Pharmacological and Behavioral Treatment for Obesity After Bariatric Surgery

Overseen By Carlos M Grilo, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Yale University

Must not be taking: MAOI, Opiates, Weight loss meds

Disqualifiers: Seizures, Bulimia, Bipolar, Hypertension, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores ways to help people lose weight and improve health after weight-loss surgery. It examines behavioral counseling and medication, both separately and combined, to determine the most effective method for weight loss and improving heart health and mental well-being. Individuals who have undergone gastric bypass or sleeve surgery but continue to struggle with weight loss might be suitable candidates. Participants will try different approaches, such as medication (including the combination of Naltrexone and Bupropion), counseling, or a combination, to identify the most effective method. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking medications that are a contraindication to NB medication (like MAOIs or opiates) or if you are using other weight loss medications.

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

Research has shown that using naltrexone and bupropion together is generally safe and effective for managing obesity. The FDA approved this combination for long-term use in 2014. Studies have found that although some people discontinue the medication, it remains safe for ongoing use.

Behavioral weight loss (BWL) involves learning to change eating and exercise habits. This method is often used after weight-loss surgery to help manage weight. Behavioral approaches are generally safe and focus on healthy lifestyle changes instead of medication.

Both treatments have demonstrated safety, but individual experiences can differ. It is important to consult a healthcare provider about possible side effects and any personal concerns before starting a new treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine pharmacological and behavioral approaches to tackle obesity after bariatric surgery. Unlike standard care options, which typically involve lifestyle changes or surgeries alone, this trial explores the added benefits of NB medication, a combination of naltrexone and bupropion, known for their roles in affecting appetite and weight control. Furthermore, the integration of Behavioral Weight Loss (BWL) counseling aims to address psychological aspects of weight management, potentially leading to more sustainable outcomes. This multi-faceted strategy is promising because it not only targets the biological factors of weight gain but also the behavioral patterns, offering a holistic approach to post-surgical weight management.

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

Studies have shown that behavioral weight loss therapy can reduce emotional eating, depression, and anxiety in individuals after weight-loss surgery. It plays a crucial role in a successful weight-loss plan for many patients. In this trial, some participants will receive Behavioral Weight Loss (BWL) counseling, either alone or with a placebo.

Research has indicated that combining two medications, naltrexone and bupropion, can lead to significant weight loss when paired with lifestyle changes. Some studies reported that patients lost about 4% of their body weight after six months. In this trial, other participants will receive the naltrexone and bupropion combination, either alone or with BWL counseling. Both treatments have shown promise in aiding weight loss and enhancing overall well-being after surgery. ^{3 4 5 6 7}

Who Is on the Research Team?

Valentina Ivezaj, Ph.D.

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults with obesity who've had bariatric surgery but haven't achieved desired weight loss. Participants must have a BMI between 27-50, be in good health, and willing to follow the study plan for up to 18 months. Women must use effective contraception; men should ensure contraception with partners.

Inclusion Criteria

Stated willingness to comply with all study procedures and availability for the duration of the study (up to 18 months: 6-month treatment plus 12-month follow up)

Must be an otherwise healthy subject without uncontrolled medical problems, as determined by the study physician and medical co-investigators (physical examination, laboratory studies)

For females of reproductive potential: must use highly effective contraception and agree to use such a method during study participation

Exclusion Criteria

I am currently taking medication to lose weight.

I have high blood pressure or a fast heart rate that hasn't been treated.

Has a history of allergy or sensitivity to bupropion or naltrexone

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 6 months of either NB medication, Behavioral Weight Loss counseling, or a combination, with daily pill intake

6 months

Follow-up

Participants are monitored for changes in depressive symptoms, cholesterol, HbA1C, BMI, and other health metrics

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Behavioral Weight Loss
• Naltrexone and Bupropion Combination
• Placebo

Trial Overview

The study tests if combining behavioral weight loss strategies with a medication (Naltrexone and Bupropion) is more effective than either approach alone or a placebo in improving post-surgery weight loss, cardiovascular health, and mental well-being.

How Is the Trial Designed?

Group I: NB medication Experimental Treatment 1 Intervention

Participants randomly assigned to this arm will receive 6 months of NB medication taken daily in pill form.

Group II: BWL + Placebo Experimental Treatment 2 Interventions

Participants randomly assigned to this arm will receive 6 months of Behavioral Weight Loss (BWL) counseling and placebo. Placebo will be inactive and taken daily in pill form.

Group III: BWL + NB medication Experimental Treatment 2 Interventions

Participants randomly assigned to this arm will receive 6 months of Behavioral Weight Loss (BWL) counseling and NB medication. The naltrexone and bupropion will be taken daily in pill form.

