Salience Network Informed rTMS for PTSD
Salience Network-guided rTMS for Veterans With PTSD
2 other identifiers
interventional
84
1 country
1
Brief Summary
The proposed study will test whether magnetic resonance imaging (MRI)-guided transcranial magnetic stimulation (TMS) can reduce posttraumatic stress disorder (PTSD) symptoms in Veterans. TMS is a noninvasive treatment that uses magnetic pulses to change activity in specific areas of the brain. In this study, MRI will be used to personalize the location of TMS based on brain networks involved in detecting and responding to important or threatening information. Veterans with PTSD will be randomly assigned to receive either active or non-active control TMS over 20 sessions. The study will examine whether active TMS improves PTSD symptoms and changes the brain circuits targeted by treatment. If effective, this approach may help improve and personalize TMS treatment for Veterans with PTSD. This project supports the Department of Veterans Affairs mission of developing more effective, biologically informed treatments for Veterans with PTSD.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jul 2027
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 6, 2026
CompletedFirst Posted
Study publicly available on registry
October 21, 2026
CompletedStudy Start
First participant enrolled
July 1, 2027
ExpectedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2031
Study Completion
Last participant's last visit for all outcomes
March 31, 2031
October 21, 2026
October 1, 2026
3.8 years
October 6, 2026
October 14, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Severity Score
The CAPS-5 is a clinician-administered interview used to assess PTSD symptoms according to DSM-5 criteria. Total PTSD symptom severity scores range from 0 to 80, with higher scores indicating greater PTSD symptom severity. The outcome is change in CAPS-5 total severity score from baseline to the post-treatment assessment.
Baseline and immediately following completion of treatment (approximately Week 4-6)
Change in Anterior Insula Resting-State Functional Connectivity
Resting-state functional MRI will be used to assess functional connectivity of the anterior insula (aINS). The aINS seed will be defined using the region used for personalized TMS targeting. Functional connectivity is measured as the relationship between the aINS blood-oxygen-level-dependent (BOLD) time series and BOLD time series to the brain. Higher association means higher functional connectivity. The outcome is change in aINS resting-state functional connectivity from the pre-treatment to post-treatment MRI assessment.
Baseline and immediately following completion of treatment (approximately Week 4-6)
Secondary Outcomes (3)
Change in Brain Activation During the Anticipation Task
Baseline and immediately following completion of treatment (approximately Week 4-6)
Change in Heart Rate Variability
Baseline and immediately following completion of treatment (approximately Week 4-6)
Differential Change in CAPS-5 PTSD Symptom Cluster Severity
Baseline and immediately following completion of treatment (approximately Week 4-6)
Other Outcomes (3)
Change in Patient Health Questionnaire-9 (PHQ-9) Total Score
Baseline, post-treatment (Week 4, up to Week 6), and 4-week and 8-week post-treatment follow-ups.
Change in Generalized Anxiety Disorder-7 (GAD-7) Total Score
Baseline, post-treatment (Week 4, up to Week 6), and 4-week and 8-week post-treatment follow-ups
Change in PTSD Checklist for DSM-5 (PCL-5) Total Score
Baseline, post-treatment (Week 4, up to Week 6), and 4-week and 8-week post-treatment follow-ups
Study Arms (2)
Active MRI-Guided intermittent theta burst stimulation (iTBS)
EXPERIMENTALParticipants randomized to this arm will receive 20 sessions of active intermittent theta burst stimulation (iTBS), scheduled 5 days per week for 4 weeks. When needed because of scheduling interruptions, the 20 sessions may be completed within up to 6 weeks. Treatment will be delivered to an individualized right dorsolateral prefrontal cortex target identified using MRI/fMRI-based functional connectivity.
Sham MRI-Guided intermittent theta burst stimulation (iTBS)
SHAM COMPARATORParticipants randomized to this arm will receive 20 sessions of sham intermittent theta burst stimulation (iTBS), scheduled 5 days per week for 4 weeks. When needed because of scheduling interruptions, the 20 sessions may be completed within up to 6 weeks. The same individualized MRI/fMRI-guided treatment location and treatment schedule will be used as in the active arm.
