Clinical trial NCT06034509: Cognitive and Vascular Functioning Following TBI
Official title: Cognitive and Vascular Functioning Following TBI
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Traumatic Brain Injury
Cognitive Decline
Vascular Dementia
Keywords: Traumatic Brain Injury
Cognitive Decline
Vascular Dementia
Blood Biomarkers
Cerebrovascular Reactivity
Military
Lead sponsor: Walter Reed National Military Medical Center
Sponsor class: FED
Collaborators: name: Johns Hopkins University
First posted: 2023-09-13
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study 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.

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

Detailed description: The investigators will enroll 300 Service Members (SMs) and Veterans who participated in the National Intrepid Center of Excellence (NICoE) intensive outpatient program or Defense and Veterans Brain Injury Center/Traumatic Brain Injury Center of Excellence (DVBIC/TBICoE) 15-Year TBI Natural History of TBI Study (NatHx) at least three years prior to the present evaluation and provided prior blood specimens stored for analysis. Following informed consent, participants will undergo semi-structured interviews assessing posttraumatic stress disorder (PTSD) and updated lifetime TBI history, neurological examination, neuropsychological testing, structural Magnetic Resonance Imaging (MRI) T1, T2, fluid attenuated inversion recovery (FLAIR), diffuse tensor imaging (DTI), as well as novel imaging techniques to assess imaging biomarkers of traumatic cerebrovascular injury (TCVI): 1) functional MRI (fMRI)-Blood Oxygen Level Dependent (BOLD) with hypercapnia challenge to measure cerebrovascular reactivity (CVR); and 2) Dynamic Contrast Enhanced-MRI to assess blood brain barrier integrity, and an additional research blood draw \[apolipoprotein E (APOE) genotype; plasma biomarkers including vascular (e.g., vascular endothelial growth factor, von Willebrand Factor, cholesterol, homocysteine), inflammatory (e.g., high sensitivity c-reactive protein, interleukin-6 (IL-6), chitinase-3-like protein 1 (YKL-40)), and neuronal degeneration (e.g., neurofilament light, phosphorylated tau, brain-derived neurotrophic factor, beta amyloid proteins)\]. A medical record review will be conducted specifically for current and past history of cerebrovascular risk factors (e.g., hypertension, diabetes, tobacco use) and psychological conditions (e.g., PTSD, depression). The project will also leverage previously collected data, comparing participants' symptoms, cognitive performance, imaging, and, blood biomarkers to those previously collected through the NICoE, 15-Year study and/or the DOD serum repository, with data from at least two time points on all individuals.

Eligibility criteria: Inclusion Criteria:

1. Active duty uniformed SM or Veteran who is currently eligible for treatment at WRNMMC (i.e., Defense Enrollment Eligibility Reporting System (DEERS)-eligible).
2. Ability to read, write, and speak English.
3. Ability to provide informed consent.
4. NICoE Intensive Outpatient Program (IOP) or NatHx Study comprehensive evaluation ≥3 years prior to current evaluation with valid neuropsychological test results.
5. 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):

1. Loss of consciousness (LOC) or post-traumatic amnesia (PTA)
2. Alteration of consciousness (AOC)
3. Evidence of neurologic dysfunction
4. TBI-related abnormality on structural neuroimaging (either CT or MRI). Additional Healthy Control Criteria

   1. History of military deployment.
   2. Low history of blast exposure (i.e., \<10 blasts) Additional Blast Control Criteria

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   1. History of significant blast exposure (i.e., exposure to ≥ 10 blasts)

Exclusion Criteria:

1. 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
2. Diabetes mellitus requiring drug treatment
3. Hypertension requiring more than 1 antihypertensive drug to control BP
4. History of myocardial infarction or other systemic vasculopathies
5. Dementia diagnosis at initial NICoE/NatHx Study assessment

Primary outcomes:
measure: Panel of blood biomarkers
timeFrame: 3 years
measure: Cognitive Performance- Overall Test Battery Mean
timeFrame: 3 years
Secondary outcomes:
measure: Change in panel of blood biomarkers over time
timeFrame: 3 years
measure: Change in overall test battery mean over time
timeFrame: 3 years
measure: Change in brain volume over time
timeFrame: 3 years
measure: Change in white matter lesions over time
timeFrame: 3 years
measure: Cerebrovascular Reactivity
timeFrame: 3 years
measure: DCE-MRI
timeFrame: 3 years
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
Study officials:
affiliation: Walter Reed National Military Medical Center
name: Sara M Lippa, PhD
role: PRINCIPAL_INVESTIGATOR
References: