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
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