Placebo, CD07805/47+Placebo, CD07805/47, CD07805/47, Placebo
* Drug: CD07805/47, CD07805/47+Placebo, Placebo, Placebo, CD07805/47
* Drug: Placebo, CD07805/47+Placebo, CD07805/47, Placebo, CD07805/47
|
Inclusion Criteria:~The subject is a male or female, who is at least 18 years of age or older at Screening visit.~The subject has a clinical diagnosis of mild to moderate erythemato-telangiectatic rosacea or mild to moderate papulo-pustular rosacea according to the National Rosacea Society grading (Wilkin et al., 2004)~The subject had at least five flushing episodes during the last week before Screening and Baseline visits~Exclusion Criteria:~The subject has particular forms of rosacea (rosacea conglobata, rosacea fulminans, isolated rhinophyma, isolated pustulosis of the chin), or other concomitant facial dermatoses that are similar to rosacea such as peri-oral dermatitis, demodicidosis facial keratosis pilaris, seborrheic dermatitis, acute lupus erythematosus or actinic telangiectasia;~The subject has current treatment with monoamine oxidase inhibitors, barbiturates, opiates, sedatives, systemic anesthetics, or alpha-agonists;~The subject has less than 3 months stable dose treatment with tricyclic anti-depressants, cardiac glycosides, beta blockers or other antihypertensive agents;
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Number of Flushes for Each 2-week Period | | Day 22 and Day 36/Early termination |
|
Rosacea, Flushing, Skin Diseases, Skin Manifestations
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD07805/47, CD07805/47+Placebo, Placebo, CD07805/47, Placebo<br>Period 1:~Application of 1g of CD07805/47 0.5% Gel on full face on Day 1 (cross-over design) and 500mg on a half-face (split-face design) on Day 3.~Application of 500mg of Placebo Gel on a half-face (split-face design) on Day 3 and 1g on full face on Day 5 (cross-over design)~Period 2 (cross-over design):~Application of 1g of CD07805/47 0.5% Gel on full face once daily 7 days per week for 2 weeks then 1g of Placebo Gel on full face once daily 7 days per week for 2 weeks | Drug: CD07805/47, CD07805/47+Placebo, Placebo, CD07805/47, Placebo<br>* Period 1:~1g of CD07805/47 0.5% Gel on full face on Day 1 and 500mg on a half-face on Day 3.~500mg of Placebo Gel on a half-face on Day 3 and 1g on full face on Day 5.~Period 2:~1g of CD07805/47 0.5% Gel on full face once daily 7 days per week for 2 weeks.~1g of Placebo Gel on full face once daily 7 days per week the 2 following weeks.<br>|
| Experimental: Placebo, CD07805/47+Placebo, CD07805/47, CD07805/47, Placebo<br>Period 1:~Application of 1g of Placebo Gel on full face on Day 1 (cross-over design) and 500mg on a half-face (split-face design) on Day 3.~Application of 500mg of CD07805/47 0.5% Gel on a half-face (split-face design) on Day 3 and 1g on full face on Day 5 (cross-over design).~Period 2 (cross-over design):~Application of 1g of CD07805/47 0.5% Gel on full face once daily 7 days per week for 2 weeks then 1g of Placebo Gel on full face once daily 7 days per week for 2 weeks. | Drug: Placebo, CD07805/47+Placebo, CD07805/47, CD07805/47, Placebo<br>* Period 1:~1g of Placebo Gel on full face on Day 1 and 500mg on a half-face on Day 3.~500mg of CD07805/47 0.5% Gel on a half-face on Day 3 and 1g on full face on Day 5.~Period 2:~1g of CD07805/47 0.5% Gel on full face once daily 7 days per week for 2 weeks.~1g of Placebo Gel on full face once daily 7 days per week the 2 following weeks.<br>|
| Experimental: CD07805/47, CD07805/47+Placebo, Placebo, Placebo, CD07805/47<br>Period 1:~Application of 1g of CD07805/47 0.5% Gel on full face on Day 1 (cross-over design) and 500mg on a half-face (split-face design) on Day 3.~Application of 500mg of Placebo Gel on a half-face (split-face design) on Day 3 and 1g on full face on Day 5 (cross-over design).~Period 2 (cross-over design):~Application of 1g of Placebo Gel on full face once daily 7 days per week for 2 weeks then 1g of CD07805/47 0.5% Gel on full face once daily 7 days per week for 2 weeks. | Drug: CD07805/47, CD07805/47+Placebo, Placebo, Placebo, CD07805/47<br>* Period 1:~1g of CD07805/47 0.5% Gel on full face on Day 1 and 500mg on a half-face on Day 3.~500mg of Placebo Gel on a half-face on Day 3 and 1g on full face on Day 5.~Period 2:~1g of Placebo on full face once daily 7 days per week for 2 weeks.~1g of CD07805/47 0.5% Gel on full face once daily 7 days per week the 2 following weeks.<br>|
| Experimental: Placebo, CD07805/47+Placebo, CD07805/47, Placebo, CD07805/47<br>Period 1:~Application of 1g of Placebo Gel on full face on Day 1 (cross-over design) and 500mg on a half-face (split-face design) on Day 3.~Application of 500mg of CD07805/47 0.5% Gel on a half-face (split-face design) on Day 3 and 1g on full face on Day 5 (cross-over design).~Period 2 (cross-over design):~Application of 1g of Placebo Gel on full face once daily 7 days per week for 2 weeks then 1g of CD07805/47 0.5% Gel on full face once daily 7 days per week for 2 weeks. | Drug: Placebo, CD07805/47+Placebo, CD07805/47, Placebo, CD07805/47<br>* Period 1:~1g of Placebo Gel on full face on Day 1 and 500mg on a half-face on Day 3.~500mg of CD07805/47 0.5% Gel on a half-face on Day 3 and 1g on full face on Day 5.~Period 2:~1g of Placebo on full face once daily 7 days per week for 2 weeks.~1g of CD07805/47 0.5% Gel on full face once daily 7 days per week the 2 following weeks.<br>|
|
Effect of CD07805/47 Gel in Rosacea Flushing
Study Overview
=================
Brief Summary
-----------------
Phase 2a study to assess the efficacy and safety of CD07805/47 0.5% gel in the prevention of the flush of rosacea.
Detailed Description
-----------------
The objectives of this study in rosacea patients (type I&II) are: to demonstrate objectively that CD07805/47 0.5% gel is able to prevent a flush induced by a specific trigger (hot water) in controlled condition; to demonstrate that CD07805/47 0.5% gel is able to prevent a flush whatever the trigger in everyday life condition; to investigate if reduction in redness is associated with a decrease in skin sensations such as heat, stinging/burning, skin tension and sweating; to demonstrate that such efficacy on transient redness and sensations takes place in both populations (rosacea type I and rosacea type II). This is a single-centre, randomized, Investigator masked, placebo controlled study comprising the following periods: A screening period of maximum 4 weeks A one-week treatment phase (Period 1) with 3 sessions using the flush model, every other day. This Period 1 includes a cross-over design (first and third sessions) and a split face design (second session). During this period, thirty six (36) subjects will receive on site the study drugs as follows (the order of each session being randomized): CD07805/47 placebo gel on both sides of the face, one side of the face treated with CD07805/47 0.5% gel, the other side treated with the CD07805/47 placebo gel (the allocation of treatment on each half-face will be determined according to a randomization list), CD07805/47 0.5% gel on both sides of the face; A 2-days wash-out period (between Period 1 and Period 2) with no treatment on either side of the face A 4-week treatment phase (Period 2) corresponding to a cross-over design during which the subjects will apply themselves the study drugs at home on the whole face, once daily 7 days per week. The subjects will be divided in 2 groups of eighteen (18) subjects and will receive either the CD07805/47 0.5% gel the first 2 weeks and then the CD07805/47 placebo gel or the CD07805/47 placebo gel the first 2 weeks and then the CD07805/47 0.5% gel, according to randomization. All the subjects taking part into the study will not be randomized separately in the two periods but to the full sequence at the beginning of the clinical trial (same randomization number during all the study), explaining the arms/groups detailed in the section Arms and Interventions. Only primary efficacy endpoint: total number of flushes for each 2-week period will be detailed in the outcome measures section. The other endpoints are secondary or exploratory. The purpose of Period 1 is to assess whether simpler and shorter designs based on flush induced by a trigger could be as efficient to detect prevention of flush than the more classical and longer design of Period 2.
Official Title
-----------------
Effect of CD07805/47 Gel in Subjects Presenting With Flushing Related to Erythematotelangiectatic or Papulopustular Rosacea
Conditions
-----------------
Rosacea
Intervention / Treatment
-----------------
* Drug: CD07805/47, CD07805/47+Placebo, Placebo, CD07805/47, Placebo
* Drug: Placebo, CD07805/47+Placebo, CD07805/47, CD07805/47, Placebo
* Drug: CD07805/47, CD07805/47+Placebo, Placebo, Placebo, CD07805/47
* Drug: Placebo, CD07805/47+Placebo, CD07805/47, Placebo, CD07805/47
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The subject is a male or female, who is at least 18 years of age or older at Screening visit. The subject has a clinical diagnosis of mild to moderate erythemato-telangiectatic rosacea or mild to moderate papulo-pustular rosacea according to the National Rosacea Society grading (Wilkin et al., 2004) The subject had at least five flushing episodes during the last week before Screening and Baseline visits Exclusion Criteria: The subject has particular forms of rosacea (rosacea conglobata, rosacea fulminans, isolated rhinophyma, isolated pustulosis of the chin), or other concomitant facial dermatoses that are similar to rosacea such as peri-oral dermatitis, demodicidosis facial keratosis pilaris, seborrheic dermatitis, acute lupus erythematosus or actinic telangiectasia; The subject has current treatment with monoamine oxidase inhibitors, barbiturates, opiates, sedatives, systemic anesthetics, or alpha-agonists; The subject has less than 3 months stable dose treatment with tricyclic anti-depressants, cardiac glycosides, beta blockers or other antihypertensive agents;
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD07805/47, CD07805/47+Placebo, Placebo, CD07805/47, Placebo<br>Period 1: Application of 1g of CD07805/47 0.5% Gel on full face on Day 1 (cross-over design) and 500mg on a half-face (split-face design) on Day 3. Application of 500mg of Placebo Gel on a half-face (split-face design) on Day 3 and 1g on full face on Day 5 (cross-over design) Period 2 (cross-over design): Application of 1g of CD07805/47 0.5% Gel on full face once daily 7 days per week for 2 weeks then 1g of Placebo Gel on full face once daily 7 days per week for 2 weeks | Drug: CD07805/47, CD07805/47+Placebo, Placebo, CD07805/47, Placebo<br>* Period 1: 1g of CD07805/47 0.5% Gel on full face on Day 1 and 500mg on a half-face on Day 3. 500mg of Placebo Gel on a half-face on Day 3 and 1g on full face on Day 5. Period 2: 1g of CD07805/47 0.5% Gel on full face once daily 7 days per week for 2 weeks. 1g of Placebo Gel on full face once daily 7 days per week the 2 following weeks.<br>|
| Experimental: Placebo, CD07805/47+Placebo, CD07805/47, CD07805/47, Placebo<br>Period 1: Application of 1g of Placebo Gel on full face on Day 1 (cross-over design) and 500mg on a half-face (split-face design) on Day 3. Application of 500mg of CD07805/47 0.5% Gel on a half-face (split-face design) on Day 3 and 1g on full face on Day 5 (cross-over design). Period 2 (cross-over design): Application of 1g of CD07805/47 0.5% Gel on full face once daily 7 days per week for 2 weeks then 1g of Placebo Gel on full face once daily 7 days per week for 2 weeks. | Drug: Placebo, CD07805/47+Placebo, CD07805/47, CD07805/47, Placebo<br>* Period 1: 1g of Placebo Gel on full face on Day 1 and 500mg on a half-face on Day 3. 500mg of CD07805/47 0.5% Gel on a half-face on Day 3 and 1g on full face on Day 5. Period 2: 1g of CD07805/47 0.5% Gel on full face once daily 7 days per week for 2 weeks. 1g of Placebo Gel on full face once daily 7 days per week the 2 following weeks.<br>|
| Experimental: CD07805/47, CD07805/47+Placebo, Placebo, Placebo, CD07805/47<br>Period 1: Application of 1g of CD07805/47 0.5% Gel on full face on Day 1 (cross-over design) and 500mg on a half-face (split-face design) on Day 3. Application of 500mg of Placebo Gel on a half-face (split-face design) on Day 3 and 1g on full face on Day 5 (cross-over design). Period 2 (cross-over design): Application of 1g of Placebo Gel on full face once daily 7 days per week for 2 weeks then 1g of CD07805/47 0.5% Gel on full face once daily 7 days per week for 2 weeks. | Drug: CD07805/47, CD07805/47+Placebo, Placebo, Placebo, CD07805/47<br>* Period 1: 1g of CD07805/47 0.5% Gel on full face on Day 1 and 500mg on a half-face on Day 3. 500mg of Placebo Gel on a half-face on Day 3 and 1g on full face on Day 5. Period 2: 1g of Placebo on full face once daily 7 days per week for 2 weeks. 1g of CD07805/47 0.5% Gel on full face once daily 7 days per week the 2 following weeks.<br>|
| Experimental: Placebo, CD07805/47+Placebo, CD07805/47, Placebo, CD07805/47<br>Period 1: Application of 1g of Placebo Gel on full face on Day 1 (cross-over design) and 500mg on a half-face (split-face design) on Day 3. Application of 500mg of CD07805/47 0.5% Gel on a half-face (split-face design) on Day 3 and 1g on full face on Day 5 (cross-over design). Period 2 (cross-over design): Application of 1g of Placebo Gel on full face once daily 7 days per week for 2 weeks then 1g of CD07805/47 0.5% Gel on full face once daily 7 days per week for 2 weeks. | Drug: Placebo, CD07805/47+Placebo, CD07805/47, Placebo, CD07805/47<br>* Period 1: 1g of Placebo Gel on full face on Day 1 and 500mg on a half-face on Day 3. 500mg of CD07805/47 0.5% Gel on a half-face on Day 3 and 1g on full face on Day 5. Period 2: 1g of Placebo on full face once daily 7 days per week for 2 weeks. 1g of CD07805/47 0.5% Gel on full face once daily 7 days per week the 2 following weeks.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Number of Flushes for Each 2-week Period | | Day 22 and Day 36/Early termination |
|
||
NCT03081806
|
A Study to Evaluate the Efficacy and Safety of X0002 Spray in Subjects With Osteoarthritis Knee Pain
|
This is a Phase 3, Multicenter, 22-Week, double-blind and 30-Week open label Study to Evaluate the Efficacy and Safety of X0002 Spray in relief of pain of subjects with Osteoarthritis of the Knee.
|
The study comprises a 14-day Screening Period, a 22-week Double-blind Treatment Period, and a 30-week Open-label Treatment Period, with an additional 4-week Follow-up Visit. Subjects will be randomized into a low-dose or high-dose group receiving either active or placebo treatment during the DB period.~The WOMAC version 3.1 using the NRS will be used for the primary and secondary efficacy endpoints. Safety assessments will include assessment of AEs, vital signs (blood pressure, respiratory rate, pulse rate, and oral temperature), clinical laboratory tests, physical examination, skin irritation, and electrocardiograms (ECGs).
|
A Phase 3, Multicenter, Randomized, Placebo-controlled, Double-blind, 22-Week and 30-Week Open-label Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of X0002 Spray in Relief of the Pain for Subjects With Osteoarthritis of the Knee
|
Pain Associated With Osteoarthritis of the Knee
|
* Drug: X0002
|
Inclusion Criteria:~Ability to read and provide written, personally signed, and dated informed consent to participate in the study, in accordance with the ICH GCP Guideline E6 and applicable regulations, before completing any study related procedures.~An understanding, ability, and willingness to fully comply with study procedures and restrictions.~Subject must be a male or female between 35 and 85 years of age, inclusive.~Female subjects must either not be of childbearing potential (defined as postmenopausal for at least 1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy, or hysterectomy]) or be willing to Practice at least 1 of the following medically acceptable methods of birth control.~Subject must have a body mass index (BMI) between 18.5 and 45 kg/m2, inclusive.~Must have a history of clinically symptomatic OA of the knee for ≥6 months.~Must meet the American College of Rheumatology clinical classification criteria for knee OA. These criteria include the presence of knee pain in addition to at least 3 of the following 6 items:~age of ≥50 years~stiffness lasting <30 minutes~crepitus on knee motion~Bony Tenderness~Bony Enlargement~No palpable warmth~A subject must have a Kellgren Lawrence Grade of 2,3 or 4 as determined by a central radiologist at the first screening visit. .~Subject must have had knee pain while standing, walking, and/or in motion for at least 14 days during the month prior to Screening.~Subject must have a knee pain score ≥4 and <9 on 0-10 pain intensity NRS (without analgesic medication) on at least 7 of the 10 days prior to randomization.~Subject must be willing to discontinue any NSAIDs or other analgesic (eg, aspirin, acetaminophen) or potentially confounding concomitant treatments (eg, physiotherapy, acupuncture) starting on the first screening visit until completing participation in the study. (The use of ≤325 mg acetylsalicylic acid per day as cardiac prophylaxis is permitted.) The subject will be allowed to take rescue medication (acetaminophen) for pain during the study except during the 24 hours prior to the Second Screening Visit, Baseline (Day1), Week 2, Week 4, Week 8, Week 12, Week 22, Week 32, Week 42, and Week 52/EOS.~Subject must be willing to discontinue applying any topical preparations containing Vitamin A acids (including all trans retinoic acid (tretinoin), 13 cis retinoic acid [isotretinoin], 9 cis retinoic acid [alitretinoin], vitamin A [retinol], retinal, and their derivatives) to the lower limbs starting on the first screening visit until completing participation in the study. (Topical preparations containing Vitamin A acids or retinol may be applied to areas of the skin above the waist, but should not be applied to areas of the skin exposed to study medication.)~Subject must be willing to avoid unaccustomed physical activity (eg, starting a new weight lifting routine) for the duration of the study starting on the first screening visit.~With the exception of OA of the knee subjects with medical history must be stable as determined by the investigator.~Exclusion Criteria:~Has worker's compensation injuries affecting the knee or back.~Has a history of or is currently in litigation regarding joint injuries.~Has secondary OA of the target knee or OA of lower limb joints other than the knee that, in the investigator's opinion, could interfere with pain and functional assessments related to the target knee.~Has a history of total or partial knee replacement, arthroplasty, or other knee surgery on the target knee.~In the investigator's opinion, has had significant injury involving the target knee within the 6 months before Screening.~Has skin lesions or wounds on or near the target knee at Screening or at Baseline (Day 1) that, in the investigator's opinion, would affect absorption of the medication.~Has used opiates (including tramadol or tapentadol) or systemic corticosteroids within 30 days before Screening or requires treatment with chronic opiates or systemic corticosteroids.~Subjects with a placebo response exceeding 25% improvement in the average Western Ontario and McMaster Osteoarthritis Index [WOMAC] pain subscale score from Screening Visit to Day 1 will be excluded.~Has used gabapentin, pregabalin, antiepileptics, or specific antidepressants (i.e., tricyclics, serotonin norepinephrine reuptake inhibitors, or selective serotonin reuptake inhibitors) to treat pain in the 14 days before Screening. Other uses not related to the pain treatment may be permitted at the medical monitor's discretion provided they have been at a stable dose for at least 90 days.~Has had intra articular (IA) injections of corticosteroids, hyaluronic acid, or viscosupplements (e.g., Synvisc®) to the target knee within the 12 weeks before Screening~Has had IA or intravenous (IV) stem cell therapy in the 6 months prior to Screening~Is receiving or is planning to receive concomitant nonpharmacologic treatments (e.g., physiotherapy, acupuncture) that in the investigator's opinion could confound efficacy assessments within 14 days of Day 1.~Has a history of significant hypersensitivity, intolerance, or allergy to ibuprofen or any other NSAIDs, aspirin, or acetaminophen.~Has had an active gastrointestinal (GI) ulceration in the 6 months prior to Screening or a history of GI bleeding within 5 years of Screening.~Has used an anticoagulant or antiplatelet agent (except aspirin up to 325 mg/day for cardiac prophylaxis) in the 30 days prior to Screening.~Has a documented history of chronic inflammatory disease (e.g., rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, gouty arthritis) OR chronic pain condition (e.g., fibromyalgia), OR has other conditions that may affect the target joint for the functional and pain assessments (e.g., osteonecrosis, chondrocalcinosis).~Has uncontrolled depression or other uncontrolled psychiatric disorder (subjects with controlled depression or other psychiatric disorder, if using medication, must be on a stable dose of a medication other than an epileptic, tricyclic, serotonin norepinephrine reuptake inhibitor, or selective reuptake inhibitor for ≥12 weeks prior to Screening to participate in the study).~Has asthma requiring treatment with systemic corticosteroids in the last year prior to Screening. Asthmatic subjects using inhaled corticosteroids are eligible.~Has uncontrolled hypertension defined as systolic blood pressure >170 mmHg and diastolic blood pressure >90 mmHg at the Screening or Baseline Visit (may be repeated after 5 minutes rest to verify).~Is receiving systemic chemotherapy, has an active malignancy, lymphoproliferative disorder, or blood dyscrasia of any type, or has been diagnosed with cancer within 5 years before Screening. Subjects with completely excised squamous or basal cell carcinoma of the skin will be allowed.~Has any clinically significant unstable cardiac, respiratory, neurological, immunological, hematological, hepatic, or renal disease, or any other condition that, in the Investigator's opinion, could confound the study results, compromise the subject's welfare, interfere with the ability to communicate with the study staff, or otherwise contraindicate study participation.~Has any of the following conditions at Screening:~Acute hepatitis~Cirrhosis~Stage 4 or 5 end-stage renal disease~Subject has any other clinically significant laboratory finding at Screening that in the investigator's opinion contraindicates study participation.~Has clinically significant abnormality at Screening or Baseline (Day 1) on 12-lead ECG, including a QT interval calculated using Fridericia's correction (QTcF) interval >500 milliseconds (msec) or evidence of cardiac ischemia (i.e., Evident q waves: t wave inversion).~Is pregnant, planning to become pregnant during the study, or lactating. Has a positive serum and urine pregnancy test at Screening Visit, or a positive urine pregnancy test at Baseline (Day 1).~Has a positive urine drug screen for a nonprescribed drug prohibited by the protocol at Screening.~Has known alcohol or other substance abuse in the investigator's opinion.~Has participated in a previous clinical study with X0002.~Has participated in any other clinical trial within the past 30 days or within 5 half-lives of the study drug prior to Screening, whichever is longer.~Is a participating investigator, sub-investigator, study coordinator, or employee of a participating investigator, or is an immediate family member of the aforementioned.~Has any factor that, in the investigator's opinion, would jeopardize the evaluation or safety or be associated with poor adherence to the protocol.~Is without access to telephone and/or ability to gain technology access.
|
35 Years
|
85 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WOMAC pain subscale score in the target knee at Week 12 compared to Baseline | To evaluate the effect of X0002 spray compared to placebo for relief of knee pain in subjects with OA of the knee as measured by the WOMAC pain subscale score in the target knee at Week 12. | Week 12 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject's Global Assessment of Disease Status at Week 12. | To evaluate the effect of X0002 spray for Subject's Global Assessment of Disease Status in subjects with OA of the knee in the target knee. | Week 12 of treatment |
| WOMAC fuctional subscale score in the target knee at Week 12 | To evaluate the effect of X0002 spray for relief of fuctional subscale in subjects with OA of the knee as measured by the WOMAC pain subscale score in the target knee at Week 12. | Week 12 of treatment |
| WOMAC (NRS) pain subscale in the target knee at Week 2, 4, 8, and 22 | To evaluate the efficacy of X0002 spray in average WOMAC (NRS) pain subscale in the target knee at Weeks 2, 4, 8, and 22 | Week 2, 4, 8 , and 22 of treatment |
| WOMAC function subscale score | To evaluate the efficacy of X0002 spray in changes of WOMAC function subscale score of subjects with osteoarthritis (OA) of the target knee at Week 2, 4, 8 and 22. | Week 2, 4, 8 , and 22 of treatment |
| Average eDiary daily (NRS) score in the target knee | To evaluate the change from Baseline in average eDiary daily (NRS) score in the target knee for the 7 days prior to Weeks 2, 4, 8, 12, and 22. | Week 2, 4, 8, 12 and 22 of treatment |
| WOMAC overall score | To evaluate the efficacy of X0002 spray in change WOMAC overall score of subjects with osteoarthritis (OA) of the target knee at Weeks 2, 4,8,12 and 22. | Week 2, 4, 8, 12 and 22 of treatment |
| WOMAC stiffness subscale | To evaluate the efficacy of X0002 spray in change WOMAC stiffness subscale of subjects with osteoarthritis (OA) of the target knee at Weeks 2, 4,8,12 and 22. | Week 2, 4, 8, 12 and 22 of treatment |
|
Phase 3, Efficacy, Safety, Osteoarthritis, Knee, Pain
|
Osteoarthritis, Osteoarthritis, Knee, Arthritis, Joint Diseases, Musculoskeletal Diseases, Rheumatic Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>High dose group: X0002, BID (approximately every 12 hours; n=102); Placebo, BID(approximately every 12 hours; n=102) | Drug: X0002<br>* Subjects will complete 22 weeks of double-blind treatment and then enter into 30 weeks open-label treatment.<br>|
| Placebo Comparator: Group B<br>Low dose group: X0002, BID (approximately every 12 hours; n=102); Placebo, BID(approximately every 12 hours; n=102) | Drug: X0002<br>* Subjects will complete 22 weeks of double-blind treatment and then enter into 30 weeks open-label treatment.<br>|
|
A Study to Evaluate the Efficacy and Safety of X0002 Spray in Subjects With Osteoarthritis Knee Pain
Study Overview
=================
Brief Summary
-----------------
This is a Phase 3, Multicenter, 22-Week, double-blind and 30-Week open label Study to Evaluate the Efficacy and Safety of X0002 Spray in relief of pain of subjects with Osteoarthritis of the Knee.
Detailed Description
-----------------
The study comprises a 14-day Screening Period, a 22-week Double-blind Treatment Period, and a 30-week Open-label Treatment Period, with an additional 4-week Follow-up Visit. Subjects will be randomized into a low-dose or high-dose group receiving either active or placebo treatment during the DB period. The WOMAC version 3.1 using the NRS will be used for the primary and secondary efficacy endpoints. Safety assessments will include assessment of AEs, vital signs (blood pressure, respiratory rate, pulse rate, and oral temperature), clinical laboratory tests, physical examination, skin irritation, and electrocardiograms (ECGs).
Official Title
-----------------
A Phase 3, Multicenter, Randomized, Placebo-controlled, Double-blind, 22-Week and 30-Week Open-label Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of X0002 Spray in Relief of the Pain for Subjects With Osteoarthritis of the Knee
Conditions
-----------------
Pain Associated With Osteoarthritis of the Knee
Intervention / Treatment
-----------------
* Drug: X0002
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ability to read and provide written, personally signed, and dated informed consent to participate in the study, in accordance with the ICH GCP Guideline E6 and applicable regulations, before completing any study related procedures. An understanding, ability, and willingness to fully comply with study procedures and restrictions. Subject must be a male or female between 35 and 85 years of age, inclusive. Female subjects must either not be of childbearing potential (defined as postmenopausal for at least 1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy, or hysterectomy]) or be willing to Practice at least 1 of the following medically acceptable methods of birth control. Subject must have a body mass index (BMI) between 18.5 and 45 kg/m2, inclusive. Must have a history of clinically symptomatic OA of the knee for ≥6 months. Must meet the American College of Rheumatology clinical classification criteria for knee OA. These criteria include the presence of knee pain in addition to at least 3 of the following 6 items: age of ≥50 years stiffness lasting <30 minutes crepitus on knee motion Bony Tenderness Bony Enlargement No palpable warmth A subject must have a Kellgren Lawrence Grade of 2,3 or 4 as determined by a central radiologist at the first screening visit. . Subject must have had knee pain while standing, walking, and/or in motion for at least 14 days during the month prior to Screening. Subject must have a knee pain score ≥4 and <9 on 0-10 pain intensity NRS (without analgesic medication) on at least 7 of the 10 days prior to randomization. Subject must be willing to discontinue any NSAIDs or other analgesic (eg, aspirin, acetaminophen) or potentially confounding concomitant treatments (eg, physiotherapy, acupuncture) starting on the first screening visit until completing participation in the study. (The use of ≤325 mg acetylsalicylic acid per day as cardiac prophylaxis is permitted.) The subject will be allowed to take rescue medication (acetaminophen) for pain during the study except during the 24 hours prior to the Second Screening Visit, Baseline (Day1), Week 2, Week 4, Week 8, Week 12, Week 22, Week 32, Week 42, and Week 52/EOS. Subject must be willing to discontinue applying any topical preparations containing Vitamin A acids (including all trans retinoic acid (tretinoin), 13 cis retinoic acid [isotretinoin], 9 cis retinoic acid [alitretinoin], vitamin A [retinol], retinal, and their derivatives) to the lower limbs starting on the first screening visit until completing participation in the study. (Topical preparations containing Vitamin A acids or retinol may be applied to areas of the skin above the waist, but should not be applied to areas of the skin exposed to study medication.) Subject must be willing to avoid unaccustomed physical activity (eg, starting a new weight lifting routine) for the duration of the study starting on the first screening visit. With the exception of OA of the knee subjects with medical history must be stable as determined by the investigator. Exclusion Criteria: Has worker's compensation injuries affecting the knee or back. Has a history of or is currently in litigation regarding joint injuries. Has secondary OA of the target knee or OA of lower limb joints other than the knee that, in the investigator's opinion, could interfere with pain and functional assessments related to the target knee. Has a history of total or partial knee replacement, arthroplasty, or other knee surgery on the target knee. In the investigator's opinion, has had significant injury involving the target knee within the 6 months before Screening. Has skin lesions or wounds on or near the target knee at Screening or at Baseline (Day 1) that, in the investigator's opinion, would affect absorption of the medication. Has used opiates (including tramadol or tapentadol) or systemic corticosteroids within 30 days before Screening or requires treatment with chronic opiates or systemic corticosteroids. Subjects with a placebo response exceeding 25% improvement in the average Western Ontario and McMaster Osteoarthritis Index [WOMAC] pain subscale score from Screening Visit to Day 1 will be excluded. Has used gabapentin, pregabalin, antiepileptics, or specific antidepressants (i.e., tricyclics, serotonin norepinephrine reuptake inhibitors, or selective serotonin reuptake inhibitors) to treat pain in the 14 days before Screening. Other uses not related to the pain treatment may be permitted at the medical monitor's discretion provided they have been at a stable dose for at least 90 days. Has had intra articular (IA) injections of corticosteroids, hyaluronic acid, or viscosupplements (e.g., Synvisc®) to the target knee within the 12 weeks before Screening Has had IA or intravenous (IV) stem cell therapy in the 6 months prior to Screening Is receiving or is planning to receive concomitant nonpharmacologic treatments (e.g., physiotherapy, acupuncture) that in the investigator's opinion could confound efficacy assessments within 14 days of Day 1. Has a history of significant hypersensitivity, intolerance, or allergy to ibuprofen or any other NSAIDs, aspirin, or acetaminophen. Has had an active gastrointestinal (GI) ulceration in the 6 months prior to Screening or a history of GI bleeding within 5 years of Screening. Has used an anticoagulant or antiplatelet agent (except aspirin up to 325 mg/day for cardiac prophylaxis) in the 30 days prior to Screening. Has a documented history of chronic inflammatory disease (e.g., rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, gouty arthritis) OR chronic pain condition (e.g., fibromyalgia), OR has other conditions that may affect the target joint for the functional and pain assessments (e.g., osteonecrosis, chondrocalcinosis). Has uncontrolled depression or other uncontrolled psychiatric disorder (subjects with controlled depression or other psychiatric disorder, if using medication, must be on a stable dose of a medication other than an epileptic, tricyclic, serotonin norepinephrine reuptake inhibitor, or selective reuptake inhibitor for ≥12 weeks prior to Screening to participate in the study). Has asthma requiring treatment with systemic corticosteroids in the last year prior to Screening. Asthmatic subjects using inhaled corticosteroids are eligible. Has uncontrolled hypertension defined as systolic blood pressure >170 mmHg and diastolic blood pressure >90 mmHg at the Screening or Baseline Visit (may be repeated after 5 minutes rest to verify). Is receiving systemic chemotherapy, has an active malignancy, lymphoproliferative disorder, or blood dyscrasia of any type, or has been diagnosed with cancer within 5 years before Screening. Subjects with completely excised squamous or basal cell carcinoma of the skin will be allowed. Has any clinically significant unstable cardiac, respiratory, neurological, immunological, hematological, hepatic, or renal disease, or any other condition that, in the Investigator's opinion, could confound the study results, compromise the subject's welfare, interfere with the ability to communicate with the study staff, or otherwise contraindicate study participation. Has any of the following conditions at Screening: Acute hepatitis Cirrhosis Stage 4 or 5 end-stage renal disease Subject has any other clinically significant laboratory finding at Screening that in the investigator's opinion contraindicates study participation. Has clinically significant abnormality at Screening or Baseline (Day 1) on 12-lead ECG, including a QT interval calculated using Fridericia's correction (QTcF) interval >500 milliseconds (msec) or evidence of cardiac ischemia (i.e., Evident q waves: t wave inversion). Is pregnant, planning to become pregnant during the study, or lactating. Has a positive serum and urine pregnancy test at Screening Visit, or a positive urine pregnancy test at Baseline (Day 1). Has a positive urine drug screen for a nonprescribed drug prohibited by the protocol at Screening. Has known alcohol or other substance abuse in the investigator's opinion. Has participated in a previous clinical study with X0002. Has participated in any other clinical trial within the past 30 days or within 5 half-lives of the study drug prior to Screening, whichever is longer. Is a participating investigator, sub-investigator, study coordinator, or employee of a participating investigator, or is an immediate family member of the aforementioned. Has any factor that, in the investigator's opinion, would jeopardize the evaluation or safety or be associated with poor adherence to the protocol. Is without access to telephone and/or ability to gain technology access.
Ages Eligible for Study
-----------------
Minimum Age: 35 Years
Maximum Age: 85 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>High dose group: X0002, BID (approximately every 12 hours; n=102); Placebo, BID(approximately every 12 hours; n=102) | Drug: X0002<br>* Subjects will complete 22 weeks of double-blind treatment and then enter into 30 weeks open-label treatment.<br>|
| Placebo Comparator: Group B<br>Low dose group: X0002, BID (approximately every 12 hours; n=102); Placebo, BID(approximately every 12 hours; n=102) | Drug: X0002<br>* Subjects will complete 22 weeks of double-blind treatment and then enter into 30 weeks open-label treatment.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WOMAC pain subscale score in the target knee at Week 12 compared to Baseline | To evaluate the effect of X0002 spray compared to placebo for relief of knee pain in subjects with OA of the knee as measured by the WOMAC pain subscale score in the target knee at Week 12. | Week 12 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject's Global Assessment of Disease Status at Week 12. | To evaluate the effect of X0002 spray for Subject's Global Assessment of Disease Status in subjects with OA of the knee in the target knee. | Week 12 of treatment |
| WOMAC fuctional subscale score in the target knee at Week 12 | To evaluate the effect of X0002 spray for relief of fuctional subscale in subjects with OA of the knee as measured by the WOMAC pain subscale score in the target knee at Week 12. | Week 12 of treatment |
| WOMAC (NRS) pain subscale in the target knee at Week 2, 4, 8, and 22 | To evaluate the efficacy of X0002 spray in average WOMAC (NRS) pain subscale in the target knee at Weeks 2, 4, 8, and 22 | Week 2, 4, 8 , and 22 of treatment |
| WOMAC function subscale score | To evaluate the efficacy of X0002 spray in changes of WOMAC function subscale score of subjects with osteoarthritis (OA) of the target knee at Week 2, 4, 8 and 22. | Week 2, 4, 8 , and 22 of treatment |
| Average eDiary daily (NRS) score in the target knee | To evaluate the change from Baseline in average eDiary daily (NRS) score in the target knee for the 7 days prior to Weeks 2, 4, 8, 12, and 22. | Week 2, 4, 8, 12 and 22 of treatment |
| WOMAC overall score | To evaluate the efficacy of X0002 spray in change WOMAC overall score of subjects with osteoarthritis (OA) of the target knee at Weeks 2, 4,8,12 and 22. | Week 2, 4, 8, 12 and 22 of treatment |
| WOMAC stiffness subscale | To evaluate the efficacy of X0002 spray in change WOMAC stiffness subscale of subjects with osteoarthritis (OA) of the target knee at Weeks 2, 4,8,12 and 22. | Week 2, 4, 8, 12 and 22 of treatment |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Phase 3, Efficacy, Safety, Osteoarthritis, Knee, Pain
|
NCT00398970
|
Utility of Endobronchial Ultrasound in the Investigation of Suspected Lung Cancer.
|
Bronchoscopy of non visible lesions in the lung, have a low diagnostic yield. The use of endoscopic ultrasound might increase the diagnostic yield. This prospective study randomises between bronchoscopy with the use of a ultrasound miniprobe and bronchoscopy without the use of a miniprobe in clinical practice at Haukeland University Hospital.~The study hypothesis:~The use of the ultrasound miniprobe will increase the diagnostic yield of bronchoscopy in non visible lesions.
|
Bronchoscopy is usually the primary investigation of lesions in the lung. X-ray fluorescence guides the sampling with brushing, biopsy or trans bronchial needle aspiration (TBNA) if the lesion not is visible. Ct guided trans-thoracic sampling will be performed if a the sample is non representative. This will delay the diagnosis, and trans-thoracic sampling has a higher risk of pneumothorax. The use of a ultrasound miniprobe might increase the diagnostic yield of bronchoscopy in non visible lesions. The ultrasound probe in a guide sheath is advanced to the lesion with use of X-ray fluorescence. When the lesion is visualised the miniprobe is removed and sampling is performed with TBNA, biopsy and brushing through the guide sheath. If rapid on site cytoevaluation is negative, new TBNA is performed. Previous trials have shown a diagnostic yield without ultrasound between 40-50% and with ultrasound between 60-80%. The studies with ultrasound have been performed by super specialists. This study will evaluate bronchoscopy with the use of ultrasound miniprobe in clinical practice without super specialists. It is a prospective randomised trial.
|
Diagnostic Utility of Endobronchial Ultrasound in the Investigation of Suspected Malignant Lung Lesions Where the Lesions Are Not Visible During Bronchoscopy.
|
Lung Cancer
|
* Device: Endobronchial ultrasound miniprobe
|
Inclusion Criteria:~All patients with lesions suspicious of malignancy in the lung.~Exclusion Criteria:~Patients with lesions assumed to be visible by bronchoscopy.~Later proven visible lesion by bronchoscopy.~Patients not able to be investigated by bronchoscopy.
| null | null |
All
|
No
|
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic yield of bronchoscopy | | 6 months |
|
Endobronchial ultrasonography, Fluoroscopy, Guide sheath, Peripheral pulmonary lesion, Transbronchial biopsy
|
Neoplasms, Lung Neoplasms, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, Lung Diseases, Respiratory Tract Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Traditional flouroscopy guided sampling<br> | Device: Endobronchial ultrasound miniprobe<br>* Endobronchial ultrasound miniprobe is used to identify solid mass in lung parenchyma.<br>|
| Experimental: Ultrasound guide sampling<br> | Device: Endobronchial ultrasound miniprobe<br>* Endobronchial ultrasound miniprobe is used to identify solid mass in lung parenchyma.<br>|
|
Utility of Endobronchial Ultrasound in the Investigation of Suspected Lung Cancer.
Study Overview
=================
Brief Summary
-----------------
Bronchoscopy of non visible lesions in the lung, have a low diagnostic yield. The use of endoscopic ultrasound might increase the diagnostic yield. This prospective study randomises between bronchoscopy with the use of a ultrasound miniprobe and bronchoscopy without the use of a miniprobe in clinical practice at Haukeland University Hospital. The study hypothesis: The use of the ultrasound miniprobe will increase the diagnostic yield of bronchoscopy in non visible lesions.
Detailed Description
-----------------
Bronchoscopy is usually the primary investigation of lesions in the lung. X-ray fluorescence guides the sampling with brushing, biopsy or trans bronchial needle aspiration (TBNA) if the lesion not is visible. Ct guided trans-thoracic sampling will be performed if a the sample is non representative. This will delay the diagnosis, and trans-thoracic sampling has a higher risk of pneumothorax. The use of a ultrasound miniprobe might increase the diagnostic yield of bronchoscopy in non visible lesions. The ultrasound probe in a guide sheath is advanced to the lesion with use of X-ray fluorescence. When the lesion is visualised the miniprobe is removed and sampling is performed with TBNA, biopsy and brushing through the guide sheath. If rapid on site cytoevaluation is negative, new TBNA is performed. Previous trials have shown a diagnostic yield without ultrasound between 40-50% and with ultrasound between 60-80%. The studies with ultrasound have been performed by super specialists. This study will evaluate bronchoscopy with the use of ultrasound miniprobe in clinical practice without super specialists. It is a prospective randomised trial.
