CAP - Doxazosin in the Treatment of Co-Occurring PTSD and Alcohol Use Disorders

CAP - 多沙唑嗪治疗同时发生的 PTSD 和酒精使用障碍

• 批准号: 10039493
• 负责人: SUDIE E BACK
• 金额: --
• 依托单位: RALPH H JOHNSON VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-10-01 至 2020-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10039493
• 关键词: Address; Adrenergic Antagonists; Affect; Afghanistan; Alcohol consumption; Anxiety; Area; Caring; Chronic; Chronic Disease; Clinical; Clinical Practice Guideline; Clinical Research; Clinical trial protocol document; Collaborations; Common Data Element; Complex; Conflict (Psychology); Department of Defense; Dose; Double-Blind Method; Doxazosin; Early treatment; Employment; Ensure; Evidence based intervention; Experimental Designs; Faculty; Family; Family Relationship; Feeling suicidal; Freedom; Functional Magnetic Resonance Imaging; Functional disorder; Half-Life; Health; Health Expenditures; Home environment; Hour; Impairment; Individual; Investigation; Iraq; Knowledge; Left; Measurement; Measures; Medical; Medical center; Mental Depression; Mental Health; Mental Health Services; Methodology; Military Personnel; Mission; Nightmare; Outcome; Patient Care; Pharmaceutical Preparations; Phase II Clinical Trials; Pilot Projects; Placebos; Post-Traumatic Stress Disorders; Prazosin; Prediction of Response to Therapy; Procedures; Prognostic Marker; Public Health; Randomized; Readiness; Research; Research Personnel; Risk; Risk Behaviors; Science; Services; Severities; Sleep; Social Functioning; South Carolina; Standardization; Substance Use Disorder; Suicide attempt; Symptoms; Testing; Time; Translating; Treatment outcome; Universities; Veterans; Violence; Work; alcohol comorbidity; alcohol use disorder; arm; behavioral health; clinical practice; clinically relevant; combat; common treatment; comorbidity; data standards; design; efficacy testing; evidence base; experimental group; follow-up; improved; innovation; multidisciplinary; neuroimaging; novel; open label; operation; outcome prediction; physical conditioning; pre-clinical; public health relevance; randomized placebo-controlled clinical trial; reduce symptoms; reduced substance use; relating to nervous system; resilience; service member; symptomatology; treatment strategy

 DESCRIPTION (provided by applicant): Due to sustained military conflicts in Afghanistan and Iraq over the past decade, there are an increasing number of U.S. military personnel and Veterans returning home with posttraumatic stress disorder (PTSD) and comorbid alcohol use disorders (AUD). If left untreated, Veterans with co-occurring PTSD and substance use disorders are at increased risk for developing other mental health problems (e.g., depression, anxiety), suicidal ideation and attempts, physical health problems, reduced resiliency and military readiness, employment problems, violence, and family/relationship impairment. While mental health services are in place for U.S. service members, substantial gaps in the treatment of co-occurring PTSD and AUD exist and there is little scientific evidence available to guide the provision of care. The proposed study directly addresses this critical knowledge gap by testing the efficacy of doxazosin, a long-acting and selective alpha-1 adrenergic antagonist, as compared to placebo in reducing PTSD and AUD severity among U.S. military personnel who have served in Operation Enduring Freedom, Operation Iraqi Freedom, or Operation New Dawn (OEF/OIF/OND). The most common substance use disorder among Veterans is alcohol use disorder (AUD); thus the proposed study targets Veterans with co-occurring PTSD and AUD. The medication to be investigated (doxazosin) represents a novel treatment approach for PTSD/AUD. While prazosin, also an alpha-1 adrenergic antagonist, has been shown to improve sleep and nightmares in military personnel with PTSD and may help reduce substance use severity, it has a short half-life of 2-3 hours and requires multiple doses each day, which is a significant limitation. In several pilot studies, doxazosin has shown promise in significantly reducing symptoms of PTSD and AUD and, in contrast to prazosin, it requires once per day dosing which confers a significant advantage in terms of translating positive findings into routine clinical practice. In this Stage I study, we will (1) employ a two-arm randomized, double-blind, between-groups experimental design that will consist of 12 weeks of treatment with doxazosin or placebo medication; (2) use standardized, repeated dependent measures to rigorously assess PTSD symptomatology and AUD severity at 5 time points (baseline, week 4, week 8, week 12 and 1-month follow-up); (3) measure impairment in associated mental and behavioral health problems (e.g., depression, anxiety, sleep, risky behaviors, family/social functioning); and (4) use functional magnetic resonance imaging (fMRI) to investigate the underlying pathophysiology of comorbid PTSD/AUD and identify prognostic indicators of treatment outcome. To achieve these aims, we have assembled a multidisciplinary team of investigators with nationally-recognized expertise in combat-related PTSD, substance use disorders and neuroimaging who have successfully collaborated in the past and are uniquely qualified to implement this type of investigation. The investigators represent a collaboration of faculty at the Ralph H. Johnson Veterans Affairs (VA) Medical Center and the Medical University of South Carolina (MUSC) in Charleston, SC. The proposed project is directly responsive to the mission of the Consortium to Alleviate PTSD (CAP) in that it seeks to enhance and accelerate research on the treatment of early, chronic and latent onset PTSD and common comorbidities such as AUD. The findings of this study will provide critically needed empirical evidence to help inform clinical practice guidelines and better serve the needs of U.S. service members, Veterans and their families.

