Clinical Trial to Evaluate the Safety and Efficacy of MeRT Treatment in Persistent Post-Concussive Symptoms (PPCS)

MeRT-TBI-005 is a prospective, double blind, randomized, sham-controlled, parallel group,
adaptive clinical trial designed to evaluate the efficacy of EEG/EKG-guided MeRT in active
duty military service men and women, reservists on active duty orders, and military retirees
with Persistent Post-Concussion Symptoms (PPCS) and Traumatic Brain Injury. A total of 150
participants will be randomized, with blinded adaptive sample size reassessment up to 250
participants, and a contingent group-sequential single look at interim efficacy data by the
Data and Safety Monitoring Board (DSMB).

Participants will be recruited from military bases, and their vicinities, in two locations.
Eligible participants will be randomly assigned to either MeRT or Sham MeRT treatment groups
in a 1:1 allocation ratio, with stratification on recruitment site and two levels of PTSD
co-morbidity (+/-). Treatment will be initiated on Day 1 of the study, following eligibility
evaluation and data collection at the Screening Visit (SC) and Baseline (BL) Visit. Following
the SC and BL visits, there will be a 4-week treatment period. Main study outcomes will be
collected at the second follow-up visit (F2) at the conclusion of the 4-week treatment
period. An abbreviated data collection visit will occur at the conclusion of the second
treatment week (the F1 follow-up visit). Participants, clinicians, and all personnel who
participate in evaluation, or who interface with treatment protocol downloading software,
will be blind to study treatment group assignment.

Inclusion Criteria

Participants must meet all of the following inclusion criteria to qualify for enrollment in
the study:

1. Willing and able to consent to participate in the study

2. Active duty, reservist on active duty orders, National Guard on active duty orders, or
military retiree, United States military service men and women

3. Age 18 - 55 years

4. TBI according to the following American Congress of Rehabilitation Medicine (ACRM)
criteria for mTBI, excepting that the severity of injury associated with focal
neurological deficit(s) may exceed the ACRM criteria for mild injury:

Sustaining of a traumatically induced physiological disruption of brain function, as
manifested by at least one of the following -

- Any period of loss of consciousness

- Any loss of memory for events immediately before or after the accident

- Any alteration in mental state at the time of the accident

- Focal neurological deficit(s) that may or may not be transient

5. The TBI was followed within a maximum of 4 weeks by symptoms persisting for at least 6
months as of the Screening Visit in at least 3 of the following 6 categories listed in
the ICD-10 criteria for Post-Concussive syndrome:

- Headache, dizziness, malaise, fatigue, noise tolerance

- Irritability, depression, anxiety, emotional lability

- Subjective concentration, memory, or intellectual difficulties without
neuropsychological evidence of marked impairment

- Insomnia

- Reduced alcohol tolerance

- Preoccupation with above symptoms and fear of brain damage with hypochondriacal
concern and adoption of sick role

6. Rivermead Post-Concussion Questionnaire (RPQ-16) score ≥ 16

Exclusion Criteria

Participants will be excluded from study participation if one or more of the following
exclusion criteria apply:

1. History of open skull injury

2. History of a neurological disorder including, but not limited to:

- Seizure disorder

- Any condition likely to be associated with increased intracranial pressure

- Space occupying brain lesion

3. History of cerebrovascular accident

4. History of cerebral aneurysm

5. EEG abnormalities that indicate risk of seizure, i.e., abnormal focal or general
slowing, or ictal spikes, during the EEG recording

6. Participation in any interventional research protocol within 3 months prior to the
Screening Visit

7. History of any type of ECT, MeRT, or rTMS

8. Treated within 30 days of the Screening Visit with any antipsychotic medication

9. Treated within 30 days of the Screening Visit with any anticonvulsant or anxiolytic
medications listed as exclusionary in this protocol

10. Intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants,
stents, or electrodes) or any other metal object within the head, excluding the mouth,
or on the head, that cannot be safely removed

11. Biomedical devices, including those not in or on the head, that are either implanted
or not safe to remove, that may be affected by the magnetic field of the stimulator
(e.g., cardiac pacemaker, cardioverter defibrillator (ICD), or medication dispensing
device)

12. Clinically significant medical illness or condition, including, but not limited to,
any uncontrolled thyroid disorders, hepatic, cardiac, pulmonary and renal malfunction,
or chronic excessive alcohol consumption, that in the Investigator's judgment might
pose a potential safety risk to the participant or limit the interpretation of trial
results

13. Clinically significant psychopathology, including, but not limited to, schizophrenia
or bipolar disorder, or other psychiatric disorder that in the Investigator's judgment
might pose a potential safety risk to the participant, or limit the interpretation of
trial results

14. An elevated risk of suicide or violence to others

15. Current psychotherapeutic treatment, expected to continue throughout the trial, that
was begun in the preceding 30 days at the time of the Screening Visit

16. Current treatment with any prohibited concomitant medication (i.e., Gabapentin,
Pregabalin, Topiramate) that has not been stable for the preceding 30 days at the time
of the Screening Visit

17. Inability to acquire a satisfactory EEG/ECG at Baseline, or on a routine basis

18. Pregnant, or female unwilling to use effective birth control during the course of the
trial

19. Plan to move away from the area, or knowledge that there will be a deployment, prior
to 9 weeks from the Screening Visit

20. Unwilling or unable to adhere to the study treatment, data collection schedule, or
study procedures, or any condition, including inability to communicate in English,
which in the judgment of the Investigator would prevent the participant from
completing the study