Metabolic and Behavioural Effects of CONTRAVE as Potential Mechanisms of Weight Loss in Adults With Obesity

Summary

Obesity is a common chronic disease linked with increased risk for other illnesses and earlier death. Our team and others have shown that many bodily and psychological changes occur when individuals are on calorie-restricted diets. These changes might undermine dietary adherence and help to explain the relatively poor long-term efficacy of diets. These include increased appetite, increased food 'value' and 'wanting' that leads to overconsumption. Other factors include more sensitive sensory cues (e.g., smelling), higher food liking and craving, and a drop in resting energy expenditure (REE). REE has been shown to predict weight regain.

The standard care for obesity may include the use of the weight-loss drug CONTRAVE®. The Federal Drug Agency (FDA) and Health Canada have approved this drug for weight management and obesity treatment.

Although CONTRAVE® was designed to reduce appetite, food-related impulsivity and cravings, its mechanisms of action are unclear. In other words, the effects of CONTRAVE® on REE, executive function, and brain changes remain unknown in humans. A better understanding of how this drug works on the brain and body could lead to improvements in obesity management in the future.

As such, the goal of this research is to study the effects of 4 weeks of CONTRAVE® (+ diet program) vs. control (placebo pill + diet program) on mood, body composition changes, biological/metabolic measures, and brain measures.

Adults aged 18-64 with obesity will be randomized to one of two groups: diet + CONTRAVE® (CONTRAVE®, 20 participants) or diet + Placebo (Placebo, 20 participants). Both groups will be assigned the same study procedures for the entire study duration. The only difference is that Group 1 will receive CONTRAVE® while Group 2 will receive a placebo (non-medical) pill.

The study design and intervention is as follows:

Participants who meet all the telephone screening criteria will be invited to the Clinical EEG \& Neuroimaging Laboratory at The Royal's IMHR for an in-person screening and test-dose session. Participants who are cleared by the study physician, Dr. Pierre Blier, during the in-person screening will be enrolled in the 4-weeks trial.

After the in-person screening visit, participants will attend two baseline testing visits (before starting the medication + diet program). The first will occur at the Behavioural and Metabolic Research Unit at the University of Ottawa. During this in-person visit, measures of body composition, resting energy expenditure, appetite, food craving, impulsivity, eating behaviours, taste and odour sensitivity, energy intake, and food preference will be collected.

The second baseline visit (within a week of the first one) will occur at The Royal/IMHR. During this visit, participants will be asked to complete questionnaires. They will undergo an EEG recording while resting and performing computer tasks. They will also get a brain imaging scan, during which they are asked to rest and complete a computer task.

Both testing sessions (University of Ottawa and Royal Ottawa testing sessions) will be repeated after four weeks of treatment. The section below provides further description and timing of these visits.

As part of the treatment, you will receive an individualized dietary intervention with appropriate energy restriction from a registered dietitian at Dr. Judy Shiau's LEAF weight management clinic (called the 4-week BUDS program). The program involves weekly touch points with a registered dietitian and meal planning/coaching. The diet intervention will commence the same week as the start of the placebo/CONTRAVE®.

During the 4-week intervention, participants will be asked to complete online questionnaires at various times.

Conditions

• Obesity
• Weight Loss
• Weight Management
• Dietary Intervention
• Obesity/Therapy

Interventions

DRUG

Contrave

CONTRAVE® will be titrated up to a therapeutic dose (Naltrexone 32mg/Bupropion 360mg) over a 4-week period as per clinical guidelines, and what is typical in the LEAF clinic. Dose recommendation for CONTRAVE® is tablet based, with each tablet containing 8mg of naltrexone and 90mg of bupropion. The maximum recommended daily dose is two tablets, administered orally, twice daily (32mg/360mg), taken once in the morning and once in the evening. Tablets and dispensing schedule will be done under the oversight of The Royal pharmacy (i.e., they will instruct the participants on the dosing schedule). Medication adherence and side effects will be reported daily using our online data capture system (REDCap) (approximately 1min) starting on the evening of the first dose of administration. If adverse events are significantly concerning, there is a mechanism in place for dealing with such events.

DRUG

Placebo

Placebo intervention will follow the exact same protocol in terms of tablet numbers as the CONTRAVE intervention. Generic Placebo pills will be packaged by The Royal Pharmacy into blister packs identical to Contrave.

BEHAVIORAL

Diet Program

All participants will receive an individualized dietary intervention with appropriate energy restriction from registered dietitians at Dr. Shiau's LEAF weight management clinic (called the 4-week BUDS program, which is offered to clients with obesity at the LEAF clinic). The program involves weekly touch points with a registered dietitian, and meal planning/coaching and integrates a partial meal replacement with a commercial shake.

Sponsors & Collaborators

• University of Ottawa

  collaborator OTHER

• The Royal Ottawa Mental Health Centre

  collaborator OTHER

• Bausch Health, Canada Inc.

  collaborator UNKNOWN

• Cheo Research Institute

  collaborator OTHER

• LEAF Weight Management Clinic

  collaborator UNKNOWN

• The Royal's Institute of Mental Health Research

  lead OTHER

Principal Investigators

• Pierre Blier, M.D., Ph.D · University of Ottawa

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

64 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-07-04

Primary Completion

2026-01-01

Completion

2026-07-31

Countries

• Canada

Study Locations