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Seizure Detection and Automatic Magnet Mode Performance Study (E-36)

Primary Purpose

Epilepsy

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Model 106 VNS Therapy System
Sponsored by
Cyberonics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring Automatic Magnet Mode (AMM), Vagal Nerve Stimulation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with a clinical diagnosis of medically refractory epilepsy dominated by partial seizures suitable for implantation with the Model 106 VNS Therapy System.
  • Patients with a history of increased heart rate (tachycardia) associated with seizure onset based on clinical data obtained from medical history, admission/hospital charts, or prior neurophysiologic evaluations.
  • Patients willing to undergo an EMU evaluation for a period of at least three days with activation of the AMM feature during that time.
  • Patients having an average of ≥ 3 seizures per month based upon diary or patient reporting for the 3 months prior to the screening visit.
  • Patients must have peak-peak R-wave amplitude greater than or equal to 0.40 mV on ECG measured from the proposed electrode location in the neck to the proposed generator location in the chest via surface ECG electrodes in 7 different body positions.
  • Patients must be at least 18 years old.
  • Patients must be in good general health and ambulatory.
  • Patient must be willing and able to complete informed consent.

Exclusion Criteria:

  • Patients have had a bilateral or left cervical vagotomy.
  • Patients currently use, or are expected to use, short-wave diathermy, microwave diathermy, or therapeutic ultrasound diathermy.
  • A VNS Therapy System implant would (in the investigator's judgment) pose an unacceptable surgical or medical risk for the patient.
  • Patients expected to require full body magnetic resonance imaging.
  • Patients have a history of VNS Therapy.
  • Patients have a documented history of clinically meaningful bradycardia (heart rate less than 50 bpm) associated with seizures.
  • Patients with a significant psychiatric disorder, significant cognitive impairment, history of major depression, or suicidality as defined by DSM IV-TR that in the investigator's judgment would pose an unacceptable risk for the patient or prevent the patient's successful completion of the study.
  • Patients with a history of status epilepticus within 3 months of study enrollment.
  • Patients prescribed drugs specifically for a cardiac or autonomic disorder that in the investigator's opinion would affect heart rate response unless the patient has ictal tachycardia while taking said drugs. These include, but are not limited to, beta adrenergic antagonists ("beta blockers").
  • Patients with known clinically meaningful cardiovascular arrhythmias as well as patients with clinically meaningful cardiovascular arrhythmias determined by a 24-hour Holter recording obtained at the screening visit.
  • Patients dependent on alcohol or narcotic drugs as defined by DSM IV-TR within the past 2 years.
  • Patients with a history of only psychogenic or pseudo seizures.
  • Women who are pregnant. Women of childbearing age must take a pregnancy test.
  • Patients currently enrolled in another investigational study.

Sites / Locations

  • Hôpital Erasme
  • Cliniques Universitaires Saint-Luc
  • Universitair Ziekenhuis Gent
  • Epilepsie-Zentrum Bethel
  • Universitätsklinikum Bonn
  • Universitätsklinikum Erlangen
  • Albert-Ludwigs-Universität
  • Ludwig-Maximilians-Universität München
  • Universitätsklinikum Tübingen
  • Kempenhaege
  • Oslo University Hospital
  • King's College Hospital
  • The National Hospital for Neurology and Neurosurgery
  • Royal Hallamshire Hospital

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Model 106 VNS Therapy System

Arm Description

Model 106 VNS Therapy System includes a new Seizure Detection Algorithm (SDA) and corresponding Automatic Magnet Mode (AMM) feature.