Official Title
-----------------
Diagnostic Utility of Endobronchial Ultrasound in the Investigation of Suspected Malignant Lung Lesions Where the Lesions Are Not Visible During Bronchoscopy.
Conditions
-----------------
Lung Cancer
Intervention / Treatment
-----------------
* Device: Endobronchial ultrasound miniprobe
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All patients with lesions suspicious of malignancy in the lung. Exclusion Criteria: Patients with lesions assumed to be visible by bronchoscopy. Later proven visible lesion by bronchoscopy. Patients not able to be investigated by bronchoscopy.
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Traditional flouroscopy guided sampling<br> | Device: Endobronchial ultrasound miniprobe<br>* Endobronchial ultrasound miniprobe is used to identify solid mass in lung parenchyma.<br>|
| Experimental: Ultrasound guide sampling<br> | Device: Endobronchial ultrasound miniprobe<br>* Endobronchial ultrasound miniprobe is used to identify solid mass in lung parenchyma.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic yield of bronchoscopy | | 6 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Endobronchial ultrasonography, Fluoroscopy, Guide sheath, Peripheral pulmonary lesion, Transbronchial biopsy
|
|
NCT01668940
|
Freezie Remedy to Alleviate Morning Sickness
|
The primary objective of this study is to assess the effectiveness of Lillipops in the improvement of morning sickness symptoms. Secondary objectives are to assess if there are any changes to concurrent symptoms that may intensify NVP, such as metallic taste or gastrointestinal issues (e.g. heartburn, acid reflux, indigestion and gas), as well as preference for freezie flavours.
|
Nausea and vomiting of pregnancy (NVP) is the most common medical condition of pregnancy, also known as morning sickness which affects up to 80% of pregnant women. Lillipops Iced Soothies are naturally flavoured freezies developed in the United Kingdom for women with morning sickness. They are available in 5 different flavours: grapefruit and tangerine, lemon and mint, chamomile and orange, lime and vanilla, and ginger. The flavours are derived from steam distillation of the peels (grapefruit, tangerine, lemon, orange, lime), mint leaves, and chamomile flowers to release and collect their essential oils. Vanilla pods and ginger are macerated and their resin is used. These flavours are chosen because they may provide relief of symptoms as they are either traditional remedies for NVP, such as ginger, or soothing and refreshing flavours, such as chamomile, vanilla and citrus.~This study hypothesizes that using Lillipops Iced Soothies will reduce the severity of NVP symptoms according to the PUQE-24 (pregnancy-unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy. In addition, we hypothesize concurrent symptoms that may intensify NVP, such as metallic taste or gastrointestinal disorders (e.g. heartburn, acid reflux, indigestion and gas), will be alleviated. We hypothesize that improvements to NVP and concurrent symptoms will be greater with Lillipop freezies compared to another commercially available freezie.
|
Effectiveness of a Natural Non-medicinal Freezie Remedy to Alleviate Morning Sickness
|
Morning Sickness
|
* Other: Lillipops Iced Soothies (4 flavours)
* Other: Mr. Freeze Freezies
* Other: Lillipop Iced Soothies (Ginger flavour)
|
Inclusion Criteria:~Pregnancy between 4 and 12 weeks gestation.~Pregnant women with NVP, regardless of treatment (if any) for their NVP.~Provide the signed informed consent form prior to initial interview.~Able to come in person to Sick Kids or meet at an agreed location.~Exclusion Criteria:~Gestational age beyond 12 weeks of pregnancy.~Pregnant women less than 18 years of age.~Women who are not proficient in the English language.~Unable to consume any of the ingredients listed in Lillipops or Mr. Freeze freezies due to allergies, medication interactions or other reasons.~Women refusing to avoid sources of ginger products for the duration of the study.
|
18 Years
|
45 Years
|
Female
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Four parallel groups: 1) Lillipops Group (4 flavours): 2) Ginger Lillipops Group; 3) Mr. Freeze Control Group; 4) Natural Course Group. The main comparison is Group 1 vs Group 3.
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of Nausea and Vomiting of Pregnancy (NVP) | To assess the effectiveness of Lillipops in the improvement of NVP symptoms. The primary endpoint of interest is the severity of NVP as compared between the 4 groups, defined according to the PUQE-24 (pregnancy-unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy that was developed and validated by Motherisk. | Baseline, +1, +3, +5, +7 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concurrent Symptoms | To assess if there are any changes to concurrent symptoms that may intensify NVP, such as metallic taste or gastrointestinal issues (e.g. heartburn, acid reflux, indigestion and gas). The secondary endpoint of interest is the effect of the 4 groups on the status of concurrent symptoms that may intensify NVP, such as metallic taste or gastroesophageal reflux disease, as well as preference for freezie flavours, according to the PUQE-24 (pregnancy-unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy that was developed and validated by Motherisk. | Baseline, +1, +3, +5, +7 days |
| Freezie Flavour Preference | To assess preference for freezie flavours. | Baseline, +1, +3, +5, +7 days |
|
Morning Sickness, Lillipops Iced Soothies, Pregnancy, Obstetrics
|
Morning Sickness, Pregnancy Complications, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Vomiting, Signs and Symptoms, Digestive
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lillipops Iced Soothies (4 flavours)<br>Initially, women will be given 1 multiflavour box of Lillipop samples minus the ginger flavour (4 flavours). Each box contains 24 freezies (20 mL each), 6 of each flavor. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 per day, and to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days). They can request an additional multiflavour box of freezies at each follow-up, as needed.~All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol | Other: Lillipops Iced Soothies (4 flavours)<br>* Lillipops Iced Soothies are naturally flavoured freezies developed in the United Kingdom for women with morning sickness. They are available in 5 different flavours: grapefruit and tangerine, lemon and mint, chamomile and orange, lime and vanilla, and ginger. The flavours are derived from steam distillation of the peels (grapefruit, tangerine, lemon, orange, lime), mint leaves, and chamomile flowers to release and collect their essential oils. Vanilla pods and ginger are macerated and their resin is used. These flavours were chosen because they may provide relief of symptoms as they are either traditional remedies for NVP, such as ginger, or soothing and refreshing flavours, such as chamomile, vanilla and citrus.<br>|
| Experimental: Lillipop Iced Soothies (Ginger flavour)<br>Initially, women will be given 1 Ginger flavor box of Lillipop samples. Each box contains 24 freezies (20 mL each). Each 20ml contains 80mg of dried ginger root. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 a day and to not have any other popsicles, freezies or other ginger products throughout the duration of the study (7 days). Due ginger's antiemetic property, a maximum daily dose is up to 1000mg/day of dried ginger root powder in pregnancy.They can request an additional box of freezies at each follow-up, as needed.All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol. | Other: Lillipop Iced Soothies (Ginger flavour)<br>* Lillipops Iced Soothies are naturally flavoured freezies developed in the United Kingdom for women with morning sickness. They are available in 5 different flavours: grapefruit and tangerine, lemon and mint, chamomile and orange, lime and vanilla, and ginger.The flavours are derived from steam distillation of the peels (grapefruit, tangerine, lemon, orange, lime), mint leaves, and chamomile flowers to release and collect their essential oils. Vanilla pods and ginger are macerated and their resin is used. These flavours were chosen because they may provide relief of symptoms as they are either traditional remedies for NVP, such as ginger, or soothing and refreshing flavours, such as chamomile, vanilla and citrus.<br>|
| Active Comparator: Mr. Freeze Freezies (4 flavours)<br>Initially, women will be given 1 multiflavour box of Mr. Freeze samples. Each box contains 24 freezies (20 mL each), 6 of each flavor. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 per day, and to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days). They can request an additional multiflavour box of freezies at each follow-up, as needed.~All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol | Other: Mr. Freeze Freezies<br>* There are other commercially available freezies, such as Mr. Freeze. Mr. Freeze freezies contain simulated flavours of watermelon, cherry, blue raspberry and cream soda. However, there have been no reports, studies or claims that they are effective as a remedy for the treatment of NVP.<br>|
| No Intervention: Natural Course Group<br>Women will not receive any freezies and will be asked to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days).~All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol | |
|
Freezie Remedy to Alleviate Morning Sickness
Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to assess the effectiveness of Lillipops in the improvement of morning sickness symptoms. Secondary objectives are to assess if there are any changes to concurrent symptoms that may intensify NVP, such as metallic taste or gastrointestinal issues (e.g. heartburn, acid reflux, indigestion and gas), as well as preference for freezie flavours.
Detailed Description
-----------------
Nausea and vomiting of pregnancy (NVP) is the most common medical condition of pregnancy, also known as morning sickness which affects up to 80% of pregnant women. Lillipops Iced Soothies are naturally flavoured freezies developed in the United Kingdom for women with morning sickness. They are available in 5 different flavours: grapefruit and tangerine, lemon and mint, chamomile and orange, lime and vanilla, and ginger. The flavours are derived from steam distillation of the peels (grapefruit, tangerine, lemon, orange, lime), mint leaves, and chamomile flowers to release and collect their essential oils. Vanilla pods and ginger are macerated and their resin is used. These flavours are chosen because they may provide relief of symptoms as they are either traditional remedies for NVP, such as ginger, or soothing and refreshing flavours, such as chamomile, vanilla and citrus. This study hypothesizes that using Lillipops Iced Soothies will reduce the severity of NVP symptoms according to the PUQE-24 (pregnancy-unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy. In addition, we hypothesize concurrent symptoms that may intensify NVP, such as metallic taste or gastrointestinal disorders (e.g. heartburn, acid reflux, indigestion and gas), will be alleviated. We hypothesize that improvements to NVP and concurrent symptoms will be greater with Lillipop freezies compared to another commercially available freezie.
Official Title
-----------------
Effectiveness of a Natural Non-medicinal Freezie Remedy to Alleviate Morning Sickness
Conditions
-----------------
Morning Sickness
Intervention / Treatment
-----------------
* Other: Lillipops Iced Soothies (4 flavours)
* Other: Mr. Freeze Freezies
* Other: Lillipop Iced Soothies (Ginger flavour)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pregnancy between 4 and 12 weeks gestation. Pregnant women with NVP, regardless of treatment (if any) for their NVP. Provide the signed informed consent form prior to initial interview. Able to come in person to Sick Kids or meet at an agreed location. Exclusion Criteria: Gestational age beyond 12 weeks of pregnancy. Pregnant women less than 18 years of age. Women who are not proficient in the English language. Unable to consume any of the ingredients listed in Lillipops or Mr. Freeze freezies due to allergies, medication interactions or other reasons. Women refusing to avoid sources of ginger products for the duration of the study.
Ages Eligible for Study
-----------------
Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Four parallel groups: 1) Lillipops Group (4 flavours): 2) Ginger Lillipops Group; 3) Mr. Freeze Control Group; 4) Natural Course Group. The main comparison is Group 1 vs Group 3.
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lillipops Iced Soothies (4 flavours)<br>Initially, women will be given 1 multiflavour box of Lillipop samples minus the ginger flavour (4 flavours). Each box contains 24 freezies (20 mL each), 6 of each flavor. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 per day, and to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days). They can request an additional multiflavour box of freezies at each follow-up, as needed. All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol | Other: Lillipops Iced Soothies (4 flavours)<br>* Lillipops Iced Soothies are naturally flavoured freezies developed in the United Kingdom for women with morning sickness. They are available in 5 different flavours: grapefruit and tangerine, lemon and mint, chamomile and orange, lime and vanilla, and ginger. The flavours are derived from steam distillation of the peels (grapefruit, tangerine, lemon, orange, lime), mint leaves, and chamomile flowers to release and collect their essential oils. Vanilla pods and ginger are macerated and their resin is used. These flavours were chosen because they may provide relief of symptoms as they are either traditional remedies for NVP, such as ginger, or soothing and refreshing flavours, such as chamomile, vanilla and citrus.<br>|
| Experimental: Lillipop Iced Soothies (Ginger flavour)<br>Initially, women will be given 1 Ginger flavor box of Lillipop samples. Each box contains 24 freezies (20 mL each). Each 20ml contains 80mg of dried ginger root. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 a day and to not have any other popsicles, freezies or other ginger products throughout the duration of the study (7 days). Due ginger's antiemetic property, a maximum daily dose is up to 1000mg/day of dried ginger root powder in pregnancy.They can request an additional box of freezies at each follow-up, as needed.All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol. | Other: Lillipop Iced Soothies (Ginger flavour)<br>* Lillipops Iced Soothies are naturally flavoured freezies developed in the United Kingdom for women with morning sickness. They are available in 5 different flavours: grapefruit and tangerine, lemon and mint, chamomile and orange, lime and vanilla, and ginger.The flavours are derived from steam distillation of the peels (grapefruit, tangerine, lemon, orange, lime), mint leaves, and chamomile flowers to release and collect their essential oils. Vanilla pods and ginger are macerated and their resin is used. These flavours were chosen because they may provide relief of symptoms as they are either traditional remedies for NVP, such as ginger, or soothing and refreshing flavours, such as chamomile, vanilla and citrus.<br>|
| Active Comparator: Mr. Freeze Freezies (4 flavours)<br>Initially, women will be given 1 multiflavour box of Mr. Freeze samples. Each box contains 24 freezies (20 mL each), 6 of each flavor. They will be told to eat the freezies as needed to alleviate symptoms, up to a maximum of 12 per day, and to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days). They can request an additional multiflavour box of freezies at each follow-up, as needed. All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol | Other: Mr. Freeze Freezies<br>* There are other commercially available freezies, such as Mr. Freeze. Mr. Freeze freezies contain simulated flavours of watermelon, cherry, blue raspberry and cream soda. However, there have been no reports, studies or claims that they are effective as a remedy for the treatment of NVP.<br>|
| No Intervention: Natural Course Group<br>Women will not receive any freezies and will be asked to not have any other popsicles, freezies or any ginger products throughout the duration of the study (7 days). All participants will initially receive counselling and advice by the Motherisk NVP Counsellor about symptom management. This includes advice about dietary, non-medicinal and medical treatments as per the Motherisk NVP protocol | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of Nausea and Vomiting of Pregnancy (NVP) | To assess the effectiveness of Lillipops in the improvement of NVP symptoms. The primary endpoint of interest is the severity of NVP as compared between the 4 groups, defined according to the PUQE-24 (pregnancy-unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy that was developed and validated by Motherisk. | Baseline, +1, +3, +5, +7 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concurrent Symptoms | To assess if there are any changes to concurrent symptoms that may intensify NVP, such as metallic taste or gastrointestinal issues (e.g. heartburn, acid reflux, indigestion and gas). The secondary endpoint of interest is the effect of the 4 groups on the status of concurrent symptoms that may intensify NVP, such as metallic taste or gastroesophageal reflux disease, as well as preference for freezie flavours, according to the PUQE-24 (pregnancy-unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy that was developed and validated by Motherisk. | Baseline, +1, +3, +5, +7 days |
| Freezie Flavour Preference | To assess preference for freezie flavours. | Baseline, +1, +3, +5, +7 days |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Morning Sickness, Lillipops Iced Soothies, Pregnancy, Obstetrics
|
NCT01086761
|
Study of MP0112 Intravitreal Injection in Patients With Wet Age Related Macular Degeneration
|
The purpose of this study is to assess the safety and tolerability of MP0112 (a novel, potentially long acting VEGF inhibitor) in patients with wet Age Related Macular Degeneration.
|
A Phase I/II, Open-label, Non-controlled, Escalating Dose, Multicentre Clinical Trial Evaluating the Safety, Preliminary Efficacy, and Pharmacokinetics of MP0112 Injected Intravitreally in Patients With Wet Age Related Macular Degeneration (AMD)
|
Wet Age-Related Macular Degeneration
|
* Biological: MP0112
|
Inclusion Criteria:~Clinical signs and angiographic evidence of active primary progressive subfoveal choroidal neovascularisation (CNV), including juxtafoveal lesions that affect the fovea on FA in the study eye that is at least 50% of the total lesion area~ETDRS best-corrected visual acuity of: 20/40 to 20/320 in the study eye at 4 meters~Male or female age > 50 years~Written informed consent prior to any study procedures~Willing, committed, and able to return for ALL clinic visits and complete all study-related procedures.~Exclusion Criteria:~Prior treatment with anti-VEGF therapy in the study eye, including bevacizumab, ranibizumab, or pegaptanib, as well as photodynamic therapy with verteporfin~Any prior or concomitant therapy with another investigational agent to treat neovascular AMD in the study eye, except dietary supplements or vitamins~Subfoveal thermal laser therapy, external-beam radiation therapy, or transpupillary thermotherapy in the study eye~Extrafoveal laser coagulation treatment within 12 weeks prior to Baseline in the study eye~Total lesion size > 20mm2 (including blood, scars and neovascularization) as assessed by FA in the study eye~Subretinal hemorrhage that is either 50% or more of the total lesion area, or if the blood is under the fovea and is 2.54mm2 or more in size in the study eye~Scar or fibrosis, making up > 50% of total lesion in the study eye~Scar, fibrosis, or atrophy involving the center of the fovea~Presence of retinal pigment epithelial tears or rips~History of any vitreous hemorrhage within 4 weeks prior to Visit 1 or current hemorrhage in the study eye~Presence of other causes of CNV, including pathologic myopia (spherical equivalent of -8 diopters or more negative, or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye~History or clinical evidence of diabetic retinopathy, diabetic macular oedema or any other vascular disease affecting the retina, other than AMD, in either eye~Prior vitrectomy in the study eye~History of retinal detachment or treatment or surgery for retinal detachment in the study eye~Ocular surgery (including cataract removal) in the study eye within 3 months of enrolment~Active intraocular inflammation (grade trace or above) in the study eye~History of allergy to any components of the study drug or diagnostic devices, such as fluorescein~Advanced glaucoma or intraocular pressure above 22 mmHg in the study eye despite treatment~Inability to obtain fundus photographs or fluorescein angiogram of sufficient quality to be analyzed and graded by the central reading center~History of idiopathic or autoimmune-associated uveitis in either eye~Infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye~Aphakia or absence of the posterior capsule in the study eye~Presence of a non-healing wound, ulcer, fracture or any other medical condition associated with bleeding~Use of antimitotic or antimetabolite therapy within 30 days or 5 elimination half-lives of enrolment~Premenopausal women~Any disorder or condition that contraindicates the use of an investigational drug~Participation in another investigational drug study within 3 months of enrolment~Uncontrolled hypertension~Previous stroke within 12 months of study entry~Systemic treatment with any anti-VEGF drug~Current treatment for active systemic infection
|
50 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal Tolerated Dose (MTD) Following a Single Injection | MTD was defined as one dose level below the lower of the dose level in which a severe (sight-threatening) drug-related Adverse Event occurred or the dose level at which more than 2 patients experienced a moderate ocular (eye) drug-related toxicity. | 16 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Stable or Improved Best Corrected Visual Acuity (BCVA) | BCVA was measured using an eye chart and was reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye at Baseline and Week 4. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The higher the letters read correctly on the eye chart the better the vision. Stable or Improved BCVA was defined as a loss of <15 letters read correctly compared to Baseline. | Baseline, Week 4 |
| Change From Baseline in Central Area Retinal Thickness | Optical Coherence Tomography (OCT), a laser based non-invasive diagnostic system providing high-resolution imaging sections of the retina, was performed in the study eye after pupil dilation at Baseline and Week 4. A negative change from Baseline indicated improvement (less retinal thickness). A positive change from Baseline indicated worsening (definite retinal thickening). | Baseline, Week 4 |
| Area of Leakage as Measured by Fluorescein Angiography | Fluorescein angiography (FA) is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc. FA was performed on the dilated study eye 10 minutes after fluorescein application at Baseline and Week 4. A lower number indicated a smaller area of leakage. | Baseline, Week 4 |
| Area of Lesion as Measured by Fluorescein Angiography | Fluorescein angiography (FA) is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc. FA was performed on the dilated study eye after fluorescein application at Baseline and Week 4. A lower number indicated a smaller lesion area. | Baseline, Week 4 |
| Maximum Serum Concentration (Cmax) of MP0112 at Day 3 | Blood samples were collected for MP0112 levels on Day 3. The serum samples (liquid portion of the blood after cells and clotting factors were removed) were sent to a laboratory and were analyzed for MP0112 levels using an enzyme-linked immunosorbent assay. Maximum concentration at Day 3 was calculated. | Day 3 |
| Number of Participants With Positive Binding Anti-MP0112 Antibodies | Blood samples were collected Pre-treatment (Baseline) and Weeks 4, 8 and 12. Samples were analyzed for Anti-MP0112 antibodies using an enzyme-linked immunosorbent assay. | 12 weeks |
|
Macular Degeneration, Retinal Degeneration, Retinal Diseases, Eye Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MP0112 (0.04 mg)<br>Single 0.04 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye.<br>|
| Experimental: MP0112 (0.15 mg)<br>Single 0.15 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye.<br>|
| Experimental: MP0112 (0.4 mg)<br>Single 0.4 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye.<br>|
| Experimental: MP0112 (1.0 mg)<br>Single 1.0 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye.<br>|
| Experimental: MP0112 (2.0 mg)<br>Single 2.0 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye.<br>|
| Experimental: MP0112 (3.6 mg)<br>Single 3.6 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye.<br>|
|
Study of MP0112 Intravitreal Injection in Patients With Wet Age Related Macular Degeneration
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the safety and tolerability of MP0112 (a novel, potentially long acting VEGF inhibitor) in patients with wet Age Related Macular Degeneration.
Official Title
-----------------
A Phase I/II, Open-label, Non-controlled, Escalating Dose, Multicentre Clinical Trial Evaluating the Safety, Preliminary Efficacy, and Pharmacokinetics of MP0112 Injected Intravitreally in Patients With Wet Age Related Macular Degeneration (AMD)
Conditions
-----------------
Wet Age-Related Macular Degeneration
Intervention / Treatment
-----------------
* Biological: MP0112
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinical signs and angiographic evidence of active primary progressive subfoveal choroidal neovascularisation (CNV), including juxtafoveal lesions that affect the fovea on FA in the study eye that is at least 50% of the total lesion area ETDRS best-corrected visual acuity of: 20/40 to 20/320 in the study eye at 4 meters Male or female age > 50 years Written informed consent prior to any study procedures Willing, committed, and able to return for ALL clinic visits and complete all study-related procedures. Exclusion Criteria: Prior treatment with anti-VEGF therapy in the study eye, including bevacizumab, ranibizumab, or pegaptanib, as well as photodynamic therapy with verteporfin Any prior or concomitant therapy with another investigational agent to treat neovascular AMD in the study eye, except dietary supplements or vitamins Subfoveal thermal laser therapy, external-beam radiation therapy, or transpupillary thermotherapy in the study eye Extrafoveal laser coagulation treatment within 12 weeks prior to Baseline in the study eye Total lesion size > 20mm2 (including blood, scars and neovascularization) as assessed by FA in the study eye Subretinal hemorrhage that is either 50% or more of the total lesion area, or if the blood is under the fovea and is 2.54mm2 or more in size in the study eye Scar or fibrosis, making up > 50% of total lesion in the study eye Scar, fibrosis, or atrophy involving the center of the fovea Presence of retinal pigment epithelial tears or rips History of any vitreous hemorrhage within 4 weeks prior to Visit 1 or current hemorrhage in the study eye Presence of other causes of CNV, including pathologic myopia (spherical equivalent of -8 diopters or more negative, or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye History or clinical evidence of diabetic retinopathy, diabetic macular oedema or any other vascular disease affecting the retina, other than AMD, in either eye Prior vitrectomy in the study eye History of retinal detachment or treatment or surgery for retinal detachment in the study eye Ocular surgery (including cataract removal) in the study eye within 3 months of enrolment Active intraocular inflammation (grade trace or above) in the study eye History of allergy to any components of the study drug or diagnostic devices, such as fluorescein Advanced glaucoma or intraocular pressure above 22 mmHg in the study eye despite treatment Inability to obtain fundus photographs or fluorescein angiogram of sufficient quality to be analyzed and graded by the central reading center History of idiopathic or autoimmune-associated uveitis in either eye Infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye Aphakia or absence of the posterior capsule in the study eye Presence of a non-healing wound, ulcer, fracture or any other medical condition associated with bleeding Use of antimitotic or antimetabolite therapy within 30 days or 5 elimination half-lives of enrolment Premenopausal women Any disorder or condition that contraindicates the use of an investigational drug Participation in another investigational drug study within 3 months of enrolment Uncontrolled hypertension Previous stroke within 12 months of study entry Systemic treatment with any anti-VEGF drug Current treatment for active systemic infection
Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MP0112 (0.04 mg)<br>Single 0.04 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye.<br>|
| Experimental: MP0112 (0.15 mg)<br>Single 0.15 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye.<br>|
| Experimental: MP0112 (0.4 mg)<br>Single 0.4 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye.<br>|
| Experimental: MP0112 (1.0 mg)<br>Single 1.0 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye.<br>|
| Experimental: MP0112 (2.0 mg)<br>Single 2.0 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye.<br>|
| Experimental: MP0112 (3.6 mg)<br>Single 3.6 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal Tolerated Dose (MTD) Following a Single Injection | MTD was defined as one dose level below the lower of the dose level in which a severe (sight-threatening) drug-related Adverse Event occurred or the dose level at which more than 2 patients experienced a moderate ocular (eye) drug-related toxicity. | 16 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Stable or Improved Best Corrected Visual Acuity (BCVA) | BCVA was measured using an eye chart and was reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye at Baseline and Week 4. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The higher the letters read correctly on the eye chart the better the vision. Stable or Improved BCVA was defined as a loss of <15 letters read correctly compared to Baseline. | Baseline, Week 4 |
| Change From Baseline in Central Area Retinal Thickness | Optical Coherence Tomography (OCT), a laser based non-invasive diagnostic system providing high-resolution imaging sections of the retina, was performed in the study eye after pupil dilation at Baseline and Week 4. A negative change from Baseline indicated improvement (less retinal thickness). A positive change from Baseline indicated worsening (definite retinal thickening). | Baseline, Week 4 |
| Area of Leakage as Measured by Fluorescein Angiography | Fluorescein angiography (FA) is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc. FA was performed on the dilated study eye 10 minutes after fluorescein application at Baseline and Week 4. A lower number indicated a smaller area of leakage. | Baseline, Week 4 |
| Area of Lesion as Measured by Fluorescein Angiography | Fluorescein angiography (FA) is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc. FA was performed on the dilated study eye after fluorescein application at Baseline and Week 4. A lower number indicated a smaller lesion area. | Baseline, Week 4 |
| Maximum Serum Concentration (Cmax) of MP0112 at Day 3 | Blood samples were collected for MP0112 levels on Day 3. The serum samples (liquid portion of the blood after cells and clotting factors were removed) were sent to a laboratory and were analyzed for MP0112 levels using an enzyme-linked immunosorbent assay. Maximum concentration at Day 3 was calculated. | Day 3 |
| Number of Participants With Positive Binding Anti-MP0112 Antibodies | Blood samples were collected Pre-treatment (Baseline) and Weeks 4, 8 and 12. Samples were analyzed for Anti-MP0112 antibodies using an enzyme-linked immunosorbent assay. | 12 weeks |
|
||
NCT04214639
|
Clinical Study Comparing the Efficacy and Safety of IDP-126 Gel in the Treatment of Acne Vulgaris
|
This is a multicenter, randomized, double-blind, vehicle-controlled, 12-week study designed to assess the safety, tolerability, and efficacy of IDP-126 Gel in comparison IDP-126 Vehicle Gel at Weeks 2, 4, 8, and 12.
|
A Phase 3, Multicenter, Randomized, Double-Blind, Vehicle Controlled, Parallel-Group, Clinical Study Comparing the Efficacy and Safety of IDP-126 Gel in the Treatment of Acne Vulgaris
|
Acne Vulgaris
|
* Drug: IDP-126 Gel
* Drug: IDP-126 Vehicle Gel
|
Inclusion Criteria:~Male or female at least 9 years of age and older.~Written and verbal informed consent must be obtained. Subjects less than age of consent must sign an assent for the study and a parent or a legal guardian must sign the informed consent (if subject reaches age of consent during the study they should be re-consented at the next study visit).~Subject must have an Evaluator's Global Severity Score (EGSS) of 3 (moderate) or 4 (severe) at the baseline visit.~Subjects with a facial acne inflammatory lesion (papules, pustules, and nodules) count no less than 30, but no more than 100.~Subjects with a facial acne non-inflammatory lesion (open and closed comedones) count no less than 35, but no more than 150.~Subjects with 2 or fewer facial nodules.~Exclusion Criteria:~Any dermatological conditions on the face that could interfere with clinical evaluations such as acne conglobata, acne fulminans, secondary acne, perioral dermatitis, clinically significant rosacea, gram negative folliculitis, dermatitis, eczema.~Any underlying disease(s) or some other dermatological condition of the face that requires the use of interfering topical or systemic therapy or makes evaluations and lesion count inconclusive.~Subjects with more than 2 facial nodules.~Female subjects who are pregnant, nursing mothers, planning a pregnancy during the course of the study, or become pregnant during the study.~Use of estrogens (eg, Depogen, Depo-Testadiol, Gynogen, Valergen, etc) for less than 12 weeks immediately preceding study entry; subjects treated with estrogens 12 or more consecutive weeks immediately prior to study entry need not be excluded unless the subject expects to change dose, drug or discontinue estrogen use during the study.~Treatment of any type of cancer within the last 6 months, with the exception of complete surgical excision of skin cancer outside the treatment area.~Subjects who have not undergone specified washout period(s) for topical preparations/physical treatments used on the face or subjects who require the concurrent use in the treatment area.~Subjects who have not undergone specified washout period(s) for systemic medications or subjects who require the concurrent use of systemic medications.~Subjects with any underlying disease that the investigator deems uncontrolled, and poses a concern for the subject's safety while participating in the study.
|
9 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change from Baseline to Week 12 in inflammatory lesion counts | | 12 weeks |
| Absolute change from Baseline to Week 12 in non-inflammatory lesion counts | | 12 weeks |
| Percentage of subjects who achieve at least a two-grade reduction from baseline and are Clear or Almost Clear at Week 12 in the Evaluator's Global Severity Score (EGSS) | EGSS evaluations will be scored on a scale of 0-4, with 0 being clear and 4 being severe. | 12 weeks |
|
Acne Vulgaris, Acneiform Eruptions, Skin Diseases, Sebaceous Gland Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IDP-126 Gel<br> | Drug: IDP-126 Gel<br>* IDP-126 Gel applied topically to the face once daily for 12 weeks.<br>|
| Placebo Comparator: IDP-126 Vehicle Gel<br> | Drug: IDP-126 Vehicle Gel<br>* IDP-126 Vehicle Gel applied topically to the face once daily for 12 weeks.<br>|
|
Clinical Study Comparing the Efficacy and Safety of IDP-126 Gel in the Treatment of Acne Vulgaris
Study Overview
=================
Brief Summary
-----------------
This is a multicenter, randomized, double-blind, vehicle-controlled, 12-week study designed to assess the safety, tolerability, and efficacy of IDP-126 Gel in comparison IDP-126 Vehicle Gel at Weeks 2, 4, 8, and 12.
Official Title
-----------------
A Phase 3, Multicenter, Randomized, Double-Blind, Vehicle Controlled, Parallel-Group, Clinical Study Comparing the Efficacy and Safety of IDP-126 Gel in the Treatment of Acne Vulgaris
Conditions
-----------------
Acne Vulgaris
Intervention / Treatment
-----------------
* Drug: IDP-126 Gel
* Drug: IDP-126 Vehicle Gel
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female at least 9 years of age and older. Written and verbal informed consent must be obtained. Subjects less than age of consent must sign an assent for the study and a parent or a legal guardian must sign the informed consent (if subject reaches age of consent during the study they should be re-consented at the next study visit). Subject must have an Evaluator's Global Severity Score (EGSS) of 3 (moderate) or 4 (severe) at the baseline visit. Subjects with a facial acne inflammatory lesion (papules, pustules, and nodules) count no less than 30, but no more than 100. Subjects with a facial acne non-inflammatory lesion (open and closed comedones) count no less than 35, but no more than 150. Subjects with 2 or fewer facial nodules. Exclusion Criteria: Any dermatological conditions on the face that could interfere with clinical evaluations such as acne conglobata, acne fulminans, secondary acne, perioral dermatitis, clinically significant rosacea, gram negative folliculitis, dermatitis, eczema. Any underlying disease(s) or some other dermatological condition of the face that requires the use of interfering topical or systemic therapy or makes evaluations and lesion count inconclusive. Subjects with more than 2 facial nodules. Female subjects who are pregnant, nursing mothers, planning a pregnancy during the course of the study, or become pregnant during the study. Use of estrogens (eg, Depogen, Depo-Testadiol, Gynogen, Valergen, etc) for less than 12 weeks immediately preceding study entry; subjects treated with estrogens 12 or more consecutive weeks immediately prior to study entry need not be excluded unless the subject expects to change dose, drug or discontinue estrogen use during the study. Treatment of any type of cancer within the last 6 months, with the exception of complete surgical excision of skin cancer outside the treatment area. Subjects who have not undergone specified washout period(s) for topical preparations/physical treatments used on the face or subjects who require the concurrent use in the treatment area. Subjects who have not undergone specified washout period(s) for systemic medications or subjects who require the concurrent use of systemic medications. Subjects with any underlying disease that the investigator deems uncontrolled, and poses a concern for the subject's safety while participating in the study.
Ages Eligible for Study
-----------------
Minimum Age: 9 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: IDP-126 Gel<br> | Drug: IDP-126 Gel<br>* IDP-126 Gel applied topically to the face once daily for 12 weeks.<br>|
| Placebo Comparator: IDP-126 Vehicle Gel<br> | Drug: IDP-126 Vehicle Gel<br>* IDP-126 Vehicle Gel applied topically to the face once daily for 12 weeks.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change from Baseline to Week 12 in inflammatory lesion counts | | 12 weeks |
| Absolute change from Baseline to Week 12 in non-inflammatory lesion counts | | 12 weeks |
| Percentage of subjects who achieve at least a two-grade reduction from baseline and are Clear or Almost Clear at Week 12 in the Evaluator's Global Severity Score (EGSS) | EGSS evaluations will be scored on a scale of 0-4, with 0 being clear and 4 being severe. | 12 weeks |
|
|||
NCT02318862
|
Assessment of Esophageal Epithelium Integrity With Mucosal Impedance
|
Gastroesophageal reflux disease (GERD) is a common condition affecting more than 100 million adults in the U.S., and it significantly impacts patients' quality of life while imposing billions of dollars of direct and indirect costs each year upon our healthcare system. Current diagnostic tests for GERD are highly invasive and medically inadequate, and the goal of this project is to develop a novel, minimally invasive Mucosal Impedance technique for more accurate detection of GERD while reducing costs.
|
Assessment of Esophageal Epithelium Integrity With Mucosal Impedance
|
Gastroesophageal Reflux Disease (GERD), Non-erosive Reflux Disease (NERD)
|
* Procedure: Standard of Care esophagogastroduodenoscopy (EGD) with mucosal impedance testing
|
Inclusion Criteria:~Patients undergoing standard of care EGD with 48-hr pH testing by BRAVO~Previous diagnosis of reflux~At least 18 years of age~Exclusion Criteria:~Those less than 18 years of age~Unable to give informed consent~Use of acid suppressive therapy within the last 10 days~Known history of Barrett's esophagus, gastric surgery, alcoholism, or significant motility condition
|
18 Years
| null |
All
|
No
|
Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of lower esophageal impedance using mucosal impedance catheter | Mucosal impedance is obtained during routine care EGD and readings are compared to 48-hour Bravo capsule results. Mucosal impedance only takes one minute to perform during endoscopy. | During standard of care EGD |
|
reflux, GERD, EGD, pH testing
|
Gastroesophageal Reflux, Esophageal Motility Disorders, Deglutition Disorders, Esophageal Diseases, Gastrointestinal Diseases, Digestive System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: GERD<br>Those who have abnormal pH and abnormal esophageal mucosa and those who have abnormal pH and normal esophageal mucosa and are scheduled for standard of care esophagogastroduodenoscopy (EGD) with mucosal impedance testing | Procedure: Standard of Care esophagogastroduodenoscopy (EGD) with mucosal impedance testing<br> <br> |
| Other: non-GERD<br>Those who have normal pH and normal esophageal mucosa and are scheduled for standard of care esophagogastroduodenoscopy (EGD) with mucosal impedance testing | Procedure: Standard of Care esophagogastroduodenoscopy (EGD) with mucosal impedance testing<br> <br> |
|
Assessment of Esophageal Epithelium Integrity With Mucosal Impedance
Study Overview
=================
Brief Summary
-----------------
Gastroesophageal reflux disease (GERD) is a common condition affecting more than 100 million adults in the U.S., and it significantly impacts patients' quality of life while imposing billions of dollars of direct and indirect costs each year upon our healthcare system. Current diagnostic tests for GERD are highly invasive and medically inadequate, and the goal of this project is to develop a novel, minimally invasive Mucosal Impedance technique for more accurate detection of GERD while reducing costs.
Official Title
-----------------
Assessment of Esophageal Epithelium Integrity With Mucosal Impedance
Conditions
-----------------
Gastroesophageal Reflux Disease (GERD), Non-erosive Reflux Disease (NERD)
Intervention / Treatment
-----------------
* Procedure: Standard of Care esophagogastroduodenoscopy (EGD) with mucosal impedance testing
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients undergoing standard of care EGD with 48-hr pH testing by BRAVO Previous diagnosis of reflux At least 18 years of age Exclusion Criteria: Those less than 18 years of age Unable to give informed consent Use of acid suppressive therapy within the last 10 days Known history of Barrett's esophagus, gastric surgery, alcoholism, or significant motility condition
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: GERD<br>Those who have abnormal pH and abnormal esophageal mucosa and those who have abnormal pH and normal esophageal mucosa and are scheduled for standard of care esophagogastroduodenoscopy (EGD) with mucosal impedance testing | Procedure: Standard of Care esophagogastroduodenoscopy (EGD) with mucosal impedance testing<br> <br> |
| Other: non-GERD<br>Those who have normal pH and normal esophageal mucosa and are scheduled for standard of care esophagogastroduodenoscopy (EGD) with mucosal impedance testing | Procedure: Standard of Care esophagogastroduodenoscopy (EGD) with mucosal impedance testing<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of lower esophageal impedance using mucosal impedance catheter | Mucosal impedance is obtained during routine care EGD and readings are compared to 48-hour Bravo capsule results. Mucosal impedance only takes one minute to perform during endoscopy. | During standard of care EGD |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
reflux, GERD, EGD, pH testing
|
||
NCT03795441
|
A Shedding Study of Adenovirus Serotype 26 Based Respiratory Syncytial Virus Pre-fusion F Protein (Ad26.RSV.preF) Vaccine in Adults
|
The purpose of this study is to assess the shedding and kinetics of the Adenovirus Serotype 26 Based Respiratory Syncytial Virus Pre-fusion F Protein (Ad26.RSV.preF) vaccine after one intramuscular injection of Ad26.RSV.preF in adults.
|
Open Label, Single Arm Phase 1 Study to Evaluate the Shedding, Biodistribution, Safety and Immunogenicity of Ad26.RSV.preF Vaccine in Adults
|
Healthy
|
* Biological: Ad26.RSV.preF
|
Inclusion Criteria:~In the investigator's clinical judgment, participant must be in good or stable health. Participants may have underlying illnesses such as hypertension, Type 2 diabetes mellitus, hyperlipoproteinemia, or hypothyroidism, as long as their symptoms and signs are medically controlled. If they are on medication for a condition, the medication dose must have been stable for at least 12 weeks preceding vaccination and expected to remain stable for the duration of the study. Participants will be included on the basis of physical examination, medical history, vital signs measurement and 12-lead electrocardiogram (ECG; for participants greater than [>] 65 years of age only) performed at screening~Contraceptive use by women should be consistent with local regulations regarding the use of contraceptive methods for participants in clinical studies~All women of childbearing potential must have a negative highly sensitive serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening and a negative urine beta-hCG pregnancy test immediately prior to study vaccine administration~From the time of vaccination through 3 months after vaccination, participant agrees not to donate blood~Participant must be willing to provide verifiable identification, have means to be contacted and to contact the investigator during the study~Exclusion Criteria:~Participant has a serious chronic disorder, including severe chronic obstructive pulmonary disease or clinically significant congestive heart failure, requirement for supplemental oxygen, end-stage renal disease with or without dialysis, clinically unstable cardiac disease, Alzheimer's disease, or has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise well-being) or that could prevent, limit, or confound the protocol-specified assessments~Per medical history, participant has chronic active hepatitis B or hepatitis C infection~Participant has received an investigational drug or used an invasive investigational medical device within 30 days or received an investigational vaccine within 6 months before the planned administration of study vaccine or is currently enrolled or plans to participate in another investigational study during the course of this study~Participant has received treatment with immunoglobulin in the 2 months, or blood products in the 4 months before the planned administration of study vaccine or has any plans to receive such treatment during the study~Participant has received any RSV vaccine in any previous RSV vaccine study at any time prior to randomization
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Presence of Ad26.RSV.preF (shedding) as Assessed by qPCR | Percentage of Participants with presence of Ad26.RSV.preF in the adhesive bandage covering the injection site, the injection site area, nares (mid-turbinate), throat, rectum, urine, semen and blood, will be assessed by Quantitative Polymerase Chain Reaction (qPCR). Percentage of participants with presence of Ad26.RSV.preF (shedding) will be assessed. | Up to Day 183 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Serious Adverse Events (SAEs) | Number of participants with SAEs will be evaluated. An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life threatening experience, is a congenital anomaly/birth defect, is suspected transmission of any infectious agent via a medicinal product, is medically important, and may jeopardize participant or may require medical or surgical intervention to prevent one of the outcomes listed above. | First vaccination (Day 1) to the end of the study (Day 183) |
| Number of Participants with Solicited Local and Systemic Adverse Events (AEs) After Vaccination | Number of participants with solicited local and systemic AEs will be evaluated. Solicited local AEs (erythema, swelling/induration, and pain/tenderness at the injection site) and solicited systemic AEs (fatigue, headache, myalgia, arthralgia, chills, nausea, and fever) will be noted in the participant diary through the 7 days post-vaccination. Local and systemic AEs will be graded according to severity as mild (Grade 1), moderate (Grade 2), severe (Grade 3) and potentially life threatening (Grade 4). | 7 days after vaccination (Day 1 up to Day 7) |
| Number of Participants with Unsolicited AEs as a Measure of Safety | Number of participants with unsolicited AEs will be evaluated. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product, and it does not necessarily have a causal relationship with the intervention, therefore an AE can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product. Unsolicited AEs will include all AEs for which the participant is specifically not questioned in the participant diary. Unsolicited AEs will be graded according to severity as mild (Grade 1), moderate (Grade 2), severe (Grade 3) and potentially life threatening (Grade 4). | Day 1 Up to Day 28 |
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ad26.RSV.preF<br>Participants will receive one intramuscular injection of an adenovirus serotype 26- based vaccine encoding for the respiratory syncytial virus pre-fusion F protein (Ad26.RSV.preF) on Day 1. | Biological: Ad26.RSV.preF<br>* Ad26.RSV.preF will be administered as intramuscular injection on Day 1.<br>* Other names: JNJ-64400141;|
|
A Shedding Study of Adenovirus Serotype 26 Based Respiratory Syncytial Virus Pre-fusion F Protein (Ad26.RSV.preF) Vaccine in Adults
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the shedding and kinetics of the Adenovirus Serotype 26 Based Respiratory Syncytial Virus Pre-fusion F Protein (Ad26.RSV.preF) vaccine after one intramuscular injection of Ad26.RSV.preF in adults.
