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

NCT ID: NCT01745952

Last Updated: 2023-05-11

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

11 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-11-30

Study Completion Date

2015-12-31

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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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.

Conditions

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Epilepsies, Partial

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

figure-of-eight active rTMS coil

Intervention Type DEVICE

navigated rTMS over epileptogenic focus using figure-of-eight active rTMS coil

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.

Group Type EXPERIMENTAL

round active rTMS coil

Intervention Type DEVICE

navigated rTMS over epileptogenic focus using round active rTMS coil

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.

Group Type SHAM_COMPARATOR

sham rTMS coil (figure-of-eight)

Intervention Type DEVICE

commercially available placebo coil that provides slight sensory stimulation and discharge noise without stimulating cortical tissue

Interventions

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figure-of-eight active rTMS coil

navigated rTMS over epileptogenic focus using figure-of-eight active rTMS coil

Intervention Type DEVICE

round active rTMS coil

navigated rTMS over epileptogenic focus using round active rTMS coil

Intervention Type DEVICE

sham rTMS coil (figure-of-eight)

commercially available placebo coil that provides slight sensory stimulation and discharge noise without stimulating cortical tissue

Intervention Type DEVICE

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
Minimum Eligible Age

16 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Van Paesschen Wim, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Universitaire Ziekenhuizen KU Leuven

Locations

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University Hospitals Leuven, department of Neurology

Leuven, , Belgium

Site Status

Countries

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Belgium

References

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Sun W, Mao W, Meng X, Wang D, Qiao L, Tao W, Li L, Jia X, Han C, Fu M, Tong X, Wu X, Wang Y. Low-frequency repetitive transcranial magnetic stimulation for the treatment of refractory partial epilepsy: a controlled clinical study. Epilepsia. 2012 Oct;53(10):1782-9. doi: 10.1111/j.1528-1167.2012.03626.x. Epub 2012 Sep 5.

Reference Type BACKGROUND
PMID: 22950513 (View on PubMed)

Fregni F, Otachi PT, Do Valle A, Boggio PS, Thut G, Rigonatti SP, Pascual-Leone A, Valente KD. A randomized clinical trial of repetitive transcranial magnetic stimulation in patients with refractory epilepsy. Ann Neurol. 2006 Oct;60(4):447-55. doi: 10.1002/ana.20950.

Reference Type BACKGROUND
PMID: 17068786 (View on PubMed)

Theodore WH, Hunter K, Chen R, Vega-Bermudez F, Boroojerdi B, Reeves-Tyer P, Werhahn K, Kelley KR, Cohen L. Transcranial magnetic stimulation for the treatment of seizures: a controlled study. Neurology. 2002 Aug 27;59(4):560-2. doi: 10.1212/wnl.59.4.560.

Reference Type BACKGROUND
PMID: 12196649 (View on PubMed)

Cantello R, Rossi S, Varrasi C, Ulivelli M, Civardi C, Bartalini S, Vatti G, Cincotta M, Borgheresi A, Zaccara G, Quartarone A, Crupi D, Lagana A, Inghilleri M, Giallonardo AT, Berardelli A, Pacifici L, Ferreri F, Tombini M, Gilio F, Quarato P, Conte A, Manganotti P, Bongiovanni LG, Monaco F, Ferrante D, Rossini PM. Slow repetitive TMS for drug-resistant epilepsy: clinical and EEG findings of a placebo-controlled trial. Epilepsia. 2007 Feb;48(2):366-74. doi: 10.1111/j.1528-1167.2006.00938.x.

Reference Type BACKGROUND
PMID: 17295632 (View on PubMed)

Tergau F, Naumann U, Paulus W, Steinhoff BJ. Low-frequency repetitive transcranial magnetic stimulation improves intractable epilepsy. Lancet. 1999 Jun 26;353(9171):2209. doi: 10.1016/S0140-6736(99)01301-X. No abstract available.

Reference Type BACKGROUND
PMID: 10392988 (View on PubMed)

Daniele O, Brighina F, Piazza A, Giglia G, Scalia S, Fierro B. Low-frequency transcranial magnetic stimulation in patients with cortical dysplasia - a preliminary study. J Neurol. 2003 Jun;250(6):761-2. doi: 10.1007/s00415-003-1080-6. No abstract available.

Reference Type BACKGROUND
PMID: 12862035 (View on PubMed)

Tergau F, Neumann D, Rosenow F, Nitsche MA, Paulus W, Steinhoff B. Can epilepsies be improved by repetitive transcranial magnetic stimulation?--interim analysis of a controlled study. Suppl Clin Neurophysiol. 2003;56:400-5. doi: 10.1016/s1567-424x(09)70244-2. No abstract available.

Reference Type BACKGROUND
PMID: 14677417 (View on PubMed)

Brasil-Neto JP, de Araujo DP, Teixeira WA, Araujo VP, Boechat-Barros R. Experimental therapy of epilepsy with transcranial magnetic stimulation: lack of additional benefit with prolonged treatment. Arq Neuropsiquiatr. 2004 Mar;62(1):21-5. doi: 10.1590/s0004-282x2004000100004. Epub 2004 Apr 28.

Reference Type BACKGROUND
PMID: 15122428 (View on PubMed)

Kinoshita M, Ikeda A, Begum T, Yamamoto J, Hitomi T, Shibasaki H. Low-frequency repetitive transcranial magnetic stimulation for seizure suppression in patients with extratemporal lobe epilepsy-a pilot study. Seizure. 2005 Sep;14(6):387-92. doi: 10.1016/j.seizure.2005.05.002.

Reference Type BACKGROUND
PMID: 16046153 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18495500 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17223384 (View on PubMed)

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.

Reference Type RESULT
PMID: 26642974 (View on PubMed)

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.

Reference Type RESULT
PMID: 27492628 (View on PubMed)

Other Identifiers

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s52486

Identifier Type: -

Identifier Source: org_study_id

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