Chronic Traumatic Encephalopathy (CTE)NCT06860828
The DIAGNOSE CTE Research Project-II
An observational study of Chronic Traumatic Encephalopathy (CTE) and Alzheimer Disease, run by Boston University at 5 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 50 years and older, men onlyHealthy volunteers can take part
- Conditions the study is for
- Chronic Traumatic Encephalopathy (CTE), Alzheimer Disease, Alzheimer Disease and Related Dementias (ADRD)
- How many people
- 350 participants
- Where
- 5 sitesUnited States
- Study dates
- 9 Apr 2025to Jul 2029
- 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 50 years and older
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Former National Football League Players, Former Varsity Level College Football Players, Healthy Controls, Alzheimer's Disease with cognitive impairment.
Who may be able to join
- 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 at least 1 season professionally where they played in at least 1 game (as corroborated by https://www.pro-football-reference.com)
- Control (n=75) will include those retained from DIAGNOSE-I (n=50) and newly recruited (n=25). Inclusion criteria for control include:
- 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
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- No known traumatic brain injury (TBI) and/or moderate/severe concussion (severity determined on phone screening).
- No history of RHI including participation in contact and collision sports (i.e., football, ice hockey, rugby, soccer, lacrosse, wrestling, boxing gymnastics, martial arts, kickboxing), or military service (refers to active combat experience or combat training involving exposure to IED blasts or combatant stick training). These are examples and there might be instances of other RHI sources that could be exclusionary as determined by investigators.
- 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.
- AD-CI (n=50) will come from the local ADRCs where Clinical Dementia Rating (CDR) and amyloid biomarker status are known for most participants being followed annually. Inclusion criteria include:
- CDR of 0.5-1.0 within 6-12 months of study visit
- 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).
- No history of RHI including participation in contact and collision sports (i.e., football, ice hockey, rugby, soccer, lacrosse, wrestling, boxing gymnastics, martial arts, kickboxing), or military service (refers to active combat experience or combat training involving exposure to IED blasts or combatant stick training). These are examples and there might be instances of other RHI sources that could be exclusionary as determined by investigators.
- BMI of 24 or higher to be similar in body habitus to former professional and college football players.
- If possible, baseline visit should be conducted before the initiation of anti-amyloid monoclonal antibody treatments or therapeutic trials targeting amyloid; however, will allow participants that recently started treatment. Baseline must be completed within 3-months of treatment initiation.
- No prior 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:
- 60+ years old to increase likelihood of meaningful pathology
- Must have played professionally
- Participant was amyloid PET negative at the baseline DIAGNOSE-I evaluation to rule out potential confounding from AD
- To further enrich the sample, we will also use the following to guide selection of participants:
- Must have TES-Cognitive Impairment (from baseline DIAGNOSE-I consensus conference) and participant QDRS >=2 (consistent with CDR diagnosis of mild cognitive impairment ) with a prioritization of individuals who have a QDRS >= 6.0 (equivalent to a CDR=1 or mild dementia) AND/OR
- Must have evidence of tau (FTP) PET uptake from their baseline DxCTE-1 scan, as determined by Dr. Rabinovici's lab.
- For newly recruited, those individuals who meet any of the following criteria are not eligible for enrollment as study participants.
Who cannot join
- 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
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- 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.)
- For all participants (retention and expansion), the following will be exclusionary for participating in PET scan activities:
- Medical radiation exposure will be assessed by the study physician. If the candidate participant has had more than one research nuclear medicine study in the prior 12 months, study inclusion will require joint PI approval.
- Investigational agents are prohibited 30 days prior to entry
- Initiated medication (via participation in clinicaltrials) against tau 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
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites
Boston University Alzheimer Disease Research Center (ADRC)
Boston, Massachusetts, 02118
1Florida ADRC, University of Florida
Gainesville, Florida, 32610
Banner Alzheimer's Institute (BAI) and Mayo Clinic Arizona
Phoenix, Arizona, 85006
South Texas ADRC University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
University of California, San Francisco (UCSF) Alzheimer Disease Research Center (ADRC)
San Francisco, California, 94143
About this study
Official title: Risk and Resilience, Clinical Presentation, and Biomarker Profiles of Chronic Traumatic Encephalopathy and Related Dementias: The DIAGNOSE CTE Research Project-II
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.
