Effects of Exercise on Endothelial Function in Stroke Patients

Study Overview
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Brief Summary
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This study examines the hypothesis that 6 months of treadmill aerobic exercise training improves fibrinolysis (clot defense mechanism) and vasomotor function in chronic hemiparetic (muscular weakness or partial paralysis restricted to one side of the body) stroke patients compared to a control intervention, and that these changes are associated with reduced plasma insulin levels and improved insulin sensitivity / glucose metabolism in this population.

Detailed Description
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Stroke is the leading cause of disability and third leading cause of death in the United States. Each year approximately 750,000 individuals suffer a stroke, after which they remain at high risk for recurrent stroke and cardiovascular events. Incidence of stroke nearly doubles with each successive decade in older adults, with about 90% of strokes occurring in individuals over 55 years of age. Following stroke, physical inactivity in advancing age increases the incidence of elevated insulin levels and the insulin resistance syndrome, which are powerful factors that heighten risk for recurrent stroke and myocardial infarction (MI) by impairing fibrinolysis and vasomotor reactivity. Currently, prevention of recurrent stroke and MI depends on best medical management, including antiplatelet therapy, which has limited efficacy. Though aerobic exercise training (AEX) has been shown to improve insulin-glucose metabolism, fibrinolysis profiles, and vasomotor reactivity in healthy elderly and type 2 diabetics, there are no data on the effects of AEX on insulin sensitivity and related vascular endothelial cell function in the chronic hemiparetic stroke population. This trial addresses a significant public health gap, in that aerobic exercise rehabilitation therapy has never been systematically studied as a means to improve cardiovascular health profiles in this population.

Official Title
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Effects of Exercise on Endothelial Function in Stroke Patients

Conditions
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Stroke, Cerebrovascular Disorders

Intervention / Treatment
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* Behavioral: Treadmill Exercise
* Behavioral: Stretching/ROM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ischemic Stroke greater than 6 months prior in men or women ages 40-85 Residual hemiparetic gait deficits Already completed all conventional inpatient and outpatient physical therapy Adequate language and neurocognitive function to participate in exercise testing and training Exclusion Criteria: Already performing greater than 20 minutes aerobic exercise 3 times per week All insulin dependent diabetics; non-insulin dependent diabetics with fasting glucose greater than 180 mg/dl Alcohol consumption greater than 2oz. liquor or equivalent per day Cardiac history of: (a) unstable angina, (b) recent (less than 3 months) myocardial infarction, (c) symptomatic congestive heart failure, (d) hemodynamically significant valvular dysfunction Medical History of: (a) recent (less than 3 months) hospitalization for severe medical disease, (b) PAOD (Peripheral Arterial Obstructive Disease) with claudication, (c) orthopedic or chronic pain condition restricting exercise, (d) pulmonary or renal failure, (e) active cancer, (f) poorly controlled hypertension (greater than 160/100) (g) Anemia defined by hematocrit less than 30 Neurological History of: (a) dementia with Mini-Mental Status Score less than 23 (less than 17 if education level at or below 8th grade), and diagnostic confirmation by neurologist or geropsychiatrist, (b) severe receptive or global aphasia which confounds testing and training, operationally defined as unable to follow 2 point commands, (c) hemiparetic gait from prior stroke preceding the index stroke defining eligibility, (d) non-stroke neurological disorder restricting exercise (e.g. Parkinson's Syndrome), (e) untreated major depression Pregnancy

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Behavioral: Treadmill Exercise<br>* 3 times per week for 6 months, with target of 45 minutes at 60-70% heart rate range<br>|
| Active Comparator: 2<br> | Behavioral: Stretching/ROM<br>* 3 times per week for 6 months, passive and active stretching and range of motion (ROM) exercises for the upper and lower extremities<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting and Post-Stressor Fibrinolysis |  | Baseline and 6 months | 
| Cerebral and lower extremity vasomotor reactivity |  | Baseline and 6 months | 
| Nitric oxide biomarkers |  | Baseline and 6 months | 
| Fasting insulin, HOMA-IR, post-load insulin response, glucose tolerance, insulin sensitivity, insulin signaling |  | Baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak aerobic capacity |  | Baseline and 6 months | 
| Mobility Function (Timed walks etc..) |  | Baseline and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exercise, glucose metabolism, insulin sensitivity, Vascular Function