EpilepsyPhase 3NCT00101933

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

A Phase 3 study testing Medtronic DBS Therapy for epilepsy in people with Epilepsy, run by MedtronicNeuro.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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… Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Epilepsy
What is being tested?: Medtronic DBS Therapy for epilepsy
Type of treatment: Medical device
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 157 participants
Where: No sites listed yet
Study dates: Dec 2003to Oct 2017
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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.

About this study

Read the 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.

Conditions: Epilepsy
Being tested: Medtronic DBS Therapy for epilepsy
Keywords: Deep brain stimulation, DBS, SANTE
Medical subject headings: Epilepsy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Medtronic DBS Therapy for epilepsyDevice
Stimulation On
Medtronic DBS Therapy for epilepsyDevice
Stimulation Off

Study groups in NCT00101933
Study group	Role	What they receive
1	Experimental	Active Stimulation Receives: Device: Medtronic DBS Therapy for epilepsy
2	Sham comparator	No Stimulation Receives: Device: Medtronic DBS Therapy for epilepsy

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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).
Measured: Through the end of the three-month blinded phase

Secondary outcomes (6)

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'.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Through the end of the three-month blinded phase

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2003Oct 2017

First posted19 Jan 2005 (estimated)
Study startDec 2003
Primary completionJun 2008
Study completionOct 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for EpilepsyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 157 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00101933
Sponsor's protocol ID: 1604
Status last verified: Feb 2018
First submitted: 18 Jan 2005
Last updated: 22 Mar 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Miller PM, Gross RE. Wire tethering or 'bowstringing' as a long-term hardware-related complication of deep brain stimulation. Stereotact Funct Neurosurg. 2009;87(6):353-9. doi: 10.1159/000236369. Epub 2009 Sep 10.
PubMed 19752594
Fisher R, Salanova V, Witt T, Worth R, Henry T, Gross R, Oommen K, Osorio I, Nazzaro J, Labar D, Kaplitt M, Sperling M, Sandok E, Neal J, Handforth A, Stern J, DeSalles A, Chung S, Shetter A, Bergen D, Bakay R, Henderson J, French J, Baltuch G, Rosenfeld W, Youkilis A, Marks W, Garcia P, Barbaro N, Fountain N, Bazil C, Goodman R, McKhann G, Babu Krishnamurthy K, Papavassiliou S, Epstein C, Pollard J, Tonder L, Grebin J, Coffey R, Graves N; SANTE Study Group. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia. 2010 May;51(5):899-908. doi: 10.1111/j.1528-1167.2010.02536.x. Epub 2010 Mar 17.
PubMed 20331461
Troster AI, Meador KJ, Irwin CP, Fisher RS; SANTE Study Group. Memory and mood outcomes after anterior thalamic stimulation for refractory partial epilepsy. Seizure. 2017 Feb;45:133-141. doi: 10.1016/j.seizure.2016.12.014. Epub 2016 Dec 23.
PubMed 28061418
Salanova V, Witt T, Worth R, Henry TR, Gross RE, Nazzaro JM, Labar D, Sperling MR, Sharan A, Sandok E, Handforth A, Stern JM, Chung S, Henderson JM, French J, Baltuch G, Rosenfeld WE, Garcia P, Barbaro NM, Fountain NB, Elias WJ, Goodman RR, Pollard JR, Troster AI, Irwin CP, Lambrecht K, Graves N, Fisher R; SANTE Study Group. Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy. Neurology. 2015 Mar 10;84(10):1017-25. doi: 10.1212/WNL.0000000000001334. Epub 2015 Feb 6.
PubMed 25663221

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Not yet recruiting
Clinical Trial of SEEG for Drug-resistant Epilepsy
Drug-Resistant Epilepsy
RecruitingPhase 3
Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
Seizures, Lennox Gastaut Syndrome
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures
Focal Seizure, Epilepsy
Active, not recruitingObservational study
Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Traumatic Brain Injury, Post-traumatic Epilepsy
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures FOCUS-1
Focal Seizure, Epilepsy

All Epilepsy trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: SANTE - Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy
ClinicalTrials.gov ID: NCT00101933
Acronym / sponsor ID: 1604
Conditions: Epilepsy
Keywords: Deep brain stimulation, DBS, SANTE
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 157 participants (actual)
Lead sponsor: MedtronicNeuroIndustry (pharma, biotech, devices)
Study start: Dec 2003 (actual)
Primary completion: Jun 2008 (actual)
Study completion: Oct 2017 (actual)
First posted: 19 Jan 2005 (estimated)
Results: Posted 21 Jan 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
1	Experimental	Device: Medtronic DBS Therapy for epilepsyActive Stimulation
2	Sham comparator	Device: Medtronic DBS Therapy for epilepsyNo Stimulation

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (4 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Medtronic DBS Therapy for epilepsyStimulation On	Device	1
Medtronic DBS Therapy for epilepsyStimulation Off	Device	2

Primary outcome

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).
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).

