Efficacy and Mechanisms of Naltrexone+Bupropion for Binge Eating Disorder

纳曲酮安非他酮治疗暴食症的疗效和机制

基本信息

批准号：
10200788
负责人：
CARLOS M GRILO
金额：
$ 68.37万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-25 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10200788
关键词：
Adult Adverse effects Aftercare Binge Eating Binge eating disorder Biosensor Body Weight decreased Brain Bupropion Calories Categories Cells Cellular Phone Clinical Consumption DSM-V Data Diagnosis Double-Blind Method Eating Eating Behavior Epidemiology FDA approved Food Gestures Hand Health Human Hunger Hypothalamic structure Interdisciplinary Study Laboratories Leptin Literature Maintenance Mediating Medical Moods Morbid Obesity Naltrexone Non obese Obesity Oral cavity Outcome Participant Patients Peptides Pharmaceutical Preparations Pharmacological Treatment Pharmacology Pharmacotherapy Placebos Refractory Rewards System Time Treatment Efficacy Weight Woman Work comorbidity craving design drinking behavior effectiveness evaluation effectiveness testing efficacy evaluation efficacy testing experience follow-up food craving ghrelin hedonic high risk improved innovation men moderate obesity multimodality novel obese patients obesity treatment reduced food intake smart watch therapeutic evaluation treatment duration treatment trial wearable sensor technology

项目摘要

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.

项目概要/摘要暴食症 (BED) 是 DSM-5 的一项正式诊断，是一种普遍存在、难治性且严重的健康问题男性和女性所经历的问题以及哮喘、精神和医学合并症。 BED 与肥胖密切相关，BED 分布在几乎所有的治疗试验中。尽管流行病学估计，其中 58% 的人患有暴食症，但仍要求存在共病肥胖患有 BED 的人并不肥胖，目前的药物治疗选择有限，并且是 FDA 批准的唯一药物。 BED 药物对于减肥和治疗肥胖有“使用限制”，理想情况下，这是一种最佳选择。 BED 的药理学方法将减少肥胖者和非肥胖者的暴饮暴食，并且具有对于患有肥胖症的人来说，减轻体重还有额外的好处。盐酸纳曲酮和盐酸安非他酮 (NB) 的联合使用旨在改变下丘脑黑皮质素系统和大脑奖励系统，这两种化合物的开发尽管 NB 的目标系统与 BED 患者高度相关，但其仍可协同减少食物摄入量。减少暴食的功效尚不清楚。我们的试验数据表明，NB 可以降低暴食率。行为以及减轻患有 BED+肥胖症的患者的体重主要目的是进行一项研究。双盲、安慰剂对照平行组随机对照试验，评估 NB 与安慰剂相比减少 BED 患者暴饮暴食，按肥胖状态分层（每个细胞 n=50，总共 n=200），持续 12 周第二个主要目标是评估潜在的机制。 NB 对暴饮暴食的影响将使用已建立的人类实验室范例来评估饮食。行为包括抵制偏好的高热量食物的能力和随后的暴饮暴食的潜力。将检查涉及饮食的稳态和享乐方面的机制。在饮食行为、饮食肽和食物渴望方面评估的潜在药物相关变化实验室将在 12 周 RCT 期间调节临床结果（即暴食率）。探索性目标，评估前 6 天内的饮食行为、食物渴望和“现场”情绪我们使用创新的生物传感器系统对一部分参与者（n = 60）进行了数周的 NB 治疗。将检查自然饮食行为中与药物相关的变化是否与临床结果相关（即，暴食率）。这项创新的跨学科研究将：（1）提供治疗潜力和相关的首次测试肥胖和非肥胖患者的 NB 治疗 BED 的机制 (2) 确定相关性和潜力。 NB 对暴饮暴食影响的机制评估创新人类的结果。实验室和使用可穿戴生物传感器的新颖现场评估将优化内部和外部有效性，并提供迄今为止所有 BED 治疗研究中最全面的多模式评估。