A Randomized, Multicenter, Study for the prEvention and Acute Treatment of Migraine (REAL) (REAL)

GM-18 - A Randomized, Multicenter, Study for the prEvention and Acute Treatment of Migraine Using Open Label Non-invasive Vagal Nerve Stimulation, Versus Standard of Care (REAL)

This is a randomized study for the prevention and acute treatment of migraine using open label nVNS and standard of care versus standard of care.

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Study Overview

• Status: Withdrawn
• Conditions: Migraine
• Intervention / Treatment: Device: non-invasive vagus nerve stimulation

Detailed Description

A randomized study for the prevention and acute treatment of migraine using open label nVNS and standard of care versus standard of care.

Eligible subjects will participate in a 4 week run-in period after which they will be randomized (1:1) to either nVNS and standard of care (nVNS group) or standard of care (SOC group) for 12 weeks. The nVNS group will use the nVNS device preventatively and acutely for the treatment of migraine. The SOC group will continue to use their regular standard of care migraine treatment medications for the duration of the 12 week randomized period.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Glostrup, Denmark, DK-2600
    • Danish Headache Center
• Germany
  • Hamburg, Germany, D-20251
    • CTC, University Medical Center Hamburg-Eppendorf
  • Königstein im Taunus, Germany, D-61462
    • Migräne- und Kopfschmerzklinik Königstein
  • München, Germany, D-81377
    • Klinik für Neurologie, Ludwig-Maximilliams-Universität, Klinikum Grosshadern
  • Rostock, Germany, D-18147
    • Klinik und Poliklinik für Neurologie, Universitätsmedizin Rostock
• Italy
  • Milan, Italy, 20133
    • U.O. Neurologia III - Cefalee e Neuroalgologia, Fondazione IRCCS Istituto
  • Rome, Italy, 00163
    • Department of Neurological, Motor and Sensorial Sciences, IRCCS San Raffaele
  • Turin, Italy, 10124
    • University of Turin
  • Pavia
    • Mondino, Pavia, Italy, 27100
      • National Neurological Institute C. Mondino Foundatio
• Spain
  • Barcelona, Spain, 08035
    • Headache Unit, University Hospital Vall d'Hebron
  • Madrid, Spain, 28034
    • Servicio de Neurologia, Hospital Ruber Internacional
  • Pamplona, Spain, ES-31008
    • Servicio de Neurologia, Clinica Universidad de Navarra
  • Valencia, Spain, ES-46010
    • Servicio de Neurologia, Hospital Clinico Universitario de Valencia
• United Kingdom
  • Birmingham, United Kingdom, B15 2TT
    • University of Birmingham
  • Gateshead, United Kingdom, NE9 6SX
    • Queen Elizabeth Hospital Queen
  • Sunderland, United Kingdom, SR4 7TP
    • Sunderland Royal Hospital
  • East Yorkshire
    • Hull, East Yorkshire, United Kingdom, HU3 2JZ
      • Hull Royal Infirmary, Neurology Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Is 18 years of age or above.
• Has been previously diagnosed with episodic or chronic migraine (with or without aura) in accordance with the ICHD-3 Classification criteria.
• Experience at least 6 and no more than 24 headache days per month and a minimum of 4 migraine attacks per month (over the last 3 months).
• Has age of onset of migraine less than 50 years old.
• Stable regime for any migraine preventative medications for the last 3 months and agrees to maintain stable regime for duration of the study.
• Agrees to and in clinician opinion is able to use the nVNS device as intended, follow all of the requirements of the study including follow-up visit requirements, record required study data in the subject dairy, and other self-assessment questionnaires.
• Availability of internet/Web access for Web-based e-diary completion
• Is able to provide written Informed Consent.

Exclusion Criteria:

