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

项目摘要/摘要 儿童严重肥胖是一种高度流行的严重慢性病，直接导致严重肥胖。 对成年人造成的危害，以及由此给社会带来的巨大社会和财政负担。生活方式疗法是 儿童肥胖治疗的基石，但单独使用这种干预措施往往不足以实现 临床上显著和持久的BMI降低。辅助的抗肥胖药物可能会改善这一结果 治疗儿童肥胖症的药物选择极其有限。因此，有一种 迫切需要确定在儿科人群中使用的安全、有效、容易使用的减肥药物 管理得当，负担得起。精神刺激剂，第二种最常用的处方药物 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 生活方式疗法的有益补充，用于治疗这一人群的严重肥胖症。因此，这一试点的目标是 可行性临床试验是评估一种常见的精神刺激剂，左旋糖胺的治疗效果， 用于治疗儿童严重肥胖症。具体地说，44名6岁至12岁的严重肥胖症儿童 (体重指数≥为第95百分位数的120%)将以1：1的比例随机分为左旋糖胺加生活方式疗法或安慰剂 外加为期24周的生活方式治疗。主要目标的主要结果将是体重指数的变化， 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。 第二个目标是确定参与者对推荐起始剂量的左旋糖胺的耐受性。 临床上出现明显的血压和心率升高。潜在机制，由 还将探讨哪种左旋糖胺能降低BMI，包括执行功能、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)。这一关键的试点试验的结果将直接为更大、更强大、更具决定性的 研究，最终，通过确定安全、有效和可推广的治疗方法，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.