Clinical trial NCT06334952: Efficacy of Personnalized Transcranial Direct Current Electrical Stimulation (tDCS) in Drug-resistant Epileptic
Official title: Model-based Multichannel Transcranial Direct Current Electrical Stimulation (tDCS) in Drug-resistant Epilepsy: a Cross-over Study of Efficacy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Epilepsy
Drug Resistant Epilepsy
Keywords: epilepsy
transcranial direct current stimulation
numerical models
quality of life
Lead sponsor: Assistance Publique Hopitaux De Marseille
Sponsor class: OTHER
Collaborators: name: CRMBM-CEMEREM
name: Institut National de la Santé Et de la Recherche Médicale, France - LTSI
name: Neuroelectrics Corporation
First posted: 2024-03-28
Enrollment: 60
Sex: ALL
Minimum age (years): 9
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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. 4) SEEG previously performed before inclusion with an adequate definition of the epileptogenic zone with all data required (pre-SEEG MRI, CT-scan or MRI with electrodes during SEEG and SEEG files) for personalization ;
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 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, vagus nerve stimulator) ;
5. Substance use abuse that may include alcohol , opioids (heroin, fentanyl) stimulants (Cocaine, methamphetamine) , hallucinogens (LSD, psilocybin (magic mushrooms), MDMA (Ecstasy))
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 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)).

Primary outcomes:
measure: 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.
timeFrame: Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
measure: 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.
timeFrame: V5 - 8 weeks after the end of first cycle (each cycle is 10 days)
measure: 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.
timeFrame: V7 - 4 weeks after the end of the second cycle (each cycle is 10 days)
measure: 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.
timeFrame: V8 - 8 weeks after the end of the second cycle (each cycle is 10 days)
Secondary outcomes:
measure: Evaluation of the number of responders (defined as patient with >50% of seizure reduction)
timeFrame: Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
measure: Evaluation of the number of responders (defined as patient with >50% of seizure reduction)
timeFrame: V5 - 8 weeks after the end of first cycle (each cycle is 10 days)
measure: Evaluation of the number of responders (defined as patient with >50% of seizure reduction)
timeFrame: V7 - 4 weeks after the end of the second cycle (each cycle is 10 days)
measure: Evaluation of the number of responders (defined as patient with >50% of seizure reduction)
timeFrame: V8 - 8 weeks after the end of the second cycle (each cycle is 10 days)
measure: Evaluate the number of seizure-free patients
timeFrame: Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
measure: Evaluate the number of seizure-free patients
timeFrame: V5 - 8 weeks after the end of first cycle (each cycle is 10 days)
measure: Evaluate the number of seizure-free patients
timeFrame: V7 - 4 weeks after the end of the second cycle (each cycle is 10 days)
measure: Evaluate the number of seizure-free patients
timeFrame: V8 - 8 weeks after the end of the second cycle (each cycle is 10 days)
measure: Quality of life after stimulation sessions with the baseline period
timeFrame: Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
measure: Quality of life after stimulation sessions with the baseline period
timeFrame: V5 - 8 weeks after the end of first cycle (each cycle is 10 days)
measure: Quality of life after stimulation sessions with the baseline period
timeFrame: V7 - 4 weeks after the end of the second cycle (each cycle is 10 days)
measure: Quality of life after stimulation sessions with the baseline period
timeFrame: V8 - 8 weeks after the end of the second cycle (each cycle is 10 days)
measure: Evaluation of the change in seizure severity
timeFrame: Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
measure: Evaluation of the change in seizure severity
timeFrame: V5 - 8 weeks after the end of first cycle (each cycle is 10 days)
measure: Evaluation of the change in seizure severity
timeFrame: V7 - 4 weeks after the end of the second cycle (each cycle is 10 days)
measure: Evaluation of the change in seizure severity
timeFrame: V8 - 8 weeks after the end of the second cycle (each cycle is 10 days)
measure: Changes in psychiatric comorbidities
timeFrame: Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
measure: Changes in psychiatric comorbidities
timeFrame: V5 - 8 weeks after the end of first cycle (each cycle is 10 days)
measure: Changes in psychiatric comorbidities
timeFrame: V7 - 4 weeks after the end of the second cycle (each cycle is 10 days)
measure: Changes in psychiatric comorbidities
timeFrame: V8 - 8 weeks after the end of the second cycle (each cycle is 10 days)
measure: Safety assessment and possible side effects
timeFrame: Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
measure: Safety assessment and possible side effects
timeFrame: V5 - 8 weeks after the end of first cycle (each cycle is 10 days)
measure: Safety assessment and possible side effects
timeFrame: V7 - 4 weeks after the end of the second cycle (each cycle is 10 days)
measure: Safety assessment and possible side effects
timeFrame: V8 - 8 weeks after the end of the second cycle (each cycle is 10 days)
Other outcomes:
measure: Compare brain functional connectivity before and after tDCS treatment
timeFrame: V5 - 8 weeks after the end of first cycle (each cycle is 10 days)
measure: Evaluation of the impact of tDCS on interictal epileptic spikes (IESs)
timeFrame: Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
measure: Evaluation of the impact of tDCS on interictal epileptic spikes
timeFrame: Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
measure: Evaluation of the impact of tDCS on interictal epileptic spikes
timeFrame: V7 - 4 weeks after the end of the second cycle (each cycle is 10 days)
measure: Evaluation of the impact of tDCS on interictal epileptic spikes
timeFrame: Visit 4 (V4) - 4 weeks after the end of first cycle (each cycle is 10 days)
measure: Evaluation of the impact of tDCS on interictal epileptic spikes
timeFrame: V7 - 4 weeks after the end of the second cycle (each cycle is 10 days)
Locations:
city: Bordeaux
country: France
facility: Service de Neurophysiologie Clinique de l'Enfant et de L'Adulte, Pôle de Neurosciences Cliniques
city: Bron
country: France
facility: Département Neurologie Fonctionnelle et Epilepsie, Hôpital neurologique - Hospices Civils de Lyon
city: Lille
country: France
facility: Service de Neurophysiologie clinique - Hôpital Roger Salengro, CHU Lille
city: Marseille
country: France
facility: Service Epileptologie et Rythmologie Cérébrale, Hôpital La Timone
city: Paris
country: France
facility: Service de Neurophysiologie clinique - GHU Psychiatrie et Neurosciences Sainte-Anne
city: Rennes
country: France
facility: Service de Neurologie - CHU de Rennes - Hôpital Pontchaillou
city: Toulouse
country: France
facility: Explorations neurophysiologiques - Pôle neurosciences, CHU de Toulouse, Hôpital Pierre Paul Riquet
Study officials:
References: