Phentermine/Topiramate for Hypothalamic Obesity

Recruiting at 1 trial location

Overseen By Stephanie Purdy

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Seattle Children's Hospital

Must be taking: Pituitary replacements, Appetite-modulating

Must not be taking: MAO inhibitors, Carbonic anhydrase inhibitors

Disqualifiers: Cardiovascular conditions, Diabetes, Liver disease, others

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: 7

Duration: 28 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called phentermine/topiramate (Ph/T) on individuals with hypothalamic obesity (HO), a condition characterized by significant weight gain following treatment for hypothalamic brain tumors. The goal is to determine if Ph/T, known for aiding appetite control and alertness, can also benefit those with HO. The trial seeks participants who have experienced rapid weight gain after tumor treatment and have a stable medical condition. It will assess safety and effectiveness, focusing on weight loss and any side effects. Participants will be randomly assigned to receive either the active drug or a placebo for 28 weeks. As a Phase 2 trial, this research aims to measure the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you have been stable on pituitary replacement and/or appetite-modulating medications for at least 2 months before joining. If you are on a new weight management medication, stimulant, or investigational medication, you must have been on it for at least 2 months before the trial.

Is there any evidence suggesting that phentermine/topiramate is likely to be safe for humans?

Research has shown that the drug phentermine/topiramate (Ph/T) is generally safe for children and teens with obesity. This medication, already approved by the FDA for treating common obesity, has been proven to help people lose a significant amount of weight. This suggests it might also be a safe option for hypothalamic obesity, although it hasn't been tested for this condition yet.

In studies with adults, those taking Ph/T lost about 7.73 kg more than those who took a placebo. Most people tolerate the treatment well, but some may experience mild side effects like dry mouth or tingling in the hands and feet. These side effects are common with weight loss medications and are usually manageable.

Since this trial is in Phase 2, researchers are still learning about the full safety of Ph/T for hypothalamic obesity. The main goal now is to find the best dose that works well with the fewest side effects. While the treatment is still being studied, its previous FDA approval for other types of obesity suggests it is generally safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hypothalamic obesity?

Researchers are excited about the use of Phentermine/Topiramate for hypothalamic obesity because it offers a fresh approach to managing this challenging condition. Unlike standard treatments, which typically focus on lifestyle changes and sometimes involve medication that targets metabolism or appetite in less specific ways, this combination drug acts on both the central nervous system to suppress appetite and the metabolic system to enhance weight loss. This dual action could potentially offer more effective weight management for patients with hypothalamic obesity, addressing both hunger and energy expenditure in a way that current single-action treatments do not.

What evidence suggests that Phentermine/Topiramate might be an effective treatment for hypothalamic obesity?

Research has shown that combining Phentermine and Topiramate can aid weight loss in people with obesity, with effects lasting up to two years. This treatment reduces appetite and may increase alertness. Although approved for general obesity, it has not been specifically tested for hypothalamic obesity (HO) before. Early results suggest it might help reduce body mass index (BMI) in individuals with HO, who often find standard weight-loss methods ineffective. This trial will compare the effects of Phentermine/Topiramate with a placebo to further explore these potential benefits. ^{3 4 5 6 7}

Who Is on the Research Team?

Christian L Roth, MD

Principal Investigator

University of Washington, Dept. of Pediatrics

Shana McCormack

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for young people aged 12-28 with hypothalamic obesity, often due to brain tumors like craniopharyngioma. Participants should have issues with excessive hunger or sleepiness. Key eligibility details are not provided, so it's assumed that standard health requirements and consent apply.

Inclusion Criteria

I am between 12 and 28 years old.

History of rapid weight gain related to tumor onset or treatment, as assessed by an experienced endocrinologist

I am using effective birth control or have a condition that prevents me from getting pregnant.

Exclusion Criteria

History of substance abuse, depression of moderate or greater severity, psychiatric disorder and/or suicidality

History of allergy or sensitivity to test agents. Including individuals with known aspirin allergy or hypersensitivity and/or known allergy to FD&C Yellow No. 5 (tartrazine)

My kidney function is low (GFR under 60).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive phentermine/topiramate or placebo for 28 weeks with dose titration and monitoring for safety and efficacy

28 weeks

5 visits (in-person), 2 visits (remote)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of withdrawal effects

1 week

1 visit (remote or in-person if needed)

What Are the Treatments Tested in This Trial?

Interventions

• Phentermine/Topiramate

Trial Overview The trial tests Phentermine/Topiramate capsules (Qsymia), which may reduce appetite and increase alertness in patients with hypothalamic obesity. It's a double-blinded study comparing the drug against a placebo over 28 weeks to see if it helps lower BMI and improve other health aspects.

How Is the Trial Designed?

Group I: Drug Intervention Experimental Treatment 1 Intervention

Active drug dose escalation and adjustment: The drug had been used in adolescents with obesity before. For this trial, the FDA approved dose titration will be followed until the highest tolerable dose is reached.

Group II: Placebo Placebo Group 2 Interventions

Matching placebo using capsules matching the appearance of the active drug.