Official Title
-----------------
Open Label, Single Arm Phase 1 Study to Evaluate the Shedding, Biodistribution, Safety and Immunogenicity of Ad26.RSV.preF Vaccine in Adults
Conditions
-----------------
Healthy
Intervention / Treatment
-----------------
* Biological: Ad26.RSV.preF
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: In the investigator's clinical judgment, participant must be in good or stable health. Participants may have underlying illnesses such as hypertension, Type 2 diabetes mellitus, hyperlipoproteinemia, or hypothyroidism, as long as their symptoms and signs are medically controlled. If they are on medication for a condition, the medication dose must have been stable for at least 12 weeks preceding vaccination and expected to remain stable for the duration of the study. Participants will be included on the basis of physical examination, medical history, vital signs measurement and 12-lead electrocardiogram (ECG; for participants greater than [>] 65 years of age only) performed at screening Contraceptive use by women should be consistent with local regulations regarding the use of contraceptive methods for participants in clinical studies All women of childbearing potential must have a negative highly sensitive serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening and a negative urine beta-hCG pregnancy test immediately prior to study vaccine administration From the time of vaccination through 3 months after vaccination, participant agrees not to donate blood Participant must be willing to provide verifiable identification, have means to be contacted and to contact the investigator during the study Exclusion Criteria: Participant has a serious chronic disorder, including severe chronic obstructive pulmonary disease or clinically significant congestive heart failure, requirement for supplemental oxygen, end-stage renal disease with or without dialysis, clinically unstable cardiac disease, Alzheimer's disease, or has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise well-being) or that could prevent, limit, or confound the protocol-specified assessments Per medical history, participant has chronic active hepatitis B or hepatitis C infection Participant has received an investigational drug or used an invasive investigational medical device within 30 days or received an investigational vaccine within 6 months before the planned administration of study vaccine or is currently enrolled or plans to participate in another investigational study during the course of this study Participant has received treatment with immunoglobulin in the 2 months, or blood products in the 4 months before the planned administration of study vaccine or has any plans to receive such treatment during the study Participant has received any RSV vaccine in any previous RSV vaccine study at any time prior to randomization
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
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ad26.RSV.preF<br>Participants will receive one intramuscular injection of an adenovirus serotype 26- based vaccine encoding for the respiratory syncytial virus pre-fusion F protein (Ad26.RSV.preF) on Day 1. | Biological: Ad26.RSV.preF<br>* Ad26.RSV.preF will be administered as intramuscular injection on Day 1.<br>* Other names: JNJ-64400141;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Presence of Ad26.RSV.preF (shedding) as Assessed by qPCR | Percentage of Participants with presence of Ad26.RSV.preF in the adhesive bandage covering the injection site, the injection site area, nares (mid-turbinate), throat, rectum, urine, semen and blood, will be assessed by Quantitative Polymerase Chain Reaction (qPCR). Percentage of participants with presence of Ad26.RSV.preF (shedding) will be assessed. | Up to Day 183 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Serious Adverse Events (SAEs) | Number of participants with SAEs will be evaluated. An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life threatening experience, is a congenital anomaly/birth defect, is suspected transmission of any infectious agent via a medicinal product, is medically important, and may jeopardize participant or may require medical or surgical intervention to prevent one of the outcomes listed above. | First vaccination (Day 1) to the end of the study (Day 183) |
| Number of Participants with Solicited Local and Systemic Adverse Events (AEs) After Vaccination | Number of participants with solicited local and systemic AEs will be evaluated. Solicited local AEs (erythema, swelling/induration, and pain/tenderness at the injection site) and solicited systemic AEs (fatigue, headache, myalgia, arthralgia, chills, nausea, and fever) will be noted in the participant diary through the 7 days post-vaccination. Local and systemic AEs will be graded according to severity as mild (Grade 1), moderate (Grade 2), severe (Grade 3) and potentially life threatening (Grade 4). | 7 days after vaccination (Day 1 up to Day 7) |
| Number of Participants with Unsolicited AEs as a Measure of Safety | Number of participants with unsolicited AEs will be evaluated. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product, and it does not necessarily have a causal relationship with the intervention, therefore an AE can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product. Unsolicited AEs will include all AEs for which the participant is specifically not questioned in the participant diary. Unsolicited AEs will be graded according to severity as mild (Grade 1), moderate (Grade 2), severe (Grade 3) and potentially life threatening (Grade 4). | Day 1 Up to Day 28 |
|
|||
NCT04321109
|
Alveolar Ridge Preservation Using Collagen Material and Allograft
|
Seven Patients who need implants to replace non-restorable teeth in the esthetic zone.~Intervention Group (1): Seven extraction sockets that received the collagen matrix (Collagen cone) for alveolar ridge preservation.~Comparison Group (2): Seven extraction sockets that were treated with mineralized cortico-cancellous bone allograft for alveolar ridge preservation.~Outcome~Alveolar ridge preservation both in height and in width to improve implant success rate~The height of alveolar ridge was assessed clinically using a periodontal probe.~The width of the alveolar ridge was measured after three months after extraction using a caliper clamp.~Changes in the width and height of alveolar bone were evaluated in merged axial and sagittal views using the I-CAT superimposition system (CBCT).~2- Evaluation of newly formed bone quality was performed by histological examination and histomorphometric analysis.~3- Immuno-histochemical staining was done using polyclonal antibody to detect (BMP-2) marker of bone formation
|
The aim of the present study was to compare three months post-extraction augmented ridge using collagen matrix versus mineralized cortico-cancellous bone allograft. This comparison was done clinically, histologically, immunohisto-chemically and radiologically.~• Clinical parameters included; vertical bone height and bone width that were recorded at baseline and at three months after extraction. Moreover, histomorphometric parameters included; area fraction of osteoid and mature bone three months after extraction by histomorphometric analysis. Immunohistochemical analysis using polyclonal antibody to detect BMP-2 marker of bone formation. Radiographic parameters included superimposition of baseline CBCT, three months after extraction and another one six months after loading with subsequent measurement of bone height, bone width and bone density.~A core biopsy was taken three months after tooth extraction which has undergone histomorphometric and immunohistochemical analysis; implant placement was also done at the same time.~In the present study, it was found that the mean bone height decreased with a higher percent in collagen matrix group than mineralized cortico-cancellous bone allograft group with a non significant difference between both groups.~In addition, this study showed that the mean bone width decreased more in collagen matrix group than mineralized cortico-cancellous bone allograft group with a non significant difference between them.~Moreover, in the present study, Histomorphometric analysis revealed new bone trabeculae formation with osteoblastic rimming, the surrounding fibrous tissue is cellular and remnants of the graft materials was detected , with no marked difference in the amount of newly formed bone between two groups .~Regarding immunohistochemical analysis in both groups, the osteoblasts in the fibrous tissue and osteocytes in newly formed bone are showing nuclear staining, with increasing area of immunopositive cells in mineralized cortico-cancellous bone allograft group.~Radiographically, CBCT superimposition revealed that a greater percent decrease in bone height was denoted in collagen matrix than mineralized cortico-cancellous bone allograft group with a significant difference between both groups after 3 and 6 months.~Accordingly bone width showed a higher decrease in mineralized cortico-cancellous bone allograft group than Collagen matrix group with a non significant difference between both groups after 3 and 6 months.~Finally, bone density showed a greater decrease in Collagen matrix group than mineralized cortico-cancellous bone allograft group with a non significant difference after 3 months but significant difference was found after 6 months between both groups.
|
Alveolar Ridge Preservation Using Collagen Material and Allograft: A Randomized Controlled Trial
|
Alveolar Ridge Preservation
|
* Other: Allograft
* Other: Collagen cone
|
Inclusion Criteria:~Patients were medically free .~Two teeth indicated for extraction due to either severe decay, tooth fracture or failed endodontic treatment.~Exclusion Criteria:~Patients with poor oral hygiene or not willing to perform oral hygiene measures.~Pregnant and breast-feeding females.~Smokers , Teeth with periodontal or periapical infections.~Patients with malocclusion.~All patients who had known contraindication to dental implant surgery (e.g: bleeding tendency, radiotherapy, taking bisphosphonate)
|
20 Years
|
40 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Group (1): Seven extraction sockets that received the collagen matrix (Collacone) for alveolar ridge preservation.~Group (2): Seven extraction sockets that were treated with mineralized cortico-cancellous bone allograft (Maxgraft) for alveolar ridge preservation
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical score | Dimensional changes in alveolar ridge after alveolar ridge preservation both clinically and radiographically | change from baseline at 12 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMP-2 | Bone morphogenic protein -2 immunopositive cells in immunostained sections | detected at 12 weeks |
|
Alveolar ridge preservation, Allograft, Collagen cone
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Collagen cone<br>Collagen matrix | Other: Collagen cone<br>* Collagen matrix<br>|
| Active Comparator: Allograft<br>mineralized corticocancellous allograft | Other: Allograft<br>* Corticocancellous mineralized allograft<br>|
|
Alveolar Ridge Preservation Using Collagen Material and Allograft
Study Overview
=================
Brief Summary
-----------------
Seven Patients who need implants to replace non-restorable teeth in the esthetic zone. Intervention Group (1): Seven extraction sockets that received the collagen matrix (Collagen cone) for alveolar ridge preservation. Comparison Group (2): Seven extraction sockets that were treated with mineralized cortico-cancellous bone allograft for alveolar ridge preservation. Outcome Alveolar ridge preservation both in height and in width to improve implant success rate The height of alveolar ridge was assessed clinically using a periodontal probe. The width of the alveolar ridge was measured after three months after extraction using a caliper clamp. Changes in the width and height of alveolar bone were evaluated in merged axial and sagittal views using the I-CAT superimposition system (CBCT). 2- Evaluation of newly formed bone quality was performed by histological examination and histomorphometric analysis. 3- Immuno-histochemical staining was done using polyclonal antibody to detect (BMP-2) marker of bone formation
Detailed Description
-----------------
The aim of the present study was to compare three months post-extraction augmented ridge using collagen matrix versus mineralized cortico-cancellous bone allograft. This comparison was done clinically, histologically, immunohisto-chemically and radiologically. • Clinical parameters included; vertical bone height and bone width that were recorded at baseline and at three months after extraction. Moreover, histomorphometric parameters included; area fraction of osteoid and mature bone three months after extraction by histomorphometric analysis. Immunohistochemical analysis using polyclonal antibody to detect BMP-2 marker of bone formation. Radiographic parameters included superimposition of baseline CBCT, three months after extraction and another one six months after loading with subsequent measurement of bone height, bone width and bone density. A core biopsy was taken three months after tooth extraction which has undergone histomorphometric and immunohistochemical analysis; implant placement was also done at the same time. In the present study, it was found that the mean bone height decreased with a higher percent in collagen matrix group than mineralized cortico-cancellous bone allograft group with a non significant difference between both groups. In addition, this study showed that the mean bone width decreased more in collagen matrix group than mineralized cortico-cancellous bone allograft group with a non significant difference between them. Moreover, in the present study, Histomorphometric analysis revealed new bone trabeculae formation with osteoblastic rimming, the surrounding fibrous tissue is cellular and remnants of the graft materials was detected , with no marked difference in the amount of newly formed bone between two groups . Regarding immunohistochemical analysis in both groups, the osteoblasts in the fibrous tissue and osteocytes in newly formed bone are showing nuclear staining, with increasing area of immunopositive cells in mineralized cortico-cancellous bone allograft group. Radiographically, CBCT superimposition revealed that a greater percent decrease in bone height was denoted in collagen matrix than mineralized cortico-cancellous bone allograft group with a significant difference between both groups after 3 and 6 months. Accordingly bone width showed a higher decrease in mineralized cortico-cancellous bone allograft group than Collagen matrix group with a non significant difference between both groups after 3 and 6 months. Finally, bone density showed a greater decrease in Collagen matrix group than mineralized cortico-cancellous bone allograft group with a non significant difference after 3 months but significant difference was found after 6 months between both groups.
Official Title
-----------------
Alveolar Ridge Preservation Using Collagen Material and Allograft: A Randomized Controlled Trial
Conditions
-----------------
Alveolar Ridge Preservation
Intervention / Treatment
-----------------
* Other: Allograft
* Other: Collagen cone
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients were medically free . Two teeth indicated for extraction due to either severe decay, tooth fracture or failed endodontic treatment. Exclusion Criteria: Patients with poor oral hygiene or not willing to perform oral hygiene measures. Pregnant and breast-feeding females. Smokers , Teeth with periodontal or periapical infections. Patients with malocclusion. All patients who had known contraindication to dental implant surgery (e.g: bleeding tendency, radiotherapy, taking bisphosphonate)
Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 40 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Group (1): Seven extraction sockets that received the collagen matrix (Collacone) for alveolar ridge preservation. Group (2): Seven extraction sockets that were treated with mineralized cortico-cancellous bone allograft (Maxgraft) for alveolar ridge preservation
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Collagen cone<br>Collagen matrix | Other: Collagen cone<br>* Collagen matrix<br>|
| Active Comparator: Allograft<br>mineralized corticocancellous allograft | Other: Allograft<br>* Corticocancellous mineralized allograft<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical score | Dimensional changes in alveolar ridge after alveolar ridge preservation both clinically and radiographically | change from baseline at 12 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMP-2 | Bone morphogenic protein -2 immunopositive cells in immunostained sections | detected at 12 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alveolar ridge preservation, Allograft, Collagen cone
|
|
NCT03440008
|
Improving the Detection, Classification and Treatment of Misaligned Arthritic Ankles
|
The Veteran population is prone to foot and ankle maladies from common injuries such as sprains, and diseases such as ankle osteoarthritis (cartilage damage). More specific to Veterans are prior service injuries of the foot and ankle, which historically account for nearly a quarter of injuries received. These injuries include bone fractures and ligament damage. Some of these injuries may lead to poor ankle joint alignment, which over time could lead to osteoarthritis due to abnormal wear on a day to day basis. The goal of this proposal is to use a novel technology - biplane fluoroscopy, to study the movement of ankles which are misaligned in subjects with ankle osteoarthritis. This proposal will also benefit current diagnostic methods with additional information. Last, this proposal will test the effectiveness of a conservative treatment (modified shoe insoles) to correct or reduce the misalignment in ankles. This proposal will create evidence about: the nature of ankle osteoarthritis, the accuracy of diagnosing alignment, and conservative treatment for patients with ankle OA.
|
Ankle osteoarthritis (OA) is a debilitating and mobility limiting condition. It can commonly stem from the result of a traumatic injury - such trauma has a high prevalence in military service. If cartilage is not severely damaged in that trauma, the stability and alignment of the joint may be. Over time, an unstable or misaligned ankle joint can experience abnormal rates of cartilage wear and tear due to aberrant kinematics. While OA may take decades to develop, the resulting arthritic state from this trauma will ultimately require ankle replacement or fusion, consequences with a tremendous financial burden and quality of life impact.~With regards to alignment, particularly in the coronal plane, current clinical diagnosis relies on static X-ray of the ankle joint. Static images may not indicate dynamic misalignment during gait. Further, the effect of wedged insoles, a potential conservative treatment, on the restoration of ankle function is undocumented.~This proposal aims to use biplane fluoroscopy, an X-ray based dynamic imaging approach, to measure ankle kinematics in OA subjects (with varus, neutral and valgus ankle alignment) and controls. With this method, tibio-talar kinematics during gait can be measured. Furthermore, subjects classified as neutral from their static radiograph, but that exhibit ankle varus or valgus alignment during gait, will be identified. Improving the accuracy of a diagnostic outcome provides a patient group with additional avenues for treatment. The investigators will investigate correlations between the investigators' 3D kinematics and clinical 2D imaging - to the benefit of clinical diagnostics. The investigators will also be able to measure the effect of wedged insoles on the restoration of ankle function. With this in mind, the following aims and methodology are proposed.~Specific Aim 1: To investigate ankle kinematics in controls and subjects with OA. In support of Specific Aim 1, 90 ankle OA subjects will be recruited (30 each of varus, neutral or valgus aligned ankles). The investigators will also recruit 20 control subjects. Subjects will receive CT scans of their feet to quantify bone geometry (a step necessary for biplane fluoroscopy). Subjects will then be imaged in the biplane system during gait trials and while wearing neutral study shoes. This will yield tibio-talar kinematics during gait for these populations. Specific Aim 2: To identify dynamically misaligned ankles in OA subjects who are currently classified as neutrally aligned using static analysis. The investigators will compare the static X-ray and the gait kinematics of OA subjects, particularly those with clinically determined neutral alignment. The investigators will determine what proportion of neutral OA subjects actually exhibit misalignment during gait and are thus improperly categorized. The investigators will also re-create 2D clinical X-ray views from the investigators' 3D data in an attempt to translate the investigators' improvement (with 3D fluoroscopy) to more accurately classify alignment to clinical 2D diagnostics. Specific Aim 3: To evaluate the potential of lateral or medial wedging to restore alignment in misaligned ankle OA subjects. OA subjects will be imaged wearing shoes with wedged insoles which correspond to their type of misalignment. Neutral OA subjects, who demonstrate misalignment during gait, will be recalled for a wedged insole session. This yields conservative treatment kinematics.~This study will generate baseline data describing the kinematics of control and ankle OA subjects. This data is not currently available in the literature, and represents a novel contribution to the field. Second, this proposal determines how accurate current 2D X-ray methods are at detecting dynamic misalignment. This information can inform clinicians about the accuracy of their diagnostic tools, and may lead to improvements. Third, this proposal will generate data to evaluate the utility of wedged insoles for the conservative management of ankle misalignment. In Summary, this study has immediate impact potential on the diagnosis and treatment of ankle OA. Last, there are numerous additional avenues of classification, diagnostic, and preventative research for the benefit of the Veterans which will stem from this Career Development Award.~As a consequence of the COVID-19 pandemic, and after consultation with the appropriate research oversight, regulatory and monitoring entities, screening and enrollment has been placed on temporary administrative hold as of 03/16/2020.
|
Improving the Detection, Classification and Treatment of Misaligned Arthritic Ankles
|
Ankle Osteoarthritis
|
* Other: Dynamic 3D bone motion capture
* Device: wedged insole
|
Inclusion Criteria:~Be ambulatory (able to walk at least 15 m, and tolerate ~1 hour of standing and walking with rest periods)~Exclusion Criteria:~Recent (<1 year) surgical, neurological, metabolic or lower limb musculoskeletal problem that might impair the ambulation measures in the study~Such as severe knee or hip osteoarthritis~Diagnosed with diabetes, peripheral neuropathy, or peripheral vascular disease~For OA subjects, a radiographic discontinuity of the cartilage of the tibial plafond or talar dome~Also for OA subjects, rapid onset of OA (<3 years) following ankle fracture~Diagnosis of severe ankle instability or deformity such as pes planus~Inadequate cognitive or language function to consent or to participate
|
45 Years
|
70 Years
|
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tibio-talar kinematics during gait | The 3D movement between the tibia and talus bones will be assessed using biplane fluoroscopy, for OA and control subjects during shod gait. | 4 hour session |
| Static ankle alignment sensitivity | The sensitivity to correctly diagnose dynamic misalignment by using static x-ray images, will be determined for the OA population. | 4 hour session |
| Decrease in misalignment during gait using wedged insoles | The effect that wedged insoles have on varus / valgus misalignment will be assessed using dynamic 3D x-ray | 4 hour session |
|
Osteoarthritis, Arthritis, Joint Diseases, Musculoskeletal Diseases, Rheumatic Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control<br>Able-bodied, age matched subjects with no foot and ankle pathology | Other: Dynamic 3D bone motion capture<br>* Two x-ray systems will image the subjects ankle while they walk, allowing us to calculate ankle joint angle and alignment<br>* Other names: Biplane fluoroscopy;|
| OA<br>Subjects with ankle OA, with all classifications of ankle misalignment (varus, neutral, valgus) | Other: Dynamic 3D bone motion capture<br>* Two x-ray systems will image the subjects ankle while they walk, allowing us to calculate ankle joint angle and alignment<br>* Other names: Biplane fluoroscopy;Device: wedged insole<br>* medial or lateral wedge (appropriate for varus or valgus misalignment) will be applied during 1 data collection session to evaluate effect of wedging on misalignment<br>* Other names: orthotic/insole;|
|
Improving the Detection, Classification and Treatment of Misaligned Arthritic Ankles
Study Overview
=================
Brief Summary
-----------------
The Veteran population is prone to foot and ankle maladies from common injuries such as sprains, and diseases such as ankle osteoarthritis (cartilage damage). More specific to Veterans are prior service injuries of the foot and ankle, which historically account for nearly a quarter of injuries received. These injuries include bone fractures and ligament damage. Some of these injuries may lead to poor ankle joint alignment, which over time could lead to osteoarthritis due to abnormal wear on a day to day basis. The goal of this proposal is to use a novel technology - biplane fluoroscopy, to study the movement of ankles which are misaligned in subjects with ankle osteoarthritis. This proposal will also benefit current diagnostic methods with additional information. Last, this proposal will test the effectiveness of a conservative treatment (modified shoe insoles) to correct or reduce the misalignment in ankles. This proposal will create evidence about: the nature of ankle osteoarthritis, the accuracy of diagnosing alignment, and conservative treatment for patients with ankle OA.
Detailed Description
-----------------
Ankle osteoarthritis (OA) is a debilitating and mobility limiting condition. It can commonly stem from the result of a traumatic injury - such trauma has a high prevalence in military service. If cartilage is not severely damaged in that trauma, the stability and alignment of the joint may be. Over time, an unstable or misaligned ankle joint can experience abnormal rates of cartilage wear and tear due to aberrant kinematics. While OA may take decades to develop, the resulting arthritic state from this trauma will ultimately require ankle replacement or fusion, consequences with a tremendous financial burden and quality of life impact. With regards to alignment, particularly in the coronal plane, current clinical diagnosis relies on static X-ray of the ankle joint. Static images may not indicate dynamic misalignment during gait. Further, the effect of wedged insoles, a potential conservative treatment, on the restoration of ankle function is undocumented. This proposal aims to use biplane fluoroscopy, an X-ray based dynamic imaging approach, to measure ankle kinematics in OA subjects (with varus, neutral and valgus ankle alignment) and controls. With this method, tibio-talar kinematics during gait can be measured. Furthermore, subjects classified as neutral from their static radiograph, but that exhibit ankle varus or valgus alignment during gait, will be identified. Improving the accuracy of a diagnostic outcome provides a patient group with additional avenues for treatment. The investigators will investigate correlations between the investigators' 3D kinematics and clinical 2D imaging - to the benefit of clinical diagnostics. The investigators will also be able to measure the effect of wedged insoles on the restoration of ankle function. With this in mind, the following aims and methodology are proposed. Specific Aim 1: To investigate ankle kinematics in controls and subjects with OA. In support of Specific Aim 1, 90 ankle OA subjects will be recruited (30 each of varus, neutral or valgus aligned ankles). The investigators will also recruit 20 control subjects. Subjects will receive CT scans of their feet to quantify bone geometry (a step necessary for biplane fluoroscopy). Subjects will then be imaged in the biplane system during gait trials and while wearing neutral study shoes. This will yield tibio-talar kinematics during gait for these populations. Specific Aim 2: To identify dynamically misaligned ankles in OA subjects who are currently classified as neutrally aligned using static analysis. The investigators will compare the static X-ray and the gait kinematics of OA subjects, particularly those with clinically determined neutral alignment. The investigators will determine what proportion of neutral OA subjects actually exhibit misalignment during gait and are thus improperly categorized. The investigators will also re-create 2D clinical X-ray views from the investigators' 3D data in an attempt to translate the investigators' improvement (with 3D fluoroscopy) to more accurately classify alignment to clinical 2D diagnostics. Specific Aim 3: To evaluate the potential of lateral or medial wedging to restore alignment in misaligned ankle OA subjects. OA subjects will be imaged wearing shoes with wedged insoles which correspond to their type of misalignment. Neutral OA subjects, who demonstrate misalignment during gait, will be recalled for a wedged insole session. This yields conservative treatment kinematics. This study will generate baseline data describing the kinematics of control and ankle OA subjects. This data is not currently available in the literature, and represents a novel contribution to the field. Second, this proposal determines how accurate current 2D X-ray methods are at detecting dynamic misalignment. This information can inform clinicians about the accuracy of their diagnostic tools, and may lead to improvements. Third, this proposal will generate data to evaluate the utility of wedged insoles for the conservative management of ankle misalignment. In Summary, this study has immediate impact potential on the diagnosis and treatment of ankle OA. Last, there are numerous additional avenues of classification, diagnostic, and preventative research for the benefit of the Veterans which will stem from this Career Development Award. As a consequence of the COVID-19 pandemic, and after consultation with the appropriate research oversight, regulatory and monitoring entities, screening and enrollment has been placed on temporary administrative hold as of 03/16/2020.
Official Title
-----------------
Improving the Detection, Classification and Treatment of Misaligned Arthritic Ankles
Conditions
-----------------
Ankle Osteoarthritis
Intervention / Treatment
-----------------
* Other: Dynamic 3D bone motion capture
* Device: wedged insole
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Be ambulatory (able to walk at least 15 m, and tolerate 1 hour of standing and walking with rest periods) Exclusion Criteria: Recent (<1 year) surgical, neurological, metabolic or lower limb musculoskeletal problem that might impair the ambulation measures in the study Such as severe knee or hip osteoarthritis Diagnosed with diabetes, peripheral neuropathy, or peripheral vascular disease For OA subjects, a radiographic discontinuity of the cartilage of the tibial plafond or talar dome Also for OA subjects, rapid onset of OA (<3 years) following ankle fracture Diagnosis of severe ankle instability or deformity such as pes planus Inadequate cognitive or language function to consent or to participate
Ages Eligible for Study
-----------------
Minimum Age: 45 Years
Maximum Age: 70 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control<br>Able-bodied, age matched subjects with no foot and ankle pathology | Other: Dynamic 3D bone motion capture<br>* Two x-ray systems will image the subjects ankle while they walk, allowing us to calculate ankle joint angle and alignment<br>* Other names: Biplane fluoroscopy;|
| OA<br>Subjects with ankle OA, with all classifications of ankle misalignment (varus, neutral, valgus) | Other: Dynamic 3D bone motion capture<br>* Two x-ray systems will image the subjects ankle while they walk, allowing us to calculate ankle joint angle and alignment<br>* Other names: Biplane fluoroscopy;Device: wedged insole<br>* medial or lateral wedge (appropriate for varus or valgus misalignment) will be applied during 1 data collection session to evaluate effect of wedging on misalignment<br>* Other names: orthotic/insole;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tibio-talar kinematics during gait | The 3D movement between the tibia and talus bones will be assessed using biplane fluoroscopy, for OA and control subjects during shod gait. | 4 hour session |
| Static ankle alignment sensitivity | The sensitivity to correctly diagnose dynamic misalignment by using static x-ray images, will be determined for the OA population. | 4 hour session |
| Decrease in misalignment during gait using wedged insoles | The effect that wedged insoles have on varus / valgus misalignment will be assessed using dynamic 3D x-ray | 4 hour session |
|
|||
NCT01998100
|
Maximizing Treatment Outcome in Post-Traumatic Stress Disorder (PTSD)
|
The purpose of this study is to examine the efficacy of exercise + therapy to therapy alone to determine if they can improve the effects of prolonged exposure therapy (PE) in reducing symptoms of anxiety associated with Post-traumatic Stress Disorder (PTSD). In addition the two strategies (i.e., exercise + therapy and therapy alone condition) will be compared in terms of levels of brain-derived neurotrophic factor (BDNF). BDNF is a protein that helps to support the survival of existing neurons and stimulate the growth of new neurons and synapses. BDNF is important to learning and memory in general and therefore may be associated with the learning and memory as it relates to PE and corresponding symptoms PTSD improvement.
| null |
Post-Traumatic Stress Disorder
|
* Behavioral: Prolonged Exposure
* Behavioral: Exercise
|
Inclusion Criteria:~You have PTSD.~You are between the ages of 18 and 65.~You have written physician approval/medical clearance to participate in an exercise protocol.~You are currently taking no psychotropic medications or are able and willing to discontinue these medications prior to the first PE session.~Exclusion Criteria:~You are currently participating in a structured exercise program.~You have severe depression.~You have any history of bipolar disorder, psychotic disorder, or obsessive compulsive disorder.~You have a diagnosis of eating disorder, or substance abuse or dependence (excluding nicotine) within the past six months.~You have any history of a suicide attempt, or are at a significant risk or self-harm or harm to others.~You have ever been diagnosed with organic brain syndrome, mental retardation, or other cognitive dysfunction.
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PTSD Symptoms | Self-report measure that assesses PTSD symptoms. Will be assessed at each visit throughout the three month protocol. | 3 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BDNF (by blood sample) | Small blood sample taken twice (at the beginning and end of the 3 month protocol). | 3 months |
| General Mood and Anxiety Symptoms | Self-report measures that assesses mood and anxiety. Will be assessed at each visit throughout the 3 month protocol. | 3 months |
|
PTSD, Anxiety, Behavior Therapy, Prolonged Exposure, Exercise, Wellness, Post-traumatic, Stress
|
Stress Disorders, Traumatic, Stress Disorders, Post-Traumatic, Trauma and Stressor Related Disorders, Mental Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prolonged Exposure + Exercise<br> | Behavioral: Prolonged Exposure<br>* 75-90 minute weekly psychotherapy sessions x 12 weeks, focused on gradually confronting distressing trauma-related memories and reminders.<br>Behavioral: Exercise<br>* 30 minutes of moderate-intensity treadmill exercise prior to the Prolonged Exposure<br>|
| Active Comparator: Prolonged Exposure Alone<br> | Behavioral: Prolonged Exposure<br>* 75-90 minute weekly psychotherapy sessions x 12 weeks, focused on gradually confronting distressing trauma-related memories and reminders.<br>|
|
Maximizing Treatment Outcome in Post-Traumatic Stress Disorder (PTSD)
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to examine the efficacy of exercise + therapy to therapy alone to determine if they can improve the effects of prolonged exposure therapy (PE) in reducing symptoms of anxiety associated with Post-traumatic Stress Disorder (PTSD). In addition the two strategies (i.e., exercise + therapy and therapy alone condition) will be compared in terms of levels of brain-derived neurotrophic factor (BDNF). BDNF is a protein that helps to support the survival of existing neurons and stimulate the growth of new neurons and synapses. BDNF is important to learning and memory in general and therefore may be associated with the learning and memory as it relates to PE and corresponding symptoms PTSD improvement.
Conditions
-----------------
Post-Traumatic Stress Disorder
Intervention / Treatment
-----------------
* Behavioral: Prolonged Exposure
* Behavioral: Exercise
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: You have PTSD. You are between the ages of 18 and 65. You have written physician approval/medical clearance to participate in an exercise protocol. You are currently taking no psychotropic medications or are able and willing to discontinue these medications prior to the first PE session. Exclusion Criteria: You are currently participating in a structured exercise program. You have severe depression. You have any history of bipolar disorder, psychotic disorder, or obsessive compulsive disorder. You have a diagnosis of eating disorder, or substance abuse or dependence (excluding nicotine) within the past six months. You have any history of a suicide attempt, or are at a significant risk or self-harm or harm to others. You have ever been diagnosed with organic brain syndrome, mental retardation, or other cognitive dysfunction.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prolonged Exposure + Exercise<br> | Behavioral: Prolonged Exposure<br>* 75-90 minute weekly psychotherapy sessions x 12 weeks, focused on gradually confronting distressing trauma-related memories and reminders.<br>Behavioral: Exercise<br>* 30 minutes of moderate-intensity treadmill exercise prior to the Prolonged Exposure<br>|
| Active Comparator: Prolonged Exposure Alone<br> | Behavioral: Prolonged Exposure<br>* 75-90 minute weekly psychotherapy sessions x 12 weeks, focused on gradually confronting distressing trauma-related memories and reminders.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PTSD Symptoms | Self-report measure that assesses PTSD symptoms. Will be assessed at each visit throughout the three month protocol. | 3 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BDNF (by blood sample) | Small blood sample taken twice (at the beginning and end of the 3 month protocol). | 3 months |
| General Mood and Anxiety Symptoms | Self-report measures that assesses mood and anxiety. Will be assessed at each visit throughout the 3 month protocol. | 3 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PTSD, Anxiety, Behavior Therapy, Prolonged Exposure, Exercise, Wellness, Post-traumatic, Stress
|
|
NCT04051671
|
Effects of Dual-transcranial Direct Current Stimulation During Physical Therapy in Sub-acute Stroke
|
The aim of the present study is to evaluate the possible effect of using dual-tDCS applied during conventional physical therapy on lower limb function in stroke patients.
|
Recently dual-tDCS applied before the conventional physical therapy show positive effect of lower limb performance. However to explore the time during which dual-tDCS can be combined with physical therapy to maximize motor performance is required. Results from the present study with be compared with our previous study that used dual-tDCS applied before physical therapy.
|
Effects of Dual-transcranial Direct Current Stimulation During Physical Therapy in Sub-acute Stroke
|
Stroke
|
* Device: Transcranial direct current stimulation
|
Inclusion Criteria:~Age range 18-75 years.~First ever-ischemic lesion in the territory of middle cerebral artery or anterior cerebral artery. CT scan/MRI result is thus required.~Sub acute phase of stroke (less than 6 months)~Able to sit-to-stand and stand-to-sit independently~Able to walk without physical assistance at least 6 m~Free of any neurological antecedent, unstable medical conditions or condition that may increase the risk of stimulation such as epilepsy~Exclusion Criteria:~Pre-stroke disability~Pregnant~Be unable to understand the instruction~No clear neurological antecedent history or psychiatric disorder~Excessive pain in any joint of the paretic limb (numerical pain rating score > 7)~Presence of intracranial metal implantation, cochlea implant, or cardiac pacemaker~Subjects are participating in the other protocol or receiving alternative treatment such as acupuncture
|
18 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Five-Times-Sit-To-Stand test (FTSST) | sling. Subjects will be instructed as the following I want you to stand up and sit down 5 times as quickly as you can when I say 'Go'. Subjects must be fully standing between repetitions. Timing will begin at GO and ends when the patient's buttocks touch the seat after the fifth sit-to-stand. | 5 minutes |
| Timed Up & Go test (TUG) | Subjects will sits on the chair and place their back against the chair. Timing will begin at GO, the subjects will be asked to walk 3m, turn, walk back, and sit down. The stopwatch stops when the patient's buttocks touch the seat. | 5 minutes |
|
Brain Diseases, Stroke, Cerebrovascular Disorders, Central Nervous System Diseases, Nervous System Diseases, Vascular Diseases, Cardiovascular Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active tDCS & PT<br>Dual transcranial direct current stimulation (tDCS) will be applied over the leg motor area (M1) during the first 20 mins of conventional physical therapy (about 1 hours). Anodal on affected hemisphere, Cathodal on unaffected hemisphere. Current intensity is fixed at 2 mA and current will flow continuously during 20. Physical therapist will give an intervention program exactly the same in all cases. The scope of intervention is administered to improve strength of weakened and postural lower limbs muscles such as trunk muscles, hip flexors/extensors/abductors, knee flexors/extensors. | Device: Transcranial direct current stimulation<br>* Dual Active/sham tDCS will be applied over the leg motor area (M1) during the first 20 mins of conventional physical therapy. Anodal on affected hemisphere, Cathodal on unaffected hemisphere. Each participant will complete two experiments (active/sham tDCS). The interval between two experiments is at least 2 weeks. The two experiments will be performed in random order for each subject.<br>|
| Active Comparator: Sham tDCS & PT<br>Dual transcranial direct current stimulation (tDCS) will be applied over the leg motor area (M1) during the first 20 mins (sham mode) of conventional physical therapy (about 1 hours). Anodal on affected hemisphere, Cathodal on unaffected hemisphere. Physical therapist will give an intervention program exactly the same in all cases. The scope of intervention is administered to improve strength of weakened and postural lower limbs muscles such as trunk muscles, hip flexors/extensors/abductors, knee flexors/extensors. | Device: Transcranial direct current stimulation<br>* Dual Active/sham tDCS will be applied over the leg motor area (M1) during the first 20 mins of conventional physical therapy. Anodal on affected hemisphere, Cathodal on unaffected hemisphere. Each participant will complete two experiments (active/sham tDCS). The interval between two experiments is at least 2 weeks. The two experiments will be performed in random order for each subject.<br>|
|
Effects of Dual-transcranial Direct Current Stimulation During Physical Therapy in Sub-acute Stroke
Study Overview
=================
Brief Summary
-----------------
The aim of the present study is to evaluate the possible effect of using dual-tDCS applied during conventional physical therapy on lower limb function in stroke patients.
Detailed Description
-----------------
Recently dual-tDCS applied before the conventional physical therapy show positive effect of lower limb performance. However to explore the time during which dual-tDCS can be combined with physical therapy to maximize motor performance is required. Results from the present study with be compared with our previous study that used dual-tDCS applied before physical therapy.
