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

Neuropathic Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05168319
• Other study ID #: 2021-0751
• Status: Completed
• Phase: N/A
• Start date: February 28, 2022
• Est. completion date: January 30, 2023

Study information

• Verified date: January 2022
• Source: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: January 30, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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;

Related Conditions & MeSH terms

• Neuralgia
• Neuropathic Pain
• Repetitive Transcranial Magnetic Stimulation

Intervention

Device:
• Repetitive transcranial magnetic stimulation
Participants received 10HZ rTMS protocol consisted of 5 sessions over 5 consecutive workdays
• Repetitive transcranial magnetic stimulation
Participants received pcTBS protocol consisted of 5 sessions over 5 consecutive workdays
• Sham stimulation
Participants received Sham rTMS stimulations consisted of 5 sessions over 5 consecutive workdays

Locations

Country	Name	City	State
China	The second affiliated hospital of Zhejiang University hangzhou	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Second Affiliated Hospital, School of Medicine, Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The mean change from baseline in pain intensity measured with the visual-analogic scale (VAS)	The primary outcome measure was the mean change from baseline over the course of 5 (group by time interaction) in average pain intensity measured with the visual-analogic scale (VAS) ( 0= no pain and 10= maximal pain). Baseline average pain intensity was assessed at inclusion then on the day of randomization, just before the first rTMS session (day 1) and corresponded to the average of these two values.	through study completion, an average of 8 months
Secondary	Motor-evoked potential (MEP)	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).	through study completion, an average of 8 months
Secondary	Cortical silent period (CSP)	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).	through study completion, an average of 8 months
Secondary	The sensory dimension of pain and affective dimension of pain	The sensory dimension of pain (rated on 33) and affective dimension of pain (rated on 12) from the 15-items Short form of the McGill Pain questionnaire (SF-MPQ) .	through study completion, an average of 8 months
Secondary	Pain interference scale	7 items rated from 0= does not interfere to 10= complete interference, total score 70 from the Brief Pain Inventory.	through study completion, an average of 8 months
Secondary	Patients global impression of change	the 7 items Patients global impression of change (PGIC) (from very much worse to very much improved)	through study completion, an average of 8 months
Secondary	The depression score	ranging from 0 to 13 with higher scores indicating more severe depression from the 13 items Beck Depression Inventory (BDI)	through study completion, an average of 8 months
Secondary	release of neurotransmitters	Measured with magnetic resonance spectroscopy,MRS	through study completion, an average of 8 months