NCT03598140

Sildenafil Treatment for Mild TBI

Sildenafil Treatment for Traumatic Vascular Injury in Athletes

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 22 (actual)
• Sponsor: University of Texas Southwestern Medical Center · Academic / Other
• Sex: Male
• Age: 18 Years – 35 Years
• Healthy volunteers: Accepted

Summary

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.

Detailed description

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.

Conditions

• Vascular System Injuries
• Concussion, Brain
• Post-Concussion Syndrome

Interventions

Type	Name	Description
DRUG	Sildenafil Citrate	Sildenafil 60mg once (Group 1) or daily for 2 weeks (Group 2)
DRUG	Placebo oral capsule	Placebo once (Group 1) or daily for 2 weeks (Group 2)

Timeline

• Start date: 2018-07-25
• Primary completion: 2019-05-29
• Completion: 2019-05-29
• First posted: 2018-07-26
• Last updated: 2020-11-19
• Results posted: 2020-11-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study