Ischemic StrokePhase 1NCT00452582
Sildenafil (Viagra) Treatment of Subacute Ischemic Stroke
A Phase 1 study testing Sildenafil (Viagra) in people with Ischemic Stroke, run by Henry Ford Health System at 1 site in United States.
Trial summary
Stroke is the third leading cause of death in the United States and the leading cause of serious long-term disability. Approximately 50% of the 750,000 people affected by stroke each year have residual physical impairment. Treatment options for recovery are limited at this time. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Ischemic Stroke
- What is being tested?
- Sildenafil (Viagra)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2005to not given
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with ischemic stroke between 4 and 7 days after symptom onset.
- Patients age 18-80 years old.
- NIHSS score of 5-21 prior to treatment (within each cohort, there will be no more than 4 patients with NIHSS < 9 and no fewer than 4 patients with NIHSS > 11).
- Signed IRB-approved informed consent by patient or authorized representative.
Who cannot join
- General:
- Participation in another study with an investigational drug or device.
- Women known to be pregnant, lactating, or of childbearing potential with a positive urine beta-HCG.
- Patients who cannot receive oral medications.
- Patients using sildenafil or other phosphodiesterase inhibitors within the previous 7 days of stroke.
- Safety Related:
Show all 30Show fewer
- Unstable angina.
- Myocardial infarction within 3 months.
- Current use of nitrate agents.
- Current use of alpha-channel antagonists.
- Current use of medications that inhibit the cytochrome p450 3A4 system. These medications include: amiodarone, aprepitant, bosentan, cimetidine, cisapride, clarithromycin, delavirdine, diltiazem, efavirenz, erythromycin, fluconazole, fluvoxamine, grapefruit juice, imatinib, itraconazole, ketoconazole,loratadine, mibefradil, mifepristone (RU-486), niacin, nefazodone, quinidine, quinine, ritonavir, saquinavir, tacrolimus, verapamil, voriconazole.
- St. John's Wort and phenytoin (inducers of cytochrome P450 3A4)
- Baseline systolic blood pressure less than 100 mmHg.
- Penile deformities.
- Creatinine > 1.5.
- Abnormal liver function studies.
- Patients with a previous history of sudden monocular vision loss Potentially Interfering with Outcomes Assessment:
- Prior history of dementia.
- Patients without fixed address or those deemed unlikely to present for follow-up by the investigator.
- Patients whose life expectancy is less than 90 days.
- Pre-stroke modified Rankin score > 2.
- Glucose greater than or equal to 400 mg/dL at presentation.
- Other serious illness (e.g., severe hepatic, cardiac, or renal failure; acute myocardial infarction; or a complex disease that may confound treatment assessment).
- Previous stroke or TIA within 30 days.
- Allergy or hypersensitivity to sildenafil or other phosphodiesterase inhibitors.
- History of sudden monocular visual disturbance.
- History of sudden unilateral hearing problem.
- Imaging Related:
- Evidence of primary intraparenchymal hemorrhage on initial neuroimaging study.
- Neuroimaging evidence of nonvascular cause for the neurological symptoms.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 1 Study of Sildenafil (Viagra) Treatment of Subacute Ischemic Stroke
Stroke is the third leading cause of death in the United States and the leading cause of serious long-term disability. Approximately 50% of the 750,000 people affected by stroke each year have residual physical impairment. Treatment options for recovery are limited at this time. Sildenafil (Viagra) has demonstrated the capability of significantly improving recovery in several animal experiments of stroke. This study is aiming to establish the safety of treatment with sildenafil in people with stroke with the ultimate aim of testing its usefulness to improve recovery.
Read the detailed description
Stroke is the third leading cause of death and the leading cause of serious long-term disability in the United States. Approximately 15-30% of stroke survivors are permanently disabled. Twenty eight percent of stroke patients are under age 65 which results in a loss of work income. While many restorative therapies are touted as promising for the treatment of ischemic stroke, to date none are approved for this purpose. Sildenafil (Viagra®), a phosphodiesterase type 5 inhibitor, has been shown to reduce mortality and improve the functional outcomes of young and aged rats when administered 24 hours and 7 days after stroke onset. Such results are encouraging and warrant further investigation in human stroke.
The specific aims of this study are to assess the safety of treating ischemic stroke patients with sildenafil (Viagra®) and to evaluate their outcomes at day 90. This will be a phase I dose-escalation study with cohort sizes of 12 patients (depending on the occurrence of serious adverse events). A total enrollment of 120 patients is planned. Patients who are between 4 and 7 days from stroke onset will receive 25, 50, 75, 100, 125, 150, 175, and 200 mg daily of sildenafil for a period of 14 days. Of the 120 patients, 24 will be randomly selected to receive standard treatment but will not receive sildenafil. All patients and physicians will be aware of treatment assignment. Evaluation of potential toxicity will be monitored throughout the course of treatment and during a formal visit at day 16 after initiation of treatment. Plasma monitoring of vascular endothelial growth factor (VEGF) will be made prior to treatment, at days 7, 16, 30, 60, and 90. Measurements of NIHSS scores, Rankin scores, and Barthel indices will be made at days 30, 60, and 90. Patients will also be assessed for color vision changes and sexual function during day 16 and day 90 visits. There will be every other day phone calls to patients while on treatment. The primary outcome measure will be death, recurrent stroke, and myocardial infarction during treatment. Exploratory analysis will include functional outcomes as measured on the neurological scales, and changes in VEGF levels in relation to clinical outcome.
The long-term objective is to identify a safe and easily administered treatment that improves functional outcome in patients with ischemic stroke.
- Conditions
- Ischemic Stroke
- Being tested
- Sildenafil (Viagra), Usual care
- Keywords
- ischemic stroke, recovery, sildenafil
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sildenafil (Viagra)Drug
Dose escalation (one of the following): 25 mg daily for 2 weeks, 50 mg daily for 2 weeks, 75 mg daily for 2 weeks, 50 mg twice daily for two weeks, 50 mg AM and 75 mg PM for 2 weeks, 75 mg twice daily for 2 weeks, 75 mg in AM and 100 mg in PM for 2 weeks, 100 mg twice daily for 2 weeks.
Usual careOther
Physical therapy, occupational therapy, speech therapy
| Study group | Role | What they receive |
|---|---|---|
| Sildenafil | Experimental | Orally administered sildenafil in addition to usual care. Receives: Drug: Sildenafil (Viagra) |
| Usual post-stroke care | Active comparator | Usual post-stroke treatment including physical, occupational, and speech therapy. Receives: Other: Usual care |
What is being measured
The primary outcome is the main question the study is designed to answer.
The maximum tolerated dose and toxicity profile of sildenafil treatment in patients with subacute ischemic stroke.
Measured: 2 weeks
Secondary outcomes (1)
The estimated efficacy of sildenafil in comparison with concurrent patients randomized assigned to usual care.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2007 (estimated)
- Study startApr 2005
Why it stopped: Failure to recruit in expected time period.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- More trials run by Henry Ford Health SystemThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Henry Ford Health System
- Sponsor type
- University, hospital or other
- Investigators
- Brian Silver, MD, Principal investigator, Henry Ford Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00452582
- Sponsor's protocol ID
- HF-N-1
- Status last verified
- Mar 2011
- First submitted
- 26 Mar 2007
- Last updated
- 16 Mar 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 19717023
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Sildenafil (Viagra) Treatment of Subacute Ischemic Stroke
- ClinicalTrials.gov ID
- NCT00452582
- Acronym / sponsor ID
- HF-N-1
- Conditions
- Ischemic Stroke
- Keywords
- ischemic stroke, recovery, sildenafil
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Failure to recruit in expected time period.
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Henry Ford Health SystemUniversity, hospital or other
- Study start
- Apr 2005
- First posted
- 27 Mar 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Stroke is the third leading cause of death in the United States and the leading cause of serious long-term disability. Approximately 50% of the 750,000 people affected by stroke each year have residual physical impairment. Treatment options for recovery are limited at this time. Sildenafil (Viagra) has demonstrated the capability of significantly improving recovery in several animal experiments of stroke. This study is aiming to establish the safety of treatment with sildenafil in people with stroke with the ultimate aim of testing its usefulness to improve recovery.
