Hyperbaric Oxygen for Traumatic and Non-traumatic Brain Injury

This is a single center, randomized, double-blind study with a subsequent open-label
intervention period to explore whether a course of hyperbaric oxygen can ameliorate
persistent symptoms after brain injury. In this study, adult men and women with persistent
symptoms 6 months to 10 years after injury will be randomized to receive 40 hyperbaric oxygen
sessions (100% oxygen at 1.5 atmospheres absolute, 60 minutes door-to-door) or sham chamber
sessions (room air chamber excursion at near-ambient pressure, 60 minutes door-to-door).
Chamber sessions will be provided Monday through Friday, excluding holidays, and participants
will have up to 12 weeks to complete their 40 sessions.

Participants will be evaluated before the chamber sessions, at 13 weeks, and at 6 months.
Assessments include self-administered questionnaires, neuropsychological function, a brief
neurological examination, electroencephalography, visual function tests, and a
neuro-optometry evaluation. These outcome tools will measure symptoms and deficit at the time
of enrollment and subsequent evaluations, and provide insight into whether hyperbaric oxygen
can play a role in recovery from brain injury.

Once the participants have completed their 6 month evaluations, they will enter an open
intervention group, receiving 40 hyperbaric sessions at 1.5 atmospheres absolute for 60
minutes. Participants will have up to 12 weeks to complete these sessions. Participants will
be evaluated after the second set of chamber sessions (at 9 months and again at 12 months).
Individuals will then be assessed annually until study closure (12-month follow-up of the
last enrolled participant).

Participants will be asked to provide blood for long-term storage of serum, plasma, and DNA
for future investigations, including apolipoprotein E genotype.

Inclusion Criteria:

- Adults, age 18-70 years, both men and women

- Able to speak and read English as primary language

- Able and willing to provide written informed consent for study participation.

- Able and willing to complete outcome assessments and provide blood and urine samples
as required by the study protocol.

- Able to tolerate the chamber environment and hood placement and to equalize middle ear
pressure.

- Past history of at least one brain injury with persistent symptoms that meets all of
the following criteria:

- Brain injury of non-stroke etiology that occurred at least 6 months but no more
than 10 years prior to enrollment.

- At least 3 of the following persistent symptoms from the injury: headaches,
dizziness or balance problems, blurred vision, tiredness/fatigue or sleep
problems, seizures, remembering things or solving problems, managing stress or
emotional upsets, controlling temper/irritability, depression, anxiety,
post-traumatic stress, or ringing in the ears.

- Normal thyroid stimulating hormone and hematocrit value greater than 35% within the
previous 6 months.

Exclusion Criteria:

- Contraindications to hyperbaric oxygen

- Insulin-dependent diabetes mellitus, or diabetes mellitus that is not reasonably
controlled.

- Uncontrolled seizure disorder (participants must be on therapy and seizure-free
for at least 6 months).

- Claustrophobia precluding chamber or hood tolerance.

- Implanted devices not cleared for hyperbaric pressurization.

- Pregnancy or plans to become pregnant during the study participation period.
Women of childbearing potential will be asked to use an acceptable form of birth
control during study participation.

- Lung disease, such as emphysema, chronic bronchitis, asthma that is not
well-controlled, or bullous lung disease that raises the risk for pulmonary
barotrauma due to air trapping.

- Active malignancy, previous malignancy (except basal cell carcinoma) in the last
5 years, or any prior treatment with bleomycin (Blenoxane). Prior treatment with
doxorubicin (Adriamycin) is acceptable as long follow-up echocardiography is
normal.

- Chronic disease such as heart or renal failure would raise the participant's risk
of adverse events during hyperbaric oxygen.

- Confounds to the outcome assessments

- Inability to speak English as their primary language (English fluency required
because many of the outcomes are only in available in English)

- Instability with walking requiring more than a cane for assistance

- Alcohol abuse, by self-report, within the last year.

- Lifetime history of illicit drug use, by self-report, except remote (greater than
one year), non-habitual use of marijuana.

- Failed urine drug screen during study participation.

- Continued participation during the intervention period in sports activities where
head injury is likely, such as contact football, boxing, mixed martial arts, etc.

- Blind or deaf.

- Major psychiatric disorder or degenerative mental disease (such as multiple
sclerosis).

- Prior therapeutic radiation to the central nervous system.

- Personal history of any condition that pre-dates their brain injury that resulted
in diminished capacity (such as chromosomal disorders) or that, in the opinion of
the investigators, affects cognition to such a degree that the outcome
assessments are invalidated (such as learning disability or attention deficit
hyperactivity disorder requiring pharmaceutical therapy as an adult).

- Any brain injury from stroke (ischemic or hemorrhagic)

- Known untreated chronic or acute medical conditions, such as hypothyroidism,
Cushing's disease, untreated hypertension, etc., that would confound the outcome
assessments or inhibit compliance with the study protocol. If treated, these
disorders would not be excluded.

- Concomitant enrollment in any other drug/device clinical trial.

- Prior hyperbaric oxygen for any reason within the last year.