Analgesic Effects of rTMS in Peripheral Neuropathic Pain

Study Overview
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Brief Summary
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This study aims to evaluate the long term efficacy over 25 weeks of repeated sessions of magnetic transcranial stimulation of the motor cortex or prefrontal cortex on average pain intensity, quality of life, sleep, neuropathic symptoms, return to work, in patients with peripheral neuropathic pain. The medical device of study: transcranial magnetic stimulator (TMS).

Detailed Description
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The present multicenter parallel session randomized placebo controlled study (4 French centers) aims to evaluate the long term efficacy over 25 weeks of repeated sessions of magnetic transcranial stimulation of the motor cortex or prefrontal cortex on average pain intensity (primary outcome) and several secondary outcome measures (e.g. quality of life, sleep, neuropathic symptoms, return to work), in patients with peripheral neuropathic pain. The patients will be randomized to receive one of 3 treatment arms : rTMS of the motor cortex, rTMS of the prefrontal cortex, or placebo (sham stimulation) of the motor or prefrontal cortex. The study will be double blind, eg the patient and the investigator will not know the nature of treatment. the stimulation protocol will consist of an induction phasse of 5 daily sessions then a maintenance phase of several sessions : 3 sessions a week apart, 3 sessions a fortnight apart, and 3 sessions 3 weeks apart. The statistical analysis will be conducted in the intent to treat population and using a modified ITT analysis excluding all the patients with protocol violation (primary outcome). The per protocol population will also be assessed.

Official Title
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Long-term Efficacy of Repetitive Transcranial Magnetic Stimulation (rTMS) of the Motor or Prefrontal Cortex in Peripheral Neuropathic Pain: a Multicenter Randomized Placebo Controlled Trial

Conditions
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Neuropathic Pain

Intervention / Treatment
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* Device: rTMS of prefrontal or motor cortex


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Peripheral neuropathic pain (unilateral or bilateral) probable or defined according to the criteria proposed in 2008 (Treede et al 2008), Diagnostic DN4 questionnaire score greater than or equal to 4/10 (Bouhassira et al 2005), chronic pain, the average intensity is greater than or equal to 40/100 Daily or almost daily pain (at least 4 days out of 7) This pain is present for more than 6 months Patients over 18 and under 75 years old Patients who signed informed consent, Patients whose pain medication is stable for 15 days before inclusion, and will not need to be changed during the study period, Patients who can be monitored during the study period (30 weeks) Patients insured by a health insurance plan or entitled. Exclusion Criteria: Previous treatment using rTMS, Work Accident or dispute rTMS Cons-indications (ECT treatment during the previous month, epilepsy and / or a history of epilepsy; history of head trauma, neurosurgical lesion, intracranial hypertension, metal clip, pacemaker, pregnant or lactating women) Abuse of drugs or psychoactive substances (DSM IV) Central neuropathic pain, Neuropathic pain within the framework of a progressive disease (HIV, cancer, non-stabilized system disease) Neuropathic pain very limited extent, of neuroma type Current major depression or psychosis according to DSM IV criteria, Intermittent pain, Pain for less than six months, Presence of another pain more severe than the one justifying the inclusion Lack of proper filling of self-assessment of pain from baseline and randomization (at least 4 weekly pain scores 7 days) notebooks Lack of stability of pain scores on two successive evaluations, defined as a change of more than 30% between the two assessments of the average pain on the short questionnaire about pain between the first two visits inclusion Subject unable to understand informed consent, under guardianship, Subject who refuses to stop or can not stop prohibited treatment during the study, Patients participating in another research protocol involving a drug within 30 days before enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rTMS of the motor cortex (Magventure)<br>experimental : rTMS of the motor cortex : repetitive magnetic stimulation targeting the motor cortex assisted by neuronavigation | Device: rTMS of prefrontal or motor cortex<br>* description:rTMS of the motor or prefrontal cortex (repetitive magnetic stimulation targeting the motor or prefrontal cortex) assisted with neuronavigation<br>|
| Placebo Comparator: rTMS placebo (magventure)<br>sham stimulation of the motor or prefrontal cortex with the placebo face of the device | Device: rTMS of prefrontal or motor cortex<br>* description:rTMS of the motor or prefrontal cortex (repetitive magnetic stimulation targeting the motor or prefrontal cortex) assisted with neuronavigation<br>|
| Experimental: rTMS prefrontal cortex (magventure)<br>Experimental : repetitive transcranial stimulation targeting the prefrontal cortex as indicated by neuronavigation | Device: rTMS of prefrontal or motor cortex<br>* description:rTMS of the motor or prefrontal cortex (repetitive magnetic stimulation targeting the motor or prefrontal cortex) assisted with neuronavigation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in average pain intensity from baseline to week 25 | Change in average pain intensity from baseline to week 25, average pain intensity corresponds to average pain over the last 24 hours on the Brief Pain Inventory | each visit for up to 25 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in minimal pain intensity over the last 24 hours from baseline to week 25 | change in minimal pain over the last 24 hours on the Brief Pain inventory | each visit for up 25 weeks | 
| quality of life assessment | quality of life on the Eurogol questionnaire | each visit up to 25 weeks | 
| Proportion of responders to rTMS | Proportion of responders (patients whose pain is improved by at least 30% and 50% compared to their pain before treatment | at the end of treatment (25 weeks) | 
| Predictors of the response | Evaluation of predictors of response (nature of neuropathic symptoms, severity of anxiety or depressive symptoms, presence or absence of mechanical allodynia, or dramatization importance of catastrophism related to pain) | Baseline | 
| Safety evaluation | Collection of side effects at each session and between sessions of rTMS | each follow up visit for up to 25 weeks | 
| Onset of the analgesic effect of rTMS | Determine the onset of the analgesic effect based on patient pain diaries for up to 1 month | one mont afer the beginning of rTMS | 
| Return to work | Return to work on a specific questionnaire at the end of the study | 25 weeks | 
| Maximal pain | Maximal pain over the past 24 hours on the Brief Pain Inventory | each visit up to 25 weeks | 
| Pain right now | Pain right now immediately after each rtMS session and between sessions for up to 25 weeks | each visit up to 25 weeks | 
| Sleep | sleep quality and quantity on MOS sleep | each visit up to 25 weeks | 
| Neuropathic symptoms | Neuropathic symptoms on the Neuropathic Pain Symptom Inventory | each visit up to 25 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rTMS, peripheral neuropathic pain, randomized controlled trial