Clinical trial NCT01745952: Treatment of Difficult to Control Focal Epilepsy With Repetitive Transcranial Magnetic Stimulation (rTMS)
Official title: Multimodal Image-guided Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Refractory Partial Epilepsy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Epilepsies, Partial
Keywords: Epilepsies, Partial
Transcranial Magnetic Stimulation
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2012-12-10
Enrollment: 11
Sex: ALL
Minimum age (years): 16
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 1. 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.
2. 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.
3. 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.
4. 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.

Eligibility criteria: 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

Primary outcomes:
measure: 50% Responder Rate After Active rTMS Treatment Compared With Placebo Treatment
timeFrame: week 12 after each intervention
Secondary outcomes:
measure: Seizure Frequency After Active rTMS Treatment Compared With Placebo Treatment
timeFrame: week 12 after each treatment
Other outcomes:
measure: Alteration of Brain Activation as Measured by 18-2-fluoro-2-deoxy-D-glucose Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) on Individual Patient Level
timeFrame: within one week after the last treatment day of each session
measure: Difference in Seizure Reduction Using Different Coil Types
timeFrame: 9 months
measure: Questionnaires: Quality of Life in Epilepsy (QOLIE-31), Global Impression of Change-scales, Visual Analogue Scale, Columbia Suicide Severity Rating Scale
timeFrame: before the first treatment of each session and at the last evaluation visit
measure: Drop Out-rate
timeFrame: during the 9 months of the study
measure: Adverse Event Rate
timeFrame: during the 9 months of the study
Locations:
city: Leuven
country: Belgium
facility: University Hospitals Leuven, department of Neurology
Study officials:
affiliation: Universitaire Ziekenhuizen KU Leuven
name: Van Paesschen Wim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Santiago-Rodriguez E, Cardenas-Morales L, Harmony T, Fernandez-Bouzas A, Porras-Kattz E, Hernandez A. Repetitive transcranial magnetic stimulation decreases the number of seizures in patients with focal neocortical epilepsy. Seizure. 2008 Dec;17(8):677-83. doi: 10.1016/j.seizure.2008.04.005. Epub 2008 May 20.
citation: Joo EY, Han SJ, Chung SH, Cho JW, Seo DW, Hong SB. Antiepileptic effects of low-frequency repetitive transcranial magnetic stimulation by different stimulation durations and locations. Clin Neurophysiol. 2007 Mar;118(3):702-8. doi: 10.1016/j.clinph.2006.11.008. Epub 2007 Jan 16.
citation: Seynaeve L, Devroye A, Dupont P, Van Paesschen W. Randomized crossover sham-controlled clinical trial of targeted low-frequency transcranial magnetic stimulation comparing a figure-8 and a round coil to treat refractory neocortical epilepsy. Epilepsia. 2016 Jan;57(1):141-50. doi: 10.1111/epi.13247. Epub 2015 Dec 8.
citation: Seynaeve L, Van Paesschen W. Response to "Safety of repetitive transcranial magnetic stimulation in patients with epilepsy: A systematic review" by Luisa Santos Pereira and colleagues. Epilepsy Behav. 2016 Sep;62:308. doi: 10.1016/j.yebeh.2016.07.002. Epub 2016 Aug 1. No abstract available.