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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01745952
First Posted: December 10, 2012
Last Update Posted: April 26, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Universitaire Ziekenhuizen Leuven
  Purpose
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.

Condition Intervention
Epilepsies, Partial Device: figure-of-eight active rTMS coil Device: round active rTMS coil Device: sham rTMS coil (figure-of-eight)

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by Universitaire Ziekenhuizen Leuven:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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 ]

Enrollment: 11
Study Start Date: November 2012
Study Completion Date: December 2015
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   16 Years to 75 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01745952


Locations
Belgium
University Hospitals Leuven, department of Neurology
Leuven, Belgium, 3000
Sponsors and Collaborators
Universitaire Ziekenhuizen Leuven
Investigators
Principal Investigator: Van Paesschen Wim, MD, PhD University Hospitals Leuven
  More Information

Publications:
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.
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.
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.
Cantello R, Rossi S, Varrasi C, Ulivelli M, Civardi C, Bartalini S, Vatti G, Cincotta M, Borgheresi A, Zaccara G, Quartarone A, Crupi D, Laganà 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.
Tergau F, Naumann U, Paulus W, Steinhoff BJ. Low-frequency repetitive transcranial magnetic stimulation improves intractable epilepsy. Lancet. 1999 Jun 26;353(9171):2209.
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.
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.
Brasil-Neto JP, de Araújo DP, Teixeira WA, Araújo 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. Epub 2004 Apr 28.
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.
Santiago-Rodríguez E, Cárdenas-Morales L, Harmony T, Fernández-Bouzas A, Porras-Kattz E, Hernández 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.
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. Epub 2007 Jan 16.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Universitaire Ziekenhuizen Leuven
ClinicalTrials.gov Identifier: NCT01745952     History of Changes
Other Study ID Numbers: s52486
First Submitted: December 4, 2012
First Posted: December 10, 2012
Results First Submitted: December 15, 2015
Results First Posted: April 26, 2016
Last Update Posted: April 26, 2016
Last Verified: January 2015
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Universitaire Ziekenhuizen Leuven:
Epilepsies, Partial
Transcranial Magnetic Stimulation

Additional relevant MeSH terms:
Epilepsy
Epilepsies, Partial
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases


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