Pharmacokinetics and Pharmacodynamics of Topiramate for Weight Loss in Youth: PHARMATOP

NCT04986631 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: PEDS-2021-29920
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

Pediatric severe obesity is the fastest growing obesity category in the United States, and anti-obesity pharmacotherapies are promising adjuncts to lifestyle modification (LSM) for the treatment of this disease. While anti-obesity pharmacotherapies have overall been associated with mean weight loss, there is substantial variability in their individual-level effectiveness. While some patients lose a significant amount of weight with anti-obesity pharmacotherapies, others lose little or even gain weight. Due to this well-recognized variability in individual-level response, the National Institutes of Health (NIH) has recognized the importance of using precision medicine approaches in order to optimize treatments for pediatric severe obesity. Pharmacometrics, which uses mathematical models to study medication dose-exposure (i.e. blood drug concentrations)-response relationships, is an emerging science that can help determine optimal dosing regimens based upon patient-specific characteristics. Pharmacometrics quantitates the interplay between pharmacokinetics (PK; drug dose-exposure associations) and pharmacodynamics (PD; drug exposure-response associations). Population PK (popPK), a type of PK, can be used to quantitate variability in drug exposure among individuals in order to help inform recommendations on therapeutic individualization (e.g. through tailored dosing). In this study, investigators will use popPK/PD modeling to characterize associations between anti-obesity pharmacotherapy dose, exposure, and changes in weight and weight-related outcomes in youth with severe obesity. This study will focus on topiramate because this medication is commonly prescribed for weight loss in youth with severe obesity and has been associated with highly variable individual-level effectiveness.

Conditions

Obesity, Childhood

Outcome Measures

Primary Outcomes (1)

• To determine associations between topiramate exposure and 3-month BMI change using pharmacodynamic modeling

  Change in body mass index (BMI) as assessed by percent change in BMI from baseline to Month 3

  3 months

Study Arms (1)

Topiramate

EXPERIMENTAL

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.

Drug: Topiramate Tablets

Interventions

Topiramate Tablets DRUG

Topiramate intervention

Topiramate

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Body mass index (BMI) \</= 1.2 times the 95th percentile (age and sex-adjusted) and/or BMI \>/= 35 kg/m2
• Ages 12 to \< 18 years old
• Deemed appropriate candidates to receive topiramate (without contraindications) for weight loss by an obesity medicine specialist at the University of Minnesota

You may not qualify if:

• History of metabolic/bariatric surgery
• Obesity associated with a diagnosed genetic disorder (i.e. monogenic obesity, Prader-Willi, Bardet-Biedl syndrome)
• Clinically diagnosed hyperthyroidism or uncontrolled hypothyroidism as determined by local medical monitor (who is a board certified endocrinologist)
• History of acute angle closure glaucoma. Individuals with other types of glaucoma will need approval from the participant's ophthalmologist to be enrolled.
• History of nephrolithiasis
• History of seizures (aside from febrile seizures)
• Major psychiatric disorder as determined by local medical monitor
• History of bulimia nervosa or anorexia nervosa
• History of suicide attempt within the last year
• \* History of active suicidal ideation or self-harm within the past 30 days
• Current or recent (\< 6 months prior to enrollment) use of medication(s) associated with weight gain (e.g. oral steroids, anti-psychotics), unless participant has been on stable doses of such medication(s) for ≥ 6 months
• Current or recent (\< 6 months prior to enrollment) use of long-acting stimulant medications, unless participant has been on stable doses of such medication for ≥ 6 months. In terms of short-acting ADHD stimulant medications, the PI will determine eligibility based on weight and dose (no studies have shown this contributes to weight outcomes)
• Baseline bicarbonate \< 18 mmol/L
• Baseline creatinine \> 1.2 mg/dL
• Females: pregnant, planning to become pregnant, or, if sexually active, unwilling to use 2+ acceptable contraceptive methods during the study period

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Pediatric Obesity

Interventions

Topiramate

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Study Officials

• Eric Bomberg, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Individuals in this pilot study will be 12-\<18 years of age at enrollment. All participants will receive topiramate for 3.5 months.

Study Record Dates

• First Submitted: July 16, 2021
• First Posted: August 3, 2021
• Study Start: April 4, 2022
• Primary Completion: March 12, 2025
• Study Completion: March 12, 2026
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: The study protocol and ICF will be posted to clinicaltrials.gov
• Access Criteria: clinicaltrials.gov

Locations

US (1)