Vascular System InjuriesPhase 2NCT03598140
Sildenafil Treatment for Mild TBI
A Phase 2 study testing Sildenafil Citrate in people with Vascular System Injuries and Concussion, Brain, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Vascular System Injuries, Concussion, Brain, Post-Concussion Syndrome
- What is being tested?
- Sildenafil Citrate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Jul 2018to 29 May 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Show all 12Show fewer
- 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
Who cannot join
- 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)
Show all 18Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
About this study
Official title: 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.
Read the 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.
- Being tested
- Sildenafil Citrate, Placebo oral capsule
- Keywords
- Sildenafil, Concussion, CBF, CVR
- Medical subject headings
- Vascular System Injuries, Brain Concussion, Post-Concussion Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sildenafil CitrateDrug
Also called Viagra
Sildenafil 60mg once (Group 1) or daily for 2 weeks (Group 2)
Placebo oral capsuleDrug
Also called Placebo
Placebo once (Group 1) or daily for 2 weeks (Group 2)
| Study group | Role | What they receive |
|---|---|---|
| Placebo oral capsule | Placebo comparator | If randomized to placebo, the participant will receive single (Group 1) or multiple (once-a-day for 14 days; Group 2) treatments. Receives: Drug: Placebo oral capsule |
| Sildenafil Citrate | Active comparator | If randomized to sildenafil (60mg), the participant will receive single (Group 1) or multiple (once-a-day for 14 days; Group 2) treatments. Receives: Drug: Sildenafil Citrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Arterial Spin Labeling
Prior to and after sildenafil treatment (60mg) cerebral blood flow will be measured in the athletes and healthy controls.
Measured: 3 years
Secondary outcomes (3)
Rivermead Post Concussion Symptoms Questionnaire (RPQ)
This test will measure a range of injury severities:
0= Not experienced at all
- No more of a problem
- A mild problem
- A moderate problem
- A severe problem Improvement or worsening of symptoms (headaches, nausea, fatigue, feeling depressed, light sensitivity, double vision, etc.) will be recorded. The combined score from all symptoms will be recorded at the indicated time-points.
Measured: 3 years
Hopkins Verbal Learning Task (HVLT)
Using the HVLT, performance in learning and memory will be measured in concussed athletes and healthy controls.
Measured: 3 years
BOLD MRI With Hypercapnia
Before and after sildenafil treatment, cerebrovascular reactivity will be measured in the athletes and healthy controls.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2018
- Study start25 Jul 2018
- Primary completion29 May 2019
- Study completion29 May 2019
Why it stopped: PI, Dr. Josh Gaston, left the institution and the study has been stopped.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Vascular System InjuriesStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study is a placebo-controlled, double-blinded clinical trial. Randomization will be 1:1 sildenafil:placebo, and will be in blocks of 10. In this study, 100 boxers and 80 controls will be enrolled and randomized.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kan Ding, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03598140
- Sponsor's protocol ID
- STU 032018-063
- Status last verified
- Oct 2020
- First submitted
- 11 Jun 2018
- Last updated
- 19 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sildenafil Treatment for Traumatic Vascular Injury in Athletes
- ClinicalTrials.gov ID
- NCT03598140
- Acronym / sponsor ID
- STU 032018-063
- Keywords
- Sildenafil, Concussion, CBF, CVR
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI, Dr. Josh Gaston, left the institution and the study has been stopped.
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- 25 Jul 2018 (actual)
- Primary completion
- 29 May 2019 (actual)
- Study completion
- 29 May 2019 (actual)
- First posted
- 26 Jul 2018 (actual)
- Results
- Posted 19 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- This study is a placebo-controlled, double-blinded clinical trial. Randomization will be 1:1 sildenafil:placebo, and will be in blocks of 10. In this study, 100 boxers and 80 controls will be enrolled and randomized.
| Arm | Type | Receives |
|---|---|---|
| Placebo oral capsule | Placebo comparator | Drug: Placebo oral capsuleIf randomized to placebo, the participant will receive single (Group 1) or multiple (once-a-day for 14 days; Group 2) treatments. |
| Sildenafil Citrate | Active comparator | Drug: Sildenafil CitrateIf randomized to sildenafil (60mg), the participant will receive single (Group 1) or multiple (once-a-day for 14 days; Group 2) treatments. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- For Athletes
- Age 18-35
- Male or female professional boxers/MMA fighters
- Ability to undergo MR imaging procedures
- At least one of the following:
Key exclusion criteria (18 listed)
- Contraindication to sildenafil which includes the following:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sildenafil CitrateAlso: ViagraSildenafil 60mg once (Group 1) or daily for 2 weeks (Group 2) | Drug | Sildenafil Citrate |
| Placebo oral capsuleAlso: PlaceboPlacebo once (Group 1) or daily for 2 weeks (Group 2) | Drug | Placebo oral capsule |
Primary outcome
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 secondary outcomes
Rivermead Post Concussion Symptoms Questionnaire (RPQ)
Time frame: 3 years
Hopkins Verbal Learning Task (HVLT)
Time frame: 3 years
BOLD MRI With Hypercapnia
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sildenafil Citrate in people with Vascular System Injuries and Concussion, Brain, run by University of Texas Southwestern Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Arterial Spin Labeling (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2020.