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: 10262945
• 负责人: SUDIE E BACK
• 金额: $ 68.17万
• 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/10262945
• 关键词: Address; Aftercare; Alcohol consumption; Alcohols; Animals; Area; Back; Behavior; Behavioral; Biological Markers; Chronic Post Traumatic Stress Disorder; Clinic; 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; Mission; Morbidity - disease rate; Motivation; National Institute on Alcohol Abuse and Alcoholism; Neurobiology; Neuropeptides; 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 outcome measures; clinical practice; comorbidity; craving; disability; effective therapy; efficacy evaluation; evidence base; health care service utilization; improved; improved outcome; innovation; insight; military veteran; 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.

项目概要/摘要 酒精使用障碍 (AUD) 和创伤后应激障碍 (PTSD) 经常同时发生且相关 具有显着的发病率、死亡率和医疗保健支出。退伍军人面临更大的共同风险 发生 AUD 和 PTSD，患病率比一般人群高 2-4 倍。我们组 制定了一项名为“创伤后应激障碍和药物使用障碍的并行治疗”的综合干预措施 使用长时间暴露（COPE）。 COPE 结合了经过经验验证的认知行为技术 用于 AUD 与针对 PTSD 的长期暴露 (PE) 疗法。退伍军人中的几项随机对照试验 平民证明了 COPE 在显着减轻 AUD 和 PTSD 症状方面的功效。尽管 积极的研究结果表明，改善治疗结果和提高保留率仍有很大空间。 越来越多的数据表明，神经肽催产素 (OT) 是一种有希望的候选药物，可增强 针对同时发生的 AUD 和 PTSD 进行心理社会干预，因为 OT 的目标是神经生物学和行为 两种疾病共有的失调。临床前和临床研究证明 OT 能够 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 管理），增强恐惧消除，促进与成功相关的亲社会行为 心理社会治疗结果（例如信任、社会认知）。在一项随机对照试点研究中，我们小组 发现在每周体育治疗之前进行 OT 治疗是安全的、耐受性良好的，并且会导致 与安慰剂相比，PTSD 症状加速减轻。尽管实证和理论 对加强社会心理干预（例如通过 OT 进行应对）的支持是强有力的，但迄今为止还没有研究表明 研究了这种组合方法。拟议的第二阶段研究的主要目标是检查 与安慰剂相比，OT 在减少退伍军人中 (1) 饮酒和 (2) PTSD 症状方面的功效 接受 COPE 治疗。为了实现这一目标，我们将采用一种手动的、基于证据的认知行为方法 干预（应对）；随机、双盲、安慰剂对照研究设计；标准化、重复 多个时间点临床结果的相关测量；我们将利用与 完善的退伍军人事务部诊所已准备好将积极的发现有效地转化为实践。此外，为了评估 为了研究所谓的神经生物学变化机制，我们将采用功能性磁共振成像 (fMRI) 在治疗前和治疗后检查 AUD 生物标志物。拟议的研究直接解决了 国家酒精滥用和酒精中毒研究所 (NIAAA) 的目的是确定药理学 同时解决同时发生的 AUD 和 PTSD 的治疗方法。这项研究的结果将提供新的 信息和机制见解可直接为临床实践提供信息并加速这一高度的研究 待研究区域。