Medication + Behavioral Therapy for Post-Bariatric Surgery Weight Control

Overseen By Valentina Ivezaj, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Yale University

Must be taking: Naltrexone, Bupropion

Must not be taking: MAOI, Opiates

Disqualifiers: Seizures, Bulimia, Hypertension, Diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the best way to manage weight and control eating after bariatric surgery. It tests both behavioral counseling and a combination of two medications, naltrexone and bupropion (used for weight management), taken together or separately. The trial seeks participants who had gastric bypass or sleeve surgery about six months ago and often experience loss-of-control eating. Participants will receive different treatment combinations to determine the most effective approach.

As a Phase 2/3 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval. It offers participants a chance to contribute to potentially groundbreaking weight management solutions.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that are a contraindication to the study medication, such as MAOIs or opiates, and any other medications for weight loss. If you are on these medications, you may need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that behavioral weight loss therapy is generally safe and well-tolerated. It aids weight loss by teaching individuals to change their eating and exercise habits. No major risks have been reported with this approach.

In contrast, the medication combination of naltrexone and bupropion is approved for weight management. Studies indicate it is effective for weight loss, but some safety concerns exist. Common side effects include nausea, headache, and dizziness. Serious side effects are rare but can include increased blood pressure and seizures, particularly in individuals with certain medical conditions or those taking other medications.

Combining behavioral therapy with naltrexone and bupropion might lead to better results. However, awareness of the medication's side effects is important. Consulting a healthcare provider is essential to determine the best approach. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine medication with behavioral therapy, offering a dual approach to manage weight after bariatric surgery. Unlike most current treatments that often focus solely on diet and lifestyle changes, this approach uses Naltrexone and Bupropion (NB) medication, which targets the brain's reward system to reduce cravings and control appetite. The integration of Behavioral Weight Loss (BWL) counseling helps reinforce healthy habits, potentially leading to more sustainable weight control. This combination could be more effective than standard options by addressing both psychological and physiological aspects of weight management.

What evidence suggests that this trial's treatments could be effective for weight control after bariatric surgery?

This trial will evaluate different strategies for weight control after bariatric surgery. Studies have shown that behavioral weight loss strategies can help maintain weight loss post-surgery by focusing on long-term success. In this trial, some participants will receive Behavioral Weight Loss (BWL) therapy. Research has also shown that combining the medications naltrexone and bupropion can prevent weight gain after surgery. Specifically, after six months, about 42.5% of patients taking these medications lost at least 5% of their body weight. Participants in this trial may receive the Naltrexone and Bupropion (NB) medication. Using both behavioral therapy and medication might be even more effective for managing weight and eating habits after surgery, and this trial will test the combination of BWL and NB medication. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

Adults aged 18-70 who've had bariatric surgery (gastric bypass or sleeve gastrectomy) about six months ago, with a BMI of 30-50 (or ≥27 if they have certain health issues), experiencing weekly loss-of-control eating. They must be generally healthy, not on weight loss or contraindicated meds, and able to commit to up to 19 months in the study.

Inclusion Criteria

Provide a signed and dated written informed consent prior to study participation.

Be available for participation in the study for up to 19 months (7-month treatment plus 12-month follow up).

I have had weight loss surgery.

Exclusion Criteria

Has a co-existing psychiatric condition that requires hospitalization or more intensive treatment (such as bipolar mood disorders, psychotic illnesses, or severe depression)

My blood pressure or heart rate is higher than normal and untreated.

I am currently receiving treatment for an eating disorder or to lose weight.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 16 weeks of behavioral weight loss counseling and/or naltrexone/bupropion medication or placebo

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Behavioral Weight Loss
• Naltrexone and Bupropion medication
• Placebo

Trial Overview The trial is testing how well behavioral weight loss strategies work compared to or combined with Naltrexone/Bupropion medication for controlling eating and managing weight after bariatric surgery. Participants will either receive the drug combo, placebo, or just behavioral therapy.

How Is the Trial Designed?

Group I: NB medication Experimental Treatment 1 Intervention

Participants randomly assigned to this arm will receive 16 weeks of NB medication taken daily in pill form.

Group II: Behavioral Weight Loss (BWL) + Naltrexone and Bupropion (NB) medication Experimental Treatment 2 Interventions

Participants randomly assigned to this arm will receive 16 weeks of BWL counseling and NB medication. The naltrexone and bupropion will be taken daily in pill form.

Group III: BWL + Placebo Experimental Treatment 2 Interventions

Participants randomly assigned to this arm will receive 16 weeks of BWL counseling and placebo. Placebo will be inactive and taken daily in pill form.

Group IV: Placebo Placebo Group 1 Intervention

Participants randomly assigned to this arm will receive 16 weeks of placebo. Placebo will be inactive and taken daily in pill form.

Behavioral Weight Loss is already approved in United States, European Union for the following indications:

Approved in United States as Behavioral Weight Loss Therapy for:

• Obesity
• Weight Loss Maintenance
• Type 2 Diabetes Prevention

Approved in European Union as Intensive Behavioral Therapy for Obesity for:

• Obesity
• Weight Loss Maintenance
• Type 2 Diabetes Prevention

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

A systematic review of 13 studies indicates that weight management medications can help post-bariatric surgery patients lose additional weight, with topiramate and phentermine showing slightly better results compared to other medications.

