Non-invasive Neurostimulation of the Vagus Nerve for the Treatment of Cluster Headache

Multi-center, prospective, double-blind, randomized, sham-controlled pivotal study of non-invasive vagus nerve stimulation with the GammaCore® device for the acute treatment of cluster headache. The study compares the safety and effectiveness of an active treatment (GammaCore) against a sham treatment.

Phase 1: Prospective, randomized (1:1 active treatment:sham control allocation), double blinded, sham controlled treatment (active or sham) phase

Phase 2: Prospective, non-randomized, active treatment phase.

Phase 1 - Two Arms:

1. Active Treatment with the GammaCore Device
2. Sham Treatment with a placebo device

Phase 2 - One Arm:

Active Treatment with the GammaCore Device

Eligibility Criteria:
Inclusion Criteria:

1. Is between the ages of 18 and 75 years.
2. Has been diagnosed with cluster headache, in accordance with the ICHD-2

   Classification criteria (2ndEd):

   o At least 5 attacks fulfilling the following criteria:
   * Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes if untreated
   * Headache is accompanied by at least 1 of the following:
   * Ipsilateral conjunctival injection and/or lacrimation
   * Ipsilateral nasal congestion and/or rhinorrhea
   * Ipsilateral eyelid edema
   * Ipsilateral forehead and facial sweating
   * Ipsilateral miosis and/or ptosis
   * A sense of restlessness or agitation
3. currently experiencing cluster headaches, and from clinical history is expected to continue experiencing cluster headaches for a period of at least 4 weeks.
4. able to distinguish CH from other headaches (i.e. migraine, tension-type headaches).
5. capable of completing headache pain self-assessments.
6. \[Intentionally left blank\].
7. Agrees to use the GammaCore device as intended and follow all of the requirements of the study, including follow-up visit requirements.
8. Agrees to record usage of the GammaCore device, all required study data, and report any adverse device effects to the study center within 24 hours of any such adverse device effects.
9. able to provide written Informed Consent

Exclusion Criteria:

1. had surgery to treat cluster headache.
2. currently taking prophylactic medication (including chronic opioids and non-prescribed street drugs) for indications other than CH that in the opinion of the clinician may interfere with the study.
3. \[Intentionally left blank\].
4. undergone botulinum toxin injections in the head and/or neck in the last 3 months or nerve blocks (occipital or other) in the head or neck in the last month.
5. history of aneurysm, intracranial hemorrhage, brain tumors or significant head trauma.
6. lesion (including lymphadenopathy), dysaesthesia, previous surgery or abnormal anatomy at the treatment site.
7. structural intracranial, or cervical vascular lesions that may potentially cause headache attacks.
8. other significant pain problem (including cancer pain, fibromyalgia, and trigeminal neuralgia/TAC-cluster) that might confound the study assessments.
9. 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.
10. history of prolonged QT interval or a history of clinically significant arrhythmia.
11. 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).
12. previous bilateral or right cervical vagotomy.
13. uncontrolled high blood pressure.
14. 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.
15. history of carotid endarterectomy or vascular neck surgery on the right side.
16. implanted with metal cervical spine hardware or has a metallic implant near the GammaCore stimulation site.
17. recent or repeated history of syncope.
18. recent or repeated history of seizure.
19. known history or suspicion of substance abuse or addiction, or overuse of acute headache medication for headaches other than CH.
20. psychiatric or cognitive disorder and/or behavioral problems which in the opinion of the clinician may interfere with the study.
21. pregnant, nursing, thinking of becoming pregnant in the next 4 months, or of childbearing years and is unwilling to use an accepted form of birth control.
22. participating in any other therapeutic clinical investigation or has participated in a clinical trial in the preceding 30 days.
23. Belongs to a vulnerable population or has any condition such that his or her ability to provide informed consent, comply with follow-up requirements, or provide self-assessments is compromised