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：尽管喝酒率较低，但饮酒率较低 欧美人（EAS），非裔美国人（AA）的高度更高 来自各种酒精相关条件的死亡率，包括肝脏 肝硬化，事故和暴力。当前的提议旨在改善酒精 在AA退伍军人中的治疗，占退伍军人人口的12％。 2。研究设计：拟议的研究是一项两臂，随机的12周， 托吡酯与安慰剂的平行组比较以降低频率 大量饮酒日，增加了160 aa的节制天数 AUD的患者。 3.方法论：使用以下特定目的指导方法： 特定目的1。测试托吡酯（顶部）200 mg/天的功效 非洲的大量饮酒频率和避免日期的频率 美国（AA）酒精使用障碍患者（AUD）。我们假设这一点， 与欧美人（EAS）一样，接收顶部的AA受试者将报告更少 大量饮酒日（HDD）比接受的日子更多 安慰剂（PLA）。 分析利用所有患者提供的所有数据来估算模型 测试对大量饮酒和戒酒日的最佳影响。力量 对比将取决于最后六周的结果模式， 因此，电源估计是基于第7到第12周，为6周的试验， 调整基线与第6周之间流失的损失。根据我们 先前的研究（Kranzler 2014），我们预计前六个保留率为92％ 每组的几周，在第6周末每组可用74个，一个 在最后六个星期中，由于辍学而额外的4％损失，并受试 相关性约为0.6。 Hedeker等人（1999）的方法表明，我们将 具有80％的功率，用于D = 0.40、0.43和0.46的最高主要效应大小 受试者相关性分别为0.5、0.6和0.7，在校正的alpha水平上 0.025。 4。影响/意义：该提案具有创新性，因为它将集中于AAS 与Aud，一个没有这样的数据 目前存在。鉴于AUD及其高流行的影响很大 在退伍军人中，添加的基于证据的治疗可能会意识到健康降低 不必要的ED访问和疾病并发症减少的护理费用 例如丙型肝炎和充血性心力衰竭。