Sildenafil and Stroke Recovery

Stroke Clinical Trial

Official title:

Sildenafil and Stroke Recovery

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02628847
• Other study ID #: 53515
• Status: Terminated
• Phase: Phase 1
• First received: December 7, 2015
• Last updated: January 3, 2017
• Start date: March 2012
• Est. completion date: October 2016

Study information

• Verified date: January 2017
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: October 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Stroke

Intervention

Drug:
• sildenafil citrate

• Placebo

Locations

Country	Name	City	State
United States	University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
University of Utah

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. — View 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.107.50214 — View 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 Blo — View 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 emb — View 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: 10.1 — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of participants with unsafe Blood pressure change	blood pressure reductions or increases while taking the drug/placebo	one month	Yes
Other	number of participants with cardiovascular side effects	cardiovascular events, such as heart attack, angina pectoris, heart failure	one month	Yes
Other	number of participants with visual side effects	new abnormal color vision, light sensitivity, blurred vision or other visual side effects	one month	Yes
Other	number of participants with auditory or vestibular side effects	new loss of hearing, tinnitus, dizziness	one month	Yes
Primary	Fugl-Meyer Motor Assessment	An assessment of upper extremity and lower extremity motor impairment	change from baseline at 1 month	No
Primary	Fugl-Meyer Assessment	An assessment of upper extremity and lower extremity motor impairment	change from baseline at 3 months	No
Secondary	10 meter walk	an assessment of usual gait speed	change from baseline at one month	No
Secondary	Wolf Motor Function Test	An assessment of motor function	baseline, one month, three months	No
Secondary	Motor Activity Log	A self-report of paretic arm (frequency and perceived ability) use in every day activities	one month	No
Secondary	Stroke Impact Scale	A self-report measure of the impact of stroke on the individual for body functions, activities, and participation	one month	No
Secondary	10 meter walk	an assessment of usual gait speed	change from baseline at 3 months	No
Secondary	Wolf Motor Function Test	An assessment of motor function	change from baseline at 3 months	No
Secondary	Motor Activity Log	A self-report of paretic arm (frequency and perceived ability) use in every day	3 months	No
Secondary	Stroke Impact Scale	A self-report measure of the impact of stroke on the individual for body	3 months	No