Traumatic Brain InjuryBHINCT04708613
University of Pittsburgh Brain Health Initiative
An observational study of Traumatic Brain Injury, run by David Okonkwo, MD, PhD at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 29 to 59 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- Cognitive/Neuropsychological Testing, Vestibular/Ocular-Motor Testing and Sleep Evaluation
- How many people
- 300 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Nov 2019to Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 29 to 59 years
- Men only
- Healthy volunteers accepted
- Adult
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.
Who may be able to join
- Former professional football player/exposed group:
- Professional football retiree aged 29-59
- Played a minimum of 3 professional football seasons, with a minimum of 3 games in each season
- Fluent in English (translations are not available/validated for most neuropsychological tests)
- Control/unexposed group:
- Age 29-59 male
- High school education or beyond
- Fluent in English (translations are not available/validated for most neuropsychological tests)
Who cannot join
- Control/unexposed group:
- Played organized football beyond high school
- History of severe TBI
- Current unstable cardiovascular disorder
- For both groups:
- Prior history of psychosis (such as schizophrenia), or other major neurological disorder that would interfere with testing, in the opinion of the primary investigator.
- Contraindication to MR imaging, such as ferrous metal, pacemakers, or concerns about claustrophobia
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Pittsburgh Department of Neurosurgery
Pittsburgh, Pennsylvania, 15213
Kathryn Edelman, MS, 412-624-1077, dunfeekl@upmc.edu
Jane Sharpless, MS, 412-648-2176, sharplessjm@upmc.edu
About this study
Official title: 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.
- Conditions
- Traumatic Brain Injury
- Being tested
- Cognitive/Neuropsychological Testing, Vestibular/Ocular-Motor Testing, Sleep Evaluation, MRI, High-Resolution, Health & Physical Exam
- Keywords
- Brain Health, Football, Contact Sport, Concussion
- Medical subject headings
- Brain Injuries, Traumatic, Brain Concussion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive/Neuropsychological TestingDiagnostic test
Comprehensive testing of cognitive function and brain health.
Vestibular/Ocular-Motor TestingDiagnostic test
A series of tests and questionnaires that asses vestibular function, balance, ocular-motor coordination, and reflexes.
Sleep EvaluationDiagnostic test
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.
MRI, High-ResolutionDiagnostic test
A high-resolution MRI to provide qualitative and quantitative assessments of brain structure.
Health & Physical ExamDiagnostic test
Participants will undergo an executive history and physical exam of all body systems.
Physical FunctionDiagnostic test
These assessments will involve a series of tests and questionnaires that focus on physical function.
Blood Testing and Biomarker AnalysisDiagnostic test
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,
Applanation TonometryDiagnostic test
Also called Continuous arterial pressure
Hearth health is evaluated through testing of arterial stiffness and pulse wave reflections using a high fidelity applanation tonometer.
PET brain imagingDiagnostic test
PET imaging of the brain using tau and amyloid ligands.
[C-11]6-OH-BTA-1Drug
Also called Pittsburgh Compound B
PET imaging of the brain using an amyloid ligand.
[F-18]AV-1451Drug
Also called [F-18]T807, LY3191748
PET imaging of the brain using a tau ligand.
| Study group | Role | What they receive |
|---|---|---|
| Former Professional Football Players | Former professional football players who played in at least 3 professional seasons, with at least 3 games each season. Receives: 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 | |
| Control Groups | Friends and brothers of the Former Professional Football Player group. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1-week
Secondary outcomes (1)
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.
Measured: 1-week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2021
- Study start18 Nov 2019
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- David Okonkwo, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- National Football League, Avid Radiopharmaceuticals, Harvard University
- Responsible party
- Sponsor-investigator, David Okonkwo, MD, PhD, University of Pittsburgh
- Investigators
- David O Okonkwo, MD, PhD, Principal investigator, University of Pittsburgh Department of Neurological Surgery
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04708613
- Sponsor's protocol ID
- Brain Health Initiative
- Acronym
- BHI
- Status last verified
- Jun 2026
- First submitted
- 5 Jan 2021
- Last updated
- 22 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 14568808Petersen RC. Mild cognitive impairment clinical trials. Nat Rev Drug Discov. 2003 Aug;2(8):646-53. doi: 10.1038/nrd1155. No abstract available.
