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

项目摘要 这项研究将评估靶向剂量葛根在酗酒人群中的疗效。 使用障碍(澳大利亚)。狂饮(定义为男性一次喝五杯或更多酒，四杯 或女性更多的饮料)，在美国非常流行。狂欢饮酒占了超过一半的 每年8万人死于过度饮酒，其经济损失超过1910亿美元 在美国。国家艾滋病毒行为监测数据显示，48%的异性恋男性，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)。狂欢饮酒已经 与无避孕套的性行为和艾滋病毒感染有独立的联系。到目前为止，酗酒是最 与艾滋病毒感染有关的普遍暴露。因此，减少酗酒的有效干预措施可能起作用。 通过减少与酒精相关的性行为作为预防艾滋病毒的重要干预措施。葛根可能是一种 在东方，用于治疗酗酒的药物被用于治疗酗酒，前景看好 亚洲自公元600年以来。葛根中所含的异黄酮类化合物一直被证明能抑制所有人的酒精使用。 到目前为止进行的动物研究。在人类中，葛根与数量的显著减少有关 与安慰剂相比，饮酒量、饮酒量和饮酒率都有所下降。在双打中- 盲法、随机、安慰剂对照试验，葛根显著减少饮酒量，减少 大量饮酒的天数，并显著增加了在四周内戒酒的天数百分比 后续行动。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”的基础上预期大量饮酒时使用)。葛根可在2小时内达到峰值血浆水平 口服给药时间长，平均消除半衰期为4.3小时。单剂葛根 在饮酒与饮酒数量显著减少和饮酒速度较慢相关之前， 与安慰剂相比，提供了葛根可以根据需要服用的证据。尽管不断增加 关于葛根对酒精影响的证据，目前还没有针对葛根的疗效研究。 酗酒者，没有旨在减少与酒精相关的危险行为的试验。 研究设计：这是一项双盲、安慰剂对照试验，对象为120名酗酒者，服用12周的AUD。 葛根(2克)，预计会大量饮酒而服用。参与者将每周接受酒精代谢物检查 尿检，研究配药，以及酒精使用的简短咨询。安全评估和行为 调查将按月完成。酒精使用和酒精相关性行为的有效性(AIMS 1-3)将使用每周时间线回访、筛查乙基葡萄糖醛酸(EtG)阳性尿液、 以及电脑管理的月度面试。性传播感染检测将在基线和 第三个月访问(目标3)。将通过跟踪不良事件来评估耐受性和可接受性(目标4 以及服药依从性。治疗的持久性将在治疗后1个月和3个月的访问中进行评估。

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.