Treatment of Difficult to Control Focal Epilepsy With Repetitive Transcranial Magnetic Stimulation (rTMS)

Study Overview
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Brief Summary
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The investigators will treat patients with fully characterized refractory unifocal neocortical epilepsy with a technique that delivers magnetic waves (transcranial magnetic stimulation, TMS) to the region that causes the epilepsy. Active rTMS applied over the epileptogenic focus will reduce seizure frequency compared with sham rTMS.

Detailed Description
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Background and study aims Epilepsy is a disease that causes repetitive seizures. In 60% of people with epilepsy, these seizures start in a small zone of the brain (focal or partial epilepsy). This zone can be in the depth of the temporal lobe (mesial temporal lobe epilepsy) or in another brain region (neocortical epilepsy). Even with optimal medical care, up to 30% of people with epilepsy continue to have seizures. The investigators will treat people with neocortical partial epilepsy with a technique that delivers magnetic waves (transcranial magnetic stimulation, TMS) to the region that causes the epilepsy. The investigators have good reasons to believe that there will be fewer seizures during several weeks after treatment. Who can participate? You have neocortical focal epilepsy. A doctor who specializes in epilepsy made this diagnosis. You had at least one seizure recorded while in an epilepsy monitoring unit. You had an MRI scan of the brain. You can deliver us all the results of the tests you had. You continue to have more than 4 seizures a month. You tried a least two different schemes of anti-epileptic drugs as prescribed by your doctor and those schemes were well tolerated. Nevertheless this never cured the seizures. You are older than 16 years. You don't plan to become pregnant during the study. You need to faithfully continue your treatment as prescribed by your doctor and don't change the drugs you take from at least 4 weeks before the study until 8 weeks after the last TMS session. You need to be able to keep a diary of your seizures. What does the study involve? You will need to come to the hospital every weekday during two consecutive weeks, every three months during nine months for the TMS-treatment. So you will have three treatment sessions. You will have a brain scan (FDG-PET) before the first treatment and after each session. The magnetic pulses will be delivered differently during each of the three treatment sessions: once on a rather small area of the brain, once on a larger brain area and once using a dummy coil, i.e. you will have two active treatment sessions and one dummy or placebo session. The investigators will not tell in which order they deliver the treatments. What are the possible benefits and risks of participating? The investigators have good reasons to believe you will have fewer seizures in the weeks following the active treatment.

Official Title
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Multimodal Image-guided Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Refractory Partial Epilepsy.

Conditions
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Epilepsies, Partial

Intervention / Treatment
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* Device: figure-of-eight active rTMS coil
* Device: round active rTMS coil
* Device: sham rTMS coil (figure-of-eight)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: fully characterized refractory unifocal neocortical epilepsy (i.e. the epileptogenic zone is well defined) on a stable drug regimen for at least one month, able to complete a seizure dairy either by the patient or by a significant other Exclusion Criteria: Metal in the head including deep brain stimulators, aneurysmal clips, ventricular shunts, cochlear implants, ossicular reconstruction of the middle ear… pacemaker, implantable cardioverter-defibrillator (ICD) psychogenic non-epileptic seizures and other non-epileptic spells

Ages Eligible for Study
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Minimum Age: 16 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: figure-of-eight active rTMS coil<br>rTMS is administered using the figure-of-eight active coil, at 90% of the resting motor threshold over the epileptogenic region, in trains of 500 pulses with a total of 1500 pulses per day, during weekdays on two consecutive weeks. | Device: figure-of-eight active rTMS coil<br>* navigated rTMS over epileptogenic focus using figure-of-eight active rTMS coil<br>|
| Experimental: round active rTMS coil<br>rTMS is administered using the round active coil, at 90% of the resting motor threshold over the epileptogenic region, in trains of 500 pulses with a total of 1500 pulses per day, during weekdays on two consecutive weeks. | Device: round active rTMS coil<br>* navigated rTMS over epileptogenic focus using round active rTMS coil<br>|
| Sham Comparator: sham rTMS coil (figure-of-eight)<br>rTMS is administered using the figure-of-eight sham coil, over the epileptogenic region, in trains of 500 pulses with a total of 1500 pulses per day, during weekdays on two consecutive weeks. | Device: sham rTMS coil (figure-of-eight)<br>* commercially available placebo coil that provides slight sensory stimulation and discharge noise without stimulating cortical tissue<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 50% Responder Rate After Active rTMS Treatment Compared With Placebo Treatment | Number of participants achieving a 50% or greater reduction in seizure frequency from baseline | week 12 after each intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seizure Frequency After Active rTMS Treatment Compared With Placebo Treatment | Seizure frequency was recorded in patient diaries and reviewed with the neurologist/epileptologist (outcomes assessor) at visits 12 weeks (+/- 1 week) after each intervention. The average weekly seizure rate was calculated and compared to baseline frequency over all participants. | week 12 after each treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epilepsies, Partial, Transcranial Magnetic Stimulation