Project 4: Investigation of Clinical, Blood, and Neuroimaging Biomarkers as Predictors of Independent Walking Post-stroke

项目 4：临床、血液和神经影像生物标志物作为中风后独立行走预测因子的研究

• 批准号: 10640171
• 负责人: Denise Peters
• 金额: $ 28.34万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-06 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10640171
• 关键词: Acute; Biological Markers; Blood; Brain; Brain-Derived Neurotrophic Factor; Categories; Clinical; Clinical Trials Design; Clinical assessments; Collection; Data Collection; Discharge Plannings; Dropout; Endothelial Growth Factors; Evaluation; Exclusion Criteria; Funding; Future; Goals; Hour; Impairment; Knowledge; Longitudinal, observational study; Lower Extremity; MRI Scans; Magnetic Resonance Imaging; Measures; Medical center; Methods; Nervous System Trauma; Outcome; Patient-Centered Care; Patients; Persons; Physiological; Procedures; Process; Protocols documentation; Recovery; Rehabilitation therapy; Research; Research Design; Resources; Role; Stroke; Time; Vascular Endothelial Growth Factors; Vermont; Walking; biomarker selection; brain health; cardiovascular health; clinical investigation; gait rehabilitation; improved; improved mobility; inclusion criteria; innovation; neural; neuroimaging; neuroimaging marker; neurotrophic factor; novel; post stroke; predictive modeling; preservation; programs; recruit; rehabilitation strategy; research clinical testing; stroke symptom; success; targeted treatment; telehealth; white matter

Prediction of walking recovery after stroke can inform patient-centered care and support discharge planning. The accuracy of current prediction models is limited, however, due in part to small study designs and narrow predictors assessed. We propose a comprehensive evaluation of a novel combination of biomarkers to improve prediction of walking recovery and guide rehabilitation efforts after stroke. These include acute structural brain network disruption (utilizing MRI); blood biomarker levels (e.g., brain-derived neurotrophic factor and vascular endothelial growth factor); and clinical assessments of strength and mobility. The long-term goal is to develop a competitively funded research program to optimize gait rehabilitation strategies based on neural substrates of walking impairment and recovery after neurologic injury. The overall objectives in this application are to assess study protocol feasibility and investigate relationships between select biomarkers and walking recovery to provide strong justification for a larger study on predictors of independent walking after stroke. The proposed objectives will be pursued through the following specific aims: 1) Assess feasibility of a larger study and develop methods for telehealth data collection; 2) Establish baseline levels of biomarkers (clinical, neuroimaging, blood) and average change over time; and 3) Elucidate relationships between baseline levels of biomarkers and walking gains across time in persons after stroke. A longitudinal, observational study design will be utilized for this study. Thirty-five persons with acute (<3 days) stroke will be recruited from the local medical center. Select inclusion criteria include presence of new lower limb weakness and assistance for walking; select exclusion criteria include cerebellar stroke and contraindications to MRI. Subjects will undergo clinical evaluation within 3 days, 1, 4, 9, 12, and 26 weeks after the initial onset of stroke symptoms. MRI scans will occur 5-12 days and 12 weeks post-stroke, and blood draws 72 hours, 1 week, and 12 weeks post-stroke. To assess feasibility we will examine study processes, recruitment, resources, study management, and scientific assessment. To examine the role of acute clinical, neuroimaging, and physiological measures in predicting walking recovery, we will examine relationships between these measures and walking outcome at 12- weeks post-stroke. This study employs an innovative approach to investigate predictors of walking recovery after stroke. The proposed research is significant because it is expected to provide strong scientific support for future clinical trials designed to target therapies based on predicted functional potential. Ultimately, such knowledge has the potential of enhancing mobility gains and patient independence following stroke.

预测卒中后步行恢复可以告知以患者为中心的护理和支持出院 规划然而，目前的预测模型的准确性是有限的，部分原因是小的研究设计 并评估了狭窄的预测因素。我们提出了一个全面的评价一个新的组合， 生物标志物，以改善步行恢复的预测和指导中风后的康复工作。这些 包括急性结构性脑网络破坏（利用MRI）;血液生物标志物水平（例如，脑源 神经营养因子和血管内皮生长因子）;以及强度和 迁移率长期目标是开发一个有竞争力的资助研究计划，以优化步态 康复策略的基础上的神经基板的步行障碍和恢复后神经 损伤本申请的总体目标是评估研究方案的可行性并研究 选择生物标志物和步行恢复之间的关系，为更大的 脑卒中后独立行走预测因素的研究拟议目标将通过以下方式实现： 以下具体目标：1）评估更大规模研究的可行性，并开发远程医疗数据的方法 2）建立生物标志物（临床、神经成像、血液）的基线水平和平均变化 3）阐明生物标志物的基线水平与步行增益之间的关系， 中风后的时间。本研究将采用纵向、观察性研究设计。三十五 将从当地医疗中心招募急性（<3天）中风患者。选择包含 标准包括存在新的下肢无力和行走辅助;选择排除标准 包括小脑中风和MRI禁忌症。受试者将在3天内接受临床评价 在中风症状首次发作后的第1天、第1、4、9、12和26周。MRI扫描将在5-12天内进行 以及中风后72小时、1周和12周抽血。评估 可行性，我们将审查研究过程，招聘，资源，研究管理，和科学 考核研究急性临床、神经影像学和生理学指标在预测 步行恢复，我们将检查这些措施和步行结果之间的关系，在12- 中风后的几周这项研究采用了一种创新的方法来调查步行恢复的预测因素 中风后这项拟议中的研究意义重大，因为它有望提供强有力的科学支持 用于未来的临床试验，旨在根据预测的功能潜力进行靶向治疗。最终，这样的 知识有可能提高中风后患者的活动能力和独立性。