Cognitive and Vascular Functioning Following TBI
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18-74
SponsorWalter Reed National Military Medical Center
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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
Trial population
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.
Trial design
Design model
Case-control
Time perspective
Other
Treatments tested in this trial
No intervention. This is an observational study.
Other interventionThere are no interventions being tested in the Cognitive and Vascular Functioning Following TBI study.
Treatment groups
300 Participants
are divided into 3 treatment groupsGroup A: TBI Group1 intervention
Group B: High-blast exposed control group1 intervention
Group C: Low-blast exposed control group1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
3 years2
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).
Time frame
3 yearsSecondary outcomes
1
Change in panel of blood biomarkers over time
Linear mixed effect (LME) models will be fit to the analysis dataset which use the panel of blood biomarkers as the response variables and investigate TBI severity, number of TBI events, and time. The panel of blood biomarkers will include 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) biomarkers, all measured in pg/mL.
Time frame
3 years2
Change in overall test battery mean over time
The investigators will fit a cross-sectional multivariable regression model to the data with the response variable being the change (Time 3 - Time 2) in the OTBM T-score (mean=50, SD=10, min=0, max=100). Individual cognitive domain composite T-scores will also be evaluated to understand the main components driving change in the OTBM.
Time frame
3 years3
Change in brain volume over time
The investigators will fit a cross-sectional multivariable regression model to the data with the response variable being the change (Time 3 - Time 2) in total brain volume \[milliliters (mL)\].
Time frame
3 years4
Change in white matter lesions over time
The investigators will fit a cross-sectional multivariable regression model to the data with the response variable being the change (Time 3 - Time 2) in total and total number of white matter lesions.
Time frame
3 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Walter Reed National Military Medical Center
Lead sponsor
Johns Hopkins University
Collaborator
Source ClinicalTrials.gov