Clinical trial NCT04589130: Evaluating Contrave for Weight Maintenance in Adults With BMI >= 27 Kg/m2, After 6 Month Behaviour Modification Program.
Official title: Trial Evaluating Effectiveness of Contrave (Naltrexone HCl / Bupropion HCl) for Weight Maintenance in Adults With BMI ≥ 27 Kg/m2, After 6 Month Intensive Behavior Modification Program: Contrave Obesity Trials (COR) Weight Maintenance Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Obesity
Keywords: weight loss maintenance
Lead sponsor: St. Joseph's Healthcare Hamilton
Sponsor class: OTHER
Collaborators: name: Bausch Health, Canada Inc.
First posted: 2020-10-19
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel - 2 arms during first 6 month phase (treatment and placebo control)

Crossover - placebo control group crosses over to treatment arm during second 6 months of the study
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. Presently we do not have any evidence for the use of Contrave for weight maintenance.

The purpose of this study is to demonstrate that in participants who have ≥ 5% weight loss following the completion of a behaviour modification program with meal replacements, Contrave combined with usual care (dietary and behaviour counselling) will significantly improve maintenance of weight loss and promote further weight loss, compared to placebo with usual care.

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. Since obesity is considered a chronic disease, we need better interventions than continued calorie restriction and increased physical activity.

Sustained weight loss during the first year is a predictive factor for successful weight loss after 4 years. Clinical trials employing an intensive lifestyle intervention demonstrate that a 5-10% weight loss translates into important reductions in metabolic and cardiovascular risk factors. This benefit however, is quite often mitigated by weight regain which could occur in approximately 50% of patients after 1 year. Further behaviour modification/lifestyle intervention and or pharmacotherapy are the main pillars for treating weight regain or achieving weight maintenance. This study will refine our knowledge and understanding about the most appropriate treatment for weight maintenance.

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. Presently we do not have any evidence for the use of Contrave for weight maintenance.

This is a 1 year, phase 4, prospective, pragmatic, randomized, double-blind, placebo controlled and crossover, observational study that will be conducted in two 6 month phases, across multiple Bariatric Centres of Excellence (BCoE) in Ontario. The first 6 months is the randomized, double blind, placebo controlled phase and participants will be randomly assigned to receive Contrave with usual care (dietary and behaviour counselling) or placebo with usual care. At 6 months and the end of the blinded phase, all participants will be administered Contrave for the remaining 6 month, open-label phase of the study. In other words, participants randomly allocated to receive Contrave will continue on Contrave for the final 6 months, and participants randomly assigned to placebo will crossover to treatment with Contrave for the final 6 months. 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 successfully complete the BCoE behaviour modification program and demonstrate ≥ 5% weight loss. All participants will be followed for 1 year with multiple visits to assess safety and treatment effects.

This study aims to demonstrate that in participants who have ≥ 5% weight loss following the completion of a behaviour modification program with meal replacements, Contrave combined with usual care will significantly improve maintenance of weight loss and promote further weight loss, compared to placebo with usual care.

Eligibility criteria: Inclusion Criteria:

* ≥ 18 years of age
* Body Mass Index (BMI) of ≥ 27 Kg/m2 and the presence of at least one weight related co-morbidity
* Completed 6 month BCoE behaviour modification program with meal replacements and achieved ≥ 5% weight loss since start of program
* Able and willing to provide signed informed consent

Exclusion Criteria:

* Previous surgical treatment for obesity (excluding liposuction if performed more than one year before trial entry)
* 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
* Lifetime history of a suicide attempt or history of any suicidal behavior within the past month before entry into the trial
* 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
* Simultaneous or planned use of other weight loss medication (e.g. Saxenda / Orlistat)
* Uncontrolled hypertension, severe hepatic impairment, end-stage renal 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)
* 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
* A 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: Mean Percentage Change in Body Weight
timeFrame: Week 0 to Week 28
measure: Percentage of participants who maintained their weight
timeFrame: Week 0 to Week 28
measure: Percentage of participants who lost more than of equal to 5% of body weight
timeFrame: Week 0 to Week 28
Secondary outcomes:
measure: Mean Percentage Change in Body Weight from baseline to week 52
timeFrame: Week 0 to Week 52
measure: Percentage of participants who maintained their weight
timeFrame: Week 0 to Week 52
measure: Percentage of participants who lost more than or equal to 5% of body weight
timeFrame: Week 0 to Week 52
measure: Percentage of participants who lost more than or equal to 10% of body weight
timeFrame: Week 0 to Week 28 and Week 52
measure: Percentage of participants with weight regain (≥ 5% from baseline)
timeFrame: Week 0 to Week 28 and Week 52
measure: Percentage of subjects with weight regain (≥ 10% from baseline)
timeFrame: Week 0 to Week 28 and Week 52
measure: Mean Percentage Change in Body Weight in participants who crossed over from placebo to Contrave
timeFrame: Week 28 to Week 52
measure: Change in blood pressure (both systolic and diastolic)
timeFrame: Week 0 to Week 28 and Week 52
measure: Change in fasting lipid profile
timeFrame: Week 0 to Week 28 and Week 52
measure: Change in fasting blood glucose
timeFrame: Week 0 to Week 28 and Week 52
measure: Changes in impulsivity behaviours from baseline as assessed by UPPS-P Impulsive Behaviour Scale (self administered questionnaire)
timeFrame: Week 0 to Week 28 and Week 52
measure: Changes in quality of life and health economic outcomes.
timeFrame: Week 0 to Week 28 and Week 52
measure: Percentage of participants who are adherent to pharmacotherapy
timeFrame: Week 0 to Week 28 and Week 52
measure: Average number of days participants took investigational product (Contrave or placebo)
timeFrame: Week 0 to Week 28 and Week 52
measure: Change in heart rate
timeFrame: Week 0 to Week 28 and Week 52
measure: Change in HbA1c
timeFrame: Week 0 to Week 28 and Week 52
measure: Changes in eating behaviours from baseline as assessed by Eating Disorder Examination Questionnaire (EDE-Q 6.0) (self administered questionnaire)
timeFrame: Week 0 to Week 28 and Week 52
measure: Changes in eating behaviours from baseline as assessed by Yale Food Addiction Scale (YFAS) (self administered questionnaire)
timeFrame: Week 0 to Week 28 and Week 52
measure: Changes in food cravings from baseline as assessed by Favourite Food Craving Scale (FFCS) (self administered questionnaire)
timeFrame: Week 0 to Week 28 and Week 52
measure: Changes in depression from baseline as assessed by Patient Health Questionnaire 9 (PHQ-9) (self administered questionnaire)
timeFrame: Week 0 to Week 28 and Week 52
measure: Changes in risk of suicidality from baseline as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Week 0 to Week 12, Week 28 and Week 52
Other outcomes:
measure: Incidences of adverse events (AE)
timeFrame: Week 0 to Week 52
measure: Incidences of serious adverse events (SAE)
timeFrame: Week 0 to Week 52
measure: Number of participants discontinuing investigational product due to AE/SAEs
timeFrame: Week 0 to Week 52
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
Study officials:
affiliation: The Research Institute at St Joseph's Hamilton
name: Tony Chetty, MD
role: PRINCIPAL_INVESTIGATOR
References: