Seizure Detection and Automatic Magnet Mode Performance Study

NCT01325623 | Completed Results DMC

• 1 other identifier: Epilepsy (E)-36
• Study Type: interventional
• Target: 31
• Locations: 5 countries
• Sites: 14

Brief Summary

The purpose of this study is to confirm cardiac-based seizure detection in Cyberonics Model 106 VNS Therapy System.

Conditions

Epilepsy

Keywords

Automatic Magnet Mode (AMM); Vagal Nerve Stimulation

Outcome Measures

Primary Outcomes (4)

• 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.

  Epilepsy Monitoring Unit Stay

• 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

  Epilepsy Monitoring Unit (EMU) Stay

• 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.

  Epilepsy Monitoring Unit (EMU) Stay

• 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.

  Epilepsy Monitoring Unit (EMU) Stay

Secondary Outcomes (12)

• Validation of Cardiac R-Wave Detection

  At Implant, First Titration Visit, Day 1 EMU and 12 Months

• Characterization of Latency Period: Analysis of Observed Latency for True Positive Detections by Randomized SDA Setting

  Epilepsy Monitoring Unit (EMU) Stay

• Human Factors and Usability of the AspireSR® VNS Therapy® System.

  At implant/recovery up to EMU Discharge (2 to 4 weeks)

• Changes From Baseline in Seizure Frequency

  Up to 24 Month visit

• Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3)

  up to 24 Months Visit

Study Arms (1)

Model 106 VNS Therapy System

OTHER

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

Device: Model 106 VNS Therapy System

Interventions

Model 106 VNS Therapy System DEVICE

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.

Also known as: AspireSR VNS Therapy System

Model 106 VNS Therapy System

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cyberonics, Inc.: lead
• PRA Health Sciences: collaborator

Study Sites (14)

Hôpital Erasme

Anderlecht, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, Belgium

Location

Epilepsie-Zentrum Bethel

Bielefeld, Germany

Location

Universitätsklinikum Bonn

Bonn, Germany

Location

Universitätsklinikum Erlangen

Erlangen, Germany

Location

Albert-Ludwigs-Universität

Freiburg im Breisgau, Germany

Location

Ludwig-Maximilians-Universität München

Munich, Germany

Location

Universitätsklinikum Tübingen

Tübingen, Germany

Location

Kempenhaege

Heeze, Netherlands

Location

Oslo University Hospital

Oslo, Norway

Location

King's College Hospital

London, United Kingdom

Location

The National Hospital for Neurology and Neurosurgery

London, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 26552564 RESULT

• 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.

  PMID: 27450311 DERIVED

MeSH Terms

Conditions

Epilepsy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Wim Van Grunderbeek, Clinical Operations Manager Cyberonics Europe
• Organization: Cyberonics Europe BVBA

wim.vangrunderbeek@cyberonics.com

+32 2 720 95 93

Study Officials

• Bryan Olin

  Cyberonics, Inc.

  STUDY DIRECTOR

• Paul Boon

  University Ghent

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2011
• First Posted: March 30, 2011
• Study Start: March 1, 2011
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2015
• Last Updated: January 22, 2016
• Results First Posted: January 22, 2016

Record last verified: 2015-12

Locations

GB (3); BE (3); NL (1); NO (1); DE (6)