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

药物治疗在对抗严重肥胖青少年体重反弹中的作用

• 批准号: 10375470
• 负责人: Aaron S Kelly
• 金额: $ 65.64万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10375470
• 关键词: 18 year old; Address; Adolescent; Adult; Area; Biological; Biological Adaptation; Blood Pressure; Body Weight decreased; Body fat; Body mass index; Cardiac; Childhood; Clinic; Clinical; Clinical Trials; Cognition; Controlled Clinical Trials; Data; Desire for food; Dose; Double-Blind Method; Drops; Energy Intake; Energy Metabolism; Eye; FDA approved; Formulation; Goals; Heart Rate; High Prevalence; Individual; Inflammation; Life Style Modification; Maintenance; Measures; Mediating; Medical; Mental Health; Morbid Obesity; Neurosecretory Systems; Obesity; Outcome; Oxidative Stress; Participant; Patients; Peripheral; Pharmaceutical Preparations; Pharmacotherapy; Phentermine; Physiological; Placebo Control; Placebos; Randomized; Regulatory Pathway; Relapse; Replacement Therapy; Reporting; Rest; Risk Factors; Role; Safety; Satiation; Starvation; Structure; Surface; United States National Institutes of Health; Visceral fat; Weight; adult obesity; arterial stiffness; base; bone health; cardiometabolic risk; clinically relevant; comorbidity; cost effectiveness; improved; metabolic rate; placebo group; prevent; primary endpoint; psychosocial; response; side effect; topiramate; total energy expenditure

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.

摘要