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

Study Overview
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Brief Summary
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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.

Detailed Description
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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: Active Treatment with the GammaCore Device Sham Treatment with a placebo device Phase 2 - One Arm: Active Treatment with the GammaCore Device

Official Title
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Non-invasive Neurostimulation of the Vagus Nerve With the GammaCore Device for the Treatment of Cluster Headache

Conditions
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Cluster Headache

Intervention / Treatment
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* Device: GammaCore
* Device: Sham GammaCore device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is between the ages of 18 and 75 years. 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 currently experiencing cluster headaches, and from clinical history is expected to continue experiencing cluster headaches for a period of at least 4 weeks. able to distinguish CH from other headaches (i.e. migraine, tension-type headaches). capable of completing headache pain self-assessments. [Intentionally left blank]. Agrees to use the GammaCore device as intended and follow all of the requirements of the study, including follow-up visit requirements. 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. able to provide written Informed Consent Exclusion Criteria: had surgery to treat cluster headache. 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. [Intentionally left blank]. 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. history of aneurysm, intracranial hemorrhage, brain tumors or significant head trauma. lesion (including lymphadenopathy), dysaesthesia, previous surgery or abnormal anatomy at the treatment site. structural intracranial, or cervical vascular lesions that may potentially cause headache attacks. other significant pain problem (including cancer pain, fibromyalgia, and trigeminal neuralgia/TAC-cluster) that might confound the study assessments. 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. history of prolonged QT interval or a history of clinically significant arrhythmia. 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). previous bilateral or right cervical vagotomy. uncontrolled high blood pressure. 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. history of carotid endarterectomy or vascular neck surgery on the right side. implanted with metal cervical spine hardware or has a metallic implant near the GammaCore stimulation site. recent or repeated history of syncope. recent or repeated history of seizure. known history or suspicion of substance abuse or addiction, or overuse of acute headache medication for headaches other than CH. psychiatric or cognitive disorder and/or behavioral problems which in the opinion of the clinician may interfere with the study. 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. participating in any other therapeutic clinical investigation or has participated in a clinical trial in the preceding 30 days. 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Sham GammaCore device<br>The Sham GammaCore device looks and operates like the Active GammaCore device, but does not deliver a therapeutic stimulation treatment. | Device: Sham GammaCore device<br>* Treatment with sham stimulator<br>|
| Experimental: GammaCore Device<br>Non-Invasive Vagus Nerve Stimulator | Device: GammaCore<br>* Treatment with active gammacore vagus nerve stimulator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Repsonse to Treatment | The primary outcome measurement for effectiveness is the rate of responders for the active treatment group, compared to the sham control group. A responder is defined as a subject who has recorded an intensity of 0 or 1 on the 5-point headache pain scale (no pain, mild, moderate, severe, very severe) at 15 minutes post-initiation of treatment of the first treated cluster headache attack of Phase 1. | 15 minutes post stimulation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Treatment Success at 1 Hour Post-Treatment | Sustained treatment success at 1 hour post-treatment was defined as having recorded an intensity of 0 or 1 on the 5-point headache pain scale at 15 minutes and 1 hour post-initiation of treatment of the first treated cluster headache attack of Phase 1, and having refrained from use of rescue medications during the full 60 minute period | For 1 hour post stimulation | 
| Average Mean Attack Intensities Experienced Per Subject | Cluster headache attack intensity was reported on a 5-point scale: no pain, mild, moderate, severe, very severe, whereas no pain =1 is the best outcome and very severe=5 is the worst outcome . The average of all subjects' mean attack intensities experienced at 15 minutes post-initiation of treatment during Phase 1 for the active treatment group, compared to the sham control group. The mean 15-minute scores were calculated for the first five attacks suffered by each subject during Phase 1. For subjects with fewer than five treated attacks, the scores for those available were averaged. | 15 minutes post-stimulation | 
| Incidence and Occurrence of Serious Adverse Events Related to Active or Sham Study Treatment and / or to Cluster Headache Events. | The primary safety measure for this study is the incidence and occurrence of serious adverse events related to active or sham study treatment and / or to cluster headache events during Phase 1 of the study. | 4 weeks, Phase 1 | 

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