Effects and Mechanism of Prolonged Continuous Theta Burst Stimulation on Neuropathic Pain

NCT ID: NCT05168319

Last Updated: 2023-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-28
• Study Completion Date: 2023-01-30

Brief Summary

Neuropathic pain (NP) is one type of refractory chronic pain condition,medical treatments for NP is limited because of its poorly response. A noninvasive brain-stimulation method called transcranial magnetic stimulation (TMS) has garnered interest as an alternative treatment for intractable NP potentially through inducing therapeutic brain plasticity.Indeed, high-frequency (≥ 5 Hz) Repetitive TMS (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,the investigation of rTMS protocols is important for improving rTMS analgesia. Theta burst stimulation (TBS) mimics the bursts of neuronal firing which results in robust long-term potentiation. Continuous TBS (cTBS) is designed to decrease excitability, whereby prolonged cTBS (pcTBS, i.e. multiple cTBS being delivered continuously) has recently been demonstrated to increase excitability. More importantly, pcTBS was found to have comparable or even better analgesic effects than standard 10 Hz rTMS. These findings together call for more studies to validate the analgesic efficacy of pcTBS.

In this study, the investigators aim to assess and compare the efficacy of prolonged continuous theta burst stimulation (pcTBS) with 10HZ rTMS in NP patients.

Detailed Description

The investigators designed a randomized, double-blind, sham-controlled study at 1 center. fifty NP patients were randomly assigned to 3 groups. A series of 5 daily pcTBS(1200 pulses/session) or 10-Hz rTMS (1500 pulses/session) of primary motor cortex (M1) or sham stimulation was applied to each patients.

Conditions

Neuropathic Pain; Repetitive Transcranial Magnetic Stimulation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

pcTBS

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. A total of 1,200 pulses were delivered with the TMS coil positioned in a posterior-anterior (PA) direction parallel to the midline.

Group Type: EXPERIMENTAL

Repetitive transcranial magnetic stimulation

Intervention Type: DEVICE

Participants received pcTBS protocol consisted of 5 sessions over 5 consecutive workdays

10HZ rTMS

The rTMS protocol included 15 trains of 10-second stimulation given at 10 Hz to the left M1 at 80% resting motor threshold (RMT), with the inter-train interval being set to 50 seconds (1500 pulses)

Group Type: ACTIVE_COMPARATOR

Repetitive transcranial magnetic stimulation

Intervention Type: DEVICE

Participants received 10HZ rTMS protocol consisted of 5 sessions over 5 consecutive workdays

Sham

The Sham stimulation was delivered using the same protocol, with the coil being orientated at 90° to the scalp so that the magnetic field would be delivered away from the scal

Group Type: SHAM_COMPARATOR

Sham stimulation

Intervention Type: DEVICE

Participants received Sham rTMS stimulations consisted of 5 sessions over 5 consecutive workdays

Interventions

Repetitive transcranial magnetic stimulation

Participants received 10HZ rTMS protocol consisted of 5 sessions over 5 consecutive workdays

Intervention Type: DEVICE

Repetitive transcranial magnetic stimulation

Participants received pcTBS protocol consisted of 5 sessions over 5 consecutive workdays

Intervention Type: DEVICE

Sham stimulation

Participants received Sham rTMS stimulations consisted of 5 sessions over 5 consecutive workdays

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• (1)woman or man over 18 and under 70 years old; （2）pain fulfilling the criteria for probable or definite peripheral neuropathic pain ; (3) pain for at least 3 months, continuous pain (at least four days per week), 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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

min yan, prof

Role: STUDY_CHAIR

The second affiliated hospital of Zhejiang University hangzhou

Locations

The second affiliated hospital of Zhejiang University hangzhou

Hangzhou, Zhejiang, China

Countries

China

Other Identifiers

2021-0751

Identifier Type: -

Identifier Source: org_study_id