Cerebrovascular Reactivity in American Football Players

NCT03417492 | Terminated Phase 1 FDA Drug

• 1 other identifier: 827103
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Traumatic Brain Injury; Mild Traumatic Brain Injury; Post-Concussion Syndrome

Keywords

TBI; CVR; Hypercapnia; fNIRS; functional magnetic resonance imaging (fMRI); American football

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Effect of single dose sildenafil citrate treatment on functional near-infrared spectroscopy (fNIRS) response to hypercapnia.

  Immediate

• Maximum tolerable dose of sildenafil therapy without severe adverse events.

  5 weeks

Other Outcomes (10)

• Effect of 5 weeks sildenafil treatment on CVR as measured by BOLD response to hypercapnia.

  5 weeks

• Effect of 5 weeks sildenafil treatment on CVR as measured by fNIRS response to hypercapnia.

  5 weeks

• Effect of 5 weeks of sildenafil treatment on attention using Trail Making Test Part A.

  5 weeks

Study Arms (1)

Sildenafil Citrate

EXPERIMENTAL

Open label treatment with forced titration of sildenafil citrate.

Drug: Sildenafil Citrate

Interventions

Sildenafil Citrate DRUG

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.

Also known as: Open label forced titration with sildenafil citrate.

Sildenafil Citrate

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pennsylvania: lead
• Boston University: collaborator

Study Sites (1)

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic; Brain Concussion; Post-Concussion Syndrome; Hypercapnia

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Head Injuries, Closed; Wounds, Nonpenetrating; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Presidential Professor

Model Details: Open-label, non-placebo controlled

Study Record Dates

• First Submitted: October 11, 2017
• First Posted: January 31, 2018
• Study Start: March 1, 2018
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2022
• Last Updated: September 21, 2022

Record last verified: 2022-09

Locations

US (1)