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.

抽象的 由于许多人，由于肥胖的人很少实现长期的体重减轻维持 在体重后损失设置中发生的生物适应，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。体重减轻后，周围和中央 机制以与饥饿相似的方式做出了反应，即传达了能源储量减少的感觉 激活强烈的反应以增加热量摄入量。此外，代谢率下降，进一步 使重量反弹的倾向更加复杂。严重肥胖的青少年不能免疫 体重恢复的烦恼问题；因此，迫切需要有效的可扩展处理。 药物疗法有可能通过针对反调节机制来预防体重恢复 体重后损失设置。不幸的是，只有一种肥胖药物是FDA批准的，供长期使用 青少年，很少是由于适度的功效和显着的副作用而被规定。最重要的是 小儿管道中有前途的候选人是苯甲酸和托吡酯的组合，这是 目前可用的最有效的成人减肥药。人们认为行动机制 减少食欲，增强饱腹感并潜在地增加能量消耗，使这种药物 特别是为了减肥的目的而特别适合维持的目的，因为它针对许多生物学 已知会诱发复发和随后的体重恢复的适应。我们的小组已经产生了初步 数据表明，在严重肥胖和 具有可接受的安全概况。在这项临床试验中，我们将利用苯丁胺/托吡酯来靶向对抗 负责体重替代疗法后体重恢复的监管途径（已知的结构化餐 热量肥胖症的青少年的热量含量），以增强减肥和减肥和 改善合并症的结果。重要的是，我们将最大化我们的临床效用和整体影响 通过全面表征苯胺/托吡酯的安全性，利用敏感的措施 心脏自主功能，动脉僵硬，认知和骨骼健康，并检查 这种药物抵消了体重的机制。