Strengthening Hearts by Addressing DisruptEd Sleep (SHADES) Mechanistic Trial

通过解决睡眠障碍 (SHADES) 机制试验来增强心脏功能

• 批准号: 10657946
• 负责人: Jesse C Stewart
• 金额: $ 68.3万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10657946
• 关键词: Address; Adult; Affect; Aftercare; Age; Attention; Autonomic Dysfunction; Behavior Therapy; Biological; Biological Factors; Biological Markers; C-reactive protein; Cardiovascular Diseases; Caring; Clinical; Clinical Trials; Cognitive Therapy; Conditioned Insomnia; Data; Development; Disparity population; Education; Effectiveness; Enrollment; Ethnic Population; Event; Exhibits; Federally Qualified Health Center; Frequencies; Functional disorder; Future; Gene Expression; Gene Expression Profiling; Glycosylated hemoglobin A; Goals; Health; Healthcare Systems; Heart; Homeostasis; Hygiene; Inflammation; Inflammatory; Insulin Resistance; Interleukin-6; Internet; Intervention; Mediating; Mediator; Metabolic; Minority; Modeling; Modernization; Monitor; Morbidity - disease rate; Myocardial Infarction; National Heart, Lung, and Blood Institute; Outcome; Participant; Pathway interactions; Patients; Peripheral Blood Mononuclear Cell; Persons; Phase; Prevention strategy; Primary Care; RNA; Randomized; Research; Risk; Risk Factors; Science; Site; Sleep; Sleep disturbances; Sleeplessness; Source; Stroke; Symptoms; Telephone; Testing; Update; Woman; active control; aged; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular risk factor; cognitive testing; cohort; collaborative care; cost; design; effective intervention; follow-up; genome-wide; heart rate variability; high risk; improved; improvement on sleep; inflammatory marker; intervention effect; intervention refinement; men; modifiable risk; next generation; patient population; phase III trial; prevent; primary care patient; primary outcome; programs; psychologic; public health relevance; racial population; safety net; screening; secondary outcome; sex; sleep onset; statistics; systemic inflammatory response

7. PROJECT SUMMARY/ABSTRACT Cardiovascular disease (CVD) affects nearly 1 in 2 U.S. adults, is the #1 killer of men and women, burdens disadvantaged groups, and has costs greater than any other condition. While these statistics highlight the importance of CVD prevention, current approaches have only partial effectiveness. This has created a need to identify new CVD prevention targets, their underlying mechanisms, and effective interventions. Insomnia, its candidate mechanisms, and insomnia treatment are strong candidates in this regard. Thirty years of evidence indicates that insomnia is an independent, clinically important, robust, and potentially causal and modifiable risk factor for CVD. In addition, biologically plausible mechanisms that could explain how insomnia promotes the development of CVD have been proposed, with the most strongly supported being systemic inflammation, autonomic dysfunction, and metabolic dysregulation. Our recent RCT of adults with insomnia disorder provides promising preliminary support for one such candidate mechanism. Adults randomized to cognitive-behavioral therapy for insomnia (CBT-I), versus education control, had a reduced risk of high C-reactive protein (CRP), an inflammation marker implicated in the pathophysiology of CVD and predictive of future CVD events, at follow- up. Because insomnia now receives limited attention in settings where CVD prevention occurs (e.g., primary care), there is a large cohort of patients with an unaddressed CVD risk factor (insomnia). This status quo and the strong state of the insomnia-to-CVD science create the current need for a well-powered, mechanistic trial to elucidate biological mechanisms underlying the insomnia-to-CVD relationship and CBT-I’s mechanisms of action, both of which are presently unknown. Therefore, we propose a mechanistic trial of 200 primary care patients (45% minority) with insomnia disorder and CVD risk factors but no clinical CVD. Patients will be randomized to 6 months of the SHADES (Strengthening Hearts by Addressing DisruptEd Sleep) Intervention or Active Control. The SHADES Intervention is our modernized collaborative care intervention consisting of well- established internet, telephonic, and face-to-face CBT-I. Active Control consists of sleep education/hygiene, symptom monitoring, and primary care for insomnia. Our proposal has four aims – Aim 1: determine the effect of the SHADES Intervention on our primary CVD mechanism of high-sensitivity CRP; Aim 2: determine the effect of the SHADES Intervention on our secondary CVD mechanisms of systemic inflammation, autonomic dysfunction, and metabolic dysregulation; Aim 3: examine if 6-month improvements in upstream sleep mechanisms mediate the SHADES Intervention effect on 6-month improvements in downstream CVD mechanisms; ExploratoryAim: explore the effect of the SHADES intervention on proinflammatory gene expression. The proposed trial would generate the critical support for the mechanistic rationale and conceptual framework needed to justify the next-step phase III, multi-site RCT to determine the SHADES Intervention effect on CVD clinical outcomes, endpoints of great

7.项目总结/摘要 心血管疾病（CVD）影响近1/2的美国成年人，是男性和女性的头号杀手，负担 弱势群体，成本高于任何其他条件。虽然这些统计数字突出了 虽然CVD预防的重要性，但目前的方法仅具有部分有效性。这就需要 确定新的心血管疾病预防目标，其基本机制和有效的干预措施。不可避免地，其 候选机制和失眠治疗是这方面的强有力的候选者。三十年的证据 表明失眠是一个独立的，临床上重要的，强大的，潜在的因果关系和修改 CVD的危险因素。此外，生物学上合理的机制，可以解释失眠如何促进 已经提出CVD的发展，最有力的支持是全身性炎症， 自主神经功能紊乱和代谢失调。我们最近对患有失眠症的成年人进行的RCT提供了 有希望为一个这样的候选机制提供初步支持。随机分配至认知-行为 与教育对照相比，失眠治疗（CBT-I）降低了高C反应蛋白（CRP）的风险， 炎症标志物牵连在CVD的病理生理学和未来的CVD事件的预测，在以下 起来因为失眠现在在预防心血管疾病的环境中受到的关注有限（例如，初级 护理），有一个未解决的CVD风险因素（失眠）的患者的大队列。这种现状和 失眠症与心血管疾病之间的科学研究的强大状态，使得目前需要一个有力的、机械的试验 阐明失眠与心血管疾病关系的生物学机制和CBT-I的机制， 这两种行为目前都是未知的。因此，我们建议对200名初级保健人员进行机械试验， 有失眠障碍和心血管疾病危险因素但无临床心血管疾病的患者（45%少数民族）。患者将 随机接受6个月的SHADES（通过解决睡眠中断来加强心脏）干预，或 主动控制。SHADES干预是我们现代化的协作护理干预，包括： 建立了互联网、电话和面对面的CBT-I。主动控制包括睡眠教育/卫生， 症状监测和失眠的初级护理。我们的建议有四个目标-目标1：确定效果 SHADES干预对我们高敏CRP的主要CVD机制的影响;目的2：确定 SHADES干预对我们的继发性CVD机制（全身炎症、自主神经功能 功能障碍和代谢失调;目标3：检查上游睡眠6个月是否有所改善 机制介导SHADES干预对下游CVD 6个月改善的影响 目的：探讨SHADES干预对促炎基因表达的影响 表情拟议的试验将产生对机械原理和概念的关键支持 证明下一步III期多中心RCT确定SHADES干预所需的框架 对CVD临床结局的影响，