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Non-invasive Vagus Nerve Stimulation for the Prevention of Migraines

Primary Purpose

Migraine Disorders

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
gammaCore Sapphire active
gammaCore Sapphire Sham
Sponsored by
ElectroCore INC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Migraine Disorders focused on measuring Prevention, Episodic, Chronic

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic
  • The Research Center of Southern California
  • Stanford University Medical Center Hoover Pavilion
  • UCSF Headache Center
  • California Medical Clinic for Headache
  • Summit Headache and Neurologic Institute, PC
  • New England Institute for Neurology and Headache
  • Hartford HealthCare Headache Center
  • University of Miami, Miller School of Medicine
  • Diamond Headache Clinic
  • NorthShore Ambulatory Care Center
  • Norton Neurology
  • Crescent City Headache and Neurology Center
  • Ochsner North Shore Medical Center
  • Beth Israel Deaconess Medical Center
  • Michigan Head Pain & Neurological Institute (MHNI)
  • Headache Neurology Research Institute
  • StudyMetrix, LLC
  • Clinvest Research
  • Dartmouth-Hitchcock Medical Center
  • Dent Neurologic Institute
  • Montefiore Headache Center
  • NY Neurology Associates
  • Island Neurological Associates
  • University Hospitals of Cleveland
  • Thomas Jefferson University
  • University of Texas Southwestern Medical Center
  • ClinPoint Trials LLC
  • Medstar Georgetown University Hospital
  • West Virginia University Hospitals - Department of Neurology

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

gammaCore Sapphire active

gammaCore Sapphire Sham

Arm Description

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

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

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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
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
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

Full Information

First Posted
October 10, 2018
Last Updated
September 10, 2020
Sponsor
ElectroCore INC
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1. Study Identification

Unique Protocol Identification Number
NCT03716505
Brief Title
Non-invasive Vagus Nerve Stimulation for the Prevention of Migraines
Official Title
A Randomized, Multicenter, Double-blind, Parallel, Sham-controlled Study of Non-invasive Vagus Nerve Stimulation for the Prevention of Migraines. (Premium II)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
November 2, 2018 (Actual)
Primary Completion Date
September 9, 2020 (Actual)
Study Completion Date
September 9, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ElectroCore INC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Migraine Disorders
Keywords
Prevention, Episodic, Chronic

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Two parallel groups, gammaCore®-Sapphire (active treatment) and a sham (inactive) treatment.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Two parallel groups, gammaCore®-Sapphire (active treatment) and a gammaCore®-Sapphire sham (inactive) treatment.
Allocation
Randomized
Enrollment
231 (Actual)

8. Arms, Groups, and Interventions

Arm Title
gammaCore Sapphire active
Arm Type
Active Comparator
Arm Description
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
Arm Title
gammaCore Sapphire Sham
Arm Type
Sham Comparator
Arm Description
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
Intervention Type
Device
Intervention Name(s)
gammaCore Sapphire active
Intervention Description
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).
Intervention Type
Device
Intervention Name(s)
gammaCore Sapphire Sham
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Description
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).
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Responder rate in the nVNS group compared to the sham group
Description
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
Time Frame
Last 4 weeks of the 12 week double-blind
Title
Mean reduction in the number of headache days
Description
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
Time Frame
Last 4 weeks of the 12 week double-blind
Title
Mean reduction in days on which acute migraine medication
Description
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
Time Frame
Last 4 weeks of the 12 week double-blind

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Staats, MD
Organizational Affiliation
Chief Medical Officer
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
The Research Center of Southern California
City
Carlsbad
State/Province
California
ZIP/Postal Code
92011
Country
United States
Facility Name
Stanford University Medical Center Hoover Pavilion
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
UCSF Headache Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
California Medical Clinic for Headache
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Summit Headache and Neurologic Institute, PC
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
Country
United States
Facility Name
New England Institute for Neurology and Headache
City
Stamford
State/Province
Connecticut
ZIP/Postal Code
06905
Country
United States
Facility Name
Hartford HealthCare Headache Center
City
West Hartford
State/Province
Connecticut
ZIP/Postal Code
06107
Country
United States
Facility Name
University of Miami, Miller School of Medicine
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Diamond Headache Clinic
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60642
Country
United States
Facility Name
NorthShore Ambulatory Care Center
City
Glenview
State/Province
Illinois
ZIP/Postal Code
60026
Country
United States
Facility Name
Norton Neurology
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Facility Name
Crescent City Headache and Neurology Center
City
Chalmette
State/Province
Louisiana
ZIP/Postal Code
70043
Country
United States
Facility Name
Ochsner North Shore Medical Center
City
Covington
State/Province
Louisiana
ZIP/Postal Code
70433
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215-5400
Country
United States
Facility Name
Michigan Head Pain & Neurological Institute (MHNI)
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48104
Country
United States
Facility Name
Headache Neurology Research Institute
City
Ridgeland
State/Province
Mississippi
ZIP/Postal Code
39157
Country
United States
Facility Name
StudyMetrix, LLC
City
Saint Peters
State/Province
Missouri
ZIP/Postal Code
63303
Country
United States
Facility Name
Clinvest Research
City
Springfield
State/Province
Missouri
ZIP/Postal Code
65810
Country
United States
Facility Name
Dartmouth-Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03766
Country
United States
Facility Name
Dent Neurologic Institute
City
Amherst
State/Province
New York
ZIP/Postal Code
14226
Country
United States
Facility Name
Montefiore Headache Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
NY Neurology Associates
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Island Neurological Associates
City
Plainview
State/Province
New York
ZIP/Postal Code
11803
Country
United States
Facility Name
University Hospitals of Cleveland
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
ClinPoint Trials LLC
City
Waxahachie
State/Province
Texas
ZIP/Postal Code
75165
Country
United States
Facility Name
Medstar Georgetown University Hospital
City
McLean
State/Province
Virginia
ZIP/Postal Code
22101
Country
United States
Facility Name
West Virginia University Hospitals - Department of Neurology
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35001643
Citation
Najib U, Smith T, Hindiyeh N, Saper J, Nye B, Ashina S, McClure CK, Marmura MJ, Chase S, Liebler E, Lipton RB. Non-invasive vagus nerve stimulation for prevention of migraine: The multicenter, randomized, double-blind, sham-controlled PREMIUM II trial. Cephalalgia. 2022 Jun;42(7):560-569. doi: 10.1177/03331024211068813. Epub 2022 Jan 9.
Results Reference
derived

Learn more about this trial

Non-invasive Vagus Nerve Stimulation for the Prevention of Migraines

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