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

基本信息

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
项目类别：
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

项目摘要

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）影响了近2个美国成年人中的近1个，是男性和女人的杀手，伯恩斯处境不利的群体，其成本比任何其他条件都要高。这些统计数据强调了预防CVD的重要性，当前的方法仅具有部分效力。这创造了需要确定新的CVD预防目标，其基本机制和有效的干预措施。失眠，它在这方面，候选机制和失眠治疗是强大的候选者。三十年的证据表明失眠是一种独立的，临床上的重要，健壮的，可能是因果关系的 CVD的危险因素。此外，可以解释失眠方式促进的生物学上合理的机制已经提出了CVD的发展，最有力的是系统性炎症，自主神经功能障碍和代谢失调。我们最近患有失眠症的成年人的RCT提供有希望的对一种这样一种候选机制的初步支持。成年人随机分配给认知行为失眠治疗（CBT-I）与教育控制的治疗降低了C反应蛋白（CRP）的风险，在CVD的病理生理和未来CVD事件的预测中实施的炎症标记，以后向上。因为失眠现在在发生CVD预防的情况下受到了有限的关注（例如，主要护理），有大量患有CVD危险因素（失眠）的患者队列。此状态和失眠至CVD科学的强烈状态创造了当前对有力，机械试验的需求阐明失眠与CVD关系的生物机制和CBT-I的机制行动，两者都未知。因此，我们提出了200个初级保健的机械试验患有失眠症和CVD危险因素的患者（45％少数民族），但没有临床CVD。患者会随机分配到6个月的阴影（通过解决睡眠中断来增强心脏的干预）或主动控制。阴影干预是我们现代化的协作护理干预措施，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保健。我们的建议有四个目标 - 目标1：确定效果对我们高敏化CRP的主要CVD机制的阴影干预；目标2：确定阴影干预对我们系统注射，自主神经的次级CVD机制的影响功能障碍和代谢失调； AIM 3：考试如果上游睡眠的6个月改善机制介导了阴影干预效果对下游CVD的6个月改善的效果机制；探索性aim：探索阴影干预对促炎基因的影响表达。拟议的试验将为机械理由和概念的关键支持产生关键支持为了确定阴影干预，需要证明下一步的III阶段III阶段需要合理的框架对CVD临床结果的影响，端点很大