Cohort Study of Blood Biomarkers for TES

Observational Cohort Study of Blood Transcriptomics and Proteomics Information as Biomarkers of Traumatic Encephalopathy Syndrome

In this study, high-throughput screening and multi-omics (transcriptomics and proteomics) joint analysis technology will be employed to explore potential CTE/TES biomarkers (RNA and protein) in blood and its exosomes. Thereafter, these biomarkers will be combined with the reported TBI biomarkers to create a novel set of CTE/TES molecular diagnostic signatures. The findings may open a new avenue for the clinical diagnosis of the disease and the future research on its therapeutic strategy.

Study Overview

• Status: Completed
• Conditions: Chronic Traumatic Encephalopathy; Traumatic Encephalopathy, Chronic; Traumatic; Encephalopathy, Postcontusional
• Intervention / Treatment: Diagnostic test: Blood tests, Cognitive function tests, head MRI (plain scan and DTI sequence) examination and head PET (FDG-PET, Tau-PET and Amyloid-PET) examination

• Study Type: Observational
• Enrollment (Actual): 120

Contacts and Locations

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300052
      • Tianjin Medical University General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

• Athletes with rmTBI history. The subjects are active or retired athletes who have engaged in weightlifting, wrestling, judo, boxing or taekwondo. All of them have a clear history of rmTBI.
• Patients with rmTBI history. The subjects have a history of multiple (≥2 times) exposure to brain trauma, and medical records in Tianjin Medical Insurance designated hospitals.
• Healthy volunteers, without rmTBI history.

Description

Inclusion Criteria:

1. Athletes and patients with traumatic brain injury

   • Age ≥ 18 and ≤ 80 years old with independent behavior ability or authorized legal representative.
   • Have a clear history of repetitive mild TBI, concussion or subconcussion.
   • The most recent head injury occurred 3 months ago.

2. Healthy Volunteers

   • Age ≥ 18 and ≤ 80 years old with independent behavior ability.
   • No history of repetitive mild TBI, concussion or subconcussion.
   • Fully understands the nature of the study, and voluntarily participates and signs the informed consent.

Exclusion Criteria:

1. Athletes and patients with traumatic brain injury

   • Pregnant or lactating women.
   • History of other neurological diseases.
   • History of tumors, hematological diseases, severe cardiopulmonary diseases, hepatic failure or renal failure.
   • Have participated in clinical trials in the past four weeks.
   • The investigator believes that not appropriate for inclusion.

2. Healthy Volunteers

   • Pregnant or lactating women.
   • History of TBI or other neurological diseases.
   • History of tumors, hematological diseases, severe cardiopulmonary diseases, hepatic failure or renal failure.
   • Have participated in clinical trials in the past four weeks.
   • The investigator believe that not appropriate for inclusion.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Athletes with rmTBI history; 50 active or retired athletes from the Weightlifting, Wrestling, Judo, Boxing and Taekwondo Sports Management Center of Tianjin Sports Bureau	Diagnostic test: Blood tests, Cognitive function tests, head MRI (plain scan and DTI sequence) examination and head PET (FDG-PET, Tau-PET and Amyloid-PET) examination; Blood tests (30-ml venous blood) for the following items. 1) Transcriptomics and proteomics high-throughput detection and quantitative verification; 2) Exosomal transcriptomics and proteomics high-throughput detection and quantitative verification; 3) Quantitative detection for classical biomarkers of traumatic brain injury, including S100B, GFAP, UCH-L1, NFL, T-Tau and p-Tau181.; Cognitive function tests, including RPQ, MMSE and MoCA.; Possible head MRI (plain scan and DTI sequence) examination and head PET (FDG-PET, Tau-PET and Amyloid-PET) examination
Patients with rmTBI history; 50 patients with multiple (≥2 times) exposure to brain trauma attending Tianjin Medical Insurance designated hospitals such as Tianjin Medical University General Hospital	Diagnostic test: Blood tests, Cognitive function tests, head MRI (plain scan and DTI sequence) examination and head PET (FDG-PET, Tau-PET and Amyloid-PET) examination; Blood tests (30-ml venous blood) for the following items. 1) Transcriptomics and proteomics high-throughput detection and quantitative verification; 2) Exosomal transcriptomics and proteomics high-throughput detection and quantitative verification; 3) Quantitative detection for classical biomarkers of traumatic brain injury, including S100B, GFAP, UCH-L1, NFL, T-Tau and p-Tau181.; Cognitive function tests, including RPQ, MMSE and MoCA.; Possible head MRI (plain scan and DTI sequence) examination and head PET (FDG-PET, Tau-PET and Amyloid-PET) examination
Healthy volunteer; 20 healthy volunteers	Diagnostic test: Blood tests, Cognitive function tests, head MRI (plain scan and DTI sequence) examination and head PET (FDG-PET, Tau-PET and Amyloid-PET) examination; Blood tests (30-ml venous blood) for the following items. 1) Transcriptomics and proteomics high-throughput detection and quantitative verification; 2) Exosomal transcriptomics and proteomics high-throughput detection and quantitative verification; 3) Quantitative detection for classical biomarkers of traumatic brain injury, including S100B, GFAP, UCH-L1, NFL, T-Tau and p-Tau181.; Cognitive function tests, including RPQ, MMSE and MoCA.; Possible head MRI (plain scan and DTI sequence) examination and head PET (FDG-PET, Tau-PET and Amyloid-PET) examination

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood level of novel protein biomarkers for CTE/TES	Novel protein biomarkers for CTE/TES will be screened out by transcriptomics + proteomics high-throughput detection and multi-omics bioinformatics analysis. Their levels will be further verified using ELISA assay.	Baseline
Blood level of novel RNA biomarkers for CTE/TES	Novel RNA biomarkers for CTE/TES will be screened out by transcriptomics + proteomics high-throughput detection and multi-omics bioinformatics analysis. Their levels will be further verified using RT-PCR.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood level of classical biomarkers for CTE/TES	Blood S100B, GFAP, UCH-L1, NFL, T-Tau and p-Tau181 level detected by ELISA assay	Baseline
Ultrasound examination of the carotid arteries and lower limb arteries	Ultrasound examination of bilateral CCA, ICA, CFA, SFA, PA, DPA and ATA	5 years post-enrollment
Serum Treg cell count and degree of senescence	Percentage of serum regulatory T (Treg) cells relative to the total T cell count; Percentage of senescent Treg cells relative to the total Treg cell count	5 years post-enrollment
Cognitive function tests - RPQ-3	Rivermead post-concussion symptoms questionnaire - 3 (RPQ-3). Reference Range: 0-12. Higher scores mean a worse outcome.	5 years post-enrollment
Cognitive function tests - RPQ-16	Rivermead post-concussion symptoms questionnaire - 16 (RPQ-16). Reference Range: 0-64. Higher scores mean a worse outcome.	5 years post-enrollment
Cognitive function tests - MoCA	Montreal cognitive assessment (MoCA). Reference Range: 0-30. Higher scores mean a better outcome.	5 years post-enrollment
Cognitive function tests - MMSE	Description: mini-mental state examination (MMSE). Reference Range: 0-30. Higher scores mean a better outcome.	5 years post-enrollment

Collaborators and Investigators

• Sponsor: Tianjin Medical University
• Collaborators: Tianjin Medical University General Hospital
• Investigators: Principal Investigator: Ping Lei, Doctor, Tianjin Medical University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2021
• Primary Completion (Actual): December 1, 2023
• Study Completion (Actual): December 1, 2023

Study Registration Dates

• First Submitted: June 6, 2021
• First Submitted That Met QC Criteria: June 9, 2021
• First Posted (Actual): June 16, 2021

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: January 8, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Injuries, Traumatic; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Pathologic Processes; Chronic Disease; Disease Attributes; Neurodegenerative Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Damage, Chronic; Brain Injuries; Brain Injury, Chronic; Pathological Conditions, Signs and Symptoms; Chronic Traumatic Encephalopathy; Brain Diseases; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hematologic Tests; Physical Examination
• Other Study ID Numbers: IRB2021-YX-056-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No