• Requires use of oral or injectable steroids for concomitant medical condition that in the opinion of the investigator will interfere with the study.
• Has a history of any intracranial aneurysm, intracranial haemorrhage, brain tumour or significant head trauma.
• Has a structural abnormality at the nVNS treatment site (e.g. lymphadenopathy previous surgery or abnormal anatomy).
• Has pain at the nVNS treatment site (e.g. dysesthesia, neuralgia and/or cervicalgia).
• Has other significant pain problem (e.g. cancer pain or other head or facial disorder) that in the opinion of the investigator may confound the study assessments
• Has known or suspected severe cardiac disease (e.g. symptomatic coronay artery disease, prior myocardial infarction, congestive heart failure (CHF)).
• Has known or suspected severe cerebrovascular disease, (e.g. prior stroke or transient ischemic attack, symptomatic carotid artery disease, prior cartoid endarterectomy or other vascular neck surgery).
• Has known or suspected own and/or family history of cardiac disease (including but not limited to ischemic heart disease, rhythm disturbances, congenital abnormalities cardiac myopathies), or presents risk factors strongly associated with risk for developing cardiologic abnormalities that in the opinion of the investigator might compromise subjects safety using n-VNS.
• Has had a cervical vagotomy.
• Has uncontrolled high blood pressure (systolic >160 diastolic > 100 after 3 repeated measurements within 24 hours).
• Is currently implanted with an electrical and/or neurostimulator device (e.g. cardiac pacemaker or defibrillator, vagal neurostimulator, deep brain stimulator, spinal stimulator, bone growth stimulator, cochlear implant, Spehnopalatine ganglion stimulator or Occiptial nerve stimulator).
• Has been implanted with metal cervical spine hardware or has a metallic implant near the nVNS stimulation site (e.g. in the head, neck of thorax).
• Presents a suspicion of secondary headache.
• Previous diagnosis of medication overuse headache within the last 3 months
• Has a history of syncope (within the last 1 year).
• Has a history of seizures (within the last 1 year).
• Has a known or suspicion of substance abuse or addiction (within the last 1 year).
• Has initiated medications for migraine prophylaxis in the previous 30 days, or in the case of Botulinum toxin and monoclonal antibodies against CGRP injections in the previous 90 days.
• Has failed an adequate trial (two months or greater) of at least 3 classes of a drug therapy for the prophylaxis of migraine.
• Is pregnant or of childbearing years and is unwilling to use and accepted form of birth control (condom or contraceptive pill).
• 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 the follow-up requirements, or provide self- assessments is compromised (e.g. homeless, developmentally disabled and prisoner).
• Has previously used the gammaCore device within the last 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: non-invasive Vagus Nerve Stimulation; nVNS (non-invasive vagus nerve stimulation) treatment with the gammaCore Sapphire device and standard of care	Device: non-invasive vagus nerve stimulation; non-invasive vagus nerve stimulation using the gammaCore Sapphire device
No Intervention: Standard of Care; Standard of Care treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in number of migraine days during the last four weeks in the twelve-week randomized period compared with the four-week run-in period	Reduction in number of migraine days during the last four weeks in the twelve-week randomized period compared with the four-week run-in period	The last four weeks in the randomization period compared to the four week run-in period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in number of headache days during the last four-weeks in the twelve-week randomized period compared to the four-week run-in period	Reduction in number of headache days during the last four-weeks in the twelve-week randomized period compared to the four-week run-in period	The last four weeks in the randomization period compared to the four week run-in period.
Reduction in number of migraine days and headache days (separately)	Reduction in number of migraine days and headache days (separately) during weeks 1 through 4, 5 through 8 in the 12 week randomised period	12 week randomised period
Rate of responders for the nVNS group compared to the standard of care group.	Rate of responders (mean reduction in migraine days during the last four weeks in the twelve-week randomization period compared to the four-week run-in period dichotomized as <25% vs. ≥25%, <50% vs ≥50% and <75% vs ≥75%, separately) for the nVNS group compared to the standard of care group.	The last four weeks in the randomization period compared to the four week run-in period.
Acute treatment response for nVNS and standard of care therapies	Acute treatment response for nVNS and standard of care therapies at 30, 60 and 120 minutes post-treatment, for all treated migraine attacks in the twelve-week randomized period	12 week randomised period
Consistency of response	Consistency of response as defined as the percentage of subjects who achieve treatment response in 25%, 50% and 75% or greater of their attacks, in subjects treating at least two attacks, for nVNS and standard of care therapies for all treated migraine attacks during the randomized period	12 week randomised period
Safety and tolerability of nVNS as measured by adverse events	Safety and tolerability of nVNS as measured by adverse events	12 week randomised period

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in acute headache medication use	Change in acute headache medication use (proportion of attacks with acute medication use prior to or at 120 minutes post-treatment) for all treated attacks in the twelve-week randomized period compared to the four week run-in period in the nVNS group	12 week randomization period compared to the four week run-in period
Presence or absence of nausea, vomiting, photophobia, phonophobia	Presence or absence of nausea, vomiting, photophobia, phonophobia at 0, 30, 60 and 120 minutes post treatment for nVNS and standard of care therapies for all treated migraine attacks in the randomized period	12 week randomised period

Collaborators and Investigators

• Sponsor: ElectroCore INC
• Investigators: Principal Investigator: Alexandra Sinclair, MD, University of Birmingham

Study record dates

Study Major Dates

• Study Start (Anticipated): May 15, 2019
• Primary Completion (Anticipated): September 1, 2020
• Study Completion (Anticipated): October 1, 2020

Study Registration Dates

• First Submitted: December 20, 2018
• First Submitted That Met QC Criteria: December 22, 2018
• First Posted (Actual): December 26, 2018

Study Record Updates

• Last Update Posted (Actual): June 14, 2019
• Last Update Submitted That Met QC Criteria: June 12, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: GM-18

Drug and device information, study documents

• 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