Clinical trial NCT05551403: Cortical Excitability and Treatment Response in People with Epilepsy
Official title: Electrophysiological Markers of Cortical Excitability to Predict Response to Treatment with Anti-seizure Medication - the ECORTA Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Epilepsy
Keywords: Epilepsy
Transcranial Magnetic Stimulation
Evoked Potentials, Visual
Electroencephalography
Anticonvulsants
Seizures
Lead sponsor: Stichting Epilepsie Instellingen Nederland
Sponsor class: OTHER
Collaborators: name: Erasmus Medical Center
First posted: 2022-09-22
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Epilepsy is a medical condition marked by the occurrence of unpredictable, recurrent seizures. One-third of people with epilepsy continue to experience seizures, despite having attempted multiple forms of anti-seizure medication (ASM). Currently, response to ASM is assessed on a trial-and-error basis as their efficacy can only be determined in hindsight. This causes delays in finding the proper treatment per individual. Responsiveness of the outer brain layer to external stimuli, termed cortical excitability (CE), may be used as additional means of treatment evaluation.

In this study, the investigators aim to measure CE before and after starting with ASM, so as to determine whether indicators of CE can be used to predict favorable response to the medication. Participants in this study are adult individuals with uncontrolled seizures that will start with the novel anti-seizure medicine cenobamate. The investigators hypothesize that, after starting with ASM, the CE will decrease in people with epilepsy who show a favorable response to the medication. Conversely, the investigators anticipate that the CE will not decrease in those that do not react to the mediation.

The investigators will address this hypothesis by evaluating both brain activity (electroencephalography, EEG) during rest and during different types of stimulation (magnetic, light flashes). Besides, the investigators will measure the subjective experiences of participants by using questionnaires on the quality of life and feelings of anxiety or depression. These measurements are performed at a baseline instance, just before starting with ASM, and at two instances after start with the ASM. Participants in the study will track the occurrence of seizures - using a diary - from 12 weeks before ASM start up till 12 months after ASM start. The investigators will compare seizure frequency with both changes in brain activity and subjective experiences by the participants.


Eligibility criteria: Inclusion Criteria:

* In agreement with their own neurologist to initiate adjuvant treatment with cenobamate
* Diagnosed with refractory focal epilepsy, which means two ASMs failed to cause seizure freedom.
* Age of 18 years or older
* Having kept a seizure diary for the past 12 weeks
* At least one seizure in the past 12 weeks.

Exclusion Criteria:

* Photosensitive epilepsy
* Any device or structure in the skull or in close proximity of the head area containing metal, including cochlear implants, implanted neurostimulators, cardiac pacemakers and intracardiac lines.
* Persistent skull opening following trauma or surgery
* Evidence (clinical or radiological) of major structural abnormality of the motor cortex or pyramidal tracts
* Any major psychiatric condition such as a psychotic disorder
* Pregnancy
* Learning disabilities preventing the comprehension of oral and/or written instructions

Primary outcomes:
measure: Influence of cenobamate initiation on the resting motor threshold (rMT) when comparing short-term responders and non-responders
timeFrame: At cenobamate initiation (T0), 7-8 weeks after cenobamate initiation (T1), and optionally at the maximum dose reached after individual treatment durations up to 1 year after cenobamate initiation (T2)
measure: Influence of cenobamate initiation on transcranial magnetic stimulation (TMS)-evoked EEG potentials (TEP) when comparing short-term responders and non-responders
timeFrame: At cenobamate initiation (T0), 7-8 weeks after cenobamate initiation (T1), and optionally at the maximum dose reached after individual treatment durations up to 1 year after cenobamate initiation (T2)
Secondary outcomes:
measure: Influence of cenobamate initiation on phase clustering and the neural network excitability index (NNEI) between visual evoked potential (VEP) trials when comparing short-term responders and non-responders
timeFrame: At cenobamate initiation (T0), 7-8 weeks after cenobamate initiation (T1), and optionally at the maximum dose reached after individual treatment durations up to 1 year after cenobamate initiation (T2)
measure: Influence of cenobamate initiation on the mean functional connectivity (MFC) and phase-amplitude coupling (PAC) in resting-state (rs-)EEG data when comparing short-term responders and non-responders
timeFrame: At cenobamate initiation (T0), 7-8 weeks after cenobamate initiation (T1), and optionally at the maximum dose reached after individual treatment durations up to 1 year after cenobamate initiation (T2)
measure: Influence of cenobamate initiation on transcranial magnetic stimulation (TMS)-EMG and EEG, intermittent photic stimulation (IPS)-EEG and resting state (rs-)EEG parameters when comparing long-term responders and non-responders
timeFrame: At cenobamate initiation (T0), 7-8 weeks after cenobamate initiation (T1), and at the maximum dose reached after individual treatment durations up to 1 year after cenobamate initiation (T2).
measure: Correlation between the pre- to post-cenobamate initiation change in the resting motor threshold (rMT) and change in the seizure frequency when comparing short-term responders and non-responders to cenobamate
timeFrame: At cenobamate initiation (T0), 7-8 weeks after cenobamate initiation (T1), and optionally at the maximum dose reached after individual treatment durations up to 1 year after cenobamate initiation (T2)
measure: Influence of cenobamate initiation on transcranial magnetic stimulation-induced EEG oscillations (TIO) when comparing short-term responders and non-responders
timeFrame: At cenobamate initiation (T0), 7-8 weeks after cenobamate initiation (T1), and optionally at the maximum dose reached after individual treatment durations up to 1 year after cenobamate initiation (T2)
measure: Influence of cenobamate initiation on phase clustering between TEP trials when comparing short-term responders and non-responders
timeFrame: At cenobamate initiation (T0), 7-8 weeks after cenobamate initiation (T1), and optionally at the maximum dose reached after individual treatment durations up to 1 year after cenobamate initiation (T2)
measure: Influence of cenobamate initiation on the neural network excitability index (NNEI) between TEP trials when comparing short-term responders and non-responders
timeFrame: At cenobamate initiation (T0), 7-8 weeks after cenobamate initiation (T1), and optionally at the maximum dose reached after individual treatment durations up to 1 year after cenobamate initiation (T2)
measure: Influence of cenobamate initiation on the short-interval intracortical inhibition (SICI) when comparing short-term responders and non-responders
timeFrame: At cenobamate initiation (T0), 7-8 weeks after cenobamate initiation (T1), and optionally at the maximum dose reached after individual treatment durations up to 1 year after cenobamate initiation (T2)
measure: Influence of cenobamate initiation on the long-interval intracortical inhibition (LICI) when comparing short-term responders and non-responders
timeFrame: At cenobamate initiation (T0), 7-8 weeks after cenobamate initiation (T1), and optionally at the maximum dose reached after individual treatment durations up to 1 year after cenobamate initiation (T2)
measure: Influence of cenobamate initiation on the cortical silent period (CSP) when comparing short-term responders and non-responders
timeFrame: At cenobamate initiation (T0), 7-8 weeks after cenobamate initiation (T1), and optionally at the maximum dose reached after individual treatment durations up to 1 year after cenobamate initiation (T2)
Other outcomes:
Locations:
city: Heemstede
country: Netherlands
facility: Stichting Epilepsie Instellingen Nederland (SEIN)
state: Noord-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: Zuid-Holland
Study officials:
References: