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，在绘制戒断症状（AW）是 与较大的治疗失败有关，较大的摄入功效的复发率更高 AUD中批准的药物是适中的，在患有AW的人中没有任何有效的药物有效。 因此，非常需要开发和评估tealation torature，以解决高的预后指标 复发和信任无法减轻相关的AUD负担。 研究，我们假设在AUD患者（AUD+AW）的AUD患者中，PR（16毫克/天）与PBO相比将 显着改善酒精使用结果，渴望并减轻相关的焦虑和抑郁 症状并改善身体健康（SBP和肝酶）功能和与患者有关的结果 在试验过程中，在3个月的随访期内具有持久的效果 验证AW作为prazosin疗效和AUD治疗结果的编程指标 II阶段，单位地点，prazosin的随机临床试验（PR：16 mg/day，T.I.D剂量）在150中提供 寻求男性的治疗和AUD+ AW（3个或更多症状）以解决以下特定 目的：目标＃1：评估PR与PBO对主要酒精使用结果的影响 没有大量饮酒的受试者（PSNHDD）和次要饮酒量为％饮酒日 （HDD％），任何饮酒日（DD％）和AUD+AW患者的平均饮料/天（AVGD）。 PR与PBO对酒精渴望，抑郁和焦虑的其他二级应力相关结果的影响 试验期间的症状。 在处理后的1个月和3个月的探索目的 1：评估试验期间PR与PBO治疗的影响，并在随访中对二级身体健康 （SBP/DBP和肝脏酶）和患者报告的功能结果2：探索 治疗前患者特征（性别，逆境/创伤病史和终生PTSD）是否影响 普泽因对原发性和二级饮酒和相关结果的影响。 大多数临床医生使用的处方药都可以使用。 有关prazosin在AUD+AW治疗以及相关的二级心理和身体中的作用的功效数据 健康结果。 在AUD+AW子组中使用丙唑嗪的治疗和使用。 精确的医学目标是提供特定的治疗选择，以使用AW AW AW AWAW AW和与压力相关 病理生理学以改善其AUD治疗结果。