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

NCT07327385 | Not Yet Recruiting

• 1 other identifier: C202405067
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

PTSD; functional near-infrared spectroscopy; Heart Rate Variability; HRV; rTMS

Outcome Measures

Primary Outcomes (1)

• Change in Prefrontal Cortical Activation

  Change in prefrontal cortical activation, measured as differences in oxygenated hemoglobin (HbO₂) concentration using multi-channel functional near-infrared spectroscopy (fNIRS). Measurements are obtained at rest immediately before and immediately after each stimulation session to assess acute neurophysiological effects of prolonged intermittent theta-burst stimulation and high-frequency repetitive transcranial magnetic stimulation.

  Immediately before stimulation and immediately after each single stimulation session (active and sham), within each study period

Secondary Outcomes (4)

• Change in Autonomic Nervous System Activity

  Immediately before stimulation and immediately after each single stimulation session (active and sham), within each study period

• Incidence of Adverse Events

  From the start of the first stimulation session through 7 days after the second stimulation session

• Change in PTSD Symptom Severity

  Baseline, before the second stimulation session (Day 8), and 7 days after completion of the crossover phase

• Change in Depressive Symptom Severity

  Baseline, before the second stimulation session (Day 8), and 7 days after completion of the crossover phase

Study Arms (2)

Prolonged iTBS With Sham Control

EXPERIMENTAL

Participants in this arm receive a single-session prolonged intermittent theta-burst stimulation (prolonged iTBS) targeting the right dorsolateral prefrontal cortex, as well as a sham stimulation session in a randomized crossover sequence. Each stimulation session is separated by a 7-day washout period. Neurophysiological and autonomic measures are obtained immediately before and after each session.

Device: Prolonged Intermittent Theta-Burst Stimulation (prolonged iTBS); Device: Sham Transcranial Magnetic Stimulation

HF-rTMS With Sham Control

EXPERIMENTAL

Participants in this arm receive a single-session high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) targeting the right dorsolateral prefrontal cortex, as well as a sham stimulation session in a randomized crossover sequence. Each stimulation session is separated by a 7-day washout period. Neurophysiological and autonomic measures are obtained immediately before and after each session.

Device: High-Frequency Repetitive Transcranial Magnetic Stimulation (HF-rTMS); Device: Sham Transcranial Magnetic Stimulation

Interventions

Sham Transcranial Magnetic Stimulation DEVICE

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.

HF-rTMS With Sham Control; Prolonged iTBS With Sham Control

Prolonged Intermittent Theta-Burst Stimulation (prolonged iTBS) DEVICE

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.

Prolonged iTBS With Sham Control

High-Frequency Repetitive Transcranial Magnetic Stimulation (HF-rTMS) DEVICE

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.

HF-rTMS With Sham Control

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 18 to 65 years.
• Clinical diagnosis of posttraumatic stress disorder (PTSD) according to DSM-5 criteria, confirmed by a board-certified psychiatrist.
• Presence of comorbid major depressive disorder with stable clinical condition.
• PTSD symptom severity defined as: PTSD Checklist for DSM-5, Chinese version (C-PCL-5) total score ≥ 31.
• Depressive symptom severity defined as: Patient Health Questionnaire-9 (PHQ-9) total score ≥ 10.
• Stable psychiatric medication regimen for at least 4 weeks prior to enrollment, or medication-free.
• Ability to understand the study procedures and provide written informed consent.
• Normal or corrected-to-normal vision and hearing.
• Ability to comply with study procedures and visit schedule.

You may not qualify if:

• Lifetime diagnosis of schizophrenia spectrum disorders, bipolar disorder, or pervasive developmental disorders.
• Alcohol or substance use disorder (excluding caffeine and nicotine) within the past 6 months.
• Ongoing trauma-focused psychotherapy during the study period.
• Prior exposure to repetitive TMS treatment exceeding five sessions.
• Current or recent (within the past year) suicidal ideation or behavior, defined as: PHQ-9 item 9 score ≥ 1, confirmed by clinical psychiatric evaluation.
• Self-injurious behavior requiring medical attention within the past 3 months.
• History of epilepsy, seizure disorder, or family history of epilepsy.
• Significant neurological disorders, severe traumatic brain injury, or history of brain surgery.
• Presence of implanted metallic or electronic medical devices (e.g., pacemakers, cochlear implants, neurostimulators).
• Uncontrolled major medical illnesses or severe cardiovascular disease.
• Pregnancy or breastfeeding.
• Skin lesions or infections at the stimulation site.
• Use of medications known to significantly lower seizure threshold (e.g., tricyclic antidepressants or certain analgesics).
• Any condition deemed by the investigator to render the participant unsuitable for rTMS.

Sponsors & Collaborators

• Tri-Service General Hospital: lead

Study Sites (1)

Tri-Service General Hospital

Taipei, Neihu, 114, Taiwan

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Study Officials

• Tien-Yu Chen, PhD, MD

  Tri-Service General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tao-Yi Chao, BS

CONTACT

886-2-87923311; loveinazuma1917@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants and outcome assessors will be blinded to treatment assignment. Active and sham stimulation will be delivered using coils identical in appearance and sound. The stimulation operator will not participate in clinical or physiological outcome assessments. Blinding codes will remain concealed until completion of data collection and database lock.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Visiting Physician

Model Details: This study uses a randomized, double-blind, sham-controlled, crossover design to examine the immediate neurophysiological effects of noninvasive brain stimulation in patients with posttraumatic stress disorder comorbid with major depressive disorder. Each participant receives both an active stimulation session (either prolonged intermittent theta-burst stimulation or high-frequency repetitive transcranial magnetic stimulation) and a sham stimulation session in a randomized sequence. A washout period of 7 days is implemented between sessions to minimize potential carryover effects. Blinding is maintained for participants and outcome assessors, while stimulation operators are not involved in outcome evaluation. Prefrontal cortical activity and autonomic nervous system responses are assessed immediately before and after each stimulation session.

Study Record Dates

• First Submitted: December 24, 2025
• First Posted: January 8, 2026
• Study Start: February 9, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

TW (1)