Clinical trial NCT02635633: Continuous Thetaburst Stimulation for the Treatment of Refractory Epilepsy - Safety, Feasibility and Proof-of-concept
Official title: Continuous Thetaburst Stimulation for the Treatment of Refractory Epilepsy - Safety, Feasibility and Proof-of-concept
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Epilepsies, Partial
Keywords: partial epilepsy
unifocal neocortical
treatment resistant
transcranial magnetic stimulation
thetaburst stimulation
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
First posted: 2015-12-21
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate a novel stimulation protocol of repetitive transcranial magnetic stimulation (rTMS) for the treatment of unifocal neocortical epilepsy, namely continuous thetaburst stimulation (cTBS). As this is a pilot study, the primary endpoint is on safety and tolerability of the treatment. However, information on clinical efficacy and mechanism of action will also be collected.

Detailed description: 1. Study design:

   This is an open label prospective pilot trial of continuous thetaburst stimulation (cTBS) in patients with unifocal neocortical epilepsy.

   The study comprises a 13-week period, consisting of 4 weeks baseline seizure frequency assessment, a one-week treatment period with baseline assessments on Monday (T0) and stimulation sessions from Tuesday to Friday (T1-T4), and an 8-week follow-up period with short-term assessments immediately after the final stimulation session on Friday afternoon (T4) and long-term assessments after 2 weeks (FU2) and 8 weeks (FU8).
2. Objectives:

   The primary objective is to assess the feasibility, safety and tolerability of cTBS in refractory epilepsy patients. The secondary objectives are to assess the clinical efficacy and associated mechanism of action of cTBS in unifocal neocortical epilepsy.
3. Rationale:

An open label prospective design allows to make a first estimate on the safety, feasibility and tolerability of cTBS in refractory epilepsy patients. There are currently no reports available of cTBS performed in epilepsy patients. The ultimate aim is to assess clinical efficacy of cTBS with regard to seizure frequency, but a feasibility and safety study is a prerequisite in order to achieve this goal.

Eligibility criteria: Inclusion Criteria:

* Refractory unifocal neocortical epilepsy with a well-defined ictal onset zone based on a standardized presurgical evaluation
* ≥ 4 seizures/month, for at least six months
* On a stable drug regimen for at least 2 months
* IQ \>70
* Reliable completion of a seizure diary by patient or caretakers
* Therapeutic compliance in the past
* Informed consent signed

Exclusion Criteria:

* Pregnancy, short-term birth wish or childbearing age without adequate birth control
* History of psychogenic non-epileptic seizures
* Intracranial metal hardware (excluding dental filling): surgical clips, shrapnell, electrodes under the stimulation area
* Presence of pacemaker, implantable cardioverter-defibrillator (ICD), permanent medication pumps, cochlear implants or deep brain stimulation (DBS)

Patients with a vagus nerve stimulator are not excluded, provided that adequate distance between the coil and the implanted material can be maintained.

As the short duration of the study will not interfere with an ongoing presurgical evaluation and/or its eventual conclusion, the patients in the course of the evaluation or awaiting surgery are also eligible for inclusion.

Primary outcomes:
measure: Seizure induction
timeFrame: Throughout stimulation, 4 days
Secondary outcomes:
measure: Seizure diary
timeFrame: Throughout the study, lasting 13 weeks
measure: Adverse events diary
timeFrame: Throughout the study, lasting 13 weeks
measure: Number of interictal epileptiform discharges (IEDs) on hd-EEG
timeFrame: Throughout the study, lasting 13 weeks: baseline (before treatment), following final stimulation session (short-term follow-up), 2 weeks after stimulation and 8 weeks after stimulation (long-term follow-up)
measure: Number of interictal epileptiform discharges (IEDs) on normal EEG
timeFrame: Throughout the study, lasting 13 weeks: assessment immediately before and after each treatment session
measure: Cortical resting motor threshold (rMT)
timeFrame: Throughout the study, lasting 13 weeks: baseline (before treatment), following final stimulation session (short-term follow-up), 2 weeks after stimulation and 8 weeks after stimulation (long-term follow-up)
measure: TMS-EEG evoked potentials (TEPs)
timeFrame: Throughout the study, lasting 13 weeks: baseline (before treatment), following final stimulation session (short-term follow-up), 2 weeks after stimulation and 8 weeks after stimulation (long-term follow-up)
measure: Magnetic resonance imaging (MRI)
timeFrame: Throughout the study, lasting 13 weeks: baseline (before treatment), following final stimulation session (short-term follow-up), 2 weeks after stimulation and 8 weeks after stimulation (long-term follow-up)
measure: High-density EEG (hd-EEG)
timeFrame: Throughout the study, lasting 13 weeks: baseline (before treatment), following final stimulation session (short-term follow-up), 2 weeks after stimulation and 8 weeks after stimulation (long-term follow-up)
measure: Change in Montreal Cognitive Assessment score (MoCA)
timeFrame: Throughout the study, lasting 13 weeks: baseline (before treatment), following final stimulation session (short-term follow-up) and 8 weeks after stimulation (long-term follow-up)
measure: Change in Computerized Visual Searching Task (CVST)
timeFrame: Throughout the study, lasting 13 weeks: baseline (before treatment), following final stimulation session (short-term follow-up), 2 weeks after stimulation and 8 weeks after stimulation (long-term follow-up)
measure: Change in Quality of life in epilepsy-31 (QOLIE-31)
timeFrame: Throughout the study, lasting 13 weeks: baseline (before treatment) and 8 weeks after stimulation (long-term follow-up)
measure: Change in Beck depression inventory (BDI-II)
timeFrame: Throughout the study, lasting 13 weeks: baseline (before treatment) and 8 weeks after stimulation (long-term follow-up)
measure: Change in Positive affect negative affect schedule (PANAS)
timeFrame: Throughout the study, lasting 13 weeks: baseline (before treatment) and 8 weeks after stimulation (long-term follow-up)
measure: Change in State-trait anxiety inventory (STAI)
timeFrame: Throughout the study, lasting 13 weeks: baseline (before treatment) and 8 weeks after stimulation (long-term follow-up)
measure: Change in Visual analogue scale (VAS) of general well-being
timeFrame: Throughout the study, lasting 13 weeks: baseline (before treatment) and 8 weeks after stimulation (long-term follow-up)
measure: Change in Visual analogue scale (VAS) of tolerability of the treatment
timeFrame: Throughout the study: after each treatment session and at the end of the study (8 weeks after stimulation)
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: University Hospital Ghent
Study officials:
affiliation: University Hospital, Ghent
name: Kristl Vonck, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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