Sleep and circadian rhythm phenotypes and mechanisms associated with opioid use disorder treatment outcomes

睡眠和昼夜节律表型以及与阿片类药物使用障碍治疗结果相关的机制

• 批准号: 10776106
• 负责人: Andrew S Huhn
• 金额: $ 118.38万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10776106
• 关键词: Affect; Affective; Animal Model; Apnea; Architecture; Buprenorphine; Central Sleep Apnea; Chronic; Circadian Rhythms; Clinical; Collaborations; Communities; Data; Development; Devices; Disease; Dose; Drug usage; Ecological momentary assessment; Enrollment; Frequencies; Future; Goals; Health; Human; Hydrocortisone; Hypoxia; Individual; Intervention; Intervention Studies; Intervention Trial; Knowledge; Link; Longitudinal Studies; Longitudinal, observational study; Measures; Mediating; Mental Health; Methadone; Methodology; Obstructive Sleep Apnea; Opioid; Outcome; Overdose; Participant; Pathway interactions; Patient Self-Report; Pattern; Persons; Pharmaceutical Preparations; Phase; Phenotype; Polysomnography; Process; Provider; Proxy; Public Health; Recovery; Research; Rest; Risk; Rodent; Severities; Sleep; Sleep Apnea Syndromes; Sleep Architecture; Sleep Stages; Sleep disturbances; Sleeplessness; Stress; Substance Use Disorder; Time; Toxicology; Translational Research; Treatment outcome; Urine; Work; Wrist; actigraphy; addiction; alcohol use disorder; buprenorphine treatment; circadian; clinically relevant; clinically significant; combat; craving; high risk; human model; illicit opioid; improved; improvement on sleep; indexing; longitudinal, prospective study; medication for opioid use disorder; methadone treatment; negative affect; novel; novel therapeutics; opioid epidemic; opioid misuse; opioid use; opioid use disorder; research and development; return to use; saliva sample; secondary analysis

Opioid use disorder (OUD) is a rapidly escalating public health crisis with recent evidence suggesting that close to 70% of drug overdoses involved opioids in the last year. Although many individuals seek treatment for OUD over half return to use despite being maintained on a medication for opioid use disorder (MOUD), underscoring the critical need to identify factors that are associated with OUD reoccurrence. Chronic opioid use has been linked to disturbances in sleep continuity and architecture, increased risk of sleep disordered breathing (SDB), and abnormalities in proxy measures of circadian rhythms. However, less is known about the longitudinal association of sleep/circadian phenotypes with non-medical opioid use among individuals in OUD treatment, and malleable pathways that may account for these associations. Such knowledge is critical to informing translational research and the development of novel interventions aimed at improving sleep, circadian rhythms, and OUD outcomes. The proposed observational, longitudinal study will capitalize on existing collaborations with community-based providers to determine the association of sleep duration, sleep architecture, SDB, and proxy measures of circadian rhythms with illicit opioid use during treatment, and potential pathways (e.g., positive and negative affect) that may influence these relationships. Participants (N = 130) will be enrolled in buprenorphine or methadone treatment and complete a 6-month longitudinal study wherein they will complete overnight, in-lab polysomnography (PSG) sessions three times to assess changes over time in sleep metrics (e.g., total sleep time, sleep architecture, SDB). Before and after PSG sessions, we will collect saliva samples from participants to determine diurnal cortisol patterns. Participants will also be fitted with a wrist-worn actigraphy device to further quantify sleep and circadian rest activity rhythms. At baseline and during the final week of each month of treatment, participants will complete a week-long “data burst” that includes ecological momentary assessments of affect, craving, and stress. Participants will complete urine toxicology screens and self-report on their drug use at the end of each data burst. Specific aims of the study are to (Aim 1) determine the bi-directional association of circadian RARs and diurnal cortisol patterns with non-medical opioid use, (Aim 2) investigate whether sleep duration and architecture over the course of treatment are associated with non-medical opioid use, and (Aim 3) examine (a) associations of MOUD use with SDB, and (b) whether SDB is associated with low positive affect and high negative affect. We will also explore whether clinically significant sleep and circadian rhythm phenotypes are associated with low positive affect, high negative affect, and non-medical opioid use, and whether affective processes mediate the association of sleep/circadian rhythm phenotypes and opioid use. Findings from this project will enhance our understanding of specific sleep and circadian rhythms parameters implicated in OUD, and the relationships among sleep phenotypes, affective processes, and non-medical opioid use. This highly rigorous study will shed light on clinically relevant endpoints for future intervention trials.

阿片类药物使用障碍 (OUD) 是一场迅速升级的公共卫生危机，最近的证据表明，接近 去年，70% 的药物过量涉及阿片类药物，尽管许多人寻求 OUD 治疗。 尽管继续服用阿片类药物使用障碍 (MOUD) 药物，但仍有超过一半的人重新使用药物，强调 迫切需要确定与 OUD 复发相关的因素。 与睡眠连续性和结构紊乱、睡眠呼吸障碍 (SDB) 风险增加有关， 以及昼夜节律代理测量的异常然而，人们对纵向知之甚少。 OUD 治疗个体中睡眠/昼夜节律表型与非医疗阿片类药物使用的关联，以及 可能解释这些关联的可塑途径对于告知转化至关重要。 研究和开发旨在改善睡眠、昼夜节律和 OUD 的新型干预措施 拟议的观察性纵向研究将利用现有的合作。 基于社区的提供者确定睡眠持续时间、睡眠架构、SDB 和代理之间的关联 治疗期间非法阿片类药物使用的昼夜节律测量以及潜在途径（例如，积极和 参与者 (N = 130) 将参加丁丙诺啡 或美沙酮治疗并完成为期 6 个月的纵向研究，他们将在实验室过夜完成 进行三次多导睡眠图 (PSG) 测试，以评估睡眠指标随时间的变化（例如总睡眠时间） 在 PSG 会议之前和之后，我们将从参与者那里收集唾液样本。 以确定昼夜皮质醇模式，参与者还将配备腕戴式体动记录仪以进一步确定。 量化基线和每月最后一周的睡眠和昼夜休息活动节律。 治疗期间，参与者将完成为期一周的“数据爆发”，其中包括生态瞬时评估 参与者将完成尿液毒理学筛查并自我报告其药物。 该研究的具体目标是（目标 1）确定双向。 昼夜 RAR 和昼夜皮质醇模式与非医疗阿片类药物使用的关联，（目标 2）调查 治疗过程中的睡眠持续时间和结构是否与非医用阿片类药物相关 （目标 3）检查 (a) MOUD 使用与 SDB 的关联，以及 (b) SDB 是否与低 我们还将探讨睡眠和昼夜节律是否具有临床意义。 节律表型与低积极情绪、高消极情绪和非医疗阿片类药物使用相关，并且 情感过程是否介导睡眠/昼夜节律表型与阿片类药物使用的关联。 该项目的研究结果将增强我们对特定睡眠和昼夜节律参数的理解 涉及 OUD 以及睡眠表型、情感过程和非医疗阿片类药物之间的关系 这项高度严格的研究将为未来干预试验的临床相关终点提供线索。