Outcomes

Primary Outcome Measures

Summary of Seizures Reported by Investigators and Triple Review
Subjects were admitted to the EMU and underwent standard continuous data collection of vEEG and ECG for 3 to 5 days. If a seizure occurred during the EMU stay, clinical investigators annotated the start and stop times, the type of seizure, the presumed seizure onset location, and the lobe of origin as applicable. Following the EMU data collection phase of the trial, the de-identified, continuous electronic records (per patient) from the EMU period were provided to an independent and blinded triple review panel. This panel evaluated the EEG data and annotated seizure onset, seizure offset, and a description of seizure type. In the absence of video, seizure types could only be specified as: partial (particular type not denoted), generalized (non-absence), absence, or partial with secondary generalization.
Observed Sensitivity Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
Sensitivity is the total number of seizures detected divided by the total number of seizures during EMU stay.Data used to support sensitivity analyses included digital ECG/EEG files,corresponding M106 device downloads,and CRF data.Seizure and non-seizure EEG segments were provided to independent reviewers to confirm seizure occurrence and define EEG seizure onset times.Seizure onset times were then compared with observed M106 device detections at the detection threshold setting for AutoStim that the patient was randomized to(SDA 2;60%,SDA 4;40%,SDA 6;20%).Sensitivity is only reported if the heart rate surpassed the programmed detection threshold.Number of participants is total number of subjects who had seizures during the EMU stay. An "Ictal tachycardia Seizure" is a seizure with Ictal Heart rate >= 100 bpm & at least 55% increase, or 35 bpm increase from baseline) Bootstrap confidence intervals using 3000 bootstrap samples. n=total number of seizures; N= number of participants
Modeled Sensitivity Based on Heart Rate Increase Associated With Seizures by SDA Setting Post-Processed Through Bench-top Device Simulant
Sensitivity is defined as the total number of seizures detected divided by the total number of seizures during the EMU stay. Data used to support sensitivity analyses included digital ECG/EEG files, corresponding M106 device downloads, and CRF data. Seizure onset times were compared with modeled M106 device detections at the least sensitive setting capable of detecting the seizure based on the corresponding change in heart rate. The participants' surface ECG data collected during the trial and passed through DMSDAT, a validated bench-top simulant of the Automatic Stimulation feature, was used to produce modeled results for each threshold for AutoStim setting (1;70%, 2;60%, 3;50%, 4;40%, 5;30% and 6;20%). Number of participants is total number of subjects who experienced seizures during the EMU stay. Bootstrap confidence intervals using 3000 bootstrap samples.
Potential False Positives Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
Potential false positive rate is defined as the sum across all patients of the total number of potential false positive detections divided by the sum across all patients of the appropriate monitoring time during the EMU stay. Data used to support the potential false positive rate analyses included digital ECG/EEG files retrieved from the EMU evaluation, corresponding M106 device downloads, and triple review results of EEG recordings. The evaluated EMU monitoring time includes a daily 3 minutes stepping exercise during which patients stepped up and down on a step stool at a submaximal effort leve.

