An experimental medicine approach toward the identification of a compulsive overeating phenotype in obesity

识别肥胖强迫性暴饮暴食表型的实验医学方法

• 批准号: 9163483
• 负责人: Ashley E. Mason
• 金额: $ 22.3万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9163483
• 关键词: Automobile Driving; Behavioral; Beverages; Binge Eating; Biological; Blood; Body Weight decreased; Cardiovascular Diseases; Cardiovascular system; Clinical Investigator; Clinical Research; Clinical Trials; Comorbidity; Consumption; Coupled; Data; Development; Dyslipidemias; Eating; Eating Behavior; Food; Food Processing; Goals; Health; Hormonal; Human; Hypertension; Impulsivity; Individual; Informal Social Control; Ingestion; Intake; Intervention; Laboratory Research; Lead; Measures; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Metabolic; Methods; Naltrexone; Narcotic Antagonists; Nausea; Non-Insulin-Dependent Diabetes Mellitus; Nutritional; Obesity; Obesity associated cardiovascular disease; Opiates; Opioid; Oral; Participant; Patient Self-Report; Phase; Phenotype; Pilot Projects; Play; Probability; Protocols documentation; Psychological Factors; Randomized; Reporting; Research; Research Methodology; Research Training; Review Literature; Rewards; Risk; Risk Factors; Role; Stress; System; Testing; Training; United States National Institutes of Health; Weight Gain; Withdrawal Symptom; Woman; Work; base; cardiovascular disorder risk; career; craving; design; effective intervention; endogenous opioids; experience; glycemic control; high risk; improved; indexing; meetings; mortality; novel; nutrition; obesity treatment; precision medicine; programs; psychologic; relating to nervous system; responders and non-responders; response; sugar; therapy development

ABSTRACT Compulsive overeating afflicts 30% of treatment-seeking individuals with obesity and correlates with cardiovascular disease (CVD) risk factors. Current obesity intervention approaches, however, do not specifically target mechanisms that underlie compulsive overeating. My research on obese women shows that compulsive overeating is associated with alterations in endogenous opioid activity as indexed by nausea (an opioidergic withdrawal symptom) following administration of the opioid antagonist naltrexone (NX). Data also show associations between compulsive overeating, highly palatable food intake, impulsivity, reward-sensitivity, and other factors, which, taken together, may characterize a compulsive overeating phenotype in obesity. This K23 Award will support the development of my independent research career focused on more effective interventions for compulsive overeating in obesity and its cardiovascular comorbidities. The proposed experimental medicine studies will advance this research program by investigating a compulsive overeating phenotype in obesity using: (1) a multimethod assessment battery (MAB) to assess behavioral, psychological, and nutritional correlates of obesity, (2) obesity-related indices of CVD risk (e.g., glycemic control, hypertension), and (3) my novel NX protocol to assess altered endogenous opioid activity (Aim 1). I will assess NX protocol test-retest reliability and, in a subset of participants who do not have a NX response (nausea) at initial testing, test whether NX response can be induced after administering our 2-week sugar-beverage consumption protocol, as sugar impacts endogenous opioid activity (Aim 2). With my mentors, I will identify intervention targets in compulsive overeating based on Study 1 results and a current review of the literature. I will then select intervention components that have produced change in these targets in prior research, and will develop, refine, and test these components in a pilot study of women with compulsive overeating and obesity (Aim 3). I will examine feasibility and acceptability of the intervention components and collect pilot data on pre- post change in the measures used in Study 1. Pilot data will inform the R34 Clinical Trial Pilot Study proposal I will submit to test an optimized intervention for compulsive overeating in obesity. The proposed training plan will provide me with the support and mentorship necessary to gain expertise in the identification of opioidergic, psychological, behavioral, and nutritional targets associated with compulsive overeating; to obtain the training needed to independently design and conduct laboratory research and to assess obesity-related CVD risk factors; and to obtain the training necessary to develop and test obesity interventions. These training experiences, coupled with the proposed research plan, will facilitate my career devoted to the development of interventions that act on mechanisms underlying compulsive overeating in obesity. This K23 Award will deepen current understanding and treatment of compulsive overeating in obesity and promote development of interventions for this distinct subset of individuals, for whom we currently lack effective interventions.

抽象的 强迫性暴饮暴食困扰着 30% 寻求治疗的肥胖症患者，并且与 心血管疾病（CVD）危险因素。然而，目前的肥胖干预方法并没有 特别针对强迫性暴饮暴食的机制。我对肥胖女性的研究表明 强迫性暴饮暴食与内源性阿片类药物活性的改变有关，如恶心（恶心） 阿片类药物拮抗剂纳曲酮（NX）给药后出现阿片样物质戒断症状）。数据还 显示强迫性暴饮暴食、高度可口的食物摄入、冲动、奖励敏感性、 和其他因素，综合起来，可能是肥胖中强迫性暴饮暴食表型的特征。这 K23奖将支持我专注于更有效的独立研究事业的发展 针对肥胖症及其心血管并发症的强迫性暴饮暴食的干预措施。拟议的 实验医学研究将通过调查强迫性暴饮暴食来推进这一研究计划 肥胖表型使用：（1）多方法评估组合（MAB）来评估行为、心理、 和肥胖的营养相关性，(2) 与肥胖相关的 CVD 风险指数（例如血糖控制、 高血压），以及（3）我的新颖的 NX 方案来评估改变的内源性阿片类药物活性（目标 1）。我会评估 NX 协议重测可靠性，并且在未出现 NX 反应（恶心）的参与者子集中 初步测试，测试服用 2 周含糖饮料后是否可以诱导 NX 反应 消费协议，因为糖会影响内源性阿片类药物活性（目标 2）。与我的导师一起，我将确定 根据研究 1 结果和当前文献综述确定强迫性暴饮暴食的干预目标。我 然后将选择在先前的研究中对这些目标产生变化的干预措施，并将 在针对强迫性暴饮暴食和肥胖女性的试点研究中开发、完善和测试这些成分 （目标 3）。我将研究干预措施的可行性和可接受性，并收集预试验数据 研究 1 中使用的措施发生变化后。试点数据将为 R34 临床试验试点研究提案 I 提供信息 将提交测试针对肥胖症强迫性暴饮暴食的优化干预措施。拟议的培训计划 将为我提供必要的支持和指导，以获得识别阿片类药物的专业知识， 与强迫性暴饮暴食相关的心理、行为和营养目标；获得培训 需要独立设计和进行实验室研究并评估肥胖相关的 CVD 风险 因素；并获得开发和测试肥胖干预措施所需的培训。这些训练 经验，加上拟议的研究计划，将促进我致力于发展的职业生涯 针对肥胖症强迫性暴饮暴食机制的干预措施。本届K23奖将深化 目前对肥胖症强迫性暴饮暴食的认识和治疗并促进肥胖症的发展 针对这个独特的个体子集的干预措施，我们目前缺乏有效的干预措施。