A Phase 1 interventional study of Sildenafil Citrate in Traumatic Brain Injury, Mild Traumatic Brain Injury and Post-Concussion Syndrome, sponsored by University of Pennsylvania. Terminated at 1 site in United States. Open to male participants aged 40 Years to 65 Years. Per ClinicalTrials.gov, last updated 2022-09-21.
Sponsored by University of Pennsylvania · Phase 1, Interventional, and Treatment
Investigators will measure cerebrovascular reactivity (CVR) using functional near-infrared spectroscopy (fNIRS) and magnetic resonance imaging (MRI) during the chronic phase after repetitive mild traumatic brain injury (rmTBI) as a biomarker of traumatic cerebrovascular injury (TCVI). We hypothesize that CVR will be decreased in patients with rmTBI and that these decreases will correlate with clinical outcomes. Furthermore, we predict that 5 week administration of a phosphodiesterase 5 (PDE5) inhibitor, sildenafil citrate, will augment CVR in patients with a history rmTBI.
Exclusion Criteria:
Open label treatment with forced titration of sildenafil citrate.
Drug: Sildenafil Citrate
Three 20 mg capsules for the single dose studies. For the 5-week treatment phase, subjects will be assigned to a titration of doses for the 5 week duration of the study. Subjects will be instructed to take 20mg twice per day for 3 days, then 40mg twice per day for 3 days, and then 80mg twice per day for 4 weeks.
Also known as: Open label forced titration with sildenafil citrate.
Effect of single dose sildenafil citrate treatment on global blood oxygen level-dependent (BOLD) response to hypercapnia.
Determine if single dose treatment with sildenafil (60 mg orally) is effective in increasing the global BOLD response to hypercapnia (5% CO2).
Time frame: Immediate
Effect of single dose sildenafil citrate treatment on functional near-infrared spectroscopy (fNIRS) response to hypercapnia.
Determine if single dose treatment with sildenafil (60 mg orally) is effective in increasing the functional near-infrared spectroscopy (fNIRS) response to hypercapnia (5% CO2).
Time frame: Immediate
Maximum tolerable dose of sildenafil therapy without severe adverse events.
The number of participants reporting treatment-related adverse events (AEs) and serious adverse events (SAEs) will be monitored after each dose increase. AEs and SAEs are assessed using CTCAE, v4.0.
Time frame: 5 weeks
Effect of 5 weeks sildenafil treatment on CVR as measured by BOLD response to hypercapnia.
To evaluate the effects of 5 weeks of treatment on CVR by measuring BOLD signal in response to hypercapnia after 5 week treatment with sildenafil, compared to within-subject CVR response before sildenafil treatment.
Time frame: 5 weeks
Effect of 5 weeks sildenafil treatment on CVR as measured by fNIRS response to hypercapnia.
To evaluate the effects of 5 weeks of treatment on CVR by measuring fNIRS signal in response to hypercapnia after 5 week treatment with sildenafil, compared to within-subject CVR response before sildenafil treatment.
Time frame: 5 weeks
Effect of 5 weeks of sildenafil treatment on attention using Trail Making Test Part A.
To evaluate the effects of 5 weeks of treatment with sildenafil citrate on attention, measured using the Trail Making Test Part A.
Time frame: 5 weeks
Effect of 5 weeks of sildenafil treatment on attention using the Digit Symbol Modalities Test.
To evaluate the effects of 5 weeks of treatment with sildenafil citrate on attention, measured using the Digit Symbol Modalities Test.
Time frame: 5 weeks
Effect of 5 weeks of sildenafil treatment on executive function using the Trail Making Test Part B.
To evaluate the effects of 5 weeks of treatment with sildenafil citrate on executive function, measured using the Trail Making Test Part B.
Time frame: 5 weeks
Effect of 5 weeks of sildenafil treatment on executive function using the Neuropsychological Assessment Battery (NAB) mazes.
To evaluate the effects of 5 weeks of treatment with sildenafil citrate on executive function, measured using the Neuropsychological Assessment Battery (NAB) mazes.
Time frame: 5 weeks
Effect of 5 weeks of sildenafil treatment on executive function using the Controlled Oral Word Association Test (COWAT).
To evaluate the effects of 5 weeks of treatment with sildenafil citrate on executive function, measured using the Controlled Oral Word Association Test (COWAT).
Time frame: 5 weeks
Effect of 5 weeks of sildenafil treatment on language and memory using the Animal Fluency test.
To evaluate the effects of 5 weeks of treatment with sildenafil citrate on language and memory, measured using the Animal Fluency test.
Time frame: 5 weeks
Effect of 5 weeks of sildenafil treatment on language and memory using the NAB List Learning test.
To evaluate the effects of 5 weeks of treatment with sildenafil citrate on language and memory, measured using the NAB List Learning test.
Time frame: 5 weeks
Effect of 5 weeks of sildenafil treatment on daily function using the Functional Activities Questionnaire.
To evaluate the effects of 5 weeks of treatment with sildenafil citrate on daily function, measured using the Functional Activities Questionnaire. The questionnaire requires the subject to rate the level of difficulty/dependency of each task listed (rating range from 0-3). A lower score indicates less difficulty in the listed activities while a higher score indicates more difficulty. The ratings are summed and the total score is reported (range 0-30).
Time frame: 5 weeks
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University of Pennsylvania