Contrave for Obesity

Recruiting at 2 trial locations

Overseen By Natalia Jaworska, Ph.D

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: The Royal's Institute of Mental Health Research

Must be taking: Contrave

Must not be taking: Antidepressants, Thyroid meds, MAO inhibitors, others

Disqualifiers: Severe depression, Diabetes, Cardiac defects, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 4 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications, including antidepressants, thyroid medication, and any medication that could affect appetite or seizure threshold. If you are currently taking these or other specified medications, you may need to stop them to participate.

Is Contrave safe for treating obesity?

Contrave, a combination of naltrexone and bupropion, has been tested in several clinical trials for obesity. Common side effects include nausea, vomiting, dizziness, and headache. Serious side effects, though less common, can include cardiovascular and kidney issues, so ongoing monitoring is important. ^{1 2 3 4 5}

How does the drug Contrave differ from other obesity treatments?

Contrave is unique because it combines two drugs, naltrexone and bupropion, which work together to increase energy expenditure and reduce appetite. This dual mechanism targets both the brain's reward system and appetite control, making it different from other treatments that may focus on just one aspect of weight management. ^{1 2 4 5 6}

What data supports the effectiveness of the drug Contrave for obesity?

Research shows that Contrave, a combination of naltrexone and bupropion, helps people lose weight when used with lifestyle changes. In clinical trials, participants lost an average of 11-22 pounds (5-9 kg) over a year, and there were improvements in heart health markers. ^{1 2 4 5 7}

Who Is on the Research Team?

Pierre Blier, M.D., Ph.D

Principal Investigator

University of Ottawa

Are You a Good Fit for This Trial?

This trial is for adults aged 18-64 with obesity (BMI >30) who can consent, speak English, and have internet access. They should be referred to the LEAF clinic for weight loss. Exclusions include heart or eye conditions, seizure history, certain medications including opioids and ADHD treatments, thyroid/liver/kidney diseases, pregnancy/nursing status, allergies to CONTRAVE®, specific dietary intolerances, substance abuse disorders, severe depression or bipolar disorder.

Inclusion Criteria

Participants able to participate in the study protocol as described

Participants who are able to provide written informed consent prior to the initiation of any protocol-required procedures

Participants with access to a secure internet connection

Exclusion Criteria

I have a history of glaucoma.

Participants with exclusionary criteria for brain imaging/MRI and EEG

Participants with current or past history of addictions or substance use disorder

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Baseline Assessment

Participants undergo baseline assessments including body composition, EEG, and MRI scans

1 week

2 visits (in-person)

Treatment

Participants receive either CONTRAVE® or placebo along with a diet program for 4 weeks

4 weeks

Weekly virtual check-ins with dietitian

Post-Intervention Assessment

Participants repeat the baseline assessments to evaluate changes after the 4-week intervention

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Contrave
• Diet Program

Trial Overview The study compares the effects of a diet program combined with either CONTRAVE® or a placebo on mood changes, body composition alterations, metabolic functions and brain activity over four weeks. Participants will undergo various tests including EEGs and MRIs before and after treatment to assess these outcomes.

How Is the Trial Designed?

Group I: CONTRAVE Experimental Treatment 2 Interventions

A diet program + CONTRAVE®

Group II: Placebo Placebo Group 2 Interventions

Diet Program + Placebo

Who Is Running the Clinical Trial?

The Royal's Institute of Mental Health Research

Lead Sponsor

Trials

8

Recruited

1,300+

The Royal Ottawa Mental Health Centre

Collaborator

Trials

24

Recruited

2,300+

LEAF Weight Management Clinic

Collaborator

Trials

1

Recruited

40+

Bausch Health, Canada Inc.

Collaborator

Trials

3

Recruited

150+

University of Ottawa

Collaborator

Trials

231

Recruited

267,000+

CHEO Research Institute

Collaborator

Trials

3

Recruited

1,100+

Cheo Research Institute

Collaborator

Published Research Related to This Trial

Contrave, a combination of naltrexone and bupropion, was shown to be effective for weight loss in a large study involving 4536 adults over 56 weeks, with participants losing an average of 11-22 lbs (5-9 kg) compared to placebo.

