Analgesic Effect of Repetitive Transcranial Magnetic Stimulation (rTMS) for Central Neuropathic Pain in Multiple Sclerosis

Study Overview
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Brief Summary
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This study is designed to evaluate the effect of repetitive Transcranial Magnetic Stimulation (rTMS) in the resolution of chronic pain. Participants will be patients with Multiple Sclerosis suffering from chronic pain of neurological origin.

Detailed Description
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On the one hand, Multiple Sclerosis (MS) is the most frequent chronic disease generating neurological disability in young adults. Among the many types of disabilities associated with MS, chronic pain is very frequent, especially neuropathic pain. This type of pain is often treatment resistant. Moreover, abnormal intra-cortical excitability has been described in MS patients. On the other hand, repetitive Transcranial Magnetic Stimulation (rTMS) has shown an analgesic effect in various chronic pain conditions (fibromyalgia, post-stroke, peripheral neuropathic pain). Three groups have shown that analgesia was correlated to defective intra-cortical excitability restoration. The goal of this study is to compare the analgesic effects of two types of primary Motor cortex (M1) rTMS, namely 10Hz and prolonged continuous Theta-Burst Stimulation (pcTBS), with sham stimulation. Patients will benefit from 1 daily session per day for 5 consecutive days and from a total follow up of 4 weeks. Pain will be assessed each day and several other signs and symptoms will be repeatedly assessed.

Official Title
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Analgesic Effect of Repetitive Transcranial Magnetic Stimulation (rTMS) for Central Neuropathic Pain in Multiple Sclerosis

Conditions
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Multiple Sclerosis With Central Neuropathic Pain

Intervention / Treatment
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* Device: Repetitive Transcranial Magnetic Stimulation (rTMS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: relapsing-remitting Multiple Sclerosis 18 to 60 years central neuropathic pain with a DN4 score of 4 or more out of 10 average pain of at least 4/10 presence of pain at least 4 days per week presence of pain for at least 3 months stable analgesic treatment Exclusion Criteria: relapse during the previous 30 days contraindication for rTMS peripheral neuropathic pain severe depression epilepsia resting motor threshold above 75%

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Repetitive transcranial magnetic stimulation (rTMS)<br>The goal of this study is to compare the analgesic effects of two types of primary Motor cortex (M1) rTMS, namely 10Hz and prolonged continuous Theta-Burst Stimulation (pcTBS), with sham stimulation | Device: Repetitive Transcranial Magnetic Stimulation (rTMS)<br> <br> |
| Other: Theta-Burst Stimulation (pcTBS)<br>The goal of this study is to compare the analgesic effects of two types of primary Motor cortex (M1) rTMS, namely 10Hz and prolonged continuous Theta-Burst Stimulation (pcTBS), with sham stimulation. | Device: Repetitive Transcranial Magnetic Stimulation (rTMS)<br> <br> |
| Other: repetitive Transcranial Magnetic Stimulation (rTMS)placebo<br>The goal of this study is to compare the analgesic effects of two types of primary Motor cortex (M1) rTMS, namely 10Hz and prolonged continuous Theta-Burst Stimulation (pcTBS), with sham stimulation. | Device: Repetitive Transcranial Magnetic Stimulation (rTMS)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in average pain score on the brief pain inventory | Variation of the Average pain score on the Brief Pain Inventory between before treatment (on a 7 days period) and day 8. | at day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline in average pain score on the brief pain inventory | Variation of the average pain at several time-points during the 4 weeks follow-up | at weekk 3 and 4 | 
| Location of MRI abnormalities | Correlation between pain and pain decrease with MRI abnormalities in several regions of interest | at week 3 and 4 | 
| Intra-cortical excitability evaluated by motor threshold, MEP amplitude, SICI and ICF |  | at week 3 and 4 | 
| Number of participants with adverse events as a measure of safety and tolerability |  | at day 1 | 
| change from baseline in specific questionnaires |  | at day 8, week 3 and 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, Repetitive transcranial magnetic stimulation (rTMS), Chronic neuropathic pain, Cortical excitability