Optimize the Effects of Repetitive Transcranial Magnetic Stimulation on Neuropathic Pain

Not Applicable

Completed

• Conditions: Repetitive Transcranial Magnetic Stimulation; Neuropathic Pain
• Interventions: Device: Repetitive transcranial magnetic stimulation

• Registration Number: NCT05338554
• Lead Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Brief Summary

Neuropathic pain (NP) is one type of refractory chronic pain condition,medical treatments for NP is limited because of its poorly response.Repetitive transcranial magnetic stimulation (rTMS) can induce neuroplastic changes which has been used to manage chronic pain conditions. Indeed, high-frequency (≥ 5 Hz) rTMS over the primary motor cortex (M1) is suggested to be able to reduce neuropathic pain in randomized controlled studies. Overall, the clinical application of rTMS in chronic pain is still limited by the response rate, whereby it is close to moderate and far from being excellent at its best. Therefore this project designed a series of clinical trials to optimize the analgesic efficacy of rTMS. According to the research results of investigators previous project, patients with neuropathic pain were divided into responders and non-responders after 5 consecutive days of 10HZ rTMS or pcTBS intervention (see project ID:2021-0751)according to the change of pain intensity, and then different trials will be applied to responders and non-responders to optimize the analgesic effect of rTMS.

Detailed Description

For non-responders (whose visuo-analogic scale (VAS) decreased less than 20 mm or T1-T0/T0×100%\<30%), a feasible method is to switch stimulation targets. So the investigator will change the stimulation target from M1 to dorsolateral prefrontal cortex (DLPFC), and then delivered another 5 days consecutive interventions to assess the efficacy.

For responders (whose VAS decreased an average of 20 mm or more or T1-T0/T0×100%≥30%), the investigator further investigate the long-lasting effect of rTMS. the patients will participate a continuous trials (2 sessions weekly for 2 weeks) and 4 weeks follow up.

Study Timeline

• Study First Submitted: 2021-12-16
• Study Start: 2022-03-01
• Study First Submitted QC: 2022-04-19
• Study First Posted: 2022-04-21
• Primary Completion: 2022-12-01
• Study Completion: 2022-12-31
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-14
• Last Update Posted: 2023-02-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• （1）woman or man over 18 years and under 85 years; （2）Clinical diagnosis of neuropathic pain (3) pain for at least 3 months, at least moderate intensity (≥ 4/10 assessed by VAS) ; (4) stable pharmacological treatment for pain at least 2 weeks before inclusion; (5) able to cooperate in completing questionnaire.

Exclusion Criteria

• (1)Any clinically significant or unstable ongoing medical or psychiatric disorder including major depression; (2) History of substance abuse (alcohol, drugs); (3) Past treatment with repetitive transcranial magnetic stimulation (rTMS); (4) Contraindications to rTMS (previous severe head trauma or neurosurgical intervention, past or current epilepsy, active brain tumor, intracranial hypertension, implanted ferromagnetic devices, e.g., cardiac pacemaker, neurostimulator, or cochlear implants); (5) other type of pain more severe than neuropathic pain; (6) Any difficulty to fill out questionnaires (due to language or cognitive problems); (7) impossibility to be followed during the time course of the study;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
pcTBS	Repetitive transcranial magnetic stimulation	The protocol is same as the previous study: pcTBS was administered to the left M1 at 80% resting motor threshold (RMT), consisting of a burst of 3 pulses given at 50 Hz repeated every 5 Hz using repetitive transcranial magnetic stimulation device . A total of 1,200 pulses were delivered with the TMS coil positioned in a posterior-anterior (PA) direction parallel to the midline.
10HZ rTMS	Repetitive transcranial magnetic stimulation	The protocol is same as the previous study: 10HZ rTMS included 15 trains of 10-second stimulation given at 10 Hz to the left M1 at 80% resting motor threshold (RMT) using repetitive transcranial magnetic stimulation device , with the inter-train interval being set to 50 seconds (1500 pulses)

Primary Outcome Measures

Name	Time	Method
pain intensity measured with the visuo-analogic scale (VAS)	through study completion, an average of 8 months	For non-responders:the primary outcome measure is the mean change from baseline over the course of 5 (group by time interaction) in average pain intensity measured with the visuo-analogic scale (VAS) ( 0= no pain and 10= maximal pain). Pain intensity is further assessed immediately before each rTMS session at days 2, 3, 4, 5, and then at weeks 2, 3, 4 after the intervention.; For responders: pain intensity is assessed after two sessions of rTMS session and then at weeks 2, 3, 4 after the intervention.

Secondary Outcome Measures

Name	Time	Method
The sensory dimension of pain	through study completion, an average of 8 months	The sensory dimension of pain (rated on 33) measured with Short form of the McGill Pain questionnaire (SF-MPQ) .
Pain interference scale	through study completion, an average of 8 months	7 items rated from 0= does not interfere to 10= complete interference, total score 70 from the Brief Pain Inventory.
Motor-evoked potential (MEP)	through study completion, an average of 8 months	Corticospinal excitability was measured with MEP at rest of the first dorsal interosseous (FDI) muscle, A total of 20 single pulses were consecutively delivered to the hand region of the left M1 at 120% RMT (45° to the midline, handle pointing backward).
Cortical silent period (CSP)	through study completion, an average of 8 months	Corticospinal excitability was measured with CSP during a sustained voluntary FDI muscle contraction, A total of 20 single pulses were consecutively delivered to the hand region of the left M1 at 120% RMT (45° to the midline, handle pointing backward).
The depression score	through study completion, an average of 8 months	ranging from 0 to 13 with higher scores indicating more severe depression from the 13 items Beck Depression Inventory (BDI)
The affective dimension of pain	through study completion, an average of 8 months	The affective dimension of pain measured with Short form of the McGill Pain questionnaire (SF-MPQ) .
Patients global impression of change	through study completion, an average of 8 months	the 7 items Patients global impression of change (PGIC) (from very much worse to very much improved)

Trial Locations

Locations (1)

The second affliated hospital of zhejiang university; 🇨🇳 Hangzhou, Zhejiang, China