Naltrexone/Bupropion for Obesity

Overseen By Sarah Borden, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Columbia University

Must be taking: Naltrexone/bupropion

Must not be taking: Dopamine agonists, Opioid analgesics

Disqualifiers: Diabetes, Cardiovascular disease, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how genetics might influence weight loss with the medication naltrexone/bupropion, which is already approved for this purpose. Researchers aim to determine if certain genetic traits result in greater weight loss. Participants will initially follow a calorie-restricted diet, then combine it with the medication. Ideal candidates include those who have struggled with obesity (BMI of 30 or higher) or have a lower BMI with a related health condition, such as controlled high blood pressure or joint issues due to weight. As a Phase 4 trial, this research seeks to understand how the FDA-approved treatment can benefit more patients.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications. The trial excludes participants using dopamine agonists, opioid analgesics, antipsychotics, antidepressants, neuroleptics, naltrexone, diabetes medications, and MAO inhibitors within 14 days prior to screening. It also excludes those using weight loss medication within the prior six months.

What is the safety track record for Naltrexone/Bupropion?

Research shows that the medication naltrexone/bupropion can aid in weight loss. Studies have found that individuals taking this medication might lose about 9.5% of their body weight in a year. However, some side effects require attention. For instance, it may increase blood pressure, so monitoring is important.

Other studies have found that while the medication supports weight loss, it may also cause more side effects than not taking it. These side effects can include nausea or headaches, but they vary among individuals.

On a positive note, research indicates that this medication does not increase the risk of heart problems compared to similar treatments. While effective for weight loss, considering these safety factors is crucial. Always consult a doctor to determine if this is the right option. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Naltrexone/Bupropion for obesity because it combines two medications that work synergistically to help with weight loss. Unlike standard treatments like lifestyle changes or medications that target only appetite suppression or fat absorption, this combination influences both the brain’s reward system and appetite regulation. Naltrexone, typically used for addiction, and Bupropion, an antidepressant, together may offer a unique dual-action approach to managing obesity, potentially improving effectiveness and patient outcomes.

What is the effectiveness track record for Naltrexone/Bupropion in treating obesity?

Research shows that the medication naltrexone/bupropion, often sold under the brand name CONTRAVE, helps people with obesity lose weight. In studies, patients taking this medication lost an average of 9.5% of their body weight over 56 weeks. This contrasts with the 2.7% weight loss seen in those taking a placebo, which contains no active medicine. Additionally, real-world evidence suggests that this treatment is effective for both individuals who have never had weight loss surgery and those who have regained weight after surgery. Participants in this trial will receive naltrexone/bupropion and are more likely to lose at least 5% of their body weight. The FDA has approved this medication for weight loss, confirming its effectiveness in treating obesity. ^{1 4 6 7 8}

Who Is on the Research Team?

Judith Korner, MD,PhD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-65 with obesity, defined as a BMI of 30-50, or overweight individuals (BMI 27-29.99) with certain weight-related health issues like controlled high blood pressure, cholesterol problems, sleep apnea, or joint arthritis.

Inclusion Criteria

My BMI is between 30-50, or 27-29.99 with a weight-related health issue.

Exclusion Criteria

My current weight is more than 5% less than my highest weight ever.

I am not taking drugs that interfere with CYP2B6.

An affirmative answer to any question in the Columbia-Suicide Severity Rating Scale

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Nutritional Counseling

Participants receive individual nutritional counseling on a calorie restricted diet, including in-person visits, blood tests, an EKG, vital signs, questionnaires, body weight, and nutritional visits

12 weeks

In-person visits

Treatment with Naltrexone/Bupropion

Participants continue dietary counseling and receive treatment with naltrexone/bupropion, including in-person and phone visits, blood tests, vital signs, questionnaires, body weight, and nutritional visits

28 weeks

In-person and phone visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Genetics and Response to Naltrexone/Bupropion

Trial Overview The study tests if genetic differences affect how well people lose weight on a calorie-restricted diet and the FDA-approved medication Naltrexone-Bupropion (NB). It's divided into three phases over one year: initial diet counseling and assessments; continued dieting plus NB treatment; then a wash-out period to see if genetics relate to maintaining weight loss.

How Is the Trial Designed?

Group I: All participants Experimental Treatment 1 Intervention

Calorie restricted diet and treatment with Naltrexone/Bupropion

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

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]

In a pilot study of 33 subjects, individuals with the A1+ genotype (carrying the A allele) experienced a mean weight loss of 5.9% with naltrexone/bupropion treatment, which was significantly above the clinically significant target of 4%.

In contrast, the A1- genotype group (without the A allele) had a mean weight loss of only 4.2%, indicating that those with the A1+ genotype may respond more effectively to this antiobesity medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight-loss response to naltrexone/bupropion is modulated by the Taq1A genetic variant near DRD2 (rs1800497): A pilot study. Mullally, JA., Chung, WK., LeDuc, CA., et al.[2022]

A systematic review of 70 studies involving naltrexone/bupropion extended release (ER) found no increased risk of major adverse cardiovascular events (MACE) in patients using this medication compared to nonusers.

