Sildenafil and Stroke Recovery

Study Overview
=================
Brief Summary
-----------------
This is a small, pilot randomized clinical trial of administering sildenafil citrate to individuals within 10 days of ischemic stroke who have motor impairment and who are undergoing inpatient rehabilitation compared to placebo. The primary outcome is motor recovery at one and three months.

Detailed Description
-----------------
Individuals who are within 4-10 days post ischemic stroke with arm hemiparesis or hemiplegia who are admitted to inpatient rehabilitation are randomized to receive either sildenafil citrate (25 mg once per day) or placebo for 14 days. These individuals receive usual rehabilitation and medical care. Primary outcomes are motor skills and walking speed at one and three months. If willing and able, participants undergo an MRI to measure the integrity of the white matter pathways in the motor system using diffusion tensor imaging. Repeat MRIs are obtained at one and three months. The investigators will examine if such white matter integrity predicts response to the drug and if the drug facilitates changes in white matter.

Official Title
-----------------
Sildenafil and Stroke Recovery

Conditions
-----------------
Stroke

Intervention / Treatment
-----------------
* Drug: sildenafil citrate
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: between 4 and 9 days post-ischemic stroke; admitted to inpatient rehabilitation; cognitively able to provide consent or assent; were living independently in the community prior to their stroke. Exclusion Criteria: hemorrhagic stroke or subarachnoid hemorrhage; other neurological or psychiatric conditions deemed by the investigator to impair participation; no previous stroke on same side of brain unless that stroke was cerebellar moribound or not expected to live 6 months; contraindications to taking sildenafil in pill or syrup form; other medical conditions that would limit ability to participate in the study, specifically a) currently taking the P450 enzyme inhibitors (erythromycin, ketoconazole, itraconazole, saquinavir), b) currently taking the protease inhibitor ritonavir, c) currently taking nitrates or have a history of requiring nitrates treatment, d) have left ventricular outflow obstruction (i.e., aortic stenosis, idiopathic hypertrophic subaortic stenosis as confirmed by review of standard of care echo received before admission to rehabilitation), e) have severely impaired autonomic control of blood pressure, f) have previous history of symptomatic hypotension, g) have severely impaired hepatic function, h) is pregnant or become pregnant during the course of the study, i) Any medical condition which, in the opinion of the investigator, may compromise compliance with the objectives and/or procedures of the protocol. scores > 50 on the upper extremity section of the Fugl-Meyer or no walking/gait impairment For the MRI portion of the study only: contraindication to MRI: ferrous metal in body, lead included body art, claustrophobia, pacemaker allergic to or had previous reaction to gadolinium

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug<br>Sildenafil citrate 25mg once per day for 14 days starting day 5-9 post stroke while undergoing usual rehabilitation | Drug: sildenafil citrate<br> <br> * Other names: Viagra;|
| Placebo Comparator: control<br>placebo capsule once per day for 14 days starting day 5-9 post stroke while undergoing usual rehabilitation | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fugl-Meyer Motor Assessment | An assessment of upper extremity and lower extremity motor impairment | change from baseline at 1 month | 
| Fugl-Meyer Assessment | An assessment of upper extremity and lower extremity motor impairment | change from baseline at 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 10 meter walk | an assessment of usual gait speed | change from baseline at one month | 
| Wolf Motor Function Test | An assessment of motor function | baseline, one month, three months | 
| Motor Activity Log | A self-report of paretic arm (frequency and perceived ability) use in every day activities | one month | 
| Stroke Impact Scale | A self-report measure of the impact of stroke on the individual for body functions, activities, and participation | one month | 
| 10 meter walk | an assessment of usual gait speed | change from baseline at 3 months | 
| Wolf Motor Function Test | An assessment of motor function | change from baseline at 3 months | 
| Motor Activity Log | A self-report of paretic arm (frequency and perceived ability) use in every day | 3 months | 
| Stroke Impact Scale | A self-report measure of the impact of stroke on the individual for body | 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stroke, rehabilitation, motor skills, sildenafil citrate, White matter