Sildenafil Treatment for Mild TBI
| Status: | Recruiting |
|---|---|
| Conditions: | Neurology |
| Therapuetic Areas: | Neurology |
| Healthy: | No |
| Age Range: | 18 - 35 |
| Updated: | 8/30/2018 |
| Start Date: | July 25, 2018 |
| End Date: | December 31, 2021 |
| Contact: | Joshua Gatson, PhD |
| Email: | joshua.gatson@utsouthwestern.edu |
| Phone: | 214-648-0499 |
Sildenafil Treatment for Traumatic Vascular Injury in Athletes
About 300,000 people are hospitalized for traumatic brain injury (TBI) each year. After TBI,
secondary brain injury escalates due in part to heightened levels of oxidant injury,
inflammation, and vascular injury. Traumatic cerebral vascular injury (TCVI) may begin almost
immediately after the primary injury and evolve into chronic neurodegenerative conditions.
TCVI is a very complex TBI endophenotype and microvascular injuries have been described in a
plethora of animal and human TBI studies. These injuries consist of endothelial injury,
disruption of the blood brain barrier (BBB), a reduction of capillary density, intravascular
microthrombi, and white-matter degeneration. Recently, use of magnetic resonance imaging
(MRI)-Blood Oxygen Level Dependent (BOLD) combined with hypercapnia (high spatial and
temporal resolution) by our research group has proven to be more sensitive at measuring
alterations of cerebral blood flow (CBF) in TBI subjects. The goal of the proposed research
is to test the efficacy of Viagra® (sildenafil) at normalizing CBF and improving cognitive
outcomes in people that have experienced a TBI. Sildenafil is a phosphodiesterase-5 (PDE-5)
inhibitor that has previously been administered as a therapy for high blood pressure and
erectile dysfunction. In people that have been affected by stroke-induce neurotrauma,
sildenafil improved CBF and was found to be neuroprotective. With respect to chronic TBI,
previous studies have demonstrated that sildenafil therapy potentiates cardiovascular
reactivity (CVR) in areas of the brain with damaged endothelium. In this proposal, the
investigators will test the hypothesis that sildenafil treatment in boxers/Mixed Martial Arts
(MMA) fighters soon after concussion normalizes CBF, potentiates CVR, reduces post-concussion
symptoms, and improves cognition.
secondary brain injury escalates due in part to heightened levels of oxidant injury,
inflammation, and vascular injury. Traumatic cerebral vascular injury (TCVI) may begin almost
immediately after the primary injury and evolve into chronic neurodegenerative conditions.
TCVI is a very complex TBI endophenotype and microvascular injuries have been described in a
plethora of animal and human TBI studies. These injuries consist of endothelial injury,
disruption of the blood brain barrier (BBB), a reduction of capillary density, intravascular
microthrombi, and white-matter degeneration. Recently, use of magnetic resonance imaging
(MRI)-Blood Oxygen Level Dependent (BOLD) combined with hypercapnia (high spatial and
temporal resolution) by our research group has proven to be more sensitive at measuring
alterations of cerebral blood flow (CBF) in TBI subjects. The goal of the proposed research
is to test the efficacy of Viagra® (sildenafil) at normalizing CBF and improving cognitive
outcomes in people that have experienced a TBI. Sildenafil is a phosphodiesterase-5 (PDE-5)
inhibitor that has previously been administered as a therapy for high blood pressure and
erectile dysfunction. In people that have been affected by stroke-induce neurotrauma,
sildenafil improved CBF and was found to be neuroprotective. With respect to chronic TBI,
previous studies have demonstrated that sildenafil therapy potentiates cardiovascular
reactivity (CVR) in areas of the brain with damaged endothelium. In this proposal, the
investigators will test the hypothesis that sildenafil treatment in boxers/Mixed Martial Arts
(MMA) fighters soon after concussion normalizes CBF, potentiates CVR, reduces post-concussion
symptoms, and improves cognition.
In this study, 100 professional boxers that experience a concussion will be enrolled,
randomized to either placebo or sildenafil (60mg) drug treatment, and arterial spin labeling
and BOLD-MRI with hypercapnia will used to assess CBF and CVR, respectively. Symptom
reporting, blood biomarkers, and neuropsychological testing will also be conducted. The
timepoints for this study are baseline (pre-fight), and once between days 1 and 3 and day 30
after injury.
randomized to either placebo or sildenafil (60mg) drug treatment, and arterial spin labeling
and BOLD-MRI with hypercapnia will used to assess CBF and CVR, respectively. Symptom
reporting, blood biomarkers, and neuropsychological testing will also be conducted. The
timepoints for this study are baseline (pre-fight), and once between days 1 and 3 and day 30
after injury.
Inclusion Criteria:
For Athletes
1. Age 18-35
2. Male or female professional boxers/MMA fighters
3. Ability to undergo MR imaging procedures
4. At least one of the following:
1. Knockout (KO)/Technical Knockout (TKO) scored by fight referee.
2. Greater than 25 blows to the head.
5. Significant post-concussive symptoms (Symptom Score > 1 on at least 3 items from the
Rivermead Post-Concussion Questionnaire)
For Controls
1. Age 18-35
2. Male of female who do not participate in contact sports
3. Screen negative for mild TBI (mTBI) using Ohio State TBI Identification
Exclusion Criteria:
1. Contraindication to sildenafil which includes the following:
1. Current use of organic nitrate vasodilators
2. Use of ritonavir (HIV-protease inhibitor)
3. Current use of erythromycin, ketoconazole, or itraconazole
4. Current use of cimetidine
5. Current resting hypotension (BP < 90/50 mm Hg)
6. Current severe renal insufficiency (Creatinine Clearance < 30 milliliters/minute)
7. Current hepatic cirrhosis
8. Current cardiac failure or coronary artery disease causing unstable angina
9. Retinitis pigmentosa
10. Known hypersensitivity or allergy to sildenafil of any of its components
2. Daily therapy with a PDE5 inhibitor within the past 2 months
3. Immediate hospitalization for severe concussion
4. History of neurological or psychiatric disorder not related to TBI
5. Known inclusion in another interventional clinical trial
6. Subjects with metal implants that would interfere with the MR imaging procedures
7. Sickle cell disease
8. History of priapism
We found this trial at
1
site
1801 Inwood Rd
Dallas, Texas 75390
Dallas, Texas 75390
(214) 645-3300
Phone: 214-648-0499
University of Texas Southwestern Medical Center UT Southwestern is an academic medical center, world-renowned for...
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