Continuous Thetaburst Stimulation for the Treatment of Refractory Epilepsy - Safety, Feasibility and Proof-of-concept
Trial Snapshot
- Phase
- Not Applicable
- Status
- Terminated
- Sponsor
- University Hospital, Ghent
- Enrollment
- 7
- Locations
- 1
- Primary Endpoint
- Seizure induction
Study Overview
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
- 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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •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.
Arms & Interventions
continuous thetaburst stimulation
Transcranial magnetic stimulation over the epileptogenic focus using a cTBS stimulation protocol.
Intervention: continuous thetaburst stimulation (Device)
Outcomes
Primary Outcomes
Seizure induction
Time Frame: Throughout stimulation, 4 days
Induction of epileptic seizures during or in-between rTMS stimulation trains as a measure of safety
Secondary Outcomes
- Seizure diary(Throughout the study, lasting 13 weeks)
- Adverse events diary(Throughout the study, lasting 13 weeks)
- Number of interictal epileptiform discharges (IEDs) on hd-EEG(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))
- Number of interictal epileptiform discharges (IEDs) on normal EEG(Throughout the study, lasting 13 weeks: assessment immediately before and after each treatment session)
- Cortical resting motor threshold (rMT)(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))
- TMS-EEG evoked potentials (TEPs)(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))
- Magnetic resonance imaging (MRI)(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))
- High-density EEG (hd-EEG)(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))
- Change in Montreal Cognitive Assessment score (MoCA)(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))
- Change in Computerized Visual Searching Task (CVST)(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))
- Change in Quality of life in epilepsy-31 (QOLIE-31)(Throughout the study, lasting 13 weeks: baseline (before treatment) and 8 weeks after stimulation (long-term follow-up))
- Change in Beck depression inventory (BDI-II)(Throughout the study, lasting 13 weeks: baseline (before treatment) and 8 weeks after stimulation (long-term follow-up))
- Change in Positive affect negative affect schedule (PANAS)(Throughout the study, lasting 13 weeks: baseline (before treatment) and 8 weeks after stimulation (long-term follow-up))
- Change in State-trait anxiety inventory (STAI)(Throughout the study, lasting 13 weeks: baseline (before treatment) and 8 weeks after stimulation (long-term follow-up))
- Change in Visual analogue scale (VAS) of general well-being(Throughout the study, lasting 13 weeks: baseline (before treatment) and 8 weeks after stimulation (long-term follow-up))
- Change in Visual analogue scale (VAS) of tolerability of the treatment(Throughout the study: after each treatment session and at the end of the study (8 weeks after stimulation))
Investigators
Prof. Dr. Kristl Vonck
Prof. Dr. Boon
University Hospital, Ghent