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: 10470718
• 负责人: Michael D. Ellis
• 金额: $ 47.41万
• 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/10470718
• 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 上肢卒中恢复期慢性期的临床前康复研究表明 通过减少表达，改善严重受损个体的独立联合控制能力 在基于科学的数据驱动下，异常的肩外展/肘关节屈曲耦合，或屈曲协同作用 干预方法。二十年的定量马达系统研究支撑着 系统地瞄准这一人群中的独立联合控制。解释中风的主要假说是- 相关的独立联合控制的丧失是对对侧皮质网状脊髓束的依赖增加 在受影响的手臂中产生的运动。独立联合控制的部分恢复 临床前研究通过将改善的运动归因于对残留物的优化利用，在逻辑上扩展了这一假设 单侧皮质脊髓束可能起源于缺血半暗带。残留物的解剖回路 单侧皮质脊髓束是唯一可用于产生独立关节控制的神经通路， 或者在功能上，向外伸展，对抗地心引力。通过对重症患者的神经成像研究 慢性中风支持这一假说，它揭示了优化使用半暗带的假设 皮质脊髓束可能在恢复期早期达到，特别是神经可塑性的关键期 有严重初始运动障碍的个人。中风实践指南得出结论，患有严重中风的人 早期运动障碍最需要新颖有效的康复干预措施。因此， 我们的中心假设是，给予渐进式外展负荷疗法，被证明可以诱导持续的 严重慢性卒中患者病情的改善将增强常规的急性和亚急性 通过改善前伸功能和减缓独立关节丧失的发展进行康复 控制力。为了验证这一假设，我们将招募有严重初始运动障碍的个体并对其进行 循序渐进的外展负荷疗法作为常规住院和日间康复的辅助。一个 对照组采用无外展负重的剂量匹配到达练习。学习 参与者将在入院时接受评估，每周一次，直到出院，然后每隔一个月进行一次评估，直到一年。 遵循基线。将在恢复的第一年(AIM)的持续时间内进行组间比较 1)。大约一半的研究参与者将在住院后过渡到日间康复 康复并继续接受学习干预。延长累进诱拐的效果 为亚急性康复加载治疗将通过增加登记的二分变量进行测试 日间康复或不康复(目标2)。药效和剂量数据将为未来提供一个继续前进的信号 管理一项大规模关键的III期临床试验。纵向数据将决定是否累进 外展负荷疗法可减轻独立关节控制力丧失的发展。