Read the detailed description
The aims of the DIAGNOSE CTE Research Project-II are to:
- retain and grow DIAGNOSE-I and examine the clinical and biomarker course of Traumatic Encephalopathy Syndrome (TES);
- investigate risk and resilience factors of TES; and
- compare biomarkers of amyloid (Aβ), p-tau, neurodegeneration, neuroinflammation, and white matter (WM) injury between TES and AD.
The investigators hypothesize that TES has unique clinical and biomarker profiles, and RHI and non-RHI risk factors influence the development of TES.
There will be 3 study groups:
- Retention, 150 former football players and 50 controls retained from DIAGNOSE-I;
- Expansion, the investigators will grow DIAGNOSE-I by newly recruiting 75 former college and professional football players and 25 controls;
- AD, 50 Aβ+ participants with cognitive impairment. In total, the investigators will study 225 former football players, 75 controls, and 50 AD.
Participants will complete a single visit, including clinical exams, social determinants of health (SDOH) measures, MRI, blood draw, and tau PET, at 1 of 5 P30 AD Research Centers (ADRCs): Boston University (BU), University of California, San Francisco (UCSF), Arizona/Banner Alzheimer's Institute (BAI), University of Florida (1Florida), and University of Texas Health Science Center at San Antonio (South Texas).
The Retention Cohort will have 18F-Flortaucipir (18F-AV-1451, Tauvid (FTP)) PET to study its longitudinal value. The Expansion Cohort will have 18F-MK-6240 (MK-6240) PET to build on the investigators' preliminary data. A subset of the Retention Cohort (n=20) will have FTP and MK-6240 for tracer comparison. Blood will be analyzed for 6 p-tau epitopes, Aβ40/42, neuroinflammation, and WM injury. DIAGNOSE-I participants were asked to pledge to donate their brain.
This study will permit continued brain donation and clinical-pathological validation studies. Results will provide insight into the detection, diagnosis, and prognosis for people living with CTE, paving the way for treatment trials.
- Conditions
- Chronic Traumatic Encephalopathy (CTE), Alzheimer Disease, Alzheimer Disease and Related Dementias (ADRD), Brain Injuries, Traumatic
- Keywords
- Traumatic encephalopathy syndrome (TES), Repetitive head impacts (RHI), Former national football league players, Former varsity level college football players, Neuroimaging
- Medical subject headings
- Chronic Traumatic Encephalopathy, Alzheimer Disease, Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2025
- Study start9 Apr 2025
- Primary completionJul 2029 (estimated)
- Study completionJul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Traumatic Encephalopathy (CTE)Studies 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Boston University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), University of California, San Francisco, University of Florida, University of Texas Health Science Center at San Antonio (South Texas) ADRC, Laboratory of Neuro Imaging (LONI) at University of Southern California (USC), Concussion Legacy Foundation (CLF), Banner Alzheimer's Institute
- Responsible party
- Sponsor
- Investigators
- Michael Alosco, PhD, Principal investigator, Boston University Alzheimer's Disease and CTE Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06860828
- Sponsor's protocol ID
- H-45461
- Other IDs
- 1R01NS139383-01
- Status last verified
- May 2026
- First submitted
- 14 Feb 2025
- Last updated
- 2 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Risk and Resilience, Clinical Presentation, and Biomarker Profiles of Chronic Traumatic Encephalopathy and Related Dementias: The DIAGNOSE CTE Research Project-II
- ClinicalTrials.gov ID
- NCT06860828
- Acronym / sponsor ID
- H-45461
- Conditions
- Chronic Traumatic Encephalopathy (CTE), Alzheimer Disease, Alzheimer Disease and Related Dementias (ADRD), Brain Injuries, Traumatic
- Keywords
- Traumatic encephalopathy syndrome (TES), Repetitive head impacts (RHI), Former national football league players, Former varsity level college football players, Neuroimaging
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- Boston UniversityUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), University of California, San Francisco, University of Florida, University of Texas Health Science Center at San Antonio (South Texas) ADRC, Laboratory of Neuro Imaging (LONI) at University of Southern California (USC), Concussion Legacy Foundation (CLF), Banner Alzheimer's Institute
- Study start
- 9 Apr 2025 (actual)
- Primary completion
- Jul 2029 (estimated)
- Study completion
- Jul 2029 (estimated)
- First posted
- 6 Mar 2025 (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.
