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，其中一半以上患有残余运动缺陷。运动功能，特别是上肢（UE），是中风后恢复独立性的关键。UE功能在很大程度上取决于运动皮层及其下行纤维的完整性，统称为皮质运动系统（CMS）。迫切需要经验证的临床相关生物标志物来识别生物学上不同的患者亚组，特别是对于经常受影响和功能重要的CMS。它们的缺乏是开发和个性化新恢复疗法的主要障碍，特别是在中风后的早期。运动诱发电位（MEP）对TMS的反应的存在或不存在以及MRI测量的涉及皮质脊髓束（CST）的急性损伤负荷的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，它顺序地结合急性临床信息和MEP状态，是准备多站点验证。我们目前的目标与StrokeNet的目标一致，是在临床、经颅磁刺激（TMS）和MRI测量的第一个大规模、前瞻性、急性数据集中验证缺血性卒中后90天UE运动结局的最具生物学相关性和最佳生物标志物。中心假设是患者具有不同的UE结果，这取决于TMS测量的CMS功能和MRI测量的CST损伤。拟议的研究，“验证中风后恢复结局的早期预后数据，用于未来，更高产量的试验”（VERIFY），将收集来自美国30个研究中心的657名患者的数据，以解决以下具体目标。目标1：外部验证卒中后< 7天获得的CMS完整性的TMS和MRI生物标志物与缺血性卒中后90天的UE运动损伤结果之间的关系。目标二：外部验证卒中后< 7天使用PREP 2预测工具预测缺血性卒中个体患者90天UE功能结局。我们对UE运动结果的多维方法是对以前生物标志物研究的创新性进展，这些研究通常仅限于预测一个或两个领域的结果。我们将在世界卫生组织国际功能、残疾和健康分类中确定的运动性能的三个领域-损伤、功能和使用-全面测量卒中后90天的UE结果。我们的跨学科团队在多中心急性试验、神经生理学、神经影像学以及卒中恢复和康复方面具有专业知识。这些结果预计将产生积极的影响，因为在急性卒中期间用于识别具有不同第90天结果的患者亚组的生物标志物可以帮助卒中恢复试验并为康复决策提供信息。