Brief Summary
Background:
<br />
<br /> - Traumatic brain injury may have a range of effects, from severe and permanent disability to
<br /> more subtle functional and cognitive deficits that often go undetected during initial
<br /> treatment. To improve treatments and therapies and to provide a uniform quality of care,
<br /> researchers are interested in developing more standardized criteria for diagnosing and
<br /> classifying different types of traumatic brain injury. By identifying imaging and other
<br /> indicators immediately after the injury and during the initial treatment phrase, researchers
<br /> hope to better understand the nature and effects of acute traumatic brain injury.
<br />
<br /> Objectives:
<br />
<br /> - To study the natural history of traumatic brain injury by examining the changes in brain
<br /> scans, blood samples, and brain function over 5 years after injury.
<br />
<br /> Eligibility:
<br />
<br /> - Individuals 18 years of age and older who have had a traumatic brain injury within the past
<br /> 1 year.
<br />
<br /> Design:
<br />
<br /> - This study will include about eight visits to the NIH Clinical Center over 5 years.
<br /> Participants will have four visits in the first year, and one visit each year for the
<br /> following 4 years. Each visit will take between 1 and 4 days, and participants will be
<br /> in the outpatient clinic for about 8 hours each day of the visit.
<br />
<br /> - At each study visit, participants will have some or all of the following tests:
<br />
<br /> - Medical history and physical examination
<br />
<br /> - Blood and urine tests
<br />
<br /> - Questionnaires and assessments of thinking and memory, which may be spoken aloud,
<br /> written down, or entered into a computer
<br />
<br /> - Imaging scans, such as magnetic resonance imaging (MRI) or positron emission
<br /> tomography/computed tomography (PET/CT).
<br />
<br /> - This study does not provide treatment and does not replace any current therapies.
<br /> However, participants who are eligible for other National Institutes of Health studies
<br /> may be referred to these studies by researchers.
Detailed Description
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.
Study Criteria
INCLUSION CRITERIA:
Subjects eligible for participation in the TBI prospective cohort must meet the following
inclusion criteria:
- Diagnosis of non-penetrating mild, moderate, or severe TBI
- Injury occurred less than one year before enrollment
- Age 18 years of age and older
- Able to provide informed consent or with a legally-authorized representative able to
provide consent
Subjects eligible for participation in the cross-sectional sub-study must meet the
following inclusion criteria:
- Diagnosis of non-penetrating mild, moderate, or severe TBI
- Injury occurred less than five years before enrollment
- Age 18 years of age and older
- Able to provide informed consent or with a legally-authorized representative able to
provide consent
Subjects eligible for participation in the healthy volunteer control group must meet the
following inclusion criteria:
- Age 18 and older
- Able to provide written informed consent
- Able to lie flat for up to 2 hours
- Good general medical and psychological health based on History and Physical (H&P)
Subjects eligible for participation in the Select Exposure prospective cohort must meet the
following inclusion criteria:
- Referral from US State Department, Department of Health and Human Services or other
governmental entity based on their assessment of symptomatology and potential exposure
(may include, for example, abnormal auditory sensations and subsequent oculomotor,
vestibular, and cognitive symptoms)
- Age 18 years of age and older
- Able to provide informed consent or with a legally-authorized representative able to
provide consent
Subjects eligible for participation in the Select Exposure Matched Unaffected volunteer
control group must meet the following inclusion criteria:
- Age 18 and older
- Able to provide written informed consent
- Good general medical and psychological health based on History and Physical (H&P)
Subjects eligible for participation in the Remote Select Exposure Samples cohort must meet
the following inclusion criteria:
- Referral from US State Department, Department of Health and Human Services or other
governmental entity based on their assessment of symptomatology and potential exposure
(may include, for example, abnormal auditory sensations and subsequent oculomotor,
vestibular, and cognitive symptoms)
- Age 18 years of age and older
- Able to provide informed consent (telephone or electronic signature)
EXCLUSION CRITERIA:
Subjects are not eligible for participation in the prospective cohort if any of the
following conditions exist:
- Contraindication to MRI scanning including certain metal implants or devices such as:
cardiac pacemaker, insulin infusion pump, implanted drug infusion device, cochlear,
otologic, or ear implant, transdermal medication patch (Nitroglycerine) that cannot be
removed for the study, body piercing(s), bone/joint pin, screw, nail, plate, wire
sutures or surgical staples, shunts, cerebral aneurysms clips, shrapnel or other metal
imbedded in a patient s body (such as from war wounds or accidents or previous work in
metal fields or machines that may have left any metallic fragments in or near the
patient s eyes).
