Evaluation, Pathogenesis, and Outcome of Subjects With or Suspected Traumatic Brain Injury

Objective

To generate natural history data for cohort-based comparisons to serve as the basis for
future hypothesis-driven protocols and to contribute to the clinical and physiological
understanding of traumatic brain injury (TBI) through the description of manifestations of
the injury and the relationship among radiological, hematological, clinical variables and
standard functional outcome measures.

Study Population

One thousand male and female adult subjects with history of recent head injury with or
suspected non-penetrating acute TBI, will be enrolled. Subjects having varying degrees of TBI
severity will be recruited from the collaborative programs between NIH and non-NIH hospitals.
We anticipate approximately 80% of subjects will be classified as mild TBI, concussion, or no
injury, with approximately two thirds of those subjects enrolled being discharged directly
from the emergency department.

Design

This is a prospective cohort study of subjects with known and suspected non-penetrating acute
traumatic brain injury. Subjects presenting to the emergency department or trauma service at
participating hospitals with a history of recent head injury will be studied during the
course of their hospital stay and after discharge using radiological, hematological, clinical
and functional outcome measures. Subjects will be stratified according to findings into
cohorts for comparison. The design is intentionally broad in scope to allow acquisition of
initial data for the development of future hypothesis-driven protocols. Research performed
under this protocol will not interfere with standard of care and subjects will not be treated
with experimental therapies as part of the research study. Data collected under this research
study may be shared without personal identifiers with other researchers if subjects approve
this option on the informed consent.

Outcome Measures

A variety of outcome measures will be used including diagnosis, evidence of injury on
magnetic resonance imaging (MRI) and positron emission tomography (PET), functional
impairment, and quality of life (QOL) assessments. The initial research questions will focus
on a positive diagnosis of brain injury and monitoring the natural history. Statistical
analysis plans will be developed as specific research questions and hypotheses are generated.

- INCLUSION CRITERIA:

Suspected TBI Subjects

Suspected TBI subjects must meet the following inclusion criteria:

1. History of acute head injury with or suspected non-penetrating acute TBI

2. Age 18 years or older

3. Deemed medically safe for study participation by the subject s attending physician

4. Able to provide consent or have a legally-authorized representative provide consent.

Healthy Volunteers

Healthy volunteers must meet the following inclusion criteria:

1. Healthy without past or present history of TBI or other brain disease, as evaluated by
medical history and physical exam

2. Age 18 or older.

3. Able to provide informed consent

EXCLUSION CRITERIA:

Suspected TBI Subjects

Suspected TBI subjects are not eligible for participation in this research study if any of
the following conditions exist:

1. Considered to be psychiatrically unstable by the patient s attending physician

2. Contraindication to MRI scanning including: pacemakers or other implanted electrical
devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips
on the wall of a large artery), metallic prostheses (including metal pins and rods,
heart valves, and cochlear implants), permanent eyeliner, implanted delivery pump, or
shrapnel fragments.

3. Conditions precluding entry into the scanner such as morbid obesity or claustrophobia
or conditions requiring sedation.

4. In female subjects, pregnancy.

Healthy Volunteers

Healthy volunteers are not eligible for participation in this research study if any of the
following conditions exist:

1. Presence of cognitive impairment based on medical history and/or Mini Mental State
Examination (MMSE) score of < 27

2. Current or past DSM-IV diagnosis of a psychiatric disorder including substance use
disorder as determined by self-report, medical history, and/or clinical exam

3. Major medical problems that can impact brain function (e.g., problems of the CNS
including seizures and psychosis; cardiovascular disease including hypertension and
arrhythmias; metabolic, autoimmune, endocrine disorders) as determined by self-report,
medical history and/or clinical exam;

4. 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 subject 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
subject s eyes).

5. Conditions precluding entry into the scanners (e.g. morbid obesity, claustrophobia,
etc.).

6. In female subjects, pregnancy or breastfeeding.

7. Exposure to research related radiation in the past year that, when combined with this
study, would place subjects above the allowable limits.

Currently phase 1 of enrollment for healthy volunteers in the A Beta PET pilot is complete.
At this time enrollment of healthy volunteers is on hold until analysis complete.
Enrollment of A Beta PET pilot TBI subjects and healthy matches may resume under Phase-2 if
analysis of initial data suggests update