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

August 13, 2026 updated by: University of Minnesota

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The weight loss achieved with topiramate occurs through several purported mechanisms including reductions in appetite, food cravings, and binge eating, and adverse alterations in taste for carbonated beverages. It is hypothesized that some of the individual-level effectiveness of this medication on weight loss response is secondary to patient-specific differences in these factors. In a 3.5-month pragmatic-based prospective cohort study (n=65), the investigators will develop a popPK model using sparse sampling by drawing a series of topiramate concentration measures over time in order to begin determining patient-specific factors that contribute to topiramate exposure variability. The investigators will also identity associations between topiramate exposure, changes in eating behaviors, and weight loss outcomes through PD models using regression techniques. It is hypothesized that patient-specific characteristics (i.e. age, body mass index (BMI), and sex) will explain some variability in topiramate exposure in youth, and that higher topiramate exposure will be associated with greater improvements in weight loss response and eating behaviors among youth prescribed this medicine for the treatment of pediatric severe obesity.

Study Type

Interventional

Enrollment (Actual)

65

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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 anti-obesity medication(s) defined as orlistat, phentermine, topiramate, combination phentermine/topiramate, liraglutide (or other glucagon-like peptide (GLP1-RA)), and/or combination naltrexone/bupropion (monotherapy use of naltrexone or bupropion is not an exclusion), unless participant has been on stable doses for >/= 6 months. Of note, if phentermine was increased from 15 mg daily to 18.75 mg daily during this period, it is not considered a dose increase.
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Topiramate
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
Topiramate intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent BMI Change
Time Frame: 14 Weeks
Percent change in body mass index (BMI) from baseline to 14 weeks (mean change from baseline to 14 weeks of follow up, analysis using paired t-tests)
14 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Minnesota

Collaborators

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

Investigators

  • Principal Investigator: Eric Bomberg, MD, University of Minnesota

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 4, 2022

Primary Completion (Actual)

September 26, 2024

Study Completion (Actual)

September 26, 2024

Study Registration Dates

First Submitted

July 16, 2021

First Submitted That Met QC Criteria

August 2, 2021

First Posted (Actual)

August 3, 2021

Study Record Updates

Last Update Posted (Actual)

August 24, 2026

Last Update Submitted That Met QC Criteria

August 13, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PEDS-2021-29920
  • 5K23DK125668-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Summary data that has been de-identified will be made available to other researchers

IPD Sharing Time Frame

The study protocol and ICF will be posted to clinicaltrials.gov

IPD Sharing Access Criteria

clinicaltrials.gov

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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