Interventions
Active intermittent theta burst stimulation (iTBS) will be delivered using the MagVenture TMS Therapy System. An individualized right dorsolateral prefrontal cortex treatment target will be identified using MRI/fMRI-based functional connectivity with the right anterior insula of the salience network. The Brainsight neuronavigation system will be used to localize the individualized target and guide TMS coil positioning. Each treatment session will consist of 600 pulses. Participants will receive 20 treatment sessions, scheduled 5 days per week for 4 weeks. When needed because of scheduling interruptions, the 20 sessions may be completed within up to 6 weeks.
Sham intermittent theta burst stimulation (iTBS) will be delivered using the MagVenture TMS Therapy System. An individualized right dorsolateral prefrontal cortex treatment target will be identified using MRI/fMRI-based functional connectivity with the right anterior insula of the salience network. The Brainsight neuronavigation system will be used to localize the individualized target and guide TMS coil positioning. Sham stimulation will use the same treatment location, session structure, and treatment schedule as the active condition and is designed to mimic the treatment experience without delivering active therapeutic stimulation. Participants will receive 20 sham treatment sessions, scheduled 5 days per week for 4 weeks. When needed because of scheduling interruptions, the 20 sessions may be completed within up to 6 weeks.
Eligibility Criteria
You may qualify if:
- Veteran status
- Current diagnosis of posttraumatic stress disorder (PTSD), as determined by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
- Able to provide informed consent
- Able to speak, read, and write English
- Willing and able to complete 20 intermittent theta burst stimulation (iTBS) treatment sessions, scheduled 5 days per week for 4 weeks, with completion permitted within up to 6 weeks when needed
- Willing and able to complete magnetic resonance imaging (MRI) assessments before and after the iTBS treatment course
You may not qualify if:
- History of a neurological disorder associated with cognitive dysfunction, such as dementia or mild cognitive impairment
- History of traumatic brain injury associated with an estimated loss of consciousness greater than 30 minutes
- Current acute suicidal ideation or recent psychiatric hospitalization when, in the judgment of the study clinician or treating psychiatrist, the condition would interfere with safe study participation
- Current psychotic disorder or bipolar disorder/mania
- Pregnancy; less than 3 months postpartum; or less than 3 months since cessation of breastfeeding
- Contraindication to magnetic resonance imaging (MRI) or transcranial magnetic stimulation (TMS), including MRI/TMS-incompatible implanted metallic or electronic devices, retained metallic foreign bodies, or other implants determined to be unsafe following MRI/TMS safety review
- History of neurosurgery when incompatible with safe MRI or TMS participation
- Claustrophobia that would prevent completion of MRI
- Inability to lie still in the MRI scanner for approximately 60 minutes
- Vision impairment that cannot be adequately corrected for completion of study procedures
- Initiation of a new psychiatric medication within 4 weeks before enrollment or anticipated inability to maintain a stable medication regimen during study participation
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
VA San Diego Healthcare System, San Diego, CA
San Diego, California, 92161-0002, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Daniel M Stout, PhD
VA San Diego Healthcare System, San Diego, CA
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Participants, transcranial magnetic stimulation (TMS) technicians administering stimulation, investigators, and clinical outcome assessors will be blinded to treatment assignment. A designated unblinded study team member who is not involved in treatment administration, outcome assessment, or data analysis will conduct stratified randomization and assign the corresponding blinded Brainsight/MagVenture treatment code. TMS technicians will enter the assigned code into the stimulation system without knowing whether the code corresponds to active or control (sham) stimulation. Treatment assignments will remain concealed from the blinded study team unless unblinding is required for participant safety.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- FED
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 6, 2026
First Posted
October 21, 2026
Study Start (Estimated)
July 1, 2027
Primary Completion (Estimated)
March 31, 2031
Study Completion (Estimated)
March 31, 2031
Last Updated
October 21, 2026
Record last verified: 2026-10
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- Data will become available following publication of the primary study results and will remain available in accordance with applicable VA data-retention and data-sharing requirements.
- Access Criteria
- Data will be made available to qualified investigators for scientifically appropriate research purposes following review and approval by the appropriate VA and institutional authorities. Access will require compliance with applicable VA privacy and security requirements and execution of any required data use agreement.
Coded individual participant data underlying publications resulting from this study will be made available after removal of personal identifiers and in accordance with applicable VA requirements. Data sharing will be subject to appropriate privacy protections and any required data use agreements to prevent identification or re-identification of participants.