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: 9115305
• 负责人: Aaron S Kelly
• 金额: $ 10.85万
• 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/9115305
• 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; prevent; psychosocial; response; sobriety; subcutaneous

 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.