Topiramate for Childhood Obesity

(PHARMATOP Trial)

Overseen By Eric Bomberg, MD

Age: < 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Minnesota

Must be taking: Topiramate

Must not be taking: Anti-obesity, Steroids, Antipsychotics, others

Disqualifiers: Bariatric surgery, Genetic disorders, Hyperthyroidism, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 3.5 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of the drug topiramate for weight loss in teenagers with severe obesity. Researchers aim to understand how different doses affect weight and related outcomes, using pharmacometrics to tailor treatment to individual needs. The trial targets teens with a significantly higher-than-normal body mass index (BMI) who a specialist has identified as suitable for topiramate. As an Early Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial requires that you have not used certain anti-obesity medications or medications associated with weight gain in the past 6 months unless you've been on a stable dose for at least 6 months. If you're taking long-acting stimulant medications, you must also have been on a stable dose for at least 6 months. Check with the trial team to see if your specific medications are affected.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that topiramate has treated seizures in children as young as two for many years, indicating some level of safety for young patients. However, topiramate can cause side effects. Some studies have highlighted possible issues like slower growth in height and weight in children. Additionally, topiramate might raise body temperature and decrease sweating, potentially leading to dehydration, especially in kids. While often prescribed for weight loss in young people with severe obesity, these risks should be considered when evaluating participation in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for childhood obesity, which often include lifestyle changes, dietary adjustments, and medications like metformin, topiramate offers a unique approach. Originally an anticonvulsant medication, topiramate works by targeting the brain's neurotransmitters to help reduce appetite and manage weight. Researchers are excited about topiramate because it has the potential to provide an effective pharmacological option that directly addresses the neurological components of obesity, potentially leading to better long-term weight management in children.

What evidence suggests that topiramate might be an effective treatment for childhood obesity?

Research has shown that topiramate, the investigational treatment in this trial, combined with lifestyle changes, can significantly lower body mass index (BMI) in teenagers. Studies have found that this combination can lead to an average BMI reduction of 4–6%. Although topiramate is primarily approved for treating epilepsy and migraines, it is also used for weight loss in adults, often with another drug called phentermine. Topiramate seems to work by altering brain chemicals that control appetite. While results can vary among individuals, these findings suggest that topiramate could help manage weight in young people with severe obesity. ^{3 6 7 8 9}

Who Is on the Research Team?

Eric Bomberg, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for youth aged 12 to under 18 with severe obesity, defined as a BMI at or above certain thresholds. Candidates must be considered appropriate for topiramate treatment by an obesity specialist and have no history of metabolic surgery, significant thyroid disorders, major psychiatric disorders, eating disorders, recent suicide attempts or use of certain weight-related medications.

Inclusion Criteria

I am between 12 and 17 years old.

My BMI is either less than or equal to 1.2 times the 95th percentile for my age and sex, or it is 35 kg/m2 or more.

I am considered a good candidate for topiramate for weight loss by a specialist.

Exclusion Criteria

Baseline bicarbonate < 18 mmol/L

I have had weight loss surgery in the past.

I am not pregnant, not planning to become pregnant, and willing to use two or more forms of birth control if sexually active.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive topiramate with dose escalation from 25 mg to 75 mg daily over 3.5 months

3.5 months

Weekly visits for dose adjustment in the first 3 weeks, then monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Topiramate

Trial Overview The PHARMATOP study tests how the drug topiramate affects weight loss in young people with severe obesity. It uses pharmacometrics to understand the relationship between dosage and individual responses to optimize dosing based on patient-specific characteristics.

How Is the Trial Designed?

Group I: Topiramate Experimental Treatment 1 Intervention

Individuals will receive 75 mg of topiramate daily. The dose will start at 25 mg daily for the first week. The second week participants will receive 50 mg daily. Starting at week 3 participants will take 75 mg daily.

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Published Research Related to This Trial

Combination pharmacotherapy, such as using phentermine and topiramate together, may provide better weight loss results for pediatric patients with obesity compared to single-agent treatments, which often have limited efficacy.

This case report of a 10-year-old girl illustrates the potential benefits of combining medications after lifestyle modifications were insufficient, highlighting the need for more effective treatment options in pediatric obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Potential Role of Combination Pharmacotherapy to Improve Outcomes of Pediatric Obesity: A Case Report and Discussion. Fox, CK., Kelly, AS.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7257846/

Medications for the treatment of obesity in adolescents - PMC Topiramate is currently FDA approved for the treatment of epilepsy (⩾2 years old), migraines (⩾12 years old), and obesity, in combination with phentermine (⩾18 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5958908/

Topiramate for Weight Reduction in Adolescents with ... The results demonstrate that topiramate with concurrent lifestyle modification is associated with clinically-significant BMI reduction, on the order of 4–6% ...

3. medpagetoday.com medpagetoday.com/meetingcoverage/obesityweek/95501

Paired Anti-Obesity Drugs May Help Teens Shed More ... "Initial efficacy data support greater reduction in BMI with phentermine and topiramate versus placebo at 12 weeks." Patients in the study ...

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/04/NCT04095104/Prot_SAP_000.pdf

Adjunctive Anti-Obesity Pharmacotherapy in Adolescents ... 2) Phentermine and Topiramate were paired to theoretically reduce/neutralize the side effects seen with either medication alone, and additively or ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0031699724000024

Review Article Emerging pharmacotherapies for obesity Completed phase 2 trials on incretin-based therapies showed a mean percent weight loss of 7.4% to 24.2%. Almost half of the drugs undergoing phase 2 trials are ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/205122s011lbl.pdf

qudexy® xr - accessdata.fda.gov The safety data presented below are from 249 patients ... The safety and effectiveness of QUDEXY XR in pediatric patients is based on controlled trials.

7. mayoclinic.org mayoclinic.org/drugs-supplements/topiramate-oral-route/description/drg-20067047

Topiramate (oral route) - Side effects & dosage Safety and efficacy have not been established. Appropriate studies have not been performed on the relationship of age to the effects of Trokendi ...

8. trokendixrhcp.com trokendixrhcp.com/about-trokendi-xr

Topiramate Clinical Data | Trokendi XR® HCP Immediate-release topiramate monotherapy demonstrated negative effects on growth (height and weight) among pediatric patients in a one-year active controlled ...

9. drugs.com drugs.com/topiramate.html

Topiramate: Uses, Dosage, Side Effects, Warnings Topiramate can increase body temperature and decrease sweating, leading to life-threatening dehydration (especially in children). Avoid the use ...