rTMS Efficacy Coupled With Mirror Therapy

Study Overview
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Brief Summary
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Neuropathic pain is particularly difficult to treat with classic first-line drugs. Neuromodulation techniques using repetitive transcranial magnetic stimulation (rTMS) are useful alternative, but there is a need to improve their analgesic effect.Virtual reality mirror therapy has shown the capacity to alleviate pain and may be easily coupled with rTMS.The present project will investigate in individuals with neuropathic pain the effects of the rTMS coupled with virtual reality mirror therapy.

Detailed Description
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This project introduces a new research question that incorporates virtual reality mirror therapy into an established treatment protocol of repetitive transcranial magnetic stimulation (rTMS) for neuropathic pain relief. Neuropathic pain is particularly difficult to treat with classic first-line drugs. Neuromodulation techniques using repetitive transcranial magnetic stimulation (rTMS) are useful alternative, but there is a need to improve their analgesic effect. Virtual reality mirror therapy has shown the capacity to alleviate pain and may be easily coupled with rTMS. The efficacy of using both techniques in neuropathic pain treatment is unknown. The present project will investigate in individuals with neuropathic pain the effects of the rTMS coupled with virtual reality mirror therapy on: 1) daily pain intensity (i.e. analgesic efficacy); 2) other components of pain and the quality of life; 3) brain activity. It will be the first to provide insight into the efficacy of using together both non-invasive technics of cortical neuromodulation to alleviate pain.

Official Title
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Clinical Study of Repetitive Transcranial Magnetic Stimulation (RTMS) Efficacy Coupled With Mirror Therapy for Neuropathic Pain Relief

Conditions
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Neuropathic Pain

Intervention / Treatment
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* Other: Repetitive transcranial magnetic stimulation (rTMS)
* Other: Mirror therapy using virtual reality
* Other: Mirror therapy using sham mirror


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical symptoms typical of neuropathic pain Refractory to drug therapies Lasting for at least 6 months, with a moderate to severe pain intensity (≥4/10 on Visual Analog Scale, VAS) and a stable pain treatment since 1month at least Having right to health benefits Exclusion Criteria: Ferromagnetic components and implanted microprocessors (i.e. cochlear implants) Drug-resistant or active epilepsy, pacemaker, pregnancy, ongoing depression or personality troubles, and ongoing opioid treatment. Any other contraindications to MRI scanner (e.g., claustrophobia, etc.).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Interventional Model Description: Group 1: patient with 4 sessions of active mirror therapy followed by an rTMS stimulation session of the primary motor cortex (M1), Group 2: patient with 4 sessions of sham mirror therapy followed by rTMS of the primary motor cortex (M1).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rTMS active and active mirror-based therapy using virtual reality<br>The patient will have an amount of 4 sessions (S3, S5, S7 and S9) for 1.5 months: 1 session every 2 weeks. The patient will receive rTMS active and active mirror-based therapy using virtual reality. | Other: Repetitive transcranial magnetic stimulation (rTMS)<br>* 20 minutes of high frequency (20Hz) rTMS.<br>Other: Mirror therapy using virtual reality<br>* active mirror-based therapy<br>|
| Sham Comparator: rTMS active and sham mirror-based therapy using virtual reality<br>The patient will have an amount of 4 sessions (S3, S5, S7 and S9) for 1.5 months: 1 session every 2 weeks. The patient will receive rTMS active and sham mirror-based therapy using virtual reality. | Other: Repetitive transcranial magnetic stimulation (rTMS)<br>* 20 minutes of high frequency (20Hz) rTMS.<br>Other: Mirror therapy using sham mirror<br>* 20 minutes of sham mirror-based therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity measurement | Averages of the daily visual analogue scale scores (min no pain max pain imaginable) measured during the first week (Week 1) and that measured during the week following the last session (week 9) | Week 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life after treatment | EQ5D scale (min = 0 worst imaginable health condition and max = 100 best health condition imaginable) and Analgesic consumption of Appeal | week 12 | 
| Spontaneous brain activity | Functional MRI at rest | week 12 | 
| neuropathic dimension | overall score of the neuropathic pain symptoms inventory (NPSI) (min = 0 no neuropathic pain and max = 100 intensive neuropathic pain) | Week 3, 5, 7, 9,12 | 
| Adverse events | Nature and number of adverse events | Week 3, 5, 7, 9,12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transcranial magnetic stimulation, virtual reality, mirror therapy, brain networks, predictive model