Secondary Outcome Measures

Validation of Cardiac R-Wave Detection
Cardiac R-wave detection was evaluated against concurrent ECG data (i.e. detailed R-wave test) collected during implant, the first titration visit, at the beginning of the EMU stay, and at the 12 month visit. R-R intervals were calculated using detected R-waves from the Implantable Pulse Generator (IPG) and from a standard ECG monitor during a pre-specified time interval. A time series 10 seconds was recorded using the IPG SyncPulse feature. Simultaneously, a corresponding time series over the same interval was recorded using a standard ECG monitor. The total number of beats accurately detected in the entire study population is reported.
Characterization of Latency Period: Analysis of Observed Latency for True Positive Detections by Randomized SDA Setting
Latency is defined as the time difference between SDA detection time and the annotated seizure onset time. The earliest SDA detection was considered for each seizure. Seizure onset times were compared with M106 device detections at the randomized SDA setting. Negative latencies indicate that the SDA detection preceded the seizure onset time. The median latency is presented for seizures which met the definition of ictal tachycardia as well as all seizure types and indicate the observed latency range.
Human Factors and Usability of the AspireSR® VNS Therapy® System.
Usability survey data were collected from all site personnel who used the handheld programmer to evaluate the usability of the AspireSR® VNS Therapy® System.The device usability survey contained 17 questions that measure usability on a five-point Likert scale ranging from "Extremely Difficult" (5) to "Extremely Easy" (1). Site personnel were asked to assess usability of the software features, instructions for use, training materials, and overall usability of the system at four different time points. The time points include implant/recovery and the end of EMU. Usability was calculated as percentage of the users who found the usability of system to be "easy-2" or extremely easy-1".
Changes From Baseline in Seizure Frequency
Seizure frequency was calculated at 3, 6, 12, 18 and 24 month follow-up visits based on seizure diary information and compared to baseline estimates. Response rate was computed and summarized for partial seizures (SPS, CPS and CPS with 2nd GTCs) and overall seizure types as the percentage of patients that achieved ≥50% seizure reduction per month from baseline by visit.
Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3)
Investigators completed the National Hospital Seizure Severity Scale (NHS3) questionnaire at screening, at the end of the EMU stay (provided a seizure occurred during the EMU stay), and at follow-up visits. Severity was evaluated by seizure type. The range of NHS3 scale is 1-27 with 1 being the least severe and 27 being the most severe. Negative median value means improvement.
Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Seizure Severity Questionnaire (SSQ)
Clinical outcomes such as seizure severity, intensity and post-ictal duration were also assessed during the long-term follow-up visits (3, 6, 12, 18 and 24 months) with patient reported questionnaires (SSQ; Seizure Severity Questionnaire). The range for SSQ (all sub-scores) is 1-7 with 1 being the least severe and 7 being the most severe. Mean SSQ scores at 3, 6, 12, 18 and 24 months were compared to baseline. A change from baseline is calculated as baseline minus follow-up visit score to correspond to the Minimally Important Change (MIC) criteria as defined in the Scoring Scheme for SSQ v2. Questionnaire. Subscale scores were averaged to compute the SSQ Total Score
Proportion of Seizures Ending During Stimulation by Type
Clinical outcomes including seizure duration and cessation were assessed with vEEG during EMU stay. Number of seizures treated with Automatic Stimulation during EMU were evaluated. Of these seizures, those ending during the 60 second course of Automatic Stimulation were assessed and tabulated by seizure type.
Summary of Seizure Duration (Seconds) for All Seizure Types by Subgroup(ITT Population) (Only Seizures With Post Ictal Duration (Seconds) Annotated)
Seizure duration was calculated using historical EEG data from patients enrolled in the trial and compared to the duration of seizures that occurred during the study EMU stay. The seizure start and end times were determined via clinical observation and/or through an adjudication process with qualified EEG reviewers.
Summary of Post Ictal Duration (Seconds) for All Seizure Types (ITT Population) (Only Seizures With Post Ictal Duration (Seconds) Annotated)
Post-ictal duration was quantified by identifying the time at which the number of EEG channels within the 95% confidence interval of relative power reaches a number that is consistent with that during the pre-seizure period. This measure represents the amount of time required following a seizure until the EEG recovers to the pre-seizure state. It is used to objectively estimate patient recovery time. Historical seizures were baseline EEG recordings measured during monitoring prior to implantation. Post-ictal duration is only reported for seizures with Post Ictal Duration (seconds) annotated and >= 20% Heart Rate Rise
Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P)
Quality of life data was collected using patient-completed QOLIE-31-P surveys and compared between baseline and follow-up visits. The MIC score for each subscale defines the threshold for Minimally Important Change. If a score exceeds the MIC Score, the improvement from baseline is considered clinically significant. The range for QOLIE-31-P (all sub-scores) is 0-100 with higher scores reflecting greater well-being.Subscale scores were averaged to compute the QOLIE Total Score.
Overall Summary of Seizure Intensity by Subgroup
Quantitative evaluation of EEG was used to characterize the seizures that were treated with Automatic Stimulation. Intensity was evaluated by surveying the average power level from the 10-20 system EEG channel of maximum output during the course of the seizure. Intensity was only reported for seizures with intensity annotated and >= 20% Heart Rate Rise. The relative intensity was calculated by normalizing the power calculations to the pre-seizure state, and thus the reported changes are dimensionless. n= number of seizures
Post-stimulation Heart Rate Changes
During a 1 hour period during the EMU stay, the VNS Therapy device was programmed to normal mode stimulation ON time 30 seconds, OFF time 5 minutes. AutoStim and Magnet Mode were programmed OFF. In this hour, 10 to 11 normal mode stimulations can be expected. Around each of these stimulations, ECG data were collected to assess potential stimulation related heart rate changes (during stimulation, after stimulation and after black-out time). A black-out time is a period after stimulation during which no seizure detections can occur, to ensure that potential stimulation related heart rate changes were not seen as ictal tachycardia that would trigger false positive detection. During the trial, the black-out time was programmed to 30 seconds. The heart rate changes for all stimulations and all patients were averaged.

Full Information

First Posted
March 23, 2011
Last Updated
December 21, 2015
Sponsor
Cyberonics, Inc.
Collaborators
PRA Health Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT01325623
Brief Title
Seizure Detection and Automatic Magnet Mode Performance Study
Acronym
E-36
Official Title
Seizure Detection and Automatic Magnet Mode Performance Study
Study Type
Interventional

2. Study Status

Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
July 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cyberonics, Inc.
Collaborators
PRA Health Sciences

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to confirm cardiac-based seizure detection in Cyberonics Model 106 VNS Therapy System.
Detailed Description
Prospective, observational, unblinded, multi-site study designed to collect data on patients implanted with a Model 106 VNS Therapy System from baseline through an EMU stay of up to 5 days. After the EMU stay, patients will continue follow-up for safety for approximately two years or until final regulatory approval of the product.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy
Keywords
Automatic Magnet Mode (AMM), Vagal Nerve Stimulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Model 106 VNS Therapy System
Arm Type
Other
Arm Description
Model 106 VNS Therapy System includes a new Seizure Detection Algorithm (SDA) and corresponding Automatic Magnet Mode (AMM) feature.
Intervention Type
Device
Intervention Name(s)
Model 106 VNS Therapy System
Other Intervention Name(s)
AspireSR VNS Therapy System
Intervention Description
The VNS Therapy System is an adjunctive therapy for the treatment of epilepsy. VNS Therapy is available as a scheduled stimulation, this is cyclic stimulation between programmable On- and Off- times (e.g., a 30-second burst every 5 minutes). VNS Therapy is also available as on-demand stimulation, that is, when a magnet is introduced briefly over the implanted device (Magnet Mode). The AspireSR VNS Therapy System includes a new feature, Automatic Magnet Mode or AutoStim. In addition to Normal Mode and Magnet Mode, AspireSR uses a Seizure Detection Algorithm to identify a potential seizure onset based on associated heart rate increases known as ictal tachycardia. The purpose is to deliver stimulation at or near the onset of a seizure.
Primary Outcome Measure Information:
Title
Summary of Seizures Reported by Investigators and Triple Review
Description
Subjects were admitted to the EMU and underwent standard continuous data collection of vEEG and ECG for 3 to 5 days. If a seizure occurred during the EMU stay, clinical investigators annotated the start and stop times, the type of seizure, the presumed seizure onset location, and the lobe of origin as applicable. Following the EMU data collection phase of the trial, the de-identified, continuous electronic records (per patient) from the EMU period were provided to an independent and blinded triple review panel. This panel evaluated the EEG data and annotated seizure onset, seizure offset, and a description of seizure type. In the absence of video, seizure types could only be specified as: partial (particular type not denoted), generalized (non-absence), absence, or partial with secondary generalization.
Time Frame
Epilepsy Monitoring Unit Stay
Title
Observed Sensitivity Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
Description
Sensitivity is the total number of seizures detected divided by the total number of seizures during EMU stay.Data used to support sensitivity analyses included digital ECG/EEG files,corresponding M106 device downloads,and CRF data.Seizure and non-seizure EEG segments were provided to independent reviewers to confirm seizure occurrence and define EEG seizure onset times.Seizure onset times were then compared with observed M106 device detections at the detection threshold setting for AutoStim that the patient was randomized to(SDA 2;60%,SDA 4;40%,SDA 6;20%).Sensitivity is only reported if the heart rate surpassed the programmed detection threshold.Number of participants is total number of subjects who had seizures during the EMU stay. An "Ictal tachycardia Seizure" is a seizure with Ictal Heart rate >= 100 bpm & at least 55% increase, or 35 bpm increase from baseline) Bootstrap confidence intervals using 3000 bootstrap samples. n=total number of seizures; N= number of participants
Time Frame
Epilepsy Monitoring Unit (EMU) Stay
Title
Modeled Sensitivity Based on Heart Rate Increase Associated With Seizures by SDA Setting Post-Processed Through Bench-top Device Simulant
Description
