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
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Change in Prefrontal Cortical Activation
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 ≥
- •Depressive symptom severity defined as: Patient Health Questionnaire-9 (PHQ-9) total score ≥
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Prolonged Intermittent Theta-Burst Stimulation (prolonged iTBS) (Device)
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.
干预措施: Sham Transcranial Magnetic Stimulation (Device)
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.
干预措施: High-Frequency Repetitive Transcranial Magnetic Stimulation (HF-rTMS) (Device)
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.
干预措施: Sham Transcranial Magnetic Stimulation (Device)
结局指标
主要结局
Change in Prefrontal Cortical Activation
时间窗: Immediately before stimulation and immediately after each single stimulation session (active and sham), within each study period
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.
次要结局
- 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)
研究者
Tien-Yu Chen
Visiting Physician
Tri-Service General Hospital