Official Title
-----------------
Effects of Dual-transcranial Direct Current Stimulation During Physical Therapy in Sub-acute Stroke
Conditions
-----------------
Stroke
Intervention / Treatment
-----------------
* Device: Transcranial direct current stimulation
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age range 18-75 years. First ever-ischemic lesion in the territory of middle cerebral artery or anterior cerebral artery. CT scan/MRI result is thus required. Sub acute phase of stroke (less than 6 months) Able to sit-to-stand and stand-to-sit independently Able to walk without physical assistance at least 6 m Free of any neurological antecedent, unstable medical conditions or condition that may increase the risk of stimulation such as epilepsy Exclusion Criteria: Pre-stroke disability Pregnant Be unable to understand the instruction No clear neurological antecedent history or psychiatric disorder Excessive pain in any joint of the paretic limb (numerical pain rating score > 7) Presence of intracranial metal implantation, cochlea implant, or cardiac pacemaker Subjects are participating in the other protocol or receiving alternative treatment such as acupuncture
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active tDCS & PT<br>Dual transcranial direct current stimulation (tDCS) will be applied over the leg motor area (M1) during the first 20 mins of conventional physical therapy (about 1 hours). Anodal on affected hemisphere, Cathodal on unaffected hemisphere. Current intensity is fixed at 2 mA and current will flow continuously during 20. Physical therapist will give an intervention program exactly the same in all cases. The scope of intervention is administered to improve strength of weakened and postural lower limbs muscles such as trunk muscles, hip flexors/extensors/abductors, knee flexors/extensors. | Device: Transcranial direct current stimulation<br>* Dual Active/sham tDCS will be applied over the leg motor area (M1) during the first 20 mins of conventional physical therapy. Anodal on affected hemisphere, Cathodal on unaffected hemisphere. Each participant will complete two experiments (active/sham tDCS). The interval between two experiments is at least 2 weeks. The two experiments will be performed in random order for each subject.<br>|
| Active Comparator: Sham tDCS & PT<br>Dual transcranial direct current stimulation (tDCS) will be applied over the leg motor area (M1) during the first 20 mins (sham mode) of conventional physical therapy (about 1 hours). Anodal on affected hemisphere, Cathodal on unaffected hemisphere. Physical therapist will give an intervention program exactly the same in all cases. The scope of intervention is administered to improve strength of weakened and postural lower limbs muscles such as trunk muscles, hip flexors/extensors/abductors, knee flexors/extensors. | Device: Transcranial direct current stimulation<br>* Dual Active/sham tDCS will be applied over the leg motor area (M1) during the first 20 mins of conventional physical therapy. Anodal on affected hemisphere, Cathodal on unaffected hemisphere. Each participant will complete two experiments (active/sham tDCS). The interval between two experiments is at least 2 weeks. The two experiments will be performed in random order for each subject.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Five-Times-Sit-To-Stand test (FTSST) | sling. Subjects will be instructed as the following I want you to stand up and sit down 5 times as quickly as you can when I say 'Go'. Subjects must be fully standing between repetitions. Timing will begin at GO and ends when the patient's buttocks touch the seat after the fifth sit-to-stand. | 5 minutes |
| Timed Up & Go test (TUG) | Subjects will sits on the chair and place their back against the chair. Timing will begin at GO, the subjects will be asked to walk 3m, turn, walk back, and sit down. The stopwatch stops when the patient's buttocks touch the seat. | 5 minutes |
|
||
NCT03073070
|
RBC Lifespan Measurement in Diabetic Children
|
HbA1c, a measure of mean blood glucose over the lifespan of a red blood cell (RBC), is a marker of increasing importance both for assessing glycemic control in children with known diabetes and for the diagnosis of diabetes in children. HbA1c has demonstrated poor reliability in diagnosis and management of pediatric diabetes and the most plausible reason for this unreliability is that the reference ranges of HbA1c were established based on 120-day RBC lifespan observed in adults, without considering the RBC lifespan difference between children and adults. The proposed studies will for the first time determine RBC lifespan in diabetic children
|
Screening visit: There will be one screening visit before the study. We will do some blood tests that will determine if the subjects can be in this study. If the subject is qualify, he/she will be asked to return for the following scheduled visits.~Study visit 1: We will draw a small amount of subject's blood from the IV. The study subject's blood will then be marked with biotin. We will give back the subject's blood marked with biotin through IV within 4 to 6 hours. Endotoxin analysis (conducted pre-infusion) and bacterial culture analysis (conducted post-infusion) will be performed. Twenty minutes after the blood transfusion, we will draw blood from the IV. After that, we will take out the IV and the subject can go home.~All follow-up study visits:~The subject will have a study visit 24 hours after receiving blood marked with biotin. After that, the subject will have a clinic visit every 7-10 days. These visits will end when we can no longer find the biotin marked blood cells in the subject's blood. This is expected to be approximately 12 weeks later.~At these visits, we will draw blood and also collect all blood glucose results in the past 7-10 days.~After the study visits are completed, there will be one follow-up visit 4-6 months after the subject receives the biotin marked RBCs. We will draw about 0.25 ml of blood.~Continuous glucose monitoring and HbA1c determination-- We will monitor continuous glucose concentrations throughout the study. This will be accomplished by setting up FreeStyle Libre Pro continuous glucose monitoring (CGM) device for each study subject. In addition, HbA1c will be measured once in the middle of the study (likely visit 6) and in the end of the study (likely visit 12).
|
Red Blood Cell Lifespan Measurement in Diabetic Children
|
Diabetes, Red Blood Cell Survival
|
* Drug: biotin labeled RBCs
|
Inclusion Criteria:~children with either type1 or type 2 diabetes between 4-18 years old~Exclusion Criteria:~consumption of biotin supplements or raw eggs within 30 days;~history of gastrointestinal blood loss;~heart failure ;~active viral or bacterial infection;~hemoglobinopathy;~prior history of liver disease with transaminases more than 3 times the upper limit of normal for age;~uncontrolled thyroid disease;~anemia (whole blood HCT<33);~history of renal disease (prior serum creatinine more than >1.5 mg/dlL);~detectable antibody to biotin.
|
4 Years
|
18 Years
|
All
|
No
|
Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of RBC survival in diabetic children using biotin-labeled RBCs | the lifespan of red blood cells in children with diabetes | 50 days to 120 days |
|
diabetic children, RBC lifespan
|
Biotin, Vitamin B Complex, Vitamins, Micronutrients, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biotin labeled RBCs in 4-10 year old diabetes children<br>Biotin labeled autologous RBCs will be transfused to the subjects | Drug: biotin labeled RBCs<br>* Autologous red blood cells are biotin labeled and transfused to the subjects. Survival of these red blood cells is tracked through examination of blood samples until no biotin-labeled red blood cells is detectable.<br>* Other names: biotinylated RBCs;|
| Experimental: Biotin labeled RBCs in 10-18 year old diabetes children<br>Biotin labeled autologous red blood cells will be transfused to the subjects | Drug: biotin labeled RBCs<br>* Autologous red blood cells are biotin labeled and transfused to the subjects. Survival of these red blood cells is tracked through examination of blood samples until no biotin-labeled red blood cells is detectable.<br>* Other names: biotinylated RBCs;|
|
RBC Lifespan Measurement in Diabetic Children
Study Overview
=================
Brief Summary
-----------------
HbA1c, a measure of mean blood glucose over the lifespan of a red blood cell (RBC), is a marker of increasing importance both for assessing glycemic control in children with known diabetes and for the diagnosis of diabetes in children. HbA1c has demonstrated poor reliability in diagnosis and management of pediatric diabetes and the most plausible reason for this unreliability is that the reference ranges of HbA1c were established based on 120-day RBC lifespan observed in adults, without considering the RBC lifespan difference between children and adults. The proposed studies will for the first time determine RBC lifespan in diabetic children
Detailed Description
-----------------
Screening visit: There will be one screening visit before the study. We will do some blood tests that will determine if the subjects can be in this study. If the subject is qualify, he/she will be asked to return for the following scheduled visits. Study visit 1: We will draw a small amount of subject's blood from the IV. The study subject's blood will then be marked with biotin. We will give back the subject's blood marked with biotin through IV within 4 to 6 hours. Endotoxin analysis (conducted pre-infusion) and bacterial culture analysis (conducted post-infusion) will be performed. Twenty minutes after the blood transfusion, we will draw blood from the IV. After that, we will take out the IV and the subject can go home. All follow-up study visits: The subject will have a study visit 24 hours after receiving blood marked with biotin. After that, the subject will have a clinic visit every 7-10 days. These visits will end when we can no longer find the biotin marked blood cells in the subject's blood. This is expected to be approximately 12 weeks later. At these visits, we will draw blood and also collect all blood glucose results in the past 7-10 days. After the study visits are completed, there will be one follow-up visit 4-6 months after the subject receives the biotin marked RBCs. We will draw about 0.25 ml of blood. Continuous glucose monitoring and HbA1c determination-- We will monitor continuous glucose concentrations throughout the study. This will be accomplished by setting up FreeStyle Libre Pro continuous glucose monitoring (CGM) device for each study subject. In addition, HbA1c will be measured once in the middle of the study (likely visit 6) and in the end of the study (likely visit 12).
Official Title
-----------------
Red Blood Cell Lifespan Measurement in Diabetic Children
Conditions
-----------------
Diabetes, Red Blood Cell Survival
Intervention / Treatment
-----------------
* Drug: biotin labeled RBCs
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: children with either type1 or type 2 diabetes between 4-18 years old Exclusion Criteria: consumption of biotin supplements or raw eggs within 30 days; history of gastrointestinal blood loss; heart failure ; active viral or bacterial infection; hemoglobinopathy; prior history of liver disease with transaminases more than 3 times the upper limit of normal for age; uncontrolled thyroid disease; anemia (whole blood HCT<33); history of renal disease (prior serum creatinine more than >1.5 mg/dlL); detectable antibody to biotin.
Ages Eligible for Study
-----------------
Minimum Age: 4 Years
Maximum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biotin labeled RBCs in 4-10 year old diabetes children<br>Biotin labeled autologous RBCs will be transfused to the subjects | Drug: biotin labeled RBCs<br>* Autologous red blood cells are biotin labeled and transfused to the subjects. Survival of these red blood cells is tracked through examination of blood samples until no biotin-labeled red blood cells is detectable.<br>* Other names: biotinylated RBCs;|
| Experimental: Biotin labeled RBCs in 10-18 year old diabetes children<br>Biotin labeled autologous red blood cells will be transfused to the subjects | Drug: biotin labeled RBCs<br>* Autologous red blood cells are biotin labeled and transfused to the subjects. Survival of these red blood cells is tracked through examination of blood samples until no biotin-labeled red blood cells is detectable.<br>* Other names: biotinylated RBCs;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of RBC survival in diabetic children using biotin-labeled RBCs | the lifespan of red blood cells in children with diabetes | 50 days to 120 days |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
diabetic children, RBC lifespan
|
|
NCT01458912
|
Study on BI 54903 (Inhaled Corticosteroid) Administered Once Daily or Twice Daily Via Respimat Inhaler in Patients With Asthma Inadequately Controlled on Low Dose Inhaled Corticosteroids
|
The aim of this study is to assess and compare efficacy and safety of BI 54903 at medium doses twice daily and high doses once daily (evening dosing) and placebo over an 12-week treatment period in asthmatic patients aged 12 to 65 years inadequately controlled on low dose inhaled corticosteroid (ICS) therapy as demonstrated by a decrease in Forced Expiratory Volume in one second (FEV1) (not less than 10 %, and equal to or less than 25%) and an Asthma Control Questionnaire (ACQ)-6 score of not less than 1.5 at time of randomisation.
|
A Randomised, Double-blind, Placebo-controlled, Parallel-group Study to Assess and Compare Efficacy and Safety of a 12-week Treatment With BI 54903 at Doses of 181.8 Mcg b.i.d. and 363.6 Mcg q.d. (p.m. Dosing) Administered Via Respimat® Inhaler in Patients With Asthma Inadequately Controlled on Low Dose ICS Therapy
|
Asthma
|
* Drug: Placebo matching Respimat
* Drug: Placebo matching Respimat
* Drug: BI 54903 MD
* Drug: BI 54903 HD
|
Inclusion criteria:~Male and female patients aged at least 12 to 65 years.~All patients must have a history of asthma diagnosed by a physician for at least three months at the time of enrolment into the trial according to the 2009 Global Initiative for Asthma (GINA) Guidelines. The initial diagnosis of asthma must have been made before the age of 40 years.~All patients must be on a maintenance treatment with either medium-dose ICS plus Long-acting beta agonist (LABA) or high-dose ICS without LABA, stable for at least six weeks prior to Visit 1 (see also Section 3.3.1 and Appendix 10.3).~All patients must have a pre-bronchodilator FEV1 of not less than 60 to 90% of predicted normal and an ACQ-6 mean score of less than 1.5 at the pre-screening Visit 1.~All patients must have an improvement in FEV1 not less than 12 % above baseline and an absolute change of at least 200 mL within 15-30 min after administration of 400 mcg salbutamol/albuterol Hydrofluoroalkane (HFA) Metered Dose Inhaler (MDI). When the reversibility is not achieved at Visit 1, there will be the option to repeat reversibility test at any visit during the run-in period.~Variation of absolute pre-bronchodilator FEV1 values at Visit 2 as compared to Visit 1 must be within plus/minus 20 %.~Patients must be never-smokers or ex-smokers with a smoking history of less than10 pack-years and smoking cessation at least one year prior to screening .~Patients must be able to use Respimat® inhaler and MDI correctly~Patients must be able to perform all trial-related procedures including technically acceptable pulmonary function tests and electronic PEF measurements, and must be able to maintain records during the study period as required in the protocol.~To enter treatment period following additional criteria have to be met (at randomisation visit):~All patients must have an improvement in FEV1 not less than 12 % above baseline and an absolute change of at least 200 mL within 15-30 min after administration of 400 mcg salbutamol/albuterol HFA MDI. When the reversibility is not achieved at Visit 1, there will be the option to repeat reversibility test at any visit during the run-in period.~During the run-in period (at the same clinic visit) all patients must be both symptomatic (ACQ-6 mean score equal to or greater than 1.5) and have shown a decrease in morning pre-bronchodilator FEV1 not less than 10% and less than or equal to 25% from pre-screening baseline FEV1 at Visit 2.~Exclusion criteria:~Patients with significant pulmonary disease other than asthma or other significant medical conditions (as determined by medical history, examination and clinical investigations at screening) that may, in the opinion of the investigator, result in any of the following: (i) put the patient at risk because of participation in this trial or (ii) influence the results of the trial or (iii) cause concern regarding the patient's ability to participate in the trial.~Patients with a clinically relevant, abnormal screening haematology and/or blood chemistry finding, if the abnormality indicates a significant disease as defined in exclusion criterion no. 1.~Patients with a history of upper or lower respiratory tract infection (URTI/LRTI) in the past four weeks prior to the pre-screening Visit 1, and during pre-screening and run-in periods.~Patients with any exacerbation of their underlying asthma during the eight weeks prior to the pre-screening Visit 1.~Patients with active allergic rhinitis requiring treatment with systemic corticosteroids.~Any of the following criteria are met during the pre-screening / run-in period (Visits 1 - 6):~in clinic pre-bronchodilator FEV1 % predicted less than 40%,~more than 12 puffs rescue salbutamol/albuterol HFA MDI per day for > 2 consecutive days,~exacerbation of asthma.~Patients with a history of pneumonectomy or who are planning to undergo thoracotomy for any reason.~Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the six weeks prior to the first screening visit 1.~Patients with two or more hospitalizations for asthma within the previous 12 months.~Patients with a recent history of myocardial infarction during the last twelve months or known coronary heart disease that requires treatment~Patients with a history of hospitalisation due to heart failure in the past twelve months~Patients with myocarditis or any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year~Patients with significant alcohol or drug abuse in the opinion of the investigator within the past two years~Patients with rheumatoid arthritis or other systemic diseases that require immune system modulating treatment~Patients suffering from or with a history of glaucoma, increased intraocular pressure, and/or cataracts~Pregnant or nursing women~Women of childbearing potential not using a highly effective method of birth control.~Patients who have been treated with anti-IgE-antibodies (e.g. omalizumab - Xolair®) or other immune system modulating antibodies such as TNF-alpha blockers within six months prior to Visit 1.~Patients who have been treated with the following drugs during the past four weeks prior to Visit 1 or are foreseen to need this during the study:~Non-selective ß-blockers (topical cardio-selective beta-blocker eye medications for non-narrow angle glaucoma are allowed),~Oral or other systemic corticosteroids,~Oral beta-agonists,~Changes in allergen desensitisation therapy in last 6 months,~Immune system modulating agents such as methotrexate or cyclosporine,~Inhibitors of cytochrome P450 3A4 such as antifungals (e.g. ketoconazole, itraconazole), antibiotics (e.g. erythromycin) or antiretroviral drugs.~Patients who have been treated with leukotriene modifiers, cromones or theophylline within two weeks prior to Visit 1.~Patients who have been treated with tiotropium within 3 weeks prior to Visit 1.
|
12 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from randomisation baseline to the end of the 12-week treatment period in evening trough (pre-dose and pre-rescue bronchodilator) FEV1 | | 12 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from randomisation baseline to the end of the 12-week treatment period in morning and evening trough (pre-dose and pre-rescue bronchodilator) Forced Vital Capacity (FVC) | | 12 weeks |
| Mean change from randomisation baseline in morning and evening trough (pre-dose and pre-rescue bronchodilator) FEV1 and FVC after 2, 4 and 8-week treatment periods, and in morning trough FEV1 after 12 week treatment period | | 12 weeks |
| Mean pre-dose (and pre-rescue) Peak Expiratory Flow (PEF) as assessed via Asthma Monitor2+ (AM2+) device (in the morning and evening) of the last week of the 12-week treatment period | | 12 weeks |
| Mean rescue medication use (daytime and night-time) as assessed via AM2+ device (in the morning and evening) of the last week of the 12-week treatment period | | 12 weeks |
| Asthma control questionnaire (ACQ-6). | | 12 weeks |
| Asthma quality of life questionnaire (AQLQ(S)+12) | | 12 weeks |
| Time to withdrawal due to first asthma exacerbation | | 12 weeks |
| Daytime 12-h FEV1 profiles after 12-week treatment period (FEV1 Area Under Curve (AUC) 0-12h) | | 12 weeks |
|
Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive, Lung Diseases, Respiratory Hypersensitivity, Hypersensitivity, Immediate, Hypersensitivity, Immune System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 54903 HD q.d.<br>Patients receive 2 puffs BI 54903 HD q.d. via Respimat inhaler (p.m.) combined with 2 puffs placebo (a.m.) | Drug: Placebo matching Respimat<br>* 2 puffs a.m. via Respimat inhaler<br>Drug: BI 54903 HD<br>* 2 puffs HD p.m. via Respimat inhaler<br>|
| Placebo Comparator: Placebo<br>Patients receive 2 puffs Placebo b.i.d. via Respimat inhaler | Drug: Placebo matching Respimat<br>* 2 puffs a.m. via Respimat inhaler<br>|
| Experimental: BI 54903 MD b.i.d.<br>Patients receive 2 puffs BI 54903 MD b.i.d.via Respimat inhaler | Drug: BI 54903 MD<br>* 2 puffs MD b.i.d. via Respimat inhaler<br>|
|
Study on BI 54903 (Inhaled Corticosteroid) Administered Once Daily or Twice Daily Via Respimat Inhaler in Patients With Asthma Inadequately Controlled on Low Dose Inhaled Corticosteroids
Study Overview
=================
Brief Summary
-----------------
The aim of this study is to assess and compare efficacy and safety of BI 54903 at medium doses twice daily and high doses once daily (evening dosing) and placebo over an 12-week treatment period in asthmatic patients aged 12 to 65 years inadequately controlled on low dose inhaled corticosteroid (ICS) therapy as demonstrated by a decrease in Forced Expiratory Volume in one second (FEV1) (not less than 10 %, and equal to or less than 25%) and an Asthma Control Questionnaire (ACQ)-6 score of not less than 1.5 at time of randomisation.
Official Title
-----------------
A Randomised, Double-blind, Placebo-controlled, Parallel-group Study to Assess and Compare Efficacy and Safety of a 12-week Treatment With BI 54903 at Doses of 181.8 Mcg b.i.d. and 363.6 Mcg q.d. (p.m. Dosing) Administered Via Respimat® Inhaler in Patients With Asthma Inadequately Controlled on Low Dose ICS Therapy
Conditions
-----------------
Asthma
Intervention / Treatment
-----------------
* Drug: Placebo matching Respimat
* Drug: Placebo matching Respimat
* Drug: BI 54903 MD
* Drug: BI 54903 HD
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Male and female patients aged at least 12 to 65 years. All patients must have a history of asthma diagnosed by a physician for at least three months at the time of enrolment into the trial according to the 2009 Global Initiative for Asthma (GINA) Guidelines. The initial diagnosis of asthma must have been made before the age of 40 years. All patients must be on a maintenance treatment with either medium-dose ICS plus Long-acting beta agonist (LABA) or high-dose ICS without LABA, stable for at least six weeks prior to Visit 1 (see also Section 3.3.1 and Appendix 10.3). All patients must have a pre-bronchodilator FEV1 of not less than 60 to 90% of predicted normal and an ACQ-6 mean score of less than 1.5 at the pre-screening Visit 1. All patients must have an improvement in FEV1 not less than 12 % above baseline and an absolute change of at least 200 mL within 15-30 min after administration of 400 mcg salbutamol/albuterol Hydrofluoroalkane (HFA) Metered Dose Inhaler (MDI). When the reversibility is not achieved at Visit 1, there will be the option to repeat reversibility test at any visit during the run-in period. Variation of absolute pre-bronchodilator FEV1 values at Visit 2 as compared to Visit 1 must be within plus/minus 20 %. Patients must be never-smokers or ex-smokers with a smoking history of less than10 pack-years and smoking cessation at least one year prior to screening . Patients must be able to use Respimat® inhaler and MDI correctly Patients must be able to perform all trial-related procedures including technically acceptable pulmonary function tests and electronic PEF measurements, and must be able to maintain records during the study period as required in the protocol. To enter treatment period following additional criteria have to be met (at randomisation visit): All patients must have an improvement in FEV1 not less than 12 % above baseline and an absolute change of at least 200 mL within 15-30 min after administration of 400 mcg salbutamol/albuterol HFA MDI. When the reversibility is not achieved at Visit 1, there will be the option to repeat reversibility test at any visit during the run-in period. During the run-in period (at the same clinic visit) all patients must be both symptomatic (ACQ-6 mean score equal to or greater than 1.5) and have shown a decrease in morning pre-bronchodilator FEV1 not less than 10% and less than or equal to 25% from pre-screening baseline FEV1 at Visit 2. Exclusion criteria: Patients with significant pulmonary disease other than asthma or other significant medical conditions (as determined by medical history, examination and clinical investigations at screening) that may, in the opinion of the investigator, result in any of the following: (i) put the patient at risk because of participation in this trial or (ii) influence the results of the trial or (iii) cause concern regarding the patient's ability to participate in the trial. Patients with a clinically relevant, abnormal screening haematology and/or blood chemistry finding, if the abnormality indicates a significant disease as defined in exclusion criterion no. 1. Patients with a history of upper or lower respiratory tract infection (URTI/LRTI) in the past four weeks prior to the pre-screening Visit 1, and during pre-screening and run-in periods. Patients with any exacerbation of their underlying asthma during the eight weeks prior to the pre-screening Visit 1. Patients with active allergic rhinitis requiring treatment with systemic corticosteroids. Any of the following criteria are met during the pre-screening / run-in period (Visits 1 - 6): in clinic pre-bronchodilator FEV1 % predicted less than 40%, more than 12 puffs rescue salbutamol/albuterol HFA MDI per day for > 2 consecutive days, exacerbation of asthma. Patients with a history of pneumonectomy or who are planning to undergo thoracotomy for any reason. Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the six weeks prior to the first screening visit 1. Patients with two or more hospitalizations for asthma within the previous 12 months. Patients with a recent history of myocardial infarction during the last twelve months or known coronary heart disease that requires treatment Patients with a history of hospitalisation due to heart failure in the past twelve months Patients with myocarditis or any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year Patients with significant alcohol or drug abuse in the opinion of the investigator within the past two years Patients with rheumatoid arthritis or other systemic diseases that require immune system modulating treatment Patients suffering from or with a history of glaucoma, increased intraocular pressure, and/or cataracts Pregnant or nursing women Women of childbearing potential not using a highly effective method of birth control. Patients who have been treated with anti-IgE-antibodies (e.g. omalizumab - Xolair®) or other immune system modulating antibodies such as TNF-alpha blockers within six months prior to Visit 1. Patients who have been treated with the following drugs during the past four weeks prior to Visit 1 or are foreseen to need this during the study: Non-selective ß-blockers (topical cardio-selective beta-blocker eye medications for non-narrow angle glaucoma are allowed), Oral or other systemic corticosteroids, Oral beta-agonists, Changes in allergen desensitisation therapy in last 6 months, Immune system modulating agents such as methotrexate or cyclosporine, Inhibitors of cytochrome P450 3A4 such as antifungals (e.g. ketoconazole, itraconazole), antibiotics (e.g. erythromycin) or antiretroviral drugs. Patients who have been treated with leukotriene modifiers, cromones or theophylline within two weeks prior to Visit 1. Patients who have been treated with tiotropium within 3 weeks prior to Visit 1.
Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 65 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 54903 HD q.d.<br>Patients receive 2 puffs BI 54903 HD q.d. via Respimat inhaler (p.m.) combined with 2 puffs placebo (a.m.) | Drug: Placebo matching Respimat<br>* 2 puffs a.m. via Respimat inhaler<br>Drug: BI 54903 HD<br>* 2 puffs HD p.m. via Respimat inhaler<br>|
| Placebo Comparator: Placebo<br>Patients receive 2 puffs Placebo b.i.d. via Respimat inhaler | Drug: Placebo matching Respimat<br>* 2 puffs a.m. via Respimat inhaler<br>|
| Experimental: BI 54903 MD b.i.d.<br>Patients receive 2 puffs BI 54903 MD b.i.d.via Respimat inhaler | Drug: BI 54903 MD<br>* 2 puffs MD b.i.d. via Respimat inhaler<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from randomisation baseline to the end of the 12-week treatment period in evening trough (pre-dose and pre-rescue bronchodilator) FEV1 | | 12 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from randomisation baseline to the end of the 12-week treatment period in morning and evening trough (pre-dose and pre-rescue bronchodilator) Forced Vital Capacity (FVC) | | 12 weeks |
| Mean change from randomisation baseline in morning and evening trough (pre-dose and pre-rescue bronchodilator) FEV1 and FVC after 2, 4 and 8-week treatment periods, and in morning trough FEV1 after 12 week treatment period | | 12 weeks |
| Mean pre-dose (and pre-rescue) Peak Expiratory Flow (PEF) as assessed via Asthma Monitor2+ (AM2+) device (in the morning and evening) of the last week of the 12-week treatment period | | 12 weeks |
| Mean rescue medication use (daytime and night-time) as assessed via AM2+ device (in the morning and evening) of the last week of the 12-week treatment period | | 12 weeks |
| Asthma control questionnaire (ACQ-6). | | 12 weeks |
| Asthma quality of life questionnaire (AQLQ(S)+12) | | 12 weeks |
| Time to withdrawal due to first asthma exacerbation | | 12 weeks |
| Daytime 12-h FEV1 profiles after 12-week treatment period (FEV1 Area Under Curve (AUC) 0-12h) | | 12 weeks |
|
||
NCT05511298
|
Empowering Students Project
|
The Empowering Students Project is an evaluation of the effectiveness of a psychoeducational program for adolescents, intended to help youth build healthy relationship skills while supporting positive socioemotional development and promoting successful transition to young adulthood.
|
Participants complete measures of the primary outcomes immediately prior to beginning the intervention and again immediately after completion of the program. Analyses will examine within-person change from pre-test to post-test.
|
Empowering Students Project
|
Relationship, Social
|
* Behavioral: Relationship Smarts Combo
|
Inclusion Criteria:~None~Exclusion Criteria:~None
| null |
23 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Relationship Quality | For participants who are in a relationship: Ten items, scored on a 5-point scale and averaged, for a possible range of 1-5. Sample item: My boyfriend/girlfriend and I talk about the things that really matter.~For participants who are not in a relationship: Six items, scored on a 4-point scale and averaged, for a possible range of 1-4. Sample item: I have the skills needed for a lasting, stable romantic relationship.~Higher scores reflect better outcomes. | Baseline: Immediately prior to the first workshop session; Follow-up: Immediately following the last workshop session (ranging from ~4-8 weeks in between time points, depending on how the workshop is delivered) |
| Change in Communication Skills | For participants who are in a relationship: Six items, scored on a 5-point scale and averaged, for a possible range of 1-5. Sample item: How often do you discuss your disagreements?~For participants who are not in a relationship: Five items, scored on a 4-point scale and averaged, for a possible range of 1-4. Sample item: Listening to another person's opinion during a disagreement.~Higher scores reflect better outcomes. | Baseline: Immediately prior to the first workshop session; Follow-up: Immediately following the last workshop session (ranging from ~4-8 weeks in between time points, depending on how the workshop is delivered) |
| Change in Knowledge About Healthy Relationships | Eight items, scored on a 4-point scale and averaged, for a possible range of 1-4. Sample item: In a healthy relationship, how important is it that couples do not cheat on each other?~Higher scores reflect better outcomes. | Baseline: Immediately prior to the first workshop session; Follow-up: Immediately following the last workshop session (ranging from ~4-8 weeks in between time points, depending on how the workshop is delivered) |
| Knowledge about Intimate Partner Violence | Four items, scored on a 4-point scale and averaged, for a possible range of 1-4. Sample item: It's okay to stay in a relationship even if you're afraid of your boyfriend/girlfriend.~Higher scores reflect better outcomes. | Baseline: Immediately prior to the first workshop session; Follow-up: Immediately following the last workshop session (ranging from ~4-8 weeks in between time points, depending on how the workshop is delivered) |
| Change in Increased Knowledge, Skills, and Confidence | Three items, scored on a 4-point scale and averaged, for a possible range of 1-4. Sample item: I have learned new skills in this program that I plan to use in my relationships.~Higher scores reflect better outcomes. | Baseline: Immediately prior to the first workshop session; Follow-up: Immediately following the last workshop session (ranging from ~4-8 weeks in between time points, depending on how the workshop is delivered) |
|
| Intervention/Treatment |
| --- |
|Behavioral: Relationship Smarts Combo|The intervention is a combination of Mind Matters, Relationship Smarts 4.0, and Money Habitudes curricula, developed by the Dibble Institute|
|
Empowering Students Project
Study Overview
=================
Brief Summary
-----------------
The Empowering Students Project is an evaluation of the effectiveness of a psychoeducational program for adolescents, intended to help youth build healthy relationship skills while supporting positive socioemotional development and promoting successful transition to young adulthood.
Detailed Description
-----------------
Participants complete measures of the primary outcomes immediately prior to beginning the intervention and again immediately after completion of the program. Analyses will examine within-person change from pre-test to post-test.
Official Title
-----------------
Empowering Students Project
Conditions
-----------------
Relationship, Social
Intervention / Treatment
-----------------
* Behavioral: Relationship Smarts Combo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: None Exclusion Criteria: None
Ages Eligible for Study
-----------------
Maximum Age: 23 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Intervention/Treatment |
| --- |
|Behavioral: Relationship Smarts Combo|The intervention is a combination of Mind Matters, Relationship Smarts 4.0, and Money Habitudes curricula, developed by the Dibble Institute|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Relationship Quality | For participants who are in a relationship: Ten items, scored on a 5-point scale and averaged, for a possible range of 1-5. Sample item: My boyfriend/girlfriend and I talk about the things that really matter. For participants who are not in a relationship: Six items, scored on a 4-point scale and averaged, for a possible range of 1-4. Sample item: I have the skills needed for a lasting, stable romantic relationship. Higher scores reflect better outcomes. | Baseline: Immediately prior to the first workshop session; Follow-up: Immediately following the last workshop session (ranging from 4-8 weeks in between time points, depending on how the workshop is delivered) |
| Change in Communication Skills | For participants who are in a relationship: Six items, scored on a 5-point scale and averaged, for a possible range of 1-5. Sample item: How often do you discuss your disagreements? For participants who are not in a relationship: Five items, scored on a 4-point scale and averaged, for a possible range of 1-4. Sample item: Listening to another person's opinion during a disagreement. Higher scores reflect better outcomes. | Baseline: Immediately prior to the first workshop session; Follow-up: Immediately following the last workshop session (ranging from 4-8 weeks in between time points, depending on how the workshop is delivered) |
| Change in Knowledge About Healthy Relationships | Eight items, scored on a 4-point scale and averaged, for a possible range of 1-4. Sample item: In a healthy relationship, how important is it that couples do not cheat on each other? Higher scores reflect better outcomes. | Baseline: Immediately prior to the first workshop session; Follow-up: Immediately following the last workshop session (ranging from 4-8 weeks in between time points, depending on how the workshop is delivered) |
| Knowledge about Intimate Partner Violence | Four items, scored on a 4-point scale and averaged, for a possible range of 1-4. Sample item: It's okay to stay in a relationship even if you're afraid of your boyfriend/girlfriend. Higher scores reflect better outcomes. | Baseline: Immediately prior to the first workshop session; Follow-up: Immediately following the last workshop session (ranging from 4-8 weeks in between time points, depending on how the workshop is delivered) |
| Change in Increased Knowledge, Skills, and Confidence | Three items, scored on a 4-point scale and averaged, for a possible range of 1-4. Sample item: I have learned new skills in this program that I plan to use in my relationships. Higher scores reflect better outcomes. | Baseline: Immediately prior to the first workshop session; Follow-up: Immediately following the last workshop session (ranging from 4-8 weeks in between time points, depending on how the workshop is delivered) |
|
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NCT03760133
|
The Change of Gut Microbiota After Bowel Preparation and the Effect of Probiotics
|
The purpose of this study is to investigate the relationship between the change of intestinal bacterial flora and the recovery, and the incidence of symptoms such as abdominal discomfort after colonoscopy. And the investigators will also analyze the effects of probiotics on the degree of change, recovery, and symptom development in intestinal flora.
|
The investigators divided two groups. (total number = 100 subjects)~with probiotics group - 50 subjects~Participants included in this group will be taken probiotics for 1 month after bowel preparation for colonoscopy.~without probiotics group - 50 subjects~Participants included in this group will not be taken probiotics for 1 month after bowel preparation for colonoscopy.
|
The Change of Gut Microbiota After Bowel Preparation and the Effect of Probiotics: Randomized Controlled, Open-label Trial
|
Gut Microbiota, Bowel Preparation, Colonoscopy
|
* Drug: Duolac
|
Inclusion Criteria:~adults between the age of 30 and 70~Exclusion Criteria:~subjects with cancer or IBD (inflammatory bowel disease)~subjects with history of abdominal surgery~subjects who take medication related to gastrointestinal motility within 3 months~subjects who take antibiotics within 3 months
|
30 Years
|
70 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of probiotics on the change of gut microbiota after bowel preparation. | Analysis the change of gut microbiota before and after bowel preparation for colonoscopy, and the effect of probiotics. | eight months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The occurrence of symptoms | Analysis the occurrence of symptoms including abdominal discomfort, diarrhea, constipation or abdominal blotting after bowel preparation for colonoscopy. | eight months |
| The correlation between symptoms and gut microbiota.. | Analysis the the correlation between the symptoms after bowel preparation for colonoscopy and the changes of gut microbiota. | eight months |
|
Gut microbiota, Colonoscopy, Bowel preparation, Probiotics
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: with Probiotics<br>Participants included in this group will be taken probiotics for 1 month after bowel preparation for colonoscopy. | Drug: Duolac<br>* Participants included in this group will be taken probiotics for 1 month after bowel preparation for colonoscopy.<br>|
| No Intervention: without Probiotics<br>Participants included in this group will not be taken probiotics for 1 month after bowel preparation for colonoscopy. | |
|
The Change of Gut Microbiota After Bowel Preparation and the Effect of Probiotics
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the relationship between the change of intestinal bacterial flora and the recovery, and the incidence of symptoms such as abdominal discomfort after colonoscopy. And the investigators will also analyze the effects of probiotics on the degree of change, recovery, and symptom development in intestinal flora.
Detailed Description
-----------------
The investigators divided two groups. (total number = 100 subjects) with probiotics group - 50 subjects Participants included in this group will be taken probiotics for 1 month after bowel preparation for colonoscopy. without probiotics group - 50 subjects Participants included in this group will not be taken probiotics for 1 month after bowel preparation for colonoscopy.
Official Title
-----------------
The Change of Gut Microbiota After Bowel Preparation and the Effect of Probiotics: Randomized Controlled, Open-label Trial
Conditions
-----------------
Gut Microbiota, Bowel Preparation, Colonoscopy
Intervention / Treatment
-----------------
* Drug: Duolac
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: adults between the age of 30 and 70 Exclusion Criteria: subjects with cancer or IBD (inflammatory bowel disease) subjects with history of abdominal surgery subjects who take medication related to gastrointestinal motility within 3 months subjects who take antibiotics within 3 months
Ages Eligible for Study
-----------------
Minimum Age: 30 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: with Probiotics<br>Participants included in this group will be taken probiotics for 1 month after bowel preparation for colonoscopy. | Drug: Duolac<br>* Participants included in this group will be taken probiotics for 1 month after bowel preparation for colonoscopy.<br>|
| No Intervention: without Probiotics<br>Participants included in this group will not be taken probiotics for 1 month after bowel preparation for colonoscopy. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of probiotics on the change of gut microbiota after bowel preparation. | Analysis the change of gut microbiota before and after bowel preparation for colonoscopy, and the effect of probiotics. | eight months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The occurrence of symptoms | Analysis the occurrence of symptoms including abdominal discomfort, diarrhea, constipation or abdominal blotting after bowel preparation for colonoscopy. | eight months |
| The correlation between symptoms and gut microbiota.. | Analysis the the correlation between the symptoms after bowel preparation for colonoscopy and the changes of gut microbiota. | eight months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Gut microbiota, Colonoscopy, Bowel preparation, Probiotics
|
|
NCT00413049
|
Efficacy/Safety of Valsartan Plus Amlodipine and Amlodipine Alone in Patients With Hypertension
|
This study will evaluate the safety and efficacy of the fixed combination of valsartan/amlodipine in adult patients with mild to moderate hypertension
|
A Multi-national, Multicenter, Double-blind, Double-dummy, Randomized, Active-controlled, Parallel Study Comparing the Efficacy and Safety of Valsartan/Amlodipine 80/5 mg to Amlodipine 5 mg Alone Once Daily in Patients With Mild to Moderate Essential Hypertension Not Adequately Controlled With Amlodipine 5 mg Monotherapy
|
Hypertension
|
* Drug: Valsartan/amlodipine 80/5 mg
* Drug: Amlodipine 5 mg
|
Inclusion criteria~Male or female outpatients ≥ 18 years and < 86 years~Patients with essential hypertension measured by calibrated mercury sphygmomanometer (preferred) or an aneroid device if a mercury sphygmomanometer was not available.~At Visit 1, patients not treated with antihypertensive medications had to have a MSDBP of ≥ 95 mmHg and < 110 mmHg; those patients treated with antihypertensive medication had to have a MSDBP of < 110 mmHg.~At Visit 2, patients must have a MSDBP of ≥ 95 mmHg but < 110 mmHg.~At Visit 3, patients must have a MSDBP of ≥ 90 mmHg and < 110 mmHg.~Patients who were eligible and able to participate in the study, and who consented to do so after the purpose and nature of the investigation had been clearly explained to them (written informed consent).~Exclusion criteria~Severe hypertension (MSDBP ≥ 110 mmHg and/or MSSBP ≥ 180 mmHg).~In cases where the patient was on more than one antihypertensive drug whether in fixed or free combination, the investigator considered the efficacy and strength of each active ingredient in order to determine if the patient could be safely removed from their antihypertensive treatment.~Known or suspected contraindications, including history of allergy or hypersensitivity to angiotensin receptor blockers (ARB), calcium channel blockers (CCB), or to drugs with similar chemical structures.~Administration of any agent indicated for the treatment of hypertension after Visit 1 with the exception of those agents that required tapering down.~Inability to discontinue all prior antihypertensive medications safely for a maximum period of up to 28 days prior to Visit 2, as required by the protocol.~History of hypertensive encephalopathy, cerebrovascular accident or transient ischemic attack, myocardial infarction or all types of revascularization.~Malignant hypertension.~All patients with Type 1 diabetes mellitus and those patients with Type 2 diabetes mellitus who were not well controlled based on the investigator's clinical judgment. Patients being treated for diabetes mellitus had to have satisfactory metabolic control. Type 2 diabetic patients taking oral anti-diabetic medication had to be on a stable dose for at least 4 weeks prior to Visit 1.~Pregnant or nursing (lactating) women, where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/ml).~Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precluded intercourse with a male partner and women whose partners had been sterilized by vasectomy or other means, UNLESS they met the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 mIU/m or 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy OR were using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation, vasectomy), and double-barrier methods (any double combination of: intra-uterine device [IUD], male or female condom with spermicidal gel, diaphragm, sponge, cervical cap). Acceptable methods of contraception included total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the patient ensured compliance. Reliable contraception had to be maintained throughout the study and for 7 days after study drug discontinuation. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal were not acceptable methods of contraception. Hormonal contraceptive use was disallowed.~History of heart failure Grade II-IV according to the New York Heart Association (NYHA) classification.~Second or third degree heart block with or without a pacemaker.~Concomitant potentially life threatening arrhythmia or symptomatic arrhythmia.~Angina pectoris of any type, including unstable angina pectoris.~Clinically significant valvular heart disease.~Evidence of a secondary form of hypertension, including but not limited to any of the following: coarctation of the aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing disease, pheochromocytoma, polycystic kidney disease.~Known moderate or malignant retinopathy, defined as: moderate (retinal signs of hemorrhage, microaneurysm, cotton-wool spot, hard exudates, or a combination thereof) or malignancy (signs of moderate retinopathy plus swelling of the optic disk).~Evidence of hepatic disease as determined by any one of the following: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values greater than two times the upper limit of normal at Visit 1, a history of hepatic encephalopathy, a history of esophageal varices, or a history of a portocaval shunt.~Evidence of renal impairment as determined by anyone of the following: serum creatinine > 1.5 times the upper limit of normal at Visit 1, a history of dialysis, or a history of nephrotic syndrome.~History of clinically significant allergies including asthma, and/or multiple drug allergies.~Any surgical or medical condition with the potential to significantly alter the absorption, distribution, metabolism, or excretion of any drug including but not limited to any of the following: history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, gastric bypass, gastric stapling, or gastric banding, currently active or active inflammatory bowel syndrome within 12 months prior to Visit 1, currently active gastritis, ulcers, or gastrointestinal/rectal bleeding, or urinary tract obstruction regarded as clinically meaningful by the investigator.~Any surgical or medical condition, which in the opinion of the investigator or the Novartis monitor, placed the patient at higher risk from his/her participation in the study, or were likely to prevent the patient from complying with the requirement of the study or completing the trial period.~Volume depletion based on the investigator's clinical judgment using vital signs, skin turgor, moistness of mucous membranes, and laboratory values.~Any chronic inflammatory condition requiring chronic anti-inflammatory therapy.~History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there was evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.~History of drug of alcohol abuse within the last 2 years.~Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever was longer.~Inability to communicate and comply with all study requirements including the unwillingness or inability to provide informed consent.~Persons directly involved in the execution of this protocol.~History of non-compliance to medical regimens, or unwillingness to comply with the study protocol.~Currently taking prohibited concomitant medications(s) listed and inability/unwillingness to discontinue them for the entire study period.~Any severe, life-threatening disease within the past five years.~Arm circumference > 42 cm for patients participating in ambulatory blood pressure monitoring (ABPM).
