Progressive Abduction Loading Therapy: A Phase IIb Stroke Rehabilitation Trial with Longitudinal Tracking

渐进性外展负荷疗法：纵向追踪的 IIb 期中风康复试验

• 批准号: 10011891
• 负责人: Michael D. Ellis
• 金额: $ 48.38万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-06 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10011891
• 关键词: Acute; Adjuvant; Admission activity; Affect; Anatomy; Apoptosis; Attenuated; Behavioral; Brain Edema; Caring; Chronic; Chronic Phase; Clinical Trials; Clinical assessments; Corticospinal Tracts; Coupling; Data; Development; Elbow; Enrollment; Equipment; Exercise; Financial compensation; Force of Gravity; Future; Goals; Height; Impairment; Individual; Intervention; Intervention Studies; Investigation; Ischemic Penumbra; Joints; Lesion; Motor; Motor Neurons; Motor Pathways; Movement; Necrosis; Neural Pathways; Neuronal Plasticity; Outpatients; Participant; Pathway interactions; Patients; Phase; Phase III Clinical Trials; Population; Practice Guidelines; Production; Randomized Clinical Trials; Recovery; Rehabilitation therapy; Residual state; Science; Shoulder; Signal Transduction; Standardization; Stroke; Surface; Testing; Translations; Upper Extremity; Work; arm; base; chronic stroke; comparison group; comparison intervention; critical period; dosage; experimental group; haptics; hemiparesis; improved; ischemic injury; motor impairment; neuroimaging; novel; pre-clinical; preclinical study; prevent; recruit; relating to nervous system; response; restoration; stroke recovery; stroke rehabilitation; synergism; systems research; virtual

Project Summary Preclinical rehabilitation studies in the chronic phase of upper extremity stroke recovery have demonstrated the capacity to improve independent joint control in individuals with severe impairment, by reducing the expression of abnormal shoulder abduction/elbow flexion coupling, or flexion synergy, following a science-based data-driven intervention approach. Two decades of quantitative motor systems research underpins the concept of systematically targeting independent joint control in this population. The leading hypothesis explaining stroke- related loss of independent joint control is the increased reliance on contralesional corticoreticulospinal tract for the production of movement in the affected arm. Partial restoration of independent joint control demonstrated in preclinical studies logically extend this hypothesis by attributing improved movement to optimized use of residual ipsilesional corticospinal tract likely originating in the ischemic penumbra. The anatomical circuit of residual ipsilesional corticospinal tract is the only neural pathway available for the production of independent joint control, or in functional terms, outward reaching against gravity. With neuroimaging studies of individuals with severe chronic stroke supporting this hypothesis, it brings to light the supposition that optimized use of penumbral corticospinal tract may be achieved early in recovery, specifically the critical period of neural plasticity, in individuals with severe initial motor impairment. Stroke practice guidelines conclude that individuals with severe initial motor impairment are in the greatest need of novel and efficacious rehabilitation interventions. Therefore, our central hypothesis is that administration of progressive abduction loading therapy, shown to elicit sustained improvements in individuals with severe chronic stroke, will augment conventional acute and subacute rehabilitation through improved reaching function and attenuated development of loss of independent joint control. To test this hypothesis, we will recruit individuals with severe initial motor impairment and administer progressive abduction loading therapy as adjuvant to conventional in-patient and day-rehabilitation. A comparison group of dosage-matched reaching practice without abduction loading will be utilized. Study participants will be evaluated at admission, weekly until discharge, and then every other month until 1 year following baseline. Between group comparisons will be made over the duration of the first year of recovery (Aim 1). Approximately half of the study participants will transition to day-rehabilitation following in-patient rehabilitation and continue to receive the study interventions. The effect of extending progressive abduction loading therapy into subacute recovery will be tested with the addition of a dichotomous variable of enrollment in day-rehabilitation or not (Aim 2). Efficacy and dosage data will provide a go-no-go signal for the future administration of a large-scale pivotal phase III clinical trial. Longitudinal data will determine if progressive abduction loading therapy attenuates the development of loss of independent joint control.

项目摘要 上肢中风恢复慢性阶段的临床前康复研究表明 通过降低表达方式来改善严重损害的个体独立关节控制的能力 根据科学基于数据驱动 干预方法。二十年的定量运动系统研究基于 系统地针对该人群中的独立关节控制。主要的假设解释了中风 - 独立关节控制的相关损失是增加对对侧皮质肺导脊髓段的依赖性 受影响的手臂运动的产生。部分恢复独立关节控制 临床前研究从逻辑上扩展了这一假设，通过将改进的运动归因于优化的剩余使用 ipsiles性皮质脊髓束可能起源于缺血性半阴茎。残留的解剖回路 ipsilesipal corticolostinal束是唯一可用于生产独立关节控制的神经途径， 或用功能性的角度，向外伸出重力。对患有严重的个体的神经影像学研究 支持这一假设的慢性中风，它可以阐明优化使用半体的假设 皮质脊髓道可以在恢复早期，特别是神经可塑性的关键时期，在 严重初始运动障碍的人。中风实践指南得出的结论是，患有严重的人 最初的运动障碍最需要新颖有效的康复干预措施。所以， 我们的核心假设是，进行性外展负荷疗法的给药，证明是持续的 严重慢性中风的个体的改善，会增加常规急性和亚急性 通过改善达到功能的康复和衰减独立关节损失的发展 控制。为了检验这一假设，我们将招募严重初始运动障碍的人并进行管理 作为常规住院和日间治疗的辅助术进行了进行性外展疗法。一个 将利用剂量匹配的剂量匹配实践的比较组，而无需外展负荷。学习 参与者将在入场时进行评估，每周直到出院，然后每隔一个月直到1年 遵循基线。在小组比较之间将在恢复第一年的时间内进行（AIM 1）。大约一半的研究参与者将过渡到住院后的日间纠正 康复并继续接受研究干预措施。扩展渐进绑架的效果 通过添加二分法变量，将测试将疗法加载到亚急性恢复中 是否在日间理通中（AIM 2）。功效和剂量数据将为未来提供无关的信号 给予大规模关键阶段III临床试验。纵向数据将确定是否进行 外展负荷疗法减弱了独立关节控制丧失的发展。