- Multiple trauma or accidents in the past with non-certainty that metal objects are
still present in the body
- Conditions precluding entry into the scanners (e.g. morbid obesity, claustrophobia,
etc.).
- Pregnant women.
- Women who are breast-feeding may enroll in the study, but will not receive PET-MRI.
- Inability to read or speak enough English to complete the clinical phenotyping
testing.
- Medical or Psychological instability such that the subject could not reasonably be
expected to fulfill the study requirements.
- Penetrating head injury.
Subjects are not eligible for participation in the cross-sectional sub-study if any of the
following conditions exist:
- Contraindication to MRI scanning including certain metal implants or devices such as:
cardiac pacemaker, insulin infusion pump, implanted drug infusion device, cochlear,
otologic, or ear implant, transdermal medication patch (Nitroglycerine) that cannot be
removed for the study, body piercing(s), bone/joint pin, screw, nail, plate, wire
sutures or surgical staples, shunts, cerebral aneurysms clips, shrapnel or other metal
imbedded in a patient s body (such as from war wounds or accidents or previous work in
metal fields or machines that may have left any metallic fragments in or near the
patient s eyes).
- Multiple trauma or accidents in the past with non-certainty that metal objects are
still present in the body
- Conditions precluding entry into the scanners (e.g. morbid obesity, claustrophobia,
etc.).
- Pregnant women.
- Inability to read or speak enough English to complete the clinical phenotyping
testing.
- Medical or Psychological instability such that the subject could not reasonably be
expected to fulfill the study requirements.
- Penetrating head injury.
Subjects are not eligible to participate in the Select Exposure cohort if any of the
following conditions exist:
- Pregnant women, may enroll in the study, but will not receive an MRI.
- Women who are breast-feeding may enroll in the study, but will not receive contrast
MRI (gadolinium).
- Inability to read or speak enough English to complete the clinical phenotyping testing
- Medical or Psychological instability such that the subject could not reasonably be
expected to fulfill the study requirements (such schizophrenia, uncontrolled
hypertension, serious heart, lung, or kidney disease, or other condiditon that would
make participation unsafe)
Subjects are not eligible for participation in the healthy volunteer control group if any
of the following conditions exist:
- Contraindication to MRI scanning including certain metal implants or devices such as:
cardiac pacemaker, insulin infusion pump, implanted drug infusion device, cochlear,
otologic, or ear implant, transdermal medication patch (Nitroglycerine) that cannot be
removed for the study, body piercing(s), bone/joint pin, screw, nail, plate, wire
sutures or surgical staples, shunts, cerebral aneurysms clips, shrapnel or other metal
imbedded in a patient s body (such as from war wounds or accidents or previous work in
metal fields or machines that may have left any metallic fragments in or near the
patient s eyes).
- Pregnant women
- Inability to read or speak enough English to complete the clinical phenotyping
testing.
- History of a head injury, regardless of cause:.(Causes including: vehicle/bicycle
accidents, falls, sports injuries, firearm injuries, blast injuries, violent shaking,
etc)
- Weight more than 250 lbs.
- Height greater than 6 4
- Any current or prior alcohol or substance abuse.
Heavy alcohol use: The Substance Abuse and Mental Health Services Administration (SAMHSA)
defines heavy alcohol use as binge drinking on 5 or more days in the past month. SAMHSA
defines binge drinking as 5 or more alcoholic drinks for males or 4 or more alcoholic
drinks for females on the same occasion (i.e., at the same time or within a couple of hours
of each other) on at least 1 day in the past month.
Subjects are not eligible for participation in the Select Exposure Matched Unaffected
volunteer group if any of the following conditions exist:
- Pregnant women, may enroll into the study but will not receive an MRI
- Inability to read or speak enough English to complete the clinical phenotyping
testing.
- Any current or prior heavy alcohol or substance use.
- Have a medical or psychological condition, such schizophrenia, uncontrolled
hypertension, serious heart, lung, or kidney disease, or other condition that would
make it difficult for to do the study tests, might make participation unsafe, or would
interfere with the study result
Subjects are not eligible for participation in the Remote Select Exposure Samples group if
any of the following conditions exist:
- Have a blood disorder (such as anemia, bleeding disorders such as hemophilia, blood
clots, and blood cancers such as leukemia, lymphoma, and myeloma) which would make
participation in a blood draw dangerous, or would interfere with the study results
- Have a medical or psychological condition, such schizophrenia, uncontrolled
hypertension serious heart, lung, or kidney disease, or other condition that would
make it difficult to complete the study tests, might make participation unsafe, or
would interfere with the study result