Detailed description
Stroke is the third leading cause of death and the leading cause of serious long-term disability in the United States. Approximately 15-30% of stroke survivors are permanently disabled. Twenty eight percent of stroke patients are under age 65 which results in a loss of work income. While many restorative therapies are touted as promising for the treatment of ischemic stroke, to date none are approved for this purpose. Sildenafil (Viagra®), a phosphodiesterase type 5 inhibitor, has been shown to reduce mortality and improve the functional outcomes of young and aged rats when administered 24 hours and 7 days after stroke onset. Such results are encouraging and warrant further investigation in human stroke.
The specific aims of this study are to assess the safety of treating ischemic stroke patients with sildenafil (Viagra®) and to evaluate their outcomes at day 90. This will be a phase I dose-escalation study with cohort sizes of 12 patients (depending on the occurrence of serious adverse events). A total enrollment of 120 patients is planned. Patients who are between 4 and 7 days from stroke onset will receive 25, 50, 75, 100, 125, 150, 175, and 200 mg daily of sildenafil for a period of 14 days. Of the 120 patients, 24 will be randomly selected to receive standard treatment but will not receive sildenafil. All patients and physicians will be aware of treatment assignment. Evaluation of potential toxicity will be monitored throughout the course of treatment and during a formal visit at day 16 after initiation of treatment. Plasma monitoring of vascular endothelial growth factor (VEGF) will be made prior to treatment, at days 7, 16, 30, 60, and 90. Measurements of NIHSS scores, Rankin scores, and Barthel indices will be made at days 30, 60, and 90. Patients will also be assessed for color vision changes and sexual function during day 16 and day 90 visits. There will be every other day phone calls to patients while on treatment. The primary outcome measure will be death, recurrent stroke, and myocardial infarction during treatment. Exploratory analysis will include functional outcomes as measured on the neurological scales, and changes in VEGF levels in relation to clinical outcome.
The long-term objective is to identify a safe and easily administered treatment that improves functional outcome in patients with ischemic stroke.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sildenafil | Experimental | Drug: Sildenafil (Viagra)Orally administered sildenafil in addition to usual care. |
| Usual post-stroke care | Active comparator | Other: Usual careUsual post-stroke treatment including physical, occupational, and speech therapy. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients with ischemic stroke between 4 and 7 days after symptom onset.
- Patients age 18-80 years old.
- NIHSS score of 5-21 prior to treatment (within each cohort, there will be no more than 4 patients with NIHSS < 9 and no fewer than 4 patients with NIHSS > 11).
- Signed IRB-approved informed consent by patient or authorized representative.
Key exclusion criteria (30 listed)
- Participation in another study with an investigational drug or device.
- Women known to be pregnant, lactating, or of childbearing potential with a positive urine beta-HCG.
- Patients who cannot receive oral medications.
- Patients using sildenafil or other phosphodiesterase inhibitors within the previous 7 days of stroke.
- Unstable angina.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sildenafil (Viagra)Dose escalation (one of the following): 25 mg daily for 2 weeks, 50 mg daily for 2 weeks, 75 mg daily for 2 weeks, 50 mg twice daily for two weeks, 50 mg AM and 75 mg PM for 2 weeks, 75 mg twice daily for 2 weeks, 75 mg in AM and 100 mg in PM for 2 weeks, 100 mg twice daily for 2 weeks. | Drug | Sildenafil |
| Usual carePhysical therapy, occupational therapy, speech therapy | Other | Usual post-stroke care |
Primary outcome
The maximum tolerated dose and toxicity profile of sildenafil treatment in patients with subacute ischemic stroke.
Time frame: 2 weeks
1 secondary outcome
The estimated efficacy of sildenafil in comparison with concurrent patients randomized assigned to usual care.
Time frame: 3 months
Results and safety
The study was stopped early (reason given: Failure to recruit in expected time period.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2011.
- Results publication: PubMed 19717023Silver 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian Silver, MD principal investigator
Henry Ford Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sildenafil (Viagra) in people with Ischemic Stroke, run by Henry Ford Health System at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Mar 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Failure to recruit in expected time period.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The maximum tolerated dose and toxicity profile of sildenafil treatment in patients with subacute ischemic stroke. (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00452582, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2011; AzTrials last refreshed its copy on 8 Nov 2026.