The evidence suggests that naltrexone/bupropion ER is safe regarding cardiovascular events, with no significant differences in MACE rates compared to other treatments or placebo, indicating it can be a viable option for patients with obesity or overweight and cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Contrave, Naltrexone with Bupropion, Bupropion, or Naltrexone and Major Adverse Cardiovascular Events: A Systematic Literature Review. Dahlberg, S., Chang, ET., Weiss, SR., et al.[2022]

Pharmacotherapy, when combined with lifestyle changes, can significantly enhance weight loss in obese patients, serving as a viable alternative to bariatric surgery for some individuals.

Pharmacogenetics aims to identify which patients will benefit most from obesity medications while reducing the risk of side effects, highlighting the importance of personalized treatment strategies in obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacogenetics of obesity drug therapy. Guzman, AK., Ding, M., Xie, Y., et al.[2021]

Research suggests that the same brain circuits that drive drug addiction are also involved in food cravings, particularly in overweight and obese individuals, indicating a potential link between obesity and addictive behaviors.

A specific genetic variation in the D2 dopamine receptor may reduce sensitivity to dopamine, which could lead to increased cravings for food and substances, highlighting the need to explore interactions with other obesity-related genes and the role of inflammation in promoting these behaviors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addictive genes and the relationship to obesity and inflammation. Heber, D., Carpenter, CL.[2021]

A 33-year-old patient with severe obesity due to a genetic variant experienced significant weight loss of -48.9 kg (-26.7%) after 17 months of treatment with naltrexone-bupropion, following unsuccessful attempts with other treatments.

Naltrexone-bupropion not only led to substantial weight loss but also improved the patient's hyperphagia and overall quality of life, highlighting its potential as an effective treatment for genetic obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful naltrexone-bupropion treatment after several treatment failures in a patient with severe monogenic obesity. Welling, MS., Mohseni, M., van der Valk, ES., et al.[2023]

Bupropion and naltrexone have both been shown to promote weight loss individually, with bupropion demonstrating greater efficacy when used alone.

The combination of sustained-release formulations of naltrexone and bupropion may enhance weight loss effects beyond what is achieved with either drug alone, and ongoing Phase III trials will provide more information on their safety and effectiveness together.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupropion and naltrexone: a review of their use individually and in combination for the treatment of obesity. Plodkowski, RA., Nguyen, Q., Sundaram, U., et al.[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 a 56-week study involving 505 overweight or obese individuals with type 2 diabetes, the combination of naltrexone and bupropion (NB) led to significantly greater weight loss (-5.0% vs. -1.8%) and a higher percentage of participants achieving at least 5% weight loss compared to placebo (44.5% vs. 18.9%).

NB therapy also improved glycemic control, with a greater reduction in HbA1c levels (-0.6% vs. -0.1%) and a higher proportion of patients reaching HbA1c <7% (44.1% vs. 26.3%), although it was associated with increased gastrointestinal side effects like nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Hollander, P., Gupta, AK., Plodkowski, R., et al.[2022]

Citations

1. 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).

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40897847/

Real world efficacy of naltrexone/bupropion for weight ... Conclusion: Real-world data show that NB treatment is equally effective in surgery-naive patients and in patients experiencing weight regain ...

3. prnewswire.com prnewswire.com/news-releases/currax-announces-obesityweek-data-showing-that-contrave-helps-curb-cravings-and-offers-marked-effectiveness-in-certain-populations-with-obesity-302604348.html

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).

4. bpspubs.onlinelibrary.wiley.com bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.14210

Naltrexone–bupropion (Mysimba) in management of obesity ... Significantly more participants who took naltrexone–bupropion achieved ≥5% reduction in body weight: risk ratio (RR) = 2.1 (95% confidence ...

5. dmsjournal.biomedcentral.com dmsjournal.biomedcentral.com/articles/10.1186/s13098-024-01319-7

The effects of bupropion alone and combined with naltrexone ... The pooled findings showed that bupropion administration has an effect on lowering weight (WMD: -3.67 kg, 95% CI: -4.43 to -2.93) and WC (WMD: -2.98 cm, 95% CI ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7098870/

Naltrexone–bupropion (Mysimba) in management of obesity Naltrexone–bupropion significantly reduces body weight by a small amount but significantly increases the risk of adverse events.

7. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00599-6/fulltext

Safety and effects of anti-obesity medications on weight ... Naltrexone/bupropion carries a risk of increased blood pressure. Phentermine/topiramate should be used with caution due to its higher risk of ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2667368125000130

Cardiovascular safety of fixed-dose extended-release ... EHR data showed fixed-dose extended-release naltrexone/bupropion (NB-ER) vs lorcaserin did not have increased CV events. •. Patients initiating NB-ER vs ...