Clinical trial NCT04587843: A Trial Evaluating the Effectiveness of Contrave in Patients Who Have Weight Recidivism Following Bariatric Surgery
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Obesity
Keywords: weight recidivism
weight regain
inadequate weight loss
Lead sponsor: St. Joseph's Healthcare Hamilton
Sponsor class: OTHER
Collaborators: name: Bausch Health, Canada Inc.
First posted: 2020-10-14
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel, randomized, double blind, placebo controlled
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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:

1. \< 10% total body weight (TBW) loss at 6 months or;
2. \< 20% TBW loss at 12 months or;
3. Weight regain of \> 25% of weight loss.

The aim 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.

Eligibility criteria: Inclusion Criteria:

* \>=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:

  1. \< 10% total body weight (TBW) loss at 6 months or;
  2. \< 20% TBW loss at 12 months or;
  3. 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change in absolute weight (Kg)
timeFrame: Baseline to 12 months
measure: Proportion of participants achieving 5 percent total weight loss
timeFrame: Baseline to 12 months
Secondary outcomes:
measure: Change in Body Mass Index (BMI) (Kg/m2)
timeFrame: Baseline to 12 months
measure: Percentage total body weight loss (percentage TBWL)
timeFrame: Baseline to 12 months
measure: Proportion of participants losing at least 10 percent baseline weight at 12 months
timeFrame: Baseline to 12 months
measure: Percent change in HbA1c level
timeFrame: Baseline to 12 months
measure: Change in blood pressure
timeFrame: Baseline to 12 months
measure: Change in lipid profile
timeFrame: Baseline to 12 months
measure: Changes in impulsivity behaviours from baseline as assessed by UPPS-P Impulsive Behaviour Scale (self administered questionnaire)
timeFrame: Baseline to 12 months
measure: Changes in quality of life and health economic outcomes as measured with the EQ-5D-5L self administered questionnaire
timeFrame: Baseline to 12 months
measure: Percentage of participants who are adherent to pharmacotherapy
timeFrame: Week 0 to Week 52
measure: Average number of days participants took investigational product (Contrave or placebo)
timeFrame: Week 0 to Week 52
measure: Change in diabetes medication requirements
timeFrame: Baseline to 12 months
measure: Change in hypertension (high blood pressure) medication requirements
timeFrame: Baseline to 12 months
measure: Change in lipid (cholesterol) medication requirements
timeFrame: Baseline to 12 months
measure: Changes in eating behaviours from baseline as assessed by Eating Disorder Examination Questionnaire (EDE-Q 6.0) (self administered questionnaire)
timeFrame: Baseline to 12 months
measure: Changes in eating behaviours from baseline as assessed by Yale Food Addiction Scale (YFAS) (self administered questionnaire)
timeFrame: Baseline to 12 months
measure: Changes in food cravings from baseline as assessed by Favourite Food Craving Scale (FFCS) (self administered questionnaire)
timeFrame: Baseline to 12 months
measure: Changes in depression from baseline as assessed by Patient Health Questionnaire 9 (PHQ-9) (self administered questionnaire)
timeFrame: Baseline to 12 months
measure: Changes in risk of suicidality from baseline as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline to 12 months
Other outcomes:
measure: Incidences of adverse events (AE)
timeFrame: Baseline to 12 months
measure: Incidences of serious adverse events (SAE)
timeFrame: Baseline to 12 months
measure: Number of participants discontinuing investigational product due to AE/SAEs
timeFrame: Baseline to 12 months
Locations:
city: Guelph
country: Canada
facility: Guelph General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: St Joseph's Healthcare Hamilton
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre
state: Ontario
city: North York
country: Canada
facility: Humber River Hospital
state: Ontario
Study officials:
affiliation: St Joseph's Healthcare Hamilton / McMaster University
name: Aristithes G Doumouras, MD
role: PRINCIPAL_INVESTIGATOR
References: