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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Parkinson's Disease
• Intervention / Treatment: Device: rTMS real stimulation stage1; Device: rTMS real stimulation stage 2; Device: rTMS shame stimulation stage1

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaoying Zhu, doctor; Phone Number: +86 21 63240090; Email: docxiaoying@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Recruiting
      • Shanghai Jiao Tong University School of Medicine
      • Contact: Xiaoying Zhu, MD; Phone Number: +86 13817659260; Email: docxiaoying@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Meet the clinically definite or clinically probable PD according to the MDS 2015 version.
2. 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.
3. Hoehn-Yahr stages 1-4.
4. The dose of levodopa drug therapy was stable three weeks before enrollment and during the follow-up period.
5. Right-handed.
6. The patient signed a written informed consent.

Exclusion Criteria:

1. Any form of Parkinsonism other than primary PD.
2. Those who have received neurosurgical intervention or stereotaxic brain surgery for PD, or have previously received TMS treatment.
3. Cognitive dysfunction (MMSE ≤ 24 points) or those who cannot cooperate with the scale score.
4. Persons with mental disabilities.
5. Pregnant women.
6. There are contraindications for rTMS treatment.
7. There are contraindications for MRI examination.
8. Baseline PSG suggests other sleep disorders such as moderate to severe OSAS; BMI>=30.
9. 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.

10. 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.

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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: the early treatment group; stage1+stage2 real stimulation	Device: rTMS real stimulation stage1; In the first stage, the early treatment group use low-frequency rTMS real stimulation,; Device: rTMS real stimulation stage 2; 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.
Other: the control group (delayed treatment group); stage1 sham stimulation + stage2 real stimulation	Device: rTMS real stimulation stage 2; 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.; Device: rTMS shame stimulation stage1; In the first stage, the control group (delayed treatment group) all use sham stimulation.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of low-frequency rTMS stimulation on brain connectivity in the PD brain	functional magnetic resonance imaging (fMRI) (Default mode network, DMN）	Day0,Day14,Day28
Changes in salivary melatonin levels	salivary melatonin levels(Fasting)	Day0,Day14,Day28,Day56

Collaborators and Investigators

• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: Xiaoying Zhu, doctor, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2023
• Primary Completion (Estimated): July 28, 2026
• Study Completion (Estimated): July 28, 2026

Study Registration Dates

• First Submitted: July 11, 2023
• First Submitted That Met QC Criteria: August 15, 2023
• First Posted (Actual): August 21, 2023

Study Record Updates

• Last Update Posted (Actual): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: rTMS; Parkinson's disease; progression; slow-wave sleep; motor symptom
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Disease Progression; Parkinson Disease
• Other Study ID Numbers: CCTR-2022B05

Drug and device information, study documents

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