Traumatic Brain InjuryPhase 1NCT03417492
Cerebrovascular Reactivity in American Football Players
A Phase 1 study testing Sildenafil Citrate in people with Traumatic Brain Injury and Mild Traumatic Brain Injury, run by University of Pennsylvania at 1 site in United States.
Trial summary
Investigators will measure cerebrovascular reactivity (CVR) using functional near-infrared spectroscopy (fNIRS) and magnetic resonance imaging (MRI) during the chronic phase after repetitive mild traumatic brain injury (rmTBI) as a biomarker of traumatic cerebrovascular injury (TCVI). Read more about this study
- Who is it for?
- Ages 40 to 65 years, men only
- Conditions the study is for
- Traumatic Brain Injury, Mild Traumatic Brain Injury, Post-Concussion Syndrome
- What is being tested?
- Sildenafil Citrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2018to 30 Jun 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 40 to 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 40-65 years
- Former National Football League (NFL) players or former varsity college football players
- Ability to undergo MRI scanning
- Ability to read, write, and speak English
- Stable doses of concomitant medications for last 2 weeks prior to enrollment
- Diagnosis of post-concussive syndrome according to Diagnostic and Statistical Manual 5 (DSM-5) criteria
Who cannot join
- Contraindication to sildenafil
- Past medical history or evidence of penetrating brain injury
- Daily therapy with a PDE5 inhibitor within the past 2 months, or taken as needed within past 4 weeks
- History or evidence of pre-existing disabling neurological or psychiatric disorder not related to previous head injuries
- History of melanoma
- History of diagnosed obstructive/ restrictive pulmonary disease 7 .) Contraindication to MRI
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, 19104
About this study
Official title: Cerebrovascular Reactivity Assessed With Functional Near-infrared Spectroscopy and Magnetic Resonance Imaging as a Biomarker of Traumatic Microvascular Injury in American Football Players
Investigators will measure cerebrovascular reactivity (CVR) using functional near-infrared spectroscopy (fNIRS) and magnetic resonance imaging (MRI) during the chronic phase after repetitive mild traumatic brain injury (rmTBI) as a biomarker of traumatic cerebrovascular injury (TCVI). We hypothesize that CVR will be decreased in patients with rmTBI and that these decreases will correlate with clinical outcomes. Furthermore, we predict that 5 week administration of a phosphodiesterase 5 (PDE5) inhibitor, sildenafil citrate, will augment CVR in patients with a history rmTBI.
- Being tested
- Sildenafil Citrate
- Keywords
- TBI, CVR, Hypercapnia, fNIRS, functional magnetic resonance imaging (fMRI), American football
- Medical subject headings
- Brain Injuries, Traumatic, Brain Concussion, Post-Concussion Syndrome, Hypercapnia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sildenafil CitrateDrug
Also called Open label forced titration with sildenafil citrate.
Three 20 mg capsules for the single dose studies. For the 5-week treatment phase, subjects will be assigned to a titration of doses for the 5 week duration of the study. Subjects will be instructed to take 20mg twice per day for 3 days, then 40mg twice per day for 3 days, and then 80mg twice per day for 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Sildenafil Citrate | Experimental | Open label treatment with forced titration of sildenafil citrate. Receives: Drug: Sildenafil Citrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of single dose sildenafil citrate treatment on global blood oxygen level-dependent (BOLD) response to hypercapnia.
Determine if single dose treatment with sildenafil (60 mg orally) is effective in increasing the global BOLD response to hypercapnia (5% CO2).
Measured: Immediate
Secondary outcomes (2)
Effect of single dose sildenafil citrate treatment on functional near-infrared spectroscopy (fNIRS) response to hypercapnia.
Determine if single dose treatment with sildenafil (60 mg orally) is effective in increasing the functional near-infrared spectroscopy (fNIRS) response to hypercapnia (5% CO2).
Measured: Immediate
Maximum tolerable dose of sildenafil therapy without severe adverse events.
The number of participants reporting treatment-related adverse events (AEs) and serious adverse events (SAEs) will be monitored after each dose increase. AEs and SAEs are assessed using CTCAE, v4.0.
