Normative Datasets for Assessments Planned for Mild Traumatic Brain Injury (NORMAL)

The primary purpose of this study will develop a database from normal healthy participants
for the same outcomes used in a program of studies of hyperbaric oxygen (HBO2) vs. sham
control in participants with persistent post-concussive symptoms. This study will
characterize the distribution of responses and change in responses over time for each of the
outcomes and will examine associations between measures within a given normal participant and
across participant characteristics such as age and gender. It will evaluate the test-retest
reliability of a series of assessments anticipated for use in the primary, secondary, and
exploratory outcomes of this program of studies.

A secondary purpose of this study is to compare normative values to results from randomized
exploratory studies of HBO2 vs. sham control in participants with persistent post-concussive
symptoms. Also, investigators will examine relationships between outcome measures from normal
participants (with respect to clinical equivalence, participant burden, and risk) and compare
to associations observed in other studies.

In this study, normal, healthy, non-brain injured civilians and military participants (active
or inactive) will undergo a battery of outcome assessments at defined test intervals to
replicate the assessment battery used in a program of studies investigating the safety of
HBO2 in patients with post-concussive symptoms following mild traumatic brain injury (TBI).

The planned comprehensive assessments will obtain robust neuropsychological, physiological,
and neuroimaging data. Other evaluations will include laboratory testing and evaluations of
the auditory, vestibular, and visual systems. Neuroimaging (magnetic resonance imaging and
computed tomography angiography) will be assessed in participants at baseline and 6 months.
Neurological function and electroencephalography (EEG) will be assessed at baseline only. All
other in-person outcome measures will be assessed in participants at baseline, at 13 weeks,
and 6 months.

Inclusion Criteria:

- Active duty or civilian in the Colorado Springs area.

- Men 18-65 years old and women 18-35 years old at the time of enrollment.

- Able to speak and read English, as primary language.

- Agrees to, and appears able to participate in all outcome assessments.

- Agrees to provide blood samples for laboratory tests and specimen banking.

- Demonstrates the ability to offer informed consent and signs the study informed
consent document.

- No known brain imaging abnormalities.

- Known history of full term non-complicated birth.

- Estimated glomerular filtration rate (eGFR) >90.

Exclusion Criteria:

- Prisoners.

- Pregnant Women.

- Minors.

- Civilian participants with planned leave conflicting with study visits or relocation
within 6 months of study enrollment, and unwilling or unable to return for follow up.

- Active duty participants with planned leave or deployment conflicting with assessment
intervals.

- Any lifetime history of brain injury.

- Diagnosis of, or a persistent history of, or symptoms of a neurological disorder
(e.g., tinnitus, vertigo, chronic fatigue, numbness, tingling, chronic migraine,
fibromyalgia, multiple sclerosis).

- Active therapy for affective disorders, behavioral disorders, or psychological
disorders.

- Diagnosis of diabetes mellitus

- Current complaints of brain injury symptoms such as cognitive or affective problems.

- Diagnosis of recurrent migraine or cluster headaches that are under medical
management.

- Headaches that occur more than two times per week.

- Recurrent dizziness that requires medical management.

- Dizziness more than two times per week.

- History of theater or war zone activity that placed the participant within a combat
zone environment.

- Diagnosis of PTSD or sub-clinical post-traumatic symptoms.

- Known neuroimaging abnormalities.

- Use of daily prescription drugs that could impact a normal outcome (e.g., beta
blockers, antidepressants), with the following exceptions:

- Participants who are 45 or more years old may be taking statins or ACE inhibitors.

- Oral or injectable contraceptives are permitted

- Participants <45 years old who are taking any daily prescriptions (exception - oral or
injectable contraceptives)

- Known atrial septal defect.

- History of hydrocephalus/microcephaly/macrocephaly.

- History of developmental delay or learning disorder as a child.

- Women who are breastfeeding.

- Women of childbearing potential who do not agree to practice an acceptable form of
birth control during the study period.

- Allergy to iodine-based contrast dye (exclusion criteria for neuroimaging assessment
measures).

- Those who are unable to participate fully in outcome assessments unless enrollment is
reviewed and approved (in writing) by the Study Director.

- Binocular vision not correctable to 20/50.

- Deafness in both ears defined as 90 decibel hearing loss or greater through speech
frequencies.

- Anxiety or claustrophobia precluding participation in neuroimaging or vestibular
procedures.

- History of therapeutic ionizing radiation to the head.

- Foreign material in head that would interfere with brain imaging.

- Foreign material within the individual that poses risk from MRI.

- History of illicit drug use, except remote, non-habitual use of marijuana.

- History in the last year, of alcohol abuse.

- Current positive urine test for an illicit substance(s).

- Active or prior malignancy except basal cell carcinoma within the last 5 years.

- Unable to abstain from caffeine or tobacco products for at least a 2-hour interval.

- Concurrent enrollment in any other research trial.

- Unable or unwilling to cease participation in sports or activities in which head
injury is likely (e.g., mixed martial arts, boxing) during the study period.