Toward Repurposing a Commonly-Used Medication for the Treatment of Pediatric Severe Obesity

重新利用治疗儿童严重肥胖症的常用药物

• 批准号: 10711874
• 负责人: Claudia K Fox
• 金额: $ 30.91万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10711874
• 关键词: Acute; Adolescence; Adolescent; Adult; Affect; Age; Agonist; Attention deficit hyperactivity disorder; Binge Eating; Binge eating disorder; Body Composition; Body fat; Body mass index; Cardiovascular Diseases; Characteristics; Child; Childhood; Chronic Disease; Clinic; Clinical Trials; Data; Desire for food; Diet; Disease; Disease Outcome; Dopamine; Dose; Double-Blind Method; Drug Prescriptions; Eating; Eating Behavior; Education; Employment; Energy Intake; Energy Metabolism; FDA approved; Familiarity; Financial Hardship; Functional disorder; GLP-I receptor; Goals; Growth; Health; Health behavior; Heart Rate; Informal Social Control; Injections; Intervention; Lifestyle Therapy; Malignant Neoplasms; Mental Depression; Metabolic syndrome; Mission; Morbid Obesity; Morbidity - disease rate; Names; National Institute of Diabetes and Digestive and Kidney Diseases; Norepinephrine; Obesity; Obstructive Sleep Apnea; Oral; Participant; Pharmaceutical Preparations; Phase; Phentermine; Physical activity; Pilot Projects; Placebo Control; Placebos; Play; Population; Premature Mortality; Public Health; Quality of life; Randomized; Randomized, Controlled Trials; Recommendation; Rest; Rewards; Role; Safety; Societies; Translating; Vyvanse; Weight; Weight Gain; Weight maintenance regimen; Youth; blood pressure elevation; cardiometabolism; clinically significant; comorbidity; cost; design; efficacy evaluation; executive function; feasibility trial; high risk population; improved; improved outcome; liraglutide; metabolic rate; non-alcoholic fatty liver disease; obesity in children; obesity treatment; pediatrician; pharmacologic; phase 3 study; pilot trial; placebo group; preadolescence; primary endpoint; primary outcome; psychostimulant; public health relevance; randomized placebo-controlled clinical trial; reuptake; reward processing; secondary outcome; sex; social; treatment effect

Project Summary/Abstract Severe obesity in children is a highly prevalent, serious and chronic disease that directly leads to severe obesity in adults and the subsequent enormous social and financial burden on society. Lifestyle therapy is the cornerstone of pediatric obesity treatment, but this intervention when used alone is often insufficient for achieving clinically significant and durable BMI reduction. Adjunct anti-obesity medications may improve outcomes of this disease, but the pharmacological options used for obesity in children are extremely limited. Thus there is an urgency to identify anti-obesity medications for use in the pediatric population, which are safe, effective, easily administered and affordable. Psychostimulants, the second most commonly prescribed class of medications in children, have a long-standing safety profile and because of their favorable effect on weight, may serve as a useful adjunct to lifestyle therapy for the treatment of severe obesity in this population. Thus, the goal of this pilot and feasibility clinical trial is to estimate the treatment effect of a common psychostimulant, lisdexamfetamine, for the treatment of severe obesity in children. Specifically, 44 children ages 6 to <12 years with severe obesity (BMI ≥120% of the 95th percentile) will be randomized, 1:1, to lisdexamfetamine plus lifestyle therapy or placebo plus lifestyle therapy for 24 weeks of treatment. The primary outcome of the main aim will be change in BMI, and secondary outcomes will include changes in body composition, cardiometabolic health, and quality of life. The second aim will be to identify participant tolerability of the recommended starting dose of lisdexamfetamine and the emergence of clinically significant increases in blood pressure and heart rate. Potential mechanisms by which lisdexamfetamine reduces BMI will also be explored including changes in executive functioning, reward processing, appetite, resting energy expenditure, and health behaviors (diet, eating behaviors, and physical activity). The results of this pivotal pilot trial will directly inform the conduct of the larger, fully powered, definitive study, which ultimately, by identifying a safe, effective and scalable treatment, will improve the outcomes of the millions of children affected by this serious, chronic disease.

项目概要/摘要 儿童重度肥胖是一种高发、严重、慢性的疾病，直接导致重度肥胖。 以及随后给社会带来的巨大社会和经济负担。生活方式疗法是 儿科肥胖治疗的基石，但这种干预措施单独使用时往往不足以实现 临床上显着且持久的体重指数降低。辅助抗肥胖药物可能会改善这种结果 但用于治疗儿童肥胖症的药物选择极其有限。因此有一个 迫切需要找到适合儿科人群使用的安全、有效、简便的抗肥胖药物 管理且负担得起。精神兴奋剂是第二大最常用处方药物 儿童，具有长期的安全性，并且由于其对体重的有利影响，可以作为 生活方式疗法的有用辅助手段，用于治疗该人群的严重肥胖症。因此，本次试点的目标 可行性临床试验是评估一种常见的精神兴奋剂赖右苯丙胺的治疗效果， 用于治疗儿童严重肥胖症。具体来说，44 名 6 岁至 12 岁以下患有严重肥胖的儿童 （BMI ≥ 95% 的 120%）将按 1:1 随机分配至赖右苯丙胺加生活方式疗法或安慰剂 加上为期 24 周的生活方式疗法。主要目标的主要结果将是体重指数的变化， 次要结果包括身体成分、心脏代谢健康和生活质量的变化。 第二个目标是确定参与者对赖右苯丙胺推荐起始剂量的耐受性 以及出现临床上显着的血压和心率升高。潜在机制 还将探讨赖右苯丙胺降低体重指数的方式，包括执行功能、奖励的变化 加工、食欲、静息能量消耗和健康行为（饮食、饮食行为和身体状况） 活动）。这一关键试点试验的结果将直接为更大、动力更足、最终的行动提供信息。 研究最终通过确定一种安全、有效和可扩展的治疗方法，将改善治疗结果 数百万儿童受到这种严重的慢性疾病的影响。