Prazosin Treatment for Alcohol Use Disorder with Alcohol Withdrawal Symptoms

哌唑嗪治疗伴有酒精戒断症状的酒精使用障碍

• 批准号: 10403666
• 负责人: David Fiellin
• 金额: $ 73.43万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-15 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10403666
• 关键词: Accident and Emergency department; Address; Adrenal Glands; Adrenergic Antagonists; Advertising; Aftercare; Alcohol abuse; Alcohol consumption; Alcohol withdrawal syndrome; Alcoholism; Ambulatory Care; Anxiety; Blood Pressure; Brain; Characteristics; Chronic; Clinical Research; Consult; Data; Development; Distress; Dose; Double-Blind Method; Drug Metabolic Detoxication; Drug Prescriptions; Enrollment; Enzymes; FDA approved; Foxes; Functional disorder; Gender; Glucuronides; Goals; Health Care Costs; Heavy Drinking; Hospitals; Human; Hypothalamic structure; Individual; Institutes; Laboratory Research; Liver; Medical; Mental Depression; Mental Health; Neurobiology; Outcome; Patient Self-Report; Patients; Peripheral; Pharmaceutical Preparations; Phase; Placebo Control; Placebo Effect; Placebos; Post-Traumatic Stress Disorders; Prazosin; Prevalence; Public Health; Randomized Clinical Trials; Randomized Controlled Trials; Recording of previous events; Relapse; Reporting; Research; Risk; Role; Services; Site; Stress; Subgroup; Surgeon; Symptoms; Testing; Time; Titrations; Trauma; Treatment Failure; Treatment outcome; Withdrawal Symptom; Woman; addiction; alcohol abuse therapy; alcohol craving; alcohol relapse; alcohol use disorder; anxiety symptoms; associated symptom; base; chronic alcohol ingestion; craving; depressive symptoms; drinking; efficacy testing; follow up assessment; follow-up; improved; improved functioning; men; mood symptom; noradrenergic; patient subsets; physical conditioning; precision medicine; prognostic indicator; recruit; relapse risk; response; secondary outcome; symptom treatment; treatment effect

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.

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以及更高的复发率和酒精摄入量相关。 AUD 批准的药物数量不多，而且没有一种药物被证明对 AW 患者有效。 因此，非常需要开发和评估治疗方法来解决高风险的特定预后指标。 复发和治疗未能减轻 AUD 的相关负担。 研究发现，在患有 AW（AUD+AW）的 AUD 患者中，与 PBO 相比，PR（16 毫克/天）将 显着改善饮酒结果、渴望，并减少相关的焦虑和抑郁 症状并改善身体健康（收缩压和肝酶）功能和患者相关结果 在试验过程中以及在超过 3 个月的随访期间产生持久影响，从而 验证 AW 作为哌唑嗪疗效和 AUD 12 周治疗结果的预后指标。 拟在 150 名患者中开展哌唑嗪 II 期单中心随机临床试验（PR：16 mg/天，t.i.d 给药） 寻求患有 AUD+ AW（3 种或更多症状）的男性和女性的治疗，以解决以下具体问题 目标： 目标 1：评估 PR 与 PBO 对主要酒精使用结果的影响（百分比） 无大量饮酒日 (PSNHDD) 的受试者和%大量饮酒日的二次饮酒结果 (HDD%)、AUD+AW 患者的任何饮酒日 (DD%) 和平均饮酒量/天 (AvgD) 目标 2：评估 AUD+AW 患者的饮酒量。 PR 与 PBO 对酒精渴望、抑郁和焦虑等其他继发压力相关结果的影响 目标 3：评估 PR 与 PBO 对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果。 1：评估试验期间 PR 与 PBO 治疗以及后续身体健康状况的效果 （收缩压/舒张压和肝酶）和患者报告的功能结果 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 哌唑嗪对主要和次要酒精使用及相关结果的影响是一种常见的现象。 如果成功的话，研究结果将提供重要的信息。 关于哌唑嗪在 AUD+AW 治疗以及相关继发性心理和身体方面的作用的功效数据 它将进一步验证门诊治疗时的 AW 作为 AUD 的预后指标。 治疗和哌唑嗪在 AUD+AW 亚组患者中的使用也将支持该药物的开发。 精准医疗的目标是为患有 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 AUD 治疗结果。