Individualized (fMRI-guided) TMS Intervention for Post-Traumatic Stress Disorder (PTSD)
Trial statusNot yet recruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18-65
SponsorUniversity of Pennsylvania
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
18-65 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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Active Transcranial Magnetic Stimulation (TMS)
DeviceThe 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.
Sham Transcranial Magnetic Stimulation (TMS)
DeviceThe 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.
Treatment groups
60 Participants
are divided into 2 treatment groupsGroup A: Active iTBSExperimental treatment 1 intervention
Group B: Sham iTBSPlacebo comparator 1 intervention
Trial outcomes
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.
Time frame
Single visit (~2 hours)Secondary outcomes
1
Difference in average amygdala-evoked response from TMS stimulation to fMRI-guided sites versus TMS stimulation of control sites.
This secondary endpoint provides further mechanistic knowledge regarding amygdala engagement in PTSD when using individualized resting-state fMRI connectivity to guide TMS targeting by comparing the effectiveness of the fMRI-guided targeting to stimulation of a control site that is not expected to evoke a response in the amygdala.
Time frame
Single visit (~2 hours)2
(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.
This secondary endpoint evaluates whether repeated stimulation of an individualized amygdala-connected cortical target is associated with measurable changes in amygdala responsivity following treatment relative to a sham rTMS condition. Differential changes in the amygdala-evoked response between active and sham rTMS would provide evidence that the targeted cortico-amygdala circuit can be modulated with rTMS. Fear extinction retention measures will serve as a complementary physiological index of treatment-related changes in fear-processing circuits relative to sham.
Time frame
Up to 7 weeksLocations
Sponsors and contacts
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Source ClinicalTrials.gov
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