Personalized Repetitive Transcranial Magnetic Stimulation (PrTMS) for Treatment of Post-Traumatic Stress Disorder (PTSD)

This study is testing a personalized form of brain stimulation called PrTMS as a treatment for post-traumatic stress disorder (PTSD) in military service members and veterans. Unlike standard approaches, this treatment uses a simple brainwave test (EEG) to tailor the therapy to each individual. Participants will be randomly assigned to receive either active treatment or a comparison (sham) treatment over 6 weeks. Researchers will track changes in PTSD symptoms, mood, sleep, and overall well-being, including using wearable devices to measure things like sleep and heart rate. The goal is to see whether this personalized approach can provide greater and longer-lasting relief for individuals living with PTSD.

Study Overview

• Status: Not yet recruiting
• Conditions: Posttraumatic Stress Disorder (PTSD)
• Intervention / Treatment: Device: Transcranial Magnetic Stimulation; Device: Transcranial Magnetic Stimulation Sham

Detailed Description

This study is a randomized, double-blind, sham-controlled trial evaluating a personalized approach to repetitive transcranial magnetic stimulation (PrTMS) for the treatment of post-traumatic stress disorder (PTSD) in military service members and veterans. PrTMS integrates spectral electroencephalography (sEEG) with neurocognitive assessments to individualize stimulation parameters, including frequency and intensity, and to allow for dynamic adjustment over the course of treatment based on each participant's evolving neurophysiological profile. Participants will undergo a 6-week treatment protocol (5 sessions per week), followed by longitudinal assessments over 6 months to evaluate durability of response. Multimodal outcomes will include clinician-administered and self-report measures of PTSD, mood, anxiety, and sleep, as well as physiologic and behavioral data collected via wearable devices. This study is designed to determine whether EEG-guided, precision neuromodulation improves clinical outcomes compared to standard, non-personalized stimulation approaches and to inform the development of individualized treatment strategies in PTSD.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Joseph Bonvie, PsyD; Phone Number: 8572053407; Email: jbonvie@mgh.harvard.edu
• Study Contact Backup: Name: Alan Berkeley, MBA; Phone Number: 8572839928; Email: aberkeley@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Charlestown, Massachusetts, United States, 02129
      • Home Base
      • Contact: Alan Berkeley, MBA; Phone Number: 8572839928; Email: aberkeley@mgh.harvard.edu
      • Principal Investigator: Sofia E Matta, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Reserve or former member of the military (veteran status)
• Age 18 years or older
• Primary diagnosis of post-traumatic stress disorder (PTSD) confirmed by the - Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
• Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5) score ≥ 33, indicating clinically significant PTSD symptoms
• Proficient in English (spoken and written) to ensure understanding of study procedures and informed consent

Exclusion Criteria:

• History of open-skull traumatic brain injury
• Clinically significant seizure disorder or history of manic episodes
• Neurological conditions associated with increased risk (e.g., increased intracranial pressure, brain lesions, stroke, cerebral aneurysm)
• Electroencephalogram (EEG) abnormalities suggesting elevated seizure risk
• Repetitive transcranial magnetic stimulation (rTMS) within 3 months prior to screening
• Current use of antipsychotic or anticonvulsant medications
• Presence of intracranial implants or non-removable metal in or near the head (excluding the mouth)
• Clinically significant or unstable medical conditions, including active suicidal ideation
• Uncontrolled medical illness (e.g., thyroid, hepatic, cardiac, pulmonary, or renal disease)
• Initiation of PTSD-specific treatment within the past 4 weeks (participants on a stable regimen may be eligible)
• Pregnancy (for women of childbearing potential)
• Any condition that, in the opinion of the investigator, may interfere with study participation or completion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active PrTMS (EEG-Guided rTMS); Participants receive personalized, EEG-guided repetitive transcranial magnetic stimulation (PrTMS) administered 5 days per week for 6 weeks, with stimulation parameters individualized and adjusted over time based on serial sEEG and neurocognitive assessments.	Device: Transcranial Magnetic Stimulation; Personalized repetitive transcranial magnetic stimulation (PrTMS) is delivered using the Neurocare Apollo TMS Therapy System for 30 minutes per session, 5 days per week, over 6 weeks. Stimulation parameters (frequency 8-13 Hz and intensity typically 50-60% of motor threshold) are individualized based on baseline and serial spectral EEG (sEEG) assessments, with adjustments made throughout treatment to optimize response.
Sham Comparator: Sham PrTMS; Participants receive sham repetitive transcranial magnetic stimulation (rTMS) administered 5 days per week for 6 weeks using a sham coil that mimics the sound and sensation of active treatment without delivering a therapeutic magnetic field.	Device: Transcranial Magnetic Stimulation Sham; Sham stimulation will be delivered using the same Neurocare Apollo TMS Therapy System as the active intervention, with identical treatment schedule (5 days per week for 6 weeks; 30 minutes per session). A sham coil identical in appearance to the active coil will be used, which does not generate a therapeutic magnetic field. To mimic the sensory experience of active treatment, the sham procedure will produce similar auditory clicking and will include a surface electrical stimulation (TENS) applied to the forehead to replicate scalp sensations and mild muscle contraction. This approach is designed to maintain blinding while delivering no active neuromodulatory effect.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)	The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a structured interview and gold standard for diagnosing and assessing PTSD in clinical and research settings. It assesses current or lifetime PTSD based on DSM-5 criteria and measures symptom severity across the 20 PTSD symptoms, including the dissociative subtype, in relation to a single index traumatic event. Total severity scores range from 0 to 80, with higher scores indicating worse PTSD symptom severity.	At baseline and the end of treatment at Week 6.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5)	The Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5) is a 20-item self-report measure that assesses PTSD symptom presence and severity across DSM-5 symptom clusters, including re-experiencing, avoidance, negative alterations in cognition and mood, and arousal. Total scores range from 0 to 80, with higher scores indicating greater PTSD symptom severity.	At baseline, and weekly during Weeks 1-6, and at Week 10, Week 22, and Week 34.
Generalized Anxiety Disorder-7 (GAD-7)	The Generalized Anxiety Disorder-7 (GAD-7) is a seven-item self-report scale used to assess the severity of generalized anxiety symptoms and to screen for anxiety over the past two weeks. Total scores range from 0 to 21, with higher scores indicating greater anxiety severity.	At baseline, and weekly during Weeks 1-6, and at Week 10, Week 22, and Week 34.
Patient Health Questionnaire-9 (PHQ-9)	The Patient Health Questionnaire-9 (PHQ-9) is a 9-item self-report measure used to screen, diagnose, monitor, and assess the severity of depression. Total scores range from 0 to 27, with higher scores indicating greater depression severity.	At baseline, and weekly during Weeks 1-6, and at Week 10, Week 22, and Week 34.
Tinnitus Functional Index (TFI)	The Tinnitus Functional Index (TFI) is a 25-item self-report questionnaire designed to measure the severity, negative impact, and treatment-related changes of tinnitus on a person's daily life over the past week. Total scores range from 0 to 100, with higher scores indicating greater tinnitus severity and functional impact.	At baseline, and weekly during Weeks 1-6, and at Week 10, Week 22, and Week 34.
TMS Tolerability Worksheet (TTW)	The TMS Tolerability Worksheet (TTW) is a clinician-administered tool used to document session-related side effects and adverse events associated with transcranial magnetic stimulation (TMS), including symptoms such as headache, neck pain, discomfort at the stimulation site, and hearing changes, with severity categorized as none, mild, moderate, or severe.	At baseline and weekly during Weeks 1-6.
Pittsburgh Sleep Quality Index Addendum (PSQI-A)	The Pittsburgh Sleep Quality Index Addendum for PTSD (PSQI-A) is a self-report measure that assesses disruptive nocturnal behaviors associated with PTSD, including nightmares, panic, hot flashes, and acting out dreams. Total scores range from 0 to 21, with higher scores indicating greater severity of disruptive nocturnal behaviors.	At baseline, and weekly during Weeks 1-6, and at Week 10, Week 22, and Week 34.
Total Sleep Time (Oura Ring)	Total sleep time, measured in hours per night using the Oura Ring wearable device.	Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34.
Sleep Efficiency (Oura Ring)	Sleep efficiency, expressed as a percentage (0-100%) representing the ratio of time spent asleep relative to the total time in bed, using the Oura Ring wearable device.	Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34.
Sleep Latency (Oura Ring)	Sleep latency, measured in minutes, defined as the time from the start of the sleep period to sleep onset, as recorded by the Oura Ring wearable device. Typical values range from approximately 0 to 60 minutes.	Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34.
REM Sleep Duration (Oura Ring)	Duration of rapid eye movement (REM) sleep, measured in minutes using the Oura Ring wearable device.	Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34.
REM Sleep Percentage (Oura Ring)	REM sleep expressed as a percentage of total sleep time, measured using the Oura Ring wearable device.	Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34.
Light Sleep Duration (Oura Ring)	Duration of light sleep, measured in minutes using the Oura Ring wearable device.	Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34.
Light Sleep Percentage (Oura Ring)	Light sleep expressed as a percentage of total sleep time, measured using the Oura Ring wearable device.	Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34.
Deep Sleep Duration (Oura Ring)	Duration of deep (slow-wave) sleep, measured in minutes using the Oura Ring wearable device.	Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34.
Deep Sleep Percentage (Oura Ring)	Deep (slow-wave) sleep expressed as a percentage of total sleep time, measured using the Oura Ring wearable device.	Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34.
Resting Heart Rate (Oura Ring)	Resting heart rate, measured in beats per minute (bpm) using the Oura Ring wearable device.	Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34.
Heart Rate Variability (Oura Ring)	Heart rate variability (HRV), measured in milliseconds (ms) using the Oura Ring wearable device.	Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34.
Body Temperature (Oura Ring)	Nightly body temperature deviation from baseline, measured in degrees Fahrenheit (°F) using the Oura Ring wearable device.	Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34.
Daily Step Count (Oura Ring)	Daily step count, measured as the number of steps per day using the Oura Ring wearable device.	Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34.
Active Energy Expenditure (Oura Ring)	Active energy expenditure, measured in kilocalories per day (kcal/day) using the Oura Ring wearable device.	Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34.
Total Energy Expenditure (Oura Ring)	Total energy expenditure, measured in kilocalories per day (kcal/day) using the Oura Ring wearable device.	Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34.
Sedentary Activity Duration (Oura Ring)	Duration of sedentary activity, measured in minutes per day using the Oura Ring wearable device.	Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34.
Light Activity Duration (Oura Ring)	Duration of light physical activity, measured in minutes per day using the Oura Ring wearable device.	Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34.
Moderate Activity Duration (Oura Ring)	Duration of moderate physical activity, measured in minutes per day using the Oura Ring wearable device.	Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34.
Vigorous Activity Duration (Oura Ring)	Duration of vigorous physical activity, measured in minutes per day using the Oura Ring wearable device.	Continuously from enrollment through Week 6, and at follow-up at Week 10, Week 22, and Week 34.

