ROPINIROLE IN STROKE RECOVERY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。中风是导致成人残疾的主要原因。运动障碍是中风后最常见的损伤之一，也是中风相关残疾的主要原因。中风后，大脑结构、化学和功能发生了许多变化。针对这些变化的医学治疗可能是减少中风后残疾的治疗途径。局灶性中风后早期，脑内儿茶酚胺水平普遍降低。许多研究表明，中风后早期增加大脑α - 1-去甲肾上腺素能活性可以改善运动预后。中风后，大脑中包括多巴胺在内的儿茶酚胺含量普遍会增加。多巴胺通常在运动、边缘和认知活动的调节中起重要作用。这表明多巴胺的减少可能在中风后运动缺陷中起作用，而多巴胺的增加则在运动恢复中起作用。左旋多巴和安非他明的人体试验发现，与治疗相关的运动状态显著改善。本研究旨在确定多巴胺激动剂罗匹尼罗对脑卒中患者是否安全，以及当与物理治疗联合使用时，罗匹尼罗是否与改善步态和运动状态有关。研究目的为了验证随机接受罗匹尼罗+物理治疗的患者与随机接受安慰剂+物理治疗的患者相比，在参与研究的12周内步态速度会有所改善的假设。子分析将探讨(a)治疗是否改善最终步态速度，即在研究开始后12周，而不考虑时间进程；(b)治疗是否改善研究开始后9周的步态速度，即在系统中仍存在罗匹尼罗的情况下。2. 为了验证罗匹尼罗将在研究开始后12周改善三个次要终点的假设：无显著残疾的患者比例（Barthel指数>/= 95）；整体运动状态，用手臂/腿部FM评分测量；整体身体功能，定义为中风影响量表-16 （SIS-16）的得分。一个子假设是，这三个次要终点中的每一个都将在研究开始后9周显示与罗匹尼罗相关的获益，即当罗匹尼罗仍然存在于系统中时。步态耐力和HAM-D量表评分也将跟进。3. 评价罗匹尼罗在脑卒中恢复期患者中的安全性。4. 确定哪些人口统计学、临床和放射学特征可以预测改善的步态速度，哪些特征可以预测治疗相关的益处。研究终点主要功效：步态速度2。次要疗效：Barthel指数、FM、SIS-16、步态耐力、HAM-D - 3。安全性：不良事件，包括严重不良事件，体位血压和脉搏测量，伴随药物的审查

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Scientific Rationale Stroke is the leading cause of adult disability. Motor deficits are among the most common domain of impairment after stroke, and a major contributor to stroke-related disability. After a stroke, a number of changes in brain structure, chemistry, and function have been described. Medical therapies that target these changes may represent a therapeutic avenue for reducing disability after stroke. Early after focal stroke, brain catecholamine levels are generally reduced. A number of studies suggest that increasing brain alpha 1-noradrenergic activity early after stroke improves motor outcome. Late after stroke, levels of brain catecholamines, including dopamine, generally increase. Dopamine normally plays an important role in regulation of motor, limbic, and cognitive activity. This suggests that decreased dopamine may play a role in post-stroke motor deficits, and increased dopamine, a role in motor recovery. Human trials of L-dopa and amphetamine have found significant treatment-related gains in motor status. This study aims to determine if the dopamine agonist ropinirole is safe in stroke patients, and if, when combined with physiotherapy, ropinirole is associated with improved gait and motor status. Study Objectives 1. To test the hypothesis that patients randomized to ropinirole+physiotherapy will show improved gait velocity over the 12 weeks of study participation as compared to patients randomized to placebo+physiotherapy. Sub-analysis will explore (a) whether treatment improves final gait velocity, i.e., at 12 weeks after study entry, without respect to time course, and (b) whether treatment improves gait velocity at 9 weeks after study entry, i.e., while ropinirole is still present in the system. 2. To test the hypothesis that ropinirole will improve three secondary endpoints at 12 weeks after study entry: the proportion of patients with no significant disability (Barthel Index >/= 95); overall motor status, measured with the arm/leg FM score; and overall physical function, defined as the score on the Stroke Impact Scale-16 (SIS-16). A sub-hypothesis is that each of these three secondary endpoints will show ropinirole-related gains at 9 weeks after study entry, i.e., while ropinirole is still present in the system. Gait endurance and the HAM-D scale scores will also be followed. 3. To evalute the safety of ropinirole in patients recovering from stroke. 4. To determine which demographic, clinical, and radiological characteristics predict improved gait velocity, and which characteristics predict treatment-related benefit. Study Endpoints 1. Primary efficacy: gait velocity 2. Secondary efficacy: Barthel Index, FM, SIS-16, gait endurance, HAM-D 3. Safety: adverse events, including serious adverse events, and orthostatic blood pressure and pulse measurements, review of concomitant medications