Oxytocin to Enhance Integrated Exposure-Based Treatment of Co-occurring Alcohol Use Disorder and PTSD

催产素可增强对同时发生的酒精使用障碍和创伤后应激障碍的综合暴露治疗

• 批准号: 10097893
• 负责人: SUDIE E BACK
• 金额: $ 66.6万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10097893
• 关键词: Address; Aftercare; Alcohol consumption; Alcohols; Animals; Area; Back; Behavior; Behavioral; Biological Markers; Chronic Post Traumatic Stress Disorder; Clinic; Clinical; Clinical Research; Cognitive; Cognitive Therapy; Collaborations; Cues; Data; Disease; Double-Blind Method; Economic Burden; Ethanol; Exposure to; Extinction (Psychology); Fright; Functional Magnetic Resonance Imaging; General Population; Health Expenditures; Human; Individual; Intervention; Investigation; Knowledge; Measures; Mental Health; Military Personnel; Mission; Morbidity - disease rate; Motivation; National Institute on Alcohol Abuse and Alcoholism; Neurobiology; Neuropeptides; Outcome; Oxytocin; Participant; Patient Care; Patient Self-Report; Pharmacological Treatment; Pharmacotherapy; Pilot Projects; Placebos; Post-Traumatic Stress Disorders; Prevalence; Psychotherapy; Public Health; Randomized; Randomized Controlled Trials; Research; Research Design; Risk; Science; Self Administration; Standardization; Strategic Planning; Substance Use Disorder; Symptoms; Techniques; Testing; Therapeutic Intervention; Time; TimeLine; Translating; Trauma; Treatment outcome; Trust; Veterans; Withdrawal Symptom; alcohol behavior; alcohol response; alcohol use disorder; associated symptom; base; blood oxygen level dependent; care outcomes; clinical practice; comorbidity; craving; disability; effective therapy; evidence base; health care service utilization; improved; improved outcome; innovation; insight; mortality; multidisciplinary; neurobiological mechanism; neuroimaging; novel; physical conditioning; placebo controlled study; preclinical study; psychosocial; reduce symptoms; reduced alcohol use; response; social cognition; treatment effect; treatment optimization

PROJECT SUMMARY/ABSTRACT Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) frequently co-occur and are associated with significant morbidity, mortality, and health care expenditures. Military Veterans are at increased risk for co- occurring AUD and PTSD, with prevalence rates 2-4 times higher than the general population. Our group developed an integrated intervention entitled Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure (COPE). COPE incorporates empirically validated cognitive-behavioral techniques for AUD with Prolonged Exposure (PE) therapy for PTSD. Several randomized controlled trials among Veterans and civilians demonstrate efficacy of COPE in significantly reducing AUD and PTSD symptoms. Despite the positive findings, there remains substantial room for improving treatment outcomes and enhancing retention. Accumulating data suggest that the neuropeptide oxytocin (OT) is a promising candidate to enhance psychosocial interventions for co-occurring AUD and PTSD, as OT targets neurobiological and behavioral dysregulation common to both disorders. Preclinical and clinical studies demonstrate the ability of OT to ameliorate a variety of alcohol-related behaviors (e.g., craving, withdrawal symptoms, tolerance, ethanol self- administration), enhance fear extinction, and promote prosocial behaviors associated with successful psychosocial treatment outcomes (e.g., trust, social cognition). In a randomized controlled pilot study, our group found that OT administration prior to weekly PE therapy sessions was safe, well-tolerated, and resulted in accelerated reduction in PTSD symptoms as compared to placebo. Although the empirical and theoretical support for augmenting psychosocial interventions such as COPE with OT is robust, no studies to date have examined this combined approach. The primary objective of the proposed Stage II study is to examine the efficacy of OT as compared to placebo in reducing (1) alcohol use, and (2) PTSD symptoms among Veterans receiving COPE therapy. To accomplish this, we will employ a manualized, evidence-based, cognitive-behavioral intervention (COPE); a randomized, double-blind, placebo-controlled study design; standardized, repeated dependent measures of clinical outcomes at multiple time points; and we will leverage close collaboration with well-established VA clinics prepared to efficiently translate positive findings into practice. In addition, to evaluate purported neurobiological mechanisms of change, we will employ functional magnetic resonance imaging (fMRI) at pre- and post-treatment and examine AUD biomarkers. The proposed study directly addresses the mission of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in that it aims to identify pharmacologic treatments to address co-occurring AUD and PTSD simultaneously. The findings from this study will provide new information and mechanistic insights to directly inform clinical practice and accelerate the research in this highly understudied area.

项目摘要/摘要 酒精使用障碍（AUD）和创伤后应激障碍（PTSD）经常同时发生，并且相关 有大量发病率，死亡率和医疗保健支出。退伍军人的共同风险增加 发生AUD和PTSD，患病率是一般人群的2-4倍。我们的小组 开发了一项综合干预措施，标题为PTSD和药物使用障碍 使用长时间的暴露（COPE）。 COPE结合经验验证的认知行为技术 用于长期暴露（PE）治疗PTSD的AUD。退伍军人中的几个随机对照试验 平民表现出应对在大大减轻AUD和PTSD症状的功效。尽管有 积极的发现，仍然有很大的空间来改善治疗结果并增强保留率。 累积数据表明神经肽氧毒素（OT）是有前途的候选人增强的候选者 同时发生的AUD和PTSD的社会心理干预措施，因为OT针对神经生物学和行为 两种疾病常见的失调。临床前和临床研究表明了OT的能力 改善各种与酒精相关的行为（例如，渴望，戒断症状，​​耐受性，乙醇自我 行政），增强恐惧灭绝并促进与成功相关的亲社会行为 社会心理治疗结果（例如，信任，社会认知）。在一项随机对照试验研究中，我们的小组 发现在每周的PE治疗会议之前给药是安全，耐受性良好的，并导致 与安慰剂相比，PTSD症状的降低加速。虽然经验和理论 支持增加诸如OT之类的社会心理干预措施是强大的，迄今为止尚无研究 检查了这种合并的方法。拟议的II期研究的主要目标是检查 与安慰剂相比，OT的功效在减少（1）饮酒方面，以及（2）退伍军人的PTSD症状 接受应对疗法。为此，我们将采用手动的，循证的，认知行为 干预（COPE）；随机，双盲，安慰剂控制的研究设计；标准化，重复 在多个时间点的临床结果的依赖度量；我们将利用与 公认的VA诊所准备有效地将积极的发现转化为实践。另外，评估 据称的变化神经生物学机制，我们将采用功能磁共振成像（fMRI） 在治疗前后，检查AUD生物标志物。拟议的研究直接解决了 美国国家酒精滥用与酒精中毒研究所（NIAAA）旨在确定药理学 治疗以同时解决同时发生的AUD和PTSD。这项研究的发现将提供新的 信息和机械见解，可以直接为临床实践提供信息并加速这一高度研究 研究的区域。