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Sildenafil and Stroke Recovery

Primary Purpose

Stroke

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
sildenafil citrate
Placebo
Sponsored by
University of Utah
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stroke focused on measuring stroke, rehabilitation, motor skills, sildenafil citrate, White matter

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. between 4 and 9 days post-ischemic stroke;
  2. admitted to inpatient rehabilitation;
  3. cognitively able to provide consent or assent;
  4. were living independently in the community prior to their stroke.

Exclusion Criteria:

  1. hemorrhagic stroke or subarachnoid hemorrhage;
  2. other neurological or psychiatric conditions deemed by the investigator to impair participation;
  3. no previous stroke on same side of brain unless that stroke was cerebellar
  4. moribound or not expected to live 6 months;
  5. contraindications to taking sildenafil in pill or syrup form;
  6. 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.
  7. scores > 50 on the upper extremity section of the Fugl-Meyer or no walking/gait impairment

    For the MRI portion of the study only:

  8. contraindication to MRI: ferrous metal in body, lead included body art, claustrophobia, pacemaker
  9. allergic to or had previous reaction to gadolinium

Sites / Locations

  • University of Utah

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Drug

control

Arm Description

Sildenafil citrate 25mg once per day for 14 days starting day 5-9 post stroke while undergoing usual rehabilitation

placebo capsule once per day for 14 days starting day 5-9 post stroke while undergoing usual rehabilitation

Outcomes

Primary Outcome Measures

Fugl-Meyer Motor Assessment
An assessment of upper extremity and lower extremity motor impairment
Fugl-Meyer Assessment
An assessment of upper extremity and lower extremity motor impairment

Secondary Outcome Measures

10 meter walk
an assessment of usual gait speed
Wolf Motor Function Test
An assessment of motor function
Motor Activity Log
A self-report of paretic arm (frequency and perceived ability) use in every day activities
Stroke Impact Scale
A self-report measure of the impact of stroke on the individual for body functions, activities, and participation
10 meter walk
an assessment of usual gait speed
Wolf Motor Function Test
An assessment of motor function
Motor Activity Log
A self-report of paretic arm (frequency and perceived ability) use in every day
Stroke Impact Scale
A self-report measure of the impact of stroke on the individual for body

Full Information

First Posted
December 7, 2015
Last Updated
January 3, 2017
Sponsor
University of Utah
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1. Study Identification

Unique Protocol Identification Number
NCT02628847
Brief Title
Sildenafil and Stroke Recovery
Official Title
Sildenafil and Stroke Recovery
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Terminated
Why Stopped
Recruitment was problematic
Study Start Date
March 2012 (undefined)
Primary Completion Date
October 2016 (Actual)
Study Completion Date
October 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Utah

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke
Keywords
stroke, rehabilitation, motor skills, sildenafil citrate, White matter

