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

Epilepsy Clinical Trial

— GALVANI GS-3  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06334952
• Other study ID #: RCAPHM23_0074
• Secondary ID: ID-RCB
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2024
• Est. completion date: April 30, 2027

Study information

• Verified date: March 2024
• Source: Assistance Publique Hopitaux De Marseille
• Contact: Fabrice Bartolomei, MD, PhD
• Phone: 0491384990
• Email: fabrice.bartolomei[@]ap-hpm.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: April 30, 2027
• Est. primary completion date: May 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 9 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Drug Resistant Epilepsy
• Epilepsy

Intervention

Device:
• transcranial direct current stimulation
Research MRI includes 3D-T1 weighted MRI (3D-T1), diffusion MRI (dMRI), resting-state functional MRI (rsfMRI).

Locations

Country	Name	City	State
France	Service de Neurophysiologie Clinique de l'Enfant et de L'Adulte, Pôle de Neurosciences Cliniques	Bordeaux
France	Département Neurologie Fonctionnelle et Epilepsie, Hôpital neurologique - Hospices Civils de Lyon	Bron
France	Service de Neurophysiologie clinique - Hôpital Roger Salengro, CHU Lille	Lille
France	Service Epileptologie et Rythmologie Cérébrale, Hôpital La Timone	Marseille
France	Service de Neurophysiologie clinique - GHU Psychiatrie et Neurosciences Sainte-Anne	Paris
France	Service de Neurologie - CHU de Rennes - Hôpital Pontchaillou	Rennes
France	Explorations neurophysiologiques - Pôle neurosciences, CHU de Toulouse, Hôpital Pierre Paul Riquet	Toulouse

Sponsors (4)

Lead Sponsor	Collaborator
Assistance Publique Hopitaux De Marseille	CRMBM-CEMEREM, Institut National de la Santé Et de la Recherche Médicale, France - LTSI, Neuroelectrics Corporation

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Other	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)
Other	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)
Other	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)
Other	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)
Other	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)