6 secondary outcomes

Adverse Events Experienced With the Medtronic DBS System
Time frame: 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)
Seizure Responder Rate
Time frame: 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
Percentage Change in the Maximum Length of Seizure-free Intervals
Time frame: Through the end of the three-month blinded phase
Proportion of Treatment Failures
Time frame: Through the end of the three-month blinded phase

Results and safety

Results posted to the registry on 21 Jan 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Active Stimulation	54	54
No Stimulation	55	55

Primary outcome: Primary Analysis: Change in Seizure Rate

Time frame: Through the end of the three-month blinded phase. Median (Inter-Quartile Range). Unit: Percentage change from baseline

Measure	Active Stimulation n = 54	No Stimulation n = 54
Value	-40.4 (-62.9 to -21.6)	-14.5 (-50.3 to 20.0)

Active Stimulation vs No Stimulation: p = 0.0017, Generalized Estimating Equations

Population analysed: This analysis used the protocol-prespecified "Primary analysis data set" which required that subjects had at least 70 days of diary in the blinded phase. One control subject was not included in this analysis as they had 66 of the required 70 days.

Primary outcome: Alternative Primary Analysis: Change in Seizure Rate

Time frame: Through the end of the three-month blinded phase. Median (Inter-Quartile Range). Unit: Percentage change from baseline

Measure	Active Stimulation n = 53	No Stimulation n = 54
Value	-35.0 (-53.9 to -14.5)	-21.1 (-51.5 to 7.5)

Active Stimulation vs No Stimulation: p = 0.0387, Generalized Estimating Equations

Population analysed: This analysis used the protocol-prespecified "Primary analysis data set" with one additional outlier subject removed from the active group. This subject had 210 stimulation initiated seizures within 48 hours of the device being turned on and was determined to be an outlier using both a statistical and clinical rationale.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected throughout the study. The summaries below include events that occurred during the blinded phase. A summary of device related events (operative phase through Year 2) is in the safety characterization objective.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Active Stimulation	2 of 54 (3.7%)	42 of 54 (77.8%)	Not reported
No Stimulation	6 of 55 (10.9%)	41 of 55 (74.5%)	Not reported

Limitations and caveats (from the sponsor): No limitations leading to unreliable data were identified.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 19752594Miller PM, Gross RE. Wire tethering or 'bowstringing' as a long-term hardware-related complication of deep brain stimulation. Stereotact Funct Neurosurg. 2009;87(6):353-9. doi: 10.1159/000236369. Epub 2009 Sep 10.
Results publication: PubMed 20331461Fisher R, Salanova V, Witt T, Worth R, Henry T, Gross R, Oommen K, Osorio I, Nazzaro J, Labar D, Kaplitt M, Sperling M, Sandok E, Neal J, Handforth A, Stern J, DeSalles A, Chung S, Shetter A, Bergen D, Bakay R, Henderson J, French J, Baltuch G, Rosenfeld W, Youkilis A, Marks W, Garcia P, Barbaro N, Fountain N, Bazil C, Goodman R, McKhann G, Babu Krishnamurthy K, Papavassiliou S, Epstein C, Pollard J, Tonder L, Grebin J, Coffey R, Graves N; SANTE Study Group. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia. 2010 May;51(5):899-908. doi: 10.1111/j.1528-1167.2010.02536.x. Epub 2010 Mar 17.
Results publication: PubMed 28061418Troster AI, Meador KJ, Irwin CP, Fisher RS; SANTE Study Group. Memory and mood outcomes after anterior thalamic stimulation for refractory partial epilepsy. Seizure. 2017 Feb;45:133-141. doi: 10.1016/j.seizure.2016.12.014. Epub 2016 Dec 23.
Results publication: PubMed 25663221Salanova V, Witt T, Worth R, Henry TR, Gross RE, Nazzaro JM, Labar D, Sperling MR, Sharan A, Sandok E, Handforth A, Stern JM, Chung S, Henderson JM, French J, Baltuch G, Rosenfeld WE, Garcia P, Barbaro NM, Fountain NB, Elias WJ, Goodman RR, Pollard JR, Troster AI, Irwin CP, Lambrecht K, Graves N, Fisher R; SANTE Study Group. Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy. Neurology. 2015 Mar 10;84(10):1017-25. doi: 10.1212/WNL.0000000000001334. Epub 2015 Feb 6.

Related trials for Epilepsy

Not yet recruiting
Clinical Trial of SEEG for Drug-resistant Epilepsy
Drug-Resistant Epilepsy
RecruitingPhase 3
Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
Seizures, Lennox Gastaut Syndrome
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures
Focal Seizure, Epilepsy
Active, not recruitingObservational study
Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Traumatic Brain Injury, Post-traumatic Epilepsy
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures FOCUS-1
Focal Seizure, Epilepsy

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Medtronic DBS Therapy for epilepsy in people with Epilepsy, run by MedtronicNeuro.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Jan 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Primary Analysis: Change in Seizure Rate (time frame: Through the end of the three-month blinded phase). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00101933, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2018.