Ethanol metabolites for monitoring drinking in clinical trials.

描述(由申请人提供)：识别最近的酒精消费是专注于酒精使用障碍的临床试验和治疗计划的关键组成部分。与其他药物滥用治疗计划不同的是，尿液药物筛查提供了最近使用药物的客观证据，窗口为几天，而专注于酒精的计划通常必须依赖于自我报告才能获得这些信息。乙基葡萄糖醛酸苷(EtG)和硫酸乙酯(ETS)是乙醇的次要代谢物，是近期酒精摄入的高度特异和敏感的指标，在生物液中的测量时间比乙醇本身长得多。因此，他们有希望成为监测最近乙醇使用的迫切需要的客观标记物，或者相反，在治疗试验和治疗计划中记录戒酒情况。与法医或流行病学不同的是，它们在治疗环境中的应用尚未在有充分记录的受控临床试验的背景下得到充分调查。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：目标1：我们将表征尿中EtG和ETS的消除，包括受试者间和受试者内的变异性和剂量依赖关系，根据选定的一系列乙醇剂量来产生预期在轻度饮酒到重度饮酒后的血液酒精浓度。目的2：我们将在一项以戒毒为目标的临床试验和以适度为目标的单独临床试验中，以规定的间隔确定受试者的EtG和ETS浓度及其变化。在这两种方法中，我们都会将这些指标与更传统的结果指标相关联，包括自我报告、血液酒精浓度、碳水化合物缺乏的转铁蛋白和伽马谷氨基转移酶。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希望的新标记物提供指导。 公共卫生相关性：需要一个客观的标记物和最近饮酒的衡量标准，以便分别对临床试验和治疗计划中的患者进行最佳治疗方案的调查和管理。我们建议的研究应该确定在研究新的治疗方法的同时，测量次要的乙醇代谢物乙基葡萄糖醛酸乙酯和乙基硫酸乙酯的效用，并为这些标志物在酒精使用障碍的治疗中的适当使用提供指南。

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.