Non-invasive Vagus Nerve Stimulation for the Prevention of Migraines

Study Overview
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Brief Summary
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The purpose of the study is to investigate if the use of gammaCore Sapphire™ device reduces the number of migraines preventatively.

Detailed Description
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The study is a prospective randomized, multi-center, double-blind, parallel, sham-controlled study, designed for comparison of two parallel groups, gammaCore®-Sapphire (active treatment) and a sham (inactive) treatment. The study period will begin with a four-week run-in period, during which there is no investigational treatment. The purpose of the run-in period will be to establish a baseline of the subject's headache/migraine history for longitudinal comparison. The run-in period will be followed by a 12-week randomized period when the subjects will be randomized (1:1) to either active treatment or sham (inactive) treatment. Subjects will dose themselves 3 times per day for 12 weeks.

Official Title
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A Randomized, Multicenter, Double-blind, Parallel, Sham-controlled Study of Non-invasive Vagus Nerve Stimulation for the Prevention of Migraines. (Premium II)

Conditions
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Migraine Disorders

Intervention / Treatment
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* Device: gammaCore Sapphire active
* Device: gammaCore Sapphire Sham


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Between the ages of 18 and 75 years Been previously diagnosed with migraine (with or without aura), in accordance with the ICHD-3 criteria Experiences between 8 to 20 headaches days per month (during the last 3 months), with at least 5 of them being migraine days Onset of migraine at age 50 years or younger Agrees to refrain from initiating or changing any prophylactic medications for indications other than migraine Key Exclusion Criteria: Concomitant medical condition that will require oral or injectable steroids during the study Currently on a stable regime of more than 1 migraine preventative therapy Other significant pain problem (e.g., cancer pain, fibromyalgia, other head or facial pain disorder) Known or suspected severe cardiac disease (e.g., symptomatic coronary artery disease, prior myocardial infarction, congestive heart failure) Known or suspected cerebrovascular disease Previous cervical vagotomy Currently implanted with an electrical and/or neurostimulator device Been implanted with metal cervical spine hardware or has a metallic implant near the nVNS stimulation site Known history or suspicion of secondary headache Currently using marijuana (including medical marijuana) or has used marijuana (including medical marijuana) or cannabidiol oil within the last 6 months Currently takes simple analgesics or NSAIDs >15 days per month or triptans, ergots, or combined analgesics >10 days per month for headaches or other body pain Currently takes prescription opioids more than 2 days per month for headaches or body pain Failed an adequate trial (2 months or greater) of at least 3 classes of a drug therapy for migraine prevention Surgery for migraine prevention Undergone nerve block (occipital or other) in the head or neck within the last 3 months Received Botox or CGRP mAb injections within the last 6 months Pregnant or thinking of becoming pregnant during the study period, or of childbearing years and unwilling to use an accepted form of birth control Previously used gammaCore

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two parallel groups, gammaCore®-Sapphire (active treatment) and a sham (inactive) treatment.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: gammaCore Sapphire active<br>Treatment 3 times per day, every day for the 12-week treatment period Each of the 3 daily treatments comprises 2 consecutive 120-second stimulations on 1 side, ipsilateral (2 stimulations) to the side of predominate pain, upon waking, lunch time (i.e., between 11:00 AM and 2:00 PM), and prior to sleep, for a total of 6 stimulations per day | Device: gammaCore Sapphire active<br>* GammaCore Sapphire™ is a handheld, non-invasive, low voltage electrical device which stimulates the vagus nerve by producing weak 120 second electrical stimulation cycles that may help reduce, ease, lessen or stop your migraine symptoms. GammaCore Sapphire™ has been approved for the treatment of headache, including migraine by the United States Food and Drug Administration (FDA).<br>|
| Sham Comparator: gammaCore Sapphire Sham<br>Treatment 3 times per day, every day for the 12-week treatment period Each of the 3 daily treatments comprises 2 consecutive 120-second stimulations on 1 side, ipsilateral (2 stimulations) to the side of predominate pain, upon waking, lunch time (i.e., between 11:00 AM and 2:00 PM), and prior to sleep, for a total of 6 stimulations per day | Device: gammaCore Sapphire Sham<br>* The sham device is a hand-held portable device that appears identical to gammaCore Sapphire, in look, weight, visual and audible feedback, user application, and control. Like gammaCore Sapphire, the sham device is a multi-use device.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and effectiveness of gammaCore Sapphire as a treatment for the prevention of a migraine during the double-blind period measured by Incidence of Unexpected Adverse Events. | The primary outcome measurement for effectiveness is the difference between the active and sham treatment groups in the mean reduction in number of migraine days during the last 4 weeks of the 12-week double-blind period (versus during the 4-week run-in period). | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder rate in the nVNS group compared to the sham group | A subject who reports at least a 50% decrease in the number of migraine days during the last 4 weeks in the 12-week double-blind period | Last 4 weeks of the 12 week double-blind | 
| Mean reduction in the number of headache days | Difference between the nVNS and sham treatment groups in mean reduction in the number of headache days during the last 4 weeks of the 12-week double-blind period | Last 4 weeks of the 12 week double-blind | 
| Mean reduction in days on which acute migraine medication | Difference between the nVNS and sham treatment groups in the mean reduction in days on which acute migraine medication was taken during the last 4 weeks of the 12 week double-blind period | Last 4 weeks of the 12 week double-blind | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prevention, Episodic, Chronic