The DIAGNOSE CTE Research Project-II

NCT06860828 | Enrolling By Invitation

• 2 other identifiers: H-454611R01NS139383-01
• Study Type: observational
• Target: 350
• Locations: 1 country
• Sites: 5

Brief Summary

Each year, millions of people are exposed to repetitive head impacts (RHI) through contact sports. RHI can result in concussions and asymptomatic non-concussions to confer risk for Alzheimer's disease (AD) and related dementias (ADRD) including chronic traumatic encephalopathy (CTE). Presently, a diagnosis of CTE can only be rendered at autopsy and it has been neuropathological diagnosed in several hundreds of American football players particularly those who played at elite levels (college and professional). The ability to make an accurate diagnosis of CTE is needed to facilitate research on risk factors, mechanisms, prevention, and treatment. In 2015, the investigators were awarded a NINDS funded 7-year U01 known as the DIAGNOSE CTE Research Project (NCT02798185) designed to develop biomarkers, characterize the clinical presentation, and examine genetic and RHI risk factors for CTE. This current 5-year NIH funded multicenter study DIAGNOSE CTE Research Project-II will build on and extend those findings.

Conditions

Alzheimer Disease; Alzheimer Disease and Related Dementias (ADRD); Brain Injuries, Traumatic; Chronic Traumatic Encephalopathy (CTE)

Keywords

Traumatic encephalopathy syndrome (TES); Repetitive head impacts (RHI); Former national football league players; Former varsity level college football players; Neuroimaging

Outcome Measures

Primary Outcomes (1)

• Delayed recall memory

  Memory will be assessed by the Rey Auditory Verbal Learning Test Delay Recall. The range of scores on this domain is 0 - 15, with a lower score indicating more problems with memory and a higher risk of dementia.

  12 months

Study Arms (3)

Former college and professional football players

150 football players from DIAGNOSE I and an additional 75 former college and football players will be enrolled in DIAGNOSE II for a total anticipated cohort size of 225.

Asymptomatic non-RHI/Controls

50/60 controls from DIAGNOSE I and an additional 25 controls will be enrolled in DIAGNOSE II for a total anticipated cohort size of 75.

Cognitive impairment due to Alzheimer's disease (AD-CI)

50 participants with cognitive impairment due to AD will be enrolled in DIAGNOSE II for an anticipated cohort size of 50.

Eligibility Criteria

• Age: 50 Years+
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Former National Football League Players, Former Varsity Level College Football Players, Healthy Controls, Alzheimer's Disease with cognitive impairment.

You may qualify if:

• Former college or professional football players (n=225) will include those retained from DIAGNOSE-I (n=150) and newly recruited (n=75). Criteria will include
• Former college football players must have played more than 6 years of football including 3 or more years at the college level. They must not have played organized football or other contact sports following college.
• Former professional football players must have played 12 or more years of total football including 3 or more years in college and 4 or more seasons professionally.
• Asymptomatic at screening
• 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
• No known traumatic brain injury (TBI) and/or moderate/severe concussion (severity determined on phone screening).
• BMI of 24 or higher to be similar in body habitus to former professional and college football players.
• Must have at least 2 years of 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.
• CDR of 0.5-1.0
• Positive amyloid PET or CSF AD biomarker within 12 months of study visit (done as part of their participation in the local ADRCs and/or clinical care).
• BMI of 24 or higher to be similar in body habitus to former professional and college football players.
• No prior anti-amyloid monoclonal antibody treatments or therapeutic trials targeting amyloid or tau prior to initiating study
• Tracer comparison sub-sample: 20 professional football players from DIAGNOSE-I will have FTP and MK-6240 tau PET (done at the same site, scanner). The 20 participants at highest risk for having CTE pathology will be selected based on the following:
• + years old to increase likelihood of meaningful pathology
• Must have played professionally

You may not qualify if:

• Unstable medical conditions that confound our ability to diagnose neurodegenerative disease accurately (e.g., active cancer with recent chemotherapy or radiation treatments, unstable heart disease particularly if oxygen dependent, kidney disease requiring dialysis)
• Neurological conditions that confound our ability to diagnose neurodegenerative disease accurately (e.g., acute clinical stroke, severe traumatic brain injury with ongoing symptoms \[post-football for football players\])
• Serious mental Illnesses that confound our ability to diagnose neurodegenerative disease accurately (e.g., active psychosis)
• Inability to fulfill research protocol requirements due to physical, visual, or hearing impairment
• English is not primary language
• Unable to travel to 1 of the five study sites to participate
• Lack of an adequate informant to be available in-person or by telephone for each annual research evaluation. Informant must be 18 years or older, speaks/visits with the participant at least 1X per week for a minimum of 6 months, agree to complete questionnaires about participant, able to travel to study visit if determined it is needed, and is knowledgeable regarding changes to the participant's cognition, mood and behavior
• Lack of capacity to provide informed consent (IC) or does not have a legal authorized representative or guardian who can provide surrogate IC
• Unwilling to attempt to have an MRI
• If willing to complete MRI, contraindications to 3T MRI (e.g., pacemaker, select aneurismal clip, artificial heart valve, select ear implants, select stents incompatible with 3T MRI, metal fragments or foreign objects in the eyes, skin or body, etc.)
• Investigational agents are prohibited 30 days prior to entry
• Initiated medication (investigational or for clinical care) against tau or amyloid proteins prior to their baseline study visit
• History of a relevant severe drug allergy or hypersensitivity
• Inability to urinate
• Any serious illness that, in the study physician's opinion could interfere with the completion of the PET scans or post a potential safety risk

Sponsors & Collaborators

• Boston University: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• University of California, San Francisco (UCSF) Alzheimer Disease Research Center (ADRC): collaborator
• 1Florida ADRC, University of Florida: collaborator
• University of Texas Health Science Center at San Antonio (South Texas) ADRC: collaborator
• Laboratory of Neuro Imaging (LONI) at University of Southern California (USC): collaborator
• Concussion Legacy Foundation (CLF): collaborator
• Banner Alzheimer's Institute: collaborator

Study Sites (5)

Banner Alzheimer's Institute (BAI) and Mayo Clinic Arizona

Phoenix, Arizona, 85006, United States

Location

University of California, San Francisco (UCSF) Alzheimer Disease Research Center (ADRC)

San Francisco, California, 94143, United States

Location

1Florida ADRC, University of Florida

Gainesville, Florida, 32610, United States

Location

Boston University Alzheimer Disease Research Center (ADRC)

Boston, Massachusetts, 02118, United States

Location

South Texas ADRC University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

DNA will be extracted from the buffy coat for APOE genotyping as well as to develop a genetic risk score algorithm for CTE. Interactions between RHI and select Single Nucleotide Polymorphisms (SNPs) will be used to examine the modification of RHI-related risk by genetic susceptibility for CTE.

MeSH Terms

Conditions

Chronic Traumatic Encephalopathy; Alzheimer Disease; Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Injury, Chronic; Neurodegenerative Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Damage, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Wounds and Injuries; Dementia; Tauopathies; Neurocognitive Disorders; Mental Disorders

Study Officials

• Michael Alosco, PhD

  Boston University Alzheimer's Disease and CTE Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2025
• First Posted: March 6, 2025
• Study Start: April 9, 2025
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)