Repetitive Transcranial Magnetic Stimulation(rTMS) Regulating Slow-wave to Delay the Progression of Parkinson's Disease

Study Overview
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Brief Summary
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At present, no drug therapy has been proven to delay the progression of Parkinson's disease (PD). rTMS, as a non-invasive neuromodulation method, can regulate Slow-wave sleep (SWS). SWS is recognized closely related to neurodegeneration. However, there has been no clinical studies on if rTMS could delay the progression of PD by regulating SWS. The main purpose of this study is to explore the changes of SWS in non-rapid eye movement (NREM) sleep period in PD patients by using rTMS, and the relationship with potential improvements of SWS and motor symptom delay. The study aims to find a potential new treatment strategy to delay the neurodegenerative process in PD patients by modulating SWS by rTMS.

Official Title
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Clinical Study on the Efficacy and Safety of rTMS Regulating Slow-wave Sleep to Delay the Progression of Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Device: rTMS real stimulation stage1
* Device: rTMS shame stimulation stage1
* Device: rTMS real stimulation stage 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet the clinically definite or clinically probable PD according to the MDS 2015 version. Chinese Han population (three generations), age greater than or equal to 50 years old, less than or equal to 80 years old, male or female. Hoehn-Yahr stages 1-4. The dose of levodopa drug therapy was stable three weeks before enrollment and during the follow-up period. Right-handed. The patient signed a written informed consent. Exclusion Criteria: Any form of Parkinsonism other than primary PD. Those who have received neurosurgical intervention or stereotaxic brain surgery for PD, or have previously received TMS treatment. Cognitive dysfunction (MMSE ≤ 24 points) or those who cannot cooperate with the scale score. Persons with mental disabilities. Pregnant women. There are contraindications for rTMS treatment. There are contraindications for MRI examination. Baseline PSG suggests other sleep disorders such as moderate to severe OSAS; BMI>=30. Patients who are addicted to alcohol, taking SSRIs, TCAs, sedative hypnotics, histamine antagonists and other drugs and food that may affect NREM and REM sleep structure. Those who are unwilling to participate in the study or unable to sign the informed consent form; and other circumstances that the researcher considers inappropriate to participate in the study. -

Ages Eligible for Study
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Minimum Age: 50 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 |
| --- | --- |
| Experimental: the early treatment group<br>stage1+stage2 real stimulation | Device: rTMS real stimulation stage1<br>* In the first stage, the early treatment group use low-frequency rTMS real stimulation,<br>Device: rTMS real stimulation stage 2<br>* In the second stage, both the early treatment group and the control group (delayed treatment group) will be treated with true stimulation low-frequency rTMS.<br>|
| Other: the control group (delayed treatment group)<br>stage1 sham stimulation + stage2 real stimulation | Device: rTMS shame stimulation stage1<br>* In the first stage, the control group (delayed treatment group) all use sham stimulation.<br>Device: rTMS real stimulation stage 2<br>* In the second stage, both the early treatment group and the control group (delayed treatment group) will be treated with true stimulation low-frequency rTMS.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Motor Function in PD by Low Frequency rTMS Stimulation | the score of Unified Parkinson's Disease Rating ScaleⅢ (UPDRSIII)[off] The higher the score, the more severe the motor dysfunction | Day14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of low-frequency rTMS stimulation on motor symptoms | the score of Unified Parkinson's Disease Rating ScaleⅢ (UPDRSIII) [on] The higher the score, the more severe the motor dysfunction | Day28,Day56 | 
| Measurement of improved balance function in patients with Parkinson's disease | the score of Berg Balance Scale (BBS)[0-56] The higher the score, the better the balance | Day14,Day28,Day56 | 
| Assessment of sleep structure in patients with Parkinson's disease | Use polysomnography (PSG) to record the proportion of slow-wave sleep | Day14,Day28,Day56 | 
| Effects of low-frequency rTMS stimulation on anxiety | the score of Hamilton Anxiety Rating Scale（HAMA)[0-64] The higher the score, the more anxious | Day14,Day28,Day56 | 
| Effects of low-frequency rTMS stimulation on cognition | the score of Montreal Cognitive Assessment（Moca)[0-30] The lower the score, the more severe the cognitive dysfunction | Day14,Day28,Day56 | 
| Effects of low-frequency rTMS stimulation on cortical excitability | short-interval cortical inhibition(SICI) | Day14,Day28 | 
| Effects of low-frequency rTMS stimulation on depression | the score of Hamilton Depression Rating Scale（HAMD） Total score ≥ 20 points: may be mild or moderate depression; The higher the score, the more depressed | Day14,Day28,Day56 | 
| Assessment of daytime sleepiness in patients with Parkinson's disease | the score of The Epworth Sleeping Scale(ESS)[0-24] The higher the score, the more lethargic | Day14,Day28,Day56 | 
| Effects of low-frequency rTMS stimulation on gait | Use a quantitative gait analysis system to analyze the change of gait | Day14,Day28,Day56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, slow-wave sleep, rTMS, motor symptom, progression