Assessment of Pioglitazone to Address Stress Reactivity and Alcohol Use Disorder

吡格列酮解决应激反应和酒精使用障碍的评估

• 批准号: 10491667
• 负责人: Jin Ho Yoon
• 金额: $ 18.53万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10491667
• 关键词: Address; Affect; Agonist; Alcohol consumption; Alcohol withdrawal syndrome; Alcohols; Animal Experimentation; Anti-Inflammatory Agents; Anxiety; Attention; Attenuated; Behavioral; Biological; Blood Pressure; Data; Diabetes Mellitus; Disulfiram; Dose; Double-Blind Method; Environment; Exhibits; FDA approved; Health; Heart Rate; Heavy Drinking; Human; Hydrocortisone; Hypothalamic structure; Individual; Laboratories; Life; Measures; Metabolic Diseases; Modeling; Modernization; Naltrexone; Opioid; Outcome; PPAR gamma; Participant; Peroxisome Proliferator-Activated Receptors; Pharmaceutical Preparations; Pharmacotherapy; Pilot Projects; Pioglitazone; Pituitary Gland; Placebos; Process; Psychometrics; Public Health; Rattus; Reporting; Research; Rewards; Role; Salivary; Sampling; Single-Blind Study; Societies; Standardization; Stress; System; Time; Time Factors; Withdrawal Symptom; acamprosate; addiction; alcohol abuse therapy; alcohol availability; alcohol craving; alcohol demand; alcohol use disorder; behavioral economics; craving; discounting; drinking; economic cost; eligible participant; model design; new therapeutic target; novel; pre-clinical; relapse risk; response; screening; social; stress reactivity; theories; therapeutic target; tool

ABSTRACT Alcohol use disorder (AUD) is significant public health concern. Stress is a central component in modern theories of alcohol use, and stress is intimately related to drinking for many individuals. There are a number of approved medications for AUD, but the majority of individuals do not respond to these medications and no medications address the role of stress. The current proposal looks affect alcohol use by targeting stress-related systems in the body through peroxisome proliferator-activated receptors (PPARs), which may effect stress reactivity, stress-induced alcohol craving, and alcohol use. Pioglitazone (Actos) targets PPARγ and is FDA- approved for treating individuals with diabetes and metabolic disorders. Promising results from both human trials and animal research suggest that pioglitazone holds great promising for addressing AUD, including preliminary data from our own research. The current proposal will attempt to expand on our preliminary findings targeting alcohol use among treatment-seeking individuals with AUD and elevated stress and/or anxiety with the following specific aims: 1) to assess if pioglitazone decreases stress reactivity and stress- induced craving in a human laboratory model; and 2) to assess if pioglitazone changes weekly psychometric reports of stress/anxiety, craving, and alcohol consumption. Notable strengths of the current proposal include: 1) targeting individuals with elevated stress/anxiety and AUD; 2) biological assessment of stress reactivity (heart rate, blood pressure, salivary cortisol); 3) a multi-dimensional assessment of alcohol craving incorporating relatively novel behavioral economic measures (i.e., alcohol demand, delay discounting); and 4) inclusion of powerful Bayesian statistical tools that are well suited for smaller samples, such as the current proposal.

抽象的 酒精使用障碍（AUD）是一个重要的公共卫生问题，压力是现代人的一个核心组成部分。 对于许多人来说，饮酒和压力与饮酒密切相关的理论有很多。 已批准用于 AUD 的药物，但大多数人对这些药物没有反应，也没有 目前的建议似乎是通过针对与压力相关的药物来影响酒精的使用。 通过过氧化物酶体增殖物激活受体 (PPAR) 调节体内系统，这可能会影响压力 反应性、压力引起的酒精渴望和酒精使用，吡格列酮 (Actos) 的目标是 PPARγ，并且已获得 FDA 批准。 批准用于治疗患有糖尿病和代谢紊乱的个体。 试验和动物研究表明，吡格列酮在解决 AUD 问题上具有巨大的前景，包括 我们自己研究的初步数据。当前的提案将尝试扩展我们的初步数据。 针对患有 AUD 且压力升高和/或寻求治疗的个体饮酒的调查结果 焦虑症具有以下具体目的：1）评估吡格列酮是否降低应激反应性和应激性 在人类实验室模型中诱发渴望；2) 评估吡格列酮每周心理测量是否发生变化 关于压力/焦虑、渴望和饮酒的报告当前提案的显着优势包括： 1) 针对压力/焦虑和 AUD 升高的个体 2) 压力反应性的生物学评估； （心率、血压、唾液皮质醇）3）对酒精渴望的多维度评估； 纳入相对新颖的行为经济措施（即酒精需求、延迟折扣）；4) 包含强大的贝叶斯统计工具，非常适合较小的样本，例如当前的 提议。