Clinical Trial to Evaluate the Safety and Efficacy of MeRT Treatment in Post-Traumatic Stress Disorder

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of individualized, Biometrics-guided Magnetic e-Resonance Therapy (MeRT) treatment of Post-Traumatic Stress Disorder with and without Persistent Post-Concussive Symptoms (PPCS) following Traumatic Brain Injury (TBI).

Detailed Description
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MERT-005-B is a prospective, double blind, randomized, sham-controlled, parallel group, stratified, adaptive clinical trial designed to evaluate the efficacy of EEG-guided MeRT in persons with Post-Traumatic Stress Disorder with and without Persistent Post-Concussive Symptoms (PPCS) following Traumatic Brain Injury (TBI). A total of 152 participants will be randomized in the Test Phase, with blinded adaptive sample size reassessment up to 176 participants, and a group-sequential approach to efficacy monitoring by the Data and Safety Monitoring Board (DSMB). A Pilot Phase was completed in which 74 participants were randomized. The Pilot Phase data will be used for confirming the safety of MeRT. For the Test Phase, 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 PPCS co-morbidity (+/-). Initial eligibility evaluation and data collection will occur at the Screening Visit (SC). Following the SC visit, there will be a 5-week treatment period in which active or sham investigative treatment will be administered during daily weekday visits to the study site. All participants who continue to be eligible will be offered 2 additional weeks of active MeRT study treatment. Main study outcomes will be collected at the second follow-up visit (F2) at the conclusion of the 5-week treatment period. An abbreviated data collection visit will occur during the third treatment week (the F1 follow-up visit). Additional follow up visits will occur 90 days (F3) and 180 days (F4) after the first day of study treatment. Participants, clinicians, and all personnel who participate in evaluation will be blind to study treatment group assignment. The first phase of this trial was conducted in partnership with the United States Special Operations Command (USSOCOM) and the Henry Jackson Foundation.

Official Title
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A Prospective, Double Blind, Randomized, Sham-Controlled, Clinical Trial to Evaluate The Safety And Efficacy Of Biometrics-Guided Magnetic EEG Resonance Therapy (MeRT) Treatment Of Post-Traumatic Stress Disorder With And Without Persistent Post-Concussive Symptoms (PPCS) Following Traumatic Brain Injury (TBI)

Conditions
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PostTraumatic Stress Disorder, Traumatic Brain Injury, Postconcussive Symptoms

Intervention / Treatment
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* Device: Active MeRT Treatment
* Device: Sham MeRT Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must meet all inclusion criteria to qualify for enrollment in the study: Willing and able to consent to participate in the study Age 18 - 65 years Diagnosis of PTSD according to DSM-V criteria via CAPS-5 Onset of symptoms meeting the DSM-5 criteria for PTSD symptoms persisting for a minimum of 6 months prior to the Screening Visit Minimum PCL-5 score of 30 Exclusion Criteria Participants will be excluded from study participation if one or more of the following exclusion criteria apply: Index trauma occurred before the age of 16 years History of open skull injury 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 History of cerebrovascular accident History of cerebral aneurysm EEG abnormalities that indicate risk of seizure, i.e., abnormal focal or general slowing, or ictal spikes, during the EEG recording Inability to calculate the EEG intrinsic alpha frequency at Screening Participation in any interventional research protocol within 3 months prior to the Screening Visit History of any type of ECT, rTMS, or MeRT treatment Treated within 30 days of the Screening Visit with any antipsychotic medication Treated within 30 days of the Screening Visit with any benzodiazepine or anticonvulsant medications Current treatment with any restricted concomitant medication (i.e., NDRI, SSRI, SNRI, or QBDZ) that has not been stable for the preceding 60 days at the time of the Screening Visit 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 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) 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 Pregnant, or female unwilling to use effective birth control during the course of the trial Plan to move away from the area, or knowledge that there will be an absence from the area, within 80 days following the Screening Visit (inclusive) 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 might prevent the participant from completing the study, render study results uninterpretable, or represent an unacceptable safety risk to the participant or study personnel that is not otherwise listed in exclusion criteria. 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 An elevated risk of suicide or violence to others Current psychotherapeutic treatment, expected to continue throughout the trial, that was begun in the preceding 60 days at the time of the Screening Visit

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active MeRT Treatment<br>Active treatment will consist of 6 seconds a minute for 30 minutes a day, 5 days a week for 5 weeks. | Device: Active MeRT Treatment<br>* A personalized biometrics-guided protocol known as magnetic EEG/ECG resonance therapy (MeRT) treatment that is tailored specifically to each participant's EEG intrinsic alpha frequency (IAF). rTMS is applied at the participant's IAF.<br>* Other names: rTMS Active Stimulator;|
| Sham Comparator: Sham MeRT Treatment<br>Sham treatment will consist of 6 seconds a minute for 30 minutes a day, 5 days a week for 5 weeks. | Device: Sham MeRT Treatment<br>* rTMS coil does not emit magnetic stimulation.<br>* Other names: rTMS Sham Stimulator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PTSD Symptoms | Change in PTSD symptoms as measured by the PTSD Checklist-5 (PCL-5). | Five weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PPCS | Change in Persistent Post-Concussion Symptoms as measured by reduction in Rivermead Post-Concussion Symptoms Questionnaire (RPQ-16) total severity score in the subset of participants with PPCS following TBI. | Five weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PTSD, Concussion, TBI, TMS, Post Traumatic Stress Disorder, Posttraumatic Stress Disorder, Post-traumatic Stress Disorder, MERT, rTMS, Transcranial Magnetic Stimulation, Repetitive Transcranial Magnetic Stimulation, Traumatic Brain Injury