Phentermine/Topiramate is already approved in United States for the following indications:

Approved in United States as Qsymia for:

• Obesity in adults with a BMI of 27 kg/m^2 or greater and at least one weight-related comorbidity, or with a BMI of at least 30 kg/m^2

Who Is Running the Clinical Trial?

Seattle Children's Hospital

Lead Sponsor

Trials

319

Recruited

5,232,000+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Published Research Related to This Trial

Phentermine/topiramate controlled-release (PHEN/TPM CR) led to significant weight loss of 8.1-10.9% in patients, compared to only 1.4-1.8% in placebo groups, and also reduced waist circumference and improved metabolic markers like blood pressure and lipid profiles.

The treatment was generally well-tolerated, with severe adverse events being similar to those in placebo groups, although common side effects included paresthesia, dry mouth, and insomnia. Long-term safety and efficacy still need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the metabolic effects of controlled-release Phentermine/Topiramate. Kiortsis, DN.[2019]

In a 108-week study involving 676 overweight and obese participants with cardiometabolic disease, controlled-release phentermine/topiramate (PHEN/TPM CR) led to significant and sustained weight loss compared to placebo, with mean percentage changes in body weight of -9.3% and -10.5% for the lower and higher doses, respectively.

PHEN/TPM CR not only facilitated weight loss but also improved cardiovascular and metabolic health, showing a reduction in diabetes incidence, and was well tolerated over the study duration, with fewer adverse events reported in the second half of the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Garvey, WT., Ryan, DH., Look, M., et al.[2023]

Phentermine/topiramate (Qsymia®) is a combination medication approved in July 2022 for chronic weight management in pediatric patients aged 12 and older with obesity, specifically those with a BMI in the 95th percentile or greater.

This medication works by decreasing appetite and increasing feelings of fullness, and it is also being studied for other conditions like sleep apnea and type 2 diabetes in obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phentermine/Topiramate: Pediatric First Approval. Dhillon, S.[2022]

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]

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]

The combination of phentermine and topiramate (PHEN/TPM CR) has been shown to effectively promote weight loss and improve metabolic diseases associated with 'sick fat' in thousands of patients, addressing the limitations of traditional weight loss therapies.

PHEN/TPM CR is generally well-tolerated and works by targeting multiple physiological processes that contribute to body fat accumulation, making it a promising option for treating obesity and its related metabolic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phentermine, topiramate and their combination for the treatment of adiposopathy ('sick fat') and metabolic disease. Bays, H.[2018]

This study protocol outlines a Phase I/IIa trial involving 30 adults with binge eating disorder (BED) and bulimia nervosa (BN) to evaluate the safety and preliminary efficacy of Qsymia, a combination of phentermine and topiramate, over a 12-week period.

The trial aims to measure the impact of Qsymia on binge eating frequency and related psychological factors, addressing the need for more effective treatments for these eating disorders, as current therapies leave many patients symptomatic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol and rationale for a randomized double-blinded crossover trial of phentermine-topiramate ER versus placebo to treat binge eating disorder and bulimia nervosa. Dalai, SS., Adler, S., Najarian, T., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06299891

Efficacy and Safety of Phentermine/Topiramate in Youth ... To assess safety and maximum tolerated dose as well as efficacy on weight loss of Phentermine/Topiramate in individuals with hypothalamic obesity.

2. research.chop.edu research.chop.edu/phenterminetopiramate-in-hypothalamic-obesity

Phentermine/Topiramate in Hypothalamic Obesity The purpose of this study is to evaluate how safe and effective the drug Qsymia (Phentermine/Topiramate of Ph/T) is for children, adolescents, ...

3. withpower.com withpower.com/trial/phase-2-hypothalamic-tumor-2-2024-47b9f

Phentermine/Topiramate for Hypothalamic Obesity It's a double-blinded study comparing the drug against a placebo over 28 weeks to see if it helps lower BMI and improve other health aspects.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3626409/

Clinical utility of phentermine/topiramate (Qsymia ... Weight loss efficacy of PHEN/TPM has been demonstrated to sustain for up to 2 years. Teratogenic potential and a slight increase in heart rate ...

5. reporter.nih.gov reporter.nih.gov/project-details/10890185

a pilot and feasibility study - NIH RePORTER While these results are encouraging, in 50% of participants, BMI did not decrease with exenatide, highlighting the need to address treatment non-response.

6. trialx.com trialx.com/clinical-trials/listings/307135/efficacy-and-safety-of-phenterminetopiramate-in-youth-with-hypothalamic-obesity/

Efficacy and Safety of Phentermine/Topiramate in Youth ... In this pilot trial, our objective is to gather key preliminary data about phentermine/topiramate (Ph/T) that is FDA-approved for "common" ...

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/oby.23152

Efficacy and Safety of Phentermine/Topiramate in Adults ... Phentermine/topiramate therapy resulted in an average weight loss of 7.73 kg (95% CI: 6.60-8.85) in general compared with placebo. The weight ...