Repetitive Transcranial Magnetic Stimulation for Musculoskeletal Pain in Patients With Parkinson's Disease：Efficacy and Safety, Electrophysiological Mechanisms and Influence on Motor and Other Non-motor Symptoms
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Change From Baseline Over 2 Months (Group by Time Interaction) in Modified KING'S PD Pain Scale Domain 1
研究概览
简要总结
Pain is an increasingly recognized non-motor symptom of Parkinson's disease (PD), with significant prevalence and negative impact on the quality of life of patients.
Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex（M1）has been proposed to provide definite analgesic effect for pain syndromes. However, very few placebo-controlled studies have been performed specifically to relieve pain in PD. What's more, based on behavioral measures alone, it is impossible to reveal the full network dynamics reflecting the impact of TMS.
Electroencephalography (EEG), with high temporal resolution, records signal that its origin in electrical neural activity, which makes it suitable for measuring TMS-evoked activation. By recording the TMS induced neuronal activation directly from the cortex, TMS-EEG provides information on the excitability, effective connectivity of cortical area, thus exploring cortical network properties in different functional brain states. In addition, the use of EEG offers great prospects as a tool to select the right patients in order to achieve adequate, long-term pain relief.
Besides assessing the efficacy and safety of high-frequency neuronavigated M1-rTMS in PD patients with musculoskeletal pain, the objective of this study additionally aimed to characterize cortical activation behind pain relief. Influence on motor and other non-motor symptoms after rTMS were also investigated.
详细描述
Pain can appear as a pre-motor symptom, and its intensity could be severe enough to be the dominant non-motor symptom in the course of PD patients.
It estimated the prevalence of painful phenomena in PD to be 30 to 85% (mean 66%), which is significantly greater than the age-matched general population. Painful experiences in PD are highly heterogeneous and complex, which is difficult to describe for patients but also diagnose for neurologists. In addition, this common and disabling symptom receives inadequate analgesic treatment.
The distinction between these pain subtypes is required so that different therapeutic strategies can be established for each type of pain. The King's Parkinson's Pain scale (KPPS) was validated to identify and rate the various types of pain in PD. Fourteen items cover seven main domains, including musculoskeletal pain, chronic body pain (central or visceral), fluctuation-related pain, dyskinetic-dystonic pain, nocturnal pain, oro-facial pain, discolouration/oedema/swelling, and radicular pain. Of these subtypes, musculoskeletal pain is common.
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that may be useful for the treatment of various psychiatric and neurological disorders. The mechanisms underlying rTMS effects remain to be elucidated.
rTMS is postulated to induce neuronal excitability changes in a set of cortical and subcortical areas involved in pain processing and modulation. Interestingly, M1 stimulation had a positive effect on brain structures that are related to the affective-emotional components of pain, such as the insular cortex and cingulate cortex.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Idiopathic PD was diagnosed according to the 2015 Movement Disorder Society (MDS) clinical diagnostic criteria
- •Hoehn and Yahr stages of I to III
- •musculoskeletal pain was detected based on the Ford classification system for pain in PD. Pain duration of at least 3 months, with continuous moderate intensity pain (≥ 3/10 on a 0-10 numerical rating scale) occurring at least three days per week.
- •stable antiparkinsonian therapy for ≥4 weeks
排除标准
- •Contraindications to rTMS
- •unstable ongoing psychiatric disorder, history of substance abuse (alcohol, drugs)
- •histories of deep brain stimulation surgery
- •Mini-mental State Examination scores ≤24
- •Other pain conditions, such as apparent osteoarthritis, or rheumatoid arthritis depended on laboratory or imaging findings
研究组 & 干预措施
M1-rTMS group
active M1-rTMS
干预措施: active M1-rTMS (Procedure)
sham-rTMS group
sham rTMS
干预措施: sham rTMS (Procedure)
结局指标
主要结局
Change From Baseline Over 2 Months (Group by Time Interaction) in Modified KING'S PD Pain Scale Domain 1
时间窗: before the first rTMS session (baseline), after rTMS therapy (day8、1month、2months)
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 From Baseline Over 2 Months (Group by Time Interaction) in KING'S PD Pain Scale Domain 1
时间窗: before the first rTMS session (day 1), after rTMS therapy (day8、1month、2months)
KING'S PD Pain Scale (KPPS) Domain 1 focused on musculoskeletal pain, covering one item, which was scored by multiplying severity (from 0 \[no pain\] to 3 \[very severe pain\]) by frequency (from 0 \[never\] to 4 \[all the time\]), yielding sub-scores between 0 and 12. Higher scores indicate greater symptom severity.
Change in 0-10 Numeric Rating Scale
时间窗: before the first rTMS session (baseline), after rTMS therapy (day8、1month、2months)
Pain intensity was assessed over the past 24 hours using a 0-10 number, where 0 indicating no pain and 10 indicating maximal pain.
次要结局
- Changes in Resting-state EEG Oscillations(before the first rTMS session (day 1), after rTMS therapy (day8))
- Changes in Movement Disorder Society-Unified PD Rating Scale Part I(before the first rTMS session (baseline), after rTMS therapy (day8、1month、2months))
- Change in Movement Disorder Society-Unified PD Rating Scale Part II(before the first rTMS session (baseline), after rTMS therapy (day8、1month、2months))
- Change in Movement Disorder Society-Unified PD Rating Scale Part III(before the first rTMS session (baseline), after rTMS therapy (day8、1month、2months))
- Change in Movement Disorder Society-Unified PD Rating Scale Part IV(before the first rTMS session (baseline), after rTMS therapy (day8、1month、2months))
- Changes in Hamilton Depression Scale(before the first rTMS session (baseline), after rTMS therapy (day8、1month、2months))
- Changes in Hamilton Anxiety Scale(before the first rTMS session (baseline), after rTMS therapy (day8、1month、2months))
- Changes in PD Sleep Scale-2(before the first rTMS session (baseline), after rTMS therapy (day8、1month、2months))
- Changes in Epworth Sleeping Scale(before the first rTMS session (day 1), after rTMS therapy at day8、1month、2months)
- Changes in PD for Autonomic Symptoms(before the first rTMS session (baseline), after rTMS therapy (day8、1month、2months))
- Changes in PD Questionnaire-39(before the first rTMS session (baseline), after rTMS therapy (day8、1month、2months))
研究者
Cheng-Jie Mao
Associate Professor
Second Affiliated Hospital of Soochow University