Controlled Randomized Stimulation Versus Resection (CoRaStiR)

Study Overview
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Brief Summary
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Patients will be prospectively randomized to 3 different treatment arms: Treatment group 1: patients who undergo medial temporal lobe resection Treatment group 2: patients who receive immediate hippocampal neurostimulation Treatment group 3: patients who are implanted with an intracranial electrode but in whom hippocampal neurostimulation is delayed for 6 months. Twelve months after inclusion unblinding will occur. Patients in group 2 and 3 will have the option to choose between continuing neurostimulation treatment or resective surgery. Study visits will occur every 3 months.

Official Title
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Prospective Randomized Controlled Study of Neurostimulation in the Medial Temporal Lobe for Patients With Medically Refractory Medial Temporal Lobe Epilepsy; Controlled Randomized Stimulation Versus Resection (CoRaStiR)

Conditions
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Epilepsy

Intervention / Treatment
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* Device: Implantation of an intracranial electrode
* Procedure: amygddohyppocampertomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presurgical candidates with pharmacoresistant partial seizures despite optimal medical treatment and history of temporal lobe epilepsy Age above 18 years TIQ > 80 Able to give informed consent Average of 2 partial seizures per month during a baseline of 3 months. Recording of seizures must have been done in a prospective manner using standard seizure diaries. Able to adequately report seizure frequencies using standard seizure diaries Video-EEG characteristics showing temporal lobe seizure onset (left-sided or right-sided seizure onset) in at least one recorded habitual seizure Presence of a structural abnormality in the medial temporal lobe, suggestive of hippocampal sclerosis as evidenced by optimum MRI Women of child-bearing age will be required to use a reliable method of contraception during the study duration Exclusion Criteria: Extratemporal epilepsy; multifocal epilepsy; evidence of bilateral medial temporal lobe epilepsy MR evidence of potentially epileptogenic lesions outside the medial temporal lobe such as dysplasias, tumours or cavernomas Prior resective intracranial surgery Patients who are candidates for invasive video-EEG recording or have previously been investigated with invasive video-EEG recording Patients who previously underwent any other type of neurostimulation for treating epilepsy Patients who are unable to fill in questionnaires and comply with protocol requirements Progressive neurological or medical conditions Medical or psychiatric conditions precluding surgery or compliance Patients taking antidepressant medication Pregnancy at study onset Previous (within the last 3 months), ongoing or planned participation in other treatment study protocols for epilepsy Contraindication for intracranial surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Implantation intracranial electrode with immediate stimulation<br> | Device: Implantation of an intracranial electrode<br>* Implantation of an intracranial electrode will be followed.<br>|
| Placebo Comparator: Implantation intracranial electrode without stimulation<br> | Device: Implantation of an intracranial electrode<br>* Implantation of an intracranial electrode will be followed.<br>|
| Active Comparator: Resective surgery: amygddohyppocampertomy<br> | Procedure: amygddohyppocampertomy<br>* Resective surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess whether stimulation and/or resection produces a reduction in mean monthly seizure frequency that is greater than in the control group over 6 months of follow-up. |  | 6 months | 
| To assess whether stimulation produces a reduction in mean monthly seizure frequency that is comparable to resection at 6 and 12 months of follow-up. |  | at 6 and 12 months of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess whether stimulation yields better neuropsychological outcome compared to resection at 12 months of follow-up. |  | at 12 months of follow-up | 
| responder rates during 3 month intervals |  | 3 months intervals | 
| mean seizure free interval during 3 month intervals |  | 3 month intervals | 
| seizure severity and seizure type during 3-month intervals |  | 3-month intervals | 
| quality of life: changes in QOLIE 89 score at 6 and 12 months |  | at 6 and 12 months | 
| mood assessment: changes in Beck depression scale scores at 6 and 12 month |  | at 6 and 12 month | 
| Safety Objectives: |  | during twelve months after inclusion | 
| Operative and postoperative complications and long-term side effects |  | during twelve months after inclusion |