Cognitive and Vascular Functioning Following TBI
2 other identifiers
observational
300
1 country
1
Brief Summary
This observational study will examine the association of chronic traumatic cerebrovascular injury and cardiovascular risk factors with TBI-related cognitive impairment and vascular dementia. Cerebrovascular, inflammatory, and neurodegenerative blood biomarkers as well as clinical and neuroimaging data
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Nov 2023
Typical duration for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 17, 2023
CompletedFirst Posted
Study publicly available on registry
September 13, 2023
CompletedStudy Start
First participant enrolled
November 27, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 1, 2027
September 26, 2025
July 1, 2025
3.1 years
April 17, 2023
September 22, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Panel of blood biomarkers
A panel of blood biomarkers including vascular (e.g., vascular endothelial growth factor, von Willebrand Factor, cholesterol, lipoproteins, homocysteine, fibrinogen, hemoglobin A1C), inflammatory (e.g., high sensitivity c-reactive protein, Tumor Necrosis Factor-alpha, IL-6, IL-12p70, YKL-40), and neuronal degeneration (e.g., neurofilament light, Glial Fibrillary Acidic Protein, phosphorylated tau, Clusterin, brain-derived neurotrophic factor, beta amyloid proteins) will be compared between TBI groups. One-way ANOVAs will be run with TBI severity as the independent variable and each individual blood biomarker (measured in pg/mL) as the dependent variable. Spearman's rank order correlations will evaluate the relationship between blood biomarkers, number of TBIs, and TBI severity.
3 years
Cognitive Performance- Overall Test Battery Mean
Neurocognitive data will be corrected for age, gender, education, and race, as available. An overall test battery mean (OTBM) T-score will be calculated as the average of seven cognitive domain T-scores (attention/processing speed, working memory, executive functioning, learning/immediate memory, delayed memory, language, perceptual reasoning). Each biomarker will be correlated with the OTBM using Spearman's rank order correlations. Cognitive domain T-scores will also be evaluated to understand which are driving changes in the OTBM. All scores will be evaluated as T-scores (mean=50, SD=10, min=0, max=100), for which higher scores indicate higher cognitive performance. Multivariable logistic regression will be used to evaluate the relationship between TBI number, TBI severity, blood biomarkers and normal cognition vs. mild cognitive impairment (MCI).
3 years
Secondary Outcomes (6)
Change in panel of blood biomarkers over time
3 years
Change in overall test battery mean over time
3 years
Change in brain volume over time
3 years
Change in white matter lesions over time
3 years
Cerebrovascular Reactivity
3 years
- +1 more secondary outcomes
Study Arms (3)
TBI Group
Participants in this group will have been identified as sustaining a traumatic brain injury (mild, moderate, severe, or penetrating).
High-blast exposed control group
Participants in this group will have no history of traumatic brain injury AND will have a lifetime history of greater than 10 blast exposures.
Low-blast exposed control group
Participants in this group will have no history of traumatic brain injury AND will have a lifetime history of less than 10 blast exposures.
Interventions
There are no interventions being tested in the Cognitive and Vascular Functioning Following TBI study.
Eligibility Criteria
Male and female active duty service members or DEERS-eligible veterans at least 18 years of age who have participated in the NICoE Intensive Outpatient Program or 15 Year Natural History Study will be invited to participate.
You may qualify if:
- Active duty uniformed SM or Veteran who is currently eligible for treatment at WRNMMC (i.e., Defense Enrollment Eligibility Reporting System (DEERS)-eligible).
- Ability to read, write, and speak English.
- Ability to provide informed consent.
- NICoE Intensive Outpatient Program (IOP) or NatHx Study comprehensive evaluation ≥3 years prior to current evaluation with valid neuropsychological test results.
- Consent to allow access to prior research data collected through the NICoE TBI Neuroimaging Core Project or NatHx Study and consent to allow access to at least 1 prior blood specimen previously collected through these studies or the DoD Serum Biorepository.
- \. History of at least one mild, moderate, severe, or penetrating TBI \> 3 years prior to enrollment. TBI will be diagnosed if any one of the following criteria immediately after the injury is met and attributed to the brain injury, rather than environmental/psychological/other injury factors (DoD-VA criteria246):
- Loss of consciousness (LOC) or post-traumatic amnesia (PTA)
- Alteration of consciousness (AOC)
- Evidence of neurologic dysfunction
- TBI-related abnormality on structural neuroimaging (either CT or MRI). Additional Healthy Control Criteria
- History of military deployment.
- Low history of blast exposure (i.e., \<10 blasts) Additional Blast Control Criteria
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- History of significant blast exposure (i.e., exposure to ≥ 10 blasts)
You may not qualify if:
- Disabling neurologic or psychological disorders such as autism, cerebral palsy, developmental disorder, stroke, brain tumor, multiple sclerosis, meningitis, encephalitis, brain abscess, vascular malformation, pre-injury epilepsy, schizophrenia, bipolar disorder, personality disorder
- Diabetes mellitus requiring drug treatment
- Hypertension requiring more than 1 antihypertensive drug to control BP
- History of myocardial infarction or other systemic vasculopathies
- Dementia diagnosis at initial NICoE/NatHx Study assessment
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889, United States
Biospecimen
Blood serum and plasma
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sara M Lippa, PhD
Walter Reed National Military Medical Center
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- CASE CONTROL
- Time Perspective
- OTHER
- Sponsor Type
- FED
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 17, 2023
First Posted
September 13, 2023
Study Start
November 27, 2023
Primary Completion (Estimated)
January 1, 2027
Study Completion (Estimated)
May 1, 2027
Last Updated
September 26, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- Data will be uploaded to the FITBIR system at the end of each funded year and at the completion of the study. This data will be made available to researchers using the FITBIR system 12 months after the end of the award period.
- Access Criteria
- FITBIR qualified investigators will be provided access.
Non-identified IPD will be made available through the Federal Interagency TBI Research (FITBIR) Database.