Cerebrovascular Reactivity in American Football Players

Traumatic Brain Injury Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03417492
• Other study ID #: 827103
• Status: Terminated
• Phase: Phase 1
• Start date: March 1, 2018
• Est. completion date: June 30, 2022

Study information

• Verified date: September 2022
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Concussion
• Brain Injuries
• Brain Injuries, Traumatic
• Mild Traumatic Brain Injury
• Post-Concussion Syndrome
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	Boston University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Effect of 5 weeks sildenafil treatment on CVR as measured by BOLD response to hypercapnia.	To evaluate the effects of 5 weeks of treatment on CVR by measuring BOLD signal in response to hypercapnia after 5 week treatment with sildenafil, compared to within-subject CVR response before sildenafil treatment.	5 weeks
Other	Effect of 5 weeks sildenafil treatment on CVR as measured by fNIRS response to hypercapnia.	To evaluate the effects of 5 weeks of treatment on CVR by measuring fNIRS signal in response to hypercapnia after 5 week treatment with sildenafil, compared to within-subject CVR response before sildenafil treatment.	5 weeks
Other	Effect of 5 weeks of sildenafil treatment on attention using Trail Making Test Part A.	To evaluate the effects of 5 weeks of treatment with sildenafil citrate on attention, measured using the Trail Making Test Part A.	5 weeks
Other	Effect of 5 weeks of sildenafil treatment on attention using the Digit Symbol Modalities Test.	To evaluate the effects of 5 weeks of treatment with sildenafil citrate on attention, measured using the Digit Symbol Modalities Test.	5 weeks
Other	Effect of 5 weeks of sildenafil treatment on executive function using the Trail Making Test Part B.	To evaluate the effects of 5 weeks of treatment with sildenafil citrate on executive function, measured using the Trail Making Test Part B.	5 weeks
Other	Effect of 5 weeks of sildenafil treatment on executive function using the Neuropsychological Assessment Battery (NAB) mazes.	To evaluate the effects of 5 weeks of treatment with sildenafil citrate on executive function, measured using the Neuropsychological Assessment Battery (NAB) mazes.	5 weeks
Other	Effect of 5 weeks of sildenafil treatment on executive function using the Controlled Oral Word Association Test (COWAT).	To evaluate the effects of 5 weeks of treatment with sildenafil citrate on executive function, measured using the Controlled Oral Word Association Test (COWAT).	5 weeks
Other	Effect of 5 weeks of sildenafil treatment on language and memory using the Animal Fluency test.	To evaluate the effects of 5 weeks of treatment with sildenafil citrate on language and memory, measured using the Animal Fluency test.	5 weeks
Other	Effect of 5 weeks of sildenafil treatment on language and memory using the NAB List Learning test.	To evaluate the effects of 5 weeks of treatment with sildenafil citrate on language and memory, measured using the NAB List Learning test.	5 weeks
Other	Effect of 5 weeks of sildenafil treatment on daily function using the Functional Activities Questionnaire.	To evaluate the effects of 5 weeks of treatment with sildenafil citrate on daily function, measured using the Functional Activities Questionnaire. The questionnaire requires the subject to rate the level of difficulty/dependency of each task listed (rating range from 0-3). A lower score indicates less difficulty in the listed activities while a higher score indicates more difficulty. The ratings are summed and the total score is reported (range 0-30).	5 weeks
Primary	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).	Immediate
Secondary	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).	Immediate
Secondary	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.	5 weeks