Efficacy of Repetitive Transcranial Magnetic Stimulation for Improving Depressive Symptoms in Patients With Parkinson's Disease

Efficacy of Repetitive Transcranial Magnetic Stimulation for Improving Depressive Symptoms in Patients With Parkinson's Disease : A Single-Center, Randomized, Single-Blinded, Sham-Controlled, Parallel-Design, Investigator-Initiated Exploratory Clinical Trial

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 establish an optimal treatment protocol using a neuronavigation system and to validate treatment responses through various digital biomarkers such as facial expression analysis and eye-tracking.

Study Overview

• Status: Enrolling by invitation
• Conditions: Depression; Parkinson's Disease
• Intervention / Treatment: Device: Repetitive Transcranial Magnetic Stimulation (rTMS); Device: Sham Repetitive Transcranial Magnetic Stimulation (Sham rTMS)

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• South Korea
  • Buk-gu
    • Daegu, Buk-gu, South Korea, 41404
      • Kyungpook National University Chilgok Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
• BDI-II score ≥ 14 (mild depression) or ≥ 20 (moderate depression)
• Able to read and write Korean and capable of independently completing questionnaires

Exclusion Criteria:

• 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)
• Diagnosed with psychiatric disorders
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Device: Repetitive Transcranial Magnetic Stimulation (rTMS); High-frequency rTMS is delivered to bilateral primary motor cortex (M1) using neuronavigation guidance (BrainEyes). Parameters: 10 Hz, 90% of resting motor threshold (RMT), 50 pulses per train, 55-second inter-train interval, 20 trains per session, 1,000 pulses per session, once daily for 5 consecutive weekdays.
Sham Comparator: 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.	Device: Sham Repetitive Transcranial Magnetic Stimulation (Sham rTMS); Sham rTMS is delivered with the coil tilted 90 degrees perpendicular to the scalp to prevent magnetic field delivery to the cortex. The same click sound and scalp sensation are maintained. Session parameters are identical to active rTMS group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beck Depression Inventory-II (BDI-II)	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 from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up)
Neuropsychiatric Inventory (NPI)	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).	Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parkinson's Disease Questionnaire-39 (PDQ-39)	Disease-specific questionnaire assessing quality of life in Parkinson's disease patients across 8 domains: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. Scores range from 0 to 100; higher scores indicate worse quality of life.	Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up)
Unified Parkinson's Disease Rating Scale (UPDRS)	Comprehensive clinician-administered scale assessing motor and non-motor symptoms of Parkinson's disease across 6 subscales: non-motor experiences of daily living, motor experiences of daily living, motor examination, motor complications, Hoehn and Yahr staging, and Schwab and England ADL scale. Higher scores indicate greater disease severity.	Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up)
Parkinson's Disease Sleep Scale (PDSS)	Self-reported scale assessing sleep disturbances in Parkinson's disease patients, consisting of 15 items rated on a 5-point Likert scale (0-4). Covers three domains: nocturnal motor symptoms, PD-specific nocturnal symptoms, and sleep-specific disturbances. Higher scores indicate more frequent sleep disturbances.	Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up)
Toronto Alexithymia Scale-20 Korean Version (TAS20-K)	Korean validated version of the Toronto Alexithymia Scale consisting of 20 items rated on a 5-point Likert scale, assessing three factors: difficulty identifying feelings (DIF), difficulty describing feelings (DDF), and externally oriented thinking (EOT). Higher total scores indicate greater alexithymia.	Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up)
Montreal Cognitive Assessment (MoCA)	Brief cognitive screening tool assessing multiple cognitive domains including attention, concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Scores range from 0 to 30; higher scores indicate better cognitive function.	Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up)
Facial Expression Analysis (FaceReader)	Automated facial expression analysis using FaceReader software to quantitatively assess facial action units (AUs) and emotional expression patterns. Participants perform facial emotion recognition and imitation tasks. Measures include response speed, latency, accuracy, and facial expression accuracy based on Action Unit analysis.	Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up)
Eye Movement Assessment (Eye-tracking)	Quantitative assessment of eye movements using screen-based Tobii Pro Spark. Measures include gaze speed, gaze position, gaze duration, gaze latency, and pupil size during task performance, providing objective evaluation of oculomotor function.	Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up)
Electromyography (EMG)	Muscle activity is measured using DELSYS Trigno Avanti Sensor and Trigno Quattro Sensor attached to the skin with medical tape. Wireless measurement technology enables free movement during task performance, with real-time data collection via dedicated software.	Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up)
Static Balance Assessment (BT4)	Quantitative assessment of postural stability using BT4 balance evaluation system, measuring center of pressure (COP) displacement during standing. Assesses limits of stability in anterior, posterior, and lateral directions, and COP movement during Romberg test under eyes-open and eyes-closed conditions.	Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up)
Body Composition Analysis (InBody)	Basic physical information is collected using InBody580 with 4-pole 8-point tactile electrode method. Bioelectrical impedance is measured across 3 frequency bands (5kHz, 50kHz, 250kHz) in 5 body segments (right arm, left arm, trunk, right leg, left leg), yielding 15 impedance measurements.	Change from Baseline (T0) at 1 week (T1) and 5 weeks (T2, 1-month follow-up)
Brain Structural and Functional MRI	Neuroimaging assessment of brain structure and function using MRI with three sequences: T1-weighted and T2-weighted structural imaging, and Diffusion Tensor Imaging (DTI) to assess white matter integrity and structural connectivity. Used to evaluate changes in brain structure before and after rTMS treatment, and to guide neuronavigation-based TMS targeting.	Change from Baseline (T0) at 1 week (T1) after stimulation
Blood-based biomarkers	Quantitative measurement of candidate plasma biomarkers including Amyloid beta 40/42, Tau, phosphorylated Tau (p-Tau), and Neurofilament light chain (NfL) using antibody-based quantitative analysis methods (SIMOA, Luminex, or ELISA).	Change from Baseline (T0) at 1 week (T1) after stimulation

Collaborators and Investigators

• Sponsor: Ho-Won Lee
• Collaborators: Korea Brain Research Institute
• Investigators: Principal Investigator: Howon Lee, MD, Kyungpook National University Chilgok Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 4, 2026
• Primary Completion (Estimated): October 23, 2026
• Study Completion (Estimated): October 23, 2026

Study Registration Dates

• First Submitted: April 28, 2026
• First Submitted That Met QC Criteria: April 28, 2026
• First Posted (Actual): May 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Neurodegeneration; rTMS; Motor Cortex; Neuronavigation; Digital Biomarkers
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Behavioral Symptoms; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Pathological Conditions, Signs and Symptoms; Behavior; Depression; Parkinson Disease; Nerve Degeneration; Therapeutics; Magnetic Field Therapy; Transcranial Magnetic Stimulation
• Other Study ID Numbers: KNUCH 2025-08-046-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be publicly shared to protect the privacy of the participants. However, de-identified data may be available from the principal investigator upon reasonable request for research purposes, subject to institutional review board approval.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No