A Randomized Controlled Trial Evaluating the Effectiveness of Contrave (Naltrexone HCl and Bupropion HCl) in Patients Who Have Weight Recidivism Following Bariatric Surgery: Contrave Obesity Trials (COR) Weight Regain Study
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 18
- 试验地点
- 4
- 主要终点
- Proportion of participants achieving 5 percent total weight loss
研究概览
简要总结
Contrave (naltrexone HCl and bupropion HCl) extended-release tablet is an approved drug and indicated to be used with a low calorie diet and increased physical activity for chronic weight management in obese adults (BMI 30 Kg/m2 or greater) or overweight adults (BMI 27 Kg/m2 or greater) with at least one weight related condition such as hypertension or diabetes. It is unknown how many or which medical treatments for weight loss, such as Contrave work in the subjects who have had bariatric surgery.
The purpose of this study is to explore the effectiveness of Contrave combined with usual care (dietary and behaviour counselling) compared to placebo with usual care, in patients who have inadequate weight loss or significant weight regain following bariatric surgery.
详细描述
Obesity is associated with increased mortality and morbidity and represents a worldwide epidemic that is increasing in prevalence and remains a significant problem in Canada and a burden on our healthcare system. Maintaining long-term weight loss is the "Achilles' heel" of obesity therapy. Treatment for obesity with surgery is increasing because it has been shown to produce the best results for long-term weight loss and improving obesity related risk factors and diseases. But, these benefits are often reduced by inadequate weight loss or by weight regain in many patients after surgery.
Contrave (naltrexone HCl and bupropion HCl) extended-release tablet is an approved drug and indicated to be used with a low calorie diet and increased physical activity for chronic weight management in obese adults (BMI 30 Kg/m2 or greater) or overweight adults (BMI 27 Kg/m2 or greater) with at least one weight related condition such as hypertension or diabetes. It is unknown how many or which medical treatments for weight loss, such as Contrave work in the subjects who have had bariatric surgery.
This is a 1 year, phase 4, prospective, randomized, double-blind, placebo controlled study that will be conducted across multiple Bariatric Centres of Excellence (BCoE) in Ontario. Consenting participants will be randomly assigned to receive Contrave with usual care (dietary and behaviour counselling) or placebo with usual care. All subjects will also continue to receive usual care. The study includes several follow up visits to assess safety and treatment effects, some in person and others by telephone or video conferencing. Body weight, blood pressure, heart rate, waist circumference, lab tests, and subject completed questionnaires will be collected as part of usual care or for the study. Changes in medications and any possible side effects will also be monitored during the study.
To qualify, men and women must have had prior bariatric surgery (roux en-y gastric bypass or sleeve gastrectomy) at a surgical Center of Excellence within the Ontario Bariatric Network, and have inadequate weight loss or significant weight regain, based on the following OBN criteria:
- < 10% total body weight (TBW) loss at 6 months or;
- < 20% TBW loss at 12 months or;
- Weight regain of > 25% of weight loss.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •>=18 years of age
- •prior primary roux en-y gastric bypass (RYGB) or sleeve gastrectomy (SG) at a surgical Center of Excellence within the Ontario Bariatric Network (OBN)
- •inadequate weight loss or significant weight regain based on the OBN criteria13, defined as one of the following:
- •< 10% total body weight (TBW) loss at 6 months or;
- •< 20% TBW loss at 12 months or;
- •Weight regain of > 25% of weight loss.
- •body Mass Index (BMI) of ≥ 30 Kg/m2 or ≥ 27 Kg/m2 and the presence of at least one weight related co-morbidity
- •able and willing to provide signed informed consent
排除标准
- •pregnancy, planned pregnancy in the next 18 months and or breastfeeding
- •does not agree to use highly effective method of birth control if a woman of child bearing potential, for the duration of the study
- •revisional bariatric procedure or duodenal switch
- •simultaneous or planned use of other weight loss medication (e.g. Saxenda / Orlistat) or meal replacement products (e.g. Optifast)
- •uncontrolled hypertension, severe hepatic impairment, end-stage renal disease, end stage cardiac disease
- •myocardial infarction or stroke within 6 months prior to consent
- •renal impairment defined as eGFR < 60
- •seizure disorder or a history of seizures or following conditions that may predispose subjects to risk of seizure: history of head trauma, arteriovenous malformation, central nervous system tumor or infection, or a metabolic disorder that in opinion of the investigator may contraindicate treatment with Contrave and increase risk of seizure (e.g. hypoglycemia, hyponatremia)
- •lifetime history of a suicide attempt or history of any suicidal behavior within the past month before entry into the trial
- •history of major depressive disorder or a PHQ-9 (Patient Health Questionnaire-9) score of more than 15 within the last 2 years or history of other severe psychiatric disorders
- •use of other bupropion-containing products (including, but not limited to, Wellbutrin, Wellbutrin SR, Wellbutrin XL, and Zyban), because the incidence of seizure is dose dependent
- •current or prior diagnosis of bulimia or anorexia nervosa, because of a higher incidence of seizures
- •chronic opioid or opiate agonist (eg, methadone) or partial agonists (eg, buprenorphine) use, or acute opiate withdrawal
- •excessive use of alcohol or sedatives, addiction to cocaine or stimulants (street drugs), or withdrawal from sedatives
- •patients undergoing an abrupt discontinuation of alcohol, benzodiazepines or other sedatives and antiepileptic drugs
- •concomitant administration of monoamine oxidase inhibitors (MAOI). At least 14 days should elapse between discontinuation of a MAOI and initiation of treatment with Contrave
- •concomitant administration of the antipsychotic thioridazine, since bupropion may inhibit thioridazine metabolism, thus causing an increase in thioridazine levels and a potential increased risk of thioridazine-related serious ventricular arrythmias and sudden death
- •known hypersensitivity (or known allergic reaction) to the investigational product(s) or any of its ingredients including lactose
- •current participation in another interventional clinical trial
- •not able to complete subject reported, self administered questionnaires or cannot fully understand all instructions in English
研究组 & 干预措施
Contrave 8mg/90mg Extended Release Tablet
Group treated with Contrave Extended Release Tablets
干预措施: Contrave 8Mg-90Mg Extended-Release Tablet (Drug)
Placebo
Group given placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of participants achieving 5 percent total weight loss
时间窗: Baseline to 12 months
To determine the weight loss effect of Contrave with usual care compared to placebo with usual care, in a post-bariatric surgery population with weight loss failure compared to a placebo with usual care.
Change in absolute weight (Kg)
时间窗: Baseline to 12 months
To determine the weight loss effect of Contrave with usual care compared to placebo with usual care, in a post-bariatric surgery population with weight loss failure.
次要结局
- Percentage total body weight loss (percentage TBWL)(Baseline to 12 months)
- Average number of days participants took investigational product (Contrave or placebo)(Week 0 to Week 52)
- Percentage of participants who are adherent to pharmacotherapy(Week 0 to Week 52)
- Change in lipid profile(Baseline to 12 months)
- Change in lipid (cholesterol) medication requirements(Baseline to 12 months)
- Changes in eating behaviours from baseline as assessed by Yale Food Addiction Scale (YFAS) (self administered questionnaire)(Baseline to 12 months)
- Changes in food cravings from baseline as assessed by Favourite Food Craving Scale (FFCS) (self administered questionnaire)(Baseline to 12 months)
- Changes in depression from baseline as assessed by Patient Health Questionnaire 9 (PHQ-9) (self administered questionnaire)(Baseline to 12 months)
- Change in Body Mass Index (BMI) (Kg/m2)(Baseline to 12 months)
- Proportion of participants losing at least 10 percent baseline weight at 12 months(Baseline to 12 months)
- Percent change in HbA1c level(Baseline to 12 months)
- Change in blood pressure(Baseline to 12 months)
- Changes in impulsivity behaviours from baseline as assessed by UPPS-P Impulsive Behaviour Scale (self administered questionnaire)(Baseline to 12 months)
- Change in diabetes medication requirements(Baseline to 12 months)
- Changes in eating behaviours from baseline as assessed by Eating Disorder Examination Questionnaire (EDE-Q 6.0) (self administered questionnaire)(Baseline to 12 months)
- Changes in quality of life and health economic outcomes as measured with the EQ-5D-5L self administered questionnaire(Baseline to 12 months)
- Change in hypertension (high blood pressure) medication requirements(Baseline to 12 months)
- Changes in risk of suicidality from baseline as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)(Baseline to 12 months)
研究者
Tony Chetty
Associate Professor Pathology and Molecular Medicine
St. Joseph's Healthcare Hamilton