The DIAGNOSE-CTE Research Project

Chronic Traumatic Encephalopathy Clinical Trial

— DIAGNOSE-CTE  

Official title:

Diagnostics, Imaging And Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02798185
• Other study ID #: H-34799
• Secondary ID: U01NS093334
• Status: Completed
• Start date: August 2016
• Est. completion date: November 15, 2023

Study information

• Verified date: December 2023
• Source: Boston University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: November 15, 2023
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 45 Years to 74 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Diseases
• Brain Injuries, Traumatic
• Chronic Traumatic Encephalopathy

Locations

Country	Name	City	State
United States	Boston University School of Medicine	Boston	Massachusetts

Sponsors (7)

Lead Sponsor	Collaborator
Boston University	Banner Health, Brigham and Women's Hospital, Mayo Clinic, National Institute of Neurological Disorders and Stroke (NINDS), NYU Langone Health, The Cleveland Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neuroimaging Positron Emission Tomography for Amyloid Biomarker	Subjects will undergo a Florbetapir Positron Emission Tomography (PET) scan.; The Outcome Measurement for the Florbetapir PET Scan will be "elevated" or "not elevated"	One-Time
Primary	Fluid Biomarkers	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 Years
Primary	Neuropsychiatric and Neurocognitive Tests	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	3 years
Primary	Neurological Evaluation	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.	3 years
Primary	Magnetic Resonance Imagining Biomarkers	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.	3 years
Primary	Neuroimaging Positron Emission Tomography for Tau Biomarker	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.	3 years
Primary	Magnetic Resonance Spectroscopy Biomarkers	Subject will also undergo Magnetic Resonance Spectroscopy (MRS) to measure glutamate, glutamine and myoinosotol.	3 years

External Links

•   Study website