ETMS4Stress: Electroencephalogram (EEG) Enhanced Transcranial Magnetic Stimulation (eTMS) for Chronic Trauma and Stressor-Related Disorders (TSRD)

Sponsor

Marcia Bockbrader, MD PhD (Other)

Overall Status

Recruiting

CT.gov ID

NCT05835414

Collaborator

(none)

Enrollment

Location

Arm

26.7

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this clinical trial is to learn about the safety, feasibility, and preliminary efficacy of EEG-enhanced transcranial magnetic stimulation (eTMS) as an adjunct to standard-of-care therapies for chronic trauma and stressor related disorders (TSRD) among US military veterans.

The main questions the study aims to answer are:

Is it safe to provide 30 sessions of eTMS for veterans with chronic TSRD?
Is it feasible to provide 30 sessions of eTMS as an adjunct to standard-of-care therapies for veterans with chronic TSRD?
Does health-related quality of life improve among veterans after 30 sessions of eTMS as an adjunct to standard-of-care therapies for chronic TSRD?

Participants will undergo 30 sessions of eTMS as an adjunct to standard-of-care therapies for veterans with chronic TSRD, weekly reassessment during treatment, and intermittent follow-up for 36 weeks post-enrollment.

Condition or Disease	Intervention/Treatment	Phase
Trauma and Stressor Related Disorders	Device: Adjunctive, midline prefrontal, lower intensity, shorter session, EEG-enhanced, repetitive transcranial magnetic stimulation (eTMS)	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This will be a staged, open-label, Phase II/III safety, feasibility, and efficacy investigational device trial. A staged approach will be utilized to assess safety, feasibility, and preliminary efficacy with 30 participants with an interim analysis after data collection at 6 weeks. If safety benchmarks are passed, the study will proceed with Stage 2, in which an additional 270 participants will be enrolled using randomization to multiple baselines for efficacy analyses.This will be a staged, open-label, Phase II/III safety, feasibility, and efficacy investigational device trial. A staged approach will be utilized to assess safety, feasibility, and preliminary efficacy with 30 participants with an interim analysis after data collection at 6 weeks. If safety benchmarks are passed, the study will proceed with Stage 2, in which an additional 270 participants will be enrolled using randomization to multiple baselines for efficacy analyses.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Electroencephalogram (EEG) Enhanced Transcranial Magnetic Stimulation (eTMS) for Chronic Trauma and Stressor-Related Disorders (TSRD) (ETMS for Stress)

Actual Study Start Date :

Apr 10, 2023

Anticipated Primary Completion Date :

Jun 30, 2024

Anticipated Study Completion Date :

Jun 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Adjunctive eTMS treatment (no delay) 6 weeks (30 sessions) of daily eTMS as an adjunct to standard of care TSRD treatment	Device: Adjunctive, midline prefrontal, lower intensity, shorter session, EEG-enhanced, repetitive transcranial magnetic stimulation (eTMS) Approximately 2000 pulses per session (x30 sessions) of midline prefrontal, repetitive transcranial magnetic stimulation at 50% or less of motor threshold, calibrated via EEG to a resonant alpha frequency of the participant, and given over approximately 12 minutes. Given as an adjunct to standard of care and integrative treatment for TSRD.

Arm

Intervention/Treatment

Experimental: Adjunctive eTMS treatment (no delay)

6 weeks (30 sessions) of daily eTMS as an adjunct to standard of care TSRD treatment

Device: Adjunctive, midline prefrontal, lower intensity, shorter session, EEG-enhanced, repetitive transcranial magnetic stimulation (eTMS)

Approximately 2000 pulses per session (x30 sessions) of midline prefrontal, repetitive transcranial magnetic stimulation at 50% or less of motor threshold, calibrated via EEG to a resonant alpha frequency of the participant, and given over approximately 12 minutes. Given as an adjunct to standard of care and integrative treatment for TSRD.

Outcome Measures

Primary Outcome Measures

Number of participants with device-related serious adverse events [6 weeks]
To address safety of the procedure, the study investigators will report number of participants (of 30 initial cohort) with expected, device-related serious adverse events (SAE's) or unexpected, device-related SAE's during treatment
Rate of participants completing 80% of scheduled visits [6 weeks]
To assess feasibility of the procedure, the study investigators will report the rate of participants (for initial cohort of 30) completing >= 80% of the 30 scheduled eTMS sessions

Secondary Outcome Measures

Mean change in Veterans RAND 36-item health survey (VR-36) mental component scores (MCS) [6 weeks]
To assess efficacy of the procedure to improve health related quality of life, the study investigators will report the mean change from baseline to week 6 in mental component score (MCS) on Veterans RAND 36-item health survey (VR-36) for participants (in initial cohort of 30) who completed >=80% of eTMS sessions

Eligibility Criteria

Criteria

Ages Eligible for Study:

22 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Positive identification as a Veteran per discharge paperwork (DD-214, DD-215, NGB-22, NGB-22A) and photo ID, or Veterans Health Administration Veteran Health Identification Card (VHIC)
Presence of deployment-related stressful events (as defined by the Deployment Risk & Resilience Inventory-2, DRRI-2)
Trauma event(s) (defined on the Life Experiences Checklist for DSM-5, LEC-5)
Presence of 6 months or more of 6 or more "moderate" or worse symptoms from any of the five categories associated with stress disorders as operationalized on the PTSD Checklist for DSM-5 (PCL-5; intrusion, altered mood and cognitions, dissociation, avoidance, and arousal).
Informed consent for study participation, off label-eTMS, and data use
Enrollment in addiction services, if meets standard addiction treatment criteria
Enrollment in opioid reduction services, if dependent on opioids and morphine equivalent daily dose exceeds 50 mg (50 morphine equivalent daily dose, MEDD)
Agreement to limit daily alcoholic beverage consumption to no more than 2 servings
Signed pain contract, if MEDD >= 80, per State of Ohio prescribing guidelines

Exclusion Criteria:

Uncontrolled medical, psychological or neurological conditions including, but not limited to:
Uncontrolled psychosis or mania
Uncontrolled seizure disorder or EEG abnormalities that indicate risk of seizure, i.e., epileptiform discharges during the EEG recording
Uncontrolled cardiac, pulmonary, or endocrine disorder (e.g., diabetes)
Acute pain or illness
Active, untreated addiction to prescription drugs, alcohol or illicit substances (not including cannabis or derivatives, which are available in many states under medical prescription or for recreational use)
Clinically significant medical condition or abnormality that in the Investigator's judgment might pose a potential safety risk to the subject or limit the interpretation of the trial results
Pregnant, or female unwilling to use effective birth control during the course of the trial (unless cleared for participation by obstetrician/gynecologist)
Absolute contraindications to TMS: Presence of aneurysm clips or coils, cochlear or ocular implant, cortical epidural stimulator, deep brain stimulator, pacemaker or defibrillator, retained intracranial metal foreign body (bullets, shrapnel - excluding titanium and oral implants), steel stents or shunts, active vagal nerve stimulator, ventriculoperitoneal (VP) shunt.
Prior TMS treatment
Unwilling or unable to adhere to the study treatment, data collection schedule, or study procedures