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

A-HACK 项目：用葛根解决重度酒精消费问题

基本信息

批准号：
10224742
负责人：
Glenn-Milo Santos
金额：
$ 51.47万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-20 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10224742
关键词：
AIDS prevention Address Adverse event Aftercare Age Alcohol abuse Alcohol consumption Alcohols American Animal Model Animals Back Behavior Behavioral Cessation of life China Chlamydia trachomatis Clinical Computer Assisted Computers Consumption Counseling Data Data Collection Dose Double-Blind Method Drug Kinetics Enrollment Epidemic Event Far East Glucuronides HIV HIV Infections HIV risk Half-Life Health Heavy Drinking Herbal supplement Heterosexuals Hour Human Human immunodeficiency virus test Incidence Individual Intervention Interview Isoflavones Japan Kudzu Laboratories Laboratory Study Link Medical Monitor Multiple Partners Neisseria gonorrhoeae Oral Administration Participant Patient Self-Report Pharmaceutical Preparations Placebos Plasma Prevalence Prevention strategy Property Randomized Randomized Controlled Trials Reporting Research Research Design Risk Risk Behaviors Rodent Safety San Francisco Sex Behavior Sexually Transmitted Diseases Social Interaction Surveys Syphilis Testing Text Messaging Time TimeLine Unsafe Sex Urine Visit Woman alcohol intervention alcohol measurement alcohol use disorder binge drinker binge drinking double-blind placebo controlled trial drinking economic cost effective intervention efficacy evaluation efficacy study ethnic diversity follow-up high risk interest medication compliance men men who have sex with men monitoring device nonhuman primate placebo controlled study preventive intervention problem drinker racial and ethnic randomized placebo controlled trial randomized placebo-controlled clinical trial safety assessment screening sexual HIV transmission sexual risk behavior sexually active social surveillance data systematic review treatment arm

项目摘要

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.

项目摘要这项研究将评估定向剂量葛根对酗酒者的功效酗酒（定义为男性一次喝五杯或更多饮料，男性则为四杯）。在美国，酗酒现象非常普遍，占一半以上。每年有 8 万人因过度饮酒而死亡，其经济损失超过 1,910 亿美元在美国，国家艾滋病毒行为监测数据表明，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）。迄今为止，酗酒与无套性行为和艾滋病毒感染独立相关。因此，减少酗酒的有效干预措施可能会起作用。作为一种重要的艾滋病毒预防干预措施，葛根可能是通过减少与酒精相关的性危险行为来实现的。治疗酗酒的方法在东方有望用于治疗酒精滥用的药用目的自公元 600 年以来，亚洲地区的葛根就含有异黄酮，事实证明它可以抑制所有人的饮酒。迄今为止在人类中进行的动物研究表明，葛根与数量的显着减少有关。与安慰剂相比，饮用的饮料量、每口的酒精量和饮酒速度较慢。盲法、随机、安慰剂对照试验中，葛根显着减少了饮用的饮料数量，减少了大量饮酒的天数，并显着增加了 4 周内戒酒的天数百分比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以在 2 内达到峰值血浆水平。口服给药的平均消除半衰期为 4.3 小时。饮酒前与饮酒次数显着减少和饮酒速度减慢有关，与安慰剂相比，提供了证据表明葛根可以按需服用，尽管剂量不断增加。尽管有证据表明葛根对酒精有影响，但目前还没有针对葛根的功效研究来评估其对酒精的影响。酗酒者，并且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，受试者为 120 名酗酒者，服用澳元至 12 周。葛根（2克），在预计会酗酒时服用，每周都会检查参与者的酒精代谢情况。尿液检测、研究药物配药以及关于饮酒的安全评估和行为的简短咨询。每月完成一次关于饮酒和与酒精相关的性危险行为的效果的调查（目标）。 1-3) 将使用每周时间线随访进行评估，筛查乙基葡萄糖醛酸 (EtG) 阳性尿液，每月进行计算机管理的访谈，以进行基线和性传播感染检测。第 3 个月的访视（目标 3）将通过跟踪不良事件来评估。治疗的持久性将在治疗后 1 个月和 3 个月就诊时进行评估。