Treatment of Difficult to Control Focal Epilepsy With Repetitive Transcranial Magnetic Stimulation (rTMS)
|Epilepsies, Partial||Device: figure-of-eight active rTMS coil Device: round active rTMS coil Device: sham rTMS coil (figure-of-eight)|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Multimodal Image-guided Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Refractory Partial Epilepsy.|
- 50% Responder Rate After Active rTMS Treatment Compared With Placebo Treatment [ Time Frame: week 12 after each intervention ]Number of participants achieving a 50% or greater reduction in seizure frequency from baseline
- Percentage of Seizure Reduction After Active rTMS Treatment Compared With Placebo Treatment [ Time Frame: week 12 after each 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.
- Alteration of Brain Activation as Measured by 18-2-fluoro-2-deoxy-D-glucose Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) on Individual Patient Level [ Time Frame: within one week after the last treatment day of each session ]Alterations were assessed by visual inspection of PET scans generated by subtracting the baseline individual PET scan from each of the follow-up scans. The subtraction PET scans were overlayed on the anatomical MRI of the patient and the focus of stimulation determined and an sphere with a 1cm radius around this point was analysed.
- Difference in Seizure Reduction Using Different Coil Types [ Time Frame: 9 months ]any difference between the four conditions (baseline/ figure-of-eight treatment/ round coil treatment/ sham treatment) based in negative binomial model for count data
- Questionnaires: Quality of Life in Epilepsy (QOLIE-31), Global Impression of Change-scales, Visual Analogue Scale, Columbia Suicide Severity Rating Scale [ Time Frame: before the first treatment of each session and at the last evaluation visit ]
- Quality of life in epilepsy (QOLIE-31): self-report (if cognitive faculties allowed) questionnaire of emotional well-being, social functioning, energy/ fatigue, cognitive functioning, seizure worry, medication effects & overall quality of life. Range 0-100, with higher numbers indicating better quality of life.
- Global impression of change-scales (score 1-7, with 4 no change and lower/higher numbers implying grade of improvement/worsening) and Visual analogue scale (0-10: no problem to horrible): self-report or parent report about effect of treatment
- Columbia Suicide Severity Rating Scale (CSSR): structured interview about suicidal risk
- change in QOLIE scores considered better/worse are based on cut-off reported in DOI 10.1016/j.yebeh.2011.12.023 For global impression of change, the scoring was <4, 4 or >4.
- Drop Out-rate [ Time Frame: during the 9 months of the study ]exclusion by investigator was due to necessity to change drug regimen due to toxicity
- Adverse Event Rate [ Time Frame: during the 9 months of the study ]
|Study Start Date:||November 2012|
|Study Completion Date:||December 2015|
|Primary Completion Date:||May 2015 (Final data collection date for primary outcome measure)|
Experimental: figure-of-eight active rTMS coil
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
navigated rTMS over epileptogenic focus using figure-of-eight active rTMS coil
Experimental: round active rTMS coil
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
navigated rTMS over epileptogenic focus using round active rTMS coil
Sham Comparator: sham rTMS coil (figure-of-eight)
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)
commercially available placebo coil that provides slight sensory stimulation and discharge noise without stimulating cortical tissue
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01745952
|University Hospitals Leuven, department of Neurology|
|Leuven, Belgium, 3000|
|Principal Investigator:||Van Paesschen Wim, MD, PhD||University Hospitals Leuven|