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: 10292444
• 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 2022-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10292444
• 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：尽管饮酒和大量饮酒的比例低于 欧洲裔美国人（EA），非洲裔美国人（AA） 各种酒精相关疾病的死亡率，包括肝脏 肝硬化事故和暴力目前的提案旨在改善酒精 AA退伍军人的治疗，占退伍军人人口的12%。 2.研究设计：拟议的研究是一项为期12周的双臂、随机研究， 托吡酯与安慰剂的平行组比较，以降低频率 增加160个AA中的戒酒天数 患者AUD 3.方法：以下具体目标用于指导方法： 具体目标1.为了测试托吡酯（TOP）200 mg/天在降低 非洲人酗酒的频率和禁欲的天数增加， 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治疗的AA受试者报告的 酗酒日（HDDs）和更多的禁欲日比那些接受 安慰剂（PLA）。 这些分析利用所有患者提供的所有数据来估计模型， 在大量饮酒和戒酒的日子里测试TOP效应。执政为 对比将由最后六周的结果模式决定， 因此，功效估计是基于第7周至第12周的6周试验， 调整基线和第6周之间的损耗。基于我们 之前的研究（Kranzler 2014），我们预计前六年的保留率为92% 每个组的时间为24周，在第6周结束时，每个组有74个可用， 在最后6周内，由于脱落而额外损失4%， 相关系数约为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主效应量，具有80%的功效， 受试者相关性分别为0.5、0.6和0.7，校正α水平为 0.025. 4.影响/意义：该提案具有创新性，因为它将重点放在AA上 AUD是一个研究不足、服务不足的人群， 目前存在。鉴于AUD的深远影响及其高患病率， 在退伍军人中，增加基于证据的治疗可能会降低健康水平， 不必要的艾德就诊和减少疾病并发症的护理成本 如丙型肝炎和充血性心力衰竭。