Efficacy and Mechanisms of Naltrexone+Bupropion for Binge Eating Disorder

项目摘要/摘要 暴饮暴食障碍(Bed)是DSM-5的正式诊断，是一种普遍、顽固和严重的健康问题 男性和女性所经历的问题，以及精神疾病和医学共病的加剧。虽然 床与肥胖密切相关，床是跨体重类别分布的。几乎所有的治疗试验 尽管流行病学估计有58%的人患有肥胖症 有床的人并不肥胖。目前的药物治疗选择有限，FDA批准的唯一 床上药物在减肥和治疗肥胖症方面有“使用限制”。理想情况下，最优的 对床的药理学方法将减少肥胖者和非肥胖者的暴饮暴食，并具有 对那些患有肥胖症的人来说，减轻体重有额外的好处。 盐酸纳曲酮和盐酸安非他酮(NB)的联合使用是为了针对 下丘脑黑素皮质素系统和大脑奖励系统，这两种化合物被假设为 协同工作，减少食物摄入量。尽管NB的目标系统与那些有BED的人高度相关，但其 减少暴饮暴食的效果尚不清楚。我们的试点数据显示，NB可以降低暴饮率 同时还能减轻床+肥胖者的体重。主要目标是进行一项 双盲、安慰剂对照的平行组随机对照试验，评估NB与安慰剂的疗效 有床的患者暴饮暴食，按肥胖状况分层(每个细胞50人，总共200人)，为期12周 治疗期间和12个月的随访期。第二个主要目标是评估潜在的机制 NB对暴饮暴食的影响。已建立的人体实验室范例将被用来评估进食 包括抗拒进食的能力在内的行为倾向于高卡路里食物和随后的暴饮暴食。潜力 本课程将研究饮食的动态平衡和享乐性两个方面的机制。我们假设 这项研究评估了饮食行为、进食肽和食物渴望方面与药物有关的潜在变化 实验室将在12周的随机对照试验期间调节临床结果(即暴饮率)。第三，以及 探索性目标，评估前6个月的饮食行为、食物渴望和情绪 使用创新的生物传感器系统对一组参与者(n=60)进行数周的NB治疗。我们 将研究自然饮食行为中与药物相关的变化是否与临床结果有关(即， 暴饮率)。 这项创新的跨学科研究将：(1)提供治疗潜力和相关的第一个测试 肥胖者与非肥胖者床上神经营养物质的作用机制(2)确定相关因素和潜力 NB对暴饮暴食影响的机制。用创新的人来评估结果 使用可穿戴生物传感器的实验室和新的现场评估将优化内部和外部 有效性，并提供迄今为止最全面的床上治疗研究的多模式评估。

Project Summary/Abstract Binge eating disorder (BED), a formal DSM-5 diagnosis, is a prevalent, refractory, and serious health problem experienced by men and women and with heightened psychiatric and medical comorbidity. Although BED is associated strongly with obesity, BED is distributed across weight categories. Nearly all treatment trials for BED have required the presence of co-morbid obesity despite epidemiological estimates that 58% of those with BED are not obese. Current pharmacological treatment options are limited and the sole FDA-approved medication for BED has a “Limitation of Use” for weight loss and treating obesity. Ideally, an optimal pharmacological approach for BED would reduce binge eating in those with and without obesity, and have the added benefit of reducing weight in those with co-morbid obesity. The combined use of naltrexone HCI and bupropion HCI (NB) was developed to target alterations in the hypothalamic melanocortin system and the brain reward system, with the two compounds hypothesized to work synergistically to reduce food intake. Although NB targets systems highly relevant for those with BED, its efficacy for reducing binge eating is unknown. Our pilot data shows that NB reduces rates of binge eating behavior as well as reduces weight in those with co-morbid BED+obesity. The primary aim is to conduct a double-blind, placebo-controlled parallel group RCT to evaluate the efficacy of NB versus placebo to reduce binge eating in patients with BED, stratified by obesity status (n=50 per cell, n=200 total) for a 12-week treatment period and a 12-month follow-up period. The second primary aim evaluates mechanisms underlying the effect of NB on binge eating. An established human laboratory paradigm will be used to assess eating behaviors including the ability to resist eating preferred high-caloric food and subsequent over-eating. Potential mechanisms involved in both homeostatic and hedonic aspects of eating will be examined. We hypothesize that potential medication-related changes in eating behavior, eating peptides and food craving assessed in the laboratory will mediate clinical outcomes during the 12-week RCT (i.e., rates of binge eating). The third, and exploratory aim, assesses eating and drinking behavior, food craving, and mood `in the field' during the first 6 weeks of NB treatment in a subset of participants (n=60) with the use of an innovative biosensor system. We will examine whether medication-related changes in naturalistic eating behavior relate to clinical outcomes (i.e., rates of binge eating). This innovative interdisciplinary study will: (1) Provide the first test of the therapeutic potential and related mechanisms of NB for BED in patients with obesity and without obesity. (2) Identify correlates and potential mechanisms underlying the effect of NB on binge eating. Evaluating outcomes with innovative human laboratory and with novel field assessments using wearable biosensors will optimize internal and external validity and provide the most comprehensive multi-modal assessment of any treatment study for BED to date.