|
18 Years
|
85 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8) | Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. A negative change score indicates lowered BP. | Baseline to end of study (Week 8) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study (Week 8) | Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. A negative change score indicates lowered BP. | Baseline to end of study (Week 8) |
| Percentage of Patients Achieving a Diastolic Response at the End of the Study (Week 8) | A patient achieved a diastolic response if their msDBP < 90 mmHg at Week 8 or they had a ≥ 10 mmHg decrease in msDBP compared to baseline at the end of the study (Week 8). Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. | Baseline to end of study (Week 8) |
| Percentage of Patients Achieving Diastolic Control at the End of the Study (Week 8) | A patient achieved diastolic control if their msDBP < 90 mmHg at the end of the study (Week 8). Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. | Baseline to end of study (Week 8) |
| Percentage of Patients Achieving Overall Control at the End of the Study (Week 8) | A patient achieved overall control if the msSBP/msDBP < 140/90 mmHg at the end of the study (Week 8). Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. | Baseline to end of study (Week 8) |
| Change in 24-hour Mean Ambulatory Diastolic and Systolic BP From Baseline at the End of the Study (Week 8) | Two 24 hour ambulatory blood pressure monitoring (ABPM) evaluations were performed, one at baseline prior to randomization and one at Week 8 (end of study), in a subset of the intent-to-treat population of patients. For each evaluation, the ABPM device was attached to the non-dominant arm of the patient. A correlation was made between the ABPM device readings and measurements taken with a mercury sphygmomanometer and stethoscope. Following the correlation procedure, BP was measured at study specified intervals. A negative change score indicates lowered BP. | Baseline to end of study (Week 8) |
|
Hypertension, valsartan, amlodipine, high blood pressure
|
Amlodipine, Valsartan, Antihypertensive Agents, Calcium Channel Blockers, Membrane Transport Modulators, Molecular Mechanisms of Pharmacological Action, Calcium-Regulating Hormones and Agents, Physiological Effects of Drugs, Vasodilator Agents, Angiotensin II Type 1 Receptor Blockers, Angiotensin Receptor Antagonists
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Valsartan/amlodipine 80/5 mg<br> | Drug: Valsartan/amlodipine 80/5 mg<br>* 1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.<br>|
| Active Comparator: Amlodipine 5 mg<br> | Drug: Amlodipine 5 mg<br>* 1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.<br>|
|
Efficacy/Safety of Valsartan Plus Amlodipine and Amlodipine Alone in Patients With Hypertension
Study Overview
=================
Brief Summary
-----------------
This study will evaluate the safety and efficacy of the fixed combination of valsartan/amlodipine in adult patients with mild to moderate hypertension
Official Title
-----------------
A Multi-national, Multicenter, Double-blind, Double-dummy, Randomized, Active-controlled, Parallel Study Comparing the Efficacy and Safety of Valsartan/Amlodipine 80/5 mg to Amlodipine 5 mg Alone Once Daily in Patients With Mild to Moderate Essential Hypertension Not Adequately Controlled With Amlodipine 5 mg Monotherapy
Conditions
-----------------
Hypertension
Intervention / Treatment
-----------------
* Drug: Valsartan/amlodipine 80/5 mg
* Drug: Amlodipine 5 mg
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria Male or female outpatients ≥ 18 years and < 86 years Patients with essential hypertension measured by calibrated mercury sphygmomanometer (preferred) or an aneroid device if a mercury sphygmomanometer was not available. At Visit 1, patients not treated with antihypertensive medications had to have a MSDBP of ≥ 95 mmHg and < 110 mmHg; those patients treated with antihypertensive medication had to have a MSDBP of < 110 mmHg. At Visit 2, patients must have a MSDBP of ≥ 95 mmHg but < 110 mmHg. At Visit 3, patients must have a MSDBP of ≥ 90 mmHg and < 110 mmHg. Patients who were eligible and able to participate in the study, and who consented to do so after the purpose and nature of the investigation had been clearly explained to them (written informed consent). Exclusion criteria Severe hypertension (MSDBP ≥ 110 mmHg and/or MSSBP ≥ 180 mmHg). In cases where the patient was on more than one antihypertensive drug whether in fixed or free combination, the investigator considered the efficacy and strength of each active ingredient in order to determine if the patient could be safely removed from their antihypertensive treatment. Known or suspected contraindications, including history of allergy or hypersensitivity to angiotensin receptor blockers (ARB), calcium channel blockers (CCB), or to drugs with similar chemical structures. Administration of any agent indicated for the treatment of hypertension after Visit 1 with the exception of those agents that required tapering down. Inability to discontinue all prior antihypertensive medications safely for a maximum period of up to 28 days prior to Visit 2, as required by the protocol. History of hypertensive encephalopathy, cerebrovascular accident or transient ischemic attack, myocardial infarction or all types of revascularization. Malignant hypertension. All patients with Type 1 diabetes mellitus and those patients with Type 2 diabetes mellitus who were not well controlled based on the investigator's clinical judgment. Patients being treated for diabetes mellitus had to have satisfactory metabolic control. Type 2 diabetic patients taking oral anti-diabetic medication had to be on a stable dose for at least 4 weeks prior to Visit 1. Pregnant or nursing (lactating) women, where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/ml). Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precluded intercourse with a male partner and women whose partners had been sterilized by vasectomy or other means, UNLESS they met the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 mIU/m or 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy OR were using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation, vasectomy), and double-barrier methods (any double combination of: intra-uterine device [IUD], male or female condom with spermicidal gel, diaphragm, sponge, cervical cap). Acceptable methods of contraception included total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the patient ensured compliance. Reliable contraception had to be maintained throughout the study and for 7 days after study drug discontinuation. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal were not acceptable methods of contraception. Hormonal contraceptive use was disallowed. History of heart failure Grade II-IV according to the New York Heart Association (NYHA) classification. Second or third degree heart block with or without a pacemaker. Concomitant potentially life threatening arrhythmia or symptomatic arrhythmia. Angina pectoris of any type, including unstable angina pectoris. Clinically significant valvular heart disease. Evidence of a secondary form of hypertension, including but not limited to any of the following: coarctation of the aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing disease, pheochromocytoma, polycystic kidney disease. Known moderate or malignant retinopathy, defined as: moderate (retinal signs of hemorrhage, microaneurysm, cotton-wool spot, hard exudates, or a combination thereof) or malignancy (signs of moderate retinopathy plus swelling of the optic disk). Evidence of hepatic disease as determined by any one of the following: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values greater than two times the upper limit of normal at Visit 1, a history of hepatic encephalopathy, a history of esophageal varices, or a history of a portocaval shunt. Evidence of renal impairment as determined by anyone of the following: serum creatinine > 1.5 times the upper limit of normal at Visit 1, a history of dialysis, or a history of nephrotic syndrome. History of clinically significant allergies including asthma, and/or multiple drug allergies. Any surgical or medical condition with the potential to significantly alter the absorption, distribution, metabolism, or excretion of any drug including but not limited to any of the following: history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, gastric bypass, gastric stapling, or gastric banding, currently active or active inflammatory bowel syndrome within 12 months prior to Visit 1, currently active gastritis, ulcers, or gastrointestinal/rectal bleeding, or urinary tract obstruction regarded as clinically meaningful by the investigator. Any surgical or medical condition, which in the opinion of the investigator or the Novartis monitor, placed the patient at higher risk from his/her participation in the study, or were likely to prevent the patient from complying with the requirement of the study or completing the trial period. Volume depletion based on the investigator's clinical judgment using vital signs, skin turgor, moistness of mucous membranes, and laboratory values. Any chronic inflammatory condition requiring chronic anti-inflammatory therapy. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there was evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. History of drug of alcohol abuse within the last 2 years. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever was longer. Inability to communicate and comply with all study requirements including the unwillingness or inability to provide informed consent. Persons directly involved in the execution of this protocol. History of non-compliance to medical regimens, or unwillingness to comply with the study protocol. Currently taking prohibited concomitant medications(s) listed and inability/unwillingness to discontinue them for the entire study period. Any severe, life-threatening disease within the past five years. Arm circumference > 42 cm for patients participating in ambulatory blood pressure monitoring (ABPM).
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Valsartan/amlodipine 80/5 mg<br> | Drug: Valsartan/amlodipine 80/5 mg<br>* 1 valsartan/amlodipine 80/5 mg tablet and 1 placebo capsule matching amlodipine 5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.<br>|
| Active Comparator: Amlodipine 5 mg<br> | Drug: Amlodipine 5 mg<br>* 1 amlodipine 5 mg capsule and 1 placebo tablet matching valsartan/amlodipine 80/5 mg to be taken with water at approximately 8:00 a.m. once daily, except on the morning of every scheduled study visit, when study drug was taken after the completion of all other study procedures.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8) | Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. A negative change score indicates lowered BP. | Baseline to end of study (Week 8) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study (Week 8) | Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. A negative change score indicates lowered BP. | Baseline to end of study (Week 8) |
| Percentage of Patients Achieving a Diastolic Response at the End of the Study (Week 8) | A patient achieved a diastolic response if their msDBP < 90 mmHg at Week 8 or they had a ≥ 10 mmHg decrease in msDBP compared to baseline at the end of the study (Week 8). Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. | Baseline to end of study (Week 8) |
| Percentage of Patients Achieving Diastolic Control at the End of the Study (Week 8) | A patient achieved diastolic control if their msDBP < 90 mmHg at the end of the study (Week 8). Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. | Baseline to end of study (Week 8) |
| Percentage of Patients Achieving Overall Control at the End of the Study (Week 8) | A patient achieved overall control if the msSBP/msDBP < 140/90 mmHg at the end of the study (Week 8). Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. | Baseline to end of study (Week 8) |
| Change in 24-hour Mean Ambulatory Diastolic and Systolic BP From Baseline at the End of the Study (Week 8) | Two 24 hour ambulatory blood pressure monitoring (ABPM) evaluations were performed, one at baseline prior to randomization and one at Week 8 (end of study), in a subset of the intent-to-treat population of patients. For each evaluation, the ABPM device was attached to the non-dominant arm of the patient. A correlation was made between the ABPM device readings and measurements taken with a mercury sphygmomanometer and stethoscope. Following the correlation procedure, BP was measured at study specified intervals. A negative change score indicates lowered BP. | Baseline to end of study (Week 8) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hypertension, valsartan, amlodipine, high blood pressure
|
|
NCT03729128
|
Add-on Low Dose Dextromethorphan and Memantine in Patients With Amphetamine-type Stimulants Use Disorder
|
The current study will investigate whether add-on dextromethorphan (DM) and memantine (MM) is able to improve the treatment outcomes for ATSUD, and be associated with improvement in inflammatory markers, neurotrophic factors and neuropsychological tests.
|
In current study, we will conduct a randomized double-blind placebo-controlled study. We will recruit 100-120 patients with ATSUD in three years and allocate them to add-on low dose dextromethorphan and memantine (DM 30mg/day+MM 5mg/day) or placebo group in a 1: 1 ratio (patients will also undergo usual psychosocial interventions). We will follow up the participants for 12 weeks and measure the treatment responses, urine drug tests, craving scales and side effects to evaluate the therapeutic effects of add-on DM+MM. Neuropsychological assessments and tests for inflammatory parameters and neurotrophic factors will also be measured during 12-weeks follow up. The study results will show that whether add-on DM+MM is able to improve the treatment outcomes for ATSUD, and be associated with improvement in inflammatory markers, neurotrophic factors and neuropsychological tests.
|
The Potential Therapeutic Effects of add-on Low Dose Dextromethorphan and Memantine in Patients With Amphetamine-type Stimulants Use Disorder
|
Stimulants Use Disorder
|
* Drug: dextromethorphan and memantine (DM+MM)
* Drug: Placebos
|
Inclusion Criteria:~Patients must meet all of these inclusion criteria to be eligible for enrollment into the study:~Signed informed consent by patient or legal representative.~Male or female patient aged ≧20 and ≦65 years.~A diagnosis of ATSUD according to DSM criteria made by a specialist in psychiatry.~Patient or a reliable caregiver can be expected to ensure acceptable compliance and visit attendance for the duration of the study.~Exclusion Criteria:~The presence of any of the following will exclude a patient from study enrollment:~Women of childbearing potential, not using adequate contraception as per investigator judgment or not willing to comply with contraception for the duration of the study.~Females who are pregnant or lactation.~Other major Axis-I DSM-IV diagnosis other than ATSUD, except for tobacco use disorder, ATS induced mood or psychotic disorders.~Current evidence of an uncontrolled and/or clinically significant medical condition, e.g., cardiac, hepatic and renal failure that would compromise patient safety or preclude study participation.~History of allergy or intolerable side effects of DM or MM.~Suicidal attempts or risks during screen or study period.~Presence of active infectious or autoimmune disease.
|
20 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary amphetamine tests | The urinary amphetamine tests will be examined during the 12 weeks of treatment period in patients with ATSUD and the results will be compared between the experimental and placebo groups. | 12 weeks |
| Craving severity | The Visual analog scale (VAS) will be measured during the 12 weeks of treatment period in patients with ATSUD. The results will be compared between the experimental and placebo groups. The level of conscious craving was rated from 0 (none) to 100 (very much). Higher scores indicate more severe craving. | 12 weeks |
| Side effects checklists | The investigators will use the self-reported questionnaire, side effects checklists, to evaluate the side effects during the 12 weeks of treatment period in patients with ATSUD. The side effects assessment includes, A) Mental Status/6-item, B) Genito-Urinary/4-item, C) Cardiovascular/4-item, D) Head-Neck/10-item, E) Extremities/9-item, F) Skin/4-item, and G) Gastrointestinal Tract/2-item. The severity of side effects were divided into 4 degrees as follows: 0 = Not present; 1 = Mild or occasional; 2 = Moderate or occurs several times a day; and 3 = Severe or persistent. Scores in each subscale will be summated to get the final total scores. Higher scores indicate more severe side effects. The results of side effects checklists will be compared between the experimental and placebo group. | 12 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wisconsin Card Sorting Test (WCST) | The Wisconsin Card Sorting Test (WCST) will be measured in patients with ATSUD at the initial screen period and at the endpoint (after 12 weeks of treatment). We will compare the changes from screen period to the endpoint between experimental and placebo group. Performance on the WCST was scored in terms of the total number of errors (TNE, range form 0-128), perseverative errors (PE, range from 0-118), conceptual level responses (CLRs, range from 0-100%), number of categories completed (NCC, range form 0-12), and trials to complete the first category (TCC, range from 0-128). Higher scores indicate worse performance in TNE, PE, and TCC. Higher scores indicate better performance in CLRs and NCC. | 12 weeks |
| Continuous performance tests (CPT) | The Continuous performance tests (CPT) will be measured in patients with ATSUD at the initial screen period and at the endpoint (after 12 weeks of treatment). We will compare the changes from screen period to the endpoint between experimental and placebo group. The CPT produces a standard set of performance measures that include the number of errors of omission and errors of commission. (1) Errors of omission occur when the participant fails to respond to the target stimulus. The omission errors t-scores are ranged from 20-80 (0-100%). Higher scores indicated worse performance. (2) Errors of commission occur when the participant responds to a non-target (X) stimulus. The commission errors t-scores are ranged from 20-80 (0-100%). Higher scores indicated worse performance. | 12 weeks |
| Wechsler Memory Scale - third edition (WMS-III) | The Wechsler Memory Scale - third edition (WMS-III) will be measured in patients with ATSUD at the initial screen period and at the endpoint (after 12 weeks of treatment). We will compare the changes from screen period to the endpoint between experimental and placebo group. WMS-III composite scores were calculated for the eight standardized primary indices: Auditory Immediate (AIM, range from 50-156), Visual Immediate (VIM, range from 47-162 ), Immediate Memory (IM, range from 40-164 ), Auditory Delayed (ADM, range from 46-162), Visual Delayed (VDM, range from 43-156), Auditory Recognition Delayed (ARDM, range from 55-145), General Memory (GM, range from 40-168), and Working Memory (WM, range from 45-156 ). Higher scores indicate better performance. | 12 weeks |
| Cytokines and neurotrophic factors | The plasma levels of cytokines and neurotrophic factors, tumor necrosis factor α (TNF-α[pg/mL]), transforming growth factor β1 (TGF-β1 [pg/mL]), interleukin 6( IL-6[pg/mL]), interleukin 8(IL-8[pg/mL]), interleukin 1β (IL-1β[pg/mL]), and brain-derived neurotrophic factor(BDNF[pg/mL]), will be measured in patients with ATSUD at the initial screen period, day 1(baseline), week 4, 8, and 12(endpoint). We will compare the changes from screen period to the endpoint between the experimental and placebo group. | 12 weeks |
| C-reactive protein | The plasma levels of C-reactive protein (CRP[μg/mL]) will be measured in patients with ATSUD at the initial screen period, day 1(baseline), week 4, 8, and 12(endpoint). We will compare the changes from screen period to the endpoint between the experimental and placebo group. | 12 weeks |
|
amphetamine-type stimulants use disorder, dextromethorphan, memantine, inflammation, neurodegeneration
|
Memantine, Dextromethorphan, Antiparkinson Agents, Anti-Dyskinesia Agents, Dopamine Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Physiological Effects of Drugs, Excitatory Amino Acid Antagonists, Excitatory Amino Acid Agents, Antitussive Agents, Respiratory System Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dextromethorphan and memantine (DM+MM)<br>The patients with Amphetamine-type stimulants use disorder will be recruited and received treatment of add-on dextromethorphan 30mg/day and memantine 5mg/day combination (DM+MM) for 12 weeks. | Drug: dextromethorphan and memantine (DM+MM)<br>* Patients of Amphetamine-type stimulants use disorder (ATSUD) will take dextromethorphan 30 mg/day and memantine 5 mg/day combination (DM+MM) daily for 12 weeks.<br>|
| Placebo Comparator: Placebos<br>The patients with Amphetamine-type stimulants use disorder will be recruited and received treatment of add-on placebos for 12 weeks. | Drug: Placebos<br>* Patients of Amphetamine-type stimulants use disorder (ATSUD) will take placebos daily for 12 weeks.<br>|
|
Add-on Low Dose Dextromethorphan and Memantine in Patients With Amphetamine-type Stimulants Use Disorder
Study Overview
=================
Brief Summary
-----------------
The current study will investigate whether add-on dextromethorphan (DM) and memantine (MM) is able to improve the treatment outcomes for ATSUD, and be associated with improvement in inflammatory markers, neurotrophic factors and neuropsychological tests.
Detailed Description
-----------------
In current study, we will conduct a randomized double-blind placebo-controlled study. We will recruit 100-120 patients with ATSUD in three years and allocate them to add-on low dose dextromethorphan and memantine (DM 30mg/day+MM 5mg/day) or placebo group in a 1: 1 ratio (patients will also undergo usual psychosocial interventions). We will follow up the participants for 12 weeks and measure the treatment responses, urine drug tests, craving scales and side effects to evaluate the therapeutic effects of add-on DM+MM. Neuropsychological assessments and tests for inflammatory parameters and neurotrophic factors will also be measured during 12-weeks follow up. The study results will show that whether add-on DM+MM is able to improve the treatment outcomes for ATSUD, and be associated with improvement in inflammatory markers, neurotrophic factors and neuropsychological tests.
Official Title
-----------------
The Potential Therapeutic Effects of add-on Low Dose Dextromethorphan and Memantine in Patients With Amphetamine-type Stimulants Use Disorder
Conditions
-----------------
Stimulants Use Disorder
Intervention / Treatment
-----------------
* Drug: dextromethorphan and memantine (DM+MM)
* Drug: Placebos
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must meet all of these inclusion criteria to be eligible for enrollment into the study: Signed informed consent by patient or legal representative. Male or female patient aged ≧20 and ≦65 years. A diagnosis of ATSUD according to DSM criteria made by a specialist in psychiatry. Patient or a reliable caregiver can be expected to ensure acceptable compliance and visit attendance for the duration of the study. Exclusion Criteria: The presence of any of the following will exclude a patient from study enrollment: Women of childbearing potential, not using adequate contraception as per investigator judgment or not willing to comply with contraception for the duration of the study. Females who are pregnant or lactation. Other major Axis-I DSM-IV diagnosis other than ATSUD, except for tobacco use disorder, ATS induced mood or psychotic disorders. Current evidence of an uncontrolled and/or clinically significant medical condition, e.g., cardiac, hepatic and renal failure that would compromise patient safety or preclude study participation. History of allergy or intolerable side effects of DM or MM. Suicidal attempts or risks during screen or study period. Presence of active infectious or autoimmune disease.
Ages Eligible for Study
-----------------
Minimum Age: 20 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 |
| --- | --- |
| Experimental: dextromethorphan and memantine (DM+MM)<br>The patients with Amphetamine-type stimulants use disorder will be recruited and received treatment of add-on dextromethorphan 30mg/day and memantine 5mg/day combination (DM+MM) for 12 weeks. | Drug: dextromethorphan and memantine (DM+MM)<br>* Patients of Amphetamine-type stimulants use disorder (ATSUD) will take dextromethorphan 30 mg/day and memantine 5 mg/day combination (DM+MM) daily for 12 weeks.<br>|
| Placebo Comparator: Placebos<br>The patients with Amphetamine-type stimulants use disorder will be recruited and received treatment of add-on placebos for 12 weeks. | Drug: Placebos<br>* Patients of Amphetamine-type stimulants use disorder (ATSUD) will take placebos daily for 12 weeks.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary amphetamine tests | The urinary amphetamine tests will be examined during the 12 weeks of treatment period in patients with ATSUD and the results will be compared between the experimental and placebo groups. | 12 weeks |
| Craving severity | The Visual analog scale (VAS) will be measured during the 12 weeks of treatment period in patients with ATSUD. The results will be compared between the experimental and placebo groups. The level of conscious craving was rated from 0 (none) to 100 (very much). Higher scores indicate more severe craving. | 12 weeks |
| Side effects checklists | The investigators will use the self-reported questionnaire, side effects checklists, to evaluate the side effects during the 12 weeks of treatment period in patients with ATSUD. The side effects assessment includes, A) Mental Status/6-item, B) Genito-Urinary/4-item, C) Cardiovascular/4-item, D) Head-Neck/10-item, E) Extremities/9-item, F) Skin/4-item, and G) Gastrointestinal Tract/2-item. The severity of side effects were divided into 4 degrees as follows: 0 = Not present; 1 = Mild or occasional; 2 = Moderate or occurs several times a day; and 3 = Severe or persistent. Scores in each subscale will be summated to get the final total scores. Higher scores indicate more severe side effects. The results of side effects checklists will be compared between the experimental and placebo group. | 12 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wisconsin Card Sorting Test (WCST) | The Wisconsin Card Sorting Test (WCST) will be measured in patients with ATSUD at the initial screen period and at the endpoint (after 12 weeks of treatment). We will compare the changes from screen period to the endpoint between experimental and placebo group. Performance on the WCST was scored in terms of the total number of errors (TNE, range form 0-128), perseverative errors (PE, range from 0-118), conceptual level responses (CLRs, range from 0-100%), number of categories completed (NCC, range form 0-12), and trials to complete the first category (TCC, range from 0-128). Higher scores indicate worse performance in TNE, PE, and TCC. Higher scores indicate better performance in CLRs and NCC. | 12 weeks |
| Continuous performance tests (CPT) | The Continuous performance tests (CPT) will be measured in patients with ATSUD at the initial screen period and at the endpoint (after 12 weeks of treatment). We will compare the changes from screen period to the endpoint between experimental and placebo group. The CPT produces a standard set of performance measures that include the number of errors of omission and errors of commission. (1) Errors of omission occur when the participant fails to respond to the target stimulus. The omission errors t-scores are ranged from 20-80 (0-100%). Higher scores indicated worse performance. (2) Errors of commission occur when the participant responds to a non-target (X) stimulus. The commission errors t-scores are ranged from 20-80 (0-100%). Higher scores indicated worse performance. | 12 weeks |
| Wechsler Memory Scale - third edition (WMS-III) | The Wechsler Memory Scale - third edition (WMS-III) will be measured in patients with ATSUD at the initial screen period and at the endpoint (after 12 weeks of treatment). We will compare the changes from screen period to the endpoint between experimental and placebo group. WMS-III composite scores were calculated for the eight standardized primary indices: Auditory Immediate (AIM, range from 50-156), Visual Immediate (VIM, range from 47-162 ), Immediate Memory (IM, range from 40-164 ), Auditory Delayed (ADM, range from 46-162), Visual Delayed (VDM, range from 43-156), Auditory Recognition Delayed (ARDM, range from 55-145), General Memory (GM, range from 40-168), and Working Memory (WM, range from 45-156 ). Higher scores indicate better performance. | 12 weeks |
| Cytokines and neurotrophic factors | The plasma levels of cytokines and neurotrophic factors, tumor necrosis factor α (TNF-α[pg/mL]), transforming growth factor β1 (TGF-β1 [pg/mL]), interleukin 6( IL-6[pg/mL]), interleukin 8(IL-8[pg/mL]), interleukin 1β (IL-1β[pg/mL]), and brain-derived neurotrophic factor(BDNF[pg/mL]), will be measured in patients with ATSUD at the initial screen period, day 1(baseline), week 4, 8, and 12(endpoint). We will compare the changes from screen period to the endpoint between the experimental and placebo group. | 12 weeks |
| C-reactive protein | The plasma levels of C-reactive protein (CRP[μg/mL]) will be measured in patients with ATSUD at the initial screen period, day 1(baseline), week 4, 8, and 12(endpoint). We will compare the changes from screen period to the endpoint between the experimental and placebo group. | 12 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
amphetamine-type stimulants use disorder, dextromethorphan, memantine, inflammation, neurodegeneration
|
NCT03274687
|
Hypofractionated Radiation Therapy or Conventional Radiation Therapy After Surgery in Treating Patients With Prostate Cancer
|
This randomized phase III trial studies how well hypofractionated radiation therapy works compared to conventional radiation therapy after surgery in treating patients with prostate cancer. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Conventional radiation therapy uses high energy x-rays, gamma rays, neutrons, protons, or other sources to kill tumor cells and shrink tumors. It is not yet known whether giving hypofractionated radiation therapy or conventional radiation therapy after surgery may work better in treating patients with prostate cancer.
|
PRIMARY OBJECTIVES:~I. To demonstrate that hypofractionated post-prostatectomy radiotherapy (HYPORT) does not increase patient-reported gastrointestinal (GI) or genitourinary (GU) symptoms over conventionally fractionated post-prostatectomy (COPORT) at the 2-year time point.~SECONDARY OBJECTIVES:~I. To compare patient-reported GI symptoms using the Expanded Prostate Cancer Index Composite (EPIC)-26 at end of radiation therapy (RT) and 6, 12, 24, and 60 months from end of treatment.~II. To compare patient-reported GU symptoms using the EPIC-26 at end of RT and 6, 12, 24, and 60 months from end of treatment.~III. To compare the cost effectiveness based on the cost of radiotherapy and measured utilities for health outcomes using the EuroQol five dimensions questionnaire (EQ-5D).~IV. To compare time to progression (TTP) where progression is defined as the first occurrence of biochemical failure (BF), local failure, regional failure, distant metastasis (DM), institution of new unplanned anticancer treatment, or death from prostate cancer (prostate cancer specific mortality [PCSM]).~V. To compare freedom from biochemical failure (FFBF) and TTP rates with an alternate prostate specific antigen (PSA) >= PSA nadir + 2 ng/mL definition of BF.~VI. To compare local failure, regional failure, salvage therapy (i.e. institution of new unplanned anticancer treatment), DM, PCSM, and overall survival (OS) rates.~VII. Assessment of adverse events. VIII. Paraffin-embedded tissue block, serum, plasma, whole blood, and urine for future translational research analyses for predictors of toxicity following hypofractionated or conventionally fractionated post-prostatectomy radiotherapy.~After completion of study treatment, patients are followed up every 6 months for 2 years and every year for 3 years and thereafter.
|
A Randomized Phase III Trial of Hypofractionated Post-prostatectomy Radiation Therapy (HYPORT) Versus Conventional Post-prostatectomy Radiation Therapy (COPORT)
|
Prostate Adenocarcinoma, Stage I Prostate Adenocarcinoma, Stage II Prostate Adenocarcinoma, Stage III Prostate Adenocarcinoma
|
* Radiation: Hypofractionated radiation therapy
* Radiation: Conventional radiation therapy
* Drug: Optional androgen deprivation therapy
|
Inclusion Criteria:~PRIOR TO STEP 1 REGISTRATION~Adenocarcinoma of the prostate treated primarily with radical prostatectomy~Any type of radical prostatectomy will be permitted, including retropubic, perineal, laparoscopic, or robotically assisted; there is no time limit for the date of radical prostatectomy~One of the following pathologic T-classifications: pT2 or pT3~Patients with positive surgical margins are eligible~One of the following pathologic N-classifications: pN0, pNX~If a lymph node dissection is performed, the number of lymph nodes removed per side of the pelvis and the extent of the pelvic lymph node dissection (obturator versus (vs.) extended lymph node dissection) should be noted whenever possible~No clinical evidence of regional lymph node metastasis~Computed tomography (CT) (with contrast if renal function is acceptable; a noncontrast CT is permitted if the patient is not a candidate for contrast), magnetic resonance imaging (MRI), nodal sampling, or dissection of the pelvis within 120 days prior to step 1 registration~Patients with pelvic lymph nodes equivocal or questionable by imaging are eligible if the nodes are =< 1 cm in the short axis~A post-radical prostatectomy study entry PSA >= 45 days after prostatectomy and within 30 days prior to step 1, < 2.0 ng/mL~No evidence of a local recurrence in the prostate fossa based on a digital rectal examination (DRE) within 60 days prior to step 1 registration~Patients with equivocal or questionable DRE findings should have an MRI of the pelvis to exclude the presence of a prostate fossa mass~Patients with equivocal or questionable exam findings by DRE or MRI are eligible if a biopsy of the lesion is negative for tumor~No evidence of bone metastases (M0) on bone scan (Na F positron emission tomography (PET)/CT is an acceptable substitute) within 120 days prior to step 1 registration~Equivocal bone scan findings are allowed if plain films and/or MRI are negative for metastasis~Zubrod performance status 0-1 within 60 days prior to step 1 registration~The patient or a legally authorized representative must provide study-specific informed consent prior to step 1 registration~Willingness and ability to complete the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire~Only English and French-speaking patients are eligible to participate~PRIOR TO STEP 2 REGISTRATION~The EPIC-26 must be completed in full and entered within 10 business days after step 1 registration; NRG Oncology Statistical and Data Management Center has 3 business days to score the results and send a notification to the site to proceed to step 2 randomization~Exclusion Criteria:~A post-prostatectomy PSA nadir >= 0.2 ng/mL AND Gleason >= 7~pT2 with a negative surgical margin and PSA < 0.1 ng/mL~Androgen deprivation therapy started prior to prostatectomy for > 6 months (180 days) duration;~Note: The use of finasteride or dutasteride (? tamsulosin) for longer periods prior to prostatectomy is acceptable~Androgen deprivation therapy started after prostatectomy and prior to step 1 registration for > 6 weeks (42 days)~Neoadjuvant chemotherapy before or after prostatectomy~Prior invasive (except non-melanoma skin cancer) malignancy unless disease-free for a minimum of 3 years and not in the pelvis; (for example, carcinoma in situ of the oral cavity is permissible if disease free for a minimum of 3 years; however, patients with prior history of bladder cancer are not allowed no matter the disease free duration); prior hematological (e.g., leukemia, lymphoma, myeloma) malignancy is not allowed~Previous chemotherapy for any other disease site if given within 3 years prior to step 1~Prior radiotherapy, including brachytherapy, to the region of the study cancer that would result in overlap of radiation therapy treatment volumes~Severe, active co-morbidity, defined as follows:~Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months~Transmural myocardial infarction within the last 6 months~Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 1 registration~Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 1 registration~Severe hepatic disease, defined as a diagnosis of Child-Pugh class B or C hepatic disease~Human immunodeficiency virus (HIV) positive with CD4 count < 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol~End-stage renal disease (ie, on dialysis or dialysis has been recommended)~Prior allergic reaction to the study drugs involved in this protocol~History of inflammatory bowel disease, prior bowel surgeries (or colostomy) for any reason, or prior partial/radical cystectomy for any reason
|
18 Years
| null |
Male
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Urinary Domain of the Expanded Prostate Cancer Index (EPIC) at Two Years | The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The urinary domain contains 12 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL. | Baseline (randomization), 2 years |
| Change in Bowel Domain of the Expanded Prostate Cancer Index (EPIC) at Two Years | The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The bowel domain contains 14 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL. | Baseline, 2 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Urinary Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of Radiation Therapy (RT), 6 Months, 1 and 5 Years | The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The urinary domain contains 12 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL. | Baseline, end of RT, then 6 months,1 and 5 years from the start of RT (5 year time point has not yet been reached). RT dates depend on timing and duration of androgen deprivation therapy (ADT) (optional) and RT. |
| Change in Bowel Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of RT, 6 Months, 1 and 5 Years | The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The bowel domain contains 14 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL. | Baseline, end of RT, then 6 months,1 and 5 years from the start of RT (5 year time point has not yet been reached). RT dates depend on timing and duration of ADT (optional) and RT. |
| Percentage of Participants With Biochemical Failure | Biochemical failure was analyzed using two different definitions. The protocol definition of biochemical failure is a PSA measurement ≥ 0.4 ng/mL and rising (i.e. PSA ≥ 0.4 ng/mL followed by a value higher than the first by any amount) or followed by initiation of salvage hormones. The Phoenix definition of biochemical failure is a PSA measurement ≥ PSA nadir + 2 ng/mL where nadir is the lowest post-RT PSA value. Time to biochemical failure is defined as time from randomization to the date of first biochemical failure, last known follow-up (censored), or death without biochemical failure (competing risk). Biochemical failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided. | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. |
| Percentage of Participants With Progression | Progression (failure) is defined as the first occurrence of biochemical failure, local failure, regional failure, distant failure, institution of new unplanned anticancer treatment, or death from prostate cancer. Time to progression is defined as time from randomization to the date of progression, last known follow-up (censored), or death without progression (competing risk). Progression rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided. | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. |
| Percentage of Participants With Local-Regional Failure | Local-regional failure is defined as local or regional failure. Local failure is defined as the development of a new biopsy-proven mass in the prostate bed. Regional failure is defined as radiographic evidence (CT or MRI) of lymphadenopathy (lymph node size ≥ 1.0 cm in the short axis) in a patient without the diagnosis of a hematologic/lymphomatous disorder associated with adenopathy. Time to local-regional failure is defined as time from randomization to the date of first local-regional failure, last known follow-up (censored), or death without local-regional (competing risk). Local-regional failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided. | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. |
| Percentage of Participants Receiving Salvage Therapy | Salvage therapy is defined as the initiation of new unplanned anticancer treatment. Time to salvage therapy initiation is defined as time from randomization to the date of first salvage therapy, last known follow-up (censored), or death without salvage therapy (competing risk). Salvage therapy rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of salvage initiation times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided. | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. |
| Percentage of Participants With Distant Metastasis | Distant metastasis (failure) is defined as radiographic evidence of hematogenous spread evaluated by bone scan, CT, or MRI. Time to distant metastasis is defined as time from randomization to the date of first distant metastasis, last known follow-up (censored), or death without local recurrence (competing risk). Distant metastasis rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided. | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. |
| Percentage of Participants Who Died From Prostate Cancer (Prostate Cancer Specific Mortality) | Cause of death was centrally reviewed. Count and percentage at time of analysis are reported. | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. |
| Percent of Participants Alive (Overall Survival) | Overall survival time is defined as time from registration/randomization to the date of death (failure) from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. 2-year rates are provided. | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. |
| Number of Participants With Grade 3+ Adverse Events | Common Terminology Criteria for Adverse Events (CTCAE) version 4 grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. Counts of participants with any grade 3 or higher adverse event, any grade 3 or higher gastrointestinal adverse events, and any grade 3 or higher genitourinary adverse events are reported. Adverse events of any attribution are included. | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. |
|
Androgens, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs, Hormones
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conventional radiation therapy<br>Conventional post-prostatectomy radiation therapy (COPORT) over 7 weeks. Patients may also receive optional androgen deprivation therapy per doctor recommendation. | Radiation: Conventional radiation therapy<br>* 62.5 Gy in 25 daily fractions of 2.5 Gy to the prostate bed in the absence of disease progression or unacceptable toxicity.<br>Drug: Optional androgen deprivation therapy<br>* Any luteinizing hormone-releasing hormone (LHRH) agonist/antagonist with or without an oral antiandrogen can be used up to a six-month administration dose, starting 7-9 weeks before radiation therapy and may begin as early as 42 days prior to or any time after screening. An oral antiandrogen alone is not allowed.<br>* Other names: ADT;|
| Experimental: Hypofractionated radiation therapy<br>Hypofractionated post-prostatectomy radiation therapy (HYPORT) over 5 weeks. Patients may also receive optional androgen deprivation therapy per doctor recommendation. | Radiation: Hypofractionated radiation therapy<br>* 66.6 Gy in 37 daily fractions of 1.8 Gy to the prostate bed in the absence of disease progression or unacceptable toxicity.<br>* Other names: hypofractionation;Drug: Optional androgen deprivation therapy<br>* Any luteinizing hormone-releasing hormone (LHRH) agonist/antagonist with or without an oral antiandrogen can be used up to a six-month administration dose, starting 7-9 weeks before radiation therapy and may begin as early as 42 days prior to or any time after screening. An oral antiandrogen alone is not allowed.<br>* Other names: ADT;|
|
Hypofractionated Radiation Therapy or Conventional Radiation Therapy After Surgery in Treating Patients With Prostate Cancer
Study Overview
=================
Brief Summary
-----------------
This randomized phase III trial studies how well hypofractionated radiation therapy works compared to conventional radiation therapy after surgery in treating patients with prostate cancer. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Conventional radiation therapy uses high energy x-rays, gamma rays, neutrons, protons, or other sources to kill tumor cells and shrink tumors. It is not yet known whether giving hypofractionated radiation therapy or conventional radiation therapy after surgery may work better in treating patients with prostate cancer.
Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To demonstrate that hypofractionated post-prostatectomy radiotherapy (HYPORT) does not increase patient-reported gastrointestinal (GI) or genitourinary (GU) symptoms over conventionally fractionated post-prostatectomy (COPORT) at the 2-year time point. SECONDARY OBJECTIVES: I. To compare patient-reported GI symptoms using the Expanded Prostate Cancer Index Composite (EPIC)-26 at end of radiation therapy (RT) and 6, 12, 24, and 60 months from end of treatment. II. To compare patient-reported GU symptoms using the EPIC-26 at end of RT and 6, 12, 24, and 60 months from end of treatment. III. To compare the cost effectiveness based on the cost of radiotherapy and measured utilities for health outcomes using the EuroQol five dimensions questionnaire (EQ-5D). IV. To compare time to progression (TTP) where progression is defined as the first occurrence of biochemical failure (BF), local failure, regional failure, distant metastasis (DM), institution of new unplanned anticancer treatment, or death from prostate cancer (prostate cancer specific mortality [PCSM]). V. To compare freedom from biochemical failure (FFBF) and TTP rates with an alternate prostate specific antigen (PSA) >= PSA nadir + 2 ng/mL definition of BF. VI. To compare local failure, regional failure, salvage therapy (i.e. institution of new unplanned anticancer treatment), DM, PCSM, and overall survival (OS) rates. VII. Assessment of adverse events. VIII. Paraffin-embedded tissue block, serum, plasma, whole blood, and urine for future translational research analyses for predictors of toxicity following hypofractionated or conventionally fractionated post-prostatectomy radiotherapy. After completion of study treatment, patients are followed up every 6 months for 2 years and every year for 3 years and thereafter.
