Cortical Excitability and Treatment Response in People with Epilepsy

NCT05551403 | Completed

• 2 other identifiers: NL77887.058.21P21.092
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

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.

Conditions

Epilepsy

Keywords

Epilepsy; Transcranial Magnetic Stimulation; Evoked Potentials, Visual; Electroencephalography; Anticonvulsants; Seizures

Outcome Measures

Primary Outcomes (2)

• Influence of cenobamate initiation on the resting motor threshold (rMT) when comparing short-term responders and non-responders

  Pre- to post-cenobamate initiation change in cortical excitability assessed using the rMT in responders vs. non-responders. Classification into the latter is determined by comparing the seizure frequency in the 3 months post-target dose interval to the seizure frequency in the 3 months baseline interval (responder determined by a significant seizure reduction according to Poisson distribution statistics).

  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)

• Influence of cenobamate initiation on transcranial magnetic stimulation (TMS)-evoked EEG potentials (TEP) when comparing short-term responders and non-responders

  Pre- to post-cenobamate initiation change in cortical excitability assessed using TEP amplitudes in responders vs. non-responders. Classification into the latter is determined by comparing the seizure frequency in the 3 months post-target dose interval to the seizure frequency in the 3 months baseline interval (responder determined by a significant seizure reduction according to Poisson distribution statistics).

  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 (10)

• 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

  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)

• 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

  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)

• 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

  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).

• 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

  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)

• Influence of cenobamate initiation on transcranial magnetic stimulation-induced EEG oscillations (TIO) when comparing short-term responders and non-responders

  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)

Study Arms (1)

rest-EEG, TMS-EEG/TMS-electromyography(EMG) and photic stimulation

EXPERIMENTAL

Device: Eyes-closed rest-EEG registration; Device: Transcranial Magnetic Stimulation during EEG and EMG registrations; Device: Photic stimulation during eyes-closes EEG registration

Interventions

Eyes-closed rest-EEG registration DEVICE

Recording of spontaneous brain activity while eyes are shut for the duration of 7 minutes using a tablet with instructions

rest-EEG, TMS-EEG/TMS-electromyography(EMG) and photic stimulation

Transcranial Magnetic Stimulation during EEG and EMG registrations DEVICE

Recording of TMS-evoked EEG and EMG responses according to various stimulation protocols

rest-EEG, TMS-EEG/TMS-electromyography(EMG) and photic stimulation

Photic stimulation during eyes-closes EEG registration DEVICE

Recording of visual evoked potentials in the EEG during flash stimulation by light-emitting diode (LED) goggles (while eyes are closed)

rest-EEG, TMS-EEG/TMS-electromyography(EMG) and photic stimulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Stichting Epilepsie Instellingen Nederland: lead
• Erasmus Medical Center: collaborator

Study Sites (2)

Stichting Epilepsie Instellingen Nederland (SEIN)

Heemstede, North Holland, 2103 SW, Netherlands

Location

Erasmus Medical Center

Rotterdam, South Holland, 3015 CN, Netherlands

Location

MeSH Terms

Conditions

Epilepsy; Seizures

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2022
• First Posted: September 22, 2022
• Study Start: March 16, 2022
• Primary Completion: February 29, 2024
• Study Completion: February 14, 2025
• Last Updated: February 20, 2025

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2)