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

基本信息

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
项目类别：
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

项目摘要

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。生活方式治疗给成年人带来了巨大的社会和经济负担。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可能会改善这一结果。但用于治疗儿童肥胖症的药物选择极其有限。迫切需要找到适合儿科人群使用的安全、有效、简便的抗肥胖药物精神兴奋剂是第二类最常用的处方药物。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，这就是该试点项目的目标。临床可行性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，具体为 44 名 6 岁至 12 岁以下患有严重肥胖症的儿童。（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，主要目标是改变 BMI，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临床上血压和心率显着升高的潜在机制。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）这项关键试点试验的结果将直接为更大规模、更全面、更明确的试验的开展提供信息。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。