Role of Pharmacotherapy in Counteracting Weight Regain in Adolescents With Severe Obesity
Status:
Recruiting
Trial end date:
2027-06-30
Target enrollment:
Participant gender:
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.