Efficacy of Personnalized Transcranial Direct Current Electrical Stimulation (tDCS) in Drug-resistant Epileptic (GALVANI GS-3)

Model-based Multichannel Transcranial Direct Current Electrical Stimulation (tDCS) in Drug-resistant Epilepsy: A Cross-over Study of Efficacy

The goal of this clinical trial is to to obtain a significant decrease in seizure frequency in patients with refractory focal epilepsy after applying treatment of cathodal tDCS, compared to sham stimulation drug-resistant epileptic patient. The main questions it aims to answer are:

• Changes in quality of life
• Percent of newly reported side effects after the stimulation period
• Scores in epilepsy severity. Participants will be randomized in a cross-over, and will receive 10 days of tDCS or Sham. Each day will allow 2 periods of 20 minutes stimulation separated by 20 minutes off (with 40 minutes of cathodal stimulation total).

Study Overview

• Status: Not yet recruiting
• Conditions: Epilepsy; Drug Resistant Epilepsy
• Intervention / Treatment: Device: transcranial direct current stimulation

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fabrice Bartolomei, MD, PhD; Phone Number: 33 0491384990; Email: fabrice.bartolomei@ap-hpm.fr
• Study Contact Backup: Name: Sophie Tardoski; Phone Number: 33 0491381594; Email: sophie.tardoski@ap-hm.fr

Study Locations

• France
  • Bordeaux, France, 33000
    • Service de Neurophysiologie Clinique de l'Enfant et de L'Adulte, Pôle de Neurosciences Cliniques
    • Contact: Jerome Aupy; Email: Jerome.aupy@chu-bordeaux.fr
  • Bron, France, 69677
    • Département Neurologie Fonctionnelle et Epilepsie, Hôpital neurologique - Hospices Civils de Lyon
    • Contact: Sylvain Rheims; Email: Sylvain.rheims@chu-lyon.fr
  • Lille, France, 59037
    • Service de Neurophysiologie clinique - Hôpital Roger Salengro, CHU Lille
    • Contact: Philippe Derambure; Email: Philippe.Derambure@chru-lille.fr
  • Marseille, France, 13005
    • Service Epileptologie et Rythmologie Cérébrale, Hôpital La Timone
    • Contact: Fabrice Bartolomei; Email: Fabrice.bartolomei@ap-hm.fr
  • Paris, France, 75014
    • Service de Neurophysiologie clinique - GHU Psychiatrie et Neurosciences Sainte-Anne
    • Contact: Martine Gavaret; Email: m.gavaret@ghu-paris.fr
  • Rennes, France, 35033
    • Service de Neurologie - CHU de Rennes - Hôpital Pontchaillou
    • Contact: Anca Nica; Email: Anca.nica@chu-rennes.fr
  • Toulouse, France, 31059
    • Explorations neurophysiologiques - Pôle neurosciences, CHU de Toulouse, Hôpital Pierre Paul Riquet
    • Contact: Luc Valton; Email: valton.l@chu-toulouse.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient, parents or legal representative who have given written informed consent;
2. Age: ≥ 9 years;
3. Patients with drug-resistant focal epilepsy with no surgical indication or with a previous surgical failure, refusing surgery or with a planned surgery compatible with the total duration of this study;
4. SEEG previously performed before inclusion with an adequate definition of the epileptogenic zone (within 5 years before inclusion);
5. Patient having a pre-SEEG 3D-T1 MRI and CT-scan with electrodes during SEEG available;
6. A research MRI scan that is suitable for navigated brain stimulation (NBS) and generation of electrical fields including dMRI for tractography;
7. Number of seizures ≥3/month during the baseline (before the first session of tDCS treatment);
8. Patient having stable medications for epilepsy 4 weeks before the baseline (except rescue treatment);
9. Patient's IQ, which in the investigator's opinion will enable questionnaires and neuropsychological assessments to be carried out;
10. Patient able to understand, speak and write in French;
11. Patient able to follow study's procedure;
12. Patient beneficiary or affiliated to a health insurance plan.

