The DIAGNOSE-CTE Research Project (DIAGNOSE-CTE)

• ClinicalTrials.gov Identifier: NCT02798185
• Recruitment Status: Active, not recruiting
• First Posted: June 14, 2016
• Last Update Posted: March 4, 2020
• Sponsor: Boston University
• Collaborators: Mayo Clinic; Banner Health; Brigham and Women's Hospital; NYU Langone Health; The Cleveland Clinic; National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): Robert A. Stern, Boston University

Study Description

Brief Summary:

This is a study to develop methods of diagnosing chronic traumatic encephalopathy (CTE) during life, as well as to examine possible risk factors for this neurodegenerative disease. One component of this study is the use of an investigational PET scan radio tracer to detect abnormal tau protein in the brain.

Condition or disease
Chronic Traumatic Encephalopathy

Detailed Description:

Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease characterized by a distinct deposition of phosphorylated tau (p-tau) in neurons and astrocytes in a pattern that is unique from other tauopathies, including Alzheimer's disease (AD). Although the neuropathological features of CTE have become further clarified in recent years, the clinical presentation of CTE is still not well characterized. Diagnostic criteria have only recently been published and lack validation.

Neuroimaging and fluid biomarkers developed for the diagnosis of other neurodegenerative diseases have only been used in preliminary studies of individuals at high risk for CTE, namely athletes with histories of significant exposure to repetitive head impacts (RHI), such as former football players and boxers. There is thus an urgent need to develop accurate methods for detecting and diagnosing CTE during life so that effective interventions for prevention and treatment can be developed. Moreover, though a history of RHI is a necessary risk factor for CTE, it alone is not sufficient. There is a need to understand what specific aspects of RHI exposure places an individual at increased risk for CTE and to examine potential genetic polymorphisms that modify that risk.

To address these needs, the investigators are conducting a multidisciplinary, multicenter, longitudinal study of former NFL and varsity college football players (with and without symptoms), and a control group of asymptomatic same-age men without any history of RHI exposure, traumatic brain injury or military service. Subjects will be seen at 1 of 4 participating study sites in Boston; Las Vegas, ; New York; and Scottsdale/Phoenix . Subjects will undergo a baseline evaluation and a 3 year follow-up evaluation (currently former college players will not complete the follow-up evaluation). Each evaluation will be take place over a 3 day period and consist of the following procedures/tests: neurocognitive testing, determination of functional independence, neuropsychiatric examination (with measures of mood and behavior), neurological assessment (motor, headache, postural stability), neuroimaging (including structural, diffusion, functional, biochemical, and molecular imaging), lumbar punctures (for Cerebrospinal Fluid (CSF) biomarkers), blood draws (for blood biomarkers and DNA), and saliva samples (for biomarkers).

Study Design

• Study Type: Observational
• Actual Enrollment: 240 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Diagnostics, Imaging And Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project
• Study Start Date: August 2016
• Estimated Primary Completion Date: July 2023
• Estimated Study Completion Date: July 2023

Groups and Cohorts

Group/Cohort
Former NFL Players; 120 former National Football League players with and without reported cognitive, mood and behavior symptoms will be enrolled in this study.
Former College Football Players; 60 former college football players with and without reported cognitive, mood and behavior symptoms will be enrolled in this study.
Control Group; 60 asymptomatic same-age men without any history of participation in contact sports, military service, or traumatic brain injury will be enrolled in this study.

Outcome Measures

Primary Outcome Measures :

1. Neuroimaging Positron Emission Tomography for Amyloid Biomarker [ Time Frame: One-Time ]

   Subjects will undergo a Florbetapir Positron Emission Tomography (PET) scan.

   The Outcome Measurement for the Florbetapir PET Scan will be "elevated" or "not elevated"

2. Fluid Biomarkers [ Time Frame: 3 Years ]

   The following Biospecimens will be collected from subjects:

   Saliva, blood and cerebral spinal fluid (CSF). CSF will be collected by a lumbar puncture (spinal tap) Fluid biomarkers will be analyzed for the in vivo detection of CTE.

3. Neuropsychiatric and Neurocognitive Tests [ Time Frame: 3 years ]

   Composite scores (presented as z scores) based on factor analytic methodology in the following domains:

   • Mood
   • Behavior Regulation
   • Attention, Information Processing and Psychomotor Speed
   • Executive Functioning
   • Verbal Memory
   • Visual Memory
   • Visual-Spatial Ability
   • Language
4. Neurological Evaluation [ Time Frame: 3 years ]
   Subjects will undergo The Movement Disorder Society's Unified Parkinson's Disorders Rating Scale (MDS-UPDRS) Neurological Evaluation by a physician. This evaluation will be analyzed to characterize the clinical presentation of CTE.
5. Magnetic Resonance Imagining Biomarkers [ Time Frame: 3 years ]
   Subjects will undergo Diffuser Tension Imaging (dti) and Functional MRI scans, to assess structural brain volumetrics, fractional anisotropy, radial diffusivity, and changes in brain activity associated with blood flow.
6. Neuroimaging Positron Emission Tomography for Tau Biomarker [ Time Frame: 3 years ]

   Subjects will undergo an Investigational drug: AV1451 Positron Emission Tomography (PET) scan.

   The Outcome Measurement for AV1451 PET scan will be Standardized Uptake Value Ratio (SUVR) of Tau.

7. Magnetic Resonance Spectroscopy Biomarkers [ Time Frame: 3 years ]
   Subject will also undergo Magnetic Resonance Spectroscopy (MRS) to measure glutamate, glutamine and myoinosotol.

Biospecimen Retention:   Samples With DNA

Biospecimen samples to be collected include: saliva, blood and cerebral spinal fluid (CSF)

Eligibility Criteria

• Ages Eligible for Study: 45 Years to 74 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Former National Football League Players, Former Varsity Level College Football Players, Healthy Controls

Criteria

Inclusion Criteria:

Former NFL Players:

• English as primary language
• No MRI or Lumbar Puncture (LP) contraindications
• Have played ≥12 years of organized football (including =>3 in college and =>3 seasons in the NFL)
• Must have played one of following positions offensive lineman, defensive lineman, linebacker, tight end, wide receiver, running back, or defensive back.
• Agree to provide name and contact information of a study partner who will complete questionnaires regarding subject's mood, behavior, thinking and cognitive function should the subject enroll in the study.

Former Collegiate Football Players

• English as primary language
• No MRI or Lumbar Puncture (LP) contraindications
• Must have played =>6 years of organized football (with => 3 years at the college level, but no organized football or other contact sport following college.)
• Must have played one of following positions offensive lineman, defensive lineman, linebacker, tight end, wide receiver, running back, or defensive back.
• No military service
• Agree to provide name and contact information of a study partner who will complete questionnaires regarding subject's mood, behavior, thinking and cognitive function should the subject enroll in the study.

Control Group

• English as primary language
• No MRI or Lumbar Puncture (LP) contraindications
• No history of organized contact sports or known traumatic brain injury (TBI) and/or moderate/severe concussions
• No history of participation in any of the following organized sports at any level: football, hockey, rugby, soccer, lacrosse, wrestling, boxing, gymnastics, martial arts, and kickboxing.
• No military service.
• Must have BMI >=24
• Must have at least 2 years post-secondary education at a 4-year accredited college or university, or have an associate's degree if they did not attend a 4-year accredited college or university
• Must have never been diagnosed with, or treated for, any of the following: depression, manic-depressive or bipolar disorder, anxiety, or other psychiatric or mental health problems
• Agree to provide name and contact information of a study partner who will complete questionnaires regarding subject's mood, behavior, thinking and cognitive function should the subject enroll in the study.
• Must be asymptomatic when screened by telephone.

Former NFL and Varsity Collegiate Football Players Exclusion Criteria:

• If they do not meet inclusion criteria
• If they have a history of clinical stroke confirmed on neuroimaging
• If they have vision or hearing impairment significant enough to compromise neuropsychological testing
• If they have been hospitalized or treated in an emergency room following a severe injury to their head since they stopped playing football
• If they are unable to undergo MRI/PET Scan
• If they have a spinal fusion at L3-4 and/or L4-5
• If they are unable to travel to one of 4 study sites to participate
• If they are an insulin dependent diabetic
• If they cannot provide the name and contact information of an eligible study partner
• If they are taking blood thinners that would make LP unsafe
• If they have a type of abnormal heart rhythm called Torsades de pointes AKA TdP
• If they have an abnormal heart rhythm disorder called QT Prolongation or take certain medications known to cause QT Prolongation
• If they do not agree to all study tests and procedures
• If they are unable to consent to study procedures

Control Group Exclusion:

• If they do not meet inclusion criteria
• If they have vision or hearing impairment significant enough to compromise neuropsychological testing
• If they are unable to undergo MRI/PET Scan
• If they have a spinal fusion at L3-4 and/or L4-5
• If they are an insulin dependent diabetic
• If they are unable to travel to one of 4 study sites to participate
• If they cannot provide the name and contact information of an eligible study partner
• If they report any cognitive concerns or dementia during screening process
• If they have a type of abnormal heart rhythm called Torsades de pointes AKA TdP
• If they have an abnormal heart rhythm disorder called QT Prolongation or take certain medications known to cause QT Prolongation
• If they are unable to consent to study procedures

Contacts and Locations

Locations

United States, Massachusetts

Boston University School of Medicine

Boston, Massachusetts, United States, 02118

Sponsors and Collaborators

Boston University

Mayo Clinic

Banner Health

Brigham and Women's Hospital

NYU Langone Health

The Cleveland Clinic

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Robert A Stern, PhD; Boston University

More Information

Additional Information:

Study website 

• Responsible Party: Robert A. Stern, Primary Investigator, Boston University
• ClinicalTrials.gov Identifier: NCT02798185
• Other Study ID Numbers: H-34799; U01NS093334 ( U.S. NIH Grant/Contract )
• First Posted: June 14, 2016
• Last Update Posted: March 4, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified data will be shared with FITBIR and other data sharing portals

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Brain Diseases; Brain Injuries, Traumatic; Chronic Traumatic Encephalopathy; Central Nervous System Diseases; Nervous System Diseases; Brain Injuries; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Brain Injury, Chronic; Neurodegenerative Diseases