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.

项目摘要/摘要暴饮暴食障碍（BED）是一种正式的DSM-5诊断，是一种普遍，难治性和严重的健康男人和女人经历的问题以及精神病和医疗合并症的高度。虽然床与肥胖密切相关，床分布在重量类别中。几乎所有治疗试验因为床需要合并肥胖任务流行病学估计，其中58％床不是肥胖。当前的药物治疗选项有限，唯一的FDA批准了床的药物具有“使用限制”，以减轻体重和治疗肥胖症。理想情况下，最佳床的药理方法会减少有或没有肥胖者的暴饮暴食，并具有减少肥胖症患者体重的增加。 Naltrexone HCI和Bupropion HCI（NB）的联合使用旨在靶向改变下丘脑黑色皮质素系统和大脑奖励系统，两种化合物假设尽管NB针对床的系统高度相关，但减少暴饮暴食的功效尚不清楚。我们的飞行员数据表明，NB降低了暴饮暴食率行为以及减轻床+肥胖症患者的体重。主要目的是进行双盲，安慰剂对照平行组RCT，以评估NB与安慰剂的效率床患者的暴饮暴食，由肥胖状态分层（每个细胞n = 50，n = 200）为12周治疗期和12个月的随访期。第二个主要目的评估了基础机制 NB对暴饮暴食的影响。既定的人类实验室范式将用于评估饮食行为包括抵抗饮食优选的高热量食物的能力以及随后的饮食能力。潜在的将检查饮食的体内平衡和享乐方面涉及的机制。我们假设在饮食行为，饮食中，饮食和渴望食物的潜在变化在实验室将在12周的RCT期间介导临床结果（即暴饮暴食率）。第三，然后探索目的，评估饮食行为，渴望食物和情绪在前6个使用创新的生物传感器系统，在参与者的一部分（n = 60）中进行了数周的NB处理。我们将检查与临床结局有关的自然饮食行为的与药物相关的变化（即暴饮暴食率）。这项创新的跨学科研究将：（1）提供治疗潜力和相关潜力的首次测试肥胖症患者且无肥胖症患者的NB机制。（2）确定相关性和潜力 NB对暴饮暴食的影响的基础机制。用创新的人类评估结果实验室以及使用可穿戴生物传感器的新型现场评估将优化内部和外部有效性，并为迄今为止的任何卧床治疗研究提供了最全面的多模式评估。