Migraine DisordersNCT03716505
Non-invasive Vagus Nerve Stimulation for the Prevention of Migraines
A study testing gammaCore Sapphire active in people with Migraine Disorders, run by ElectroCore INC at 30 sites in United States.
Trial summary
The purpose of the study is to investigate if the use of gammaCore Sapphire™ device reduces the number of migraines preventatively. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Migraine Disorders
- What is being tested?
- gammaCore Sapphire active
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 231 participants
- Where
- 30 sitesUnited States
- Study dates
- 2 Nov 2018to 9 Sep 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
30 sites in 1 country.
30 sites in 1 country
United States30 sites
Dent Neurologic Institute
Amherst, New York, 14226
Michigan Head Pain & Neurological Institute (MHNI)
Ann Arbor, Michigan, 48104
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215-5400
The Research Center of Southern California
Carlsbad, California, 92011
Crescent City Headache and Neurology Center
Chalmette, Louisiana, 70043
Diamond Headache Clinic
Chicago, Illinois, 60642
StudyMetrix, LLC
City of Saint Peters, Missouri, 63303
University Hospitals of Cleveland
Cleveland, Ohio, 44106
Ochsner North Shore Medical Center
Covington, Louisiana, 70433
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Summit Headache and Neurologic Institute, PC
Englewood, Colorado, 80113
NorthShore Ambulatory Care Center
Glenview, Illinois, 60026
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03766
Norton Neurology
Louisville, Kentucky, 40207
Medstar Georgetown University Hospital
McLean, Virginia, 22101
University of Miami, Miller School of Medicine
Miami, Florida, 33136
West Virginia University Hospitals - Department of Neurology
Morgantown, West Virginia, 26506
NY Neurology Associates
New York, New York, 10003
Stanford University Medical Center Hoover Pavilion
Palo Alto, California, 94304
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Island Neurological Associates
Plainview, New York, 11803
Headache Neurology Research Institute
Ridgeland, Mississippi, 39157
UCSF Headache Center
San Francisco, California, 94115
California Medical Clinic for Headache
Santa Monica, California, 90404
Mayo Clinic
Scottsdale, Arizona, 85259
Clinvest Research
Springfield, Missouri, 65810
New England Institute for Neurology and Headache
Stamford, Connecticut, 06905
Montefiore Headache Center
The Bronx, New York, 10461
ClinPoint Trials LLC
Waxahachie, Texas, 75165
Hartford HealthCare Headache Center
West Hartford, Connecticut, 06107
About this study
Official title: A Randomized, Multicenter, Double-blind, Parallel, Sham-controlled Study of Non-invasive Vagus Nerve Stimulation for the Prevention of Migraines. (Premium II)
The purpose of the study is to investigate if the use of gammaCore Sapphire™ device reduces the number of migraines preventatively.
Read the 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.
- Conditions
- Migraine Disorders
- Being tested
- gammaCore Sapphire active, gammaCore Sapphire Sham
- Keywords
- Prevention, Episodic, Chronic
- Medical subject headings
- Migraine Disorders, Recurrence, Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gammaCore Sapphire activeDevice
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).
gammaCore Sapphire ShamDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| gammaCore Sapphire active | Active comparator | 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 Receives: Device: gammaCore Sapphire active |
| gammaCore Sapphire Sham | Sham comparator | 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 Receives: Device: gammaCore Sapphire Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 12 weeks
Secondary outcomes (3)
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
Measured: 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
Measured: 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
Measured: Last 4 weeks of the 12 week double-blind
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2018
- Study start2 Nov 2018
- Primary completion9 Sep 2020
- Study completion9 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Migraine DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two parallel groups, gammaCore®-Sapphire (active treatment) and a sham (inactive) treatment.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 231 participants (actual)
Sponsor and investigators
- Lead sponsor
- ElectroCore INC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Peter Staats, MD, Study director, Chief Medical Officer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03716505
- Sponsor's protocol ID
- GM-US-10
- Status last verified
- Sep 2020
- First submitted
- 10 Oct 2018
- Last updated
- 11 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 35001643
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Multicenter, Double-blind, Parallel, Sham-controlled Study of Non-invasive Vagus Nerve Stimulation for the Prevention of Migraines. (Premium II)
- ClinicalTrials.gov ID
- NCT03716505
- Acronym / sponsor ID
- GM-US-10
- Conditions
- Migraine Disorders
- Keywords
- Prevention, Episodic, Chronic
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 231 participants (actual)
- Lead sponsor
- ElectroCore INCIndustry (pharma, biotech, devices)
- Study start
- 2 Nov 2018 (actual)
- Primary completion
- 9 Sep 2020 (actual)
- Study completion
- 9 Sep 2020 (actual)
- First posted
- 23 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Two parallel groups, gammaCore®-Sapphire (active treatment) and a sham (inactive) treatment.
| Arm | Type | Receives |
|---|---|---|
| gammaCore Sapphire active | Active comparator | Device: gammaCore Sapphire activeTreatment 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 |
| gammaCore Sapphire Sham | Sham comparator | Device: gammaCore Sapphire ShamTreatment 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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 (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| gammaCore Sapphire activeGammaCore 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). | Device | gammaCore Sapphire active |
| gammaCore Sapphire ShamThe 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. | Device | gammaCore Sapphire Sham |
Primary outcome
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.
Time frame: 12 weeks
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).
3 secondary outcomes
Responder rate in the nVNS group compared to the sham group
Time frame: Last 4 weeks of the 12 week double-blind
Mean reduction in the number of headache days
Time frame: Last 4 weeks of the 12 week double-blind
Mean reduction in days on which acute migraine medication
Time frame: Last 4 weeks of the 12 week double-blind
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2020.
- Derived from this study: PubMed 35001643Najib 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Staats, MD study director
Chief Medical Officer
30 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing gammaCore Sapphire active in people with Migraine Disorders, run by ElectroCore INC at 30 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03716505, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2020.