Clinical trial NCT03716505: 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
Overall status: COMPLETED
Phase: NA
Conditions: Migraine Disorders
Keywords: Prevention
Episodic
Chronic
Lead sponsor: ElectroCore INC
Sponsor class: INDUSTRY
First posted: 2018-10-23
Enrollment: 231
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two parallel groups, gammaCore®-Sapphire (active treatment) and a sham (inactive) treatment.
Primary purpose: PREVENTION

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.

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

Primary outcomes:
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.
timeFrame: 12 weeks
Secondary outcomes:
measure: Responder rate in the nVNS group compared to the sham group
timeFrame: Last 4 weeks of the 12 week double-blind
measure: Mean reduction in the number of headache days
timeFrame: Last 4 weeks of the 12 week double-blind
measure: Mean reduction in days on which acute migraine medication
timeFrame: Last 4 weeks of the 12 week double-blind
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Carlsbad
country: United States
facility: The Research Center of Southern California
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center Hoover Pavilion
state: California
city: San Francisco
country: United States
facility: UCSF Headache Center
state: California
city: Santa Monica
country: United States
facility: California Medical Clinic for Headache
state: California
city: Englewood
country: United States
facility: Summit Headache and Neurologic Institute, PC
state: Colorado
city: Stamford
country: United States
facility: New England Institute for Neurology and Headache
state: Connecticut
city: West Hartford
country: United States
facility: Hartford HealthCare Headache Center
state: Connecticut
city: Miami
country: United States
facility: University of Miami, Miller School of Medicine
state: Florida
city: Chicago
country: United States
facility: Diamond Headache Clinic
state: Illinois
city: Glenview
country: United States
facility: NorthShore Ambulatory Care Center
state: Illinois
city: Louisville
country: United States
facility: Norton Neurology
state: Kentucky
city: Chalmette
country: United States
facility: Crescent City Headache and Neurology Center
state: Louisiana
city: Covington
country: United States
facility: Ochsner North Shore Medical Center
state: Louisiana
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Head Pain & Neurological Institute (MHNI)
state: Michigan
city: Ridgeland
country: United States
facility: Headache Neurology Research Institute
state: Mississippi
city: Saint Peters
country: United States
facility: StudyMetrix, LLC
state: Missouri
city: Springfield
country: United States
facility: Clinvest Research
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Amherst
country: United States
facility: Dent Neurologic Institute
state: New York
city: Bronx
country: United States
facility: Montefiore Headache Center
state: New York
city: New York
country: United States
facility: NY Neurology Associates
state: New York
city: Plainview
country: United States
facility: Island Neurological Associates
state: New York
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Waxahachie
country: United States
facility: ClinPoint Trials LLC
state: Texas
city: McLean
country: United States
facility: Medstar Georgetown University Hospital
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University Hospitals - Department of Neurology
state: West Virginia
Study officials:
affiliation: Chief Medical Officer
name: Peter Staats, MD
role: STUDY_DIRECTOR
References:
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.