Effects of CONTRAVE on weight loss and behavior in adults with obesity

Identifying the Short-Term Neurobiological, Metabolic and Behavioural Effects of CONTRAVE as Potential Mechanisms of Weight Loss in Adults With Obesity: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial

This study is testing if the weight-loss drug CONTRAVE can help adults with obesity lose weight and manage their appetite better when combined with a diet.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 64 Years
• Sex: All
• Sponsor: The Royal's Institute of Mental Health Research (Academic / other)
• Locations: 3 sites (Ottawa, Ontario and 2 other locations)
• Trial ID: NCT06809166 on ClinicalTrials.gov

What this trial studies

This study investigates the metabolic and behavioral effects of the weight-loss drug CONTRAVE in adults with obesity. It employs a randomized, double-blind, placebo-controlled design with 40 participants aged 18-64 who have a BMI greater than 30. Participants will be assigned to either a diet combined with CONTRAVE or a diet with a placebo, allowing researchers to assess the drug's impact on appetite, food cravings, and overall weight management. The study aims to clarify the mechanisms by which CONTRAVE may aid in weight loss and improve adherence to dietary interventions.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18-64 with a BMI over 30 who are seeking weight loss treatment.

Not a fit: Patients who do not meet the BMI criteria or have significant mobility issues may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide insights into effective weight management strategies for individuals struggling with obesity.

How similar studies have performed: Other studies have shown promise in using pharmacological interventions for weight management, suggesting potential success for this approach.

Eligibility criteria

Inclusion Criteria:

1. Participants who are able to provide written informed consent prior to the initiation of any protocol-required procedures
2. Have been referred to the LEAF clinic by their physician or have self-referred to the LEAF clinic for weight loss, and have been deemed appropriate for weight loss treatment offered by the LEAF clinic (i.e., these criteria are at the discretion of the clinical team at the LEAF clinic, outlined below in the exclusion criteria section).
3. Adults: aged 18-64 years of age (gender and sex will be noted; recruitment is all-gender inclusive).
4. Have a BMI\>30.
5. Have normal or corrected vision as some of the study aspects will involve viewing/responding to visual stimuli.
6. Understand and speak English (as instructions for study criteria will be provided in English).
7. Able to participate in the study protocol as described, e.g. have a means of getting to the laboratories and no major mobility issues to the extent that protocols cannot be followed (details below).
8. Access to a secure internet connection (for virtual appointments with members of the LEAF clinic).

Exclusion Criteria:

1. Reporting severe depression or reporting significant suicidal ideation, or history of bipolar disorder or psychosis (i.e., major psychiatric condition; this will be ascertained during the screening carried out by research personnel, in keeping with our standard protocols in Dr. Jaworska's laboratory).\*\*\*
2. Current use of antidepressants, thyroid medication, or any medication that could affect appetite, or seizure threshold (e.g.., bupropion, tamoxifen, thioridazine).
3. Uncontrolled hypertension.
4. History of cardiac defects or symptoms suggestive of any cardiac condition (not including coronary artery disease).
5. Presence of diabetes.
6. Current or past history of addictions or substance use disorder, including undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs.
7. History of eating disorder (including Binge Eating Disorder, Bulimia Nervosa or Anorexia Nervosa).
8. History of glaucoma.
9. Personal or family history of seizure disorders.
10. Currently taking MAO inhibitors (within 14 days), pressor agents, coumadin, anticonvulsants, or phenylbutazone, or other bupropion-containing products (such as Wellbutrin, Wellbutrin SR, Wellbutrin XL, Aplenzin or Zyban), or CYP2B6 inhibitors (e.g. ticlopidine or clopidogrel).
11. History of thyroid disease, chronic liver, or renal disease.
12. Chronic use of opioid, opiate agonist (Methadone) or partial agonists (Buprenorphine).
13. Currently pregnant or planning to become pregnant during the intervention or currently nursing. Pregnancy urine test will be conducted during the in-person screening session in the laboratory.\*\*\*
14. No known allergy to any of the ingredients in CONTRAVE® (e.g. lactose).
15. Hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption.
16. Current use of obesity medications such as liraglutide or semaglutide or orlistat.
17. Current use of medication indicated in patient living with ADHD (e.g., Vivanse/Concerta) which are known to have metabolic impacts.

    There are several additional exclusionary criteria, established by research personnel in Dr. Jaworska's laboratory (i.e., not part of LEAF intake) that preclude participation in the brain imaging/magnetic resonance imaging (MRI) and EEG, these include:
18. Severe claustrophobia.
19. Inability to lie still in the scanner for approximately 30min.
20. Metal in the body that cannot be removed and might pose a safety risk to the participant.
21. History of concussion (loss of consciousness for \>5-min).
22. Major neurological illness, such as, epilepsy, stroke, tumours (as this would interfere with the interpretation of the MRI data).
23. Obesity to the extent that the participant cannot fit into the scanner. This will be established by ensuring that the individual can fit into the mock scanner at the Brain Imaging Centre (BIC) of The Royal. If a person cannot fit into the mock scanner, it is unlikely that the person can fit into the real scanner.
24. Testing positive for illicit drugs and cannabis (this will be established using a drug test that will be administered in the Clinical EEG \& Neuroimaging laboratory at the Institute of Mental Health Research \[IMHR\]). Participants who are cannabis users will be invited to participate in the study so long as they can abstain from cannabis use for approximately 2weeks prior to the baseline session and approximately 2weeks before final assessment. Ideally, participants would also abstain from cannabis use during treatment, but, this will not be tested/enforced.
25. Ability to abstain from nicotine/tobacco and caffeine for 3h prior to the baseline testing/EEG recordings, as both substances influence EEG activity.

    NOTE: If a participant cannot participate in the MRI aspect of the study (i.e., due to the above exclusion criteria), they will still be able to participate in the research study (apart from the MRI component). All MRI/EEG exclusion criteria will be established during the screening/clinical interview carried out by trained research staff from Dr. Jaworska's laboratory (details below).

    One final exclusion criterion is as follows:
26. Unable to tolerate the test dose of CONTRAVE® (details below). Such individuals would not participate in further elements of the research, but, would continue with their treatment through the LEAF clinic (as determined by the LEAF clinic, per their clinical management program).

Where this trial is running

Ottawa, Ontario and 2 other locations

• LEAF Weight Managment Clinic — Ottawa, Ontario, Canada (Recruiting)
• Behavioural and Metabolic Research Unit — Ottawa, Ontario, Canada (Recruiting)
• University of Ottawa Institute of Mental Health Research — Ottawa, Ontario, Canada (Recruiting)

Study contacts

• Principal investigator: Pierre Blier, M.D., Ph.D — University of Ottawa
• Study coordinator: Natalia Jaworska, Ph.D

Conditions Obesity; Weight Loss; Weight Management; Dietary Intervention; Obesity/Therapy; contrave; EEG; MRI