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

项目摘要 阿片类药物使用障碍（OUD）是一种慢性和复发性脑部疾病，其特征是对阿片类药物的控制丧失。 阿片类药物使用它影响了200多万美国人，每20分钟就有一人因过量服用而死亡。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，与缺乏治疗保留有关， 非法使用阿片类药物的持续循环。迫切需要进一步的研究来更好地了解这些机制 这有助于持续的非法阿片类药物使用和MAT中的不良保留，并确定新的治疗方法。响应 RFA-HL-19-029及其呼吁进行“确定睡眠和OUD方向性的机制研究” 人类的相互作用......并确定预防和改进治疗的新机会， 阿片类药物使用障碍与睡眠（“CLOUDS”）合作研究将调查MAT患者， 阐明睡眠不足和OUD之间的潜在因果机制。我们将进行一次观察 在N= 220例最近在大剂量阿片类药物治疗中接受MAT稳定的OUD患者中开展的队列研究 New Haven，CT的照片在基线时，所有患者将经历：（1）睡眠的全面评估， 昼夜节律（即，多导睡眠图、褪黑激素起始/偏移、腕动描记和经验证的睡眠， 昼夜节律调查）;（2）任务丰富的功能磁共振成像（fMRI）功能连接 方案;（3）用于测量压力和性激素的血液分析;（4）使用经验证的 访谈和调查;（5）物理家庭微环境和心理社会家庭评估。 将对患者进行为期6个月的随访，主要结局为非法使用阿片类药物的天数%。在这方面我们 将追求几个具体目标。目的1：利用功能磁共振成像网络分析，检验是否存在不同的 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 指纹”预测持续使用阿片类药物。目的2：评估潜在的生物学、精神病学和药理学 解释睡眠不足和阿片类药物使用之间因果关系的机制，通过分析 其他选定的已知OUD风险因素（包括压力、疼痛、负面影响和其他）的介导作用 物质使用。目标3：测试心理社会、家庭和邻里等生态因素对儿童的影响程度。 与OUD相关的背景因素导致MAT患者的睡眠不足。一位经验丰富 多学科的研究团队，在睡眠和昼夜节律医学，生物医学成像， 精神病学，成瘾医学，护理和心理学将进行这项研究。该提案将实现A 确定新的睡眠和昼夜节律治疗方法的关键一步， 改善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.