Clinical trial NCT03417492: Cerebrovascular Reactivity in American Football Players
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Traumatic Brain Injury
Mild Traumatic Brain Injury
Post-Concussion Syndrome
Keywords: TBI
CVR
Hypercapnia
fNIRS
functional magnetic resonance imaging (fMRI)
American football
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: Boston University
First posted: 2018-01-31
Enrollment: 7
Sex: MALE
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, non-placebo controlled
Primary purpose: TREATMENT

Brief 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). 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.


Eligibility criteria: Inclusion Criteria:

1. Age 40-65 years
2. Former National Football League (NFL) players or former varsity college football players
3. Ability to undergo MRI scanning
4. Ability to read, write, and speak English
5. Stable doses of concomitant medications for last 2 weeks prior to enrollment
6. Diagnosis of post-concussive syndrome according to Diagnostic and Statistical Manual 5 (DSM-5) criteria

Exclusion Criteria:

1. Contraindication to sildenafil
2. Past medical history or evidence of penetrating brain injury
3. Daily therapy with a PDE5 inhibitor within the past 2 months, or taken as needed within past 4 weeks
4. History or evidence of pre-existing disabling neurological or psychiatric disorder not related to previous head injuries
5. History of melanoma
6. History of diagnosed obstructive/ restrictive pulmonary disease 7 .) Contraindication to MRI

Primary outcomes:
measure: Effect of single dose sildenafil citrate treatment on global blood oxygen level-dependent (BOLD) response to hypercapnia.
timeFrame: Immediate
Secondary outcomes:
measure: Effect of single dose sildenafil citrate treatment on functional near-infrared spectroscopy (fNIRS) response to hypercapnia.
timeFrame: Immediate
measure: Maximum tolerable dose of sildenafil therapy without severe adverse events.
timeFrame: 5 weeks
Other outcomes:
measure: Effect of 5 weeks sildenafil treatment on CVR as measured by BOLD response to hypercapnia.
timeFrame: 5 weeks
measure: Effect of 5 weeks sildenafil treatment on CVR as measured by fNIRS response to hypercapnia.
timeFrame: 5 weeks
measure: Effect of 5 weeks of sildenafil treatment on attention using Trail Making Test Part A.
timeFrame: 5 weeks
measure: Effect of 5 weeks of sildenafil treatment on attention using the Digit Symbol Modalities Test.
timeFrame: 5 weeks
measure: Effect of 5 weeks of sildenafil treatment on executive function using the Trail Making Test Part B.
timeFrame: 5 weeks
measure: Effect of 5 weeks of sildenafil treatment on executive function using the Neuropsychological Assessment Battery (NAB) mazes.
timeFrame: 5 weeks
measure: Effect of 5 weeks of sildenafil treatment on executive function using the Controlled Oral Word Association Test (COWAT).
timeFrame: 5 weeks
measure: Effect of 5 weeks of sildenafil treatment on language and memory using the Animal Fluency test.
timeFrame: 5 weeks
measure: Effect of 5 weeks of sildenafil treatment on language and memory using the NAB List Learning test.
timeFrame: 5 weeks
measure: Effect of 5 weeks of sildenafil treatment on daily function using the Functional Activities Questionnaire.
timeFrame: 5 weeks
Locations:
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
Study officials:
References: