NCT06860828

The DIAGNOSE CTE Research Project-II

Risk and Resilience, Clinical Presentation, and Biomarker Profiles of Chronic Traumatic Encephalopathy and Related Dementias: The DIAGNOSE CTE Research Project-II

• Status: Enrolling By Invitation
• Phase: —
• Study type: Observational
• Enrollment: 350 (estimated)
• Sponsor: Boston University · Academic / Other
• Sex: Male
• Age: 50 Years
• Healthy volunteers: Accepted

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.

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: 1. Retention, 150 former football players and 50 controls retained from DIAGNOSE-I; 2. Expansion, the investigators will grow DIAGNOSE-I by newly recruiting 75 former college and professional football players and 25 controls; 3. 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

Timeline

• Start date: 2025-04-09
• Primary completion: 2029-07-01
• Completion: 2029-07-01
• First posted: 2025-03-06
• Last updated: 2026-03-19

Locations

5 sites across 1 country: United States