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

项目总结/摘要 儿童重度肥胖症是一种直接导致儿童重度肥胖的高发、严重、慢性疾病 在成年人中，以及随后对社会造成的巨大社会和财政负担。生活方式疗法是 儿童肥胖症治疗的基石，但这种干预时，单独使用往往是不够的， 具有临床意义且持久的BMI降低。辅助抗肥胖药物可能会改善这一结果 然而，用于治疗儿童肥胖症的药物选择极其有限。因此， 迫切需要确定用于儿科人群的抗肥胖药物，这些药物安全，有效，容易 管理和负担得起的。精神兴奋剂，第二个最常见的处方类药物， 儿童，有一个长期的安全概况，因为他们对体重的有利影响，可以作为一个 这是生活方式疗法的有用辅助手段，用于治疗这一人群中的严重肥胖症。因此，该试点的目标 可行性临床试验是评估常用精神兴奋剂利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至<12岁的严重肥胖儿童 (BMI≥第95百分位数的120%）将以1：1随机分配至利右苯丙胺+生活方式治疗组或安慰剂组 加上24周的生活方式治疗。主要目标的主要结局将是BMI的变化， 次要结果将包括身体成分、心脏代谢健康和生活质量的变化。 第二个目的是确定受试者对利右苯丙胺推荐起始剂量的耐受性 以及出现临床上显著的血压和心率增加。潜在机制 也将探讨利右苯丙胺降低BMI的方法，包括改变执行功能，奖励 加工，食欲，静息能量消耗和健康行为（饮食，饮食行为和身体 活动）。这一关键性试点试验的结果将直接为更大的、全功率的、决定性的 这项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 数百万儿童受到这种严重的慢性疾病的影响。

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.