Sildenafil Treatment for Mild TBI

NCT ID: NCT03598140

Last Updated: 2020-11-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-25
• Study Completion Date: 2019-05-29

Brief 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

Keywords

Sildenafil; Concussion; CBF; CVR

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo oral capsule

If randomized to placebo, the participant will receive single (Group 1) or multiple (once-a-day for 14 days; Group 2) treatments.

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

Placebo once (Group 1) or daily for 2 weeks (Group 2)

Sildenafil Citrate

If randomized to sildenafil (60mg), the participant will receive single (Group 1) or multiple (once-a-day for 14 days; Group 2) treatments.

Group Type: ACTIVE_COMPARATOR

Sildenafil Citrate

Intervention Type: DRUG

Sildenafil 60mg once (Group 1) or daily for 2 weeks (Group 2)

Interventions

Sildenafil Citrate

Sildenafil 60mg once (Group 1) or daily for 2 weeks (Group 2)

Intervention Type: DRUG

Placebo oral capsule

Placebo once (Group 1) or daily for 2 weeks (Group 2)

Intervention Type: DRUG

Other Intervention Names

Viagra; Placebo

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Kan Ding

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

STU 032018-063

Identifier Type: -

Identifier Source: org_study_id