In addition to weight loss, Contrave also led to significant improvements in cardiometabolic markers, highlighting its potential benefits beyond just weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone/bupropion for the treatment of obesity and obesity with Type 2 diabetes. Apovian, CM.[2016]

Contrave, a combination of naltrexone and bupropion, is being tested in Phase III clinical trials for obesity treatment, showing promising efficacy in preliminary studies.

Orexigen Therapeutics, the company behind Contrave, is currently working to address safety concerns raised by the FDA as they plan their next steps.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ACS chemical neuroscience molecule spotlight on contrave. Mercer, SL.[2021]

Naltrexone/bupropion ER, marketed as Contrave, is a newly approved medication specifically designed for chronic weight management in obese adults.

This combination therapy targets both appetite suppression and energy expenditure, offering a new option for individuals struggling with obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone/Bupropion ER (Contrave): Newly Approved Treatment Option for Chronic Weight Management in Obese Adults. Sherman, MM., Ungureanu, S., Rey, JA.[2020]

Contrave, a combination of bupropion and naltrexone, works by stimulating central melanocortin pathways to increase energy expenditure and reduce appetite, showing promise in treating obesity.

In phase III trials, Contrave demonstrated placebo-subtracted weight losses of 3 to 7% and improvements in obesity-related health issues, although nausea was a common reason for discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrave, a bupropion and naltrexone combination therapy for the potential treatment of obesity. Padwal, R.[2022]

Losing just 5% of body weight can lead to significant health improvements, but many individuals struggle to maintain weight loss through diet and exercise alone, highlighting the need for additional treatment options.

As of 2012, two new medications, lorcaserin and phentermine/topiramate, have been approved for long-term obesity treatment, and bariatric surgery is recommended for patients with severe obesity (BMI ≥40 or ≥35 with comorbidities) as a more intensive intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity consults--comprehensive obesity management in 2013: understanding the shifting paradigm. Kushner, RF., Apovian, CM., Fujioka, K.[2018]

A comprehensive analysis of the FDA Adverse Event Reporting System revealed 18,675 unique adverse event reports linked to anti-obesity medications (AOMs) among 15,143 patients, highlighting significant safety concerns.

Serious adverse events included a fatality ratio of 4.9%, with cardiovascular complications being particularly prevalent, accounting for 31% of AEs related to phentermine, and indicating a need for ongoing safety monitoring of AOMs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Descriptive analysis of reported adverse events associated with anti-obesity medications using FDA Adverse Event Reporting System (FAERS) databases 2013-2020. Alsuhibani, A., Alrasheed, M., Gari, M., et al.[2022]

Recent advancements in obesity drug therapy include new combinations of existing medications and higher doses of approved drugs, showing promise for effective weight management.

Despite the potential of these new drugs, challenges such as cost, patient acceptance, and the need for more evidence on long-term cardiovascular benefits remain significant barriers to their integration into clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New medications for treatment of obesity: metabolic and cardiovascular effects. Pucci, A., Finer, N.[2017]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Naltrexone/bupropion for the treatment of obesity and obesity with Type 2 diabetes. [2016]

2. United States pubmed.ncbi.nlm.nih.gov

ACS chemical neuroscience molecule spotlight on contrave. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Naltrexone/Bupropion ER (Contrave): Newly Approved Treatment Option for Chronic Weight Management in Obese Adults. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Contrave, a bupropion and naltrexone combination therapy for the potential treatment of obesity. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Obesity consults--comprehensive obesity management in 2013: understanding the shifting paradigm. [2018]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Descriptive analysis of reported adverse events associated with anti-obesity medications using FDA Adverse Event Reporting System (FAERS) databases 2013-2020. [2022]

7. England pubmed.ncbi.nlm.nih.gov

New medications for treatment of obesity: metabolic and cardiovascular effects. [2017]