Pharmacotherapy + Lifestyle Counseling for Obesity Management

(PROJECT-BARI Trial)

Overseen By Qin Wang

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, Irvine

Must not be taking: MAO inhibitors, Antidepressants, Stimulants, Weight loss drugs

Disqualifiers: Type 1 diabetes, Uncontrolled hypertension, Cardiovascular disease, Cancer, others

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

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 tests whether medication combined with lifestyle counseling can help manage weight regain after bariatric surgery. Participants receive various treatments, including medications like phentermine (a weight loss drug) and topiramate, or a placebo. The trial aims to identify the best approach to reverse weight gain after surgery. Individuals who have experienced significant weight regain after gastric surgery and have a body mass index (BMI) of 30 or higher, or 27 with related health issues, may be suitable for this study. As a Phase 4 trial, this research involves FDA-approved treatments that have proven effective, aiming to understand how they can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are currently taking certain medications like phentermine, topiramate, stimulants, or weight loss drugs. It's best to discuss your specific medications with the study team.

What is the safety track record for these treatments?

Research shows that the combination of phentermine and topiramate is generally well-tolerated for weight loss. Studies have found that using these drugs together can cause fewer side effects than taking each one alone. The FDA has approved this combination for weight management, indicating it is safe when used as directed. Common side effects might include tingling in the hands and feet, dizziness, or dry mouth.

For phentermine alone, research suggests it is safe for longer use than initially approved, without increasing the risk of heart problems. Although usually used for a short time, some studies suggest it can be used longer without major safety concerns. Possible side effects include a faster heartbeat, restlessness, or trouble sleeping.

Topiramate is not FDA-approved for weight loss by itself, but studies have examined its safety for this purpose. In trials, it helped with weight loss and was generally well-tolerated. Some people might experience side effects like changes in taste, tiredness, or memory issues.

Overall, these treatments seem safe for managing obesity when following the prescribed guidelines. However, discussing any concerns with a healthcare provider before starting treatment is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for obesity management because they explore a combination of medication and lifestyle changes in a new way. Unlike the standard of care, which typically involves lifestyle modifications or single-drug therapies, this study examines the potential of phentermine combined with topiramate, as well as higher doses of phentermine alone. This combination and dosing strategy aim to enhance weight loss effectiveness by potentially offering a more potent option for those who don't respond to current treatments. Additionally, the approach of pairing medication with lifestyle counseling could provide a comprehensive solution, addressing both physiological and behavioral aspects of obesity.

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

Research shows that using phentermine and topiramate together, as tested in this trial, can help people with obesity lose a significant amount of weight. Studies have found that this combination can lead to up to 13% weight loss, surpassing the effects of either drug alone. In this trial, some participants will receive phentermine alone, which has also proven effective, with weight loss ranging from 4% to 19%. Others will receive topiramate by itself, which can result in about 5% to 7% weight loss over several months. Overall, these treatments hold strong potential for managing weight regain after weight-loss surgery. ^{6 7 8 9 10}

Who Is on the Research Team?

Kishore M Gadde, MD

Principal Investigator

University of California, Irvine

Are You a Good Fit for This Trial?

Adults aged 18-70 who had bariatric surgery (SG or RYGB) between 1.5 and 10 years ago, with a BMI ≥30 kg/m2 (or ≥27 kg/m2 with weight-related issues), experiencing weight regain of at least 5%. Must not have conditions like epilepsy, uncontrolled hypertension, severe heart disease, type 1 diabetes or insulin-dependent type 2 diabetes, certain mental health disorders, recent drug abuse history, or be pregnant/breastfeeding.

Inclusion Criteria

Body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 with weight-related comorbidities

I am using birth control and my pregnancy test before the study was negative.

Must be able to provide written informed consent

Exclusion Criteria

Binge Eating Scale (BES) score of ≥27

I plan to have more weight loss surgery within the next 13 months.

Known hypersensitivity or idiosyncrasy to sympathomimetic amines

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Participants are randomized to receive topiramate, phentermine, or placebo for 4 months

4 months

Monthly visits for monitoring and dose adjustments

Re-randomization and Continued Treatment

Nonresponders are re-randomized to higher doses or combination therapy; responders continue initial treatment

8 months

Monthly visits for monitoring and dose adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Phentermine
• Placebo
• Topiramate

Trial Overview The trial is testing if Phentermine and Topiramate medications combined with lifestyle counseling can help reverse weight gain after bariatric surgery compared to a placebo. Participants are randomly assigned to different treatments in stages based on their initial response.

