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

N-乙酰半胱氨酸治疗酒精使用障碍和共病 PTSD 的随机对照试验

基本信息

批准号：
9982151
负责人：
SUDIE E BACK
金额：
$ 60.3万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-10 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9982151
关键词：
Abstinence Acetylcysteine Address Alcohol consumption Alcohols Animals Antioxidants Anxiety Area Biological Caring Chronic Post Traumatic Stress Disorder Clinical Clinical Practice Guideline Clinical Research Clinical Trials Complex Cues Data Development Disease Double-Blind Method Employment Evidence based intervention Experimental Designs Family Family Relationship Feeling suicidal Functional Magnetic Resonance Imaging Functional disorder Glutamates Health Expenditures Human Impairment Individual Investigation Knowledge Laboratories Left Legal Magnetic Resonance Spectroscopy Measurement Measures Medical Medical Economics Mental Depression Mental Health Methodology Mission National Institute on Alcohol Abuse and Alcoholism Outcome Patient Care Patient Self-Report Pharmaceutical Preparations Pharmacological Treatment Pharmacotherapy Pilot Projects Placebos Post-Traumatic Stress Disorders Prognostic Marker Protons Public Health Randomized Randomized Controlled Trials Research Research Personnel Risk Risk Behaviors Role Safety Science Severities Sleep Social Functioning Standardization Substance Use Disorder Suicide Suicide attempt Techniques Testing Therapeutic Therapeutic Agents Time Treatment outcome Veterans alcohol abuse therapy alcohol comorbidity alcohol use disorder arm behavioral health clinical practice common treatment comorbidity craving design drinking efficacy testing evidence base experimental group follow-up high risk sexual behavior improved improved outcome innovation multidisciplinary multimodality neural circuit neurobiological mechanism neurochemistry neuroimaging novel pilot trial pre-clinical psychosocial reduced alcohol use response suicide rate symptomatology treatment response

项目摘要

ABSTRACT Alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) are chronic and debilitating psychiatric conditions which frequently co-occur. If left untreated, individuals with AUD and co-occurring PTSD are at increased risk for developing other mental health problems (e.g., depression, anxiety), suicidal ideation and attempts, medical problems, family/relationship impairment, and employment problems. Despite the frequent co-occurrence and deleterious consequences associated with comorbid AUD/PTSD, 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 N-acetylcysteine (NAC) as compared to placebo in reducing AUD and PTSD severity. NAC represents a promising and novel candidate pharmacotherapy for individuals with AUD and comorbid PTSD. Accumulating preclinical and preliminary clinical research suggests a role for NAC in the treatment of substance use disorders and PTSD via glutamate modulation. Data from a randomized, double-blind pilot study recently completed by the investigative team in Veterans with substance use disorders (primarily alcohol) and PTSD provides encouraging support for the therapeutic potential of NAC in the treatment of AUD and PTSD. Moreover, NAC is an inexpensive, over-the-counter agent with a favorable tolerability profile, all of which confer ease of transferability from the research setting to clinical practice. In this Stage II study, we will (1) employ a two-arm randomized, double-blind, between-groups experimental design that will consist of 12 weeks of treatment with NAC or placebo medication; (2) use standardized, repeated dependent measures to rigorously assess AUD severity and PTSD symptomatology at 6 time points (baseline, week 6, week 12, and 3-, 6-, and 12-month follow-up); (3) measure impairment in associated mental and behavioral health problems (e.g., depression, sleep, suicidality, risky sexual behaviors, family/social functioning); and (4) use functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (MRS) to investigate the underlying pathophysiology of comorbid AUD/PTSD and prognostic indicators of treatment outcome. To achieve these aims, we have assembled a multidisciplinary team of investigators with nationally-recognized expertise in AUD and comorbid PTSD, clinical trials, human laboratory paradigms, and neuroimaging who have successfully collaborated in the past and are uniquely qualified to implement this type of investigation. The proposed project is directly responsive to the mission of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the new AUD/PTSD initiative to accelerate research on the development of effective pharmacologic treatments for this common and highly disabling comorbidity. The findings from this study will provide critically needed empirical evidence to help inform clinical practice guidelines and accelerate research on the treatment of AUD and comorbid PTSD.

抽象的酒精使用障碍（AUD）和创伤后应激障碍（PTSD）是慢性且使人衰弱的精神病学经常同时发生的条件。如果未经治疗，则具有AUD和同时发生的PTSD的人在增加了出现其他心理健康问题（例如抑郁症，焦虑），自杀意念和尝试，医疗问题，家庭/关系障碍和就业问题。尽管很频繁与合并AUD/PTSD相关的共发生和有害后果，几乎没有科学可用于指导护理提供的证据。拟议的研究直接解决了这一关键通过测试N-乙酰半胱氨酸（NAC）的功效与安慰剂相比，通过测试知识差距 AUD和PTSD严重性。 NAC代表了个体的一种有希望的新型候选药物治疗与AUD和合并症PTSD。累积的临床前和初步临床研究表明了 NAC通过谷氨酸调节治疗物质使用障碍和PTSD。来自a的数据调查团队最近在退伍军人中完成了随机，双盲试点研究使用疾病（主要是酒精），而PTSD为NAC的治疗潜力提供了令人鼓舞的支持在AUD和PTSD的治疗中。此外，NAC是一位廉价的非处方药，有利耐受性概况，所有这些都赋予了从研究环境到临床实践的可传递性。在这个第二阶段研究，我们将（1）采用两臂随机，双盲，组间实验设计这将包括用NAC或安慰剂药物治疗的12周；（2）使用标准化，重复在6个时间点（基线，第6周，第12周以及3，6和12个月的随访）；（3）衡量相关心理和行为健康问题（例如，抑郁，睡眠，自杀，有风险的性行为，家庭/社会功能）; （4）使用功能磁共振成像（fMRI）和质子磁共振光谱（MRS）研究合并症/PTSD和预后的基本病理生理学治疗结果的指标。为了实现这些目标，我们组建了一个多学科团队具有全国认可的AUD和合并症专业知识的研究人员，临床试验，人类实验室过去成功合作并且具有独特的资格，范式和神经影像学实施此类调查。拟议的项目直接响应国家的使命酒精滥用和酒精中毒研究所（NIAAA）和新的AUD/PTSD倡议，以加速研究为这种常见且高度残疾的合并症开发有效的药理治疗方法。这这项研究的结果将提供急需的经验证据，以帮助临床实践指南和加速有关AUD和合并症PTSD治疗的研究。