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

May 9, 2023 updated by: Universitaire Ziekenhuizen KU Leuven

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium, 3000
        • University Hospitals Leuven, Department of Neurology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
week 12 after each intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Seizure Frequency 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.
week 12 after each treatment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
within one week after the last treatment day of each session
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
9 months
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.
before the first treatment of each session and at the last evaluation visit
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
during the 9 months of the study
Adverse Event Rate
Time Frame: during the 9 months of the study
during the 9 months of the study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universitaire Ziekenhuizen KU Leuven

Investigators

  • Principal Investigator: Van Paesschen Wim, MD, PhD, Universitaire Ziekenhuizen KU Leuven

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2012

Primary Completion (Actual)

May 1, 2015

Study Completion (Actual)

December 31, 2015

Study Registration Dates

First Submitted

December 4, 2012

First Submitted That Met QC Criteria

December 7, 2012

First Posted (Estimate)

December 10, 2012

Study Record Updates

Last Update Posted (Estimate)

May 11, 2023

Last Update Submitted That Met QC Criteria

May 9, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • s52486

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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