Cerebrovascular Reactivity in American Football Players

Phase 1

Terminated

• Conditions: Mild Traumatic Brain Injury; Post-Concussion Syndrome; Traumatic Brain Injury
• Interventions: Drug: Sildenafil Citrate

• Registration Number: NCT03417492
• Lead Sponsor: University of Pennsylvania

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-10-11
• Study First Submitted QC: 2018-01-24
• Study First Posted: 2018-01-31
• Study Start: 2018-03-01
• Primary Completion: 2022-06-30
• Study Completion: 2022-06-30
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-16
• Last Update Posted: 2022-09-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 7

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sildenafil Citrate	Sildenafil Citrate	Open label treatment with forced titration of sildenafil citrate.

Primary Outcome Measures

Name	Time	Method
Effect of single dose sildenafil citrate treatment on global blood oxygen level-dependent (BOLD) response to hypercapnia.	Immediate	Determine if single dose treatment with sildenafil (60 mg orally) is effective in increasing the global BOLD response to hypercapnia (5% CO2).

Secondary Outcome Measures

Name	Time	Method
Effect of single dose sildenafil citrate treatment on functional near-infrared spectroscopy (fNIRS) response to hypercapnia.	Immediate	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).
Maximum tolerable dose of sildenafil therapy without severe adverse events.	5 weeks	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.

Trial Locations

Locations (1)

Penn Presbyterian Medical Center; 🇺🇸 Philadelphia, Pennsylvania, United States