Neurostimulation to the Vagus Nerve for the Reduction in Frequency of Seizures Associated With Epilepsy

Study Overview
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Brief Summary
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The purpose of this study is to see the effects of non-invasive vagal nerve stimulation for the reduction in frequency of seizure associated with epilepsy in subjects 18 or older.

Detailed Description
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The purpose of the study is to determine the effects of non-invasive vagus nerve stimulation for the reduction in frequency of seizure associated with epilepsy in subjects 18 or older. Subjects will record 4 weeks of baseline seizure activity before being randomized for a period of 8 weeks to receive and active treatment to an active-sham treatment. All subjects will then receive another 8 weeks of active treatment.

Official Title
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A Randomized, Multi-center, Double-blind, Parallel, Crossover Study of a Non-invasive Neurostimulation to the Vagus Nerve With the gammaCore Device for the Reduction in Frequency of Seizures Associated With Epilepsy.

Conditions
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Seizure

Intervention / Treatment
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* Device: gammaCore


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient is diagnosed with epilepsy with; primary generalized tonic-clonic or partial complex or simple complex or focal onset seizures, with or without secondary generalization. The patient's present antiepileptic drug (AED) therapy is ineffective or intolerable The patient is receiving a stable dose of up to 2 oral AED medication(s) and is not expected to have any change in his/her baseline AED treatment during the treatment period. The patient is having more than 2 recordable seizures a month. Exclusion Criteria: The patient has had status epilepticus within the last six months. The patient has had epilepsy surgery or a VNS implant. The patient has had a history or presence of seizures occurring only in clusters (too frequently or indistinctly separated to be reliably counted). The patient has had 4 weeks continuous seizure freedom last 2 months. The patient has psychogenic non-epileptic seizures (PNES) seizures. The patient has a concomitant progressive CNS disease including progressive myoclonus epilepsy. The patient has a significant history of cardiac, renal, neurologic (other than epilepsy), psychiatric, oncologic, endocrinologic, metabolic, or hepatic disease, which would adversely affect their participation in this study. The patient has had an episode of status epilepticus within 4 weeks of Screening. 10. Has a lesion (including lymphadenopathy), dysaesthesia, previous surgery or abnormal anatomy at the GammaCore treatment site. 11. Has known or suspected severe atherosclerotic cardiovascular disease, severe carotid artery disease (e.g. bruits or history of TIA or CVA), congestive heart failure (CHF), known severe coronary artery disease or recent myocardial infarction. 12. Has an abnormal baseline ECG (e.g. second and third degree heart block, atrial fibrillation, atrial flutter, recent history of ventricular tachycardia or ventricular fibrillation, or clinically significant premature ventricular contraction). 13. Has had a previous bilateral, right, or left cervical vagotomy. 14. Has uncontrolled high blood pressure. 15. Is currently implanted with an electrical and/or neurostimulator device, including but not limited to cardiac pacemaker or defibrillator, vagal neurostimulator, deep brain stimulator, spinal stimulator, bone growth stimulator, or cochlear implant. 16. Has a history of carotid endarterectomy or vascular neck surgery on the right side. 17. Has been implanted with metal cervical spine hardware or has a metallic implant near the GammaCore stimulation site. 18. Has a recent or repeated history of syncope. 19. Has a known history or suspicion of substance abuse or addiction. 20. In the opinion of the investigator/research staff the subject is incapable of operating the GammaCore device as intended and performing the data collection procedures. 21. Is pregnant, nursing, thinking of becoming pregnant in the next 9 months, or of childbearing years and is unwilling to use an accepted form of birth control.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: gammaCore<br>Active stimulation treatment | Device: gammaCore<br>* vagal verve stimulation 3 times a day 8 hours apart<br>|
| Placebo Comparator: sham gammaCore<br>Inactive stimulation treatment | Device: gammaCore<br>* vagal verve stimulation 3 times a day 8 hours apart<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Seizures | The seizure frequency was collected in the subject diary throughout Intervention 1/Phase 2 (8 weeks) and Intervention 2/Phase 3 (8 weeks). | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Seizure | Duration of seizure was recorded by the subject in the subject diary throughout Intervention 1/Phase 2 (8 weeks) and Intervention 2/Phase 3 (8 weeks). | 16 weeks | 
| Severity of Seizure | The Seizure Severity Questionnaire (SSQ) is a self-reported assessment tool, which categorizes seizures into three phases: warning, ictal activity and postictal recovery. The recovery phase is subdivided into three components (cognitive, emotional and physical aspects of recovery), each of which is rated for frequency, severity and bothersome. Overall assessment of seizure severity is measured with the last two items. Items are positively scored from a scale of 1-7, with lower scores representing a better status. 1 = none, never or mild and 7 = extremely frequent, severe or high. The severity was reported for seizures occuring throughout Intervention 1/Phase 2 (8 weeks) and Intervention 2/Phase 3 (8 weeks). | 16 weeks | 
| Type of Adverse Events | Type of adverse events were split in to Adverse Events, Adverse Device Effects and Serious Adverse Events. Adverse events were reported throughout Intervention 1/Phase 2 (8 weeks) and Intervention 2/Phase 3 (8 weeks). For frequency see the Adverse Event Table. | 16 weeks | 
| Number of Seizure Free Days | The number of seizure-free days was collected from the subjects' diary. The total number of days observed days for each phase and the total number of seizure free days for each phase are presented for the course of the study throughout Intervention 1/Phase 2 (8 weeks) and Intervention 2/Phase 3 (8 weeks). | 16 weeks | 
| Quality of Life in Epilepsy | The Quality of Life in Epilepsy-31 (QOLIE-31) instrument is a self- administered questionnaire. It includes seven subscales: Overall Quality of Life, Seizure Worry, Emotional Well-Being, Energy/Fatigue, Cognitive, Medication Effects, and Social Function. Questions 1-30 can yield seven individual scores (per subtest) and a total (composite) score. Higher scores indicate better QOL with values ranging from 1 to 100. Question 31 is a subjective assessment of one's general health condition.Higher scores indicate a better-reported general health condition with the range being 1-10. Scores are presented at end of Intervention 1/Phase 2 (8 weeks) and at the end of Intervention 2/Phase 3 (8 weeks). | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vagus nerve stimulation, vagal nerve stimulation, nVNS, VNS, epilepsy, non invasive, gammacore