Evaluating Suvorexant for Sleep Disturbance in Opioid Use Disorder

评估 Suvorexant 对阿片类药物使用障碍患者睡眠障碍的影响

• 批准号: 9899225
• 负责人: Kelly E Dunn
• 金额: $ 107.61万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9899225
• 关键词: Acute; Admission activity; Architecture; Benzodiazepines; Biological; Buprenorphine; Clinical; Communities; Data; Devices; Dose; Double-Blind Method; Double-blind trial; Drug Metabolic Detoxication; Early treatment; Electroencephalography; Enrollment; Evaluation; FDA approved; Heroin; Human; Hydrocortisone; Individual; Interdisciplinary Study; Investigation; Laboratory Study; Lead; Measures; Methods; Monitor; Opioid; Patient Self-Report; Patients; Persons; Pharmaceutical Preparations; Phase; Placebos; Polysomnography; Population; Public Health; Randomized; Research; Role; Salivary; Sedation procedure; Severities; Sleep; Sleep disturbances; Sleeplessness; Stress; Subgroup; Supervision; System; Time; Trazodone; Treatment Failure; Treatment outcome; Withdrawal; Withdrawal Symptom; Woman; Wrist; actigraphy; addiction; comparative efficacy; craving; drug craving; efficacy trial; experience; hypocretin; improved; meetings; men; novel; opioid use disorder; opioid withdrawal; primary outcome; prospective; receptor; secondary outcome; sex; side effect

More than 500,000 people sought opioid use disorder (OUD) treatment from state-certified addiction treatment facilities in 2016, and the most frequently accessed form of treatment was supervised opioid withdrawal (also known as detoxification). There has been surprisingly little empirical investigation into mechanisms underlying individual opioid withdrawal symptoms and corresponding best practices for their management. A recent FDA public meeting that included patients with OUD identified sleep disturbance as a primary contributor to OUD treatment failure. The scientific premise of this phased UG3/UH3 proposal is that suvorexant (SUVO; Belsomra®) will improve total sleep time in patients undergoing routine supervised withdrawal from opioids (UG3), and that SUVO will outperform a medication that is commonly administered for that indication (trazodone; UH3). SUVO is a dual orexin receptor antagonist that is FDA-approved for insomnia and is well- suited for this study because it has low abuse potential, improves sleep continuity and architecture with a single dose, has an extremely safe and mild side effect profile, has clear interactions with the opioid system, and has not yet been evaluated in OUD patients. Our interdisciplinary study team includes several experts in OUD and sleep and our proposal provides preliminary evidence of sleep impairment during OUD withdrawal. The UG3 (N=36) and UH3 (N=60) studies will use identical methods and will vary only in the medications examined. OUD patients will be admitted to a residential research unit for 11 days, and will be stabilized on buprenorphine for 3 days before undergoing a 4-day routine taper and a 4-day post-taper period. Study medication will be double-blinded and will begin on Taper day 1. Primary outcomes will be objective sleep measures (unobtrusive EEG via the Sleep ProfilerTM and wrist-worn actigraph) and abuse liability. Secondary measures will include objective, biological, and self-report measures of opioid withdrawal severity, treatment retention, craving, and stress. The UG3 phase will be a dose-finding study of SUVO (10mg, 20mg) compared to placebo. The go-no go decision (i.e. milestone) for UH3 transition will be if either SUVO dose produces a mean increase in total sleep time of at least 10 minutes relative to placebo during the taper. The UH3 phase will be a comparative efficacy trial of trazodone (100mg) vs. the SUVO dose identified in the UG3, to evaluate whether SUVO improves sleep compared to a regularly used sleep aid during opioid withdrawal. After the UH3, results will be collapsed across both studies to examine sleep and withdrawal associations more generally, and men and women will be equally enrolled in both studies to enable sex subgroup comparisons. We hypothesize SUVO will improve total sleep time during withdrawal, will not show evidence of abuse liability, and will be more efficacious than trazodone. Results will advance the treatment of OUD, the understanding of sleep and opioids, and the use of SUVO in clinical populations. These data may also support more prospective evaluations into the use of SUVO as an OUD craving medication.

超过 500,000 人通过国家认证的成瘾治疗寻求阿片类药物使用障碍 (OUD) 治疗 2016 年，最常使用的治疗形式是监督阿片类药物戒断（也 令人惊讶的是，对潜在机制的实证研究却很少。 FDA 最近的一项阿片类药物戒断症状及其相应的最佳管理实践。 包括 OUD 患者在内的公开会议确定睡眠障碍是 OUD 的主要原因 这一阶段性 UG3/UH3 提案的科学前提是 suvorexant (SUVO; Belsomra®）将改善接受常规监督的阿片类药物戒断患者的总睡眠时间 (UG3)，并且 SUVO 将优于通常用于该适应症的药物 （曲唑酮；UH3）是一种双重食欲素受体拮抗剂，经 FDA 批准用于治疗失眠，效果良好。 适合这项研究，因为它具有低滥用潜力，改善睡眠连续性和结构 单剂量，具有极其安全和轻微的副作用，与阿片类药物系统有明显的相互作用， 尚未在 OUD 患者中进行评估。我们的跨学科研究团队包括几位专家。 OUD 和睡眠以及我们的提案提供了 OUD 撤药期间睡眠损害的初步证据。 UG3 (N=36) 和 UH3 (N=60) 研究将使用相同的方法，仅在药物方面有所不同 OUD 患者将被送入住院研究室 11 天，并于 2 日病情稳定。 服用丁丙诺啡 3 天，然后进行 4 天的常规减量期和 4 天的减量后研究。 药物治疗将是双盲的，并在减量第 1 天开始。主要结果是客观睡眠 措施（通过睡眠分析仪和腕戴式活动记录仪进行不显眼的脑电图）和滥用责任。 措施将包括阿片类药物戒断严重程度、治疗的客观、生物学和自我报告措施 UG3 阶段将是 SUVO（10mg、20mg）比较的剂量探索研究。 UH3 过渡的决定（即里程碑）将是任一 SUVO 剂量是否产生 在 UH3 阶段，相对于安慰剂，总睡眠时间平均增加至少 10 分钟。 将是曲唑酮（100mg）与 UG3 中确定的 SUVO 剂量的比较疗效试验，以评估 与阿片类药物戒断期间常规使用的睡眠辅助剂相比，SUVO 是否能改善睡眠？ 这两项研究的结果将被合并，以更广泛地检查睡眠和戒断关联，并且 男性和女性将平等参与这两项研究，以便进行性别亚组比较。 SUVO 将改善戒断期间的总睡眠时间，不会显示滥用倾向的证据，并且将 比曲唑酮更有效，结果将促进 OUD 的治疗、对睡眠和睡眠的认识。 阿片类药物以及 SUVO 在临床人群中的使用也可能支持更多的前瞻性。 使用 SUVO 作为 OUD 渴望药物的评估。