- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06034509
Cognitive and Vascular Functioning Following TBI
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Sara M Lippa, PhD
- Phone Number: 301-319-3671
- Email: sara.m.lippa.civ@health.mil
Study Contact Backup
- Name: Megan E Glazer, M.S.
- Phone Number: 301-295-5208
- Email: megan.e.glazer.ctr@health.mil
Study Locations
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Maryland
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Bethesda, Maryland, United States, 20889
- Recruiting
- Walter Reed National Military Medical Center
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Contact:
- Sara Lippa, PhD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- 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.
Additional TBI Inclusion Criteria
1. 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
- History of significant blast exposure (i.e., exposure to ≥ 10 blasts)
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
TBI Group
Participants in this group will have been identified as sustaining a traumatic brain injury (mild, moderate, severe, or penetrating).
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There are no interventions being tested in the Cognitive and Vascular Functioning Following TBI study.
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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.
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There are no interventions being tested in the Cognitive and Vascular Functioning Following TBI study.
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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.
|
There are no interventions being tested in the Cognitive and Vascular Functioning Following TBI study.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Panel of blood biomarkers
Time Frame: 3 years
|
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.
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3 years
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Cognitive Performance- Overall Test Battery Mean
Time Frame: 3 years
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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).
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3 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in panel of blood biomarkers over time
Time Frame: 3 years
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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.
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3 years
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Change in overall test battery mean over time
Time Frame: 3 years
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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.
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3 years
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Change in brain volume over time
Time Frame: 3 years
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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)].
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3 years
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Change in white matter lesions over time
Time Frame: 3 years
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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.
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3 years
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Cerebrovascular Reactivity
Time Frame: 3 years
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Linear regression models will be run with the difference score in each vascular blood biomarker from the initial visit to the current study visit as the independent variable and global CVR (%S/mmHG) - (assessed during the current visit only) as the dependent variable.
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3 years
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DCE-MRI
Time Frame: 3 years
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Linear regression models will be run with the difference score in each vascular blood biomarker from the initial visit to the current study visit as the independent variable and overall blood brain barrier function (assessed during the current visit only as the percentage of brain volume with suprathreshold voxels) as the dependent variable.
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3 years
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Sara M Lippa, PhD, Walter Reed National Military Medical Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Cardiovascular Diseases
- Vascular Diseases
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Arteriosclerosis
- Arterial Occlusive Diseases
- Wounds and Injuries
- Neurocognitive Disorders
- Craniocerebral Trauma
- Trauma, Nervous System
- Cognition Disorders
- Intracranial Arterial Diseases
- Intracranial Arteriosclerosis
- Leukoencephalopathies
- Brain Injuries
- Dementia
- Brain Injuries, Traumatic
- Cognitive Dysfunction
- Dementia, Vascular
Other Study ID Numbers
- WRNMMC-2022-0409
- W81XWH-22-2 (Other Grant/Funding Number: CDMRP)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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