The POINTER Neurovascular Ancillary Study

项目总结 概述：此申请是根据PA-20-272“行政补充文件”提交的 现有的NIH补助金和合作协议(家长管理补充临床试验可选)“。目的 本行政副刊R01 AG066910题为《指针式神经血管辅助研究》，其内容如下 确保有合适的经颅多普勒(TCD)超声设备和相关用品 在所有5个参与地点，以便于评估脑自动调节和血管运动反应性。 参与网站包括拉什大学维克森林医学院、大学倡导医疗保健 加州大学戴维斯分校(UC Davis)和罗德岛。背景/意义、具体目标/假设、 和方法(包括实验程序、样本量、功率估计和分析计划)没有 自最初的申请以来发生了变化(即没有提出新的科学)。本补编将 确保可靠和一致的数据收集、增强的质量控制和改进的数据协调 跨站点。Parent Grant综述：美国通过生活方式保护大脑健康的研究 干预以降低风险(美国指针)-神经血管辅助研究(指针-NV)将利用 丰富的资源和基础设施的母公司研究美国指针，正在进行的多中心随机 一项临床试验，旨在调查随机选择两种不同的生活方式干预方式之一 在2,000名60-79岁的老年人中，形式和强度在两年内改变了认知轨迹。指针- NV将全面评估自主神经功能、脑自动调节和血管结构，并 使用辅助技术评估主动脉、颈动脉和脑血流动力学的功能 条件多种多样。这些神经血管结果将在基线、12个月和24个月进行评估 5个临床站点的500名指针参与者。主要目的是评估指示器的影响 生活方式干预对脑自动调节和压力感受器敏感性的影响。我们还将评估干预措施 对主动脉僵硬、颈动脉僵硬和脑血管舒缩反应性的影响。此外，指针-NV将 检查这些神经血管结果是否与认知有关(每6个月评估一次 父母试验的一部分)和大脑结构和功能(作为大脑成像的一部分，每1-2年评估一次 辅助研究)。行政补编的理由：拟议的行政补编将 抵消与在POINTER-NV使用TCD相关的意外成本。尽管在原文中讨论了 在确认了现场可用的具体设备的细节后，我们注意到Wake 森林是唯一有能力进行脑部所需的TCD监测的临床站点 自动调节和血管运动反应性结果。这一不可预见的成本是意想不到的，因此 包括在最初的赠款预算中。因此，建议的补充将使我们能够购买完全相同的 其他4个地点需要的设备，以充分满足我们的目标。

PROJECT SUMMARY Overview: This application is being submitted in response to PA-20-272 "Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)”. The purpose of this administrative supplement to R01 AG066910, entitled “The POINTER Neurovascular Ancillary Study” is to ensure that appropriate transcranial Doppler (TCD) ultrasound equipment and related supplies are available at all 5 participating sites in order to facilitate assessment of cerebral autoregulation and vasomotor reactivity. Participating sites include Wake Forest School of Medicine, Rush University, Advocate Health Care, University of California at Davis (UC Davis), and Rhode Island. The background/significance, specific aims/hypotheses, and approach (including experimental procedures, sample size, power estimates, and analytic plan) have not changed since the original application (i.e., no new science is being proposed). The present supplement will ensure robust and consistent data collection, enhanced quality control, and improved data harmonization across sites. Summary of Parent Grant: The U.S. study to PrOtect brain health through lifestyle INTErvention to Reduce risk (U.S. POINTER) – Neurovascular Ancillary Study (POINTER-NV) will leverage the rich resources and infrastructure of the parent study U.S. POINTER, an ongoing multi-center randomized clinical trial designed to investigate whether randomization to one of two lifestyle interventions that differ in format and intensity alters cognitive trajectory over 2 years in 2,000 older adults aged 60-79 years. POINTER- NV will comprehensively assess autonomic function, cerebral autoregulation, and vascular structure and function by evaluating aortic, carotid, and cerebral hemodynamics using complementary techniques under a variety of conditions. These neurovascular outcomes will be assessed at baseline, Month 12, and Month 24 in 500 POINTER participants across 5 clinical sites. The primary aim is to assess the effects of the POINTER lifestyle intervention on cerebral autoregulation and baroreflex sensitivity. We will also assess intervention effects on aortic stiffness, carotid stiffness, and cerebral vasomotor reactivity. In addition, POINTER-NV will examine whether these neurovascular outcomes are associated with cognition (assessed every 6 months as part of the parent trial) and brain structure and function (assessed every 1-2 years as part of a Brain Imaging ancillary study). Rationale for Administrative Supplement: The proposed administrative supplement will offset unforeseen costs related to the use of TCD in POINTER-NV. Although discussed in the original application, after confirming details of site-specific equipment available, it has come to our attention that Wake Forest is the only clinical site that has the ability to conduct the type of TCD monitoring needed for the cerebral autoregulation and vasomotor reactivity outcomes. This unforeseen cost was unanticipated and therefore not included in the original grant budget. Thus, the proposed supplement will allow us to purchase the exact equipment needed at the other 4 sites to fully address our aims.