Exclusion Criteria:

1. Patients with seizures of generalized onset in the last 12 months;
2. Patient with multifocal epileptogenic zones, bilateral epileptogenic zone, or poorly defined epileptogenic zone. The epileptogenic network should not be restricted to the orbito frontal cortex or cingulate cortex;
3. Patients with a history of psychogenic nonepileptic seizures;
4. Patient presenting a contraindication to MRI 3T (patient having a pacemaker, metallic foreign bodies, non-removably implanted electronic medical devices, claustrophobia, inability to remain in supine position, vagal nerve stimulator) ;
5. Substance use disorder, as defined in DSM-V, within the past year;
6. Patient presenting a serious intercurrent pathology and/or a progressive brain tumor
7. Patient having damaged skin or scalp that may interfere with tDCS stimulation (e.g., eczema, lesion);
8. Patient having any cranial metal implants such as shrapnel or surgical clips (excluding <1 mm thick epicranial titanium skull plates and dental fillings) or medical devices (i.e. cardiac pacemaker, deep brain stimulator, medication infusion pump, cochlear implant)
9. Patient having previous surgeries opening the skull leaving skull defects capable of allowing the insertion of a cylinder with a radius greater or equal to 5 mm;
10. 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 ;
11. Person protected by articles L1121-5, L1121-6 and L1121-8 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: tDCS - Sham; Patient will be randomized to firstly receive tDCS (10 non consecutive days, 20 minutes twice a day with 20 minutes of break) and then Sham (10 non consecutive days, 20 minutes twice a day with 20 minutes of break).	Device: transcranial direct current stimulation; Research MRI includes 3D-T1 weighted MRI (3D-T1), diffusion MRI (dMRI), resting-state functional MRI (rsfMRI).; Other Names: Research MRI, EEG
Other: Sham - tDCS; Patient will be randomized to firstly receive Sham (10 non consecutive days, 20 minutes twice a day with 20 minutes of break) and then tDCS (10 non consecutive days, 20 minutes twice a day with 20 minutes of break).	Device: transcranial direct current stimulation; Research MRI includes 3D-T1 weighted MRI (3D-T1), diffusion MRI (dMRI), resting-state functional MRI (rsfMRI).; Other Names: Research MRI, EEG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To obtain a significant seizure frequency change at the end of tDCS sessions compared to the seizure frequency calculated in the pre-treatment period of reference.	Seizure frequency counting after end of tDCS treatment compared to the baseline comparing Sham versus Active arms of the cross-over study.	Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
To obtain a significant seizure frequency change at the end of tDCS sessions compared to the seizure frequency calculated in the pre-treatment period of reference.	Seizure frequency counting after end of tDCS treatment compared to the baseline comparing Sham versus Active arms of the cross-over study.	V5 - 8 weeks after the end of first cycle (each cycle is 10 days)
To obtain a significant seizure frequency change at the end of tDCS sessions compared to the seizure frequency calculated in the pre-treatment period of reference.	Seizure frequency counting after end of tDCS treatment compared to the baseline comparing Sham versus Active arms of the cross-over study.	V7 - 4 weeks after the end of the second cycle (each cycle is 10 days)
To obtain a significant seizure frequency change at the end of tDCS sessions compared to the seizure frequency calculated in the pre-treatment period of reference.	Seizure frequency counting after end of tDCS treatment compared to the baseline comparing Sham versus Active arms of the cross-over study.	V8 - 8 weeks after the end of the second cycle (each cycle is 10 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the number of responders (defined as patient with >50% of seizure reduction)	Proportion of responders evaluated after active session of 10 days of tDCS treatment compared to the baseline comparing Sham versus Active arms of the cross-over study	Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
Evaluation of the number of responders (defined as patient with >50% of seizure reduction)	Proportion of responders evaluated after active session of 10 days of tDCS treatment compared to the baseline comparing Sham versus Active arms of the cross-over study	V5 - 8 weeks after the end of first cycle (each cycle is 10 days)
Evaluation of the number of responders (defined as patient with >50% of seizure reduction)	Proportion of responders evaluated after active session of 10 days of tDCS treatment compared to the baseline comparing Sham versus Active arms of the cross-over study	V7 - 4 weeks after the end of the second cycle (each cycle is 10 days)
Evaluation of the number of responders (defined as patient with >50% of seizure reduction)	Proportion of responders evaluated after active session of 10 days of tDCS treatment compared to the baseline comparing Sham versus Active arms of the cross-over study	V8 - 8 weeks after the end of the second cycle (each cycle is 10 days)
Evaluate the number of seizure-free patients	Number of seizure-free patients after active session of 10 days of tDCS treatment compared to the baseline comparing Sham versus Active arms of the cross-over study	Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
Evaluate the number of seizure-free patients	Number of seizure-free patients after active session of 10 days of tDCS treatment compared to the baseline comparing Sham versus Active arms of the cross-over study	V5 - 8 weeks after the end of first cycle (each cycle is 10 days)
Evaluate the number of seizure-free patients	Number of seizure-free patients after active session of 10 days of tDCS treatment compared to the baseline comparing Sham versus Active arms of the cross-over study	V7 - 4 weeks after the end of the second cycle (each cycle is 10 days)