Official Title
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A Randomized Phase III Trial of Hypofractionated Post-prostatectomy Radiation Therapy (HYPORT) Versus Conventional Post-prostatectomy Radiation Therapy (COPORT)
Conditions
-----------------
Prostate Adenocarcinoma, Stage I Prostate Adenocarcinoma, Stage II Prostate Adenocarcinoma, Stage III Prostate Adenocarcinoma
Intervention / Treatment
-----------------
* Radiation: Hypofractionated radiation therapy
* Radiation: Conventional radiation therapy
* Drug: Optional androgen deprivation therapy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: PRIOR TO STEP 1 REGISTRATION Adenocarcinoma of the prostate treated primarily with radical prostatectomy Any type of radical prostatectomy will be permitted, including retropubic, perineal, laparoscopic, or robotically assisted; there is no time limit for the date of radical prostatectomy One of the following pathologic T-classifications: pT2 or pT3 Patients with positive surgical margins are eligible One of the following pathologic N-classifications: pN0, pNX If a lymph node dissection is performed, the number of lymph nodes removed per side of the pelvis and the extent of the pelvic lymph node dissection (obturator versus (vs.) extended lymph node dissection) should be noted whenever possible No clinical evidence of regional lymph node metastasis Computed tomography (CT) (with contrast if renal function is acceptable; a noncontrast CT is permitted if the patient is not a candidate for contrast), magnetic resonance imaging (MRI), nodal sampling, or dissection of the pelvis within 120 days prior to step 1 registration Patients with pelvic lymph nodes equivocal or questionable by imaging are eligible if the nodes are =< 1 cm in the short axis A post-radical prostatectomy study entry PSA >= 45 days after prostatectomy and within 30 days prior to step 1, < 2.0 ng/mL No evidence of a local recurrence in the prostate fossa based on a digital rectal examination (DRE) within 60 days prior to step 1 registration Patients with equivocal or questionable DRE findings should have an MRI of the pelvis to exclude the presence of a prostate fossa mass Patients with equivocal or questionable exam findings by DRE or MRI are eligible if a biopsy of the lesion is negative for tumor No evidence of bone metastases (M0) on bone scan (Na F positron emission tomography (PET)/CT is an acceptable substitute) within 120 days prior to step 1 registration Equivocal bone scan findings are allowed if plain films and/or MRI are negative for metastasis Zubrod performance status 0-1 within 60 days prior to step 1 registration The patient or a legally authorized representative must provide study-specific informed consent prior to step 1 registration Willingness and ability to complete the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire Only English and French-speaking patients are eligible to participate PRIOR TO STEP 2 REGISTRATION The EPIC-26 must be completed in full and entered within 10 business days after step 1 registration; NRG Oncology Statistical and Data Management Center has 3 business days to score the results and send a notification to the site to proceed to step 2 randomization Exclusion Criteria: A post-prostatectomy PSA nadir >= 0.2 ng/mL AND Gleason >= 7 pT2 with a negative surgical margin and PSA < 0.1 ng/mL Androgen deprivation therapy started prior to prostatectomy for > 6 months (180 days) duration; Note: The use of finasteride or dutasteride (? tamsulosin) for longer periods prior to prostatectomy is acceptable Androgen deprivation therapy started after prostatectomy and prior to step 1 registration for > 6 weeks (42 days) Neoadjuvant chemotherapy before or after prostatectomy Prior invasive (except non-melanoma skin cancer) malignancy unless disease-free for a minimum of 3 years and not in the pelvis; (for example, carcinoma in situ of the oral cavity is permissible if disease free for a minimum of 3 years; however, patients with prior history of bladder cancer are not allowed no matter the disease free duration); prior hematological (e.g., leukemia, lymphoma, myeloma) malignancy is not allowed Previous chemotherapy for any other disease site if given within 3 years prior to step 1 Prior radiotherapy, including brachytherapy, to the region of the study cancer that would result in overlap of radiation therapy treatment volumes Severe, active co-morbidity, defined as follows: Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months Transmural myocardial infarction within the last 6 months Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 1 registration Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 1 registration Severe hepatic disease, defined as a diagnosis of Child-Pugh class B or C hepatic disease Human immunodeficiency virus (HIV) positive with CD4 count < 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol End-stage renal disease (ie, on dialysis or dialysis has been recommended) Prior allergic reaction to the study drugs involved in this protocol History of inflammatory bowel disease, prior bowel surgeries (or colostomy) for any reason, or prior partial/radical cystectomy for any reason
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
Male
Accepts Healthy Volunteers
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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: Conventional radiation therapy<br>Conventional post-prostatectomy radiation therapy (COPORT) over 7 weeks. Patients may also receive optional androgen deprivation therapy per doctor recommendation. | Radiation: Conventional radiation therapy<br>* 62.5 Gy in 25 daily fractions of 2.5 Gy to the prostate bed in the absence of disease progression or unacceptable toxicity.<br>Drug: Optional androgen deprivation therapy<br>* Any luteinizing hormone-releasing hormone (LHRH) agonist/antagonist with or without an oral antiandrogen can be used up to a six-month administration dose, starting 7-9 weeks before radiation therapy and may begin as early as 42 days prior to or any time after screening. An oral antiandrogen alone is not allowed.<br>* Other names: ADT;|
| Experimental: Hypofractionated radiation therapy<br>Hypofractionated post-prostatectomy radiation therapy (HYPORT) over 5 weeks. Patients may also receive optional androgen deprivation therapy per doctor recommendation. | Radiation: Hypofractionated radiation therapy<br>* 66.6 Gy in 37 daily fractions of 1.8 Gy to the prostate bed in the absence of disease progression or unacceptable toxicity.<br>* Other names: hypofractionation;Drug: Optional androgen deprivation therapy<br>* Any luteinizing hormone-releasing hormone (LHRH) agonist/antagonist with or without an oral antiandrogen can be used up to a six-month administration dose, starting 7-9 weeks before radiation therapy and may begin as early as 42 days prior to or any time after screening. An oral antiandrogen alone is not allowed.<br>* Other names: ADT;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Urinary Domain of the Expanded Prostate Cancer Index (EPIC) at Two Years | The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The urinary domain contains 12 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL. | Baseline (randomization), 2 years |
| Change in Bowel Domain of the Expanded Prostate Cancer Index (EPIC) at Two Years | The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The bowel domain contains 14 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL. | Baseline, 2 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Urinary Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of Radiation Therapy (RT), 6 Months, 1 and 5 Years | The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The urinary domain contains 12 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL. | Baseline, end of RT, then 6 months,1 and 5 years from the start of RT (5 year time point has not yet been reached). RT dates depend on timing and duration of androgen deprivation therapy (ADT) (optional) and RT. |
| Change in Bowel Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of RT, 6 Months, 1 and 5 Years | The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The bowel domain contains 14 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL. | Baseline, end of RT, then 6 months,1 and 5 years from the start of RT (5 year time point has not yet been reached). RT dates depend on timing and duration of ADT (optional) and RT. |
| Percentage of Participants With Biochemical Failure | Biochemical failure was analyzed using two different definitions. The protocol definition of biochemical failure is a PSA measurement ≥ 0.4 ng/mL and rising (i.e. PSA ≥ 0.4 ng/mL followed by a value higher than the first by any amount) or followed by initiation of salvage hormones. The Phoenix definition of biochemical failure is a PSA measurement ≥ PSA nadir + 2 ng/mL where nadir is the lowest post-RT PSA value. Time to biochemical failure is defined as time from randomization to the date of first biochemical failure, last known follow-up (censored), or death without biochemical failure (competing risk). Biochemical failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided. | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. |
| Percentage of Participants With Progression | Progression (failure) is defined as the first occurrence of biochemical failure, local failure, regional failure, distant failure, institution of new unplanned anticancer treatment, or death from prostate cancer. Time to progression is defined as time from randomization to the date of progression, last known follow-up (censored), or death without progression (competing risk). Progression rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided. | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. |
| Percentage of Participants With Local-Regional Failure | Local-regional failure is defined as local or regional failure. Local failure is defined as the development of a new biopsy-proven mass in the prostate bed. Regional failure is defined as radiographic evidence (CT or MRI) of lymphadenopathy (lymph node size ≥ 1.0 cm in the short axis) in a patient without the diagnosis of a hematologic/lymphomatous disorder associated with adenopathy. Time to local-regional failure is defined as time from randomization to the date of first local-regional failure, last known follow-up (censored), or death without local-regional (competing risk). Local-regional failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided. | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. |
| Percentage of Participants Receiving Salvage Therapy | Salvage therapy is defined as the initiation of new unplanned anticancer treatment. Time to salvage therapy initiation is defined as time from randomization to the date of first salvage therapy, last known follow-up (censored), or death without salvage therapy (competing risk). Salvage therapy rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of salvage initiation times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided. | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. |
| Percentage of Participants With Distant Metastasis | Distant metastasis (failure) is defined as radiographic evidence of hematogenous spread evaluated by bone scan, CT, or MRI. Time to distant metastasis is defined as time from randomization to the date of first distant metastasis, last known follow-up (censored), or death without local recurrence (competing risk). Distant metastasis rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided. | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. |
| Percentage of Participants Who Died From Prostate Cancer (Prostate Cancer Specific Mortality) | Cause of death was centrally reviewed. Count and percentage at time of analysis are reported. | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. |
| Percent of Participants Alive (Overall Survival) | Overall survival time is defined as time from registration/randomization to the date of death (failure) from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. 2-year rates are provided. | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. |
| Number of Participants With Grade 3+ Adverse Events | Common Terminology Criteria for Adverse Events (CTCAE) version 4 grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. Counts of participants with any grade 3 or higher adverse event, any grade 3 or higher gastrointestinal adverse events, and any grade 3 or higher genitourinary adverse events are reported. Adverse events of any attribution are included. | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. |
|
|
NCT01914679
|
A Prospective Evaluation of RINCE to Reduce Fibromyalgia Effects - University of Michigan
|
The purpose of this study is to evaluate the mechanisms of noninvasive cortical electrostimulation therapy known as Reduced Impedance Noninvasive Cortical Electrostimulation RINCE)in the management of fibromyalgia. Patients who meet the 1990 American College of Rheumatology criteria for fibromyalgia will receive up to 24 RINCE treatments delivered by a medical device called NeuroPoint. Approximately 20 patients will receive a combination of active and inactive (sham) therapy treatments over a 16-week period followed by a 4 week post-treatment evaluation. Patients will also undergo three (3) functional brain imaging scans while participating in the study: the first prior to the commencement of treatment, another mid-treatment; and the third at the completion of the treatment period.~The study's primary outcome measure will be the change from baseline in self-reported 24-hour average pain intensity. The study's hypothesis is that there will be a change in pain intensity as well brain functioning. We do not expect there to be a statistically significant improvement in pain intensity due to the small sample but do expect to see statistically significant changes in cortical function as measured by EEG and fMRI
|
A Phase 2 Clinical Trial Evaluating Use of the NeuroPoint Medical Device as a Treatment for Fibromyalgia.
|
Fibromyalgia
|
* Device: RINCE
|
Inclusion Criteria:~Patient must provide written informed consent and privacy authorization prior to participation in the study. Patient must have the ability to read and/or follow written and oral instructions, abide by the study restrictions, and agree to return for the required assessments.~Patient is female, 18-65 years of age (inclusive) at the time of consent.~Patient must have a confirmed diagnosis of fibromyalgia meeting the ACR 1990 diagnostic criteria for fibromyalgia.~Patients must have a 24-hour recall pain intensity score at both the screening and baseline visits between 40 and 90 inclusive on a 100 mm VAS scale.~Female patient of childbearing potential must be willing to use an acceptable method of birth control for the duration of their study participation.~Patients must be willing to refrain from all excluded therapies for the duration of the study.~In the opinion of the Investigator, the patient is willing and able to comply with all protocol-specified requirements.~Participants undergoing fMRI and 1H-MRS must be predominantly right handed (i.e. the subject writes with their right hand).~Exclusion Criteria:~The patient will not be eligible for enrollment if there is any history of, or in the opinion of the investigator, any of the following criteria are met:~Patient has a current significant psychological or psychiatric disorder (e.g., severe, unstable or poorly controlled depression, severe anxiety or obsessive-compulsive disorder; history of suicide attempt within preceding 5 years or suicidal ideation within preceding 6 months; or any history of bipolar disorder, schizophrenia, schizoaffective or other psychotic disorder).~Patient has a total Hospital and Anxiety Depression score of 11-21 for either anxiety or depression, or, based on the investigator's judgment, the patient is at risk of suicidal ideation or behavior.~Patient is currently using prohibited medications or treatments (see Prohibited Concomitant Therapy section of protocol) including stimulants, anesthetic patches, CPAP and/or TENS therapy.~Patient has an active diagnosis and is being treated for chronic infection or chronic condition such as lupus, rheumatoid arthritis, Parkinson's disease, multiple sclerosis, hepatitis, polio, seizures, or cancer (other than basal or squamous cell skin cancer).~Patient has any other chronic pain condition other than fibromyalgia that, in the Investigator's opinion, would interfere with the assessment of fibromyalgia (e.g., rheumatoid arthritis, post herpetic neuralgia, pain associated with diabetic neuropathy, severe pain due to degenerative joint disease, etc.)~Patient has history of seizure disorder, dementia or epilepsy anytime during his or her life except pediatric febrile seizures.~Female patient who is pregnant, planning a pregnancy, or breastfeeding.~Patient has any other disease or medical condition that, in the opinion of the investigator, would interfere with the evaluation of study device efficacy or safety, or would compromise the patient's ability to participate in or complete the study.~Patient has a history of other cranial electrical stimulation device use, or electroconvulsive therapy.~Patient has any metal implant, such as stents, aneurysm clips, shunts, pacemakers, defibrillators, neurostimulators or other contraindications with fMRI and 1H-MRS. Long-bone implants are not excluded.~Any anticipated need for surgery that might confound results or interfere with patient's ability to comply with the protocol.~Myocardial infarction during preceding 12 months, uncontrolled hypertension, active cardiac disease (American Heart Association Functional Class 2, 3 or 4 or Objective Class C or D), clinically significant cardiac rhythm or conduction abnormality, or anticipation of bypass or other cardiac surgery within the next 12 months.~Current systemic infection (e.g., HIV, hepatitis).~Patients receiving systemic corticosteroids (> 5 mg prednisone or equivalent per day).~Pending or current litigation or disability claim (including Workman's Compensation). Patients currently receiving disability benefits will require medical monitor approval on a case-by-case basis.~Patient has history of alcohol and/or drug abuse.~Patient has participated in any investigational study within 30 days prior to Screening visit or is currently participating in another clinical trial.~Patient has received any prior experimental treatment or therapy that, in the opinion of the medical monitor, would compromise the patient's ability to participate in the study.~Patient is a staff member or relative of a staff member at either the investigative site or the Cerephex Corporation.~Body Mass Index (BMI) of greater than approximately 40 kg/m2.~Claustrophobia or any other factor sufficiently significant that it is likely to prevent successful completion of fMRI and 1H-MRS procedures.
|
18 Years
|
65 Years
|
Female
|
No
|
Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: All participants went through a 4 week sham period, followed by a 12 week intervention with the device.
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Patient 24-hour Recall Average Pain Intensity | The units of measure represent self-reported average pain over the last 24 hours on a 0-100 pain rating scale where 0 is no pain and 100 is the worst pain imaginable.~. | Assessed at Baseline (Week 1), Post-Sham (Week 5), Mid-Treatment (Week 10), Mid-Treatment (Week 14), Post-Treatment (Week 18) |
|
Fibromyalgia, Pain, Brain, Stimulation, Device, Treatment
|
Fibromyalgia, Myofascial Pain Syndromes, Muscular Diseases, Musculoskeletal Diseases, Rheumatic Diseases, Neuromuscular Diseases, Nervous System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sham followed by device<br>4 weeks of inactive (sham) RINCE therapy involving no RINCE therapy followed by 12 weeks of RINCE therapy involving 24 total treatments | Device: RINCE<br>* The intervention is repeat applications of RINCE therapy. The sham is created by not delivering the therapy stimulation signal.<br>* Other names: RINCE therapy delivered by NeuroPoint Device;|
|
A Prospective Evaluation of RINCE to Reduce Fibromyalgia Effects - University of Michigan
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the mechanisms of noninvasive cortical electrostimulation therapy known as Reduced Impedance Noninvasive Cortical Electrostimulation RINCE)in the management of fibromyalgia. Patients who meet the 1990 American College of Rheumatology criteria for fibromyalgia will receive up to 24 RINCE treatments delivered by a medical device called NeuroPoint. Approximately 20 patients will receive a combination of active and inactive (sham) therapy treatments over a 16-week period followed by a 4 week post-treatment evaluation. Patients will also undergo three (3) functional brain imaging scans while participating in the study: the first prior to the commencement of treatment, another mid-treatment; and the third at the completion of the treatment period. The study's primary outcome measure will be the change from baseline in self-reported 24-hour average pain intensity. The study's hypothesis is that there will be a change in pain intensity as well brain functioning. We do not expect there to be a statistically significant improvement in pain intensity due to the small sample but do expect to see statistically significant changes in cortical function as measured by EEG and fMRI
Official Title
-----------------
A Phase 2 Clinical Trial Evaluating Use of the NeuroPoint Medical Device as a Treatment for Fibromyalgia.
Conditions
-----------------
Fibromyalgia
Intervention / Treatment
-----------------
* Device: RINCE
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient must provide written informed consent and privacy authorization prior to participation in the study. Patient must have the ability to read and/or follow written and oral instructions, abide by the study restrictions, and agree to return for the required assessments. Patient is female, 18-65 years of age (inclusive) at the time of consent. Patient must have a confirmed diagnosis of fibromyalgia meeting the ACR 1990 diagnostic criteria for fibromyalgia. Patients must have a 24-hour recall pain intensity score at both the screening and baseline visits between 40 and 90 inclusive on a 100 mm VAS scale. Female patient of childbearing potential must be willing to use an acceptable method of birth control for the duration of their study participation. Patients must be willing to refrain from all excluded therapies for the duration of the study. In the opinion of the Investigator, the patient is willing and able to comply with all protocol-specified requirements. Participants undergoing fMRI and 1H-MRS must be predominantly right handed (i.e. the subject writes with their right hand). Exclusion Criteria: The patient will not be eligible for enrollment if there is any history of, or in the opinion of the investigator, any of the following criteria are met: Patient has a current significant psychological or psychiatric disorder (e.g., severe, unstable or poorly controlled depression, severe anxiety or obsessive-compulsive disorder; history of suicide attempt within preceding 5 years or suicidal ideation within preceding 6 months; or any history of bipolar disorder, schizophrenia, schizoaffective or other psychotic disorder). Patient has a total Hospital and Anxiety Depression score of 11-21 for either anxiety or depression, or, based on the investigator's judgment, the patient is at risk of suicidal ideation or behavior. Patient is currently using prohibited medications or treatments (see Prohibited Concomitant Therapy section of protocol) including stimulants, anesthetic patches, CPAP and/or TENS therapy. Patient has an active diagnosis and is being treated for chronic infection or chronic condition such as lupus, rheumatoid arthritis, Parkinson's disease, multiple sclerosis, hepatitis, polio, seizures, or cancer (other than basal or squamous cell skin cancer). Patient has any other chronic pain condition other than fibromyalgia that, in the Investigator's opinion, would interfere with the assessment of fibromyalgia (e.g., rheumatoid arthritis, post herpetic neuralgia, pain associated with diabetic neuropathy, severe pain due to degenerative joint disease, etc.) Patient has history of seizure disorder, dementia or epilepsy anytime during his or her life except pediatric febrile seizures. Female patient who is pregnant, planning a pregnancy, or breastfeeding. Patient has any other disease or medical condition that, in the opinion of the investigator, would interfere with the evaluation of study device efficacy or safety, or would compromise the patient's ability to participate in or complete the study. Patient has a history of other cranial electrical stimulation device use, or electroconvulsive therapy. Patient has any metal implant, such as stents, aneurysm clips, shunts, pacemakers, defibrillators, neurostimulators or other contraindications with fMRI and 1H-MRS. Long-bone implants are not excluded. Any anticipated need for surgery that might confound results or interfere with patient's ability to comply with the protocol. Myocardial infarction during preceding 12 months, uncontrolled hypertension, active cardiac disease (American Heart Association Functional Class 2, 3 or 4 or Objective Class C or D), clinically significant cardiac rhythm or conduction abnormality, or anticipation of bypass or other cardiac surgery within the next 12 months. Current systemic infection (e.g., HIV, hepatitis). Patients receiving systemic corticosteroids (> 5 mg prednisone or equivalent per day). Pending or current litigation or disability claim (including Workman's Compensation). Patients currently receiving disability benefits will require medical monitor approval on a case-by-case basis. Patient has history of alcohol and/or drug abuse. Patient has participated in any investigational study within 30 days prior to Screening visit or is currently participating in another clinical trial. Patient has received any prior experimental treatment or therapy that, in the opinion of the medical monitor, would compromise the patient's ability to participate in the study. Patient is a staff member or relative of a staff member at either the investigative site or the Cerephex Corporation. Body Mass Index (BMI) of greater than approximately 40 kg/m2. Claustrophobia or any other factor sufficiently significant that it is likely to prevent successful completion of fMRI and 1H-MRS procedures.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: All participants went through a 4 week sham period, followed by a 12 week intervention with the device.
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sham followed by device<br>4 weeks of inactive (sham) RINCE therapy involving no RINCE therapy followed by 12 weeks of RINCE therapy involving 24 total treatments | Device: RINCE<br>* The intervention is repeat applications of RINCE therapy. The sham is created by not delivering the therapy stimulation signal.<br>* Other names: RINCE therapy delivered by NeuroPoint Device;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Patient 24-hour Recall Average Pain Intensity | The units of measure represent self-reported average pain over the last 24 hours on a 0-100 pain rating scale where 0 is no pain and 100 is the worst pain imaginable. . | Assessed at Baseline (Week 1), Post-Sham (Week 5), Mid-Treatment (Week 10), Mid-Treatment (Week 14), Post-Treatment (Week 18) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fibromyalgia, Pain, Brain, Stimulation, Device, Treatment
|
||
NCT01918228
|
Effect of Reassuring Information on Danish Workers Who Experience Low Back Pain in the Following Year.
|
RCT study of the effect of an educational-based intervention on low back pain-related outcomes concerning beliefs and behaviour.
|
Previous studies have strongly implied that information is a valuable means for people suffering from LBP in terms of coping appropriately. Most studies have tested the effect of information as part of a multimodal intervention.~Four Nordic studies testing the effect of 'reassuring information' based on the 'Functional Disturbance'-model (proposed by Indahl et al. 1999 - also called the 'non-injury'-model) have all been effective at positively altering the functional level and/or days of sickness absence - when provided in combination with other elements to people with subacute/chronic back pain. The present study set out to test the effect of this kind of resassuring information alone.~Between November 2012 and September 2013, we included app. 500 municipal workers perfoming either manual work, administrative work or a combination of the two. Participants worked in 5 different municipal workplaces. These workplaces were characterized by being devided into 'natural working unit', which had no or very little daily contact. All 5 workplaces participated with at least 2 units. Thus 11 units contributed to the data. Baseline assessment took place during right upon recruitment prior to randomization.~We cluster-randomized the 11 units into an intervention and a control group using a simple stepwise randomization-metod.~The intervention group received two 45-minute lectures at the workplace with an interval of 2 weeks. The lectures were coherent allthough different. They consisted of information on the scientific knowledge on the etiology of LBP, basic anatomy, common myths about LBP, a theory of non-specific LBP being caused by muscular functional disturbances (Indahl 1999), pain physiology, and scientific knowledge on seemingly appropriate coping strategies to prevent a prolonged course. Emphasis was made to reduce pain-related fear of movement and catastrophizing thoughts and beliefs. Instead, activity during pain episodes was promoted as well as a natural use of the back despite pain. A non-directive approach was used (non-imperativ wording and absence of giving advice). The purpose was to provide information but let the participant make their own conclusions on how and if to use the information in present/future coping with pain.~In addition to the lecture, the intervention group participants were provided with a leaflet showing various relevenat stretching exercises (back and related muscles) and they were offered the option to make a call to the primary investigator in case any questions would arise subsequently.~The control group was untreated by us. Both groups had access to all 'usual' help (workplace, general practitioner etc).~Upon completion of the lectures, twelve monthly assessments were conducted using Text Messaging (SMS). During each assessment, participants answered questions on no. of LBP days, no. of LBP-related cutdown days, no. of LBP-related sick days, no. of LBP-related healthcare visits, overall workability, bothersomeness last week, restricted activity last week, and use of pain medicine or degree of sadness/depression.~In addition, a separate assessment was performed at app. 5.5 monts to obtain responses on back beliefs.~The data collection was completed in 2014. Analysis are nearly finished. The sicentific paper on the study is anticipated to take place in the beginning of 2016.
|
Effect of an Educational Based Intervention on Danish Workers With Low Back Pain. A Randomized Controlled Single Blinded Study.
|
Non-specific Low Back Pain
|
* Behavioral: Talks about what science says about LBP
|
Inclusion Criteria:~-employed at one of the participating municipal workplaces~Exclusion Criteria:~pregnancy within the first 6 months of the study~physical or mental disease that has significant impact on the individual in terms of pain (eg. Rheumathoid disease, clinical depression)~present cancer disease (risk of metastasis)~planned stop at the workplace within the first 6 months of the study
|
18 Years
|
72 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Level | item 2 & 4 in the COMI (Deyo et al. 1998) cathegoric variable/numeric variable | 12 months |
| Sickness absence (analysed as work participation) | item 5 in the COMI (Deyo et al. 1998) | 12 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| No. of monthly healthcare visits | Number of monthly visits to any kind of healthcare provider | 12 months |
| Back beliefs | item 10 & 12-14 from the Back Beliefs Questionnaire | 5.5 months |
|
Back Pain, Low Back Pain, Pain, Neurologic Manifestations
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>Talks on scientific status on back pain with the purpose of reducing LBP-related insecurity/fear, reducing the focus on the pain and providing participants with alternative explanation to their LBP. They were also provided with a folder (general stretching exercises) and had telephone access to health professional if they had questions about LBP during the follow-up year. | Behavioral: Talks about what science says about LBP<br>* Two talks, a folder with general stretching exercises and possibility to contact health professional by telephone<br>|
| No Intervention: Control group<br>No intervention will be provided by the study team. | |
|
Effect of Reassuring Information on Danish Workers Who Experience Low Back Pain in the Following Year.
Study Overview
=================
Brief Summary
-----------------
RCT study of the effect of an educational-based intervention on low back pain-related outcomes concerning beliefs and behaviour.
Detailed Description
-----------------
Previous studies have strongly implied that information is a valuable means for people suffering from LBP in terms of coping appropriately. Most studies have tested the effect of information as part of a multimodal intervention. Four Nordic studies testing the effect of 'reassuring information' based on the 'Functional Disturbance'-model (proposed by Indahl et al. 1999 - also called the 'non-injury'-model) have all been effective at positively altering the functional level and/or days of sickness absence - when provided in combination with other elements to people with subacute/chronic back pain. The present study set out to test the effect of this kind of resassuring information alone. Between November 2012 and September 2013, we included app. 500 municipal workers perfoming either manual work, administrative work or a combination of the two. Participants worked in 5 different municipal workplaces. These workplaces were characterized by being devided into 'natural working unit', which had no or very little daily contact. All 5 workplaces participated with at least 2 units. Thus 11 units contributed to the data. Baseline assessment took place during right upon recruitment prior to randomization. We cluster-randomized the 11 units into an intervention and a control group using a simple stepwise randomization-metod. The intervention group received two 45-minute lectures at the workplace with an interval of 2 weeks. The lectures were coherent allthough different. They consisted of information on the scientific knowledge on the etiology of LBP, basic anatomy, common myths about LBP, a theory of non-specific LBP being caused by muscular functional disturbances (Indahl 1999), pain physiology, and scientific knowledge on seemingly appropriate coping strategies to prevent a prolonged course. Emphasis was made to reduce pain-related fear of movement and catastrophizing thoughts and beliefs. Instead, activity during pain episodes was promoted as well as a natural use of the back despite pain. A non-directive approach was used (non-imperativ wording and absence of giving advice). The purpose was to provide information but let the participant make their own conclusions on how and if to use the information in present/future coping with pain. In addition to the lecture, the intervention group participants were provided with a leaflet showing various relevenat stretching exercises (back and related muscles) and they were offered the option to make a call to the primary investigator in case any questions would arise subsequently. The control group was untreated by us. Both groups had access to all 'usual' help (workplace, general practitioner etc). Upon completion of the lectures, twelve monthly assessments were conducted using Text Messaging (SMS). During each assessment, participants answered questions on no. of LBP days, no. of LBP-related cutdown days, no. of LBP-related sick days, no. of LBP-related healthcare visits, overall workability, bothersomeness last week, restricted activity last week, and use of pain medicine or degree of sadness/depression. In addition, a separate assessment was performed at app. 5.5 monts to obtain responses on back beliefs. The data collection was completed in 2014. Analysis are nearly finished. The sicentific paper on the study is anticipated to take place in the beginning of 2016.
Official Title
-----------------
Effect of an Educational Based Intervention on Danish Workers With Low Back Pain. A Randomized Controlled Single Blinded Study.
Conditions
-----------------
Non-specific Low Back Pain
Intervention / Treatment
-----------------
* Behavioral: Talks about what science says about LBP
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: -employed at one of the participating municipal workplaces Exclusion Criteria: pregnancy within the first 6 months of the study physical or mental disease that has significant impact on the individual in terms of pain (eg. Rheumathoid disease, clinical depression) present cancer disease (risk of metastasis) planned stop at the workplace within the first 6 months of the study
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 72 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: Factorial Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>Talks on scientific status on back pain with the purpose of reducing LBP-related insecurity/fear, reducing the focus on the pain and providing participants with alternative explanation to their LBP. They were also provided with a folder (general stretching exercises) and had telephone access to health professional if they had questions about LBP during the follow-up year. | Behavioral: Talks about what science says about LBP<br>* Two talks, a folder with general stretching exercises and possibility to contact health professional by telephone<br>|
| No Intervention: Control group<br>No intervention will be provided by the study team. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Level | item 2 & 4 in the COMI (Deyo et al. 1998) cathegoric variable/numeric variable | 12 months |
| Sickness absence (analysed as work participation) | item 5 in the COMI (Deyo et al. 1998) | 12 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| No. of monthly healthcare visits | Number of monthly visits to any kind of healthcare provider | 12 months |
| Back beliefs | item 10 & 12-14 from the Back Beliefs Questionnaire | 5.5 months |
|
|
NCT05403632
|
Mediterranean Diet on Pregnancy and Foetus Development
|
The Mediterranean-style diet has been associated with longevity, long-life wellbeing, lower risk of cardiovascular disease, cancer, obesity, and metabolic syndrome. Research is pointing to the benefits that MeD could have in pregnant. Pregnancy is a very complex period and recently, the attention has been focused on the possibility that healthy dietary patterns positively influence pregnancy and the development of organs in the offspring. The mechanisms through which MeD influences pregnancy and fetal growth may partly depend on its antinflammatory properties and possibly on changes in epigenetic mechanisms. Systemic inflammation might contribute to the association between maternal obesity and less favorable neurodevelopmental outcomes. The investigators aim to define how maternal adhesion to MeD may affect pregnancy and new-born development, hence representing a notable burden from a public health and social perspective. Main objective of this project is to build up a birth cohort suitable to investigate the role of maternal dietary habits on maternal and new-born health, with special focus on MeD and its possible mechanism of action through epigenetic and inflammation changes. To establish a mother/new-born cohort, collect detailed information on maternal dietary habits and set-up a biobank of biological samples to evaluate the association between dietary habits and pregnancy outcomes. The investigators will recruit 2000 pairs (mother, new-born) in different obstetrics departments. To investigate the association between maternal dietary habits, foetal growth and offspring development and possible mediation by the inflammation profile of the mother. To understand whether maternal dietary habits are associated with epigenetic changes in the offspring and if this process is driven by the inflammation profile of the mother. Venous blood samples will be obtained at the baseline and at each gestational period for ultrasound at 11-13 gestational weeks, 20-22 weeks and 30-32 weeks. Women will be followed-up with standard clinical and 2D ultrasound examinations at gestational weeks 11-13, 20-22 and 30-32 to evaluate the fetal growth. Offspring development will be assessed at 6, 12, 18, 24 months of age. After delivery, the investigators will collect umbilical cord blood and saliva samples from new-born using standard procedures. To understand if new-born epigenetics is associated with infant physical and neurocognitive development in the following 2 years.
|
The Mediterranean diet (MeD) is an eating pattern typical of the Mediterranean basin and is characterized by a wide consumption of plant foods, cereals, legumes, fish, olive oil as main fat source, and moderate wine consumption.The Mediterranean-style diet has been associated with longevity, long-life wellbeing, reduced risk of cardiovascular disease, cancer, obesity, and metabolic syndrome. Research is now pointing to the benefits that adherence to a MeD could have in women, while pregnant. Pregnancy, indeed, is a very complex period where growth, development, and maturity take place. The future body, in addition to increasing its cellular mass, progressively acquires functional capabilities that would permit it to live and grow out of the mother's womb. The mechanisms through which MeD influences pregnancy and foetal growth may partly depend on its antinflammatory properties and possibly on changes in epigenetic mechanisms. Indeed, changes in epigenetic profiles could mediate links between specific intrauterine, early postnatal exposures and future mental health outcomes or immune status in offspring. Systemic inflammation might contribute to the observed association between maternal obesity and less favourable neurodevelopmental outcomes. Studies have demonstrated that DNA methylation is linked to an increased inflammatory response as well as increased risk of chronic disease. Still, there is a scarcity of studies analysing how maternal nutrition influences health and development outcomes in new-born, and how it alters potentially underlying molecular pathways. Here the investigators aim to better define how maternal adhesion to MeD may affect pregnancy and new-born development, which, in turn, affect the risk of disease during adulthood, hence representing a notable burden from a public health and social perspective. Should this hypothesis be confirmed, our findings may allow developing specific and targeted public health interventions, possibly personalized programs based on the peculiar characteristics shown by each pair (mother/new-born). To establish a mother/new-born cohort, collect detailed information on maternal dietary habits and set-up a biobank of biological samples to evaluate the association between dietary habits and pregnancy outcomes. The investigators will recruit 2000 pairs (mother, new-born) in different obstetrics departments of the Neuromed Clinical Research Network. To investigate the association between maternal dietary habits, foetal growth and offspring development and possible mediation by the inflammation profile of the mother. To understand whether maternal dietary habits (exposure) are associated with epigenetic changes in the offspring (outcome) and if this process is driven by the inflammation profile of the mother. To understand if new-born epigenetics is associated with infant physical and neurocognitive development in the following 2 years. The study population consists of pregnant women attending the Units of Obstetrics and Gynecology at Neuromed Clinical Research Network (Casa di Cura Villa del Sole, Salerno, Istituto Clinico mediterraneo, Agropoli (SA), Casa di Cura Villa dei Platani, Avellino e Clinica Mediterranea, Napoli). Inclusion into the study takes place during the first prenatal visit and within the first trimester of pregnancy, and involves women who express the willing to deliver at the aforementioned operating units. All recruited women will sign an informed consent to participate in the study and an informed consent for genetic studies. Each woman, as well as the father of the child, will sign the written consent to processing of personal and genetic data of their new-born. Exclusion criteria are: pregnancy with foetuses with known chromosomal or congenital malformation, history of inflammatory disease, use of immunosuppressant drugs, pre-existing diabetes or hypertension, conception by heterologous artificial insemination, malabsorptive bariatric surgery, eating disorders. Dietary habits will be assessed by one-year recall food frequency questionnaire at baseline and by a 24-hour dietary recall interview for a total of 7 days at three different time points at 11-13 gestational weeks, 20-22 weeks and 30-32 weeks. To monitor dietary habits during pregnancy in real time an Ecological Momentary Assessment will be used, based on a signal-contingent approach, so that women will be solicited to record their dietary consumption and other information at semifixed intervals. From both questionnaires, the investigators will calculate the Mediterranean Diet Score, the total Food Antioxidant Content (FAC) score, the Polyphenols Antioxidant Content (PAC) score, the inflammatory potential of the diet and extract micro and macronutrients daily intakes. Food processing will be evaluated by specific classification. Information on physiological and pathological history and other lifestyles (sleep characteristics, physical activity, smoking habits) will be obtained by validated questionnaires. Physical activity will be assessed using the Pregnancy Physical Activity Questionnaire (PPAQ). Maternal anthropometric assessment (height, weight, waist circumference and blood pressure) will be measured following standard techniques. Pre-pregnancy and post-partum weights will be evaluated according to World Health Organization classification criteria for body mass index (BMI). The rate of pregnancy weight gain will be assessed according to the Institute of Medicine BMI criteria for pregnant women. Gestational Diabetes Mellitus will be diagnosed according to the National Institute for Health and Care Excellence Diabetes in Pregnancy guidelines. Pregnancy and delivery complications will be obtained from the mother's medical records. The presence of the following obstetric and perinatal complications will be recorded: excessive weight gain, gestational diabetes, hypertension, eclampsia, spontaneous early and late abortion, spontaneous and iatrogenic preterm delivery or preterm premature rupture of membranes. Venous blood samples will be obtained at the baseline and at each gestational period in correspondence of the routinely visit for ultrasound at 11-13 gestational weeks, 20-22 weeks and 30-32 weeks. Blood will be processed and aliquots of serum, plasma ethylenediaminetetraacetic acid and buffy coats for DNA extraction will be obtained. Longitudinal association analysis will be performed using dietary mother habits before and during pregnancy as exposure and maternal health (weight gain, blood pressure, metabolic parameters) and pregnancy complications as outcomes. Seven measurements will be taken at each visit to measure foetal growth: Biparietal and Occipito-Frontal Diameters; Head Circumference; Transverse abdominal diameter; Anterio-posterior abdominal diameter; Abdominal Circumference and Femur Length. Intrauterine growth restriction will be defined as Delphi criteria. At birth the following parameters will be recorded in new-born to evaluate growth and development by trained nurses using standardized protocols: Apgar score, birthweight, length, upper arm length, upper thigh length, head circumference, abdominal circumference, skinfold thickness. Birthweight and gestational age at delivery will be used to categorize each neonate as small-for-gestational age, appropriate-for-gestational age, or large-for-gestational age, using a sex-specific reference. Gestational age will be confirmed through a first-trimester ultrasound. Preterm birth will be defined as births <37 weeks of gestation. The presence of the following perinatal complications will be recorded: neonatal acidosis, low Apgar score, perinatal mortality or presence of any major neonatal morbidity. Offspring development will be assessed at 6, 12, 18, 24 months of age for each baby. Mothers will report i) breastfeeding and weaning of the baby; ii) anthropometric assessments at each paediatric periodical check, iii) measures of cognitive development like age (days) at first word, age at object manipulation, level of social interactions of the baby and ability to imitate/respond to the language of adults, iv) sensory-related skills like ability to discriminate familial sounds and recognize familial faces (low/medium/high) and iv) any medical issue of the baby. Moreover, to evaluate neuro-cognitive development the investigators will use the Bayley Scales of Infant Development (BSID-II) score, the most widely used test of infant development. To understand whether maternal dietary habits (exposure) are associated with epigenetic changes in the new-born (outcome) and if this process is driven by the inflammation profile of the mother. To understand if new-born epigenetics is associated with infant physical and neurocognitive development in the following 2 years. After delivery, the investigators will collect umbilical cord blood and saliva samples from 2000 new-born using standard procedures. DNA will be extracted and after bisulfite conversion of DNA, Genome-wide methylation analysis will be performed. Analyses will be carried out through common statistical software like R and Statistical Analysis Software. Despite the difficulty of disentangling risk factors, the period of in utero development is one of the most critical windows during which adverse conditions and exposures may influence the growth and development of the foetus, as well as its postnatal developmental and behavioural outcomes. Prenatal and early postnatal periods are therefore crucial to identify critical windows of susceptibility. The investigators expect to find a direct association between dietary habits of the mother before and during pregnancy with maternal and new-born health, possibly mediated by inflammation pattern of the mother, that may result in changes of methylation patterns of the new-born, two secondary mechanisms involved in pregnancy and perinatal complications and foetus development.
|
Influence of Mediterranean Dietary Habits on Pregnancy and Foetus Development: the Role of Epigenetics and Inflammation
|
Pregnancy Outcomes, Fetal Development, Infant Development
|
Inclusion Criteria:~pregnant women attending the Units of Obstetrics and Gynecology at Neuromed Clinical Research Network~women within the first trimester of pregnancy~women who express the willing to deliver at the aforementioned operating units~Exclusion Criteria:~pregnancy with foetuses with known chromosomal or congenital malformation~history of inflammatory disease~use of immunosuppressant drugs~pre-existing diabetes or hypertension~conception by heterologous artificial insemination~malabsorptive bariatric surgery~eating disorders
|
18 Years
|
50 Years
|
Female
| null |
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| obstetric and perinatal complications | Pregnancy and delivery complications will be obtained from the mother's medical records. The presence of the following obstetric and perinatal complications will be recorded: excessive weight gain (kg), gestational diabetes (n,%), hypertension (n, %) , eclampsia (n, %), spontaneous early and late abortion (n, %), spontaneous and iatrogenic preterm delivery or preterm premature rupture of membranes (n, %). | 9 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| new-born growth and development | Seven measurements will be taken at each visit to measure foetal growth by using fetal ultrasound examination: Biparietal and Occipito-Frontal Diameters (in cm); Head Circumference (in cm); Transverse abdominal diameter (in cm); Anterio-posterior abdominal diameter (in cm); Abdominal Circumference (in cm) and Femur Length (in cm). Intrauterine growth restriction will be defined as Delphi criteria. At birth to evaluate growth and development by trained nurses using standardized protocols: Apgar score, birthweight (in kg), length (in cm), upper arm length (in cm), upper thigh length (in cm), head circumference (in cm), abdominal circumference (in cm). Birthweight (in kg) and gestational age (in weeks) at delivery will be used to categorize each neonate as small-for-gestational age, appropriate-for-gestational age, or large-for-gestational age, using a sex-specific reference. Gestational age (in weeks) will be confirmed through a first-trimester ultrasound examination. | 9 months |
|
Mediterranean Diet on Pregnancy and Foetus Development
Study Overview
=================
Brief Summary
-----------------
The Mediterranean-style diet has been associated with longevity, long-life wellbeing, lower risk of cardiovascular disease, cancer, obesity, and metabolic syndrome. Research is pointing to the benefits that MeD could have in pregnant. Pregnancy is a very complex period and recently, the attention has been focused on the possibility that healthy dietary patterns positively influence pregnancy and the development of organs in the offspring. The mechanisms through which MeD influences pregnancy and fetal growth may partly depend on its antinflammatory properties and possibly on changes in epigenetic mechanisms. Systemic inflammation might contribute to the association between maternal obesity and less favorable neurodevelopmental outcomes. The investigators aim to define how maternal adhesion to MeD may affect pregnancy and new-born development, hence representing a notable burden from a public health and social perspective. Main objective of this project is to build up a birth cohort suitable to investigate the role of maternal dietary habits on maternal and new-born health, with special focus on MeD and its possible mechanism of action through epigenetic and inflammation changes. To establish a mother/new-born cohort, collect detailed information on maternal dietary habits and set-up a biobank of biological samples to evaluate the association between dietary habits and pregnancy outcomes. The investigators will recruit 2000 pairs (mother, new-born) in different obstetrics departments. To investigate the association between maternal dietary habits, foetal growth and offspring development and possible mediation by the inflammation profile of the mother. To understand whether maternal dietary habits are associated with epigenetic changes in the offspring and if this process is driven by the inflammation profile of the mother. Venous blood samples will be obtained at the baseline and at each gestational period for ultrasound at 11-13 gestational weeks, 20-22 weeks and 30-32 weeks. Women will be followed-up with standard clinical and 2D ultrasound examinations at gestational weeks 11-13, 20-22 and 30-32 to evaluate the fetal growth. Offspring development will be assessed at 6, 12, 18, 24 months of age. After delivery, the investigators will collect umbilical cord blood and saliva samples from new-born using standard procedures. To understand if new-born epigenetics is associated with infant physical and neurocognitive development in the following 2 years.
