Weight Management Treatments for Obesity

Recruiting at 1 trial location

Overseen By Michelle I Cardel, PhD, RD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Michelle Cardel, PhD, MS, RD

Must be taking: GLP-1 medications

Must not be taking: Antipsychotics, Opioids, SSRIs, SNRIs

Disqualifiers: Diabetes, Pregnancy, Seizures, 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: Unknown

Duration: 12 weeks

225 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new methods to manage weight for individuals who have stopped using medications like Wegovy or Ozempic. It compares three approaches: using special medications (such as the combination drug Bupropion-Naltrexone), combining medications with support from a weight management clinic, and receiving clinic support without medications. The goal is to determine which method helps maintain or continue weight loss over 12 weeks. This trial may suit those who have lost significant weight with these medications, are willing to stop taking them, and have conditions like high blood pressure or sleep apnea. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, helping researchers understand its benefits for more patients.

Will I have to stop taking my current medications?

Yes, you will need to stop taking your GLP-1 medication (like Wegovy, Ozempic, Mounjaro, or Zepbound) to participate in this trial. The trial is specifically for those who are willing to discontinue these medications.

What is the safety track record for these treatments?

Previous studies have shown that the combination of bupropion and naltrexone, often sold under the brand name Contrave, presents no heart-related safety concerns when used for up to 12 months. This indicates that the treatment is generally well-tolerated with no major heart risks. Additionally, no evidence suggests that this medication can be abused.

For the combination of bupropion, naltrexone, and metformin, specific safety data is less available. However, studies have shown that bupropion and naltrexone together aid in weight loss without significant safety issues.

This trial is in Phase 4, indicating that the FDA has approved the treatments for other uses. Phase 4 trials typically assess the effectiveness and safety of these treatments in a larger population. While the treatments are expected to be safe for most people, ongoing monitoring helps identify any rare side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for obesity because they combine medications like Bupropion-Naltrexone and Metformin with behavioral support from the WW Clinic. Unlike standard treatments that often focus solely on medication or lifestyle changes, this approach integrates both to potentially enhance effectiveness. The Bupropion-Naltrexone-Metformin combination is particularly promising as it targets multiple pathways involved in weight management, which might offer a more comprehensive solution compared to single-action treatments. Additionally, the inclusion of the WW Clinic's support could improve long-term adherence and lifestyle changes, setting it apart from many current options.

What evidence suggests that this trial's treatments could be effective for weight management?

Research has shown that bupropion-naltrexone, one of the treatments in this trial, can aid in weight loss. In one study, participants lost an average of 9.5% of their body weight over 56 weeks, a significant reduction compared to those not taking the drug. Adding metformin to bupropion-naltrexone, another treatment option in this trial, might help maintain weight loss longer, as metformin can support continued weight reduction.

Conversely, the WW Clinic program, also under study in this trial, has demonstrated impressive results. A recent study found that participants in this program lost up to 21% of their body weight over 12 months. This suggests that the WW Clinic can be highly effective for long-term weight management. Overall, these treatments have shown promising results in helping people manage their weight effectively. ^{1 2 6 7 8}

Who Is on the Research Team?

Michelle Cardel, PhD, RD

Principal Investigator

WW International Inc

Are You a Good Fit for This Trial?

This trial is for individuals who have been using semaglutide or tirzepatide for obesity but are stopping these medications. Participants should be adults looking to manage their weight post-discontinuation.

Inclusion Criteria

Able to read and write in English

Ability to provide informed consent prior to any trial-related activities

I have had a BMI over 30, or over 27 with a condition like high blood pressure.

Exclusion Criteria

I am currently taking beta blockers.

Breastfeeding

BMI <26 kg/m2

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive behavioral or lifestyle support from WW Clinic with or without medications for weight management

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bupropion-Naltrexone
• Bupropion-Naltrexone-Metformin
• WW Clinic

Trial Overview

The study examines three treatments: a combination of Bupropion-Naltrexone-Metformin, just Bupropion-Naltrexone, and a Weight Watchers Clinic program. The goal is to see which helps maintain or reduce weight after stopping GLP-1 meds over 12 weeks.

How Is the Trial Designed?

Group I: WW Clinic - No medications Experimental Treatment 1 Intervention

Participants in this group receive behavioral or lifestyle support from WW Clinic. They receive no medications.

Group II: WW Clinic + Meds v2 Experimental Treatment 2 Interventions

Participants in this group receive behavioral or lifestyle support from WW Clinic. They receive medications prescribed through WW Clinic.

Group III: WW Clinic + Meds v1 Experimental Treatment 2 Interventions

Participants in this group receive behavioral or lifestyle support from WW Clinic. They receive medications prescribed through WW Clinic.

Who Is Running the Clinical Trial?

Michelle Cardel, PhD, MS, RD

Lead Sponsor

Trials

2

Recruited

330+

Published Research Related to This Trial

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]

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]

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]

Naltrexone/bupropion (Mysimba) is an effective treatment for adults who are obese or overweight with at least one weight-related health issue, and it is intended to be used alongside diet and lifestyle changes.

The combination product was licensed by the European Medicines Agency in 2015 and has recently been introduced in the UK, indicating its recognized safety and efficacy in managing obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone/bupropion for obesity. [2018]

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 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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4771085/

Naltrexone/Bupropion ER (Contrave) - PubMed Central - NIH

Patients treated with naltrexone/bupropion 32 mg/360 mg achieved statistically and clinically significant weight reduction when compared with placebo in all ...

2.

curraxpharma.com

curraxpharma.com/press-releases/currax-announces-obesityweek-data-showing-that-contrave-helps-curb-cravings-and-offers-marked-effectiveness-in-certain-populations-with-obesity/

Currax Announces ObesityWeek® Data Showing that ...

The study further showed that patients taking CONTRAVE had an average weight loss of 9.5% at 56 weeks compared to 2.7% for placebo (p <0.0001).

3.

ema.europa.eu

ema.europa.eu/en/news/ema-concludes-review-weight-management-medicine-mysimba

EMA concludes review of weight management medicine ...

A review of available data has concluded that the benefits of Mysimba, a medicine used for weight management, continue to outweigh its risks. · A ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S2667368125000142

Appropriate use of the fixed-dose, extended-release ...

At 56 weeks, NB-ER 16 mg was associated with 5.0 % weight reduction and NB-ER 32 mg was associated with 6.1 % weight reduction vs 1.3 % for placebo [30].

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10387935/

Medications for obesity management: Effectiveness and ...

Branded bupropion/naltrexone was cost-effective at higher thresholds only. When prescribed as combinations of their generic components, phentermine/topiramate ...

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2021/200063s020lbl.pdf

Contrave - accessdata.fda.gov

Separate studies with bupropion and naltrexone have been conducted in pregnant rats and rabbits. Safety margins were estimated using body surface area exposure ...

7.

medsafe.govt.nz

medsafe.govt.nz/profs/PUArticles/June2025/Spotlight-on-Contrave.html

Spotlight on Contrave (naltrexone + bupropion)

Contrave contains naltrexone and bupropion and is indicated for weight management in adults. Significant safety issues associated with Contrave ...

8.

mayoclinic.org

mayoclinic.org/drugs-supplements/naltrexone-and-bupropion-oral-route/description/drg-20122495

Naltrexone and bupropion (oral route) - Side effects & ...

Safety and efficacy have not been established. Geriatric. Appropriate ... For weight loss: Adults—At first, one tablet in the morning taken on week 1 ...