How Is the Trial Designed?

Group I: Group F: Phentermine 15 mg/Topiramate 100 mg Experimental Treatment 2 Interventions

Nonresponders in the phentermine group at Month 4 will be re-randomized in a 1:1 ratio to receive phentermine 30 mg or phentermine/topiramate 15/100 mg during Months 5-12. Doses will be titrated in Month 5.

Group II: Group E: Phentermine 30 mg Experimental Treatment 1 Intervention

Nonresponders in the phentermine group at Month 4 will be re-randomized in a 1:1 ratio to receive phentermine 30 mg or phentermine/topiramate 15/100 mg during Months 5-12. Doses will be titrated in Month 5.

Group III: Group D: Phentermine 15 mg Experimental Treatment 1 Intervention

Phentermine will be started at 7.5 mg daily and the dose will be increased to 15 mg after 15 days. Responders at Month 4 will continue the same treatment until Month 12.

Group IV: Group C: Phentermine 15 mg/Topiramate 100 mg Experimental Treatment 2 Interventions

Nonresponders in the topiramate group at Month 4 will be re-randomized in a 1:1 ratio to receive topiramate 100 mg or phentermine/topiramate 15/100 mg during Months 5-12. Doses will be titrated in Month 5.

Group V: Group B: Topiramate 100 mg Experimental Treatment 1 Intervention

Nonresponders in the topiramate group at Month 4 will be re-randomized in a 1:1 ratio to receive topiramate 100 mg or phentermine/topiramate 15/100 mg during Months 5-12. Doses will be titrated in Month 5.

Group VI: Group A: Topiramate 50 mg Experimental Treatment 1 Intervention

Topiramate will be started at 25 mg daily and the dose will be increased to 50 mg daily after 15 days. Responders at Month 4 will continue the same treatment until Month 12.

Group VII: Group P: Placebo Placebo Group 1 Intervention

Placebo group will receive placebo.

Who Is Running the Clinical Trial?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

Qsymia™, a combination of phentermine and topiramate, has been shown to produce greater weight loss than either drug alone, making it an effective treatment for obesity since its approval in 2012.

While Qsymia™ is effective, it carries potential risks such as teratogenicity, increased heart rate, psychiatric and cognitive side effects, and metabolic acidosis, which are consistent with the known side effects of its individual components.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of phentermine/topiramate (Qsymia™) combination for the treatment of obesity. Shin, JH., Gadde, KM.[2021]

Pharmacologic treatments for obesity, such as phentermine, sibutramine, and orlistat, typically lead to an additional weight loss of about 2-5 kg compared to placebo, but there is a need for more effective and safer options.

Several new antiobesity drugs are in late-stage development, targeting various mechanisms like appetite suppression and nutrient absorption, which may enhance treatment options for obesity in the near future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drugs in the pipeline for the obesity market. Klonoff, DC., Greenway, F.[2021]

Lorcaserin and phentermine/topiramate ER are effective pharmacologic options for obesity management, showing significant weight reduction and improvements in cardiovascular and metabolic health markers, such as blood pressure and HbA1C.

Both agents were approved by the FDA in 2012, marking a significant advancement in obesity treatment options since orlistat's approval in 1999, and they work through different mechanisms: lorcaserin acts as a serotonin agonist, while phentermine/topiramate combines a sympathomimetic agent with an antiepileptic drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New antiobesity agents: lorcaserin (Belviq) and phentermine/topiramate ER (Qsymia). Shyh, G., Cheng-Lai, A.[2018]

Pharmacotherapy can be an effective option for patients with obesity (BMI of 30 or greater) or overweight (BMI of 27 or greater with coexisting conditions) when lifestyle changes alone do not lead to sufficient weight loss, emphasizing the importance of combining medication with lifestyle interventions.

Five medications are currently approved for weight management in adults, and treatment should be personalized based on individual patient needs, with regular assessments to ensure at least 5% body weight loss is achieved within three months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity: Pharmacotherapy. Powell, A.[2020]

The fixed-dose combination of phentermine and topiramate has been recently approved by the US FDA as an effective antiobesity treatment, leveraging the weight loss mechanisms of both drugs.

Clinical trials have demonstrated the efficacy and safety of this combination therapy, making it a promising option for individuals struggling with obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fixed-dose combination of phentermine-topiramate for the treatment of obesity. Halpern, B., Faria, AM., Halpern, A.[2018]

In a study involving 42 adolescents aged 12 to 17 with obesity, the fixed-dose combination of phentermine and topiramate (VI-0521) led to significant weight loss, with 13.3% of the mid-dose group and 50.0% of the top-dose group achieving at least a 5% reduction in weight by day 56.

