University of Pittsburgh Brain Health Initiative (BHI)

Prevalence of Brain Health Versus Neurodegeneration in Former Professional Football Players

This project will define the prevalence of brain health (i.e., normal cognitive, neuromotor, behavioral function) in living professional football retirees and group-matched controls through a comprehensive assessment of clinical, neuroimaging, and biomarker measures.

Study Overview

• Status: Recruiting
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Diagnostic test: Cognitive/Neuropsychological Testing; Diagnostic test: Vestibular/Ocular-Motor Testing; Diagnostic test: Sleep Evaluation; Diagnostic test: MRI, High-Resolution; Diagnostic test: Health & Physical Exam; Diagnostic test: Physical Function; Diagnostic test: Blood Testing and Biomarker Analysis; Diagnostic test: Applanation Tonometry; Diagnostic test: PET brain imaging; Drug: [C-11]6-OH-BTA-1; Drug: [F-18]AV-1451

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Kathryn L Edelman, MS; Phone Number: 412-624-1077; Email: dunfeekl@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh Department of Neurosurgery
      • Principal Investigator: Oscar Lopez, MD
      • Principal Investigator: David O Okonkwo, MD, PhD
      • Contact: Kathryn Edelman, MS; Phone Number: 412-624-1077; Email: dunfeekl@upmc.edu
      • Contact: Jane Sharpless, MS; Phone Number: 412-648-2176; Email: sharplessjm@upmc.edu
      • Principal Investigator: James Mountz, MD, PhD
      • Principal Investigator: Anthony Kontos, PhD
      • Principal Investigator: Michael Collins, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 29 years to 59 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

1. Professional Football Players:

   There will be 2 cohorts of former professional football players in this group: (a) random sample, and (b) non-random sample.

   1. Random-Sample participants

      Recruitment of random-sample former professional football players will be conducted via collaboration with the Football Players Health Study (FPHS) at Harvard University. Subjects for the Brain Health Initiative (BHI) will include a random sample of enrollees in the FPHS who meet basic eligibility for BHI.

   2. Non-Random participants:

   We will also enroll a non-random cohort of former professional football players that will be comprised of volunteers.

2. Controls:

There will be 3 cohorts of unexposed controls in this group: (a) friends of former players, (b) brothers or former players, and (c) general population. Football players will be invited to refer friend(s) and/or brother(s), but it is not required for participation.

Description

Inclusion criteria:

Former professional football player/exposed group:

1. Professional football retiree aged 29-59
2. Played a minimum of 3 professional football seasons, with a minimum of 3 games in each season
3. Fluent in English (translations are not available/validated for most neuropsychological tests)

Control/unexposed group:

1. Age 29-59 male
2. High school education or beyond
3. Fluent in English (translations are not available/validated for most neuropsychological tests)

Exclusion criteria:

Control/unexposed group:

1. Played organized football beyond high school
2. History of severe TBI
3. Current unstable cardiovascular disorder

For both groups:

1. Prior history of psychosis (such as schizophrenia), or other major neurological disorder that would interfere with testing, in the opinion of the primary investigator.
2. Contraindication to MR imaging, such as ferrous metal, pacemakers, or concerns about claustrophobia

