Enhancing Weight Loss Maintenance with GLP-1 in Adolescents with Severe Obesity

使用 GLP-1 加强重度肥胖青少年的减肥维持

• 批准号: 9120364
• 负责人: Aaron S Kelly
• 金额: $ 55.65万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9120364
• 关键词: Address; Adolescent; Adult; Agonist; Behavior Therapy; Beta Cell; Biological Adaptation; Blood Pressure; Body Weight; Body Weight decreased; Body fat; Childhood; Clinical Trials; Comorbidity; Controlled Clinical Trials; Data; Desire for food; Diet; Double-Blind Method; Energy Intake; Energy Metabolism; Female; Functional disorder; GLP-I receptor; Gastric Emptying; Gender; Glucose; HDL-triglyceride; Health; High Prevalence; Hormones; Hypertension; Immune; Individual; Inflammation; Insulin; Insulin Resistance; Maintenance; Medical; Modification; Morbid Obesity; Obesity; Oxidative Stress; Participant; Peripheral; Pharmaceutical Preparations; Pharmacotherapy; Phase; Placebo Control; Placebos; Public Health; Randomized; Relapse; Replacement Therapy; Research; Rest; Risk Factors; Satiation; Structure; Time; United States; Visceral; Weight; Work; Youth; arterial stiffness; base; cardiometabolic risk; clinical practice; glucagon-like peptide; glucagon-like peptide 1; glucose tolerance; improved; innovation; novel; obesity in children; pleiotropism; predicting response; prevent; psychosocial; response; sobriety; subcutaneous; treatment response

 DESCRIPTION (provided by applicant): Long-term weight loss maintenance is seldom achieved by individuals with obesity owing to numerous biological adaptations involving appetite, satiety, and energy expenditure in the post- weight loss setting. Following a loss in body weight, peripheral and central mechanisms convey a sense that energy reserves have dwindled, activating a strong counter response to increase caloric intake. Adolescents with severe obesity are not immune to the vexing issue of weight regain. Indeed, only 2% are able to achieve and maintain clinically- meaningful weight loss with lifestyle modification therapy. Therefore, novel treatment paradigms focused on long-term weight loss maintenance are urgently needed. Pharmacotherapy has the potential to prevent weight regain by targeting specific counter-regulatory mechanisms in the post- weight loss setting. One of the most promising candidates is the glucagon like peptide-1 receptor agonist (GLP-1RA) class, which greatly enhanced weight loss maintenance following a short-term low calorie diet among adults with obesity. The rationale for focusing on GLP-1RA treatment to prevent weight regain is supported by the multiple central and peripheral mechanisms of action targeted by this class of drug; many of which specifically address the biological adaptations known to induce relapse. We have strong preliminary data demonstrating that GLP-1RA treatment reduces BMI in adolescents with severe obesity. Moreover, we and others have shown that although meal replacement therapy (structured meals of known caloric content) can elicit robust short-term weight loss among adolescents with severe obesity, weight regain is a pervasive problem. Therefore, in this clinical trial, our innovative approach will utilize GLP-1RA treatment to target weight regain following short-term meal replacement therapy in youth with severe obesity. Participants who achieve =5% BMI reduction during the meal replacement phase will be randomized to GLP-1RA treatment or placebo for an additional 12 months while simultaneously engaging in lifestyle modification therapy. Importantly, this study will also allow us to examine the extent to which GLP-1RA treatment addresses mechanisms of weight regain, investigate other pleiotropic benefits of GLP-1RA, and identify predictors of weight loss response. This research tackles a significant public health threat, utilizes an innovative treatment concept and approach, and exerts a powerful, sustained influence on the field of pediatric obesity by steering research and clinical practice paradigms toward the application of pharmacotherapy for meaningful and durable weight loss and risk factor modification.

 描述（由申请人提供）：由于肥胖的人在胃部，饱腹感和能量消耗中涉及大量的生物学适应，因此很少有肥胖症的人实现长期体重减轻。在体重减轻之后，外围和中心机制传达了一种能量储量减少的感觉，从而激活了强烈的反应以增加热量摄入量。严重肥胖症的青少年不能免疫体重恢复的问题。实际上，只有2％的人能够通过生活方式修改疗法实现并保持临床上有意义的体重减轻。因此，迫切需要以长期减肥维持的新型治疗范例。药物治疗有可能通过针对重量后损失设置中的特定反调节机制来预防体重恢复。最有望的候选者之一是胰高血糖素，例如胡椒1受体激动剂（GLP-1RA）类，在短期肥胖的成年人中，短期低卡路里饮食后，它大大增加了减肥。专注于GLP-1RA治疗以防止体重的理由仍然受到该类别药物针对的作用的多个中心和外围机制的支持；其中许多专门针对已知诱发救济的生物适应性。我们有强大的初步数据，表明GLP-1RA治疗可降低严重肥胖症的青少年的BMI。此外，我们和其他人已经表明，尽管替代替代疗法（已知热量含量的结构化餐）可以在严重肥胖的青少年中引起强大的短期体重减轻，但体重仍然是一个普遍的问题。因此，在这项临床试验中，我们的创新方法将利用GLP-1RA治疗来靶向 在严重肥胖的青年中，短期膳食替代疗法后，重量恢复。在替代阶段取得= 5％BMI降低的参与者将随机分配给GLP-1RA治疗或安慰剂12个月，同时进行生活方式修饰疗法。重要的是，这项研究还将使我们能够研究GLP-1RA治疗方法在多大程度上解决体重的机制，研究GLP-1RA的其他多效性益处，并确定减肥反应的预测指标。这项研究应对巨大的公共卫生威胁，利用创新的治疗概念和方法，并通过指导研究和临床实践范式来对儿科肥胖领域产生强大的，持续的影响，以将药物治疗应用于有意义且持久的体重减轻和风险因素。