Cohort Study of Blood Biomarkers for TES

Study Overview
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Brief Summary
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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.

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

Conditions
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Chronic Traumatic Encephalopathy, Traumatic Encephalopathy, Chronic, Traumatic; Encephalopathy, Postcontusional

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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: 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Athletes with rmTBI history<br>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<br>* 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<br>|
| Patients with rmTBI history<br>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<br>* 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<br>|
| Healthy volunteer<br>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<br>* 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<br>|

What is the study measuring?
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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 |