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: 10478268
• 负责人: SUDIE E BACK
• 金额: $ 64.81万
• 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/10478268
• 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; Placebo Control; 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.

项目摘要/摘要 酒精使用障碍(AUD)和创伤后应激障碍(PTSD)经常并存并相互关联 具有显著的发病率、死亡率和医疗保健支出。退伍军人面临着更高的联合- 发生AUD和PTSD，患病率比一般人群高2-4倍。我们的团队 开发了一种名为同时治疗创伤后应激障碍和药物使用障碍的综合干预措施 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 对于创伤后应激障碍的长期暴露(PE)治疗的AUD。退伍军人中的几项随机对照试验 平民在显著减少AUD和创伤后应激障碍症状方面显示出COPE的有效性。尽管 虽然研究结果呈阳性，但仍有很大的改善治疗结果和加强保留的余地。 越来越多的数据表明，神经肽催产素(OT)是一种有希望增强的候选物质 作为OT靶点的AUD和PTSD共发病的心理社会干预 这两种疾病都有共同的调节失调。临床前和临床研究表明，OT有能力 改善各种与酒精有关的行为(如渴求、戒断症状、耐受性、酒精自我 管理)，增强恐惧消退，并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)。在一项随机对照试验研究中，我们小组 发现在每周体育治疗之前服用OT是安全的，耐受性良好，并导致 与安慰剂相比，创伤后应激障碍症状加速减少。尽管经验主义和理论主义 到目前为止，还没有研究表明，支持加强心理社会干预，如应对加班 检查了这一组合方法。拟议第二阶段研究的主要目的是研究 OT与安慰剂在减少(1)酒精使用和(2)退伍军人创伤后应激障碍症状方面的疗效比较 接受应对疗法。为了实现这一点，我们将采用基于证据的、认知行为的 干预(COPE)；随机、双盲、安慰剂对照研究设计；标准化、重复 在多个时间点对临床结果进行依赖测量；我们将利用与 建立良好的退伍军人管理局诊所准备将积极的发现有效地转化为实践。此外，要评估 所谓的神经生物学机制的变化，我们将使用功能磁共振成像(Fmri)。 在治疗前和治疗后检测AUD生物标志物。拟议的研究直接涉及以下任务 国家酒精滥用和酒精中毒研究所(NIAAA)的目标是确定药理学 治疗同时发生的AUD和PTSD。这项研究的发现将提供新的 信息和机制洞察力，直接为临床实践提供信息，并加速这一高度 研究不足的地区。