The combination was found to be safe and well-tolerated, with pharmacokinetic profiles similar to those observed in adults, suggesting that both mid- and top-dose levels are suitable for further long-term studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled, pharmacokinetic and pharmacodynamic study of a fixed-dose combination of phentermine/topiramate in adolescents with obesity. Hsia, DS., Gosselin, NH., Williams, J., et al.[2022]

The FDA has approved lorcaserin and the combination of phentermine and extended-release topiramate (phentermine/topiramate ER) for obesity treatment, expanding options beyond orlistat and supporting long-term weight management alongside lifestyle changes.

Phentermine/topiramate ER has been shown to result in greater weight loss compared to using phentermine or topiramate alone, and it may also improve cardiometabolic risk factors, although more long-term safety data is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of obesity and cardiometabolic risk - role of phentermine/extended release topiramate. Sweeting, AN., Tabet, E., Caterson, ID., et al.[2021]

Qsymia™, a once-daily oral capsule combining phentermine and extended-release topiramate, has been approved in the US for treating obesity, leveraging phentermine's appetite-suppressing effects and topiramate's ability to increase feelings of fullness.

The formulation is also being explored for potential benefits in treating sleep apnea and type 2 diabetes, indicating its broader therapeutic applications beyond weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phentermine and topiramate extended release (Qsymia™): first global approval. Cameron, F., Whiteside, G., McKeage, K.[2021]

In a study of morbidly obese patients preparing for bariatric surgery, those treated with a combination of fluoxetine and topiramate lost more weight at 3 and 6 months compared to those on either medication alone.

This suggests that using both fluoxetine and topiramate may be an effective strategy for managing eating behaviors and promoting weight loss in patients with eating disorders before undergoing surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoxetine, topiramate, and combination of both to stabilize eating behavior before bariatric surgery. Guisado-Macías, JA., Méndez-Sánchez, F., Baltasar-Tello, I., et al.[2022]

In a study of 3,411 adults with obesity, anti-obesity medications (AOMs) led to an average weight loss of 3.45% over 12 weeks, demonstrating their effectiveness in real-world settings.

Phentermine hydrochloride and phentermine-topiramate were the most effective AOMs, resulting in greater weight loss compared to lorcaserin and bupropion-naltrexone, suggesting they should be prioritized in obesity treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

THE BENEFIT OF SHORT-TERM WEIGHT LOSS WITH ANTI-OBESITY MEDICATIONS IN REAL-WORLD CLINICAL PRACTICE. Shibuya, K., Ali, KF., Ji, X., et al.[2021]

Pharmacotherapy for obesity can be considered for individuals with a BMI of 30 or greater, or 27 or greater with weight-related health issues, highlighting the importance of medication in weight management when lifestyle changes alone are insufficient.

The effectiveness of antiobesity medications, such as phentermine and liraglutide, relies on customizing treatment to individual patient behaviors and health conditions, along with careful monitoring of their safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity Pharmacotherapy. Saunders, KH., Umashanker, D., Igel, LI., et al.[2022]

Citations

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Obesity pillars roundtable: Phentermine – Past, present, and ... Conversely, from the perspective of retrospective medical chart reviews, the reported weight reduction efficacy of phentermine seems to range from 4% to 19%.

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Safety and Effectiveness of Longer‐Term Phentermine Use Lifestyle interventions remain the cornerstone of treatment for patients with obesity, typically yielding a peak weight loss of 5% to 10% after.

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Adipex-p (phentermine hydrochloride) capsules label Because pediatric obesity is a chronic condition requiring long-term treatment, the use of this product, approved for short-term therapy, is not recommended.

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Safety and Effectiveness of Longer-Term Phentermine Use Greater weight loss without increased risk of incident CVD or death was observed in patients using phentermine monotherapy for longer than 3 months.

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Phentermine (oral route) - Side effects & dosage Phentermine is used for weight reduction in patients with obesity. ... Safety and efficacy have not been established. Geriatric. Appropriate ...

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Safety and Effectiveness of Longer‐Term Phentermine Use ... Our results show that longer-term phentermine users experienced greater weight loss without apparent increases in cardiovascular risk. Given the ...

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Phentermine (Adipex-P): Uses, Side Effects, Dosage & More Phentermine (Adipex-P) is meant for short-term treatment only. It's FDA-approved to be taken for up to 3 months. Talk with your primary care ...