Detailed Description
-----------------
The Mediterranean diet (MeD) is an eating pattern typical of the Mediterranean basin and is characterized by a wide consumption of plant foods, cereals, legumes, fish, olive oil as main fat source, and moderate wine consumption.The Mediterranean-style diet has been associated with longevity, long-life wellbeing, reduced risk of cardiovascular disease, cancer, obesity, and metabolic syndrome. Research is now pointing to the benefits that adherence to a MeD could have in women, while pregnant. Pregnancy, indeed, is a very complex period where growth, development, and maturity take place. The future body, in addition to increasing its cellular mass, progressively acquires functional capabilities that would permit it to live and grow out of the mother's womb. The mechanisms through which MeD influences pregnancy and foetal growth may partly depend on its antinflammatory properties and possibly on changes in epigenetic mechanisms. Indeed, changes in epigenetic profiles could mediate links between specific intrauterine, early postnatal exposures and future mental health outcomes or immune status in offspring. Systemic inflammation might contribute to the observed association between maternal obesity and less favourable neurodevelopmental outcomes. Studies have demonstrated that DNA methylation is linked to an increased inflammatory response as well as increased risk of chronic disease. Still, there is a scarcity of studies analysing how maternal nutrition influences health and development outcomes in new-born, and how it alters potentially underlying molecular pathways. Here the investigators aim to better define how maternal adhesion to MeD may affect pregnancy and new-born development, which, in turn, affect the risk of disease during adulthood, hence representing a notable burden from a public health and social perspective. Should this hypothesis be confirmed, our findings may allow developing specific and targeted public health interventions, possibly personalized programs based on the peculiar characteristics shown by each pair (mother/new-born). To establish a mother/new-born cohort, collect detailed information on maternal dietary habits and set-up a biobank of biological samples to evaluate the association between dietary habits and pregnancy outcomes. The investigators will recruit 2000 pairs (mother, new-born) in different obstetrics departments of the Neuromed Clinical Research Network. To investigate the association between maternal dietary habits, foetal growth and offspring development and possible mediation by the inflammation profile of the mother. To understand whether maternal dietary habits (exposure) are associated with epigenetic changes in the offspring (outcome) and if this process is driven by the inflammation profile of the mother. To understand if new-born epigenetics is associated with infant physical and neurocognitive development in the following 2 years. The study population consists of pregnant women attending the Units of Obstetrics and Gynecology at Neuromed Clinical Research Network (Casa di Cura Villa del Sole, Salerno, Istituto Clinico mediterraneo, Agropoli (SA), Casa di Cura Villa dei Platani, Avellino e Clinica Mediterranea, Napoli). Inclusion into the study takes place during the first prenatal visit and within the first trimester of pregnancy, and involves women who express the willing to deliver at the aforementioned operating units. All recruited women will sign an informed consent to participate in the study and an informed consent for genetic studies. Each woman, as well as the father of the child, will sign the written consent to processing of personal and genetic data of their new-born. Exclusion criteria are: pregnancy with foetuses with known chromosomal or congenital malformation, history of inflammatory disease, use of immunosuppressant drugs, pre-existing diabetes or hypertension, conception by heterologous artificial insemination, malabsorptive bariatric surgery, eating disorders. Dietary habits will be assessed by one-year recall food frequency questionnaire at baseline and by a 24-hour dietary recall interview for a total of 7 days at three different time points at 11-13 gestational weeks, 20-22 weeks and 30-32 weeks. To monitor dietary habits during pregnancy in real time an Ecological Momentary Assessment will be used, based on a signal-contingent approach, so that women will be solicited to record their dietary consumption and other information at semifixed intervals. From both questionnaires, the investigators will calculate the Mediterranean Diet Score, the total Food Antioxidant Content (FAC) score, the Polyphenols Antioxidant Content (PAC) score, the inflammatory potential of the diet and extract micro and macronutrients daily intakes. Food processing will be evaluated by specific classification. Information on physiological and pathological history and other lifestyles (sleep characteristics, physical activity, smoking habits) will be obtained by validated questionnaires. Physical activity will be assessed using the Pregnancy Physical Activity Questionnaire (PPAQ). Maternal anthropometric assessment (height, weight, waist circumference and blood pressure) will be measured following standard techniques. Pre-pregnancy and post-partum weights will be evaluated according to World Health Organization classification criteria for body mass index (BMI). The rate of pregnancy weight gain will be assessed according to the Institute of Medicine BMI criteria for pregnant women. Gestational Diabetes Mellitus will be diagnosed according to the National Institute for Health and Care Excellence Diabetes in Pregnancy guidelines. Pregnancy and delivery complications will be obtained from the mother's medical records. The presence of the following obstetric and perinatal complications will be recorded: excessive weight gain, gestational diabetes, hypertension, eclampsia, spontaneous early and late abortion, spontaneous and iatrogenic preterm delivery or preterm premature rupture of membranes. Venous blood samples will be obtained at the baseline and at each gestational period in correspondence of the routinely visit for ultrasound at 11-13 gestational weeks, 20-22 weeks and 30-32 weeks. Blood will be processed and aliquots of serum, plasma ethylenediaminetetraacetic acid and buffy coats for DNA extraction will be obtained. Longitudinal association analysis will be performed using dietary mother habits before and during pregnancy as exposure and maternal health (weight gain, blood pressure, metabolic parameters) and pregnancy complications as outcomes. Seven measurements will be taken at each visit to measure foetal growth: Biparietal and Occipito-Frontal Diameters; Head Circumference; Transverse abdominal diameter; Anterio-posterior abdominal diameter; Abdominal Circumference and Femur Length. Intrauterine growth restriction will be defined as Delphi criteria. At birth the following parameters will be recorded in new-born to evaluate growth and development by trained nurses using standardized protocols: Apgar score, birthweight, length, upper arm length, upper thigh length, head circumference, abdominal circumference, skinfold thickness. Birthweight and gestational age at delivery will be used to categorize each neonate as small-for-gestational age, appropriate-for-gestational age, or large-for-gestational age, using a sex-specific reference. Gestational age will be confirmed through a first-trimester ultrasound. Preterm birth will be defined as births <37 weeks of gestation. The presence of the following perinatal complications will be recorded: neonatal acidosis, low Apgar score, perinatal mortality or presence of any major neonatal morbidity. Offspring development will be assessed at 6, 12, 18, 24 months of age for each baby. Mothers will report i) breastfeeding and weaning of the baby; ii) anthropometric assessments at each paediatric periodical check, iii) measures of cognitive development like age (days) at first word, age at object manipulation, level of social interactions of the baby and ability to imitate/respond to the language of adults, iv) sensory-related skills like ability to discriminate familial sounds and recognize familial faces (low/medium/high) and iv) any medical issue of the baby. Moreover, to evaluate neuro-cognitive development the investigators will use the Bayley Scales of Infant Development (BSID-II) score, the most widely used test of infant development. To understand whether maternal dietary habits (exposure) are associated with epigenetic changes in the new-born (outcome) and if this process is driven by the inflammation profile of the mother. To understand if new-born epigenetics is associated with infant physical and neurocognitive development in the following 2 years. After delivery, the investigators will collect umbilical cord blood and saliva samples from 2000 new-born using standard procedures. DNA will be extracted and after bisulfite conversion of DNA, Genome-wide methylation analysis will be performed. Analyses will be carried out through common statistical software like R and Statistical Analysis Software. Despite the difficulty of disentangling risk factors, the period of in utero development is one of the most critical windows during which adverse conditions and exposures may influence the growth and development of the foetus, as well as its postnatal developmental and behavioural outcomes. Prenatal and early postnatal periods are therefore crucial to identify critical windows of susceptibility. The investigators expect to find a direct association between dietary habits of the mother before and during pregnancy with maternal and new-born health, possibly mediated by inflammation pattern of the mother, that may result in changes of methylation patterns of the new-born, two secondary mechanisms involved in pregnancy and perinatal complications and foetus development.
Official Title
-----------------
Influence of Mediterranean Dietary Habits on Pregnancy and Foetus Development: the Role of Epigenetics and Inflammation
Conditions
-----------------
Pregnancy Outcomes, Fetal Development, Infant Development
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: pregnant women attending the Units of Obstetrics and Gynecology at Neuromed Clinical Research Network women within the first trimester of pregnancy women who express the willing to deliver at the aforementioned operating units Exclusion Criteria: pregnancy with foetuses with known chromosomal or congenital malformation history of inflammatory disease use of immunosuppressant drugs pre-existing diabetes or hypertension conception by heterologous artificial insemination malabsorptive bariatric surgery eating disorders
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years
Sexes Eligible for Study
-----------------
Female
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| obstetric and perinatal complications | Pregnancy and delivery complications will be obtained from the mother's medical records. The presence of the following obstetric and perinatal complications will be recorded: excessive weight gain (kg), gestational diabetes (n,%), hypertension (n, %) , eclampsia (n, %), spontaneous early and late abortion (n, %), spontaneous and iatrogenic preterm delivery or preterm premature rupture of membranes (n, %). | 9 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| new-born growth and development | Seven measurements will be taken at each visit to measure foetal growth by using fetal ultrasound examination: Biparietal and Occipito-Frontal Diameters (in cm); Head Circumference (in cm); Transverse abdominal diameter (in cm); Anterio-posterior abdominal diameter (in cm); Abdominal Circumference (in cm) and Femur Length (in cm). Intrauterine growth restriction will be defined as Delphi criteria. At birth to evaluate growth and development by trained nurses using standardized protocols: Apgar score, birthweight (in kg), length (in cm), upper arm length (in cm), upper thigh length (in cm), head circumference (in cm), abdominal circumference (in cm). Birthweight (in kg) and gestational age (in weeks) at delivery will be used to categorize each neonate as small-for-gestational age, appropriate-for-gestational age, or large-for-gestational age, using a sex-specific reference. Gestational age (in weeks) will be confirmed through a first-trimester ultrasound examination. | 9 months |
|
|||||
NCT03832478
|
Longitudinal Virtual Reality Use in Pediatric Surgical Procedures
|
This study aims to investigate the use of virtual reality guided mindfulness meditation to reduce the pre and post-operative anxiety and pain of pediatric surgical patients.
|
Pre-procedural anxiety in pediatric patients has been previously shown to increase the likelihood of family stressors, agitation, sleep disturbances, and negative behavioral changes. Post-procedural pain has been shown to negatively impact future interactions with healthcare personnel. The purpose of this study is to determine the feasibility of using guided mindfulness meditation through a non-invasive device (virtual reality headset) to manage pre-procedure anxiety and post-procedure anxiety and pain.
|
Longitudinal Virtual Reality Use in Pediatric Surgical Procedures
|
Anxiety, Pain, Pain, Postoperative
|
* Device: Virtual Reality Headset Given
|
Inclusion Criteria:~Have parental consent if under 18 or 18 and older but unable to provide own consent~Can comprehend instructions in English language~Is undergoing surgical procedure requiring general anesthesia at Lucile Packard Children's Hospital~Children that are normally healthy (ASA I) or have a mild systemic disease (ASA II, III)~Exclusion Criteria:~Children with significant cognitive impairment or developmental delays per parental report or H&P~Children with ASA IV (severe systemic disease that is a constant threat to life) or ASA V (unstable patients not expected to survive >24hours or without operation)~Children currently taking psychotropic mediations will be excluded from this study due to the affect emotion modulation~Children with history of seizures related to photosensitivity.
|
5 Years
|
25 Years
|
All
|
No
|
Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective observational study
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Children's Fear Scale | The Children's Fear Scale (McMurty et al., 2011) is a self-report scale that uses cartoon depictions of faces to quantify on a 0-4 scale how scared a child is at the given moment. | Before and after every use of the app (from date of enrollment to surgical procedure, up to 8 weeks. If patient has not undergone surgical procedure by 8 weeks, participation in study will be concluded and subject censored during data analysis) |
| Change in Faces Pain Scale | The Faces Pain Scale (Hicks et al., 2001) is a self-report scale that uses cartoon depictions of faces to quantify on a 0-10 scale how much pain a child is experiencing at the given moment. | Before and after every use of the app (from date of enrollment to surgical procedure, up to 8 weeks. If patient has not undergone surgical procedure by 8 weeks, participation in study will be concluded and subject censored during data analysis) |
| Change in Anxiety Scale | A self-report question on a 1-5 scale will be asked to assess how much anxiety a child is experiencing at the given moment. | Before and after every use of the app (from date of enrollment to surgical procedure, up to 8 weeks. If patient has not undergone surgical procedure by 8 weeks, participation in study will be concluded and subject censored during data analysis) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient and Parent Satisfaction Surveys | Parents, and patients will be given self-report survey questions asking about their satisfaction with the technology, the patients' immersion with the technology, and desire for use in future procedures. Questions will be answered on a 1-5 scale . | Satisfaction surveys will be administered at the time of study completion (when the patient has completed his/her surgical procedure and is ready for hospital discharge/or 30 days post-procedure, whichever occurs first) |
| Clinician Satisfaction Surveys | Surgeons and anesthesiologists will be given self-report survey questions asking about their satisfaction with the technology, the patients' immersion with the technology, and desire for use in future procedures. Questions will be answered on a 1-5 scale . | Satisfaction survey will be administered to physicians within 48 hours of procedure completion. Physicians may return surveys up to one month post-procedure. |
|
Virtual Reality, Meditation, Mindfulness Meditation, Guided Mindfulness Meditation, Anxiety, Pain, Postoperative pain
|
Pain, Postoperative, Postoperative Complications, Pathologic Processes, Pain, Neurologic Manifestations
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Virtual Reality Headset Given<br>Virtual Reality headset (Samsung Gear VR) with mindfulness meditation app is given for patient use prior to surgery date and for duration of postoperative stay. | Device: Virtual Reality Headset Given<br>* Samsung Gear VR Headset with guided mindfulness meditation app<br>|
|
Longitudinal Virtual Reality Use in Pediatric Surgical Procedures
Study Overview
=================
Brief Summary
-----------------
This study aims to investigate the use of virtual reality guided mindfulness meditation to reduce the pre and post-operative anxiety and pain of pediatric surgical patients.
Detailed Description
-----------------
Pre-procedural anxiety in pediatric patients has been previously shown to increase the likelihood of family stressors, agitation, sleep disturbances, and negative behavioral changes. Post-procedural pain has been shown to negatively impact future interactions with healthcare personnel. The purpose of this study is to determine the feasibility of using guided mindfulness meditation through a non-invasive device (virtual reality headset) to manage pre-procedure anxiety and post-procedure anxiety and pain.
Official Title
-----------------
Longitudinal Virtual Reality Use in Pediatric Surgical Procedures
Conditions
-----------------
Anxiety, Pain, Pain, Postoperative
Intervention / Treatment
-----------------
* Device: Virtual Reality Headset Given
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have parental consent if under 18 or 18 and older but unable to provide own consent Can comprehend instructions in English language Is undergoing surgical procedure requiring general anesthesia at Lucile Packard Children's Hospital Children that are normally healthy (ASA I) or have a mild systemic disease (ASA II, III) Exclusion Criteria: Children with significant cognitive impairment or developmental delays per parental report or H&P Children with ASA IV (severe systemic disease that is a constant threat to life) or ASA V (unstable patients not expected to survive >24hours or without operation) Children currently taking psychotropic mediations will be excluded from this study due to the affect emotion modulation Children with history of seizures related to photosensitivity.
Ages Eligible for Study
-----------------
Minimum Age: 5 Years
Maximum Age: 25 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective observational study
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Virtual Reality Headset Given<br>Virtual Reality headset (Samsung Gear VR) with mindfulness meditation app is given for patient use prior to surgery date and for duration of postoperative stay. | Device: Virtual Reality Headset Given<br>* Samsung Gear VR Headset with guided mindfulness meditation app<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Children's Fear Scale | The Children's Fear Scale (McMurty et al., 2011) is a self-report scale that uses cartoon depictions of faces to quantify on a 0-4 scale how scared a child is at the given moment. | Before and after every use of the app (from date of enrollment to surgical procedure, up to 8 weeks. If patient has not undergone surgical procedure by 8 weeks, participation in study will be concluded and subject censored during data analysis) |
| Change in Faces Pain Scale | The Faces Pain Scale (Hicks et al., 2001) is a self-report scale that uses cartoon depictions of faces to quantify on a 0-10 scale how much pain a child is experiencing at the given moment. | Before and after every use of the app (from date of enrollment to surgical procedure, up to 8 weeks. If patient has not undergone surgical procedure by 8 weeks, participation in study will be concluded and subject censored during data analysis) |
| Change in Anxiety Scale | A self-report question on a 1-5 scale will be asked to assess how much anxiety a child is experiencing at the given moment. | Before and after every use of the app (from date of enrollment to surgical procedure, up to 8 weeks. If patient has not undergone surgical procedure by 8 weeks, participation in study will be concluded and subject censored during data analysis) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient and Parent Satisfaction Surveys | Parents, and patients will be given self-report survey questions asking about their satisfaction with the technology, the patients' immersion with the technology, and desire for use in future procedures. Questions will be answered on a 1-5 scale . | Satisfaction surveys will be administered at the time of study completion (when the patient has completed his/her surgical procedure and is ready for hospital discharge/or 30 days post-procedure, whichever occurs first) |
| Clinician Satisfaction Surveys | Surgeons and anesthesiologists will be given self-report survey questions asking about their satisfaction with the technology, the patients' immersion with the technology, and desire for use in future procedures. Questions will be answered on a 1-5 scale . | Satisfaction survey will be administered to physicians within 48 hours of procedure completion. Physicians may return surveys up to one month post-procedure. |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Virtual Reality, Meditation, Mindfulness Meditation, Guided Mindfulness Meditation, Anxiety, Pain, Postoperative pain
|
NCT00430144
|
Belotecan (CKD-602) in Recurrent or Progressive Carcinoma of Uterine Cervix
|
-list item one, The purpose of this study is to evaluate the overall response rate of belotecan (CKD-602) in recurrent or progressive carcinoma of uterine cervix
|
list item one, to evaluate toxicities of Belotecan~list item two, to evaluate duration of primary response for responding patients~list item three, to evaluate time to disease progression~list item four, to evaluate progression free survival and overall survival.
|
A Phase II Study of Belotecan (CKD-602) in Recurrent or Progressive Carcinoma of Uterine Cervix
|
Cervical Cancer
|
* Drug: Belotecan(CKD-602)
|
Inclusion Criteria:~Histologically confirmed, patients with recurrent uterine cervical carcinoma who were unsuitable candidates for curative treatment with surgery and/or radiotherapy.~One of the following histologic types~Squamous cell carcinoma~Adenocarcinoma~Adenosquamous carcinoma~Clinically measurable disease~Performance status of 0, 1, 2 on the ECOG criteria~Exclusion Criteria:~Histology of neuroendocrine tumors~Patient previously treated with topoisomerase-I inhibitor
|
18 Years
| null |
Female
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall response rate of belotecan (CKD-602) | | 1 week before the start of Cycle 4, 3 weeks later Cycle 6 or at discontinuation of study treatment, and then at least every 3 months |
|
Belotecan, Topoisomerase I Inhibitors, Topoisomerase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CKD-602<br> | Drug: Belotecan(CKD-602)<br>* Belotecan was administrated at 0.5 mg/m(2)/day for 5 consecutive days every 3-week cycle<br>* Other names: Camptobel;|
|
Belotecan (CKD-602) in Recurrent or Progressive Carcinoma of Uterine Cervix
Study Overview
=================
Brief Summary
-----------------
-list item one, The purpose of this study is to evaluate the overall response rate of belotecan (CKD-602) in recurrent or progressive carcinoma of uterine cervix
Detailed Description
-----------------
list item one, to evaluate toxicities of Belotecan list item two, to evaluate duration of primary response for responding patients list item three, to evaluate time to disease progression list item four, to evaluate progression free survival and overall survival.
Official Title
-----------------
A Phase II Study of Belotecan (CKD-602) in Recurrent or Progressive Carcinoma of Uterine Cervix
Conditions
-----------------
Cervical Cancer
Intervention / Treatment
-----------------
* Drug: Belotecan(CKD-602)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed, patients with recurrent uterine cervical carcinoma who were unsuitable candidates for curative treatment with surgery and/or radiotherapy. One of the following histologic types Squamous cell carcinoma Adenocarcinoma Adenosquamous carcinoma Clinically measurable disease Performance status of 0, 1, 2 on the ECOG criteria Exclusion Criteria: Histology of neuroendocrine tumors Patient previously treated with topoisomerase-I inhibitor
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
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CKD-602<br> | Drug: Belotecan(CKD-602)<br>* Belotecan was administrated at 0.5 mg/m(2)/day for 5 consecutive days every 3-week cycle<br>* Other names: Camptobel;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall response rate of belotecan (CKD-602) | | 1 week before the start of Cycle 4, 3 weeks later Cycle 6 or at discontinuation of study treatment, and then at least every 3 months |
|
||
NCT04306887
|
A Study of TQ-B3101 in Subjects With Relapsed or Refractory Anaplastic Large Cell Lymphoma (ALCL)
|
The objective of this study is to evaluate efficacy and safety of TQ-B3101 in subjects with relapsed/refractory anaplastic large cell lymphoma (ALCL) .
|
A Open-label, Single-arm Phase Ⅱ Clinical Trial of TQ-B3101 in Subjects With Relapsed/Refractory Anaplastic Large Cell Lymphoma (ALCL)
|
Relapsed/Refractory Anaplastic Large Cell Lymphoma (ALCL)
|
* Drug: TQ-B3101 capsule
|
Inclusion Criteria:~-1.Female or male, 10 years and older. 2.Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2. 3.Histologically or cytologically confirmed ALK positive relapsed or refractory Anaplastic Large Cell Lymphoma.~4.At least one measurable lesion. 5.Life expectancy ≥ 3 months. 6.Adequate organ system function. 7.Understood and signed an informed consent form.~Exclusion Criteria:~1.Primary cutaneous anaplastic large cell lymphoma. 2.Other malignancies occurred within 5 years, with exception of cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors.~3.Has received ALK inhibitor. 4.Has received an allogeneic stem cell transplant. 5.Has received autologous stem cell transplant within 12 weeks before the first administration.~6.Has received other anti-tumor medications within 4 weeks of the first administration.~7.Has received major surgery within 4 weeks before the first administration. 8.Has received any curative radiotherapy or minor surgery within 2 weeks before the first administration.~9.Has received palliative radiation therapy within 2 days before the first administration.~10.Has adverse events caused by previous therapy except alopecia that did not recover to ≤grade 1.~11.Has uncontrollable congestive heart failure. 12.According to the judgement of the researchers, there are other factors that subjects are not suitable for the study.
|
10 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Percentage of subjects achieving complete response (CR) and partial response (PR) according to Lugano response criteria. | Baseline up to 18 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) within 2-year | PFS was defined as the time from the date of study enrollment to the date of the first of the following events, objective disease progression or death due to any cause. | Baseline up to 24 months |
| Overall survival (OS) within 2-year | OS was defined as the time from the date of study enrollment to the date of death due to any cause. Survival time was censored at the date of last contact for patients who were still alive or lost to follow-up. | Baseline up to 24 months |
|
Lymphoma, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Anaplastic, Neoplasms by Histologic Type, Neoplasms, Lymphoproliferative Disorders, Lymphatic Diseases, Immunoproliferative Disorders, Immune System Diseases, Lymphoma, T-Cell
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TQ-B3101<br>TQ-B3101 capsule administered orally. | Drug: TQ-B3101 capsule<br>* Escalating doses starting at 200 mg bid.<br>|
|
A Study of TQ-B3101 in Subjects With Relapsed or Refractory Anaplastic Large Cell Lymphoma (ALCL)
Study Overview
=================
Brief Summary
-----------------
The objective of this study is to evaluate efficacy and safety of TQ-B3101 in subjects with relapsed/refractory anaplastic large cell lymphoma (ALCL) .
Official Title
-----------------
A Open-label, Single-arm Phase Ⅱ Clinical Trial of TQ-B3101 in Subjects With Relapsed/Refractory Anaplastic Large Cell Lymphoma (ALCL)
Conditions
-----------------
Relapsed/Refractory Anaplastic Large Cell Lymphoma (ALCL)
Intervention / Treatment
-----------------
* Drug: TQ-B3101 capsule
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: -1.Female or male, 10 years and older. 2.Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2. 3.Histologically or cytologically confirmed ALK positive relapsed or refractory Anaplastic Large Cell Lymphoma. 4.At least one measurable lesion. 5.Life expectancy ≥ 3 months. 6.Adequate organ system function. 7.Understood and signed an informed consent form. Exclusion Criteria: 1.Primary cutaneous anaplastic large cell lymphoma. 2.Other malignancies occurred within 5 years, with exception of cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors. 3.Has received ALK inhibitor. 4.Has received an allogeneic stem cell transplant. 5.Has received autologous stem cell transplant within 12 weeks before the first administration. 6.Has received other anti-tumor medications within 4 weeks of the first administration. 7.Has received major surgery within 4 weeks before the first administration. 8.Has received any curative radiotherapy or minor surgery within 2 weeks before the first administration. 9.Has received palliative radiation therapy within 2 days before the first administration. 10.Has adverse events caused by previous therapy except alopecia that did not recover to ≤grade 1. 11.Has uncontrollable congestive heart failure. 12.According to the judgement of the researchers, there are other factors that subjects are not suitable for the study.
Ages Eligible for Study
-----------------
Minimum Age: 10 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: TQ-B3101<br>TQ-B3101 capsule administered orally. | Drug: TQ-B3101 capsule<br>* Escalating doses starting at 200 mg bid.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Percentage of subjects achieving complete response (CR) and partial response (PR) according to Lugano response criteria. | Baseline up to 18 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) within 2-year | PFS was defined as the time from the date of study enrollment to the date of the first of the following events, objective disease progression or death due to any cause. | Baseline up to 24 months |
| Overall survival (OS) within 2-year | OS was defined as the time from the date of study enrollment to the date of death due to any cause. Survival time was censored at the date of last contact for patients who were still alive or lost to follow-up. | Baseline up to 24 months |
|
||
NCT02838810
|
The Optimizing Treatment of PegIFN Alfa in HBeAg-negative CHB Patients With Low Level HBsAg
|
As HBsAg clearance is uncommon in chronic hepatitis B (CHB) patients on nucleoside analogues (NAs) therapy. The purpose of this study is to optimize HBsAg clearance in CHB Patients with sequential treatment of pegylated interferon alpha and NAs.
|
In order to optimize HBsAg clearance in CHB patients with low level HBsAg, the investigators enrolled patients who had received, and responded to, NAs for more than 12 months(see the inclusion criteria), and patients are switched to receive peginterferon alfa-2a 180 micrograms/week or peginterferon alfa-2b 80 micrograms/week. The longest course of treatment is 96 weeks. After treatment, patients will be followed up for 24 weeks. During the 96 weeks course of treatment, HBsAg level will be monitored. When HBsAg level is less than 0.05 IU/mL, peginterferon treatment will be stopped and patients will receive 24 weeks follow up.
|
The Optimizing Treatment of PegIFN Alfa in HBeAg-negative Chronic Hepatitis B Patients With Low Level HBsAg
|
Chronic Hepatitis B
|
* Drug: peginterferon alfa
* Drug: Nucleoside analogues
|
Inclusion Criteria:~CHB patients who had received single NAs for more than 12 months.~Hepatitis B e antigen (HBeAg)-negative.~Hepatitis B surface antigen (HBsAg) positive and <1000 IU/mL.~Hepatitis B virus DNA <100 IU/mL.~Exclusion Criteria:~Patients with liver cirrhosis, Hepatocellular Carcinoma or AFP >2 ULN or other malignancies.~Patients with other factors causing liver diseases.~Pregnant and lactating women.~Patients with concomitant HIV infection or congenital immune deficiency diseases.~Patients with diabetes, autoimmune diseases.~Patients with important organ dysfunctions.~Patients with serious complications (e.g., infection, hepatic encephalopathy, hepatorenal syndrome, gastrointestinal bleeding.)~Patients who receive antineoplastic or immunomodulatory therapy in the past 12 months.~Patients with a previous use of IFN anti hepatitis B virus treatment or have NAs drug resistance.~Patients who can't come back to clinic for follow-up on schedule.
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBsAg Clearance | Percentage of Participants with HBsAg <0.05 IU/mL. | 120 weeks |
| HBsAg Seroconversion | Percentage of Participants with HBsAg <0.05 IU/mL and anti-HBsAg positive. | 120 weeks |
|
peginterferon alfa, Chronic Hepatitis B
|
Hepatitis A, Hepatitis B, Hepatitis B, Chronic, Hepatitis, Hepatitis, Chronic, Liver Diseases, Digestive System Diseases, Hepatitis, Viral, Human, Virus Diseases, Infections, Enterovirus Infections, Picornaviridae Infections, RNA Virus Infections, Blood-Borne Infections, Communicable Diseases, Hepadnaviridae Infections, DNA Virus Infections, Chronic Disease, Disease Attributes, Pathologic Processes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>CHB patients with low level HBsAg.Hepatitis B e antigen (HBeAg)-negative CHB patients who had received NAs for more than 12 months, with HBsAg <1000 IU/mL and Hepatitis B virus DNA <100 IU/mL, are to receive peginterferon alfa-2a 180 micrograms/week or peginterferon alfa-2b 80 micrograms/week. The longest course of treatment is 96 weeks. After treatment, patients will be followed up for 24 weeks. During the 96 weeks course of treatment, HBsAg level will be monitored. When HBsAg level is less than 0.05 IU/mL, peginterferon treatment will be stopped and patients will receive 24 weeks follow up. | Drug: peginterferon alfa<br>* peginterferon alfa-2b or peginterferon alfa-2a<br>|
| Other: Control<br>Patients do not need to change their NAs treatment. | Drug: Nucleoside analogues<br>* Nucleoside analogues<br>* Other names: NAs;|
|
The Optimizing Treatment of PegIFN Alfa in HBeAg-negative CHB Patients With Low Level HBsAg
Study Overview
=================
Brief Summary
-----------------
As HBsAg clearance is uncommon in chronic hepatitis B (CHB) patients on nucleoside analogues (NAs) therapy. The purpose of this study is to optimize HBsAg clearance in CHB Patients with sequential treatment of pegylated interferon alpha and NAs.
Detailed Description
-----------------
In order to optimize HBsAg clearance in CHB patients with low level HBsAg, the investigators enrolled patients who had received, and responded to, NAs for more than 12 months(see the inclusion criteria), and patients are switched to receive peginterferon alfa-2a 180 micrograms/week or peginterferon alfa-2b 80 micrograms/week. The longest course of treatment is 96 weeks. After treatment, patients will be followed up for 24 weeks. During the 96 weeks course of treatment, HBsAg level will be monitored. When HBsAg level is less than 0.05 IU/mL, peginterferon treatment will be stopped and patients will receive 24 weeks follow up.
Official Title
-----------------
The Optimizing Treatment of PegIFN Alfa in HBeAg-negative Chronic Hepatitis B Patients With Low Level HBsAg
Conditions
-----------------
Chronic Hepatitis B
Intervention / Treatment
-----------------
* Drug: peginterferon alfa
* Drug: Nucleoside analogues
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: CHB patients who had received single NAs for more than 12 months. Hepatitis B e antigen (HBeAg)-negative. Hepatitis B surface antigen (HBsAg) positive and <1000 IU/mL. Hepatitis B virus DNA <100 IU/mL. Exclusion Criteria: Patients with liver cirrhosis, Hepatocellular Carcinoma or AFP >2 ULN or other malignancies. Patients with other factors causing liver diseases. Pregnant and lactating women. Patients with concomitant HIV infection or congenital immune deficiency diseases. Patients with diabetes, autoimmune diseases. Patients with important organ dysfunctions. Patients with serious complications (e.g., infection, hepatic encephalopathy, hepatorenal syndrome, gastrointestinal bleeding.) Patients who receive antineoplastic or immunomodulatory therapy in the past 12 months. Patients with a previous use of IFN anti hepatitis B virus treatment or have NAs drug resistance. Patients who can't come back to clinic for follow-up on schedule.
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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>CHB patients with low level HBsAg.Hepatitis B e antigen (HBeAg)-negative CHB patients who had received NAs for more than 12 months, with HBsAg <1000 IU/mL and Hepatitis B virus DNA <100 IU/mL, are to receive peginterferon alfa-2a 180 micrograms/week or peginterferon alfa-2b 80 micrograms/week. The longest course of treatment is 96 weeks. After treatment, patients will be followed up for 24 weeks. During the 96 weeks course of treatment, HBsAg level will be monitored. When HBsAg level is less than 0.05 IU/mL, peginterferon treatment will be stopped and patients will receive 24 weeks follow up. | Drug: peginterferon alfa<br>* peginterferon alfa-2b or peginterferon alfa-2a<br>|
| Other: Control<br>Patients do not need to change their NAs treatment. | Drug: Nucleoside analogues<br>* Nucleoside analogues<br>* Other names: NAs;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBsAg Clearance | Percentage of Participants with HBsAg <0.05 IU/mL. | 120 weeks |
| HBsAg Seroconversion | Percentage of Participants with HBsAg <0.05 IU/mL and anti-HBsAg positive. | 120 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
peginterferon alfa, Chronic Hepatitis B
|
|
NCT04894292
|
The Effect of Adenomoyosis on Pregnancy Outcomes
|
Adenomyosis can be defined as the settling of endometrial gland cells in the myometrium and deformity in the uterus and the prevalence of adenomyosis is according to the patient population and countries around 20%. There are recent publications reporting that this rate increases up to 50% in women dealing with infertility. In adenomyosis, where uterine morphology is affected, it is not thought that the uterus, which is expected to provide many morphological adaptations during pregnancy, will not be affected. Therefore, in this prospective study, it was planned to investigate the effects of adenomyosis during pregnancy.~For this study the presence of adenomyosis will be questioned by using ultrasonographic morphological uterine limitation (MUSA) in women who apply to the outpatient clinic with suspicion of pregnancy and undergo transvaginal ultrasonography for the diagnosis of pregnancy before sixth gestational week.~Patients will be divided into two groups according to the presence of adenomyosis and pregnancy complications such as preterm labor, premature rupture of membranes, cesarean section rates, preeclampsia, fetal malpresentation and preeclampsia will be compared between the groups.
|
Adverse Obstetrical Outcomes for Women With Adenomyosis
|
Adenomyosis, Pregnancy Complications
|
* Other: Non intervention
|
Inclusion Criteria:~Age between 18-35 years~Being diagnosed before the 6th gestational week~Having all pregnancy follow-ups and deliveries in our hospital~Exclusion Criteria:~Previous uterine surgery~Multiple pregnancies~Pregnant women with uterine malformations~Pregnant women with fetal anomalies~Those who got pregnant using assisted reproductive technique
|
18 Years
|
35 Years
|
Female
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy complication | Preterm labour | 15 month |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy complication | placental anomalies | 16 month |
| Pregnancy complication | preeclampsia, eclampsia | 17 month |
|
adenomyosis, pregnancy complications, MUSA classification, ultrasound
|
Pregnancy Complications, Adenomyosis, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Uterine Diseases, Genital Diseases, Female, Female Urogenital Diseases, Genital Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adenomyosis Group<br> | Other: Non intervention<br>* During the study there is no extra intervention planned for the participants.<br>|
| Non-adenomyosis Group<br> | Other: Non intervention<br>* During the study there is no extra intervention planned for the participants.<br>|
|
The Effect of Adenomoyosis on Pregnancy Outcomes
Study Overview
=================
Brief Summary
-----------------
Adenomyosis can be defined as the settling of endometrial gland cells in the myometrium and deformity in the uterus and the prevalence of adenomyosis is according to the patient population and countries around 20%. There are recent publications reporting that this rate increases up to 50% in women dealing with infertility. In adenomyosis, where uterine morphology is affected, it is not thought that the uterus, which is expected to provide many morphological adaptations during pregnancy, will not be affected. Therefore, in this prospective study, it was planned to investigate the effects of adenomyosis during pregnancy. For this study the presence of adenomyosis will be questioned by using ultrasonographic morphological uterine limitation (MUSA) in women who apply to the outpatient clinic with suspicion of pregnancy and undergo transvaginal ultrasonography for the diagnosis of pregnancy before sixth gestational week. Patients will be divided into two groups according to the presence of adenomyosis and pregnancy complications such as preterm labor, premature rupture of membranes, cesarean section rates, preeclampsia, fetal malpresentation and preeclampsia will be compared between the groups.
