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

Epilepsies, Partial Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01745952
• Other study ID #: s52486
• Status: Completed
• Phase: N/A
• Start date: November 2012
• Est. completion date: December 31, 2015

Study information

• Verified date: May 2023
• Source: Universitaire Ziekenhuizen KU Leuven
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: December 31, 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Epilepsies, Partial
• Epilepsy

Intervention

Device:
• figure-of-eight active rTMS coil
navigated rTMS over epileptogenic focus using figure-of-eight active rTMS coil
• round active rTMS coil
navigated rTMS over epileptogenic focus using round active rTMS coil
• sham rTMS coil (figure-of-eight)
commercially available placebo coil that provides slight sensory stimulation and discharge noise without stimulating cortical tissue

Locations

Country	Name	City	State
Belgium	University Hospitals Leuven, department of Neurology	Leuven

Sponsors (1)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen KU Leuven

Country where clinical trial is conducted

Belgium, 

References & Publications (13)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View 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. — View Citation

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. — View 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. — View 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. 20 — View 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. Epu — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Alteration of Brain Activation as Measured by 18-2-fluoro-2-deoxy-D-glucose Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) on Individual Patient Level	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.	within one week after the last treatment day of each session
Other	Difference in Seizure Reduction Using Different Coil Types	any difference between the four conditions (baseline/ figure-of-eight treatment/ round coil treatment/ sham treatment) based in negative binomial model for count data	9 months
Other	Questionnaires: Quality of Life in Epilepsy (QOLIE-31), Global Impression of Change-scales, Visual Analogue Scale, Columbia Suicide Severity Rating Scale	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.	before the first treatment of each session and at the last evaluation visit
Other	Drop Out-rate	exclusion by investigator was due to necessity to change drug regimen due to toxicity	during the 9 months of the study
Other	Adverse Event Rate		during the 9 months of the study
Primary	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	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