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: 10454583
• 负责人: Kelly E Dunn
• 金额: $ 363.22万
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10454583
• 关键词: Acute; Admission activity; Architecture; Benzodiazepines; Biological; Buprenorphine; Clinical; Communities; Data; Devices; Dose; Double-Blind Method; Double-blind trial; Drug Metabolic Detoxication; Drug Prescriptions; 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50万人从国家认证的成瘾治疗中寻求阿片类药物使用障碍（OUD）治疗 2016年，最常见的治疗形式是监督阿片类药物戒断（也 称为解毒）。令人惊讶的是，对潜在机制的实证研究很少 个人阿片类药物戒断症状及其相应的最佳管理做法。最近FDA 一次包括OUD患者的公开会议将睡眠障碍确定为OUD的主要原因 治疗失败。该分阶段UG 3/UH 3提案的科学前提是苏沃雷生（SUVO; Belsomra®）将改善接受常规监督戒断阿片类药物的患者的总睡眠时间 (UG3)，并且SUVO将优于通常用于该适应症的药物 （曲唑酮; UH 3）。SUVO是一种双重食欲素受体拮抗剂，FDA批准用于失眠， 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，具有非常安全和轻微的副作用，与阿片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，我们的建议提供了OUD戒断期间睡眠障碍的初步证据。 UG 3（N=36）和UH 3（N=60）研究将使用相同的方法，仅在药物方面有所不同 考察OUD患者将入住住宅研究单位11天，并将在 丁丙诺啡治疗3天，然后进行4天常规减量和4天减量后阶段。研究 药物治疗将是双盲的，并将在第1天开始开始。主要结果将是客观睡眠 测量（通过Sleep ProfilerTM和腕戴式活动记录仪进行的不显眼的EEG）和滥用倾向。二次 措施将包括阿片类药物戒断严重程度的客观、生物学和自我报告措施， 保留，渴望，和压力。UG 3阶段将是SUVO（10 mg，20 mg）的剂量探索研究， 安慰剂。UH 3过渡的“通过-不通过”决定（即里程碑）将是，如果任一SUVO剂量产生 在逐渐减量期间，相对于安慰剂，总睡眠时间平均增加至少10分钟。UH 3阶段 将是一项比较曲唑酮（100 mg）与UG 3中确定的SUVO剂量的疗效试验，以评估 与阿片类药物戒断期间定期使用的睡眠辅助相比，SUVO是否改善了睡眠。在UH 3之后， 两项研究的结果将被合并，以更广泛地研究睡眠和戒断的联系， 两项研究的男女人数相等，以便进行性别分组比较。我们假设 SUVO将改善戒断期间的总睡眠时间，不会显示滥用责任的证据， 比曲唑酮更有效研究结果将促进对OUD的治疗，对睡眠的理解， 阿片类药物以及SUVO在临床人群中的使用。这些数据也可能支持更多的前瞻性 使用SUVO作为OUD渴望药物的评估。

项目成果

Treatment Disruption and Childcare Responsibility as Risk Factors for Drug and Alcohol Use in Persons in Treatment for Substance Use Disorders During the COVID-19 Crisis.

• DOI: 10.1097/adm.0000000000000813
• 发表时间: 2022-01-01
• 期刊: Journal of addiction medicine
• 影响因子: 5.5
• 作者: Huhn AS;Strain EC;Jardot J;Turner G;Bergeria CL;Nayak S;Dunn KE
• 通讯作者: Dunn KE

Method for Successfully Inducting Individuals Who Use Illicit Fentanyl Onto Buprenorphine/Naloxone.

• DOI: 10.1111/ajad.13069
• 发表时间: 2021-01
• 期刊: The American journal on addictions
• 作者: Antoine D;Huhn AS;Strain EC;Turner G;Jardot J;Hammond AS;Dunn KE
• 通讯作者: Dunn KE

The orexin neurotransmitter system as a target for medication development for opioid use disorder.

食欲素神经递质系统作为阿片类药物使用障碍药物开发的目标。

• DOI: 10.1038/s41386-023-01679-0
• 发表时间: 2024
• 期刊: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
• 作者: Huhn,AS;Dunn,KE
• 通讯作者: Dunn,KE

Protracted renal clearance of fentanyl in persons with opioid use disorder.

• DOI: 10.1016/j.drugalcdep.2020.108147
• 发表时间: 2020-09-01
• 期刊: Drug and alcohol dependence
• 影响因子: 4.2
• 作者: Huhn AS;Hobelmann JG;Oyler GA;Strain EC
• 通讯作者: Strain EC

Latent trajectories of anxiety and depressive symptoms among adults in early treatment for nonmedical opioid use.

• DOI: 10.1016/j.jad.2021.12.004
• 发表时间: 2022-02-15
• 期刊: Journal of affective disorders
• 影响因子: 6.6
• 作者: Ellis JD;Rabinowitz JA;Wells J;Liu F;Finan PH;Stein MD;Ii DGA;Hobelmann GJ;Huhn AS
• 通讯作者: Huhn AS