Official Title
-----------------
Adverse Obstetrical Outcomes for Women With Adenomyosis
Conditions
-----------------
Adenomyosis, Pregnancy Complications
Intervention / Treatment
-----------------
* Other: Non intervention
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 18-35 years Being diagnosed before the 6th gestational week Having all pregnancy follow-ups and deliveries in our hospital Exclusion Criteria: Previous uterine surgery Multiple pregnancies Pregnant women with uterine malformations Pregnant women with fetal anomalies Those who got pregnant using assisted reproductive technique
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?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adenomyosis Group<br> | Other: Non intervention<br>* During the study there is no extra intervention planned for the participants.<br>|
| Non-adenomyosis Group<br> | Other: Non intervention<br>* During the study there is no extra intervention planned for the participants.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy complication | Preterm labour | 15 month |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy complication | placental anomalies | 16 month |
| Pregnancy complication | preeclampsia, eclampsia | 17 month |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adenomyosis, pregnancy complications, MUSA classification, ultrasound
|
||
NCT05207878
|
Interhemispheric Connectivity and Compensation
|
The goal of this study is to determine which parts of the brain make it possible for some people to move skillfully with their left non-dominant hand.
|
This is a one-visit study, in which right-handed participants (individuals with unilateral peripheral nerve injury to the right upper limb, and healthy controls) will complete surveys and perform movement tasks. Movement tasks will be performed inside and outside a magnetic resonance imaging (MRI) scanner.~Some participants will also receive transcranial magnetic stimulation (TMS) to briefly interfere with these putative brain networks.
|
Interhemispheric Communication and Compensation in Peripheral Nerve Injury
|
Peripheral Nerve Injury Upper Limb, Healthy
|
* Other: STEGA-MRI
|
This study contains two groups: typical controls and patients. Participants will be matched by age and sex between the two groups. No randomization will occur.~A. Inclusion criteria (all participants):~Age ≥ 18~English speaking and reading~Able to fit in Prisma scanner bore (60 cm diameter)~Right hand dominant (self report, and Edinburgh handedness ≥ +40)~B. Inclusion criteria (patients only):~Chronic unilateral upper extremity peripheral nerve injury to the right side~Chronic defined as ≥ 6 months since injury~Upper extremity defined as hand, arm, or shoulder (including e.g. brachial plexus)~Injury defined as localized cause (e.g. mechanical/tumor, not distributed pathology), including compression~Some impairment to writing, requiring both of:~Difficulty writing, as determined by score 2+ (Mild+) on How much difficulty have you had in the last week with writing? (From Disabilities of the Arm, Shoulder, and Hand survey question #2)~Box and Blocks motor performance ≥1 standard deviation below the mean of age-matched healthy adults (Mathiowetz et al. 1985, AJOT).~C. Exclusion criteria (all participants)~Currently intoxicated or otherwise non-compliant~Chronic pain diagnosis unrelated to the nerve injury~Uncorrected visual impairment that interferes with ability to see drawings in MRI~Motor function diagnoses that affect function of the left hand, now or in past 2 years~Motor function diagnoses currently affecting the right hand, unrelated to the nerve injury~This is not meant to exclude a single event with complex consequences (e.g. nerve and tendon)~This is not meant to exclude multiple nerve injuries in the same arm, if each one is eligible (II.B.1)~This is meant to exclude e.g. injury and unrelated musculoskeletal disorder in same arm~Upper extremity surgery, including peripheral nerve surgery, within last 2 months~Contraindication for MRI~Contraindication for transcranial magnetic stimulation (TMS)~May exclude from TMS only (since not all participants undergo TMS), or exclude from full study~Amputation affecting any part of thumb, index, or middle fingers (including higher level, e.g. whole hand)~History of chronic cocaine use (based on medical record or volunteered; will not actively inquire)~Diagnosis of schizophrenia or other rare psychiatric disorder~This is not meant to exclude depression or anxiety~History of major neurological diagnosis, e.g. stroke, traumatic brain injury, Alzheimer's, Parkinson's~This is not meant to exclude concussion UNLESS < 6 months ago, or post-concussion syndrome (diagnosed or self-report)~D. Exclusion criteria (controls only)~1. Motor function diagnoses that affect function of either hand, now or in past 2 years
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: The only intervention is the movement task. All participants receive the same task.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BOLD (blood oxygen level dependent) signal in ROIs (regions of interest) | BOLD signal in key ROIs (primary motor and posterior parietal cortex). ROI selection may be revisited after preliminary data review (35 participants) | Day 1 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drawing smoothness | Velocity smoothness in STEGA-MRI (Standardized Tracing Evaluation and Grapheme Assessment - MRI version) task | Day 1 |
| Hand choice | Percentage of grasps made with right hand | Day 1 |
|
laterality of motor control, movement, functional magnetic resonance imaging, functional laterality
|
Peripheral Nerve Injuries, Peripheral Nervous System Diseases, Neuromuscular Diseases, Nervous System Diseases, Trauma, Nervous System, Wounds and Injuries
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Movement task<br>All participants perform the STEGA-MRI (standardized tracing evaluation & grapheme assessment - MRI) precision drawing task during fMRI scanning.~Motor assessments outside the MRI do not qualify as interventions. | Other: STEGA-MRI<br>* Precision drawing task (movement assessment)<br>|
|
Interhemispheric Connectivity and Compensation
Study Overview
=================
Brief Summary
-----------------
The goal of this study is to determine which parts of the brain make it possible for some people to move skillfully with their left non-dominant hand.
Detailed Description
-----------------
This is a one-visit study, in which right-handed participants (individuals with unilateral peripheral nerve injury to the right upper limb, and healthy controls) will complete surveys and perform movement tasks. Movement tasks will be performed inside and outside a magnetic resonance imaging (MRI) scanner. Some participants will also receive transcranial magnetic stimulation (TMS) to briefly interfere with these putative brain networks.
Official Title
-----------------
Interhemispheric Communication and Compensation in Peripheral Nerve Injury
Conditions
-----------------
Peripheral Nerve Injury Upper Limb, Healthy
Intervention / Treatment
-----------------
* Other: STEGA-MRI
Participation Criteria
=================
Eligibility Criteria
-----------------
This study contains two groups: typical controls and patients. Participants will be matched by age and sex between the two groups. No randomization will occur. A. Inclusion criteria (all participants): Age ≥ 18 English speaking and reading Able to fit in Prisma scanner bore (60 cm diameter) Right hand dominant (self report, and Edinburgh handedness ≥ +40) B. Inclusion criteria (patients only): Chronic unilateral upper extremity peripheral nerve injury to the right side Chronic defined as ≥ 6 months since injury Upper extremity defined as hand, arm, or shoulder (including e.g. brachial plexus) Injury defined as localized cause (e.g. mechanical/tumor, not distributed pathology), including compression Some impairment to writing, requiring both of: Difficulty writing, as determined by score 2+ (Mild+) on How much difficulty have you had in the last week with writing? (From Disabilities of the Arm, Shoulder, and Hand survey question #2) Box and Blocks motor performance ≥1 standard deviation below the mean of age-matched healthy adults (Mathiowetz et al. 1985, AJOT). C. Exclusion criteria (all participants) Currently intoxicated or otherwise non-compliant Chronic pain diagnosis unrelated to the nerve injury Uncorrected visual impairment that interferes with ability to see drawings in MRI Motor function diagnoses that affect function of the left hand, now or in past 2 years Motor function diagnoses currently affecting the right hand, unrelated to the nerve injury This is not meant to exclude a single event with complex consequences (e.g. nerve and tendon) This is not meant to exclude multiple nerve injuries in the same arm, if each one is eligible (II.B.1) This is meant to exclude e.g. injury and unrelated musculoskeletal disorder in same arm Upper extremity surgery, including peripheral nerve surgery, within last 2 months Contraindication for MRI Contraindication for transcranial magnetic stimulation (TMS) May exclude from TMS only (since not all participants undergo TMS), or exclude from full study Amputation affecting any part of thumb, index, or middle fingers (including higher level, e.g. whole hand) History of chronic cocaine use (based on medical record or volunteered; will not actively inquire) Diagnosis of schizophrenia or other rare psychiatric disorder This is not meant to exclude depression or anxiety History of major neurological diagnosis, e.g. stroke, traumatic brain injury, Alzheimer's, Parkinson's This is not meant to exclude concussion UNLESS < 6 months ago, or post-concussion syndrome (diagnosed or self-report) D. Exclusion criteria (controls only) 1. Motor function diagnoses that affect function of either hand, now or in past 2 years
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: The only intervention is the movement task. All participants receive the same task.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Movement task<br>All participants perform the STEGA-MRI (standardized tracing evaluation & grapheme assessment - MRI) precision drawing task during fMRI scanning. Motor assessments outside the MRI do not qualify as interventions. | Other: STEGA-MRI<br>* Precision drawing task (movement assessment)<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BOLD (blood oxygen level dependent) signal in ROIs (regions of interest) | BOLD signal in key ROIs (primary motor and posterior parietal cortex). ROI selection may be revisited after preliminary data review (35 participants) | Day 1 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drawing smoothness | Velocity smoothness in STEGA-MRI (Standardized Tracing Evaluation and Grapheme Assessment - MRI version) task | Day 1 |
| Hand choice | Percentage of grasps made with right hand | Day 1 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
laterality of motor control, movement, functional magnetic resonance imaging, functional laterality
|
NCT03671239
|
Rectal Microbicide Acceptability, Tolerability and Adherence
|
MTN-035 is a multi-site, randomized-sequence, three-period, open label crossover study that will enroll approximately 210 participants randomized (1:1:1:1:1:1) to one of six sequences of rectal microbicide placebo product application.
|
MTN-035 is a multi-site, randomized-sequence, three-period, open label crossover study that will enroll approximately 210 participants randomized (1:1:1:1:1:1) to one of six sequences of rectal microbicide placebo product application. At the start of each 4-week product use period, participants will receive either rectal inserts, rectal douches, or rectal suppositories and be instructed to use their assigned study product prior to each receptive anal intercourse (RAI) encounter during that period. Participants who do not have RAI in a given week will be asked to use the product without sex. There will be a 1-week washout period between each of the three product use periods. Participant follow-up will take approximately 3.5 months.
|
Acceptability, Tolerability, and Adherence of Three Rectal Microbicide Placebo Formulations Among HIV Seronegative Cisgender Men, Transgender Men and Transgender Women Who Engage in Receptive Anal Intercourse
|
HIV Prevention
|
* Behavioral: Placebo rectal insert
* Behavioral: Placebo rectal suppository
* Behavioral: Placebo rectal douche
|
Inclusion Criteria:~Men (cis or transgender) and TGW who are 18-35 years old at Screening, verified per site SOP.~Able and willing to provide written informed consent.~HIV-1/2 uninfected at Screening and Enrollment, per applicable algorithm in Appendix II and willing to receive HIV test results.~Able and willing to provide adequate locator information, as defined in site SOP.~Available to return for all study visits and willing to comply with study participation requirements.~In general good health at Screening and Enrollment, as determined by the site Investigator of Record (IoR) or designee.~At Screening, history of consensual RAI at least three times in the past three months and expecting to maintain at least this frequency of RAI during study participation per participant report.~Willing to not take part in other research studies involving drugs, medical devices, genital or rectal products, or vaccines for the duration of study participation (including the time between Screening and Enrollment).~For individuals who can get pregnant (i.e., TGM with a female reproductive system): a negative pregnancy test at Screening and Enrollment.~For individuals who can get pregnant: Per participant report at Enrollment, using an effective method of contraception for at least 30 days (inclusive) prior to Enrollment and intending to use an effective method for the duration of study participation; effective methods include:~Hormonal methods;~Intrauterine device (IUD) inserted at least 30 days prior to Enrollment (but not past the maximum length of recommended usage according to package instructions);~Sterilization (of participant or, if in a monogamous relationship, of partner, as defined in site SOPs);~Abstinence from RVI for 90 days prior to Enrollment, and intention to abstain from RVI for the duration of study participation.~Exclusion Criteria:~At Screening:~History of inflammatory bowel disease;~Current anorectal condition that would impede product placement or assessment of tolerability by participant report or exam.~Anticipated use and/or unwillingness to abstain from using non-study rectally-administered medications and products during study participation, including personal lubricants containing nonoxynol-9 (N-9).~Note: The use of non-study personal lubricants and usual pre-RAI douches that do not contain N-9 is permitted during study participation.~Known adverse reaction to any of the components of the study products.~Participation in research studies involving drugs, medical devices, genital products, or vaccines within 30 days of the Enrollment Visit.~Participation in research studies involving rectal products (ever).~Per participant report, use of post-exposure prophylaxis (PEP) for potential HIV exposure within the 3 months prior to Enrollment.~In the 3 months prior to Enrollment, participant engagement in condomless RAI or RVI while not on PrEP with a partner who is HIVpositive and either not on ART or of unknown ART use status (by self report).~In the month prior to Enrollment, participant engagement in condomless RAI or RVI while not on PrEP with a partner who is of unknown HIV status and unknown PrEP/ART use status (by self-report).~Non-therapeutic injection drug use in the 12 months prior to Enrollment.~At either Screening or Enrollment, participant-reported symptoms and/or clinical or laboratory diagnosis of active anorectal or reproductive tract infection (RTI) requiring treatment per current WHO guidelines (http://www.who.int/hiv/ pub/sti/pub6/en/), or symptomatic urinary tract infection (UTI). Infections requiring treatment include: Neisseria gonorrhea (GC), Chlamydia trachomatis (CT), syphilis, active herpes simplex virus (HSV) lesions, anogenital sores or ulcers, or symptomatic genital warts, chancroid, pelvic inflammatory disease (PID), symptomatic bacterial vaginosis (BV), symptomatic vaginal candidiasis, and trichomoniasis.~Note: Otherwise eligible participants with a symptomatic UTI or an STI/RTI requiring treatment per current WHO guidelines may be retested during the screening process and if treatment is completed and symptoms have resolved within the screening window the participant may be enrolled.~Note: HSV-1 or HSV-2 seropositive diagnosis with no active lesions is permitted since treatment is not required.~For individuals who can get pregnant: Pregnant or breastfeeding at either Screening or Enrollment or planning to become pregnant during study participation.~For individuals who can get pregnant: Last pregnancy outcome 90 days or less prior to Screening.~Has any other condition that, in the opinion of the IoR/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives.
|
18 Years
|
35 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acceptability of Future Product Use | Using a 10-point scale (1=Very Unlikely; 10=Very Likely), participants were asked to answer the following question about their most recently used product: Think about the positive and negative experiences you have had using the [study product] during the past 4-week period. If this [study product] was available and it provided some protection against HIV, how likely would you be to use it before receptive anal sex?. The endpoint was operationalized as binary, with scores 1 to 6 grouped as low acceptability and scores 7 to 10 as high acceptability. | 14 weeks (three 4-week product use periods with 1-week washout periods between them) |
| Adherence to Placebo Products | Percentage of participants who used each study product as instructed | 14 weeks (three 4-week product use periods with 1-week washout periods between them) |
| Number of Grade 2+ Related Adverse Events | Number of all Grade 2 or higher related adverse events (AE) reported in the study as defined by the DAIDS AE Grading Table | 14 weeks (three 4-week product use periods with 1-week washout periods between them) |
|
Acceptability, Rectal microbicide
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Product Sequence A<br>Participants will use placebo rectal inserts during the first 4-week product use period, placebo rectal douches during the second 4-week product use period, and placebo rectal suppositories during the third and final 4-week product use period. | Behavioral: Placebo rectal insert<br>* Participants will be instructed to insert in the rectum a placebo insert prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal suppository<br>* Participants will be instructed to insert in the rectum a placebo suppository prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal douche<br>* Participants will be instructed to insert in the rectum a placebo douche (enema bottle with approximately 120 mL of clean tap water or bottled water) prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI, or if no other RAI activity occurs in that 7-day period, to take a dose in the absence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>|
| Other: Product Sequence B<br>Participants will use placebo rectal douches during the first 4-week product use period, placebo rectal suppositories during the second 4-week product use period, and placebo rectal inserts during the third and final 4-week product use period. | Behavioral: Placebo rectal insert<br>* Participants will be instructed to insert in the rectum a placebo insert prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal suppository<br>* Participants will be instructed to insert in the rectum a placebo suppository prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal douche<br>* Participants will be instructed to insert in the rectum a placebo douche (enema bottle with approximately 120 mL of clean tap water or bottled water) prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI, or if no other RAI activity occurs in that 7-day period, to take a dose in the absence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>|
| Other: Product Sequence C<br>Participants will use rectal suppositories during the first 4-week product use period, rectal inserts during the second 4-week product use period, and rectal douches during the third and final 4-week product use period. | Behavioral: Placebo rectal insert<br>* Participants will be instructed to insert in the rectum a placebo insert prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal suppository<br>* Participants will be instructed to insert in the rectum a placebo suppository prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal douche<br>* Participants will be instructed to insert in the rectum a placebo douche (enema bottle with approximately 120 mL of clean tap water or bottled water) prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI, or if no other RAI activity occurs in that 7-day period, to take a dose in the absence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>|
| Other: Product Sequence D<br>Participants will use placebo rectal inserts during the first 4-week product use period, placebo rectal suppositories during the second 4-week product use period, and placebo rectal douches during the third and final 4-week product use period. | Behavioral: Placebo rectal insert<br>* Participants will be instructed to insert in the rectum a placebo insert prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal suppository<br>* Participants will be instructed to insert in the rectum a placebo suppository prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal douche<br>* Participants will be instructed to insert in the rectum a placebo douche (enema bottle with approximately 120 mL of clean tap water or bottled water) prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI, or if no other RAI activity occurs in that 7-day period, to take a dose in the absence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>|
| Other: Product Sequence E<br>Participants will use placebo rectal douches during the first 4-week product use period, placebo rectal inserts during the second 4-week product use period, and placebo rectal suppositories during the third and final 4-week product use period. | Behavioral: Placebo rectal insert<br>* Participants will be instructed to insert in the rectum a placebo insert prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal suppository<br>* Participants will be instructed to insert in the rectum a placebo suppository prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal douche<br>* Participants will be instructed to insert in the rectum a placebo douche (enema bottle with approximately 120 mL of clean tap water or bottled water) prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI, or if no other RAI activity occurs in that 7-day period, to take a dose in the absence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>|
| Other: Product Sequence F<br>Participants will use placebo rectal suppositories during the first 4-week product use period, placebo rectal douches during the second 4-week product use period, and placebo rectal inserts during the third and final 4-week product use period. | Behavioral: Placebo rectal insert<br>* Participants will be instructed to insert in the rectum a placebo insert prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal suppository<br>* Participants will be instructed to insert in the rectum a placebo suppository prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal douche<br>* Participants will be instructed to insert in the rectum a placebo douche (enema bottle with approximately 120 mL of clean tap water or bottled water) prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI, or if no other RAI activity occurs in that 7-day period, to take a dose in the absence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>|
|
Rectal Microbicide Acceptability, Tolerability and Adherence
Study Overview
=================
Brief Summary
-----------------
MTN-035 is a multi-site, randomized-sequence, three-period, open label crossover study that will enroll approximately 210 participants randomized (1:1:1:1:1:1) to one of six sequences of rectal microbicide placebo product application.
Detailed Description
-----------------
MTN-035 is a multi-site, randomized-sequence, three-period, open label crossover study that will enroll approximately 210 participants randomized (1:1:1:1:1:1) to one of six sequences of rectal microbicide placebo product application. At the start of each 4-week product use period, participants will receive either rectal inserts, rectal douches, or rectal suppositories and be instructed to use their assigned study product prior to each receptive anal intercourse (RAI) encounter during that period. Participants who do not have RAI in a given week will be asked to use the product without sex. There will be a 1-week washout period between each of the three product use periods. Participant follow-up will take approximately 3.5 months.
Official Title
-----------------
Acceptability, Tolerability, and Adherence of Three Rectal Microbicide Placebo Formulations Among HIV Seronegative Cisgender Men, Transgender Men and Transgender Women Who Engage in Receptive Anal Intercourse
Conditions
-----------------
HIV Prevention
Intervention / Treatment
-----------------
* Behavioral: Placebo rectal insert
* Behavioral: Placebo rectal suppository
* Behavioral: Placebo rectal douche
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men (cis or transgender) and TGW who are 18-35 years old at Screening, verified per site SOP. Able and willing to provide written informed consent. HIV-1/2 uninfected at Screening and Enrollment, per applicable algorithm in Appendix II and willing to receive HIV test results. Able and willing to provide adequate locator information, as defined in site SOP. Available to return for all study visits and willing to comply with study participation requirements. In general good health at Screening and Enrollment, as determined by the site Investigator of Record (IoR) or designee. At Screening, history of consensual RAI at least three times in the past three months and expecting to maintain at least this frequency of RAI during study participation per participant report. Willing to not take part in other research studies involving drugs, medical devices, genital or rectal products, or vaccines for the duration of study participation (including the time between Screening and Enrollment). For individuals who can get pregnant (i.e., TGM with a female reproductive system): a negative pregnancy test at Screening and Enrollment. For individuals who can get pregnant: Per participant report at Enrollment, using an effective method of contraception for at least 30 days (inclusive) prior to Enrollment and intending to use an effective method for the duration of study participation; effective methods include: Hormonal methods; Intrauterine device (IUD) inserted at least 30 days prior to Enrollment (but not past the maximum length of recommended usage according to package instructions); Sterilization (of participant or, if in a monogamous relationship, of partner, as defined in site SOPs); Abstinence from RVI for 90 days prior to Enrollment, and intention to abstain from RVI for the duration of study participation. Exclusion Criteria: At Screening: History of inflammatory bowel disease; Current anorectal condition that would impede product placement or assessment of tolerability by participant report or exam. Anticipated use and/or unwillingness to abstain from using non-study rectally-administered medications and products during study participation, including personal lubricants containing nonoxynol-9 (N-9). Note: The use of non-study personal lubricants and usual pre-RAI douches that do not contain N-9 is permitted during study participation. Known adverse reaction to any of the components of the study products. Participation in research studies involving drugs, medical devices, genital products, or vaccines within 30 days of the Enrollment Visit. Participation in research studies involving rectal products (ever). Per participant report, use of post-exposure prophylaxis (PEP) for potential HIV exposure within the 3 months prior to Enrollment. In the 3 months prior to Enrollment, participant engagement in condomless RAI or RVI while not on PrEP with a partner who is HIVpositive and either not on ART or of unknown ART use status (by self report). In the month prior to Enrollment, participant engagement in condomless RAI or RVI while not on PrEP with a partner who is of unknown HIV status and unknown PrEP/ART use status (by self-report). Non-therapeutic injection drug use in the 12 months prior to Enrollment. At either Screening or Enrollment, participant-reported symptoms and/or clinical or laboratory diagnosis of active anorectal or reproductive tract infection (RTI) requiring treatment per current WHO guidelines (http://www.who.int/hiv/ pub/sti/pub6/en/), or symptomatic urinary tract infection (UTI). Infections requiring treatment include: Neisseria gonorrhea (GC), Chlamydia trachomatis (CT), syphilis, active herpes simplex virus (HSV) lesions, anogenital sores or ulcers, or symptomatic genital warts, chancroid, pelvic inflammatory disease (PID), symptomatic bacterial vaginosis (BV), symptomatic vaginal candidiasis, and trichomoniasis. Note: Otherwise eligible participants with a symptomatic UTI or an STI/RTI requiring treatment per current WHO guidelines may be retested during the screening process and if treatment is completed and symptoms have resolved within the screening window the participant may be enrolled. Note: HSV-1 or HSV-2 seropositive diagnosis with no active lesions is permitted since treatment is not required. For individuals who can get pregnant: Pregnant or breastfeeding at either Screening or Enrollment or planning to become pregnant during study participation. For individuals who can get pregnant: Last pregnancy outcome 90 days or less prior to Screening. Has any other condition that, in the opinion of the IoR/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 35 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Product Sequence A<br>Participants will use placebo rectal inserts during the first 4-week product use period, placebo rectal douches during the second 4-week product use period, and placebo rectal suppositories during the third and final 4-week product use period. | Behavioral: Placebo rectal insert<br>* Participants will be instructed to insert in the rectum a placebo insert prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal suppository<br>* Participants will be instructed to insert in the rectum a placebo suppository prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal douche<br>* Participants will be instructed to insert in the rectum a placebo douche (enema bottle with approximately 120 mL of clean tap water or bottled water) prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI, or if no other RAI activity occurs in that 7-day period, to take a dose in the absence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>|
| Other: Product Sequence B<br>Participants will use placebo rectal douches during the first 4-week product use period, placebo rectal suppositories during the second 4-week product use period, and placebo rectal inserts during the third and final 4-week product use period. | Behavioral: Placebo rectal insert<br>* Participants will be instructed to insert in the rectum a placebo insert prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal suppository<br>* Participants will be instructed to insert in the rectum a placebo suppository prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal douche<br>* Participants will be instructed to insert in the rectum a placebo douche (enema bottle with approximately 120 mL of clean tap water or bottled water) prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI, or if no other RAI activity occurs in that 7-day period, to take a dose in the absence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>|
| Other: Product Sequence C<br>Participants will use rectal suppositories during the first 4-week product use period, rectal inserts during the second 4-week product use period, and rectal douches during the third and final 4-week product use period. | Behavioral: Placebo rectal insert<br>* Participants will be instructed to insert in the rectum a placebo insert prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal suppository<br>* Participants will be instructed to insert in the rectum a placebo suppository prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal douche<br>* Participants will be instructed to insert in the rectum a placebo douche (enema bottle with approximately 120 mL of clean tap water or bottled water) prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI, or if no other RAI activity occurs in that 7-day period, to take a dose in the absence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>|
| Other: Product Sequence D<br>Participants will use placebo rectal inserts during the first 4-week product use period, placebo rectal suppositories during the second 4-week product use period, and placebo rectal douches during the third and final 4-week product use period. | Behavioral: Placebo rectal insert<br>* Participants will be instructed to insert in the rectum a placebo insert prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal suppository<br>* Participants will be instructed to insert in the rectum a placebo suppository prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal douche<br>* Participants will be instructed to insert in the rectum a placebo douche (enema bottle with approximately 120 mL of clean tap water or bottled water) prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI, or if no other RAI activity occurs in that 7-day period, to take a dose in the absence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>|
| Other: Product Sequence E<br>Participants will use placebo rectal douches during the first 4-week product use period, placebo rectal inserts during the second 4-week product use period, and placebo rectal suppositories during the third and final 4-week product use period. | Behavioral: Placebo rectal insert<br>* Participants will be instructed to insert in the rectum a placebo insert prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal suppository<br>* Participants will be instructed to insert in the rectum a placebo suppository prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal douche<br>* Participants will be instructed to insert in the rectum a placebo douche (enema bottle with approximately 120 mL of clean tap water or bottled water) prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI, or if no other RAI activity occurs in that 7-day period, to take a dose in the absence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>|
| Other: Product Sequence F<br>Participants will use placebo rectal suppositories during the first 4-week product use period, placebo rectal douches during the second 4-week product use period, and placebo rectal inserts during the third and final 4-week product use period. | Behavioral: Placebo rectal insert<br>* Participants will be instructed to insert in the rectum a placebo insert prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal suppository<br>* Participants will be instructed to insert in the rectum a placebo suppository prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>Behavioral: Placebo rectal douche<br>* Participants will be instructed to insert in the rectum a placebo douche (enema bottle with approximately 120 mL of clean tap water or bottled water) prior to RAI. If a dose is missed, participants will be instructed to wait to take a dose at the next occurrence of RAI, or if no other RAI activity occurs in that 7-day period, to take a dose in the absence of RAI. Furthermore, if no RAI activity occurs at all in a given 7-day period, participants will be instructed to take a dose on the seventh day in the absence of RAI.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acceptability of Future Product Use | Using a 10-point scale (1=Very Unlikely; 10=Very Likely), participants were asked to answer the following question about their most recently used product: Think about the positive and negative experiences you have had using the [study product] during the past 4-week period. If this [study product] was available and it provided some protection against HIV, how likely would you be to use it before receptive anal sex?. The endpoint was operationalized as binary, with scores 1 to 6 grouped as low acceptability and scores 7 to 10 as high acceptability. | 14 weeks (three 4-week product use periods with 1-week washout periods between them) |
| Adherence to Placebo Products | Percentage of participants who used each study product as instructed | 14 weeks (three 4-week product use periods with 1-week washout periods between them) |
| Number of Grade 2+ Related Adverse Events | Number of all Grade 2 or higher related adverse events (AE) reported in the study as defined by the DAIDS AE Grading Table | 14 weeks (three 4-week product use periods with 1-week washout periods between them) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acceptability, Rectal microbicide
|
||
NCT00003752
|
Bexarotene in Treating Patients With Metastatic Breast Cancer
|
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.~PURPOSE: Randomized phase II trial to study the effectiveness of bexarotene in treating patients who have metastatic breast cancer.
|
OBJECTIVES: I. Compare the efficacy of oral bexarotene (LGD1069) at two different dose levels in patients with advanced breast cancer. II. Assess the safety and tolerability of this treatment regimen in this patient population. III. Evaluate the efficacy of oral bexarotene in terms of induction of differentiation and decreased aberrant cell proliferation in these patients.~OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to prior therapy for metastatic disease. Patients are randomized to one of two dose levels. All patients receive oral bexarotene once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every week for the first month, at weeks 6 and 8, then monthly thereafter.~PROJECTED ACCRUAL: A total of 84-180 patients will be accrued for this study.
|
A Multicenter Phase II Evaluation of Targretin (Bexarotene) Capsules in Patients With Advanced Breast Cancer
|
Breast Cancer
|
* Drug: bexarotene
|
DISEASE CHARACTERISTICS: Histologically confirmed metastatic breast cancer No CNS metastases No rapidly progressing visceral disease Previously irradiated lesions(s) may be designated as measurable indicator tumor(s) only if more than 6 months since radiotherapy, patient has no other measurable disease regrowth, and bidimensionally measurable regrowth is documented within 2 months prior to study Stratum 1 (hormonal): Must be hormone receptor positive (ER or PR) Prior hormonal therapy only allowed for metastatic disease Must have progressed on last hormonal regimen Must have at least one bidimensionally measurable tumor Stratum 2 (chemotherapy): Hormone receptor positive or negative Must have progressed on or after prior chemotherapy (1-2 regimens) for metastatic disease (bone marrow transplant counts as 2 regimens) Prior hormonal therapy allowed Must have at least one bidimensionally measurable tumor Stratum 3 (tamoxifen): Must be hormone receptor positive (ER or PR) and progressing on tamoxifen No symptomatic visceral metastasis if on adjuvant tamoxifen at time of systemic recurrence Must have at least one bidimensionally measurable tumor, or lytic bone lesion which measures at least one cm in diameter Hormone receptor status: See above~PATIENT CHARACTERISTICS: Age: Over 18 Menopausal status: Not specified Performance status: ECOG 0-2 OR Karnofsky 60-100% Life expectancy: At least 3 months Hematopoietic: WBC at least 3,000/mm3 Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Fasting triglycerides within normal range Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT and/or SGPT no greater than 2.5 times ULN Concurrent medication with drugs that significantly alter hepatic metabolism (e.g., phenobarbital, phenytoin, oral azole antifungals) allowed only if dosage stable Renal: Creatinine less than 2 times ULN OR Creatinine clearance greater than 40 mL/min Concurrent medication with drugs that significantly alter renal metabolism (e.g., probenecid) allowed only if dosage stable Other: At least 5 years since any other prior invasive malignancy except basal cell and squamous cell carcinoma of the skin No serious concurrent illness that would prevent compliance No history of or clinically significant risk factors for developing pancreatitis Fasting triglycerides within normal range Not pregnant or nursing Fertile patients must use effective contraception~PRIOR CONCURRENT THERAPY: Biologic therapy: Prior monoclonal antibody HER2 therapy for metastatic disease allowed only if combined with chemotherapy or hormonal therapy and treatment failed No concurrent immunotherapy Chemotherapy: See Disease Characteristics At least 4 weeks since prior cytotoxic chemotherapy (at least 6 weeks since prior mitomycin or nitrosourea) No prior retinoid therapy for breast cancer At least 3 months since any other prior retinoid therapy except topical application for dermatological indications No concurrent chemotherapy Endocrine therapy: See Disease Characteristics At least 2 weeks since prior non-FDA approved hormonal therapy No other concurrent hormonal therapy except chronic low dose hormone replacement therapy or low dose corticosteroids for noncancer indication Radiotherapy: See Disease Characteristics Prior radiotherapy allowed Concurrent radiotherapy allowed only to non-indicator tumor(s) that do not represent new disease or disease progression Surgery: Prior surgery allowed Other: At least one month since prior investigational therapy (except hormonal) No other concurrent investigational therapy Concurrent medication with drugs that significantly alter hepatic metabolism (e.g., phenobarbital, phenytoin, oral azole antifungals) allowed only if dosage stable No more than 15,000 IU of vitamin A consumed daily
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
stage IV breast cancer, recurrent breast cancer
|
Antineoplastic Agents, Bexarotene
|
| Intervention/Treatment |
| --- |
|Drug: bexarotene|nan|
|
Bexarotene in Treating Patients With Metastatic Breast Cancer
Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Randomized phase II trial to study the effectiveness of bexarotene in treating patients who have metastatic breast cancer.
Detailed Description
-----------------
OBJECTIVES: I. Compare the efficacy of oral bexarotene (LGD1069) at two different dose levels in patients with advanced breast cancer. II. Assess the safety and tolerability of this treatment regimen in this patient population. III. Evaluate the efficacy of oral bexarotene in terms of induction of differentiation and decreased aberrant cell proliferation in these patients. OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to prior therapy for metastatic disease. Patients are randomized to one of two dose levels. All patients receive oral bexarotene once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every week for the first month, at weeks 6 and 8, then monthly thereafter. PROJECTED ACCRUAL: A total of 84-180 patients will be accrued for this study.
Official Title
-----------------
A Multicenter Phase II Evaluation of Targretin (Bexarotene) Capsules in Patients With Advanced Breast Cancer
Conditions
-----------------
Breast Cancer
Intervention / Treatment
-----------------
* Drug: bexarotene
Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed metastatic breast cancer No CNS metastases No rapidly progressing visceral disease Previously irradiated lesions(s) may be designated as measurable indicator tumor(s) only if more than 6 months since radiotherapy, patient has no other measurable disease regrowth, and bidimensionally measurable regrowth is documented within 2 months prior to study Stratum 1 (hormonal): Must be hormone receptor positive (ER or PR) Prior hormonal therapy only allowed for metastatic disease Must have progressed on last hormonal regimen Must have at least one bidimensionally measurable tumor Stratum 2 (chemotherapy): Hormone receptor positive or negative Must have progressed on or after prior chemotherapy (1-2 regimens) for metastatic disease (bone marrow transplant counts as 2 regimens) Prior hormonal therapy allowed Must have at least one bidimensionally measurable tumor Stratum 3 (tamoxifen): Must be hormone receptor positive (ER or PR) and progressing on tamoxifen No symptomatic visceral metastasis if on adjuvant tamoxifen at time of systemic recurrence Must have at least one bidimensionally measurable tumor, or lytic bone lesion which measures at least one cm in diameter Hormone receptor status: See above PATIENT CHARACTERISTICS: Age: Over 18 Menopausal status: Not specified Performance status: ECOG 0-2 OR Karnofsky 60-100% Life expectancy: At least 3 months Hematopoietic: WBC at least 3,000/mm3 Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Fasting triglycerides within normal range Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT and/or SGPT no greater than 2.5 times ULN Concurrent medication with drugs that significantly alter hepatic metabolism (e.g., phenobarbital, phenytoin, oral azole antifungals) allowed only if dosage stable Renal: Creatinine less than 2 times ULN OR Creatinine clearance greater than 40 mL/min Concurrent medication with drugs that significantly alter renal metabolism (e.g., probenecid) allowed only if dosage stable Other: At least 5 years since any other prior invasive malignancy except basal cell and squamous cell carcinoma of the skin No serious concurrent illness that would prevent compliance No history of or clinically significant risk factors for developing pancreatitis Fasting triglycerides within normal range Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Prior monoclonal antibody HER2 therapy for metastatic disease allowed only if combined with chemotherapy or hormonal therapy and treatment failed No concurrent immunotherapy Chemotherapy: See Disease Characteristics At least 4 weeks since prior cytotoxic chemotherapy (at least 6 weeks since prior mitomycin or nitrosourea) No prior retinoid therapy for breast cancer At least 3 months since any other prior retinoid therapy except topical application for dermatological indications No concurrent chemotherapy Endocrine therapy: See Disease Characteristics At least 2 weeks since prior non-FDA approved hormonal therapy No other concurrent hormonal therapy except chronic low dose hormone replacement therapy or low dose corticosteroids for noncancer indication Radiotherapy: See Disease Characteristics Prior radiotherapy allowed Concurrent radiotherapy allowed only to non-indicator tumor(s) that do not represent new disease or disease progression Surgery: Prior surgery allowed Other: At least one month since prior investigational therapy (except hormonal) No other concurrent investigational therapy Concurrent medication with drugs that significantly alter hepatic metabolism (e.g., phenobarbital, phenytoin, oral azole antifungals) allowed only if dosage stable No more than 15,000 IU of vitamin A consumed 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: Randomized
Arms and Interventions
| Intervention/Treatment |
| --- |
|Drug: bexarotene|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
-----------------
stage IV breast cancer, recurrent breast cancer
|
|
NCT01225484
|
Perioperative Analgesia After Knee Arthroplasty
|
The purpose of this study is to compare two accepted methods of pain control in knee arthroplasty surgery.The first method combines the periarticular injection of ropivacaine with continuous blockade of the femoral nerve.The second method uses periarticular infiltration of ropivacaine in combination with an bolus of ropivacaine into an intraarticular catheter placed intraoperatively followed by a continuous intraarticular infusion of ropivacaine. All patient will also receive a sustained-release oral opioid and oral rescue opioids determined by pain severity using the Visual Analog Scale (VAS)
|
Perioperative Analgetic Therapy After Knee Arthroplasty
|
Knee Arthroplasty
|
* Procedure: Continuous femoral nerve block + periarticular infiltration
* Procedure: Intraarticular and periarticular ropivacaine
|
Inclusion Criteria:~Elective primary knee arthroplasty~ASA I,II,&III patients~Spinal Anaesthesia~Exclusion Criteria:~Patients refusing consent~Contraindications to regional anaesthesia~Preexisting neurological disease~Alcohol or drug abuse~Inability to use the outcome assessment tools~Wheel chair or walker dependent~Pregnancy
|
18 Years
|
80 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Static and dynamic pain scores (VAS) | | 72 h |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum knee flexion (active/passive)>= 90° | | 72 h |
|
Knee arthroplasty, perioperative analgesia
|
Ropivacaine, Anesthetics, Local, Anesthetics, Central Nervous System Depressants, Physiological Effects of Drugs, Sensory System Agents, Peripheral Nervous System Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CFNB, periarticular infiltration<br> | Procedure: Continuous femoral nerve block + periarticular infiltration<br>* Initial bolus of ropivacaine 5mg/ml 30mls into the femoral-nerve-catheter preoperatively. Periarticular infiltration of ropivacaine 2mg/ml 150 mls intraoperatively. Continuous perineural infusion of ropivacaine 2mg/ml at a rate of 6 mls/hr postoperatively. Rate can be adjusted to achieve optimal pain control and avoid motor blockade.<br>* Other names: CFNB plus periarticular infiltration;|
| Active Comparator: Intraarticular catheter, periarticular infiltration<br> | Procedure: Continuous femoral nerve block + periarticular infiltration<br>* Initial bolus of ropivacaine 5mg/ml 30mls into the femoral-nerve-catheter preoperatively. Periarticular infiltration of ropivacaine 2mg/ml 150 mls intraoperatively. Continuous perineural infusion of ropivacaine 2mg/ml at a rate of 6 mls/hr postoperatively. Rate can be adjusted to achieve optimal pain control and avoid motor blockade.<br>* Other names: CFNB plus periarticular infiltration;Procedure: Intraarticular and periarticular ropivacaine<br>* Periarticular infiltration of 150 mls ropivacaine 2mg/ml intraoperatively, intraarticular injection of 40 mls ropivacaine 2 mg/ml at skin closure followed by infusion of ropivacaine 2 mg/ml at a rate of 4 mls/hr delivered by an intraarticular catheter until the morning of postoperative day 3.<br>* Other names: Intraarticular ropivacaine plus periarticular ropivavaine;|
|
Perioperative Analgesia After Knee Arthroplasty
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare two accepted methods of pain control in knee arthroplasty surgery.The first method combines the periarticular injection of ropivacaine with continuous blockade of the femoral nerve.The second method uses periarticular infiltration of ropivacaine in combination with an bolus of ropivacaine into an intraarticular catheter placed intraoperatively followed by a continuous intraarticular infusion of ropivacaine. All patient will also receive a sustained-release oral opioid and oral rescue opioids determined by pain severity using the Visual Analog Scale (VAS)
Official Title
-----------------
Perioperative Analgetic Therapy After Knee Arthroplasty
Conditions
-----------------
Knee Arthroplasty
Intervention / Treatment
-----------------
* Procedure: Continuous femoral nerve block + periarticular infiltration
* Procedure: Intraarticular and periarticular ropivacaine
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Elective primary knee arthroplasty ASA I,II,&III patients Spinal Anaesthesia Exclusion Criteria: Patients refusing consent Contraindications to regional anaesthesia Preexisting neurological disease Alcohol or drug abuse Inability to use the outcome assessment tools Wheel chair or walker dependent Pregnancy
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CFNB, periarticular infiltration<br> | Procedure: Continuous femoral nerve block + periarticular infiltration<br>* Initial bolus of ropivacaine 5mg/ml 30mls into the femoral-nerve-catheter preoperatively. Periarticular infiltration of ropivacaine 2mg/ml 150 mls intraoperatively. Continuous perineural infusion of ropivacaine 2mg/ml at a rate of 6 mls/hr postoperatively. Rate can be adjusted to achieve optimal pain control and avoid motor blockade.<br>* Other names: CFNB plus periarticular infiltration;|
| Active Comparator: Intraarticular catheter, periarticular infiltration<br> | Procedure: Continuous femoral nerve block + periarticular infiltration<br>* Initial bolus of ropivacaine 5mg/ml 30mls into the femoral-nerve-catheter preoperatively. Periarticular infiltration of ropivacaine 2mg/ml 150 mls intraoperatively. Continuous perineural infusion of ropivacaine 2mg/ml at a rate of 6 mls/hr postoperatively. Rate can be adjusted to achieve optimal pain control and avoid motor blockade.<br>* Other names: CFNB plus periarticular infiltration;Procedure: Intraarticular and periarticular ropivacaine<br>* Periarticular infiltration of 150 mls ropivacaine 2mg/ml intraoperatively, intraarticular injection of 40 mls ropivacaine 2 mg/ml at skin closure followed by infusion of ropivacaine 2 mg/ml at a rate of 4 mls/hr delivered by an intraarticular catheter until the morning of postoperative day 3.<br>* Other names: Intraarticular ropivacaine plus periarticular ropivavaine;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Static and dynamic pain scores (VAS) | | 72 h |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum knee flexion (active/passive)>= 90° | | 72 h |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Knee arthroplasty, perioperative analgesia
|
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