Neuroprotective Effects of iTBS in PD

Study Overview
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Brief Summary
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Intermittent theta burst stimulation (iTBS) is an emerging non-invasive neuron regulation technique, which is widely used in neuropsychiatry for a variety of diseases and is widely accepted by patients due to its non-invasive, operable and relatively precise localization. Combining the results of previous studies and our group's previous research, sixty qualified PD patients would be enrolled to conduct a prospective single-center randomized double-blind sham controlled clinical trial to verify the long-term curative effects of iTBS treatment protocol and explore the neuron-protection of iTBS on neuronal loss of PD patients.

Official Title
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Neuroprotective Effects of Intermittent Theta Burst Stimulation in Parkinson's Disease: a Delayed-start Randomized Double-blind Sham Controlled Study

Conditions
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Neuroprotection, Parkinson Disease, Intermittent Theta Burst Stimulation

Intervention / Treatment
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* Device: intermittent theta burst stimulation
* Device: sham iTBS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet the revised clinical diagnostic criteria for Parkinson's disease of the Movement Disorder Society (MDS) International (2015 version). aged >20 years and <80 years, regardless of gender. 2 ≤ Hoehn-Yahr stage≤ 4. Maintain medication stability during the study period. Good compliance, written informed consent, and consent for long-term interventional treatment with iTBS. Exclusion Criteria: Patients with severe neuropsychiatric disorders or previous history of severe neurological disorders (e.g., epilepsy, cerebrovascular accidents, etc.) or history of traumatic brain injury or brain surgery. Patients with significant cognitive impairment (MMSE < 24) or inability to complete questionnaires independently. Prior treatment with TMS, DBS or SCS. Severe physical illness and any physical illness that can precipitate epilepsy or intracranial hypertension, including cardiovascular and respiratory disease. Have human implantable materials such as intracranial stents, pacemakers, coronary stents, cochlear implants, etc. Are currently taking other investigational drugs. Any other condition that the investigator deems unsuitable for participation in this study.

Ages Eligible for Study
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Minimum Age: 20 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 |
| --- | --- |
| Active Comparator: Early-start single iTBS group<br>The intensive period: 2 weeks The maintenance period: 12 weeks | Device: intermittent theta burst stimulation<br>* iTBS is a new form of excitatory rTMS treatment that is less time-consuming and more effective than traditional rTMS in a single treatment session.<br>* Other names: iTBS;|
| Active Comparator: Early-start double iTBS group<br>The intensive period: 2 weeks The maintenance period: 12 weeks | Device: intermittent theta burst stimulation<br>* iTBS is a new form of excitatory rTMS treatment that is less time-consuming and more effective than traditional rTMS in a single treatment session.<br>* Other names: iTBS;|
| Sham Comparator: Delayed-start single iTBS group<br>The intensive period: sham/iTBS, 2 weeks The maintenance period: daily sham/iTBS, 12 weeks | Device: intermittent theta burst stimulation<br>* iTBS is a new form of excitatory rTMS treatment that is less time-consuming and more effective than traditional rTMS in a single treatment session.<br>* Other names: iTBS;Device: sham iTBS<br>* The pseudo-stimulation device looks and sounds the same as the iTBS device<br>|
| Sham Comparator: Delayed-start double iTBS group<br>The intensive period: sham/iTBS, 2 weeks The maintenance period: twice daily sham/iTBS, 12 weeks | Device: intermittent theta burst stimulation<br>* iTBS is a new form of excitatory rTMS treatment that is less time-consuming and more effective than traditional rTMS in a single treatment session.<br>* Other names: iTBS;Device: sham iTBS<br>* The pseudo-stimulation device looks and sounds the same as the iTBS device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Group differences of part 3 of Unified Parkinson Disease Rating Scale (UPDRS) changes | Compare the changes in UPDRS scores from baseline to post-iTBS in the four intervention groups (UPDRS part3: range 0 72, higher score is related to a worse outcome). | 28 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Group differences of Hoehn-Yahr stage | Compare the changes in Hoehn-Yahr stage from baseline to post-iTBS in the four intervention groups (H-Y stage: range 0 5, higher score is related to a worse outcome). | 28 weeks | 
| Group differences of Berg Balance Scale (BBS) changes | Compare the changes in BBS scores from baseline to post-iTBS in the four intervention groups (BBS: range 0 56, higher score is related to a better outcome). | 28 weeks | 
| Group differences of Hamilton depression scale-17 (HAMD-17) changes | Compare the changes in HAMD-17 scores from baseline to post-iTBS in the four intervention groups (HAMD-17: range 0 38, higher score is related to a worse outcome). | 28 weeks | 
| Group differences of Hamilton Anxiety Scale (HAMA) changes | Compare the changes in HAMA scores from baseline to post-iTBS in the four intervention groups (HAMA: range 0 64, higher score is related to a worse outcome). | 28 weeks | 
| Group differences of Mini-mental State Examination (MMSE) changes | Compare the changes in MMSE scores from baseline to post-iTBS in the four intervention groups (MMSE: range 0 30, higher score is related to a better outcome). | 28 weeks | 
| Group differences of Montreal Cognitive Assessment (MoCA) changes | Compare the changes in MoCA scores from baseline to post-iTBS in the four intervention groups (MoCA: range 0 30, higher score is related to a better outcome). | 28 weeks | 
| Group differences of 39-item Parkinson's Disease Questionnaire (PDQ-39) changes | Compare the changes in PDQ-39 scores from baseline to post-iTBS in the four intervention groups (PDQ-39: range 0 156, higher score is related to a worse outcome). | 28 weeks | 
| Group differences of 16-item Sniffin' Sticks test (SS-16) changes | Compare the changes in SS-16 scores from baseline to post-iTBS in the four intervention groups (SS-16: range 0 16, higher score is related to a better outcome). | 28 weeks | 
| Group differences of Wexner changes | Compare the changes in Wexner scores from baseline to post-iTBS in the four intervention groups (Wexner: range 0 30, higher score is related to a worse outcome). | 28 weeks | 
| Group differences of adverse event | Compare the adverse event in four intervention groups. | 28 weeks |