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University of Pittsburgh Brain Health Initiative (BHI)

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ClinicalTrials.gov Identifier: NCT04708613
Recruitment Status : Recruiting
First Posted : January 14, 2021
Last Update Posted : January 14, 2021
Sponsor:
Collaborators:
National Football League Scientific Advisory Board
Avid Radiopharmaceuticals, Inc.
Harvard University
Information provided by (Responsible Party):
David Okonkwo, MD, PhD, University of Pittsburgh

Brief 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.

Condition or disease Intervention/treatment
Traumatic Brain Injury 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

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Study Type : Observational
Estimated Enrollment : 300 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Prevalence of Brain Health Versus Neurodegeneration in Former Professional Football Players
Actual Study Start Date : November 18, 2019
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2023

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 Name: 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 Name: Pittsburgh Compound B

Drug: [F-18]AV-1451
PET imaging of the brain using a tau ligand.
Other Name: [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 Name: 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 Name: Pittsburgh Compound B

Drug: [F-18]AV-1451
PET imaging of the brain using a tau ligand.
Other Name: [F-18]T807, LY3191748




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Clinical Syndromes of Neurodegeneration [ Time Frame: 1-week ]

    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.




Information from the National Library of Medicine

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Ages Eligible for Study:   29 Years to 59 Years   (Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Females will not be included in the study population. Participants will be prior professional football players, age 29-59, that are eligible for a pension. Control participants will be group-matched for age and gender and therefore females will not be included in the study population.
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.

Criteria

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

Control/unexposed group:

  1. Age 29-59 male
  2. High school education or beyond

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
  3. Non-native English speakers (translations are not available/validated for most neuropsychological tests)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04708613


Contacts
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Contact: Kathryn L Edelman, MS 412-624-1077 dunfeekl@upmc.edu

Locations
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United States, Pennsylvania
University of Pittsburgh Department of Neurosurgery Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Kathryn Edelman, MS    412-624-1077    dunfeekl@upmc.edu   
Contact: Jane Sharpless, MS    412-648-2176    sharplessjm@upmc.edu   
Principal Investigator: David O Okonkwo, MD, PhD         
Principal Investigator: James Mountz, MD, PhD         
Principal Investigator: Michael Collins, PhD         
Principal Investigator: Oscar Lopez, MD         
Principal Investigator: Anthony Kontos, PhD         
Sponsors and Collaborators
David Okonkwo, MD, PhD
National Football League Scientific Advisory Board
Avid Radiopharmaceuticals, Inc.
Harvard University
Investigators
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Principal Investigator: David O Okonkwo, MD, PhD University of Pittsburgh Department of Neurological Surgery
Publications:
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Responsible Party: David Okonkwo, MD, PhD, Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT04708613    
Other Study ID Numbers: Brain Health Initiative
First Posted: January 14, 2021    Key Record Dates
Last Update Posted: January 14, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by David Okonkwo, MD, PhD, University of Pittsburgh:
Brain Health
Football
Contact Sport
Concussion
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Corticosterone
Anti-Inflammatory Agents