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，其酒精戒断症状(AW)是 与更大的治疗失败风险和更高的复发率和饮酒率相关。电流的功效 在澳大利亚，批准的药物是适度的，没有一种药物被证明对AW患者有效。 因此，迫切需要开发和评估治疗方法，以解决高血压病的特定预后指标。 复发和治疗失败不能减轻与AUD相关的负担。基于此之前的临床 研究中，我们假设在AUD合并AW(AUD+AW)的患者中，PR(16 mg/天)与PBO相比将 显著改善饮酒结果、渴求，并减少相关的焦虑和抑郁 症状和改善身体健康(SBP和肝酶)功能和与患者相关的结果 在试验过程中，并在超过3个月的随访期内产生持久影响，从而 验证AW作为哌唑嗪疗效和AUD治疗结果的预后指标。为期12周的 拉唑嗪(PR：16 mg/d，ti.i.d)的II期、单部位、随机临床试验在150例中被提出 寻求治疗患有AUD+AW(3个或更多症状)的男性和女性，以解决以下具体问题 目的：目的1：评价PR和PBO对初度酒精使用结果的影响。 无重度饮酒的受试者(PSNHDD)和重度饮酒日的二次饮酒结果 (HDD%)、饮酒天数(DD%)和平均饮酒量(AvgD)。目标2：评估 PR与PBO对酒精渴求、抑郁和焦虑的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的长期短期治疗效果 治疗后1个月和3个月随访时间点的主要和其他次要结果。探险目标 1：评估PR和PBO治疗在试验期间和在次要身体健康的随访中的效果 (SBP/DBP和肝酶)和患者报告的功能结果。探索目标2：探索 治疗前患者的特征(性别、逆境/创伤史和终生创伤后应激障碍)是否会受到影响 哌唑嗪对初次和二次饮酒及相关结果的影响。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治疗中的作用及其在相关继发性心理和生理方面的疗效数据 健康结果。它将在门诊治疗开始时进一步验证AW作为AUD的预后指标 在AUD+AW亚组患者中进行治疗和使用哌唑嗪。它还将支持发展 精准医学的目标是为患有AW和应激相关的AUD患者提供特定的治疗方案 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.