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Former Professional Football Players; Former professional football players who played in at least 3 professional seasons, with at least 3 games each season.	Diagnostic test: Cognitive/Neuropsychological Testing; Comprehensive testing of cognitive function and brain health.; Diagnostic test: Vestibular/Ocular-Motor Testing; A series of tests and questionnaires that asses vestibular function, balance, ocular-motor coordination, and reflexes.; Diagnostic test: Sleep Evaluation; A full assessment of sleep health, including insomnia (duration, frequency, daytime consequences) and other sleep disorders such as obstructive sleep apnea. Overnight sleep study is included.; Diagnostic test: MRI, High-Resolution; A high-resolution MRI to provide qualitative and quantitative assessments of brain structure.; Diagnostic test: Health & Physical Exam; Participants will undergo an executive history and physical exam of all body systems.; Diagnostic test: Physical Function; These assessments will involve a series of tests and questionnaires that focus on physical function.; Diagnostic test: Blood Testing and Biomarker Analysis; A blood draw will be performed to measure standard clinical labs as part of a full history and physical, as well as additional analysis of biomarkers indicative of brain health. An optional lumbar puncture will be performed and CSF samples (20-30 mL) stored in the NCTC Biorepository until shipment to the CLIA-certified laboratory. Both CSF and blood samples will be analyzed for t-tau, p-tau, and Aβ42 and stored for future testing,; Diagnostic test: Applanation Tonometry; Hearth health is evaluated through testing of arterial stiffness and pulse wave reflections using a high fidelity applanation tonometer.; Other Names: Continuous arterial pressure; Diagnostic test: PET brain imaging; PET imaging of the brain using tau and amyloid ligands.; Drug: [C-11]6-OH-BTA-1; PET imaging of the brain using an amyloid ligand.; Other Names: Pittsburgh Compound B; Drug: [F-18]AV-1451; PET imaging of the brain using a tau ligand.; Other Names: [F-18]T807, LY3191748
Control Groups; Friends and brothers of the Former Professional Football Player group.	Diagnostic test: Cognitive/Neuropsychological Testing; Comprehensive testing of cognitive function and brain health.; Diagnostic test: Vestibular/Ocular-Motor Testing; A series of tests and questionnaires that asses vestibular function, balance, ocular-motor coordination, and reflexes.; Diagnostic test: Sleep Evaluation; A full assessment of sleep health, including insomnia (duration, frequency, daytime consequences) and other sleep disorders such as obstructive sleep apnea. Overnight sleep study is included.; Diagnostic test: MRI, High-Resolution; A high-resolution MRI to provide qualitative and quantitative assessments of brain structure.; Diagnostic test: Health & Physical Exam; Participants will undergo an executive history and physical exam of all body systems.; Diagnostic test: Physical Function; These assessments will involve a series of tests and questionnaires that focus on physical function.; Diagnostic test: Blood Testing and Biomarker Analysis; A blood draw will be performed to measure standard clinical labs as part of a full history and physical, as well as additional analysis of biomarkers indicative of brain health. An optional lumbar puncture will be performed and CSF samples (20-30 mL) stored in the NCTC Biorepository until shipment to the CLIA-certified laboratory. Both CSF and blood samples will be analyzed for t-tau, p-tau, and Aβ42 and stored for future testing,; Diagnostic test: Applanation Tonometry; Hearth health is evaluated through testing of arterial stiffness and pulse wave reflections using a high fidelity applanation tonometer.; Other Names: Continuous arterial pressure; Diagnostic test: PET brain imaging; PET imaging of the brain using tau and amyloid ligands.; Drug: [C-11]6-OH-BTA-1; PET imaging of the brain using an amyloid ligand.; Other Names: Pittsburgh Compound B; Drug: [F-18]AV-1451; PET imaging of the brain using a tau ligand.; Other Names: [F-18]T807, LY3191748

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of Brain Health versus Cognitive Impairment	The diagnosis of cognitive impairment is based on the ADRC National Alzheimer's Coordinating Center (NACC) criteria for mild cognitive impairment. This criteria is adjudicated following a comprehensive neuropsychological exam, and includes: (1) Self- or informant-reported cognitive complaint, (2) Objective cognitive impairment, (3) Preserved independence in functional abilities, and (4) No dementia.	1-week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Syndromes of Neurodegeneration	The determination of trauma-related neurodegeneration will be based on: 1) presence of cognitive deficits, and/or neuromotor manifestations, and/or behavioral/mood-related symptoms; 2) PET scans demonstrating abnormal amyloid and/or tau deposition; 3) quantitative MR evidence of cortical volume loss and/or white matter injury; and 4) elevated CSF tau/Aβ42 ratio. These multiple measures will be combined to arrive at a single overall outcome measure. This will be adjudicated at a blinded Diagnostic Consensus Conference comprised of experts from each field.	1-week

Collaborators and Investigators

• Sponsor: David Okonkwo, MD, PhD
• Collaborators: Harvard University; National Football League Scientific Advisory Board; Avid Radiopharmaceuticals, Inc.
• Investigators: Principal Investigator: David O Okonkwo, MD, PhD, University of Pittsburgh Department of Neurological Surgery

Publications and helpful links

General Publications

• Lopez OL, Jagust WJ, DeKosky ST, Becker JT, Fitzpatrick A, Dulberg C, Breitner J, Lyketsos C, Jones B, Kawas C, Carlson M, Kuller LH. Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1. Arch Neurol. 2003 Oct;60(10):1385-9. doi: 10.1001/archneur.60.10.1385.
• Petersen RC. Mild cognitive impairment clinical trials. Nat Rev Drug Discov. 2003 Aug;2(8):646-53. doi: 10.1038/nrd1155. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2019
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: January 5, 2021
• First Submitted That Met QC Criteria: January 13, 2021
• First Posted (Actual): January 14, 2021

Study Record Updates

• Last Update Posted (Actual): August 8, 2023
• Last Update Submitted That Met QC Criteria: August 4, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Concussion; Football; Brain Health; Contact Sport
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic; Anti-Inflammatory Agents; Corticosterone
• Other Study ID Numbers: Brain Health Initiative

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No