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

February 21, 2018 updated by: MedtronicNeuro
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

157

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Active Stimulation
Device: Medtronic DBS Therapy for epilepsy
Stimulation On
Device: Medtronic DBS Therapy for epilepsy
Stimulation Off
Sham Comparator: 2
No Stimulation
Device: Medtronic DBS Therapy for epilepsy
Stimulation On
Device: Medtronic DBS Therapy for epilepsy
Stimulation Off

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Analysis: Change in Seizure Rate
Time Frame: Through the end of the three-month blinded phase
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
Time Frame: Through the end of the three-month blinded phase
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
Time Frame: Through Year 2 of the long-term follow-up phase

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)
Time Frame: Inclusive of all study follow-up after device implantation (mean follow-up 3.7 years)

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
Time Frame: Through the end of the three-month blinded phase
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
Time Frame: Through the end of the three-month blinded phase
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
Time Frame: Through the end of the three-month blinded phase
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
Time Frame: Through the end of the three-month blinded phase
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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Most Severe Seizures
Time Frame: Through the end of the three-month blinded phase
Seizures were recorded on daily seizure diaries. The subject recorded the number of seizures by seizure type on the seizure diary. The subject also noted at baseline, of those they had ever experienced, which seizure they considered to be "most severe."
Through the end of the three-month blinded phase

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MedtronicNeuro

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2003

Primary Completion (Actual)

June 1, 2008

Study Completion (Actual)

October 1, 2017

Study Registration Dates

First Submitted

January 18, 2005

First Submitted That Met QC Criteria

January 18, 2005

First Posted (Estimate)

January 19, 2005

Study Record Updates

Last Update Posted (Actual)

March 22, 2018

Last Update Submitted That Met QC Criteria

February 21, 2018

Last Verified

February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1604

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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