6-week trial of oxytocin for co-occurring cocaine and opioid use disorders

催产素治疗同时发生的可卡因和阿片类药物使用障碍的 6 周试验

• 批准号: 9858240
• 负责人: Christopher Stauffer
• 金额: --
• 依托单位: PORTLAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9858240
• 关键词: Address; Adherence; Afghanistan; Animal Model; Attenuated; Award; Behavior; Biological Markers; Biometry; Caring; Client; Clinic; Clinical; Clinical Research; Clinical Trials; Cocaine; Cocaine Users; Controlled Clinical Trials; Data; Development; Diagnosis; Disadvantaged; Disease; Double-Blind Method; Dropout; Effectiveness; Equipment and supply inventories; Foundations; General Population; Health Personnel; Heroin; Human; Hydrocortisone; Intervention; Iraq; Knowledge; Life; Measurable; Measurement; Measures; Mental Health; Methods; Military Personnel; Neuropeptides; Opioid replacement therapy; Outcome Measure; Oxytocin; Patient Self-Report; Patients; Personality; Pharmaceutical Preparations; Phase II Clinical Trials; Pilot Projects; Placebos; Play; Population; Predisposition; Prevalence; Process; Property; Psychology; Psychophysiology; Psychosocial Factor; Psychosocial Influences; Randomized; Randomized Clinical Trials; Recovery; Regulation; Relapse; Research; Research Personnel; Risk; Role; Running; Salivary; Sampling; Self Administration; Severities; Social Environment; Social support; Stress; Stress Tests; Structure; Substance Use Disorder; Sum; Support System; Symptoms; Therapeutic; Time; Training; Trier Social Stress Test; United States National Institutes of Health; Urine; Variant; Veterans; Withdrawal; Work; addiction; arm; avoidance behavior; base; benzoylecgonine; cocaine use; comorbidity; craving; effectiveness evaluation; evidence base; experience; heroin use; hypothalamic-pituitary-adrenal axis; improved; innovation; intimate behavior; methadone treatment; military veteran; mortality; multidisciplinary; opioid treatment program; opioid use disorder; post-traumatic symptoms; pre-clinical; prevent; primary outcome; programs; psychopharmacologic; psychosocial; relating to nervous system; response; social; social engagement; social neuroscience; social stigma; social stress; stress management; stress reactivity; substance use; successful intervention; treatment program; treatment response; week trial

High rates of substance use disorders in Veterans compared to the general population are heavily influenced by psychosocial factors – such as difficulty reintegrating into civilian life due to avoidance of vital support systems – leading to disproportionately elevated unmet addiction treatment needs. Those using both cocaine and heroin have mortality rates 14.3 times higher than the general population. 30-60% of patients receiving methadone maintenance therapy (MMT) for opioid use disorder actively use cocaine. There are currently no approved psychopharmacological treatments for cocaine use disorder, and drop-out rates from MMT programs and vital psychosocial treatments are as high as 80% for cocaine users. What’s more, cocaine use, compared to other drugs, is particularly driven by social stress, and cocaine is associated with hyperreactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Preclinical and pilot clinical findings suggest that administration of oxytocin, a mammalian neuropeptide, may have a multitude of direct anti-addiction effects, improve engagement in psychosocial treatments, and attenuate hyperreactivity of the HPA axis in patients with cocaine use disorder. This is a double-blinded, placebo-controlled, clinical trial of fifty Veterans with active cocaine use disorder, also receiving MMT in an opioid treatment program, randomized to receive either oxytocin 40 IU or placebo intranasally twice daily for six weeks. The primary outcome measure will be oxytocin’s effectiveness at reducing cocaine use as measured by quantitative levels of the cocaine metabolite, benzoylecgonine, in weekly urine samples. Potential mechanisms of treatment response will be evaluated by measuring oxytocin’s effectiveness at a) improving therapeutic alliance with treatment providers (Working Alliance Inventory, client and therapist forms) and attendance in existing clinic-run treatment components and b) attenuating social stress-reactivity by measuring self- reported cocaine craving, psychophysiological stress measures, and salivary cortisol in response to a Trier Social Stress Test. In sum, discrepancies between Veterans and civilians in addiction prevalence, severity, and successful intervention are largely driven by higher rates of social avoidance and posttraumatic stress symptoms among Veterans. This study will uniquely combine psychopharmacological and evidence-based psychosocial interventions targeted at reducing cocaine use, improving treatment engagement, and preventing stress-related cocaine use among Veterans with co- occurring cocaine and opioid use disorders receiving MMT.

与普通人群相比，退伍军人的物质使用障碍发生率较高 受到社会心理因素的严重影响，例如难以重新融入社会 由于避开重要支持系统而损害平民生命——导致不成比例的 未满足的成瘾治疗需求增加。同时吸食可卡因和海洛因的人 死亡率比一般人群高14.3倍。 30-60% 的患者接受 用于阿片类药物使用障碍的美沙酮维持治疗（MMT）积极使用可卡因。 目前尚无批准用于可卡因使用的精神药理学治疗方法 MMT 项目和重要心理社会治疗的退出率 可卡因吸食者的比例高达 80%。更重要的是，与其他药物相比，可卡因的使用 特别是受到社会压力的驱动，可卡因与大脑的过度反应有关 下丘脑-垂体-肾上腺（HPA）轴。临床前和试点临床研究结果表明 催产素（一种哺乳动物神经肽）的施用可能具有多种作用 直接的抗成瘾作用，提高心理社会治疗的参与度，以及 减轻可卡因使用障碍患者 HPA 轴的高反应性。这是一个 对 50 名经常使用可卡因的退伍军人进行的双盲、安慰剂对照临床试验 疾病，也在阿片类药物治疗计划中接受 MMT，随机接受 催产素 40 IU 或安慰剂，每天两次鼻内注射，持续六周。初级 结果衡量标准是催产素在减少可卡因使用方面的有效性，具体如下： 每周尿样中可卡因代谢物苯甲酰爱康宁的定量水平。 将通过测量催产素来评估治疗反应的潜在机制 a) 改善与治疗提供者的治疗联盟的有效性（工作 联盟清单、客户和治疗师表格）以及现有诊所运营的出勤情况 治疗成分和b）通过测量自我减轻社会压力反应性 报告的可卡因渴望、心理生理压力测量和唾液皮质醇 对特里尔社会压力测试的反应。总而言之，退伍军人和退伍军人之间的差异 平民成瘾的患病率、严重程度和成功的干预很大程度上是由 退伍军人中社交回避和创伤后应激症状的发生率较高。 这项研究将独特地结合精神药理学和循证医学 旨在减少可卡因使用、改善治疗的社会心理干预措施 参与，并防止退伍军人中与压力有关的可卡因使用 接受 MMT 治疗后出现可卡因和阿片类药物使用障碍。