Randomized Controlled Trial of N-acetylcysteine for Alcohol Use Disorder and Comorbid PTSD

项目摘要/摘要 尽管共病饮酒经常同时发生并产生有害后果 在精神障碍(AUD)和创伤后应激障碍(PTSD)方面，几乎没有科学证据可以指导 提供护理服务。目前的研究直接解决了这一关键差距，通过测试 N-乙酰半胱氨酸(NAC)与安慰剂在降低AUD和PTSD严重程度方面的比较。积累临床前知识 临床研究为NAC在治疗慢性阻塞性肺疾病中的治疗潜力提供了令人鼓舞的支持 AUD/PTSD通过谷氨酸能调节。此外，NAC是一种廉价的非处方药代理，具有 良好的耐受性特征。父母资助是一项持续12周的双盲随机对照试验 测试NAC与安慰剂在降低AUD症状(目标1)和创伤后应激障碍严重程度(目标2)方面的差异。进阶 在治疗前和治疗后使用神经成像技术来研究疾病的病理生理学。 澳元/创伤后应激障碍(目标3)。所有参与者都接受每周一次的AUD认知行为疗法(CBT)。 本行政补编(PA-18-591)的目的是留住资深博士后Delisa Brown博士 研究员，为家长项目额外提供六个月的时间，以支持顺利完成研究目标 并保持父赠款的完整性。布朗博士以两种重要而独特的身份在 由于新冠肺炎大流行造成的挫折，她在这些角色中的工作被推迟。 (1)布朗博士是一位训练有素的研究治疗师，通过远程保健向参与者提供每周一次的澳大利亚大学硕士学位论文。 她完成了为期数天的干预理论、背景和实施培训，并已 在过去的两年中参与了每周的监督工作。布朗医生是一位杰出的临床医生，作为一名 非洲裔美国人临床医生她为该项目带来了高度重视的多样性(近20%的样本来自非洲 美国人)。她以这一身份开展的工作将有助于确保获得实现目标1和目标2所需的足够权力。 (2)布朗博士在神经成像部分发挥着至关重要的作用，他负责图像脚本的开发 会议以创建个性化的扫描仪酒精、创伤和中性线索。布朗博士完成了 耶鲁大学和马萨诸塞州总医院专门为此目的进行的专门培训。她 还协助完成图像数据前处理的关键任务，以确保质量控制和准备 以供分析。她以这一身份开展的工作对成功完成目标3至关重要。 行政副刊将确保布朗博士继续对父母补助金进行工作，并保持 执行这一重要项目的训练有素的团队的诚信。这个项目的发现有 有潜力创新临床实践，改善治疗结果，并减少显著的经济损失 与共同发生的澳大利亚/创伤后应激障碍相关的负担。

Project Summary/Abstract Despite the frequent co-occurrence and deleterious consequences associated with comorbid alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD), there is little scientific evidence available to guide the provision of care. The current study directly addresses this critical gap by testing the efficacy of N-acetylcysteine (NAC) as compared to placebo in reducing AUD and PTSD severity. Accumulating preclinical and clinical research provides encouraging support for the therapeutic potential of NAC in the treatment of AUD/PTSD via glutamatergic modulation. Moreover, NAC is an inexpensive, over-the-counter agent with a favorable tolerability profile. The parent grant is an ongoing 12-week, double-blind, randomized controlled trial testing NAC versus placebo on reduction in AUD symptoms (Aim 1) and PTSD severity (Aim 2). Advanced neuroimaging techniques are employed at pre- and post-treatment to investigate the pathophysiology of AUD/PTSD (Aim 3). All participants receive weekly, manualized cognitive-behavioral therapy (CBT) for AUD. The purpose of this Administrative Supplement (PA-18-591) is to retain Dr. Delisa Brown, a senior postdoctoral fellow, on the parent project for an additional six months to support the successful completion of the study aims and preserve the integrity of the parent grant. Dr. Brown serves in two vital and distinct capacities on the project, and her work in these roles has been delayed due to setbacks resulting from the COVID-19 pandemic. (1) Dr. Brown is a highly-trained Study Therapist, providing weekly CBT for AUD via telehealth to participants. She completed a multi-day training on the intervention theory, background, and implementation, and has participated in weekly supervision over the past two years. Dr. Brown is an exceptional clinician, and as an African American clinician she brings highly valued diversity to the project (almost 20% of the sample is African American). Her work in this capacity will help ensure sufficient power necessary to address Aims 1 and 2. (2) Dr. Brown plays a vital role on the neuroimaging component by conducting imagery script development sessions to create personalized, in-scanner alcohol, trauma, and neutral cues. Dr. Brown completed specialized training at Yale University and Massachusetts General Hospital specifically for this purpose. She also assists with the critical task of pre-processing the imaging data to ensure quality control and preparation for analysis. Her work in this capacity is crucial to the successful completion of Aim 3. The requested Administrative Supplement will ensure Dr. Brown's continued work on the parent grant and maintain the integrity of the highly trained team carrying out this important project. The findings from this project have the potential to innovate clinical practice, improve treatment outcomes, and decrease the significant economic burden associated with co-occurring AUD/PTSD.