Parkinson's Disease, Depression
Conditions
Keywords
rTMS, Digital Biomarkers, Neuronavigation, Motor Cortex, Neurodegeneration
Brief summary
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.
Detailed description
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.
Interventions
DEVICERepetitive 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 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.
Sponsors
Ho-Won Lee
Korea Brain Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
Participants are randomly assigned to either real rTMS or sham rTMS group. Both groups continue their existing Parkinson's disease medication throughout the study.
Eligibility
Sex/Gender
ALL
Age
40 Years to 90 Years
Healthy volunteers
No
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 * 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
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) * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Beck Depression Inventory-II (BDI-II) Total Score | 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 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 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 | 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 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 | 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 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 | 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 in Montreal Cognitive Assessment (MoCA) Scores | Baseline, immediately after the final stimulation session, and 4 weeks (±7 days) after the final stimulation session | 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 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 | 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 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 | 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 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 | 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 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 | 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 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 | 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 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 | Electrodermal activity is measured using the Shimmer Consensys GSR Development Kit, which records skin conductance changes between electrodes via wireless sensors. Sweat gland activation in response to internal or external stimuli alters skin moisture and ionic balance, producing measurable changes in electrodermal activity. |
| Change in Brain Structure and Connectivity on MRI | Baseline and 1 week (±2 days) after the final stimulation session | Neuroimaging assessment of brain structure using MRI with two sequences: T1-weighted and T2-weighted structural imaging. Used to evaluate structural changes before and after rTMS treatment, and to guide neuronavigation-based TMS targeting. |
| Change in Plasma Biomarker Concentrations | Baseline and immediately after the final stimulation session | 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). |
| 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 | Safety will be assessed by the number and proportion of participants experiencing treatment-emergent adverse events (TEAEs) from the initiation of rTMS or sham stimulation through the final follow-up assessment. Adverse events will be summarized by event type, severity, and relationship to the investigational device. Serious adverse events, adverse device effects, and discontinuations due to adverse events will also be recorded and summarized by treatment group. |
Countries
South Korea
Contacts
PRINCIPAL_INVESTIGATORHo-Won Lee, MD
Kyungpook National University Chilgok Hospital
Outcome results
None listed