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

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.

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.

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.

Inclusion Criteria:

1. 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.
2. The patient's present antiepileptic drug (AED) therapy is ineffective or intolerable
3. 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.
4. The patient is having more than 2 recordable seizures a month.

Exclusion Criteria:

1. The patient has had status epilepticus within the last six months.
2. The patient has had epilepsy surgery or a VNS implant.
3. The patient has had a history or presence of seizures occurring only in clusters (too frequently or indistinctly separated to be reliably counted).
4. The patient has had 4 weeks continuous seizure freedom last 2 months.
5. The patient has psychogenic non-epileptic seizures (PNES) seizures.
6. The patient has a concomitant progressive CNS disease including progressive myoclonus epilepsy.
7. 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.
8. 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.