NCT07327385

To Investigate the Change of Brain and Autonomic Function From Different Protocols of Repeated Transcranial Magnetic Stimulation Therapy for Patients With Post-traumatic Stress Disorder Comorbid Major Depressive Disorder

The Pathophysiological Mechanisms and Novel Treatments Linking Stress and Mental Health Conditions -To Investigate the Change of Brain and Autonomic Function From Different Protocols of Repeated Transcranial Magnetic Stimulation Therapy for Patients With Post-traumatic Stress Disorder Comorbid Major Depressive Disorder: a Randomized, Double-blind, Crossover Study

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Tri-Service General Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This study aims to investigate the immediate neurophysiological and autonomic effects of two noninvasive brain stimulation protocols-prolonged intermittent theta-burst stimulation (prolonged iTBS) and high-frequency repetitive transcranial magnetic stimulation (HF-rTMS)-in patients with posttraumatic stress disorder (PTSD) comorbid with major depressive disorder (MDD). Using a randomized, double-blind, sham-controlled crossover design, changes in prefrontal cortical activity measured by functional near-infrared spectroscopy (fNIRS) and autonomic nervous system function measured by heart rate variability (HRV) will be assessed before and immediately after a single stimulation session.

Detailed description

Posttraumatic stress disorder (PTSD) is a chronic psychiatric condition frequently accompanied by depressive symptoms and autonomic dysregulation. Although pharmacotherapy and psychotherapy are standard treatments, many patients show limited response or experience significant side effects. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising noninvasive neuromodulatory intervention; however, the optimal stimulation protocol for PTSD remains unclear. This randomized, double-blind, crossover study is designed to compare the immediate effects of prolonged iTBS and HF-rTMS applied to the right dorsolateral prefrontal cortex (DLPFC) on brain function and autonomic regulation in adults with PTSD comorbid with MDD. Each participant will receive one active stimulation session (either prolonged iTBS or HF-rTMS) and one sham stimulation session in a randomized order, separated by a 7-day washout period to minimize carryover effects. Prefrontal cortical activation will be measured using multi-channel functional near-infrared spectroscopy (fNIRS), and autonomic nervous system activity will be assessed using heart rate variability (HRV) analysis derived from electrocardiographic recordings. The primary objective is to characterize protocol-specific neurophysiological response patterns and identify quantifiable biomarkers of brain stimulation response that may inform future personalized treatment strategies for PTSD with comorbid depression.

Conditions

• Posttraumatic Stress Disorder (PTSD)
• Depression - Major Depressive Disorder

Interventions

Type	Name	Description
DEVICE	Prolonged Intermittent Theta-Burst Stimulation (prolonged iTBS)	Prolonged intermittent theta-burst stimulation is delivered using a Magstim Rapid2 stimulator with a figure-eight coil targeting the right dorsolateral prefrontal cortex (DLPFC), localized with the Beam F4 method. Stimulation is administered at 80% of individual motor threshold using an intermittent theta-burst pattern (2 seconds on, 8 seconds off), consisting of 3-pulse bursts at 50 Hz repeated at 5 Hz. A single session lasts approximately 9.5 minutes and delivers a total of 1,800 pulses.
DEVICE	High-Frequency Repetitive Transcranial Magnetic Stimulation (HF-rTMS)	High-frequency rTMS is delivered using a Magstim Rapid2 stimulator with a figure-eight coil targeting the right dorsolateral prefrontal cortex (DLPFC), localized with the Beam F4 method. Stimulation follows the DASH protocol at 120% of motor threshold and 10 Hz frequency, with 4-second stimulation trains (40 pulses per train) followed by an 11-second inter-train interval, for a total of 75 trains. The single-session duration is approximately 18.75 minutes, delivering 3,000 pulses.
DEVICE	Sham Transcranial Magnetic Stimulation	Sham stimulation is delivered using a placebo coil identical in appearance and acoustic output to the active coil but without producing a magnetic field sufficient to induce cortical stimulation. Sham sessions match the corresponding active stimulation protocol in duration and procedure to maintain blinding.

Timeline

• Start date: 2026-02-09
• Primary completion: 2028-12-31
• Completion: 2028-12-31
• First posted: 2026-01-08
• Last updated: 2026-02-17

Locations

1 site across 1 country: Taiwan