Ethanol metabolites for monitoring drinking in clinical trials.

描述（由申请人提供）：确定最近的酒精消费是临床试验和治疗方案的关键组成部分，重点是酒精使用障碍。与其他药物滥用治疗方案不同，尿液药物筛查提供了几天内近期药物使用的客观证据，而以酒精为重点的方案通常必须依赖于自我报告来获得这些信息。葡萄糖醛酸乙酯（EtG）和硫酸乙酯（EtS）是乙醇的次要代谢物，是最近酒精摄入的高度特异性和敏感的指标，并且可以在生物液体中测量比乙醇本身长得多的时间。因此，它们有望成为监测近期乙醇使用情况的客观标记，或者反过来，在治疗试验和治疗计划中记录戒酒情况。与法医或流行病学相比，它们在治疗环境中的应用尚未在对照的、有充分记录的临床试验中得到充分调查。我们将进行一项乙醇挑战研究，并在NIAAA资助的两项门诊临床试验的背景下调查EtG/EtS，以满足以下具体目标：目的1：我们将表征尿EtG和EtS消除，包括受试者间和受试者内部的变异性和剂量依赖性，选择一系列乙醇剂量来产生轻度到重度饮酒后预期的血液酒精浓度。目的2：我们将在一项以戒断为目标的临床试验和一项以节制为目标的单独临床试验的受试者中确定EtG和EtS的浓度和浓度变化。在这两项研究中，我们将把这些测量与更传统的结果测量相关联，包括自我报告、血液酒精浓度、碳水化合物缺乏转铁蛋白和谷氨酰转移酶。这些研究应该为在酒精使用障碍的研究和管理中最佳使用这些有前途的新标志物提供指导。

DESCRIPTION (provided by applicant): Identification of recent alcohol consumption is a critical component of clinical trials and treatment programs that focus on alcohol use disorders. Unlike other substance abuse treatment programs, wherein urine drug screening provides objective evidence of recent drug use with a window of several days, alcohol focused programs must usually depend on self reports for this information. Ethyl glucuronide (EtG), and ethyl sulfate (EtS), minor metabolites of ethanol, are highly specific and sensitive indicators of recent alcohol ingestion, and can be measured in biological fluids for considerably longer than ethanol itself. Thus, they have promise as much needed objective markers for monitoring recent ethanol use or conversely, documenting abstinence in therapeutic trials and treatment programs. Their application in the therapeutic setting, in contrast to the forensic or epidemiological, has not yet been sufficiently investigated in the context of controlled, well documented clinical trials. We will conduct an ethanol challenge study and investigate EtG/EtS in the context of two NIAAA funded outpatient clinical trials in order to meet the following Specific Aims: AIM 1: We will characterize urinary EtG and EtS elimination, including inter-subject and intrasubject variability and dose dependency following a range of ethanol doses selected to produce blood alcohol concentrations that would be expected following light to heavy drinking. AIM 2: We will determine concentrations and changes in concentration of EtG and EtS at defined intervals in subjects participating in a clinical trial that has a goal of abstinence and AIM 3: in a separate clinical trial that has a goal of moderation. In both, we will correlate these measures with more traditional outcome measures, including self reports, blood alcohol concentrations, carbohydrate deficient transferrin and gamma glutamyl transferase. These studies should provide guidelines for optimal use of these promising new markers in the study and management of alcohol use disorders. PUBLIC HEALTH RELEVANCE: An objective marker and measure of recent alcohol consumption is needed for the optimal investigation of treatment options and for the management of patients in clinical trials and treatment programs respectively. Our proposed studies should define the utility of measuring the minor ethanol metabolites, ethyl glucuronide and ethyl sulfate, in conjunction with the study of new treatments, and also yield guidelines for appropriate use of these markers in the treatment of alcohol use disorders.