Noninvasive Neuromodulation for Treatment of Symptoms Due to Mild or Moderate Traumatic Brain Injury

- Based on the results of the investigators pilot study in moderate traumatic brain
injury (M-TBI), the investigators will conduct a randomized, controlled study of
cranial nerve non-invasive neuromodulation (CN-NINM) in individuals with chronic
symptoms of mild to moderate traumatic brain injury (mTBI), post-concussive sequelae,
(PCS) and post-traumatic stress (PTS).

- The study will involve training of both balance and gait, with assessments using
standardized and relevant metrics to monitor changes in these indications, as well as
cognitive function, sleep, headache, anxiety, mood, and eye-movement control.

- The training regimen involves using a neurostimulation intervention that addresses
primary and secondary symptoms associated with mTBI, PCS, and PTS.

- This randomized double blind controlled study will enroll a total of 44 subjects (M &
F) in 2 equal subgroups: 22 with an Active PoNS™, and 22 with a Control (non-zero,
minimally perceivable stimulation) device.

- Subjects will participate in a 3-phase intervention beginning with a 2-week in-lab
training program (ITP) (2 in-lab training sessions and 1 home training session daily),
followed by 12 weeks of training at home (HTP) (3 home training sessions daily), and a
12-week withdrawal period (no training). Subjects will return to the clinic weekly
during the at-home phase for a single session of retraining and progression, and
participate in periodic retesting.

- All training and testing will be performed uniformly across all subjects in both
groups. Multiple assessment metrics will capture data at the beginning and end of the
2-week in-lab CN-NINM intervention period and at 3-week intervals. After completion of
the formal training period, subjects will stop using the device (withdrawal stage) and
will be tested every 3 weeks over an additional 12 weeks to monitor and assess changes
due to withdrawal of the PoNS. This will yield a total of 10 data points for each
subject.

- If successful, this study would indicate that CN-NINM may improve rehabilitation
outcomes and reduce time required to improve function.

Inclusion Criteria:

- All candidates will have a balance disorder as a result of a traumatic brain injury
(TBI).

- All candidates will have a NeuroCom® Sensory Organization Test (SOT) composite score
at least 8 points below normal after adjustment for age and height [based on
normative data].

- All candidates will be between the ages of 18 and 65 (at the time of screening).

- If female of childbearing potential, the candidate agrees to use adequate
contraception throughout participation in the study (from enrollment to completion).

- All candidates must have access to a treadmill.

- All candidates will be at least 1 year post-injury.

- All candidates will have a neuroradiologic scan and report after their most recent
TBI.

- All candidates will be ambulatory and able to walk for 20 minutes.

- All candidates, if on medications, will not have had any major changes in type or
dosage within 3 months of enrollment.

- All candidates will have participated in a focused physical rehabilitation program
for their TBI and feel that they have reached a plateau.

- All candidates will be able to understand and willing to give informed consent.

Exclusion Criteria:

- All candidates that have oral health problems (e.g. gum disease, active cankers,
piercings, oral surgery within the previous 3 months).

- All candidates with non-removable metal orthodontic devices (e.g., braces) or oral
cavity piercings that could interfere with PoNS™ use.

- All candidates who have chronic infectious diseases (e.g. hepatitis, HIV, TB).

- All candidates with unmanaged hypertension.

- All candidates with unmanaged diabetes, or complications due to diabetes (e.g.
retinopathy, neuropathy, renal disease).

- All candidates with neurological disorders other than those attributed to their
primary diagnosis (e.g., MS, PD, ALS, AD or other dementia, uncontrolled pain).

- All candidates with a history of oral cancer.

- All candidates who have been treated for any type of cancer other than basal cell
carcinoma within the past year.

- All candidates who have had a penetrating injury, craniotomy (with the exception of a
burr hole [trephination] for resolution of acute subdural hematoma), or refractory
subdural hematoma.

- Exceptions for other abnormalities identified in neuroradiologic scan reports that
are asymptomatic and not expected to change may be made on a case by case basis by
the Medical Advisor.

- All candidates with chronic use of psychoactive or psychostimulant medications that,
in the opinion of the investigators, would compromise the subject's ability to
comprehend and perform the study activities.

- All candidates who have a pacemaker, or are identified as at-risk for cardiovascular
events.

- All candidates who are pregnant or lactating.

- All candidates with a lower extremity biomechanical prosthetic.

- All candidates with a history of seizures (except those in the acute or post-acute
phases, and are controlled).

- All candidates who who experienced a loss of consciousness greater than 24 hours as a
result of their TBI.

- All candidates with a "severe" score in any of the Attention, Memory, or Executive
Functions categories on the Cognitive Linguistic Quick Test (CLQT).

- All candidates who, in the opinion of the investigators, are unable to feel the
stimulation and successfully complete the device level setting procedure.