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Difficulty enrolling participants due to COVID emergency, and planned start of new study to address this question in a more rigorous fashion.
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| Name | Class |
|---|---|
| Boston University | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sildenafil Citrate | Experimental | Open label treatment with forced titration of sildenafil citrate. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sildenafil Citrate | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Immediate |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Immediate |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 5 weeks |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Penn Presbyterian Medical Center | Philadelphia | Pennsylvania | 19104 | United States |
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| ID | Term |
|---|---|
| D000070642 | Brain Injuries, Traumatic |
| D001924 | Brain Concussion |
| D038223 | Post-Concussion Syndrome |
| D006935 | Hypercapnia |
| ID | Term |
|---|---|
| D001930 | Brain Injuries |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000068677 | Sildenafil Citrate |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 |
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Open-label, non-placebo controlled
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|
|
| 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. |
| 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. |
| 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. | 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. | 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. | 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. | 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). | 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. | 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. | 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). | 5 weeks |
| D006259 |
| Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
| D016489 | Head Injuries, Closed |
| D014949 | Wounds, Nonpenetrating |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Sulfur Compounds |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |