Efficacy of Repetitive Transcranial Magnetic Stimulation for Improving Depressive Symptoms in Patients With Parkinson's Disease : A Single-Center, Randomized, Double-Blinded, Sham-Controlled, Parallel-Design, Investigator-Initiated Exploratory Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Change From Baseline in Beck Depression Inventory-II (BDI-II) Total Score
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in improving depressive symptoms in patients with Parkinson's Disease(PD).
Participants will be randomly assigned to either an active rTMS group or a sham-control group.
The study aims to evaluate the efficacy and feasibility of a neuronavigation-guided bilateral M1 rTMS protocol.
详细描述
Antidepressants and other psychotropic medications must have been stable for 4 weeks before baseline and remain unchanged during the study
At each clinical assessment, the time of the most recent dopaminergic medication dose and the participant's clinical medication state (ON or OFF) will be recorded. Whenever feasible, follow-up assessments will be performed at a similar time relative to the participant's usual dopaminergic medication schedule as at baseline.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to provide written informed consent
- •Male or female aged 40 to 90 years
- •Diagnosed with Parkinson's disease with depressive symptoms
- •Hoehn and Yahr stage 1 to 3
- •On stable Parkinson's disease medication for at least 3 months prior to screening, with no planned dose increase during the study period
- •Clinically significant depressive symptoms (BDI-II score ≥14) confirmed by clinician interview, without major psychiatric conditions that may confound their assessment
- •Able to read and write Korean and capable of independently completing questionnaires
排除标准
- •History of epilepsy
- •Parkinson's disease caused by cerebrovascular disease, CNS infection, intoxication, or traumatic brain injury
- •Diagnosed with Parkinson-plus syndromes (multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies etc.)
- •Clinically significant abnormal laboratory values (AST, ALT, or total bilirubin > 2.5 x ULN)
- •Major psychiatric disorders other than depressive disorders (e.g., bipolar disorder, psychotic disorders) that may interfere with study participation or assessment of depressive symptoms
- •Unable to follow instructions or communicate
- •Pregnant, breastfeeding, or women of childbearing potential
- •Febrile patients
- •Patients with artificial hip joint implants
- •Presence of conductive, ferromagnetic, or magnetically sensitive metal near the head or treatment coil (e.g., cochlear implants, implanted electrodes/stimulators, aneurysm clips or coils)
- •Cardiac disease, especially patients with pacemakers
- •Corrected or uncorrected visual acuity less than 0.5
- •Use of drug infusion pumps or hearing aids
- •Patients with acute illness
- •Patients taking tricyclic antidepressants, neuroleptics, or other medications that may lower seizure threshold
- •History of increased intracranial pressure or head trauma
- •Evidence of external wounds on brain or neck
- •Prominent psychotic symptoms other than depression (high NPI scores for hallucinations, delusions, mania)
- •History of schizophrenia, bipolar disorder, or substance abuse
- •Suicidal ideation (BDI-II item 9 score of 2 or 3)
- •History of or planned deep brain stimulation or stereotactic surgery (pallidotomy, thalamotomy)
- •Any participant deemed ineligible by the investigator, including those with medical conditions that may increase risk or interfere with study evaluation
- •Currently enrolled in another clinical trial or used investigational drug/device within 30 days or 5 half-lives prior to consent
研究组 & 干预措施
Real rTMS
Participants receive active repetitive transcranial magnetic stimulation (rTMS) to bilateral primary motor cortex (M1), guided by neuronavigation (BrainEyes). Stimulation is delivered at 10 Hz, 90% of resting motor threshold (RMT), 1,000 pulses per session, once daily for 5 consecutive weekdays. Participants continue their existing Parkinson's disease medication throughout the study.
干预措施: Repetitive Transcranial Magnetic Stimulation (rTMS) (Device)
Sham rTMS
Participants receive sham repetitive transcranial magnetic stimulation (rTMS) to bilateral primary motor cortex (M1), guided by neuronavigation (BrainEyes). The coil is tilted 90 degrees perpendicular to the scalp so that no magnetic field is delivered to the cortex. The same click sound and scalp sensation are maintained to preserve participant blinding. The session parameters are identical to the active rTMS group (10 Hz, 1,000 pulses per session, once daily for 5 consecutive weekdays). Participants continue their existing Parkinson's disease medication throughout the study.
干预措施: Sham Repetitive Transcranial Magnetic Stimulation (Sham rTMS) (Device)
结局指标
主要结局
Change From Baseline in Beck Depression Inventory-II (BDI-II) Total Score
时间窗: Baseline, immediately after the final stimulation session, and 4 weeks (±7 days) after the final stimulation session
The BDI-II is a 21-item self-reported questionnaire assessing the severity of depressive symptoms. Each item is scored from 0 to 3, yielding a total score ranging from 0 to 63, with higher scores indicating greater severity of depressive symptoms. Changes in BDI-II total score from baseline (T0) will be compared between the real rTMS and sham rTMS groups after treatment (T1) and at the follow-up assessment (T2).
Change From Baseline in Neuropsychiatric Inventory (NPI) Scores
时间窗: Baseline, immediately after the final stimulation session, and 4 weeks (±7 days) after the final stimulation session
The NPI is a caregiver- or informant-based assessment of neuropsychiatric symptoms. It evaluates 12 neuropsychiatric symptom domains based on symptom frequency and severity. Changes in NPI scores from baseline (T0) will be compared between the real rTMS and sham rTMS groups after treatment (T1) and at the follow-up assessment (T2).
Change in Beck Depression Inventory-II (BDI-II) Total Score
时间窗: Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up)
Self-reported measure of depressive symptom severity consisting of 21 items rated on a 4-point Likert scale. Higher scores indicate greater depression severity.
Change in Neuropsychiatric Inventory (NPI) Scores
时间窗: Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up)
Caregiver-rated assessment of neuropsychiatric symptoms in Parkinson's disease patients, covering 12 domains including mood, apathy, anxiety, and psychosis. Each domain rated by frequency (1-4) and severity (1-3).
次要结局
- Change in Parkinson's Disease Questionnaire-39 (PDQ-39) Scores(Baseline, immediately after the final stimulation session, and 4 weeks (±7 days) after the final stimulation session)
- Change in Unified Parkinson's Disease Rating Scale (UPDRS) Scores(Baseline, immediately after the final stimulation session, and 4 weeks (±7 days) after the final stimulation session)
- Change in Parkinson's Disease Sleep Scale (PDSS) Scores(Baseline, immediately after the final stimulation session, and 4 weeks (±7 days) after the final stimulation session)
- Change in Toronto Alexithymia Scale-20 Korean Version (TAS-20-K) Scores(Baseline, immediately after the final stimulation session, and 4 weeks (±7 days) after the final stimulation session)
- Change in Montreal Cognitive Assessment (MoCA) Scores(Baseline, immediately after the final stimulation session, and 4 weeks (±7 days) after the final stimulation session)
- Change in Facial Expression Measures on FaceReader Analysis(Baseline, 1 week (±2 days) after the final stimulation session, and 4 weeks (±7 days) after the final stimulation session)
- Change in Eye Movement Measures on Eye-Tracking(Baseline, 1 week (±2 days) after the final stimulation session, and 4 weeks (±7 days) after the final stimulation session)
- Change in Muscle Activity Measured by Electromyography (EMG)(Baseline, 1 week (±2 days) after the final stimulation session, and 4 weeks (±7 days) after the final stimulation session)
- Change in Postural Stability and Balance Measures on BT4 Balance Assessment(Baseline, 1 week (±2 days) after the final stimulation session, and 4 weeks (±7 days) after the final stimulation session)
- Change in Body Composition Measured by Bioelectrical Impedance Analysis (InBody)(Baseline, 1 week (±2 days) after the final stimulation session, and 4 weeks (±7 days) after the final stimulation session)
- Change in Electrodermal Activity Measured by Galvanic Skin Response (GSR)(Baseline, 1 week (±2 days) after the final stimulation session, and 4 weeks (±7 days) after the final stimulation session)
- Change in Brain Structure and Connectivity on MRI(Baseline and 1 week (±2 days) after the final stimulation session)
- Change in Plasma Biomarker Concentrations(Baseline and immediately after the final stimulation session)
- Incidence of Treatment-Emergent Adverse Events (TEAEs)(From the first stimulation session to the final stimulation session, 1 week (±2 days) after the final stimulation session, and 4 weeks (±7 days) after the final stimulation session)
- Change in Parkinson's Disease Questionnaire-39 (PDQ-39) Scores(Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up))
- Change in Unified Parkinson's Disease Rating Scale (UPDRS) Scores(Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up))
- Change in Parkinson's Disease Sleep Scale (PDSS) Scores(Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up))
- Change in Toronto Alexithymia Scale-20 Korean Version (TAS-20-K) Scores(Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up))
- Change in Montreal Cognitive Assessment (MoCA) Scores(Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up))
- Change in Facial Expression Measures on FaceReader Analysis(Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up))
- Change in Eye Movement Measures on Eye-Tracking(Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up))
- Change in Muscle Activity Measured by Electromyography (EMG)(Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up))
- Change in Postural Stability and Balance Measures on BT4 Balance Assessment(Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up))
- Change in Body Composition Measured by Bioelectrical Impedance Analysis (InBody)(Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up))
- Change in Brain Structure and Connectivity on MRI(Change from Baseline (T0) at 1 week (T1) after stimulation)
- Change in Plasma Biomarker Concentrations(Change from Baseline (T0) at 1 week (T1) after stimulation)
研究者
Ho-Won Lee
Professor, Department of Neurology
Kyungpook National University Chilgok Hospital