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

项目总结 阿片类药物使用障碍(OUD)是一种慢性复发性脑部疾病，其特征是对 阿片类药物的使用。它影响了200多万美国人，每20分钟就有一人死于服药过量。尽管 有效的循证治疗，包括行为干预和FDA批准的药物治疗 对于成瘾治疗(MAT)，复发率很高，并与在治疗和治疗中缺乏保留有关 非法使用阿片类药物的持续循环。迫切需要进一步的研究，以更好地了解这些机制 导致持续非法使用阿片类药物和垫子保留率低的问题，并找出新的治疗方法。作为回应 关于RFA-HL-19-029及其要求进行“机制研究以确定睡眠和睡眠的方向性” 人类…中的相互作用并为预防和改进治疗寻找新的机会。 合作将阿片类药物使用障碍与睡眠联系起来的研究将调查垫子上的患者 阐明睡眠不足和OUD之间的潜在原因机制。我们将进行一次观测 最近在一次大剂量阿片类药物治疗中稳定在垫子上的220名OUD患者的队列研究 在康涅狄格州纽黑文的项目。在基线上，所有患者将接受：(1)全面的睡眠和 昼夜节律性(即多导睡眠图、褪黑素开始/抵消、腕部活动图、有效睡眠和 昼夜节律调查)；(2)任务丰富的功能磁共振成像(FMRI)功能连接性 方案；(3)用于压力和性激素测量的血液分析；(4)神经临床状态使用VALIDATED 访谈和调查；(5)物理家庭微环境和心理社会家庭评估。 患者将被跟踪6个月，以了解非法阿片类药物使用%天的主要结果。在这方面，我们 将追求几个具体目标。目的：使用fMRI网络分析，检验是否存在不同 大脑系统睡眠充足与睡眠不足患者之间的神经认知连接模式 成瘾(如执行功能、奖赏处理)，并评估这些“神经”的程度 指纹“预测阿片类药物的持续使用。目标2：评估潜在的生物学、精神病学和药理学 通过分析睡眠不足和阿片类药物使用之间的因果路径来解释机制 其他选定的已知危险因素的中介作用，包括压力、疼痛、负面情绪和其他 物质使用。目标3：测试诸如心理社会、家庭和邻居等生态因素的程度 与OUD相关的背景因素导致MAT患者睡眠不足。一位经验丰富的人 拥有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。这项提议将履行 朝着确定新的睡眠和以昼夜节律为重点的治疗方法迈出关键一步，这些方法可能导致 改善了OUD患者的预后。

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.