Clinical trial NCT02628847: Sildenafil and Stroke Recovery
Official title: Sildenafil and Stroke Recovery
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Stroke
Keywords: stroke
rehabilitation
motor skills
sildenafil citrate
White matter
Lead sponsor: University of Utah
Sponsor class: OTHER
First posted: 2015-12-11
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Fugl-Meyer Motor Assessment
timeFrame: change from baseline at 1 month
measure: Fugl-Meyer Assessment
timeFrame: change from baseline at 3 months
Secondary outcomes:
measure: 10 meter walk
timeFrame: change from baseline at one month
measure: Wolf Motor Function Test
timeFrame: baseline, one month, three months
measure: Motor Activity Log
timeFrame: one month
measure: Stroke Impact Scale
timeFrame: one month
measure: 10 meter walk
timeFrame: change from baseline at 3 months
measure: Wolf Motor Function Test
timeFrame: change from baseline at 3 months
measure: Motor Activity Log
timeFrame: 3 months
measure: Stroke Impact Scale
timeFrame: 3 months
Other outcomes:
measure: Number of participants with unsafe Blood pressure change
timeFrame: one month
measure: number of participants with cardiovascular side effects
timeFrame: one month
measure: number of participants with visual side effects
timeFrame: one month
measure: number of participants with auditory or vestibular side effects
timeFrame: one month
Locations:
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Utah
name: Lorie G Richards, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.
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.