 描述（由申请人提供）： 由于过去十年在阿富汗和伊拉克的持续军事冲突，越来越多的美国军事人员和退伍军人回国时患有创伤后应激障碍（PTSD）和酒精使用障碍（AUD）。如果不治疗，患有PTSD和物质使用障碍的退伍军人患其他心理健康问题的风险增加（例如，抑郁、焦虑）、自杀意念和企图、身体健康问题、复原力和军事准备下降、就业问题、暴力和家庭/关系受损。虽然美国为军人提供了心理健康服务，但在治疗同时发生的PTSD和AUD方面存在巨大差距，并且几乎没有科学证据可以指导护理的提供。这项拟议的研究通过测试多沙唑嗪（一种长效和选择性α-1肾上腺素能拮抗剂）与安慰剂相比在降低持久自由行动、伊拉克自由行动或新黎明行动（OEF/OIF/OND）中服役的美国军事人员的PTSD和AUD严重程度方面的疗效，直接解决了这一关键的知识差距。退伍军人中最常见的物质使用障碍是酒精使用障碍（AUD）;因此，拟议的研究针对患有PTSD和AUD并发症的退伍军人。待研究的药物（多沙唑嗪）代表了PTSD/AUD的新型治疗方法。虽然哌唑嗪也是一种α-1肾上腺素能拮抗剂，已被证明可以改善患有PTSD的军事人员的睡眠和噩梦，并可能有助于降低物质使用的严重程度，但它的半衰期很短，只有2-3小时，每天需要多次给药，这是一个显著的限制。在几项初步研究中，多沙唑嗪显示出显著减轻PTSD和AUD症状的前景，与哌唑嗪相比，它需要每天给药一次，这在将阳性结果转化为常规临床实践方面具有显著优势。在第一阶段研究中，我们将（1）采用两组随机、双盲、组间实验设计，包括12周的多沙唑嗪或安慰剂治疗;（2）使用标准化、重复依赖性测量，在5个时间点严格评估PTSD的病理学和AUD严重程度（基线、第4周、第8周、第12周和1个月随访）;（3）测量相关的精神和行为健康问题（例如，抑郁、焦虑、睡眠、危险行为、家庭/社会功能）;以及（4）使用功能性磁共振成像（fMRI）来研究共病PTSD/AUD的潜在病理生理学，并确定治疗结果的预后指标。为了实现这些目标，我们组建了一个多学科的调查人员团队，他们在与战斗有关的创伤后应激障碍，物质使用障碍和神经影像学方面具有全国公认的专业知识，他们过去曾成功合作，并且具有独特的资格进行此类调查。研究人员代表了拉尔夫H。约翰逊退伍军人事务部（VA）医疗中心和查尔斯顿的南卡罗来纳州医科大学（MUSC）。拟议的项目直接响应缓解PTSD（CAP）联盟的使命，因为它旨在加强和加速对早期、慢性和潜伏发作的PTSD和常见合并症（如AUD）治疗的研究。这项研究的结果将提供急需的经验证据，以帮助告知临床实践指南， 服务于美国服务人员，退伍军人及其家人的需求。