SANTE - Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy

Study Overview
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Brief Summary
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The purpose of this research is to study the safety and effectiveness of bilateral stimulation of the anterior nucleus of the thalamus as adjunctive therapy for reducing the frequency of seizures in adults diagnosed with epilepsy characterized by partial-onset seizures, with or without secondary generalization, that are refractory to antiepileptic medications.

Detailed Description
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Medtronic, Inc. is sponsoring an investigational study of the Medtronic DBS Therapy for epilepsy, the company's deep brain stimulation (DBS) therapy for patients with refractory epilepsy. Epilepsy is a condition that affects 2.3 million Americans, and about one-third of these patients are refractory, or continue to experience seizures despite a wide range of treatment options. The prospective, randomized, double-blind trial uses existing technology to test whether bilateral stimulation of the anterior nucleus of the thalamus can safely and effectively reduce seizure frequency in patients with epilepsy. It includes enrollment of 157 patients at 17 sites in the U.S. 110 patients were implanted and monitored for 13 months following implant, with long-term follow-up until the device is approved or the study is stopped. 109 of the 110 implanted subjects were randomized to Active stimulation or Control. Patients in the active group, who received neurostimulation, were monitored for a reduction in seizure rates compared to the control group, who did not receive neurostimulation during the three-month double-blind phase. After the double-blind phase, all patients received neurostimulation. Candidates for the trial were adults with partial-onset epilepsy for whom at least three antiepileptic drugs have proven ineffective. They were to have had an average of six or more seizures per month. Candidates continued to receive their epilepsy medications while participating in the trial. Deep brain stimulation therapy has already received approval in the United States, Europe, Canada, and Australia for the treatment of Essential Tremor and Parkinson's disease. Deep brain stimulation is not approved in the United States for the treatment of epilepsy.

Official Title
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SANTE - Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy

Conditions
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Epilepsy

Intervention / Treatment
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* Device: Medtronic DBS Therapy for epilepsy
* Device: Medtronic DBS Therapy for epilepsy


Participation Criteria
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Eligibility Criteria
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Relevant Inclusion and Exclusion Criteria are listed below. Inclusion Criteria Partial-onset seizures with or without secondary generalization. The final determination shall be made by the Investigator based on a clinical description of the seizures and previous diagnostic testing that includes, at a minimum, video/clinical EEG that captured at least one ictal event. Anticipated average of 6 or more partial-onset seizures (with or without secondary generalized seizures) per month during the Baseline Phase, with no more than 30 days between seizures during the Baseline Phase. Refractory to antiepileptic drugs (AEDs). Patients will be considered refractory if they have failed at least three AEDs due to lack of efficacy. Receiving one to four currently marketed AEDs Be between 18 and 65 years of age at the time of lead implant Exclusion Criteria: Multilobar (>3 different lobes) anatomic areas of seizure onset Symptomatic generalized epilepsy Previous diagnosis of psychogenic/non-epileptic seizures Presence of implanted electrical stimulation medical device anywhere in the body (e.g., cardiac pacemakers, spinal cord stimulator) or any metallic implants in the head (e.g., aneurysm clip, cochlear implant). Vagal nerve stimulators are allowed if the device has been turned off for at least 30 days prior to the Baseline Week -12 visit and the patient agrees to have the generator explanted prior to or at the time of the Kinetra Neurostimulator implant.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Active Stimulation | Device: Medtronic DBS Therapy for epilepsy<br>* Stimulation On<br>|
| Sham Comparator: 2<br>No Stimulation | Device: Medtronic DBS Therapy for epilepsy<br>* Stimulation Off<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Analysis: Change in Seizure Rate | A protocol-prespecified generalized estimating equations (GEE) analysis was used to evaluate the treatment effect on seizure frequency. The final GEE model for the primary objective evaluation included treatment effect, log of the baseline seizure count, log of age, visit (categorical), treatment-by-visit interaction (categorical), and the offset (the number of days the diary was recorded in each month). | Through the end of the three-month blinded phase | 
| Alternative Primary Analysis: Change in Seizure Rate | A generalized estimating equations (GEE) analysis was used to evaluate the treatment effect on seizure frequency. With one outlier subject removed, the GEE model for this alternative analysis included treatment effect, log of the baseline seizure count, log of age, visit (categorical), and the offset (the number of days the diary was recorded in each month). | Through the end of the three-month blinded phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events Experienced With the Medtronic DBS System | The results are for the follow-up after device implantation through Year 2 and summarized are events that occurred in greater than 5% of subjects. Only events related to the device, therapy, or surgery are included. These abbreviations were used: General dis...=General disorders and administration site conditions Injury, poison...=Injury, poisoning and procedural complications Ther.=Therapeutic. For this summary, adverse events are reported as 'MedDRA System Organ Class - adverse event'. | Through Year 2 of the long-term follow-up phase | 
| Incidence of Sudden Unexplained Death in Epilepsy (SUDEP) | The number presented is for Definite and Probable SUDEP. The rate is calculated per 1000 subject years of follow-up. The confidence interval is the 95% Poisson confidence interval. Per protocol, only definite and probable SUDEP classifications were included in the calculation. The results shown are for the entire study follow-up after device implantation. | Inclusive of all study follow-up after device implantation (mean follow-up 3.7 years) | 
| Seizure Responder Rate | A responder is defined as a subject with greater than or equal to 50% reduction in seizures as compared with baseline. | Through the end of the three-month blinded phase | 
| Change in Percentage of Days Seizure-free | Difference between active group and control group in percentage change in seizure-free days over the entire blinded phase as compared to the entire baseline phase. The number of seizure-free days was normalized to 84-day baseline and blinded phases for each subject. | Through the end of the three-month blinded phase | 
| Percentage Change in the Maximum Length of Seizure-free Intervals | Difference between active group and control group in percentage change in the maximum length of seizure-free intervals over the entire blinded phase as compared to the entire baseline phase. | Through the end of the three-month blinded phase | 
| Proportion of Treatment Failures | A treatment failure was defined in the protocol as a subject who 1) required 3 or more doses of rescue medication within 48 hours, 3 times during the blinded phase; or 2) had 3 episodes of convulsive status epilepticus during the blinded phase. | Through the end of the three-month blinded phase | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Deep brain stimulation, DBS, SANTE