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.项目摘要/摘要 心血管疾病(CVD)影响着近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，并且比任何其他疾病都要付出更大的代价。虽然这些统计数据突出了 鉴于预防心血管疾病的重要性，目前的方法只有部分效果。这就产生了一种需要 确定新的心血管疾病预防目标、其基本机制和有效干预措施。失眠，它的 候选机制和失眠治疗是这方面的有力候选者。三十年的证据 表明失眠是一种独立的、临床上重要的、健壮的、潜在的原因和可改变的 心血管疾病的危险因素。此外，生物学上看似合理的机制可以解释失眠如何促进 心血管疾病的发展已经被提出，其中最有力的支持是全身炎症， 自主神经功能障碍和代谢失调。我们最近对失眠障碍成年人进行的随机对照试验提供了 承诺初步支持一个这样的候选机制。成年人随机分为认知行为组 与教育对照组相比，失眠治疗(CBT-I)降低了高C反应蛋白(CRP)的风险， 炎症标记物与心血管疾病的病理生理学有关，并预测未来的心血管事件。 向上。因为失眠现在在发生心血管疾病预防的环境中受到有限的关注(例如，初级 护理)，有一大群患者患有未解决的心血管疾病风险因素(失眠)。这一现状和 失眠到心血管疾病科学的强大状态创造了当前对动力良好的机械性试验的需求 阐明失眠与CVD关系的生物学机制及CBT-I的作用机制 行动，这两个目前都是未知的。因此，我们建议对200名初级保健人员进行机械性试验 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%)。病人将会是 随机进行6个月的阴影(通过解决睡眠障碍来增强心脏)干预或 主动控制。Shades干预是我们现代化的协作式护理干预，由 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，以及对失眠的初级护理。我们的建议有四个目标-目标1：决定效果 对我们的高敏C反应蛋白的主要心血管机制的阴影干预；目标2：确定 阴影干预对我们继发性心血管疾病全身炎症、自主神经机制的影响 功能障碍和代谢失调；目标3：检查上游睡眠是否有6个月的改善 阴影干预对下游CVD改善6个月的作用机制 机制：探索目的：探讨阴影干预对促炎基因的影响 表情。拟议的审判将产生对机械论的理由和概念的关键支持 需要一个框架来证明下一步阶段III，多站点随机对照试验的合理性，以确定阴影干预措施 对心血管疾病临床结局、大血管病变终点的影响