Effect of rTMS of the Cerebellum on Parkinson's Disease

Study Overview
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Brief Summary
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The goal of this clinical trial is to learn about the efficacy of low-frequency rTMS of the cerebellum in Parkinson's disease.

Detailed Description
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The main question it aims to answer is: how to improve Parkinson's disease by rTMS. Participants will be treated with active low-frequency rTMS/sham rTMS over the cerebellum and receive: 1) resting state functional magnetic resonance imaging (fMRI), 2) blood sampling, and 3) Unified Parkinson Disease Rating Scale (UPDRS) before and after the treatment course. Researchers will compare the data collected from fMRI scan, blood sample analysis, and UPDRS rating between the active rTMS group and sham controls before and after the treatment to see if there are meliorating effects of rTMS on Parkinson's disease.

Official Title
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Effect of Low-frequency rTMS of the Cerebellum on Parkinson's Disease

Conditions
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Parkinson Disease, Transcranial Magnetic Stimulation

Intervention / Treatment
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* Device: sham rTMS
* Device: active rTMS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with Parkinson's disease according to the clinical diagnostic criteria for Parkinson's disease (2015 edition) by the Movement Disorder Society (MDS) Citizens of the People's Republic of China of either sex, aged between 40 and 80 years. Able to give informed consent and follow the research plan. Hoehn-Yahr (H-Y) stage ≤ 3 Patients received a Parkinson's stable medication before treatment (assessed via self report), which continued during treatment. Exclusion Criteria: History or diagnosis of severe psychiatric disorders, such as depression, anxiety disorders, schizophrenia spectrum disorders, and bipolar disorders. Subjects with a clinically defined neurological disorder (assessed via self report) including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, history of stroke, transient ischemic attack within two years, cerebral aneurysm, dementia, multiple sclerosis. Significant cognitive disorders (Mini-Mental State Exam (MMSE)<24 points) or unable to complete the questionnaire independently. Intracranial implants, such as cochlear implants, aneurysms clips, shunts, stimulators, electrodes, cardiac pacemakers and vagus nerve stimulation devices. Increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure (such as after large infarctions or trauma), or currently taking medication that lowers the seizure threshold (assess via self report). Showed significant discomfort after receiving the rTMS treatment. Participated in other clinical trials. Inability to read or understand Chinese.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: sham stimulation targeting the cerebellum<br>Patients will be randomly allocated into this group, and they will receive sham stimulation. | Device: sham rTMS<br>* The coil was held while disconnected from the stimulator, and rTMS noise was presented with computer loudspeakers with recorded sound from a real stimulation (20 minutes for each side of the lateral cerebellum everyday for 2 weeks).<br>|
| Active Comparator: real rTMS targeting the cerebellum<br>Patients will be randomly allocated into this group, and they will receive real stimulation. | Device: active rTMS<br>* Low-frequency (1 Hz) rTMS at with a stimulation intensity of 95% of the motor threshold will be delivered over the bilateral cerebellum for patients with Parkinson's disease (20 minutes for each side of the lateral cerebellum everyday for 2 weeks).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of Unified Parkinson's Disease Rating Scale (UPDRS) (version 3.0) score by rTMS treatment | UPDRS score will be collected from each participants to measure the severity and progression of Parkinson's disease with scores ranging from 0 (minimum) to 199 (maximum). The higher scores mean a worse outcome. | Baseline, 2 weeks, and 3 months after rTMS treatment | 
| Changes of brain plasticity by rTMS treatment | Resting state fMRI will be scanned from each participants, and brain activity as well as fuctional connectivity will be analyzed. | Baseline, 2 weeks, and 3 months after rTMS treatment | 
| Changes of circulating serum level of inflammatory cytokines (e.g., Interleukin-1beta (IL-1β), Interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α)) by rTMS treatment | Blood samples will be collected from each participants, and serum levels of IL-1β, IL-6, and TNF-α will be measured by enzyme-linked immunosorbent assay (ELISA). | Baseline, 2 weeks, and 3 months after rTMS treatment |