Anti-obesity Medication for Obesity

(STAY-LEAN Trial)

Overseen By Andrea Debs, MS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: The Cleveland Clinic

Must be taking: Tirzepatide, Semaglutide

Must not be taking: Glucocorticoids, Beta-blockers

Disqualifiers: Diabetes, Cardiovascular disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 4

150 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot be on anti-obesity medications or medications for weight loss within the past 6 months. Also, certain medications like glucocorticoids above a specific dose and medications affecting physical performance are not allowed.

What data supports the effectiveness of the drug Naltrexone-Bupropion Combination for weight loss?

Research shows that the combination of naltrexone and bupropion is more effective for weight loss than using each drug alone, especially when combined with lifestyle changes and calorie reduction. Studies indicate that this combination can lead to significant weight loss, with patients losing over 5% of their total body weight after 6 months to a year. ^{1 2 3 4 5}

Is the combination of naltrexone and bupropion safe for weight loss?

The combination of naltrexone and bupropion has been studied for weight loss, and while it shows promise, the FDA initially required more data on its heart-related safety before approval. It is now approved for chronic weight management, suggesting it has been deemed safe enough for use, but always consult with a healthcare provider for personal safety concerns. ^{2 4 5 6 7}

How does the drug naltrexone-bupropion differ from other obesity treatments?

Naltrexone-bupropion is unique because it combines two drugs: naltrexone, which is usually used to treat addiction, and bupropion, which is used for depression and smoking cessation. Together, they help with weight loss by affecting brain chemicals related to hunger and cravings, offering a new approach compared to other weight loss treatments. ^{2 4 5 7 8}

What is the purpose of this trial?

This is a prospective, pragmatic, 21 month, single-center, randomized, 2-phased, open-label, parallel-group trial comparing the use of enhanced lifestyle changes (ELC) in two different sequential anti obesity medication (AOM) therapies. The ELC consists of a medically-supervised and comprehensive weight loss program (Cleveland Clinic's Department of Endocrinology, Diabetes and Metabolism's Integrated Weight Management Program). In the first phase (9 months) of the study, all participants will receive tirzepatide 15 mg (option #1) or semaglutide 2.4 mg if tirzepatide is not tolerated. In the second phase, after completing 9 months of tirzpeatide or semaglutide, participants will continue ELC and will be randomly assigned to a different oral AOM therapy for another 12 months: group 1 (phentermine-topiramate or naltrexone-bupropion) or group 2 (orlistat). The primary endpoint will be the percentage weight loss at 21 months compared to weight loss at 9 months. The goal will be to show superiority of the arm receiving ELC plus AOM therapy (phentermine-topiramate or naltrexone-bupropion) when compared to the other AOM therapy group (orlistat). Secondary and exploratory endpoints will include percentage of fat mass loss, lean muscle mass, functional capacity, muscle strength and compliance to enhanced lifestyle changes. Informed consent will be obtained. IRB approval of the study will be obtained.

Research Team

Bartolome Burguera, M.D

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

The STAY-LEAN Trial is for individuals with obesity who are seeking weight loss. Participants will join a comprehensive weight management program and must be willing to take anti-obesity medications (AOMs). Specific eligibility details aren't provided, but typically participants should meet certain health criteria and commit to the full duration of the trial.

Inclusion Criteria

An Employee, or the significant other of an employee, that is covered by the Cleveland Clinic Employee Health Plan

Ethnicity: all ethnic groups

I am between 25 and 64 years old.

Exclusion Criteria

Patients with history of diabetes

Glomerular Filtration Rate <30 mL/min/1.73 m2 (calculated by the Chronic Kidney Disease Epidemiology Collaboration Equation, CKD-EPI)

Any condition, unwillingness, or inability, not covered by any of the other exclusion criteria, which, in the study clinician's opinion, might jeopardize the subject's safety or compliance with the protocol

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants receive tirzepatide 15 mg or semaglutide 2.4 mg for 9 months as part of the enhanced lifestyle changes program.

9 months

Monthly shared medical appointments

Treatment Phase 2

Participants continue enhanced lifestyle changes and are randomly assigned to a different oral AOM therapy for another 12 months.

12 months

Monthly shared medical appointments for the first 4 months, then every other month

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Comprehensive weight loss
• Naltrexone-Bupropion Combination
• Phentermine-Topiramate

Trial Overview This trial tests enhanced lifestyle changes combined with AOM therapies over 21 months. Initially, all receive tirzepatide or semaglutide for 9 months. Then they're randomly assigned to either phentermine-topiramate/naltrexone-bupropion or orlistat for another 12 months, alongside continued lifestyle changes.

Participant Groups

Group I: Group 2 AOM Experimental Treatment 3 Interventions

Comprehensive weight loss + Enhanced lifestyle changes + Group 2 AOM Sequential therapy (orlistat)

Group II: Group 1 AOM Experimental Treatment 4 Interventions

Comprehensive weight loss Program + Enhanced lifestyle changes + Group 1 AOM sequential therapy (phentermine-topiramate or naltrexone-bupropion)

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Findings from Research

In a study of 1,496 overweight and obese participants, the combination therapy of naltrexone and bupropion (NB32) resulted in significantly greater weight loss compared to placebo, with participants losing an average of 6.5% of their body weight at 28 weeks versus 1.9% for placebo.

NB32 not only led to substantial weight loss but also improved cardiometabolic risk factors and quality of life related to weight, with nausea being the most common mild side effect, and no increase in depression or suicidality observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Apovian, CM., Aronne, L., Rubino, D., et al.[2021]

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]

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]

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]

References

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

A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). [2021]

2. England pubmed.ncbi.nlm.nih.gov

Bupropion-SR plus naltrexone-SR for the treatment of mild-to-moderate obesity. [2015]

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

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

5. Poland pubmed.ncbi.nlm.nih.gov

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

6. Spain pubmed.ncbi.nlm.nih.gov

Bupropion/naltrexone fixed-dose combination for the treatment of obesity. [2017]

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

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

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

Drug safety evaluation of naltrexone/bupropion for the treatment of obesity. [2022]