Measured: 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2018
- Study start1 Mar 2018
- Primary completion30 Jun 2022
- Study completion30 Jun 2022
Why it stopped: Difficulty enrolling participants due to COVID emergency, and planned start of new study to address this question in a more rigorous fashion.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-label, non-placebo controlled
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Boston University
- Responsible party
- Principal investigator, Ramon Diaz-Arrastia, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03417492
- Sponsor's protocol ID
- 827103
- Status last verified
- Sep 2022
- First submitted
- 11 Oct 2017
- Last updated
- 21 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cerebrovascular Reactivity Assessed With Functional Near-infrared Spectroscopy and Magnetic Resonance Imaging as a Biomarker of Traumatic Microvascular Injury in American Football Players
- ClinicalTrials.gov ID
- NCT03417492
- Acronym / sponsor ID
- 827103
- Keywords
- TBI, CVR, Hypercapnia, fNIRS, functional magnetic resonance imaging (fMRI), American football
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty enrolling participants due to COVID emergency, and planned start of new study to address this question in a more rigorous fashion.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Boston University
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 30 Jun 2022 (actual)
- Study completion
- 30 Jun 2022 (actual)
- First posted
- 31 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Investigators will measure cerebrovascular reactivity (CVR) using functional near-infrared spectroscopy (fNIRS) and magnetic resonance imaging (MRI) during the chronic phase after repetitive mild traumatic brain injury (rmTBI) as a biomarker of traumatic cerebrovascular injury (TCVI). We hypothesize that CVR will be decreased in patients with rmTBI and that these decreases will correlate with clinical outcomes. Furthermore, we predict that 5 week administration of a phosphodiesterase 5 (PDE5) inhibitor, sildenafil citrate, will augment CVR in patients with a history rmTBI.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label, non-placebo controlled
| Arm | Type | Receives |
|---|---|---|
| Sildenafil Citrate | Experimental | Drug: Sildenafil CitrateOpen label treatment with forced titration of sildenafil citrate. |
Who may qualify
- Ages
- 40 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 40-65 years
- Former National Football League (NFL) players or former varsity college football players
- Ability to undergo MRI scanning
- Ability to read, write, and speak English
- Stable doses of concomitant medications for last 2 weeks prior to enrollment
Key exclusion criteria (6 listed)
- Contraindication to sildenafil
- Past medical history or evidence of penetrating brain injury
- Daily therapy with a PDE5 inhibitor within the past 2 months, or taken as needed within past 4 weeks
- History or evidence of pre-existing disabling neurological or psychiatric disorder not related to previous head injuries
- History of melanoma
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: Open label forced titration with sildenafil citrate.Three 20 mg capsules for the single dose studies. For the 5-week treatment phase, subjects will be assigned to a titration of doses for the 5 week duration of the study. Subjects will be instructed to take 20mg twice per day for 3 days, then 40mg twice per day for 3 days, and then 80mg twice per day for 4 weeks. | Drug | Sildenafil Citrate |
Primary outcome
Effect of single dose sildenafil citrate treatment on global blood oxygen level-dependent (BOLD) response to hypercapnia.
Time frame: Immediate
Determine if single dose treatment with sildenafil (60 mg orally) is effective in increasing the global BOLD response to hypercapnia (5% CO2).
2 secondary outcomes
Effect of single dose sildenafil citrate treatment on functional near-infrared spectroscopy (fNIRS) response to hypercapnia.
Time frame: Immediate
Maximum tolerable dose of sildenafil therapy without severe adverse events.
Time frame: 5 weeks
Results and safety
The study was stopped early (reason given: Difficulty enrolling participants due to COVID emergency, and planned start of new study to address this question in a more rigorous fashion.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2022.
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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 1 study testing Sildenafil Citrate in people with Traumatic Brain Injury and Mild Traumatic Brain Injury, run by University of Pennsylvania 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 6 inclusion and 6 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 21 Sep 2022. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Difficulty enrolling participants due to COVID emergency, and planned start of new study to address this question in a more rigorous fashion.). Results are not available in the source record.
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?
Effect of single dose sildenafil citrate treatment on global blood oxygen level-dependent (BOLD) response to hypercapnia. (time frame: Immediate). 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 21 Sep 2022.