STIMEP : Assessment of Subthalamic Nucleus Stimulation in Drug Resistant Epilepsy

Study Overview
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Brief Summary
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The aim of this study is to evaluate the effectiveness and the safety of deep brain stimulation in drug resistant epilepsy. This is a double blind, controlled and randomized clinical trial with two cross-over groups and four phases. Phase 1 : base line, open phase consisting of follow-up of patients with their standard treatment. Phase 2 : Randomisation, lead implantation, followed by 3 months wash out period with the stimulator switch OFF. Phase 3 : cross-over, double blind phase : 3 months with stimulator switch ON or OFF depending on randomization allocation, followed by 3 months with the stimulator switch on the opposite position. The placebo consisting of turn OFF the stimulator. Phase 4 : open phase, one year follow-up of all patients with the stimulator switch ON.

Detailed Description
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The experimental work performed for more than 15 years by several research teams shows in animal models of epilepsy, that several circuits of basal ganglia are involved in the control of epilepsy seizures. The existence of those circuits leads to the possibility of therapeutic applications in particular deep brain stimulation. Preliminary results (Benabid et al, 2002) (Chabardes et al , 2002) suggest that the neuromodulation of basal ganglia and in particular the subthalamic nucleus and the substantia nigra pars reticulata could have a therapeutic effects in patients with drug resistant epilepsy and no possibility of resection surgery. This is a double blind, controlled and randomized clinical trial with two cross-over groups and four phases. Phase 1 : base line, open phase consisting of follow-up of patients with their standard treatment. Phase 2 : Randomisation, lead implantation, followed by 3 months wash out period with the stimulator switch OFF. Phase 3 : cross-over, double blind phase : 3 months with stimulator switch ON or OFF depending on randomization allocation, followed by 3 months with the stimulator switch on the opposite position. Phase 4 : open phase, one year follow-up of all patients with the stimulator switch ON. There are two differents groups at phase 3 : Group A : 10 patients with the stimulator switch ON for three months and switch OFF for the next three months. Group B : 10 patients with the opposite sequence, OFF and ON. Main objective : - To show that high frequency deep brain stimulation of the subthalamic nucleus decrease the frequency of epileptic seizure compared with no stimulation. Secondary objectives : To show that high frequency deep brain stimulation of the subthalamic nucleus improve the quality of life. To describe the side effects of this device and compare with those described in Parkinson patients. In particular to check the onset of dyskinesia related to dopamine. To compare the distribution of seizure frequency after stimulation to the base line. To show that the number of patients responding to treatment are higher in the group with stimulator switch ON than in the group with the stimulator turn OFF. To compare the number of days without seizure with the stimulator switch ON or OFF. To evaluated the neuropsychologic effect induced by the neurostimulation To quantify the types and the ratio of different seizures during the ON phase and the OFF phase. To monitor the secondary drug use during the study. Control visits : all patients will have a control visit every 4 weeks during the study.

Official Title
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Assessment of Subthalamic Nucleus Stimulation in Drug Resistant Epilepsy Associated With Dopaminergic Metabolism Deficit. A Randomized, Double Blind, Controlled Trial.

Conditions
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Epilepsy, Drug Resistant

Intervention / Treatment
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* Device: Neurostimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Epilepsy resistant to antiepileptic drug and dopaminergic D2 agonist. No curative exeresis surgery possible Metabolism deficiency of DOPA above 1 DS, evaluated by Positron Emission Tomography (PET) using fluorodopa Age ranging from 18 to 50 capacity to consent Affiliation to the French Social Security Exclusion Criteria: pregnant woman or nursing mother change of antiepileptic, 30 days before base line convulsive etat de mal that requires an hospitalisation, 30 days before base line

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br>The stimulator is switch ON during the first phase of the cross-over and switch OFF during the second phase | Device: Neurostimulation<br>* High frequency neurostimulation of subthalamic nucleus : quadrupolar electrode, type 3389, n° : I7 02 08 39709 158, Medtronic, Minneapolis, USA<br>* Other names: Neurostimulation of subthalamic nucleus;|
| Other: 2<br>The stimulator is switch OFF during the first phase of the cross-over and switch ON during the second phase | Device: Neurostimulation<br>* High frequency neurostimulation of subthalamic nucleus : quadrupolar electrode, type 3389, n° : I7 02 08 39709 158, Medtronic, Minneapolis, USA<br>* Other names: Neurostimulation of subthalamic nucleus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - Daily seizure frequency at each phase |  | at each phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of days without seizure during each phase |  | at each phase | 
| Quality of life : SEALS, QOLIE-31 and NHP scales |  | at each phase | 
| Neuropsychological test : WAIS, GROBER and Busckhe, Wisconsin Card Sorting Test, TRAIL test, LURIA test, Beck Depression Inventory, verbal flow test, empathy test |  | at each phase | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epilepsy, deep brain stimulation, Subthalamic nucleus, Drug resistant epilepsy