Patients who underwent gastric sleeve surgery experienced less weight loss with medication compared to those who had roux-en-y bypass or adjustable gastric banding, highlighting the need for tailored approaches in weight management after different types of bariatric surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness and safety of pharmaceuticals to manage excess weight post-bariatric surgery: a systematic literature review. Wharton, S., Kamran, E., Muqeem, M., et al.[2020]

Obesity is a chronic disease that requires a comprehensive treatment approach, including lifestyle changes, physical activity, and potentially pharmacological or surgical interventions.

Combining pharmacological treatments, like naltrexone-bupropion or liraglutide, with lifestyle changes and bariatric surgery leads to the best long-term outcomes for weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiobesity drugs before and after bariatric surgery - how to make the best use of them. Šrámková, P., Fried, M.[2022]

Naltrexone/bupropion, an investigational weight loss medication, resulted in a significant mean weight loss of 4.7% after one year in obese patients, with 26-33% of participants achieving at least 5% weight loss compared to placebo.

In addition to weight loss, naltrexone/bupropion improved various health markers, including waist circumference and triglyceride levels, and reduced hemoglobin A1c by approximately 0.5% in patients with diabetes, although it had some common side effects like nausea and dizziness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone/bupropion: an investigational combination for weight loss and maintenance. Makowski, CT., Gwinn, KM., Hurren, KM.[2022]

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]

The naltrexone/bupropion combination therapy has been developed to help manage obesity by targeting brain mechanisms that regulate body weight, showing unique effects on reducing food cravings.

Clinical trials indicate that this combination therapy is generally safe and well-tolerated, but a cardiovascular outcomes study is required by the FDA to assess long-term safety in overweight and obese individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with naltrexone and bupropion for obesity. Billes, SK., Greenway, FL.[2013]

The combination of naltrexone and bupropion has been approved for obesity treatment and is more effective for weight loss than either medication alone, especially when paired with lifestyle changes and calorie reduction.

Clinical trials indicate that this combination can lead to significant weight loss (over 5% of total body weight) over 6 months to 1 year, but careful patient selection is important to minimize serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone HCI/bupropion HCI for chronic weight management in obese adults: patient selection and perspectives. Tek, C.[2022]

A systematic review of 14 studies, including 10 randomized controlled trials, found that naltrexone/bupropion is effective for weight loss in obese patients, with many achieving at least 5% or 10% weight loss as a primary outcome.

The treatment was generally well tolerated, with few reported side effects, suggesting it is a safe option for weight management, especially when combined with mental health support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of naltrexone for weight loss in adult patients - a systematic review. Kulak-Bejda, A., Bejda, G., Waszkiewicz, N.[2022]

The combination of 32 mg naltrexone and 360 mg bupropion (NB32) led to significant weight loss of 5.0-9.3% over 56 weeks, with 45-66% of patients achieving at least 5% weight loss, indicating its efficacy as a weight management treatment.

NB32 also improved metabolic health by decreasing waist circumference, serum triglycerides, and insulin resistance, while increasing HDL cholesterol, although it was associated with mild side effects like nausea and a small increase in heart rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of the naltrexone/bupropion combination for the treatment of obesity: an update. Christou, GA., Kiortsis, DN.[2019]

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]

In 56-week phase III trials, naltrexone extended-release/bupropion extended-release (Contrave) significantly reduced body weight compared to placebo, with many patients achieving weight loss of 5% or more.

The treatment also led to notable improvements in cardiometabolic risk factors and glycated hemoglobin levels in overweight or obese adults with type 2 diabetes, and was generally well tolerated, with nausea being the most common side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone ER/Bupropion ER: A Review in Obesity Management. Greig, SL., Keating, GM.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36268671/

and five-year follow-up results of a randomized controlled ... We investigated whether cognitive behavior therapy (CBT) prior to bariatric surgery improved weight maintenance and mental health after surgery.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9244319/

Behavioral Interventions After Bariatric Surgery - PMC Postoperative behavioral weight management approaches are available for optimizing weight change for both short- and long-term outcomes.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05157698

Pharmacological and Behavioral Treatment After Bariatric ... This study will compare the effectiveness of behavioral and pharmacologic treatment, alone and combined, for improvements in weight loss, cardiovascular risk ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2807934

Efficacy of Telephone-Based Cognitive Behavioral Therapy ... This study found that tele-CBT delivered 1 year after surgery resulted in no change in short-term weight outcomes but improved disordered eating and ...

5. hopkinsmedicine.org hopkinsmedicine.org/health/treatment-tests-and-therapies/intensive-behavioral-therapy-for-obesity

Intensive Behavioral Therapy for Obesity This helps you lose weight. Intensive behavioral therapy can work very well. It targets poor habits that lead to obesity. These may include unhealthy eating and ...

6. cms.gov cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?&NcaName=Intensive%20Behavioral%20Therapy%20for%20Obesity&NCAId=253

Decision Memo - Intensive Behavioral Therapy for Obesity The authors reported: “Behaviorally based treatment resulted in 3-kg (6.6-lb) greater weight loss in intervention than control participants ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6800068/

Intensive Behavioral Therapy for Obesity Combined with ... Participants in the IBT-alone group lost a mean 6.1% of baseline weight at 1 year, and 44% lost ≥5% of body weight, a common criterion of clinically meaningful ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5503454/

Behavioral Lifestyle Interventions for Moderate and Severe ... This study reviews evidence of behavioral lifestyle interventions for weight loss in this population.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT01572090

Comparison of Weight Loss Induced by Bariatric Surgery ... Conventional weight loss will be achieved by "Lifestyle changes" including advice on increasing physical activity and prescription of a hypocaloric diet ...