Sensitivity is defined as the total number of seizures detected divided by the total number of seizures during the EMU stay. Data used to support sensitivity analyses included digital ECG/EEG files, corresponding M106 device downloads, and CRF data. Seizure onset times were compared with modeled M106 device detections at the least sensitive setting capable of detecting the seizure based on the corresponding change in heart rate. The participants' surface ECG data collected during the trial and passed through DMSDAT, a validated bench-top simulant of the Automatic Stimulation feature, was used to produce modeled results for each threshold for AutoStim setting (1;70%, 2;60%, 3;50%, 4;40%, 5;30% and 6;20%). Number of participants is total number of subjects who experienced seizures during the EMU stay. Bootstrap confidence intervals using 3000 bootstrap samples.
Time Frame
Epilepsy Monitoring Unit (EMU) Stay
Title
Potential False Positives Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
Description
Potential false positive rate is defined as the sum across all patients of the total number of potential false positive detections divided by the sum across all patients of the appropriate monitoring time during the EMU stay. Data used to support the potential false positive rate analyses included digital ECG/EEG files retrieved from the EMU evaluation, corresponding M106 device downloads, and triple review results of EEG recordings. The evaluated EMU monitoring time includes a daily 3 minutes stepping exercise during which patients stepped up and down on a step stool at a submaximal effort leve.
Time Frame
Epilepsy Monitoring Unit (EMU) Stay
Secondary Outcome Measure Information:
Title
Validation of Cardiac R-Wave Detection
Description
Cardiac R-wave detection was evaluated against concurrent ECG data (i.e. detailed R-wave test) collected during implant, the first titration visit, at the beginning of the EMU stay, and at the 12 month visit. R-R intervals were calculated using detected R-waves from the Implantable Pulse Generator (IPG) and from a standard ECG monitor during a pre-specified time interval. A time series 10 seconds was recorded using the IPG SyncPulse feature. Simultaneously, a corresponding time series over the same interval was recorded using a standard ECG monitor. The total number of beats accurately detected in the entire study population is reported.
Time Frame
At Implant, First Titration Visit, Day 1 EMU and 12 Months
Title
Characterization of Latency Period: Analysis of Observed Latency for True Positive Detections by Randomized SDA Setting
Description
Latency is defined as the time difference between SDA detection time and the annotated seizure onset time. The earliest SDA detection was considered for each seizure. Seizure onset times were compared with M106 device detections at the randomized SDA setting. Negative latencies indicate that the SDA detection preceded the seizure onset time. The median latency is presented for seizures which met the definition of ictal tachycardia as well as all seizure types and indicate the observed latency range.
Time Frame
Epilepsy Monitoring Unit (EMU) Stay
Title
Human Factors and Usability of the AspireSR® VNS Therapy® System.
Description
Usability survey data were collected from all site personnel who used the handheld programmer to evaluate the usability of the AspireSR® VNS Therapy® System.The device usability survey contained 17 questions that measure usability on a five-point Likert scale ranging from "Extremely Difficult" (5) to "Extremely Easy" (1). Site personnel were asked to assess usability of the software features, instructions for use, training materials, and overall usability of the system at four different time points. The time points include implant/recovery and the end of EMU. Usability was calculated as percentage of the users who found the usability of system to be "easy-2" or extremely easy-1".
Time Frame
At implant/recovery up to EMU Discharge (2 to 4 weeks)
Title
Changes From Baseline in Seizure Frequency
Description
Seizure frequency was calculated at 3, 6, 12, 18 and 24 month follow-up visits based on seizure diary information and compared to baseline estimates. Response rate was computed and summarized for partial seizures (SPS, CPS and CPS with 2nd GTCs) and overall seizure types as the percentage of patients that achieved ≥50% seizure reduction per month from baseline by visit.
Time Frame
Up to 24 Month visit
Title
Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3)
Description
Investigators completed the National Hospital Seizure Severity Scale (NHS3) questionnaire at screening, at the end of the EMU stay (provided a seizure occurred during the EMU stay), and at follow-up visits. Severity was evaluated by seizure type. The range of NHS3 scale is 1-27 with 1 being the least severe and 27 being the most severe. Negative median value means improvement.
Time Frame
up to 24 Months Visit
Title
Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Seizure Severity Questionnaire (SSQ)
Description
Clinical outcomes such as seizure severity, intensity and post-ictal duration were also assessed during the long-term follow-up visits (3, 6, 12, 18 and 24 months) with patient reported questionnaires (SSQ; Seizure Severity Questionnaire). The range for SSQ (all sub-scores) is 1-7 with 1 being the least severe and 7 being the most severe. Mean SSQ scores at 3, 6, 12, 18 and 24 months were compared to baseline. A change from baseline is calculated as baseline minus follow-up visit score to correspond to the Minimally Important Change (MIC) criteria as defined in the Scoring Scheme for SSQ v2. Questionnaire. Subscale scores were averaged to compute the SSQ Total Score
Time Frame
Up to 24 Month visit
Title
Proportion of Seizures Ending During Stimulation by Type
Description
Clinical outcomes including seizure duration and cessation were assessed with vEEG during EMU stay. Number of seizures treated with Automatic Stimulation during EMU were evaluated. Of these seizures, those ending during the 60 second course of Automatic Stimulation were assessed and tabulated by seizure type.
Time Frame
Epilepsy Monitoring Unit (EMU) Stay
Title
Summary of Seizure Duration (Seconds) for All Seizure Types by Subgroup(ITT Population) (Only Seizures With Post Ictal Duration (Seconds) Annotated)
Description
Seizure duration was calculated using historical EEG data from patients enrolled in the trial and compared to the duration of seizures that occurred during the study EMU stay. The seizure start and end times were determined via clinical observation and/or through an adjudication process with qualified EEG reviewers.
Time Frame
Historical Seizures and Seizures during Epilepsy Monitoring Unit Stay
Title
Summary of Post Ictal Duration (Seconds) for All Seizure Types (ITT Population) (Only Seizures With Post Ictal Duration (Seconds) Annotated)
Description
Post-ictal duration was quantified by identifying the time at which the number of EEG channels within the 95% confidence interval of relative power reaches a number that is consistent with that during the pre-seizure period. This measure represents the amount of time required following a seizure until the EEG recovers to the pre-seizure state. It is used to objectively estimate patient recovery time. Historical seizures were baseline EEG recordings measured during monitoring prior to implantation. Post-ictal duration is only reported for seizures with Post Ictal Duration (seconds) annotated and >= 20% Heart Rate Rise
Time Frame
Historical Seizures and Seizures during Epilepsy Monitoring Unit Stay
Title
Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P)
Description
Quality of life data was collected using patient-completed QOLIE-31-P surveys and compared between baseline and follow-up visits. The MIC score for each subscale defines the threshold for Minimally Important Change. If a score exceeds the MIC Score, the improvement from baseline is considered clinically significant. The range for QOLIE-31-P (all sub-scores) is 0-100 with higher scores reflecting greater well-being.Subscale scores were averaged to compute the QOLIE Total Score.
Time Frame
up to 24 Months Visit
Title
Overall Summary of Seizure Intensity by Subgroup
Description
Quantitative evaluation of EEG was used to characterize the seizures that were treated with Automatic Stimulation. Intensity was evaluated by surveying the average power level from the 10-20 system EEG channel of maximum output during the course of the seizure. Intensity was only reported for seizures with intensity annotated and >= 20% Heart Rate Rise. The relative intensity was calculated by normalizing the power calculations to the pre-seizure state, and thus the reported changes are dimensionless. n= number of seizures
Time Frame
Historical Seizures and Seizures during Epilepsy Monitoing Unit Stay
Title
Post-stimulation Heart Rate Changes
Description
During a 1 hour period during the EMU stay, the VNS Therapy device was programmed to normal mode stimulation ON time 30 seconds, OFF time 5 minutes. AutoStim and Magnet Mode were programmed OFF. In this hour, 10 to 11 normal mode stimulations can be expected. Around each of these stimulations, ECG data were collected to assess potential stimulation related heart rate changes (during stimulation, after stimulation and after black-out time). A black-out time is a period after stimulation during which no seizure detections can occur, to ensure that potential stimulation related heart rate changes were not seen as ictal tachycardia that would trigger false positive detection. During the trial, the black-out time was programmed to 30 seconds. The heart rate changes for all stimulations and all patients were averaged.
Time Frame
EMU stay

