Prazosin Treatment for Alcohol Use Disorder with Alcohol Withdrawal Symptoms

项目摘要 酒精使用障碍（AUD）是一种慢性复发性疾病，其中酒精戒断症状（AW） 与更大的治疗失败风险和更高的复发率和酒精摄入量相关。电流的有效性 在AUD中批准的药物是适度的，并且没有一种药物被证明对AW有效。 因此，非常需要开发和评估治疗方法，以解决高血压的特定预后指标。 复发和治疗失败，以减少AUD的相关负担。根据之前的临床研究， 研究中，我们假设在伴有AW的AUD患者（AUD+AW）中，PR（16 mg/天）与PBO相比， 显著改善酒精使用结果，渴望，并减少相关的焦虑和抑郁 症状和改善身体健康（SBP和肝酶）功能和患者相关结局 在试验过程中，并在超过3个月的随访期内产生持久影响， 验证AW作为哌唑嗪疗效和AUD治疗结局的预后指标。12周 哌唑嗪（PR：16 mg/天，t.i.d给药）的II期、单中心、随机临床试验拟定于150例患者中进行 患有AUD+ AW（3种或3种以上症状）的男性和女性寻求治疗，以解决以下具体问题 目的：目的#1：评价PR与PBO对主要酒精使用结果的影响， 无重度饮酒日（PSNHDD）的受试者和重度饮酒日百分比的次要饮酒结局 (HDD%）、任何饮酒日（DD%）和平均饮酒/日（AvgD）。目标#2：评估 PR与PBO对酒精渴望、抑郁和焦虑等其他继发性应激相关结局的影响 试验期间的症状。目的#3：评估PR与PBO对以下患者的持久短期治疗效果： 治疗后1个月和3个月随访时间点的主要和其他次要结局。探索性目标 1：评估试验期间和随访时PR与PBO治疗对次要身体健康的影响 (SBP/DBP和肝酶）和患者报告的功能结局。探索目标2：探索 治疗前患者特征（性别、逆境/创伤史和终生PTSD）是否影响 哌唑嗪对初级和次级酒精使用的影响及相关结果。哌唑嗪是一种常见的 大多数临床医生都觉得舒服的处方药。如果成功，研究结果将提供重要的 哌唑嗪在AUD+AW治疗中的作用以及在相关继发性心理和生理方面的疗效数据 健康成果。它将进一步验证在门诊治疗进入时AW作为AUD的预后指标 AUD+AW亚组患者中的治疗和哌唑嗪使用。它还将支持发展 精准医学的目标是为患有AW和压力相关的AUD患者提供特定的治疗选择 病理生理学，以改善他们的AUD治疗结果。

Project Abstract Alcohol Use Disorder (AUD) is a chronic relapsing illness in which alcohol withdrawal symptoms (AW) are associated with greater treatment failure risk and higher rates of relapse and alcohol intake. Efficacy of current approved medications in AUD are modest, and none have been shown to be efficacious in those with AW. Thus, there is great need to develop and evaluate treatments to address specific prognostic indicators of high relapse and treatment failure to reduce the associated burden of AUD. Based on this previous clinical research, we hypothesized that in AUD patients with AW (AUD+AW), PR (16 mg/day) compared to PBO will significantly improve alcohol use outcomes, craving and also reduce associated anxiety and depression symptoms and improve physical health (SBP and liver enzymes) functioning and patient-related outcomes during the course of the trial and with enduring effects during over a 3 month follow up period, thereby validating AW as a prognostic indicator both of Prazosin efficacy and in AUD treatment outcome. A 12-week Phase II, single site, randomized clinical trial of Prazosin (PR: 16 mg/day, t.i.d dosing) is proposed in 150 treatment seeking men and women with AUD+ AW (3 or more symptoms) to address the following specific aims: Aim #1: To evaluate the effects of PR vs PBO on the primary alcohol use outcome of percent of subjects with no heavy drinking day (PSNHDD) and secondary drinking outcomes of %heavy drinking day (HDD%), any drinking day (DD%) and average drinks/day (AvgD) in AUD+AW patients. Aim #2: To assess the effects of PR vs PBO on other secondary stress-related outcomes of alcohol craving, depression and anxiety symptoms during the trial. Aim #3: To assess enduring short-term treatment effects of PR versus PBO on primary and other secondary outcomes at 1- and 3- month post-treatment follow-up time points. Exploratory Aim 1: To assess the effects of PR vs PBO treatment during the trial and at follow up on secondary physical health (SBP/DBP and liver enzymes) and patient-reported functioning outcomes. Exploratory Aim 2: To explore whether pre-treatment patient characteristics (gender, adversity/trauma history and lifetime PTSD) influence Prazosin effects on primary and secondary alcohol use and related outcomes. Prazosin is a commonly prescribed medication that most clinicians feel comfortable using. If successful, findings will provide important efficacy data on Prazosin’s role in AUD+AW treatment and in related secondary psychological and physical health outcomes. It will further validate AW at outpatient treatment entry as a prognostic indicator for AUD treatment and for Prazosin use among AUD+AW subgroup of patients. It will also support development of the precision medicine goal of providing specific treatment options for AUD patients with AW and stress-related pathophysiology to improve their AUD treatment outcomes.