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. 项目概要/摘要 心血管疾病（CVD）影响近二分之一的美国成年人，是男性和女性的第一大杀手，负担 弱势群体的成本比任何其他条件都高，而这些统计数据凸显了这一点。 CVD 预防的重要性，但目前的方法仅具有部分效果，因此有必要进行预防。 确定新的心血管疾病预防目标、其潜在机制以及失眠及其有效干预措施。 候选机制和失眠治疗是这方面三十年的有力证据。 表明失眠是一种独立的、临床上重要的、强有力的、潜在的因果关系和可改变的疾病 此外，生物学上合理的机制可以解释失眠是如何促进的。 CVD 的发展已被提出，最有力的支持是全身性炎症， 我们最近对患有失眠症的成人进行的随机对照试验提供了这一结果。 有望对这样一种候选机制提供初步支持：成人随机分配到认知行为。 与教育控制相比，失眠疗法 (CBT-I) 降低了高 C 反应蛋白 (CRP) 的风险。 炎症标志物与 CVD 的病理生理学有关，并可预测未来的 CVD 事件， 因为失眠现在在预防 CVD 的环境中（例如初级预防）受到的关注有限。 护理），有一大群患者的 CVD 危险因素（失眠）尚未得到解决。 失眠与心血管疾病的科学发展势头强劲，当前需要进行强有力的机械试验 阐明失眠与 CVD 关系的生物学机制以及 CBT-I 的机制 行动，这两者目前都是未知的，因此，我们建议对 200 个初级保健进行机械试验。 患有失眠症和 CVD 危险因素但没有临床 CVD 的患者（45% 少数）。 随机接受 6 个月的 SHADES（通过解决睡眠中断问题强化心脏）干预或 主动控制 SHADES 干预是我们现代化的协作护理干预措施，包括： 已建立的互联网、电话和面对面的 CBT-I 主动控制包括睡眠教育/卫生、 我们的建议有四个目标：目标 1：确定效果。 SHADES 干预对高灵敏度 CRP 主要 CVD 机制的影响 目标 2：确定 SHADES 干预对系统性炎症、自主神经继发性 CVD 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 机制介导 SHADES 干预对下游 CVD 6 个月改善的影响 机制；探索目的：探讨SHADES干预对促炎基因的影响 拟议的试验将为机械原理和概念提供关键支持。 需要框架来证明下一步第三阶段、多站点随机对照试验的合理性，以确定 SHADES 干预措施 对 CVD 临床结果影响很大