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

NCT ID: NCT07327385

Last Updated: 2026-01-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-17

Study Completion Date

2028-12-31

Brief Summary

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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

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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

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Posttraumatic Stress Disorder (PTSD) Depression - Major Depressive Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors
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.

Study Groups

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Prolonged iTBS With Sham Control

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.

Group Type EXPERIMENTAL

Prolonged Intermittent Theta-Burst Stimulation (prolonged iTBS)

Intervention Type 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.

Sham Transcranial Magnetic Stimulation

Intervention Type 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

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.

Group Type EXPERIMENTAL

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

Intervention Type 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.

Sham Transcranial Magnetic Stimulation

Intervention Type 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.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

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

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Tri-Service General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Tien-Yu Chen

Visiting Physician

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Tien-Yu Chen, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Tri-Service General Hospital

Locations

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Tri-Service General Hospital

Taipei, Neihu, Taiwan

Site Status

Countries

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Taiwan

Central Contacts

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Tao-Yi Chao, BS

Role: CONTACT

886-2-87923311 ext. 754660

Facility Contacts

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Tso-Yi Chao, BS

Role: primary

886-2-87923311 ext. 754660

Other Identifiers

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C202405067

Identifier Type: -

Identifier Source: org_study_id

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