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: 10597681
• 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/10597681
• 关键词: 18 year old; Address; Adolescent; Adult; Area; Binding; 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; 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; bone health; cardiometabolic risk; clinically relevant; comorbidity; cost effectiveness; improved; metabolic rate; placebo group; prevent; primary endpoint; psychosocial; response; side effect; sobriety; 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.

抽象的 由于众多原因，肥胖者很少能实现长期减肥维持。 减肥后发生的生物适应，包括神经内分泌介导的变化 食欲/饱腹感和能量消耗的减少。减肥后，外周和中枢 机制以类似于饥饿的方式做出反应，传达能量储备已经减少的感觉， 激活强烈的反反应以增加热量摄入。此外，新陈代谢率进一步下降 加剧体重反弹的倾向。严重肥胖的青少年也不能幸免 令人烦恼的体重反弹问题；因此，迫切需要有效且可扩展的治疗方法。 药物疗法有可能通过针对体内的反调节机制来防止体重反弹。 减肥后设置。不幸的是，只有一种肥胖药物获得 FDA 批准可长期使用 青少年很少使用该药物，因为疗效有限且副作用显着。其中最 儿科产品线中最有前途的候选药物是芬特明和托吡酯的组合，这是 目前最有效的成人减肥药物。其作用机制被认为是 降低食欲，增强饱腹感，并可能增加能量消耗，使这种药物 特别适合维持减肥的目的，因为它针对许多生物 已知会导致复发和随后体重反弹的适应。我们小组已初步形成 数据表明，芬特明和托吡酯均可降低严重肥胖青少年的体重指数 具有可接受的安全性。在这项临床试验中，我们将利用芬特明/托吡酯来对抗 膳食替代疗法（已知的结构化膳食）后体重恢复的调节途径 卡路里含量）在严重肥胖的青少年中，目的是加强减肥维持和 改善共病结果。重要的是，我们将最大限度地提高我们的临床效用和整体影响 通过利用敏感措施全面表征芬特明/托吡酯的安全性进行研究 心脏自主功能、动脉僵硬度、认知和骨骼健康，并检查其程度 这种药物可以抵消体重反弹的机制。