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ACTIVE NOT RECRUITING

NCT04298203

PHASE2

Role of Pharmacotherapy in Counteracting Weight Regain in Adolescents With Severe Obesity

Sponsor: University of Minnesota

View on ClinicalTrials.gov

Summary

Long-term weight loss maintenance is seldom achieved by individuals with obesity owing to numerous biological adaptations occurring in the post-weight loss setting, including neuroendocrine-mediated changes in appetite/satiety and reduction of energy expenditure. Following weight loss, peripheral and central mechanisms respond in a way similar to starvation by conveying a sense that energy reserves have dwindled, activating a strong counter-response to increase caloric intake. Moreover, metabolic rate drops, further compounding the propensity for weight rebound. Adolescents with severe obesity are not immune to the vexing issue of weight regain; therefore, effective and scalable treatments are urgently needed. Pharmacotherapy has the potential to prevent weight regain by targeting counter-regulatory mechanisms in the post-weight loss setting. Unfortunately, only one obesity medication is FDA-approved for long-term use in adolescents and is seldom prescribed owing to modest efficacy and notable side effects. Among the most promising candidates in the pediatric pipeline is the combination of phentermine and topiramate, which is the most effective adult weight loss medication currently available. The mechanisms of action are thought to reduce appetite, enhance satiety, and potentially increase energy expenditure, making this medication particularly well-suited for the purpose of weight loss maintenance since it targets many of the biological adaptations known to induce relapse and subsequent weight regain. The investigators have generated preliminary data demonstrating that both phentermine and topiramate reduce BMI in adolescents with severe obesity and have acceptable safety profiles. In this clinical trial, the investigators will utilize combination phentermine/topiramate to target counter-regulatory pathways responsible for weight regain after meal replacement therapy (structured meals of known caloric content) in adolescents with severe obesity with a goal of enhancing weight loss maintenance and improving obesity-related complications. Importantly, the investigators will maximize the clinical utility and overall impact of the study by comprehensively characterizing the safety of phentermine/topiramate utilizing sensitive measures of cardiac autonomic function, arterial stiffness, cognition, and bone health as well as examine the extent to which this medication counteracts mechanisms of weight regain.

Key Details

Gender

All

Age Range

12 Years - 18 Years

Study Type

INTERVENTIONAL

Enrollment

100

Start Date

2021-08-04

Completion Date

2027-06-30

Last Updated

2026-04-08

Healthy Volunteers

Conditions

Obesity

Interventions

DRUG

Phentermine-Topiramate

The study medication to be tested for this study is a combination of phentermine and topiramate.

DIETARY_SUPPLEMENT

Meal Replacement Therapy

The first six weeks of the study, subjects will receive meal replacement therapy in an effort to reduce their BMI by at least 5%.

OTHER

Placebo

A pill that looks like Phentermine-Topiramate but has no active medication.

Inclusion Criteria: * Severe obesity (BMI \>/= 120% of the 95th percentile or BMI \>/= 35 kg/m2) * Age 12 to \< 18 years of age at enrollment (screening) and Tanner stage \>/= 2 - Female participants who are sexually active with males and who are able to get pregnant must agree to use two forms of contraception throughout the trial Exclusion Criteria: * Diabetes (type 1 or 2) * Current or recent (\< six months prior to enrollment) use of anti-obesity medication(s) defined as orlistat, phentermine, topiramate, combination phentermine/topiramate, liraglutide, and/or combination naltrexone/bupropion (monotherapy use of naltrexone or bupropion is not an exclusion) * Previous metabolic/bariatric surgery * Current use of a stimulant medication * History of glaucoma * Current or recent (\<14 days) use of monoamine oxidase inhibitor * Known hypersensitivity to sympathomimetic amines * Any history of treatment with growth hormone * Any history of bulimia nervosa * Major psychiatric disorder as determined by the local medical monitor * Unstable and clinically-diagnosed (defined as documented in the medical record, if available) depression * Any history of active suicide attempt * History of suicidal ideation or self-harm within the previous 30 days of screening * Patient Health Questionnaire (PHQ-9) score \>15 at screening * Current pregnancy or plans to become pregnant during study participation * Current tobacco use * Alanine transaminase (ALT) or Aspartate transaminase (AST) \>/= 3 times the upper limit of normal * Bicarbonate \<18 mmol/L * Creatinine \> 1.2 mg/dL * Any history of seizures * Uncontrolled hypertension as determined by the local medical monitor * History of structural heart defect or clinically significant arrhythmia * Diagnosed monogenic obesity * Any history of cholelithiasis * Any history of nephrolithiasis * Clinically diagnosed hyperthyroidism * Untreated thyroid disorder * Any disorder, unwillingness, or inability, not covered by any other exclusion criteria, which in the investigator's opinion, might jeopardize the subject's safety or compliance with the protocol

Locations (1)

University of Minnesota

Minneapolis, Minnesota, United States