Parkinson's Disease Clinical Trial
Official title:
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
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.
Status | Not yet recruiting |
Enrollment | 40 |
Est. completion date | May 2025 |
Est. primary completion date | February 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 40 Years to 75 Years |
Eligibility | Inclusion Criteria: 1. Idiopathic PD was diagnosed according to the 2015 Movement Disorder Society (MDS) clinical diagnostic criteria 2. Hoehn and Yahr stages of I to III 3. musculoskeletal pain was detected based on the Ford classification system for pain in PD,chronic pain for =3 months 4. stable antiparkinsonian therapy for =4 weeks Exclusion Criteria: 1. Contraindications to rTMS 2. unstable ongoing psychiatric disorder, history of substance abuse (alcohol, drugs) 3. histories of deep brain stimulation surgery 4. Mini-mental State Examination scores =24 5. Other pain conditions, such as apparent osteoarthritis, or rheumatoid arthritis depended on laboratory or imaging findings |
Country | Name | City | State |
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China | Department of Neurology, Second Affiliated Hospital of Soochow University | Suzhou | Jiangsu |
Lead Sponsor | Collaborator |
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Second Affiliated Hospital of Soochow University |
China,
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. — View Citation
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. Erratum In: Clin Neurophysiol. 2020 May;131(5):1168-1169. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change from baseline over 2 months (group by time interaction) in KPPS | 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. | before the first rTMS session (day 1), after rTMS therapy at day8?1month?2month | |
Primary | Change from baseline over 2 months (group by time interaction) in MKPPS | 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. | before the first rTMS session (day 1), after rTMS therapy at day8?1month?2month | |
Primary | Change in pain intensity scores (VAS) | VAS, a 0-10 numeric rating scale with 0= no pain and 10=maximal pain | before the first rTMS session (day 1), after rTMS therapy at day8?1month?2month | |
Primary | Adverse event | Any adverse events occurred and the reasons leading to treatment discontinuation will be recorded. The severity and relevance will be rated as mild, moderate or serious by investigators. | through study completion, an average of 2 month | |
Secondary | Changes in resting-state EEG oscillations | During EEG recordings, participants will sit alone in a quiet room and be requested to minimize any other body movements, mostly with eyes closed.
We will use a TMS-compatible EEG amplifier (neuracle, changzhou, China) and a cap (Greentek, Wuhan, China) providing 64 TMS-compatible coated-electrodes with positions of the international 10/20 system. The signals recorded will be digitized at a sampling rate of 1kHz. Skin/electrode impedance will be maintained below 10KO. The EEG recording protocol consists of a 5-min resting-state paradigm without any task involvement. |
before the first rTMS session (day 1), after rTMS therapy (day8) | |
Secondary | Changes in Resting-State EEG Functional Connectivity | The functional connectivity of the identified brain region showing significant difference of cortical oscillations will be further investigated. | before the first rTMS session (day 1), after rTMS therapy (day8) | |
Secondary | Alterations of TMS-elicited evoked potentialspotentials | Single-pulse TMS of the M1 will be performed during EEG recording by means of a figure-of-eight coil oriented to elicit posterolateral-anteromedial current flow in the brain. The signal was sampled at 16 kHz. Participants will wear inserted earplugs to avoid signals contamination by the click associated with the TMS discharge.
the interval of each sTMS will be set at 4 seconds to avoid habituation with repeated stimulation. Each participant will undergo a 20-min session about 120 TMS trials at intensity of 120%RMT. |
before the first rTMS session (day 1), after rTMS therapy (day8) | |
Secondary | Changes in PD-Motor Symptoms Scale total score | The participants will be evaluated in their "ON" medication states. The scales used to assess motor symptoms are parts III (ranging from 0 to 132) and IV (ranging from 0 to 24) of the MDS-Unified PD Rating Scale (MDS-UPDRS), with higher scores indicating more severe symptoms. | before the first rTMS session (day 1), after rTMS therapy at day8?1month?2month | |
Secondary | Changes in PD-Non-Motor Symptoms Scale total score | The participants will be evaluated in their "ON" medication states. The scales used to assess non-motor symptoms included parts I (ranging from 0 to 52) and II (ranging from 0 to 52) of the MDS-UPDRS, with higher scores indicating more severe symptoms. | before the first rTMS session (day 1), after rTMS therapy at day8?1month?2month | |
Secondary | Changes in PD depression score | The depression score (ranging from 0 to 76 with higher scores indicating more severe depression) from the 24 items Hamilton Depression Scale (HAMD). | before the first rTMS session (day 1), after rTMS therapy at day8?1month?2month | |
Secondary | Changes in PD anxiety score | The anxiety score (ranging from 0 to 60 with higher scores indicating more severe anxiety) from the 14 items Hamilton Anxiety Scale (HAMA). | before the first rTMS session (day 1), after rTMS therapy at day8?1month?2month | |
Secondary | Changes in PD autonomic Symptoms score | The Scale for Outcomes in Parkinson's disease for Autonomic Symptoms (SCOUP-AUT, maximal score 67, with higher scores indicating higher autonomic nervous system dysfunction). | before the first rTMS session (day 1), after rTMS therapy at day8?1month?2month | |
Secondary | Changes in PD sleep problem score | The sleep problem index (from 0 to 68 with higher scores indicating more severe sleep problem) from the PD Sleep Scale-2 (PDSS-2). | before the first rTMS session (day 1), after rTMS therapy at day8?1month?2month | |
Secondary | Changes in PD daytime sleepiness score | The daytime sleepiness will be assessed by the Epworth Sleeping Scale (ESS), maximal score 24, with higher scores indicating more severe symptoms. | before the first rTMS session (day 1), after rTMS therapy at day8?1month?2month | |
Secondary | Changes in PD quality of life score | We will also assess change in quality of life from the Parkinson's Disease Questionnaire-39 (PDQ-39), ranging from 0 to 156 with higher scores indicating more serious influence. | before the first rTMS session (day 1), after rTMS therapy at day8?1month?2month |
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