Non-Invasive Neurostimulation for the Prevention of Chronic Migraine

Study Overview
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Brief Summary
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The purpose of this multi-center, prospective, double-blind, randomized, sham-controlled pilot study is to study feasibility and collect preliminary clinical data related to the safety and clinical benefits of daily use of non-invasive vagal nerve stimulation with the GammaCore device for the prevention of chronic migraine, and to support the development and approval of a larger pivotal study.

Official Title
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Non-Invasive Neurostimulation of the Vagus Nerve With the GammaCore Device for the Prevention of Chronic Migraine

Conditions
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Chronic Migraine

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is between the ages of 18 and 65 years. Has been previously diagnosed as suffering from migraine, in accordance with the ICHD-2 Classification criteria (2nd), with or without aura. Experiences at least 15 headache days per month (over the last 3 months). Has age of onset of migraine less than 50 years old. Agrees not to use any migraine prevention treatments (including Botox injections) and/or medications (exclusive of medications taken for acute relief of migraine symptoms). Is able to provide written Informed Consent Agrees to refrain from changing the type or dosage of any prophylactic medications for indications other than chronic migraine that in the opinion of the clinician may interfere with the study Exclusion Criteria: Has a history of aneurysm, intracranial hemorrhage, brain tumors or significant head trauma. Has a lesion (including lymphadenopathy), dysaesthesia, previous surgery or abnormal anatomy at the GammaCore treatment site. 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. 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) Has had a previous bilateral, right, or left cervical vagotomy. Has uncontrolled high blood pressure. 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. Has a history of carotid endarterectomy or vascular neck surgery on the right side. Has been implanted with metal cervical spine hardware or has a metallic implant near the GammaCore stimulation site. Has a recent or repeated history of syncope. Has a recent or repeated history of seizure. Has a known history or suspicion of substance abuse or addiction. Has had a surgery for migraine prevention. Has received Botox injections for migraine prevention within the past 6 months. Has taken medications for migraine prophylaxis in the previous 30 days. 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. 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. Is 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 (e.g., homeless, developmentally disabled, prisoner). Is a relative of or an employee of the investigator or the clinical study site.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GammaCore Active Device<br>Subjects will use an Active GammaCore Device | Device: GammaCore Active Device<br> <br> |
| Sham Comparator: GammaCore Sham Device<br>Subjects who treat with the gammacore sham device in Phase 2 will receive the active gammacore treatment during phase 3 (active treatment) of this study. | Device: GammaCore Active Device<br> <br> Device: GammaCore Sham Device<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety - Number of Participants With Adverse Events | Safety was assessed by collecting Adverse Effects | Up to 8 weeks - duration of the Randomized period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Headache Days | Mean change in headache days. Change between 4 week run in period to the 8 weeks randomized period. | Run-in period (4 weeks no treatment) and Randomized period (8 weeks) | 
| Total Number of Headache Days Per Arm With Peak Severity of Mild, Moderate, or Severe | Peak severity per headache day was reported each headache day in the subject diary. Pain was reported as mild, moderate or severe. Whereas as mild = least severe and severe = most severe. | Run-in (4 weeks no treatment) and Randomized (8 weeks) | 
| Use of Pain Relief Medication | All abortive headache medication taken during randomized period | Randomized period - 8 weeks | 
| Mean Change in Quality of Life Short Form Survey (SF-12) | The Quality of Life Short Form Survey (SF-12) is a multipurpose short form survey with 12 questions that are combined, scored and weighted to create two scales that provide glimpses into mental and physical functioning and overall health-related-quality of life. The SF-12 is weighted and summed to provide easily interpretable scales for physical and mental health. Physical and Mental Health Composite Scores (PCS & MCS) are computed using the scores of the twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. SF-12 were recorded in the subject diary at the Phase 1 follow-up visit (week 4) and during Phase 2 randomized period at week 4 and week 8. | Run-in (4 weeks) and Randomized period (8 weeks) | 

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