- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03598140
Sildenafil Treatment for Mild TBI
October 27, 2020 updated by: Kan Ding, University of Texas Southwestern Medical Center
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.
Study Overview
Status
Terminated
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
22
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Texas
-
Dallas, Texas, United States, 75390
- University of Texas Southwestern Medical Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 33 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Male
Description
Inclusion Criteria:
For Athletes
- Age 18-35
- Male or female professional boxers/MMA fighters
- Ability to undergo MR imaging procedures
At least one of the following:
- Knockout (KO)/Technical Knockout (TKO) scored by fight referee.
- Greater than 25 blows to the head.
- Significant post-concussive symptoms (Symptom Score > 1 on at least 3 items from the Rivermead Post-Concussion Questionnaire)
For Controls
- Age 18-35
- Male of female who do not participate in contact sports
- Screen negative for mild TBI (mTBI) using Ohio State TBI Identification
Exclusion Criteria:
Contraindication to sildenafil which includes the following:
- Current use of organic nitrate vasodilators
- Use of ritonavir (HIV-protease inhibitor)
- Current use of erythromycin, ketoconazole, or itraconazole
- Current use of cimetidine
- Current resting hypotension (BP < 90/50 mm Hg)
- Current severe renal insufficiency (Creatinine Clearance < 30 milliliters/minute)
- Current hepatic cirrhosis
- Current cardiac failure or coronary artery disease causing unstable angina
- Retinitis pigmentosa
- Known hypersensitivity or allergy to sildenafil of any of its components
- Daily therapy with a PDE5 inhibitor within the past 2 months
- Immediate hospitalization for severe concussion
- History of neurological or psychiatric disorder not related to TBI
- Known inclusion in another interventional clinical trial
- Subjects with metal implants that would interfere with the MR imaging procedures
- Sickle cell disease
- History of priapism
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: 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.
|
Placebo once (Group 1) or daily for 2 weeks (Group 2)
Other Names:
|
Active Comparator: 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.
|
Sildenafil 60mg once (Group 1) or daily for 2 weeks (Group 2)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Arterial Spin Labeling
Time Frame: 3 years
|
Prior to and after sildenafil treatment (60mg) cerebral blood flow will be measured in the athletes and healthy controls.
|
3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rivermead Post Concussion Symptoms Questionnaire (RPQ)
Time Frame: 3 years
|
This test will measure a range of injury severities: 0= Not experienced at all
|
3 years
|
Hopkins Verbal Learning Task (HVLT)
Time Frame: 3 years
|
Using the HVLT, performance in learning and memory will be measured in concussed athletes and healthy controls.
|
3 years
|
BOLD MRI With Hypercapnia
Time Frame: 3 years
|
Before and after sildenafil treatment, cerebrovascular reactivity will be measured in the athletes and healthy controls.
|
3 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 25, 2018
Primary Completion (Actual)
May 29, 2019
Study Completion (Actual)
May 29, 2019
Study Registration Dates
First Submitted
June 11, 2018
First Submitted That Met QC Criteria
July 13, 2018
First Posted (Actual)
July 26, 2018
Study Record Updates
Last Update Posted (Actual)
November 19, 2020
Last Update Submitted That Met QC Criteria
October 27, 2020
Last Verified
October 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Wounds and Injuries
- Craniocerebral Trauma
- Trauma, Nervous System
- Head Injuries, Closed
- Wounds, Nonpenetrating
- Brain Injuries
- Brain Injuries, Traumatic
- Post-Concussion Syndrome
- Brain Concussion
- Vascular System Injuries
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Urological Agents
- Enzyme Inhibitors
- Phosphodiesterase Inhibitors
- Phosphodiesterase 5 Inhibitors
- Sildenafil Citrate
Other Study ID Numbers
- STU 032018-063
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Post-Concussion Syndrome
-
Essentia HealthUniversity of North Dakota; Dakota Medical Foundation; The Swanson Foundation; State...Active, not recruitingConcussion Post Syndrome | Persistent Post-concussive SyndromeUnited States
-
Spaulding Rehabilitation HospitalRio Grande NeurosciencesWithdrawnConcussion | Post Concussive Syndrome
-
Boston Children's HospitalCompletedPost Concussion SymptomsUnited States
-
McMaster UniversityNot yet recruitingPost Concussion Syndrome
-
Duke UniversityEnrolling by invitation
-
Children's Hospital Medical Center, CincinnatiCompletedConcussion | Post-concussion Syndrome | Sports InjuryUnited States
-
Sunnybrook Health Sciences CentreRecruitingPost Concussion SyndromeCanada
-
University Children's Hospital, ZurichUniversity of Zurich; ETH ZurichRecruiting
-
University of OttawaUnknownConcussion Post Syndrome
-
University of ArizonaWithdrawnPost Concussion SyndromeUnited States
Clinical Trials on Placebo oral capsule
-
Sao Thai Duong Joint Stock CompanyBig Leap Clinical Research Joint Stock CompanyCompleted
-
Brigham and Women's HospitalCompleted
-
Georgetown UniversityNational Institutes of Health (NIH)RecruitingDementia With Lewy BodiesUnited States
-
Aelis FarmaNational Institute on Drug Abuse (NIDA)CompletedHealthy VolunteersUnited States
-
Brigham and Women's HospitalEnrolling by invitation
-
EicOsis Human Health Inc.National Institute of Neurological Disorders and Stroke (NINDS)CompletedHealthy AdultsUnited States
-
Brigham and Women's HospitalCompleted
-
Yale UniversityNeurocrine BiosciencesRecruitingTrichotillomania (Hair-Pulling Disorder)United States
-
Alkermes, Inc.Terminated
-
InFlectis BioScienceAssistance Publique Hopitaux De Marseille; Qualissima; Eurofins Optimed; Stragen...Completed