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

Trial Summary

What is the purpose of this trial?

This trial will test different treatments for people who have trouble controlling their eating and weight after weight-loss surgery. The treatments include behavior therapy to change eating habits and a combination of two medications to reduce cravings. The goal is to find out which approach works best for these patients.

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.

What data supports the effectiveness of the drug Naltrexone/Bupropion for weight control after bariatric surgery?

Research shows that the combination of Naltrexone and Bupropion is effective for weight loss in obese adults, especially when combined with lifestyle changes and calorie reduction. Studies indicate that this combination can lead to significant weight loss, more than using each drug alone. ^{1 2 3 4 5}

Is the combination of naltrexone and bupropion safe for weight management in humans?

The combination of naltrexone and bupropion, used for weight management, has been generally well tolerated in clinical trials, with nausea being the most common side effect. These trials showed that it is a safe option for managing weight in obese adults or those with weight-related health issues. ^{1 2 3 6 7}

How does the drug combination of naltrexone and bupropion help with weight control after bariatric surgery?

The combination of naltrexone and bupropion is unique because it targets the brain's reward system to help control eating behavior, making it more effective for weight loss when combined with lifestyle changes than either drug alone. This approach is particularly useful for managing weight regain after bariatric surgery, offering a novel option compared to traditional weight loss medications. ^{1 4 8 9 10}

Eligibility Criteria

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 am between 18 and 70 years old.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

References

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

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

Naltrexone/bupropion: an investigational combination for weight loss and maintenance. [2022]

3. Poland pubmed.ncbi.nlm.nih.gov

Safety and efficacy of naltrexone for weight loss in adult patients - a systematic review. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

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

7. New Zealand pubmed.ncbi.nlm.nih.gov

Naltrexone ER/Bupropion ER: A Review in Obesity Management. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Combination therapy with naltrexone and bupropion for obesity. [2013]

9. Czech Republic pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

The effectiveness and safety of pharmaceuticals to manage excess weight post-bariatric surgery: a systematic literature review. [2020]