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with a clinical diagnosis of medically refractory epilepsy dominated by partial seizures suitable for implantation with the Model 106 VNS Therapy System. Patients with a history of increased heart rate (tachycardia) associated with seizure onset based on clinical data obtained from medical history, admission/hospital charts, or prior neurophysiologic evaluations. Patients willing to undergo an EMU evaluation for a period of at least three days with activation of the AMM feature during that time. Patients having an average of ≥ 3 seizures per month based upon diary or patient reporting for the 3 months prior to the screening visit. Patients must have peak-peak R-wave amplitude greater than or equal to 0.40 mV on ECG measured from the proposed electrode location in the neck to the proposed generator location in the chest via surface ECG electrodes in 7 different body positions. Patients must be at least 18 years old. Patients must be in good general health and ambulatory. Patient must be willing and able to complete informed consent. Exclusion Criteria: Patients have had a bilateral or left cervical vagotomy. Patients currently use, or are expected to use, short-wave diathermy, microwave diathermy, or therapeutic ultrasound diathermy. A VNS Therapy System implant would (in the investigator's judgment) pose an unacceptable surgical or medical risk for the patient. Patients expected to require full body magnetic resonance imaging. Patients have a history of VNS Therapy. Patients have a documented history of clinically meaningful bradycardia (heart rate less than 50 bpm) associated with seizures. Patients with a significant psychiatric disorder, significant cognitive impairment, history of major depression, or suicidality as defined by DSM IV-TR that in the investigator's judgment would pose an unacceptable risk for the patient or prevent the patient's successful completion of the study. Patients with a history of status epilepticus within 3 months of study enrollment. Patients prescribed drugs specifically for a cardiac or autonomic disorder that in the investigator's opinion would affect heart rate response unless the patient has ictal tachycardia while taking said drugs. These include, but are not limited to, beta adrenergic antagonists ("beta blockers"). Patients with known clinically meaningful cardiovascular arrhythmias as well as patients with clinically meaningful cardiovascular arrhythmias determined by a 24-hour Holter recording obtained at the screening visit. Patients dependent on alcohol or narcotic drugs as defined by DSM IV-TR within the past 2 years. Patients with a history of only psychogenic or pseudo seizures. Women who are pregnant. Women of childbearing age must take a pregnancy test. Patients currently enrolled in another investigational study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bryan Olin
Organizational Affiliation
Cyberonics, Inc.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Paul Boon
Organizational Affiliation
Universitair Ziekenhuis Gent
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Erasme
City
Anderlecht
Country
Belgium
Facility Name
Cliniques Universitaires Saint-Luc
City
Brussels
Country
Belgium
Facility Name
Universitair Ziekenhuis Gent
City
Ghent
Country
Belgium
Facility Name
Epilepsie-Zentrum Bethel
City
Bielefeld
Country
Germany
Facility Name
Universitätsklinikum Bonn
City
Bonn
Country
Germany
Facility Name
Universitätsklinikum Erlangen
City
Erlangen
Country
Germany
Facility Name
Albert-Ludwigs-Universität
City
Freiburg
Country
Germany
Facility Name
Ludwig-Maximilians-Universität München
City
Munich
Country
Germany
Facility Name
Universitätsklinikum Tübingen
City
Tübingen
Country
Germany
Facility Name
Kempenhaege
City
Heeze
Country
Netherlands
Facility Name
Oslo University Hospital
City
Oslo
Country
Norway
Facility Name
King's College Hospital
City
London
Country
United Kingdom
Facility Name
The National Hospital for Neurology and Neurosurgery
City
London
Country
United Kingdom
Facility Name
Royal Hallamshire Hospital
City
Sheffield
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
26552564
Citation
Boon P, Vonck K, van Rijckevorsel K, El Tahry R, Elger CE, Mullatti N, Schulze-Bonhage A, Wagner L, Diehl B, Hamer H, Reuber M, Kostov H, Legros B, Noachtar S, Weber YG, Coenen VA, Rooijakkers H, Schijns OE, Selway R, Van Roost D, Eggleston KS, Van Grunderbeek W, Jayewardene AK, McGuire RM. A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation. Seizure. 2015 Nov;32:52-61. doi: 10.1016/j.seizure.2015.08.011. Epub 2015 Sep 21.
Results Reference
result
PubMed Identifier
27450311
Citation
Verrier RL, Nearing BD, Olin B, Boon P, Schachter SC. Baseline elevation and reduction in cardiac electrical instability assessed by quantitative T-wave alternans in patients with drug-resistant epilepsy treated with vagus nerve stimulation in the AspireSR E-36 trial. Epilepsy Behav. 2016 Sep;62:85-9. doi: 10.1016/j.yebeh.2016.06.016. Epub 2016 Jul 21.
Results Reference
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Seizure Detection and Automatic Magnet Mode Performance Study

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