Topiramate Treatment of Alcohol Use Disorder in African Americans

托吡酯治疗非裔美国人酒精使用障碍

• 批准号: 9974484
• 负责人: DAVID W. OSLIN
• 金额: --
• 依托单位: PHILADELPHIA VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9974484
• 关键词: Accidents; Affect; African American; Aftercare; Alcohol dependence; Alcohols; Alleles; American; Anticonvulsants; Congestive Heart Failure; Consumption; DSM-V; Data; Dropout; Emergency department visit; European; Evidence based treatment; Frequencies; Gene Frequency; Genes; Genetic; Genetic Polymorphism; Genotype; Glutamate Receptor; Goals; Growth; Health Care Costs; Healthcare Systems; Heavy Drinking; Hepatitis C; High Prevalence; Individual; Kainic Acid Receptors; Liver Cirrhosis; Methodology; Methods; Minor; Minority Groups; Modeling; Morbidity - disease rate; Naltrexone; National Institute on Alcohol Abuse and Alcoholism; Outcome; Patients; Pattern; Pharmaceutical Preparations; Pharmacogenetics; Pharmacological Treatment; Pharmacotherapy; Placebos; Population; Population Genetics; Randomized; Recommendation; Reporting; Research Design; Sampling; Services; Single Nucleotide Polymorphism; Subgroup; Testing; Underserved Population; United States Food and Drug Administration; Variant; Veterans; Violence; Woman; active method; alcohol abuse therapy; alcohol effect; alcohol testing; alcohol use disorder; arm; base; comparison group; disparities in morbidity; dosage; drinking; efficacy study; efficacy testing; follow-up; genome wide association study; genome-wide; improved; innovation; kainate; men; military veteran; mortality; off-label use; placebo controlled study; placebo controlled trial; precision medicine; programs; prospective; topiramate; treatment effect; treatment response; virtual; week trial

1. Objective(s): Despite having lower rates of drinking and heavy drinking than European Americans (EAs), African Americans (AA) have significantly higher rates of mortality from a variety of alcohol-related conditions, including liver cirrhosis, accidents, and violence. The current proposal aims to improve alcohol treatment in AA Veterans, who comprise 12% of the Veteran population. 2. Research Design: The proposed study is a two-arm, randomized 12-week, parallel-groups comparison of topiramate versus placebo to reduce the frequency of heavy drinking days and increase the number of abstinent days in 160 AA patients with AUD. 3. Methodology: The following specific aim is used to direct the methods: Specific Aim 1. To test the efficacy of topiramate (TOP) 200 mg/day in reducing the frequency of heavy drinking and increasing abstinent days in African- American (AA) patients with alcohol use disorder (AUD). We hypothesize that, as in European-Americans (EAs), AA subjects receiving TOP will report fewer heavy drinking days (HDDs) and more abstinent days than those receiving placebo (PLA). The analyses make use of all data provided by all patients to estimate models to test the TOP effect on days of heavy drinking and abstinent days. Power for the contrasts will be determined by the patterns of outcomes in the final six weeks, so power estimates are based on weeks 7 through 12 as a 6-week trial, with adjustments for loss to attrition between baseline and week 6. Based on our prior study (Kranzler 2014), we anticipate 92% retention through the first six weeks for each group, yielding 74 available per group at the end of week 6, an additional 4% loss due to dropout across the final six weeks, and a within-subject correlation of about 0.6. The methods of Hedeker et al (1999) show that we will have 80% power for a TOP main effect size of d=0.40, 0.43, and 0.46, for within- subject correlations of 0.5, 0.6, and 0.7, respectively, at a corrected alpha level of 0.025. 4. Impact/Significance: The proposal is innovative in that it will focus on AAs with AUD, an understudied and underserved population for whom no such data currently exist. Given the far-reaching effects of AUD and its high prevalence among veterans, added evidence based treatments may realize reduced health care costs from unnecessary ED visits and reduced complications of illnesses such as hepatitis C and congestive heart failure.

1. 目标：尽管饮酒和酗酒率低于 欧洲裔美国人 (EA)、非裔美国人 (AA) 显着更高 各种与酒精相关的疾病（包括肝脏疾病）的死亡率 肝硬化、事故和暴力。目前的提案旨在改善酒精含量 AA 退伍军人的治疗，他们占退伍军人人口的 12%。 2. 研究设计：拟议的研究是一项双臂、随机、为期 12 周的研究 托吡酯与安慰剂的平行组比较以降低频率 减少酗酒天数并增加 160 AA 中的戒酒天数 澳元患者。 3. 方法论：以下具体目标用于指导方法： 具体目标 1. 测试托吡酯 (TOP) 200 mg/天减少 非洲人酗酒的频率和禁酒天数的增加 美国（AA）酒精使用障碍（AUD）患者。我们假设， 与欧洲裔美国人 (EA) 一样，接受 TOP 的 AA 受试者报告的数量较少 酗酒天数 (HDD) 和戒酒天数比接受治疗的人更多 安慰剂（PLA）。 该分析利用所有患者提供的所有数据来估计模型 测试重度饮酒日和戒酒日的 TOP 效果。电源为 对比将由最后六周的结果模式决定， 因此，功率估算基于第 7 周到第 12 周（为期 6 周的试验），其中 对基线和第 6 周之间的损耗损失进行调整。根据我们的 之前的研究（Kranzler 2014），我们预计前六次的保留率为 92% 每组周数，在第 6 周结束时每组可获得 74 个可用周数， 由于最后六周的辍学以及受试者内的损失，额外损失了 4% 相关性约为0.6。 Hedeker 等人 (1999) 的方法表明我们将 对于 d=0.40、0.43 和 0.46 的 TOP 主效应大小，具有 80% 功效，对于 - 在校正的 alpha 水平下，受试者相关性分别为 0.5、0.6 和 0.7 0.025。 4. 影响/意义：该提案的创新之处在于它将重点关注 AA 对于 AUD，没有得到充分研究和服务的人群没有此类数据 目前存在。鉴于澳元的深远影响及其高流行率 在退伍军人中，增加基于证据的治疗可能会导致健康状况下降 不必要的急诊就诊和减少疾病并发症带来的护理费用 例如丙型肝炎和充血性心力衰竭。