Validation of Early Prognostic Data for Recovery Outcomes after Stroke for Future, Higher Yield Trials (VERIFY)

验证中风后恢复结果的早期预后数据，以进行未来更高产量的试验（VERIFY）

• 批准号: 10474279
• 负责人: Steven C. Cramer
• 金额: $ 263.13万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10474279
• 关键词: Action Research; Acute; Address; Affect; Biological Markers; Caring; Categories; Cerebral hemisphere hemorrhage; Classification; Clinical; Clinical Treatment; Corticospinal Tracts; Data; Data Set; Decision Making; Enrollment; Fiber; Future; Health; Hospitalization; Impairment; Individual; Injury; International; Ischemic Stroke; Lesion; Location; Magnetic Resonance Imaging; Measures; Motor; Motor Activity; Motor Cortex; Motor Evoked Potentials; Outcome; Patient Selection; Patient-Focused Outcomes; Patients; Performance; Physiological; Process; Randomized Controlled Trials; Recommendation; Recovery; Rehabilitation therapy; Reperfusion Therapy; Reporting; Research; Residual state; Rogaine; Sampling; Severities; Site; Stroke; System; Testing; Transcranial magnetic stimulation; Triage; Upper Extremity; Validation; World Health Organization; acute stroke; arm; base; clinical practice; clinically relevant; cohort; cost; disability; functional outcomes; improved; individual patient; individualized medicine; innovation; international health organization; magnetic resonance imaging biomarker; motor deficit; motor impairment; motor recovery; neuroimaging; neurophysiology; outcome prediction; patient stratification; patient subsets; post stroke; prevent; primary outcome; prognostic; prospective; response; stroke recovery; stroke rehabilitation; stroke survivor; tool; treatment effect

Currently, 7 million US stroke survivors have significant disability, more than half with residual motor deficits. Motor function, particularly of the upper extremity (UE), is critical for regaining independence after stroke. UE function largely depends on integrity of motor cortex and its descending fibers, collectively termed the corticomotor system (CMS). Validated, clinically relevant biomarkers that identify biologically distinct patient subgroups are critically needed, particularly for the often affected and functionally important CMS. Their absence is a major obstacle to developing and personalizing new recovery therapies, especially in the early days post- stroke. Presence or absence of motor evoked potential (MEP) responses to TMS and extent of MRI-measured acute lesion load involving corticospinal tract (CST) are ready for formal validation. Also, the Predict Recovery Potential (PREP)-2 prediction tool, which sequentially combines acute clinical information and MEP status, is primed for multi-site validation. Our current objective, well-aligned with StrokeNet’s, is to validate the most biologically relevant and primed biomarkers of 90-day UE motor outcomes after ischemic stroke in the first large- scale, prospective, acute dataset of clinical, transcranial magnetic stimulation (TMS), and MRI measures. The central hypothesis is that patients have different UE outcomes depending on CMS function measured with TMS, and on CST injury measured with MRI. The proposed study, “Validation of Early Prognostic Data for Recovery Outcomes after Stroke for Future, Higher Yield Trials” (VERIFY), will collect data from 657 patients at 30 US sites to address the following specific aims. Aim 1: To externally validate the relationships that TMS and MRI biomarkers of CMS integrity acquired < 7 days after stroke have with UE motor impairment outcome at 90 days after ischemic stroke. Aim 2: To externally validate the PREP2 prediction tool used < 7 days after stroke to predict 90-day UE functional outcome for individual patients with ischemic stroke. Our multi-dimensional approach to UE motor outcomes is an innovative advance on previous biomarker studies, which were typically limited to predicting outcomes in one or two domains. We will comprehensively measure UE outcomes 90 days post-stroke in three domains of motor performance —impairment, function, and use — identified by the World Health Organization International Classification of Functioning, Disability and Health. Our cross-disciplinary team has established expertise in multicenter acute trials, neurophysiology, neuroimaging, and stroke recovery and rehabilitation. The results are expected to have a positive impact because biomarkers used in the acute stroke period to identify patient subgroups with distinct day-90 outcomes can aid stroke recovery trials and inform rehabilitation decision-making.

目前，美国有 700 万中风幸存者患有严重残疾，其中一半以上存在残余运动缺陷。运动功能，尤其是上肢 (UE)，对于中风后恢复独立至关重要，很大程度上取决于运动皮层及其完整性。下行纤维，统称为皮质运动系统（CMS），迫切需要能够识别生物学上不同的患者亚组的经过验证的临床相关生物标志物，特别是对于经常受影响且功能重要的 CMS 来说，它们的缺乏是一个主要障碍。开发和个性化新的恢复疗法，特别是在中风后的早期，TMS 是否存在运动诱发电位 (MEP) 反应以及 MRI 测量的涉及皮质脊髓束 (CST) 的急性病变负荷程度，已准备好进行正式验证。此外，预测恢复潜力 (PREP)-2 预测工具依次结合了急性临床信息和 MEP 状态，为多站点验证做好了准备，这与 StrokeNet 的目标非常一致。在第一个大规模、前瞻性、急性临床刺激、经颅磁刺激 (TMS) 和 MRI 测量数据集中验证缺血性中风后 90 天 UE 运动结果的最具生物学相关性和启动性的生物标志物。根据 TMS 测量的 CMS 功能和 MRI 测量的 CST 损伤，患者有不同的 UE 结果。拟议的研究“中风后恢复结果的早期预后数据的验证，用于未来的更高产量试验”。 (VERIFY) 将从美国 30 个地点的 657 名患者收集数据，以实现以下具体目标 1：从外部验证中风后 7 天内获得的 CMS 完整性的 TMS 和 MRI 生物标志物与 UE 运动损伤结果之间的关系。缺血性中风后 90 天 目标 2：从外部验证中风后 7 天以内使用的 PREP2 预测工具，以预测缺血性中风个体患者的 90 天 UE 功能结果。我们对 UE 运动结果的多维方法是对先前生物标志物研究的创新进步，之前的生物标志物研究通常仅限于预测一两个领域的结果，我们将在运动性能损伤的三个领域全面测量中风后 90 天的 UE 结果。 、功能和用途——由世界卫生组织国际功能、残疾和健康分类确定。我们的跨学科团队已在多中心急性试验、神经生理学、神经影像学和中风恢复和康复方面建立了专业知识。积极的因为在急性中风期间使用生物标志物来识别具有不同第 90 天结果的患者亚组可以帮助中风恢复试验并为康复决策提供信息。