Evaluation of the Efficacy of Neurofeedback Technique Based on EEG Desynchronization in Epileptic Patients

Official title

Randomized Double-blind Placebo-controlled Study of the Evaluation of the Efficacy of Neurofeedback Technique Based on EEG Desynchronization in Pharmaco-resistant Epilepsy

Overview

A large proportion of patients (approximately 30%) with drug-resistant epilepsy are not eligible for surgical treatment. The alternatives that can be offered to reduce the frequency of seizures are neuromodulation (vagus nerve stimulation (VNS), deep brain stimulation (DBS), or transcranial direct current stimulation (tDCS)). Most of these alternatives require invasive procedures and therefore carry risks. Neurofeedback (NFB) is a potential adjunctive treatment that allows patients to self-modulate brain activity and thus reduce seizure frequency in a non-invasive manner. This technique involves measuring neurophysiological activity using a technical interface to extract a parameter of interest, which is presented in real time to the participant, who has been trained and has learned how to modify it. NFB is of interest in various neurological and psychiatric diseases and can lead to improvement in mood disorders, which are frequently associated with epilepsy. Previous NFB methods in epilepsy aimed to modulate sensorimotor rhythms or slow cortical potentials. The investigators propose an innovative EEG-NFB paradigm based on real-time estimation of EEG functional connectivity (FC) measured on the scalp EEG (NFC-FC). This paradigm was developed based on previous studies demonstrating increased functional brain connectivity during the interictal period and decreased synchrony induced by VNS and transcranial electrical stimulation as a possible anti-epileptic mechanism. This study consists of a randomized, double-blind comparison between NFB-FC and sham-NFB (control). The effect of this functional connectivity-based NeuroFeedBack (NFB-FC) will be evaluated on the number of seizures before and after treatment, as well as on their severity and on criteria related to quality of life. In this study, two healthy volunteers will be recruited in order to generate the sham sessions.

Interventions

• Procedure Neurofeedback
  The intervention will consist of 12 training sessions at the hospital conducted with the assistance of a nurse. Each session will last approximately 40 minutes, with two resting EEG phases at the beginning and end of the session. The NFB procedure will consist of 6 training blocks of 75 seconds separated by 15-second rest blocks and 15-second baseline blocks. The patient will then be required to practice what they have learned at home.
• Procedure Sham-NFB
  The intervention will consist of 12 training sessions at the hospital conducted with the assistance of a nurse. Each session will last approximately 40 minutes, with two resting EEG phases at the beginning and end of the session. The NFB procedure will consist of 6 training blocks of 75 seconds separated by 15-second rest blocks and 15-second baseline blocks. The patient will then be required to practice what they have learned at home.

Primary outcome measures

• To evaluate the effect of NFB-FC training on seizure frequency [Time frame: 3 months after the end of the training vs 3 months before training]

Secondary outcome measures (11)

• To compare between groups the psychiatric impact (depression and anxiety) [Time frame: 3-months after the end of the training]
• To compare between groups the cognitive impact [Time frame: One year after inclusion]
• To compare between groups the quality of life [Time frame: 3-months after the end of the training to the pre-training period]
• To compare between groups the number of responders [Time frame: 3-months after the end of the training]
• To compare between groups the number of seizure-free patients [Time frame: 3-months after the end of the training]
• To compare between groups the change in seizure severity [Time frame: 3-months after the end of the training]
• The impact of transfer skills [Time frame: 6 weeks of applied learned strategies]
• To assess, in the whole sample and per group (sham, active), correlations between FC changes and clinical outcomes [Time frame: At the end of the training and at 3 months after the end of the training]
• To assess, in the whole sample and per group (sham, active), correlations between FC changes and clinical outcomes [Time frame: At 3 months after the end of the training]
• To assess, in the whole sample and per group (sham, active), neurophysiological correlations, psychosocial factors and mental strategies and clinical outcomes. [Time frame: At 3 months after the end of the training]
• To assess, in the whole sample and per group (sham, active), neurophysiological correlations, psychosocial factors and mental strategies and clinical outcomes. [Time frame: After each training sessions]

Eligibility criteria

For patients :

Inclusion criteria

• Male or female patient between 18 and 65 years old
• Patient suffering from focal or multifocal drug-resistant epilepsy
• Patient having a number of seizures: at least 3 / month during the baseline
• Patient's IQ, which in the investigator's opinion will enable questionnaires and neuropsychological assessments to be carried out;
• Patient having stable medications for epilepsy 4 weeks before the baseline (except rescue treatment);
• Patient able to understand, speak and write in French;
• Patient willing to participate, and gave written consent to the study after receiving clear information
• Patient beneficiary or affiliated to a health insurance plan

Exclusion criteria

• \- Difficulty reading or understanding the French language or inability to understand information about the study
• Generalized epilepsy
• Major visual impairment incompatible with the realization of neurofeedback, based on investigator's opinion.
• Patient currently having psychogenic non-epileptic seizures
• Any condition that makes the study subject, in the opinion of the investigator, unsuitable for the study including presence of any disease, abnormality, medical or physical condition that, in the opinion of the investigator, may adversely impact, compromise, interfere, limit, affect or reduce the safety of the subject, the integrity of the data ; Person protected by articles L1121-5, L1121-6 of Public Health Code (pregnant or breastfeeding woman, deprived of liberty by judicial decision, situations of social fragility, adults unable or unable to express their consent, person under judicial safeguard (article L1122-2)).

For healthy volunteers :

Inclusion criteria

• Male or female of over 18 years of age
• IQ compatible with the realization of the study
• Patient able to understand, speak and write in French;
• Patient willing to participate, and gave written consent to the study after receiving clear information
• Subject beneficiary or affiliated to a health insurance plan

Exclusion criteria

• Subject presenting any neurological or psychiatric illnesses.
• Subject having major visual impairment incompatible with the realization of neurofeedback, based on investigator's opinion.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Sequential

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07356661 · RCAPHM22_0313 · ID-RCB 2025-A00981-48

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