Project Details
Description
Abstract
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. Our group has 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, we will utilize 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 co-morbidity outcomes. Importantly, we will maximize the clinical utility and overall impact of our
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.
Status | Finished |
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Effective start/end date | 5/1/20 → 3/31/24 |
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases: $656,445.00
- National Institute of Diabetes and Digestive and Kidney Diseases: $650,033.00
- National Institute of Diabetes and Digestive and Kidney Diseases: $654,031.00
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