Evaluate the number of seizure-free patients	Number of seizure-free patients after active session of 10 days of tDCS treatment compared to the baseline comparing Sham versus Active arms of the cross-over study	V8 - 8 weeks after the end of the second cycle (each cycle is 10 days)
Quality of life after stimulation sessions with the baseline period	Changes from baseline in the quality of life questionnaire (QOLIE 31 for adults and EFIQUACEE QOL for children) after the stimulation period	Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
Quality of life after stimulation sessions with the baseline period	Changes from baseline in the quality of life questionnaire (QOLIE 31 for adults and EFIQUACEE QOL for children) after the stimulation period	V5 - 8 weeks after the end of first cycle (each cycle is 10 days)
Quality of life after stimulation sessions with the baseline period	Changes from baseline in the quality of life questionnaire (QOLIE 31 for adults and EFIQUACEE QOL for children) after the stimulation period	V7 - 4 weeks after the end of the second cycle (each cycle is 10 days)
Quality of life after stimulation sessions with the baseline period	Changes from baseline in the quality of life questionnaire (QOLIE 31 for adults and EFIQUACEE QOL for children) after the stimulation period	V8 - 8 weeks after the end of the second cycle (each cycle is 10 days)
Evaluation of the change in seizure severity	Changes in the scores of epilepsy severity (NHS3) (investigator evaluation)	Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
Evaluation of the change in seizure severity	Changes in the scores of epilepsy severity (NHS3) (investigator evaluation)	V5 - 8 weeks after the end of first cycle (each cycle is 10 days)
Evaluation of the change in seizure severity	Changes in the scores of epilepsy severity (NHS3) (investigator evaluation)	V7 - 4 weeks after the end of the second cycle (each cycle is 10 days)
Evaluation of the change in seizure severity	Changes in the scores of epilepsy severity (NHS3) (investigator evaluation)	V8 - 8 weeks after the end of the second cycle (each cycle is 10 days)
Changes in psychiatric comorbidities	Changes from baseline in depression (NDDI-E) and anxiety (GAD-7) scores	Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
Changes in psychiatric comorbidities	Changes from baseline in depression (NDDI-E) and anxiety (GAD-7) scores	V5 - 8 weeks after the end of first cycle (each cycle is 10 days)
Changes in psychiatric comorbidities	Changes from baseline in depression (NDDI-E) and anxiety (GAD-7) scores	V7 - 4 weeks after the end of the second cycle (each cycle is 10 days)
Changes in psychiatric comorbidities	Changes from baseline in depression (NDDI-E) and anxiety (GAD-7) scores	V8 - 8 weeks after the end of the second cycle (each cycle is 10 days)
Safety assessment and possible side effects	Percent of newly reported side-effect during and after the stimulation period	Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
Safety assessment and possible side effects	Percent of newly reported side-effect during and after the stimulation period	V5 - 8 weeks after the end of first cycle (each cycle is 10 days)
Safety assessment and possible side effects	Percent of newly reported side-effect during and after the stimulation period	V7 - 4 weeks after the end of the second cycle (each cycle is 10 days)
Safety assessment and possible side effects	Percent of newly reported side-effect during and after the stimulation period	V8 - 8 weeks after the end of the second cycle (each cycle is 10 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare brain functional connectivity before and after tDCS treatment	Changes in functional connectivity measured by fMRI and EEG signal 4 weeks after the tDCS periods in comparison with baseline period	V5 - 8 weeks after the end of first cycle (each cycle is 10 days)
Evaluation of the impact of tDCS on interictal epileptic spikes (IESs)	Change in the number of IESs per time unit after each tDCS session in comparison with baseline period	Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
Evaluation of the impact of tDCS on interictal epileptic spikes	Change in localization and extent of brain areas involved in IESs before and after each tDCS session in comparison with baseline period	Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
Evaluation of the impact of tDCS on interictal epileptic spikes	Change in localization and extent of brain areas involved in IESs before and after each tDCS session in comparison with baseline period	V7 - 4 weeks after the end of the second cycle (each cycle is 10 days)
Evaluation of the impact of tDCS on interictal epileptic spikes	Changes in strength and density of functional links during IES before and after each tDCS session	Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
Evaluation of the impact of tDCS on interictal epileptic spikes	Changes in strength and density of functional links during IES before and after each DCS session	V7 - 4 weeks after the end of the second cycle (each cycle is 10 days)

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Collaborators: Neuroelectrics Corporation; CRMBM-CEMEREM; Institut National de la Santé Et de la Recherche Médicale, France - LTSI

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: March 16, 2024
• First Submitted That Met QC Criteria: March 21, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: transcranial direct current stimulation; quality of life; epilepsy; numerical models
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Drug Resistant Epilepsy
• Other Study ID Numbers: RCAPHM23_0074; ID-RCB (Other Identifier: 2019-A02945-52)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No