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Drug
Arm Type
Experimental
Arm Description
Sildenafil citrate 25mg once per day for 14 days starting day 5-9 post stroke while undergoing usual rehabilitation
Arm Title
control
Arm Type
Placebo Comparator
Arm Description
placebo capsule once per day for 14 days starting day 5-9 post stroke while undergoing usual rehabilitation
Intervention Type
Drug
Intervention Name(s)
sildenafil citrate
Other Intervention Name(s)
Viagra
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Fugl-Meyer Motor Assessment
Description
An assessment of upper extremity and lower extremity motor impairment
Time Frame
change from baseline at 1 month
Title
Fugl-Meyer Assessment
Description
An assessment of upper extremity and lower extremity motor impairment
Time Frame
change from baseline at 3 months
Secondary Outcome Measure Information:
Title
10 meter walk
Description
an assessment of usual gait speed
Time Frame
change from baseline at one month
Title
Wolf Motor Function Test
Description
An assessment of motor function
Time Frame
baseline, one month, three months
Title
Motor Activity Log
Description
A self-report of paretic arm (frequency and perceived ability) use in every day activities
Time Frame
one month
Title
Stroke Impact Scale
Description
A self-report measure of the impact of stroke on the individual for body functions, activities, and participation
Time Frame
one month
Title
10 meter walk
Description
an assessment of usual gait speed
Time Frame
change from baseline at 3 months
Title
Wolf Motor Function Test
Description
An assessment of motor function
Time Frame
change from baseline at 3 months
Title
Motor Activity Log
Description
A self-report of paretic arm (frequency and perceived ability) use in every day
Time Frame
3 months
Title
Stroke Impact Scale
Description
A self-report measure of the impact of stroke on the individual for body
Time Frame
3 months
Other Pre-specified Outcome Measures:
Title
Number of participants with unsafe Blood pressure change
Description
blood pressure reductions or increases while taking the drug/placebo
Time Frame
one month
Title
number of participants with cardiovascular side effects
Description
cardiovascular events, such as heart attack, angina pectoris, heart failure
Time Frame
one month
Title
number of participants with visual side effects
Description
new abnormal color vision, light sensitivity, blurred vision or other visual side effects
Time Frame
one month
Title
number of participants with auditory or vestibular side effects
Description
new loss of hearing, tinnitus, dizziness
Time Frame
one month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lorie G Richards, PhD
Organizational Affiliation
University of Utah
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
23118941
Citation
Zhang RL, Chopp M, Roberts C, Wei M, Wang X, Liu X, Lu M, Zhang ZG. Sildenafil enhances neurogenesis and oligodendrogenesis in ischemic brain of middle-aged mouse. PLoS One. 2012;7(10):e48141. doi: 10.1371/journal.pone.0048141. Epub 2012 Oct 31.
Results Reference
result
PubMed Identifier
15746452
Citation
Zhang L, Zhang RL, Wang Y, Zhang C, Zhang ZG, Meng H, Chopp M. Functional recovery in aged and young rats after embolic stroke: treatment with a phosphodiesterase type 5 inhibitor. Stroke. 2005 Apr;36(4):847-52. doi: 10.1161/01.STR.0000158923.19956.73. Epub 2005 Mar 3.
Results Reference
result
PubMed Identifier
12411660
Citation
Zhang R, Wang Y, Zhang L, Zhang Z, Tsang W, Lu M, Zhang L, Chopp M. Sildenafil (Viagra) induces neurogenesis and promotes functional recovery after stroke in rats. Stroke. 2002 Nov;33(11):2675-80. doi: 10.1161/01.str.0000034399.95249.59.
Results Reference
result
PubMed Identifier
17188664
Citation
Li L, Jiang Q, Zhang L, Ding G, Gang Zhang Z, Li Q, Ewing JR, Lu M, Panda S, Ledbetter KA, Whitton PA, Chopp M. Angiogenesis and improved cerebral blood flow in the ischemic boundary area detected by MRI after administration of sildenafil to rats with embolic stroke. Brain Res. 2007 Feb 9;1132(1):185-92. doi: 10.1016/j.brainres.2006.10.098. Epub 2006 Dec 26.
Results Reference
result
PubMed Identifier
18356548
Citation
Ding G, Jiang Q, Li L, Zhang L, Zhang ZG, Ledbetter KA, Gollapalli L, Panda S, Li Q, Ewing JR, Chopp M. Angiogenesis detected after embolic stroke in rat brain using magnetic resonance T2*WI. Stroke. 2008 May;39(5):1563-8. doi: 10.1161/STROKEAHA.107.502146. Epub 2008 Mar 20.
Results Reference
result
PubMed Identifier
18418368
Citation
Ding G, Jiang Q, Li L, Zhang L, Zhang ZG, Ledbetter KA, Panda S, Davarani SP, Athiraman H, Li Q, Ewing JR, Chopp M. Magnetic resonance imaging investigation of axonal remodeling and angiogenesis after embolic stroke in sildenafil-treated rats. J Cereb Blood Flow Metab. 2008 Aug;28(8):1440-8. doi: 10.1038/jcbfm.2008.33. Epub 2008 Apr 16.
Results Reference
result
PubMed Identifier
21903952
Citation
Ding G, Jiang Q, Li L, Zhang L, Zhang Z, Lu M, Li Q, Gu S, Ewing J, Chopp M. Longitudinal magnetic resonance imaging of sildenafil treatment of embolic stroke in aged rats. Stroke. 2011 Dec;42(12):3537-41. doi: 10.1161/STROKEAHA.111.622092. Epub 2011 Sep 8.
Results Reference
result
PubMed Identifier
19717023
Citation
Silver B, McCarthy S, Lu M, Mitsias P, Russman AN, Katramados A, Morris DC, Lewandowski CA, Chopp M. Sildenafil treatment of subacute ischemic stroke: a safety study at 25-mg daily for 2 weeks. J Stroke Cerebrovasc Dis. 2009 Sep-Oct;18(5):381-3. doi: 10.1016/j.jstrokecerebrovasdis.2009.01.007.
Results Reference
result

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Sildenafil and Stroke Recovery

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