Repetitive Transcranial Magnetic Stimulation for Musculoskeletal Pain in Patients With Parkinson's Disease

NCT05537597 | Completed Results

• 1 other identifier: JD-LK-2021-132-01
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Primary Motor Cortex; Electroencephalography; Parkinson's Disease; Musculoskeletal Pain; Repetitive Transcranial Magnetic Stimulation; Neuromodulation

Outcome Measures

Primary Outcomes (3)

• Change From Baseline Over 2 Months (Group by Time Interaction) in Modified KING'S PD Pain Scale Domain 1

  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.

  before the first rTMS session (baseline), after rTMS therapy (day8、1month、2months)

• Change From Baseline Over 2 Months (Group by Time Interaction) in KING'S PD Pain Scale Domain 1

  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.

  before the first rTMS session (day 1), after rTMS therapy (day8、1month、2months)

• Change in 0-10 Numeric Rating Scale

  Pain intensity was assessed over the past 24 hours using a 0-10 number, where 0 indicating no pain and 10 indicating maximal pain.

  before the first rTMS session (baseline), after rTMS therapy (day8、1month、2months)

Secondary Outcomes (11)

• 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)

Study Arms (2)

M1-rTMS group

EXPERIMENTAL

active M1-rTMS

Procedure: active M1-rTMS

sham-rTMS group

SHAM COMPARATOR

sham rTMS

Procedure: sham rTMS

Interventions

active M1-rTMS PROCEDURE

Magnetic stimulation will be carried out using a MagPro X100 machine with a MCF-B70 figure-of-eight coil (Magventure, Farum). All rTMS sessions will be assisted by a neuronavigation system (TMS Navigator，Localite GmbH), maintaining the M1 target and the orientation of coil stable during stimulation sessions. The M1 target was defined as the "hand knob" region, which corresponds to the motor cortical representation of the hand, regardless of the location of pain. Stimulation paradigm consists of 20 trains of pulses with an intra-train frequency of 20 Hz, resulting in 2000 pulses for a total duration of 20 minutes. The stimulation intensity will be 80% of RMT, defined as the lowest stimulation intensity necessary to induce a visible muscle twitch of the hand contralateral to the stimulated hemisphere. Participants will receive 7 sessions of treatment once a day in the same time continuously for 7 days, and keep antiparkinsonism drugs unchanged throughout the whole study.

M1-rTMS group

sham rTMS PROCEDURE

The sham protocol was similar to the rTMS protocol. Sham stimulations will be performed with a MCF-P-B65 figure-of-eight coil (Magventure) to M1, assisted by a neuronavigation system. The following stimulation parameters will be used: stimulus frequency 20 Hz; stimulus intensity 80 % of RMT; total stimulation pulses 2,000; total stimulation time 20 min. Participants will receive 7 sessions of treatment once a day in the same time continuously for 7 days, and keep antiparkinsonism drugs unchanged throughout the whole study.

sham-rTMS group

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Second Affiliated Hospital of Soochow University: lead

Study Sites (1)

Department of Neurology, Second Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215004, China

Location

Related Publications (6)

• Valkovic P, Minar M, Singliarova H, Harsany J, Hanakova M, Martinkova J, Benetin J. Pain in Parkinson's Disease: A Cross-Sectional Study of Its Prevalence, Types, and Relationship to Depression and Quality of Life. PLoS One. 2015 Aug 26;10(8):e0136541. doi: 10.1371/journal.pone.0136541. eCollection 2015.

  PMID: 26309254 BACKGROUND

• Silverdale MA, Kobylecki C, Kass-Iliyya L, Martinez-Martin P, Lawton M, Cotterill S, Chaudhuri KR, Morris H, Baig F, Williams N, Hubbard L, Hu MT, Grosset DG; UK Parkinson's Pain Study Collaboration. A detailed clinical study of pain in 1957 participants with early/moderate Parkinson's disease. Parkinsonism Relat Disord. 2018 Nov;56:27-32. doi: 10.1016/j.parkreldis.2018.06.001. Epub 2018 Jun 6.

  PMID: 29903584 BACKGROUND

• Chaudhuri KR, Rizos A, Trenkwalder C, Rascol O, Pal S, Martino D, Carroll C, Paviour D, Falup-Pecurariu C, Kessel B, Silverdale M, Todorova A, Sauerbier A, Odin P, Antonini A, Martinez-Martin P; EUROPAR and the IPMDS Non Motor PD Study Group. King's Parkinson's disease pain scale, the first scale for pain in PD: An international validation. Mov Disord. 2015 Oct;30(12):1623-31. doi: 10.1002/mds.26270. Epub 2015 Jun 11.

  PMID: 26096067 BACKGROUND

• Picarelli H, Teixeira MJ, de Andrade DC, Myczkowski ML, Luvisotto TB, Yeng LT, Fonoff ET, Pridmore S, Marcolin MA. Repetitive transcranial magnetic stimulation is efficacious as an add-on to pharmacological therapy in complex regional pain syndrome (CRPS) type I. J Pain. 2010 Nov;11(11):1203-10. doi: 10.1016/j.jpain.2010.02.006. Epub 2010 Apr 28.

  PMID: 20430702 BACKGROUND

• O'Connell NE, Marston L, Spencer S, DeSouza LH, Wand BM. Non-invasive brain stimulation techniques for chronic pain. Cochrane Database Syst Rev. 2018 Apr 13;4(4):CD008208. doi: 10.1002/14651858.CD008208.pub5.

  PMID: 29652088 BACKGROUND

• Lefaucheur JP, Aleman A, Baeken C, Benninger DH, Brunelin J, Di Lazzaro V, Filipovic SR, Grefkes C, Hasan A, Hummel FC, Jaaskelainen SK, Langguth B, Leocani L, Londero A, Nardone R, Nguyen JP, Nyffeler T, Oliveira-Maia AJ, Oliviero A, Padberg F, Palm U, Paulus W, Poulet E, Quartarone A, Rachid F, Rektorova I, Rossi S, Sahlsten H, Schecklmann M, Szekely D, Ziemann U. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018). Clin Neurophysiol. 2020 Feb;131(2):474-528. doi: 10.1016/j.clinph.2019.11.002. Epub 2020 Jan 1.

  PMID: 31901449 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease; Musculoskeletal Pain

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Muscular Diseases; Musculoskeletal Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Department of Neurology
• Organization: Second Affiliated Hospital of Soochow University

drchengjiemao@163.com

0512-67784179

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: The figure-of-eight coils used for active or sham stimulation are similar, including the emitted sound and the scalp tapping sensation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Patients will be randomised to receive either active or sham-rTMS according to a 2:1 ratio.

Study Record Dates

• First Submitted: September 2, 2022
• First Posted: September 13, 2022
• Study Start: October 1, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: February 17, 2026
• Results First Posted: February 17, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)