The A-HACK Project: Addressing Heavy Alcohol Consumption with Kudzu

项目摘要 这项研究将评估有针对性的剂量的利妥昔单抗的疗效与酒精酗酒的个人 使用障碍（AUD）。酗酒（定义为男性一次喝五杯或五杯以上， 或更多的女性饮料），在美国非常普遍。酗酒占了美国人口的一半以上。 每年有8万人死于过度饮酒，其经济成本超过1910亿美元 在美国.全国艾滋病毒行为监测数据表明，48%的异性恋男子，58%的男性， 与男性发生性关系，40%的异性恋女性报告酗酒（过去30天）。酗酒已经 与无安全套性行为和HIV感染独立相关。酗酒是迄今为止 与艾滋病毒感染有关的普遍暴露。因此，有效的干预措施，以减少酗酒可能发挥作用 作为一项重要的艾滋病毒预防干预措施，通过减少与酒精有关的危险性行为。葛根可能是一种 一种有希望的治疗酗酒的方法，在东部地区已被用于治疗酒精滥用的医疗目的。 公元600年以来的亚洲。葛根中含有的葛根素一直被证明可以抑制所有人的酒精使用。 迄今为止进行的动物研究。在人类中， 与安慰剂相比，饮用的饮料，每口的酒精量和饮酒速度较慢。在一个双- 一项盲法、随机、安慰剂对照试验显示， 大量饮酒的天数，并显着增加了4周内戒酒天数的百分比 随访葛根的药代动力学特性和快速起效支持靶向给药（即， 在“按需”的基础上预期使用大量酒精）。葛根可以达到峰值血浆浓度在2 小时，平均消除半衰期为4.3小时。单剂量的阿托珠 在饮酒之前，饮酒量的显著减少和饮酒速度的减慢， 与安慰剂相比，提供了证据表明，依西珠可以根据需要服用。尽管越来越多 尽管有证据表明，阿托伐他汀对酒精有影响，但目前还没有针对阿托伐他汀的疗效研究， 酗酒者，没有旨在减少酒精相关危险行为的试验。 研究设计：这是一项双盲、安慰剂对照试验，共有120名患有AUD的酗酒者参加， 2g，在预期大量饮酒时服用。参与者将每周接受酒精代谢物检查 尿检、研究药物分发和酒精使用的简短咨询。安全评估和行为 调查将每月完成。对酒精使用和酒精相关性危险行为的疗效（目的 1-3)将使用每周时间线随访、筛选乙基葡糖苷酸（EtG）阳性尿液， 和电脑管理的每月面谈性传播感染检测将在基线时进行， 3个月访视（目标3）。将通过跟踪不良事件评估耐受性和可接受性（目标4） 和药物依从性。将在治疗后1个月和3个月访视时评估治疗的持久性。

PROJECT ABSTRACT This study will evaluate the efficacy of targeted dosing of kudzu among binge drinking individuals with alcohol use disorders (AUD). Binge drinking (defined as drinking five or more drinks on one occasion for men, and four or more drinks for women), is highly prevalent in the US. Binge drinking accounts for more than half of the 80,000 annual deaths attributed to excessive alcohol consumption and its economic costs exceeds $191 billion in the US. National HIV Behavioral Surveillance data indicate that 48% of heterosexual men, 58% of men who have sex with men, and 40% of heterosexual women reported binge drinking (past 30 days). Binge drinking has been independently associated with condomless sex and HIV infection. Binge drinking is by far the most prevalent exposure linked to HIV infections. Thus, effective interventions to reduce binge drinking may function as an important HIV prevention intervention by reducing alcohol-related sexual risk behaviors. Kudzu may be a promising treatment for binge drinking that has been used for medicinal purposes to treat alcohol abuse in East Asia since 600 AD. Kudzu contain isoflavones that have been consistently shown to suppress alcohol use in all animal studies conducted to date. Among humans, kudzu was associated with significant reductions in number of drinks consumed, volume of alcohol per sip and slower rate in drinking compared to placebo. In a double- blind, randomized, placebo-controlled trial, kudzu significantly reduced the number of drinks consumed, reduced the number of heavy drinking days, and significantly increased the percent of days abstinent during a 4-week follow-up. Kudzu’s pharmacokinetic properties and rapid onset of action support targeted administration (i.e., use in anticipation of heavy alcohol use on an “as-needed” basis). Kudzu can reach peak plasma levels within 2 hours of oral administration and has a mean elimination half-life of 4.3 hours. A single dose of kudzu administered before drinking has been associated with significant reductions in number of drinks and slower rate of drinking, compared to placebo, providing evidence that kudzu can be taken on an as-needed basis. Despite the mounting evidence of kudzu’s effects on alcohol, there have been no efficacy studies evaluating targeted kudzu among binge-drinkers and no trials aimed at reducing alcohol-associated risk behaviors. Study Design: This is a double-blind, placebo-controlled trial of 120 binge-drinkers with AUD to 12 weeks of kudzu (2g), to be taken in anticipation of heavy drinking. Participants will be seen weekly for alcohol-metabolite urine testing, study drug dispensing, and brief counseling for alcohol use. Safety assessments and behavioral surveys will be completed monthly. Efficacy on alcohol use and alcohol-associated sexual risk behaviors (Aims 1-3) will be assessed using weekly time-line follow-back, screening for ethyl glucuronide (EtG)-positive urines, and computer-administered monthly interviews. Sexually transmitted infection testing will occur at baseline and month 3 visits (Aim 3). Tolerability and acceptability (Aim 4) will be assessed through tracking of adverse events and medication adherence. Durability of treatment will be assessed at 1- and 3-month post-treatment visits.