Efficacy and Mechanisms of Naltrexone+Bupropion for Binge Eating Disorder

项目总结/摘要 暴食症（BED）是DSM-5的正式诊断，是一种普遍、难治和严重的健康问题。 男性和女性所经历的问题，以及精神和医疗并发症的增加。虽然 BED与肥胖密切相关，BED分布在体重类别中。几乎所有的治疗试验 尽管流行病学估计，58%的人 没有肥胖症目前的药物治疗选择是有限的，唯一的FDA批准的 BED的药物对减肥和治疗肥胖有"使用限制"。理想情况下， BED的药理学方法将减少肥胖和非肥胖者的暴饮暴食， 在患有共病肥胖症的人中减轻体重的额外益处。 开发了盐酸纳洛酮和盐酸安非他酮（NB）的组合使用，以靶向治疗中的改变。 下丘脑黑皮质素系统和大脑奖励系统，假设这两种化合物 协同作用，减少食物摄入量。虽然NB的目标系统与BED高度相关， 减少暴饮暴食的功效尚不清楚。我们的试点数据显示，NB降低了暴饮暴食的比率 行为以及减轻体重的那些共病床+肥胖。主要目的是进行一项 双盲、安慰剂对照平行组RCT，评价NB与安慰剂相比降低 BED患者的暴饮暴食，按肥胖状态分层（n = 50/细胞，共n = 200），持续12周， 治疗期和12个月随访期。第二个主要目的是评估潜在的机制， NB对暴食的影响一个已建立的人类实验室范式将被用来评估饮食 行为包括抵制吃高热量食物的能力，以及随后的过度进食。潜在 我们将研究饮食的自我平衡和享乐两方面的机制。我们假设 在研究中评估的饮食行为、食用肽和食物渴望的潜在药物相关变化， 实验室将在12周RCT期间介导临床结局（即，暴饮暴食）。第三和 探索性的目的，评估饮食行为，食物渴望，和情绪'在现场'在前6个 使用创新的生物传感器系统在参与者的子集（n = 60）中进行NB治疗周。我们 将检查药物相关的自然饮食行为变化是否与临床结果有关（即， 暴饮暴食）。 这项创新的跨学科研究将：（1）提供治疗潜力和相关的第一次测试 NB对肥胖和非肥胖患者BED的作用机制。(2)确定相关因素和潜在因素 NB对暴饮暴食影响的潜在机制。用创新的人力资源评估成果 实验室和使用可穿戴生物传感器的新的现场评估将优化内部和外部 有效性，并提供迄今为止对BED的任何治疗研究的最全面的多模式评估。

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.