The POINTER Neurovascular Ancillary Study

项目摘要 概述：本申请是根据PA-20-272“行政补充， 现有的NIH赠款和合作协议（家长管理支持临床试验可选）"。目的 R 01 AG 066910的行政补充文件，标题为“POINTER神经血管辅助研究”， 确保提供适当的经颅多普勒（TCD）超声设备和相关用品 在所有5个参与地点进行，以促进大脑自动调节和血管舒缩反应性的评估。 参与网站包括维克森林医学院，拉什大学，倡导卫生保健，大学 位于加州的戴维斯分校（UC Davis）和罗得岛。背景/意义、具体目标/假设， 和方法（包括实验程序，样本量，功效估计和分析计划）没有 自原始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，加强质量控制，改进数据协调 跨站点。家长资助摘要：美国通过生活方式保护大脑健康的研究 降低风险的干预（美国POINTER）-神经血管辅助研究（POINTER-NV）将利用 母研究U.S. POINTER的丰富资源和基础设施，一项正在进行的多中心随机 一项临床试验，旨在调查随机分配到两种生活方式干预措施之一是否不同， 格式和强度在2年内改变了2,000名60-79岁老年人的认知轨迹。指针- NV将全面评估自主神经功能、脑自动调节和血管结构， 通过在一个特定的条件下使用互补技术评估主动脉、颈动脉和脑血流动力学， 各种条件。将在基线、第12个月和第24个月评估这些神经血管结局， 5个临床研究中心的500名POINTER参与者。主要目的是评估指针的影响 生活方式干预对脑自动调节和压力反射敏感性的影响我们还将评估干预措施 对主动脉僵硬度、颈动脉僵硬度和脑血管反应性的影响。此外，POINTER-NV将 检查这些神经血管结果是否与认知相关（每6个月评估一次， 父母试验的一部分）和大脑结构和功能（每1-2年评估一次，作为大脑成像的一部分 辅助研究）。行政补充的理由：拟议的行政补充将 抵消与在POINTER-NV使用TCD有关的意外费用。尽管在原文中讨论过 应用程序，在确认现场特定设备的详细信息后，我们注意到， Forest是唯一一个有能力进行脑血管疾病所需TCD监测的临床站点。 自动调节和血管反应性结果。这笔未预见的费用是未预料到的，因此， 已列入原始预算。因此，拟议的补充将使我们能够购买确切的 其他4个地点需要的设备，以充分实现我们的目标。

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.