Group IV: Placebo Placebo Group 1 Intervention

Participants randomly assigned to this arm will receive 6 months 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

Cognitive Behavioral Therapy (CBT) has been shown to effectively reduce disordered eating behaviors and depressive symptoms in bariatric patients, which are linked to less optimal weight loss outcomes after surgery.

Innovative CBT delivery methods, such as telephone and internet-based programs, may provide accessible and cost-effective support for bariatric patients, potentially improving their long-term weight loss success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive behavioral therapy and predictors of weight loss in bariatric surgery patients. Paul, L., van der Heiden, C., Hoek, HW.[2018]

A study involving 128 patients awaiting bariatric surgery is investigating the impact of pre-operative cognitive behavioral therapy (CBT) on long-term weight loss maintenance and lifestyle adherence after surgery.

The hypothesis is that CBT will improve eating behaviors and psychological well-being, potentially leading to better outcomes compared to surgery alone, with assessments conducted before and up to 5 years after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does cognitive behavioral therapy strengthen the effect of bariatric surgery for obesity? Design and methods of a randomized and controlled study. Paul, L., van Rongen, S., van Hoeken, D., et al.[2018]

Bariatric surgery is recognized as the most effective long-term treatment for severe obesity, and combining it with behavioral weight management strategies can enhance weight loss outcomes.

Recent studies have explored various settings and techniques, like cognitive behavioral therapy and telemedicine, for post-surgery support, but challenges such as funding and participant dropout have limited their widespread application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioral Interventions After Bariatric Surgery. Tewksbury, C., Isom, KA.[2022]

Recent advancements in weight loss medications offer new possibilities for patients seeking further weight loss after bariatric surgery or for long-term weight maintenance, addressing a significant treatment gap.

The paper emphasizes that modern anti-obesity pharmacotherapy should not be dismissed as ineffective compared to surgery, as new classes of medications have emerged that can lead to clinically significant weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of Advances in Anti-obesity Pharmacotherapy: Implications for a Multimodal Treatment Approach with Metabolic Surgery. C Sudlow, A., W le Roux, C., J Pournaras, D.[2021]

Psychotherapeutic interventions and support groups significantly enhance weight loss outcomes after bariatric surgery, with a pooled effect size correlation of 0.18 based on a systematic review of nine studies.

There was no significant difference in effectiveness between psychotherapeutic interventions and support groups, suggesting that both approaches can be beneficial for patients undergoing bariatric surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do postoperative psychotherapeutic interventions and support groups influence weight loss following bariatric surgery? A systematic review and meta-analysis of randomized and nonrandomized trials. Beck, NN., Johannsen, M., Støving, RK., et al.[2021]

Bariatric surgery is an effective treatment for severe obesity and related comorbidities, but weight regain is common, leading to recommendations for anti-obesity drugs to help manage this issue.

Current evidence for long-term pharmacotherapy after bariatric surgery is mainly from observational studies and small trials, suggesting a need for careful selection of medications and monitoring for side effects, while awaiting results from larger, well-designed trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term pharmacotherapy of obesity in patients that have undergone bariatric surgery: pharmacological prevention and management of body weight regain. Gutt, S., Schraier, S., González Bagnes, MF., et al.[2019]

A behavioral intervention for bariatric surgery patients who had poor long-term weight loss showed a trend towards greater excess weight loss compared to a wait list control group, with participants losing an average of 6.6% of excess weight at 6 months versus 1.6% in the control group.

Patients with more depressive symptoms and less weight regain before the study experienced greater weight loss, suggesting that psychological factors may influence the effectiveness of behavioral interventions in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing long-term weight control after bariatric surgery: a pilot study. Kalarchian, MA., Marcus, MD., Courcoulas, AP., et al.[2021]

After one year post-surgery, patients who underwent Roux-en-Y gastric bypass achieved an impressive average excess body weight loss of 81.7%, with sustained weight loss observed over the following years.

The surgery significantly improved obesity-related comorbidities, particularly diabetes resolution, and while quality of life improved initially, only general health and functional capacity remained elevated after four years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes on quality of life, weight loss, and comorbidities after Roux-en-Y gastric bypass. Costa, RC., Yamaguchi, N., Santo, MA., et al.[2019]

Weight regain after bariatric surgery is a common issue, highlighting the need for ongoing support and intervention for patients post-surgery.

A multidisciplinary approach, including antiobesity medications and behavioral therapies like cognitive behavioral therapy, is recommended to help patients manage weight regain effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Weight Regain Following Bariatric Surgery: Behavioral Intervention and Pharmacotherapy. Barenbaum, SR., Zhao, AS., Saunders, KH., et al.[2022]

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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 ...