Individualized (fMRI-guided) TMS Intervention for Post-Traumatic Stress Disorder (PTSD)
Engaging the Amygdala With Brain Stimulation for PTSD
1 other identifier
interventional
60
0 countries
N/A
Brief Summary
The goal of this clinical trial is to learn how transcranial magnetic stimulation (TMS) affects brain circuits involving the amygdala in adults with posttraumatic stress disorder (PTSD). The main questions it aims to answer are:
- Can MRI-guided TMS engage the amygdala by stimulating an individualized brain target connected to the amygdala?
- Does stimulation of this individualized target engage the amygdala differently than stimulation of control sites?
- Does a 6-week course of active TMS, compared with sham TMS, change amygdala responses and physiological responses to fear? Researchers will compare active TMS with sham TMS to evaluate changes in the targeted brain circuit and fear-related responses. Participants will:
- Receive active or sham TMS every weekday for 6 weeks
- Undergo MRI scans with TMS before and after the 6-week intervention to measure brain responses to stimulation
- Participate in fear learning and memory tasks while physiological responses are measured
- Undergo additional MRI scans, clinical assessments, questionnaires, and cognitive testing
- Complete remote follow-up assessments at 1, 6, and 12 months after the intervention
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for early_phase_1
Started Oct 2026
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
August 20, 2026
CompletedFirst Posted
Study publicly available on registry
August 25, 2026
CompletedStudy Start
First participant enrolled
October 12, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2028
Study Completion
Last participant's last visit for all outcomes
August 1, 2028
August 31, 2026
August 1, 2026
1.6 years
August 20, 2026
August 26, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Average amygdala blood-oxygen-level-dependent (BOLD) signal change following single-pulse fMRI-guided TMS (TMS On vs. TMS Off) to the individualized amygdala-connected target.
This primary endpoint compares amygdala BOLD signal during TMS On and TMS Off conditions, averaging across participants, providing a direct assessment of average amygdala engagement during fMRI-guided TMS. The change in BOLD signal observed in this comparison is defined as the amygdala-evoked response. This endpoint addresses the lack of mechanistic knowledge regarding amygdala engagement in PTSD when using individualized resting-state fMRI connectivity to guide TMS targeting.
Single visit (~2 hours)
Secondary Outcomes (2)
Difference in average amygdala-evoked response from TMS stimulation to fMRI-guided sites versus TMS stimulation of control sites.
Single visit (~2 hours)
(1) Difference in amygdala-evoked response from pre-treatment to post-treatment between active rTMS and sham; (2) difference in psychophysiological measures of fear extinction retention between active repetitive TMS (rTMS) and sham.
Up to 7 weeks
Study Arms (2)
Active iTBS
EXPERIMENTALParticipants will receive active intermittent theta burst stimulation (iTBS) delivered to an individualized ventrolateral prefrontal cortex (vlPFC) target selected based on positive resting-state functional connectivity with the basolateral amygdala. Active iTBS will be administered every weekday for 6 weeks (30 sessions) and is intended to stimulate the targeted vlPFC-amygdala circuit.
Sham iTBS
PLACEBO COMPARATORParticipants will receive sham iTBS at the same individualized amygdala-connected vlPFC target every weekday for 6 weeks (30 sessions).
Interventions
The sham TMS intervention will follow the same treatment schedule and session structure as active TMS. Sham stimulation will be delivered using the shielded side of the TMS coil together with synchronized scalp electrical stimulation to mimic the sensation of active TMS without delivering the intended magnetic stimulation to the targeted brain region.
The TMS intervention will involve two sets of intermittent theta-burst stimulation (iTBS) delivered every weekday for 6 weeks (30 sessions). Each iTBS set consists of 40 trains and 1,200 pulses, for a total of 2,400 pulses per treatment session. The two iTBS sets will be separated by approximately 5 minutes and delivered to the individualized amygdala-connected cortical target using MRI-guided neuronavigation.
Eligibility Criteria
You may qualify if:
- In order to participate in this study, potential participants must meet all of the following eligibility criteria:
- years old
- Current diagnosis of PTSD based on Diagnostic and Statistical Manual of Mental Disorders-5 criteria, as assessed by the Clinician-Administered PTSD Scale-5.
- Patient Health Questionnaire (PHQ-9) score = or \> than 10
- Comprehension of instructions in the English language.
- Capacity to provide informed consent and follow study procedures.
- Availability for the duration of the study.
You may not qualify if:
- Any individual who meets any of the following criteria at the time of enrollment will be excluded from participation:
- Implanted medical devices, metallic implants, or drug infusion pumps that are not MRI-safe (e.g., aneurysm clips, defibrillators, or cochlear implants)
- History of significant medical events (e.g., stroke, seizures, brain scarring) or neurological/neurodevelopmental conditions (e.g., epilepsy) that are contraindications for TMS and MRI or may adversely affect brain function and data interpretation.
- Current substance use disorder.
- History of a psychotic or bipolar disorder, including manic or hypomanic episodes.
- Prior failed response to full rTMS or Electroconvulsive Therapy (ECT)/Magnetic Seizure Therapy (MST) trial. Any successful prior treatments are acceptable and support a prognosis that a new rTMS treatment would be worth attempting.
- Inability to complete an MRI scan (e.g., claustrophobia, inability to remain still for extended periods).
- Inability to tolerate TMS administration
- Significant handicaps that would interfere with testing procedures
- Acute systemic infection, high fever
- Acute sleep deprivation or medication/substance intoxication or withdrawal (TMS seizure risk)
- Current use of cyclosporine, tacrolimus, or others that can cause leukoencephalopathy.
- Pregnancy
- Dialysis
- Suicide attempt in past 6 months (safety precaution); similarly, if ideation is particularly pronounced, Drs. Oathes and Sheline will decide with the patient whether the benefit of participating in a sham controlled (all patients given the option to receive active treatment eventually) study outweighs the risks. If the patient has a mental health provider and acquiesces, consultation with the provider will also be instrumental in this decision.
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Desmond Oathes, PhD
University of Pennsylvania
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- early phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, OUTCOMES ASSESSOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
August 20, 2026
First Posted
August 25, 2026
Study Start (Estimated)
October 12, 2026
Primary Completion (Estimated)
June 1, 2028
Study Completion (Estimated)
August 1, 2028
Last Updated
August 31, 2026
Record last verified: 2026-08
Data Sharing
- IPD Sharing
- Will not share