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.
Detailed description
The aims of the DIAGNOSE CTE Research Project-II are to:
- retain and grow DIAGNOSE-I and examine the clinical and biomarker course of Traumatic Encephalopathy Syndrome (TES);
- investigate risk and resilience factors of TES; and
- compare biomarkers of amyloid (Aβ), p-tau, neurodegeneration, neuroinflammation, and white matter (WM) injury between TES and AD.
The investigators hypothesize that TES has unique clinical and biomarker profiles, and RHI and non-RHI risk factors influence the development of TES.
There will be 3 study groups:
- Retention, 150 former football players and 50 controls retained from DIAGNOSE-I;
- Expansion, the investigators will grow DIAGNOSE-I by newly recruiting 75 former college and professional football players and 25 controls;
- AD, 50 Aβ+ participants with cognitive impairment. In total, the investigators will study 225 former football players, 75 controls, and 50 AD.
Participants will complete a single visit, including clinical exams, social determinants of health (SDOH) measures, MRI, blood draw, and tau PET, at 1 of 5 P30 AD Research Centers (ADRCs): Boston University (BU), University of California, San Francisco (UCSF), Arizona/Banner Alzheimer's Institute (BAI), University of Florida (1Florida), and University of Texas Health Science Center at San Antonio (South Texas).
The Retention Cohort will have 18F-Flortaucipir (18F-AV-1451, Tauvid (FTP)) PET to study its longitudinal value. The Expansion Cohort will have 18F-MK-6240 (MK-6240) PET to build on the investigators' preliminary data. A subset of the Retention Cohort (n=20) will have FTP and MK-6240 for tracer comparison. Blood will be analyzed for 6 p-tau epitopes, Aβ40/42, neuroinflammation, and WM injury. DIAGNOSE-I participants were asked to pledge to donate their brain.
This study will permit continued brain donation and clinical-pathological validation studies. Results will provide insight into the detection, diagnosis, and prognosis for people living with CTE, paving the way for treatment trials.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 50 years and older
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Former National Football League Players, Former Varsity Level College Football Players, Healthy Controls, Alzheimer's Disease with cognitive impairment.
Key inclusion criteria (25 listed)
- 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
- Control (n=75) will include those retained from DIAGNOSE-I (n=50) and newly recruited (n=25). Inclusion criteria for control include:
- AD-CI (n=50) will come from the local ADRCs where Clinical Dementia Rating (CDR) and amyloid biomarker status are known for most participants being followed annually. Inclusion criteria include:
- 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:
- To further enrich the sample, we will also use the following to guide selection of participants:
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Delayed recall memory
Time frame: 12 months
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.
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 2 Jun 2026.
- Individual participant dataSharing planned: No
Related trials for Chronic Traumatic Encephalopathy (CTE)
RecruitingObservational study
Contributions of mTBI to Neurodegeneration Due to Chronic Traumatic Encephalopathy (CTE) and Alzheimer's Disease (AD)
Mild Traumatic Brain Injury, Moderate Traumatic Brain Injury
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.
Michael Alosco, PhD principal investigator
Boston University Alzheimer's Disease and CTE Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Traumatic Encephalopathy (CTE) and Alzheimer Disease, run by Boston University at 5 sites 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 25 inclusion and 17 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: enrolling by invitation, as of the sponsor's last update on 2 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 5 sites 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Delayed recall memory (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Jun 2026.