PubMed 12904814
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevalence of Brain Health Versus Neurodegeneration in Former Professional Football Players
- ClinicalTrials.gov ID
- NCT04708613
- Acronym / sponsor ID
- BHI / Brain Health Initiative
- Conditions
- Traumatic Brain Injury
- Keywords
- Brain Health, Football, Contact Sport, Concussion
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- David Okonkwo, MD, PhDUniversity, hospital or other
- Collaborators
- National Football League, Avid Radiopharmaceuticals, Harvard University
- Study start
- 18 Nov 2019 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 14 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Former Professional Football Players | – | 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-1451Former professional football players who played in at least 3 professional seasons, with at least 3 games each season. |
| Control Groups | – | 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-1451Friends and brothers of the Former Professional Football Player group. |
Who may qualify
- Ages
- 29 to 59 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- 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.
Key inclusion criteria (8 listed)
- Professional football retiree aged 29-59
- Played a minimum of 3 professional football seasons, with a minimum of 3 games in each season
- Fluent in English (translations are not available/validated for most neuropsychological tests)
- Age 29-59 male
- High school education or beyond
Key exclusion criteria (7 listed)
- Played organized football beyond high school
- History of severe TBI
- Current unstable cardiovascular disorder
- Prior history of psychosis (such as schizophrenia), or other major neurological disorder that would interfere with testing, in the opinion of the primary investigator.
- Contraindication to MR imaging, such as ferrous metal, pacemakers, or concerns about claustrophobia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cognitive/Neuropsychological TestingComprehensive testing of cognitive function and brain health. | Diagnostic test | Control Groups, Former Professional Football Players |
| Vestibular/Ocular-Motor TestingA series of tests and questionnaires that asses vestibular function, balance, ocular-motor coordination, and reflexes. | Diagnostic test | Control Groups, Former Professional Football Players |
| Sleep EvaluationA 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 | Control Groups, Former Professional Football Players |
| MRI, High-ResolutionA high-resolution MRI to provide qualitative and quantitative assessments of brain structure. | Diagnostic test | Control Groups, Former Professional Football Players |
| Health & Physical ExamParticipants will undergo an executive history and physical exam of all body systems. | Diagnostic test | Control Groups, Former Professional Football Players |
| Physical FunctionThese assessments will involve a series of tests and questionnaires that focus on physical function. | Diagnostic test | Control Groups, Former Professional Football Players |
| Blood Testing and Biomarker AnalysisA 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 | Control Groups, Former Professional Football Players |
| Applanation TonometryAlso: Continuous arterial pressureHearth health is evaluated through testing of arterial stiffness and pulse wave reflections using a high fidelity applanation tonometer. | Diagnostic test | Control Groups, Former Professional Football Players |
| PET brain imagingPET imaging of the brain using tau and amyloid ligands. | Diagnostic test | Control Groups, Former Professional Football Players |
| [C-11]6-OH-BTA-1Also: Pittsburgh Compound BPET imaging of the brain using an amyloid ligand. | Drug | Control Groups, Former Professional Football Players |
| [F-18]AV-1451Also: [F-18]T807, LY3191748PET imaging of the brain using a tau ligand. | Drug | Control Groups, Former Professional Football Players |
Primary outcome
Rates of Brain Health versus Cognitive Impairment
Time frame: 1-week
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 secondary outcome
Clinical Syndromes of Neurodegeneration
Time frame: 1-week
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2026.
- Background: PubMed 14568808Lopez 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.
- Background: PubMed 12904814Petersen RC. Mild cognitive impairment clinical trials. Nat Rev Drug Discov. 2003 Aug;2(8):646-53. doi: 10.1038/nrd1155. No abstract available.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
David O Okonkwo, MD, PhD principal investigator
University of Pittsburgh Department of Neurological Surgery
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Traumatic Brain Injury, run by David Okonkwo, MD, PhD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kathryn L Edelman, MS (412-624-1077, dunfeekl@upmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rates of Brain Health versus Cognitive Impairment (time frame: 1-week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04708613, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2026.