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Blood Biomarkers as Surrogate Endpoints of Treatment Responses to Aerobic Exercise and/or Cognitive Training in Amnestic Mild Cognitive Impairment

血液生物标志物作为遗忘性轻度认知障碍有氧运动和/或认知训练治疗反应的替代终点

基本信息

批准号：
10572816
负责人：
Danni Li
金额：
$ 23.57万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2023-05-31
项目状态：
已结题

项目摘要

Project Summary The objective of the parent R01 is to investigate blood neuropathological and neurotrophic biomarkers as surrogate endpoints for treatment responses to 3 interventions in older adults with amnestic mild cognitive impairment (aMCI, a prodromal stage of AD): aerobic exercise; cognitive training; and combined aerobic exercise and cognitive training (ACT). The first goal of this supplement is to provide financial sources, so the parent R01 has sufficient funding to take advantage of the revised enrollment timeline of the ACT Trial to preserve the parent R01's overall impact within the original scope of the award. The parent R01 is built on the ACT trial, a multi-site Phase II RCT that examines the synergistic effects of a 6-month ACT intervention on cognition and MRI biomarkers (n=128). The ACT Trial paused its enrollment in March 2020 due to the Covid- 19 shutdown of research at the University of Rochester (UR) and the University of Minnesota (UMN) sites. We could not enroll the participants in the ACT Trial in 2020. The ACT Trial has re-configured its study timeline to account for the lost recruitment period due to enrollment pause. It also added a 3rd study site at the Arizona State University (ASU) to recruit. It extended its recruitment period to the end of August 31, 2022, with a hard- stop recruitment ending date of September 30, 2022. All data collections will end on Feb-March 2024. However, the parent R01 will end on May 31, 2022, and will not have sufficient funding left to take advantage of the revised enrollment timeline of the ACT Trial. Hence, we need this administrative supplement to extend the recruitment and data collection period to maximize sample size and accomplish the scope of the parent R01. The second goal of this supplement is to increase the parent R01's impact by investigating blood neuroinflammation biomarkers as surrogate endpoints for treatment responses to 3 interventions in aMCI. Neuroinflammation modulates disease progression of AD. In addition, recent evidence suggests that exercise modulate neuroinflammation through plasma clusterin. Furthermore, blood glial fibrillary acidic protein (GFAP) has emerged as a biomarker for neuroinflammation. This evidence suggests that blood neuroinflammation biomarkers such as plasma GFAP and clusterin could serve as surrogate endpoints for intervention exercise- related treatment responses. This addition is within the scope of the parent R01. The specific aims for the first goal are: (1). Continue enrolling participants following the ACT Trial scheduled to August 31, 2022, or September 30, 2022, if not meeting the enrollment goal by August 31, 2022; (2). Complete all blood collections by March 2024. The specific aims for the second goal are: (3). Determine the effects of interventions on blood neuroinflammation biomarkers in aMCI; (4). Evaluate blood neuroinflammation biomarkers as surrogate endpoints for predicting cognitive responses to interventions in aMCI.

项目摘要母体R 01的目的是研究血液神经病理学和神经营养学生物标志物，遗忘型轻度认知功能障碍老年人对3种干预措施的治疗反应的替代终点损害（aMCI，AD的前驱阶段）：有氧运动;认知训练;以及有氧运动和认知训练的组合。认知训练（ACT）。这种补充的第一个目标是提供财政来源，因此，母公司R 01有足够的资金来利用ACT试验修订后的入组时间轴，在原合同范围内保留母公司R 01的总体影响。父R 01构建在 ACT试验，一项多中心II期RCT，检查6个月ACT干预对认知和MRI生物标志物（n=128）。ACT试验于2020年3月因新型冠状病毒肺炎暂停入组。 19关闭了罗切斯特大学（UR）和明尼苏达大学（UMN）的研究基地。我们无法在2020年招募ACT试验的参与者。ACT试验已重新配置其研究时间轴，考虑到由于招募暂停而损失的招募期。它还在亚利桑那州增加了第三个研究中心州立大学（ASU）招聘。它将招募期延长至2022年8月31日，并以硬- 停止招募截止日期为2022年9月30日。所有数据收集将于2024年2月至3月结束。然而，母公司R 01将于2022年5月31日结束，并且将没有足够的资金来利用 ACT试验修订后的入组时间轴。因此，我们需要这项行政补充，招募和数据收集期，以最大限度地扩大样本量并完成母公司的范围 R01。该补充剂的第二个目标是通过研究血液来增加母体R 01的影响。神经炎症生物标志物作为aMCI中对3种干预措施的治疗应答的替代终点。神经炎症调节AD的疾病进展。此外，最近的证据表明，通过血浆聚集素调节神经炎症。此外，血胶质细胞酸性蛋白（GFAP）已经成为神经炎症的生物标志物。这一证据表明，血液神经炎症生物标志物如血浆GFAP和clusterin可以作为干预运动的替代终点- 相关的治疗反应。此添加属于父R 01的范围内。第一个目标的具体目标目标是：（1）.在计划于2022年8月31日进行的ACT试验后继续招募受试者，或 2022年9月30日，如果到2022年8月31日仍未达到入组目标;（2）。完成所有血液采集到2024年3月。第二个目标的具体目标是：（3）。确定干预措施对血液的影响 aMCI中的神经炎症生物标志物;（4）.评价血液神经炎症生物标志物作为替代物终点预测aMCI干预的认知反应。