Objective
The primary objective is to contribute to the understanding of non-penetrating traumatic brain injury (TBI) through the description of the relationships between neuroimaging, hematological, and extensive functional/cognitive phenotyping measures. We will generate natural history data for cohort-based comparisons and to serve as the basis for future hypothesis-driven protocols. In addition, we will create and test a series of new taxonomies to describe TBI severity and predict outcome.
Study Population
Three hundred adult subjects with a clinical diagnosis of non-penetrating TBI (mild, moderate and severe) will be enrolled. Subjects will be recruited from NIH, affiliated hospitals/clinics, and in the community. One hundred adult healthy volunteers without a history of TBI will be seen for comparison. Additionally, a select group of up to 115 US government associated personnel experiencing TBI-like symptoms arising after possible exposure to a non-natural energy source, will be studied (select exposure group). This select group will require a separate age and sex matched group of 115 unaffected volunteers. Participants (100) who are not able to travel to the NIH Clinical Center to participate in the Select Exposure Group study can complete study tests and questionnaires remotely, and have biospecimens sent to our lab for analysis, as part of the remote select exposure samples group.
Design
This is a natural history study following a prospective cohort of subjects with a clinical diagnosis of non-penetrating traumatic brain injury with a cross-sectional sub-study. Subjects will be enrolled in the prospective cohort within one year of their head injury and then followed periodically for five years, with neuroimaging, including Magnetic Resonance Imaging (MRI), hematological, and extensive functional/cognitive phenotyping measures. Subjects will be enrolled in the cross-sectional sub-study within five years of their head injury and may be evaluated with MRI, hematological, and functional/cognitive measures usually within a single visit. However, procedures may be scheduled during multiple visits, depending on the number of procedures performed. Study participants may be offered standard of care rehabilitation therapies provided at no cost by Investigators and supervised by Dr. Chan. Tests will be subject to investigator discretion and subject willingness to participate in evaluation. After first MRI, future MRIs will be obtained based on subject willingness and investigator discretion from findings on previous imaging. Subjects will be stratified according to findings into cohorts for comparison. Subjects will not be treated with experimental therapies as part of the research study. This study will provide direct benefit to subjects as they will receive sensitive neuro-imaging and clinical testing that may have diagnostic value and rehabilitation therapies that might not be provided to them in the community. In addition to the TBI patient group, a longitudinal control group comprised of healthy volunteers will be collected. The control group participants may complete the Neuroimaging (MRI without gadolinium), hematological and functional/cognitive phenotyping measures as the TBI patient population.
The prospective select exposure group of US government associated personnel will be followed periodically for a total of six years. Subjects may complete neuroimaging, including Magnetic Resonance Imaging (MRI), hematological, and extensive functional/cognitive, auditory, vestibular, and oculomotor phenotyping measures. In addition to the select exposure group, a longitudinal control group comprised of unaffected volunteers matched to this group will be collected. The control group participants will complete the same Neuroimaging (MRI without gadolinium), hematological and functional/cognitive phenotyping measures as the select exposure patient population. Additionally, if a select exposure matched control participant is subsequently exposed, they may enroll into the select exposure group arm of the study for pre and post exposure analysis. Participants who are unable to travel to the NIH Clinical Center to participate can remote consent, answer questionnaires remotely via telephone or electronic communication methods, and have biospecimens sent to our lab for analysis. Participants enrolled in the any arm of the study who are unable to travel to NIH for any study visit may be asked to answer questions electronically (telephone, email, videoconferencing if within the US, etc) to allow for some data collection to occur at each time point.
Outcome Measures
A variety of outcome measures may be used including MRI, to include Diffusion Tensor Imaging (DTI), Dynamic Susceptibility Contrast (DSC), and functional Magnetic Resonance Imaging (fMRI), high field 7T MRI. In addition, extensive and sensitive clinical phenotyping will be performed to assess functional and cognitive impairment, including auditory, vestibular, and oculomotor testing, and quality of life assessments. Blood and saliva (buccal cells may be collected in lieu of whole blood for subjects unwilling or unable to provide blood draw) may also be collected and sent to a biorepository for future analysis if subject agrees to participation in sample collection.
