The Collaboration Linking Opioid Use Disorder and Sleep ("CLOUDS") Study

将阿片类药物使用障碍与睡眠联系起来的合作研究（“CLOUDS”）

• 批准号: 10177515
• 负责人: Declan T. Barry
• 金额: $ 24.79万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-25 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10177515
• 关键词: Address; Affect; Alcohol or Other Drugs use; American; Award; Behavior Therapy; Biological; Biological Assay; Biological Factors; Blood; Brain; Brain Diseases; Cessation of life; Characteristics; Chronic; Chronic Insomnia; Clinical; Cohort Studies; Collaborations; Conflict (Psychology); Cross-Sectional Studies; Data; Discipline of Nursing; Discrimination; Doctor of Philosophy; Employment; Enrollment; Environmental Risk Factor; Evidence based treatment; Exclusion; FDA approved; Family; Fingerprint; Foundations; Functional Magnetic Resonance Imaging; Funding; Future; Gender; Gonadal Steroid Hormones; Health; Home environment; Housing; Human; Hypertension; Impairment; Individual; Interdisciplinary Study; Intervention; Interview; Judgment; Lead; Link; Longitudinal Studies; Measures; Mediating; Medicine; Melatonin; Mental Depression; Mental Health; Mentorship; Moods; Neighborhoods; Neurocognitive; Nurses; Obesity; Opioid; Outcome; Pain; Parents; Participant; Pathway Analysis; Pathway interactions; Patient Self-Report; Patient-Focused Outcomes; Patients; Pattern; Perception; Periodicity; Persons; Pharmaceutical Preparations; Pharmacology; Polysomnography; Prevention; Process; Protocols documentation; Psychiatry; Psychology; Psychosocial Factor; Race; Relapse; Reporting; Research; Research Activity; Research Personnel; Risk Factors; Scientist; Severities; Sleep; Sleep Deprivation; Sleep Disorders; Sleep disturbances; Sleeplessness; Stress; Students; Substance abuse problem; Surveys; System; Testing; Time; Training; Universities; Withdrawal; Work; Wrist; actigraphy; addiction; adverse outcome; awake; bioimaging; circadian; cognitive function; contextual factors; depressive symptoms; executive function; experience; health disparity; illicit opioid; improved; improved outcome; multidisciplinary; negative affect; novel; opioid misuse; opioid treatment program; opioid use; opioid use disorder; overdose death; pain perception; perceived stress; physical conditioning; prescription opioid; primary outcome; programs; psychological outcomes; psychosocial; racial bias; relating to nervous system; response; reward processing; sleep quality; social; social relationships; social stigma; stress symptom

PROJECT SUMMARY Opioid use disorder (OUD) is a chronic and relapsing brain disease that is characterized by loss of control over opioid use. It affects over 2 million Americans and causes one overdose death every 20-minutes. Despite effective evidence-based treatments in the form of both behavioral interventions and FDA-approved medication for addiction treatment (MAT), relapse rates are high and are associated with lack of retention in treatment and a continued cycle of illicit opioid use. Further research is urgently needed to better understand the mechanisms that contribute to ongoing illicit opioid use and poor retention in MAT and identify novel treatments. In response to RFA-HL-19-029 and its call to conduct “mechanistic studies to determine the directionality of sleep and OUD interactions in humans… and to identify new opportunities for prevention and improved therapy,” The Collaboration Linking Opioid Use Disorder and Sleep (“CLOUDS”) Study will investigate patients on MAT to elucidate potential causal mechanisms between sleep deficiency and OUD. We will conduct an observational cohort study of N= 220 patients with OUD who were recently stabilized on MAT at a large opioid treatment program in New Haven, CT. At baseline, all patients will undergo: (1) comprehensive assessments of sleep and circadian rhythmicity (i.e., polysomnography, melatonin onset/offset, wrist actigraphy, and validated sleep and circadian surveys); (2) a task-enriched functional magnetic resonance imaging (fMRI) functional connectivity protocol; (3) blood assays for measures of stress and sex hormones; (4) neuro-clinical status using validated interviews, and surveys; and (5) physical home microenvironment and psychosocial family assessments. Patients will be followed for 6 months for the primary outcome of % days of illicit opioid use. In this context, we will pursue several specific aims. Aim1: Using fMRI network analyses, test whether there are different neurocognitive connectivity patterns between patients with adequate vs. deficient sleep in brain systems involved in addiction (e.g., executive function, reward processing) and assess the extent to which these “neural fingerprints” predict ongoing opioid use. Aim 2: Evaluate the potential biologic, psychiatric, and pharmacologic mechanisms that explain the causal pathway between sleep deficiency and opioid use by analyzing the mediating effect of other selected known OUD risk factors including stress, pain, negative affect, and other substance use. Aim 3: Test the extent to which ecologic factors such as psychosocial, family, and neighborhood contextual factors associated with OUD contribute to sleep deficiency among patients in MAT. An experienced multidisciplinary team of investigators with expertise in Sleep and Circadian Medicine, Biomedical Imaging, Psychiatry, Addiction Medicine, Nursing, and Psychology will conduct this research. This proposal will fulfill a critical step towards identifying novel sleep and circadian-focused treatment approaches that may lead to improved outcomes for patients with OUD.

项目概要 阿片类药物使用障碍 (OUD) 是一种慢性、复发性脑部疾病，其特征是失去对药物的控制 阿片类药物的使用。它影响了超过 200 万美国人，每 20 分钟就导致 1 人服药过量死亡。尽管 以行为干预和 FDA 批准的药物形式提供有效的循证治疗 对于成瘾治疗（MAT），复发率很高，并且与治疗缺乏坚持和 非法阿片类药物的持续循环使用。迫切需要进一步研究以更好地理解其机制 导致持续非法阿片类药物使用和 MAT 保留不良，并确定新的治疗方法。作为回应 RFA-HL-19-029 及其呼吁进行“机制研究以确定睡眠和 OUD 的方向性” 人类之间的相互作用……并确定预防和改进治疗的新机会，” 将阿片类药物使用障碍与睡眠联系起来的合作研究（“CLOUDS”）将调查 MAT 患者 阐明睡眠不足与 OUD 之间的潜在因果机制。我们将进行观察 N = 220 名 OUD 患者的队列研究，这些患者最近在大量阿片类药物治疗中通过 MAT 稳定下来 康涅狄格州纽黑文的计划。在基线时，所有患者都将接受：（1）睡眠和睡眠的综合评估 昼夜节律（即多导睡眠图、褪黑激素开始/结束、手腕活动记录仪以及经过验证的睡眠和 昼夜节律调查）； （2）任务丰富的功能磁共振成像（fMRI）功能连接 协议; (3) 血液检测以测量压力和性激素； (4) 使用经过验证的神经临床状态 访谈和调查； (5) 物理家庭微环境和社会心理家庭评估。 将对患者进行为期 6 个月的随访，以了解非法阿片类药物使用天数的主要结果。在此背景下，我们 将追求几个具体目标。目标1：使用fMRI网络分析，测试是否存在不同 相关大脑系统睡眠充足与睡眠不足的患者之间的神经认知连接模式 成瘾（例如，执行功能、奖励处理）并评估这些“神经元”的程度 指纹”预测持续使用阿片类药物。目标 2：评估潜在的生物学、精神病学和药理学作用 通过分析睡眠不足和阿片类药物使用之间的因果关系机制 其他选定的已知 OUD 风险因素的中介作用，包括压力、疼痛、负面情绪和其他 物质的使用。目标 3：测试社会心理、家庭和邻里等生态因素的影响程度 与 OUD 相关的背景因素导致 MAT 患者睡眠不足。经验丰富的 多学科研究人员团队在睡眠和昼夜节律医学、生物医学成像、 精神病学、成瘾医学、护理学和心理学将进行这项研究。该提案将实现 确定新的睡眠和昼夜节律治疗方法的关键一步，这些方法可能会导致 改善 OUD 患者的预后。

项目成果

"Just fighting for my life to stay alive": a qualitative investigation of barriers and facilitators to community re-entry among people with opioid use disorder and incarceration histories.

• DOI: 10.1186/s13722-023-00377-y
• 发表时间: 2023-03-21
• 期刊: ADDICTION SCIENCE & CLINICAL PRACTICE
• 影响因子: 3.7
• 作者: Hoffman, Kim A.;Thompson, Emma;Gaeta Gazzola, Marina;Oberleitner, Lindsay M. S.;Eller, Anthony;Madden, Lynn M.;Marcus, Ruthanne;Oberleitner, David E.;Beitel, Mark;Barry, Declan T.
• 通讯作者: Barry, Declan T.

Adapting the Health Stigma and Discrimination Framework to understand the association between stigma and sleep deficiency: A systematic review.

• DOI: 10.1016/j.sleh.2022.03.004
• 发表时间: 2022-06
• 期刊: SLEEP HEALTH
• 影响因子: 4.1
• 作者: Nwanaji-Enwerem, Uzoji;Condon, Eileen M.;Conley, Samantha;Wang, Katie;Iheanacho, Theddeus;Redeker, Nancy S.
• 通讯作者: Redeker, Nancy S.

A Pilot Investigation of Nonpharmacological Pain Management Intervention Groups in Methadone Maintenance Treatment.

• DOI: 10.1097/adm.0000000000000877
• 发表时间: 2022-03-01
• 期刊: Journal of addiction medicine
• 影响因子: 5.5
• 作者: DiMeola KA;Haynes J;Barone M;Beitel M;Madden LM;Cutter CJ;Raso A;Gaeta M;Zheng X;Barry DT
• 通讯作者: Barry DT

A qualitative investigation of addiction counselors' perceptions and experiences implementing an open-access model for treating opioid use disorder.

• DOI: 10.1016/j.jsat.2020.108191
• 发表时间: 2021-03
• 期刊: Journal of substance abuse treatment
• 影响因子: 3.9
• 作者: Oberleitner LMS;Madden LM;Muthulingam D;Marcus R;Oberleitner DE;Beitel M;Gaeta M;Tamberelli JF;Barry DT
• 通讯作者: Barry DT

Characterizing the social support and functioning of a low-threshold medication for opioid use disorder treatment cohort at intake.

• DOI: 10.1186/s12888-022-03884-5
• 发表时间: 2022-04-02
• 期刊: BMC psychiatry
• 影响因子: 4.4
• 作者: Oles W;Alexander M;Kumar N;Howell B;O'Connor PG;Madden LM;Barry DT
• 通讯作者: Barry DT