Clinical Efficacy of Intermittent Theta Burst Transcranial Magnetic Stimulation With Different Modes on Parkinson's Disease
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Assessment with the KPPS
研究概览
简要总结
TMS regulates cortical excitability through electromagnetic induction, with low-frequency stimulation suppressing and high-frequency stimulation enhancing excitability. Building on theta-gamma coupling, iTBS induces broader improvements in functional brain connectivity within a shorter stimulation period, particularly by significantly reducing abnormal variability in the prefrontal and parietal regions, demonstrating superior neuromodulatory efficiency and network remodeling capacity. This study aims to compare the symptomatic effects of different iTBS protocols on Parkinson's disease, optimize stimulation parameters, and evaluate safety, while also analyzing the time-dependent trends of therapeutic efficacy through 1- and 3-month follow-ups.
详细描述
Transcranial magnetic stimulation, as a neuromodulatory strategy, has received increasing attention in the treatment of Parkinson's disease, demonstrating the ability to improve both motor and non-motor symptoms. Its mechanism is based on electromagnetic induction, using time-varying magnetic fields to modulate cortical neuronal activity. The effects of TMS are frequency-dependent: low-frequency stimulation (≤1 Hz) typically inhibits cortical excitability, resembling long-term depression, while high-frequency stimulation (≥10 Hz) enhances cortical excitability, analogous to long-term potentiation. Building on the mechanism of theta-gamma coupling, theta burst stimulation was developed by embedding high-frequency bursts within a theta rhythm, enabling efficient induction of LTP- and LTD-like effects. Among TBS protocols, intermittent TBS has been shown to exert clear modulatory effects on the motor cortex. Compared with 10 Hz repetitive TMS, iTBS induces broader improvements in functional connectivity across brain regions within a shorter stimulation period, particularly by significantly reducing abnormal variability in the prefrontal and parietal regions, indicating greater neuromodulatory efficiency and network remodeling capacity.
In this study, the iTBS protocol is applied based on the "Stanford Accelerated Intelligent Neuromodulation Therapy" (SAINT) approach. Patients are randomly assigned to one of three groups: a high-dose treatment group, a low-dose treatment group, or a sham stimulation group. Clinical scales are used to evaluate whether different modes of intermittent theta-burst transcranial magnetic stimulation improve motor and non-motor symptoms (particularly pain) in patients with Parkinson's disease. In addition, functional magnetic resonance imaging and electroencephalography are performed before and after treatment to explore the effects of different iTBS protocols on brain network activity and functional connectivity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
The figure-of-eight coils used for active or sham stimulation are similar, including the emitted sound and the scalp tapping sensation.
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 40-80 years; ② Diagnosis of idiopathic Parkinson's disease meeting the MDS Clinical Diagnostic Criteria for Parkinson's disease (2015 edition), with a disease duration of at least 3 years and Hoehn & Yahr stage < 4;
- •Stable use of anti-parkinsonian medication for 2 weeks prior to the study and throughout the entire study period, with no dosage adjustments; ④ Concurrently meeting the diagnostic criteria for Parkinson's disease-related pain, with a frequency of at least 3 times per week and duration of at least 3 months; Numerical Rating Scale (NRS) score ≥ 3; ⑤ Passing the TMS Safety Screening Questionnaire (TSSQ);
- •Passing the MRI Safety Screening Questionnaire (MSSQ);
排除标准
- •Patients with other diseases that may affect peripheral nerve sensation, including but not limited to diabetes, herpes infection, stroke, or spinal cord disorders;
- •Patients with comorbid severe depression or psychiatric disorders;
- •Presence of severe cognitive impairment, defined as a Mini-Mental State Examination (MMSE) score ≤ 9;
- •Patients with concurrent intracranial organic lesions or a history of traumatic brain injury; ⑤ Patients with severe organic diseases involving the heart, liver, kidneys, or other vital organs; ⑥ Patients unable to undergo cranial MRI examination or TMS treatment due to claustrophobia, presence of implanted devices such as pacemakers, history of epilepsy, or other contraindications.
- •Providing written informed consent.
研究组 & 干预措施
High-dose iTBS treatment group
High-dose iTBS, 5 sessions per day for 5 consecutive days.
干预措施: High-dose iTBS treatment group (Procedure)
Low-dose iTBS treatment group
Conventional-dose iTBS, once daily for 5 consecutive days.
干预措施: Low-dose iTBS treatment group (Procedure)
Sham stimulation group
Administer sham stimulation
干预措施: Sham stimulation group (Procedure)
结局指标
主要结局
Assessment with the KPPS
时间窗: at baseline, on day 1 after treatment, and at 1 month and 3 months after treatment
King's PD Pain Scale (KPPS) includes 14 items rating the severity and frequency of pain, each item scored by severity (0-3) multiplied by frequency (0-4), resulting in a subscore of 0 to 12, with a total possible score range from 0 to 168. Higher scores indicate greater symptom severities and more serious influence.
Assessment with the MKPPS
时间窗: at baseline, on day 1 after treatment, and at 1 month and 3 months after treatment
Modified King's PD Pain Scale (MKPPS)，the modified version which is more suitable for Chinese people, combined with Ford's pain subtypes basing on the original. It covers five main domains, including 16 items, each item scored by severity (0-3) multiplied by frequency (0-4), resulting in a total possible score range from 0 to 192. Higher scores indicate greater symptom severities and more serious influence.
Change in Pain Intensity Scores (VAS)
时间窗: at baseline, on day 1 after treatment, and at 1 month and 3 months after treatment
VAS, a 0-10 numeric rating scale with 0= no pain and 10=maximal pain. Higher scores indicate greater symptom severities and more serious influence.
次要结局
- Electroencephalography(The day before treatment and the first day after treatment completion.)
- Functional magnetic resonance imaging(The day before treatment and the first day after treatment completion.)
- Changes in MDS-UPDRS I(at baseline, on day 1 after treatment, and at 1 month and 3 months after treatment)
- Change in MDS-UPDRS II(at baseline, on day 1 after treatment, and at 1 month and 3 months after treatment)
- Change in MDS-UPDRS III(at baseline, on day 1 after treatment, and at 1 month and 3 months after treatment)
- Changes in PD Depression Score(at baseline, on day 1 after treatment, and at 1 month and 3 months after treatment)
- Changes in PD Anxiety Score(at baseline, on day 1 after treatment, and at 1 month and 3 months after treatment)
- Changes in PD Autonomic Symptoms Score(at baseline, on day 1 after treatment, and at 1 month and 3 months after treatment)
- Changes in PD Sleep Problem Score(at baseline, on day 1 after treatment, and at 1 month and 3 months after treatment)
- Changes in PD Daytime Sleepiness Score(at baseline, on day 1 after treatment, and at 1 month and 3 months after treatment)
- Changes in PD Quality of Life Score(at baseline, on day 1 after treatment, and at 1 month and 3 months after treatment)
研究者
Cheng-Jie Mao
Associate Professor
Second Affiliated Hospital of Soochow University