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: United States Air Force Research Laboratory
• Investigators: Principal Investigator: Sofia E Matta, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Makale MT, Nybo C, Blum K, Dennen CA, Elman I, Murphy KT. Pilot Study of Personalized Transcranial Magnetic Stimulation with Spectral Electroencephalogram Analyses for Assessing and Treating Persons with Autism. J Pers Med. 2024 Aug 12;14(8):857. doi: 10.3390/jpm14080857.
• Makale MT, Nybo C, Keifer J, Blum K, Dennen CA, Baron D, Sunder K, Elman I, Makale MR, Thanos PK, Murphy KT. Preliminary Observations of Personalized Repetitive Magnetic Stimulation (PrTMS) Guided by EEG Spectra for Concussion. Brain Sci. 2023 Aug 9;13(8):1179. doi: 10.3390/brainsci13081179.
• Makale MT, Abbasi S, Nybo C, Keifer J, Christman L, Fairchild JK, Yesavage J, Blum K, Gold MS, Baron D, Cadet JL, Elman I, Dennen CA, Murphy KT. Personalized repetitive transcranial magnetic stimulation (prtms(R)) for post-traumatic stress disorder (ptsd) in military combat veterans. Heliyon. 2023 Aug 8;9(8):e18943. doi: 10.1016/j.heliyon.2023.e18943. eCollection 2023 Aug.

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): January 31, 2029

Study Registration Dates

• First Submitted: March 24, 2026
• First Submitted That Met QC Criteria: April 10, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Veterans; Transcranial Magnetic Stimulation; Posttraumatic Stress Disorder; Precision Medicine
• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Therapeutics; Magnetic Field Therapy; Transcranial Magnetic Stimulation
• Other Study ID Numbers: 2025P003206

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared. Only de-identified, aggregate data may be shared with collaborators, including the United States Air Force Research Laboratory (USAFRL), under a data sharing agreement.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No