Clinical trial NCT02686034: RCT of Non-Invasive Vagus Nerve Stimulation (nVNS) With gammaCore®, for the Acute Treatment of Migraine Attacks
Official title: A Prospective, Multi-centre, Randomized, Double-blind, Sham-controlled Study of gammaCore® Non-invasive Vagus Nerve Stimulator (nVNS), for the Acute Treatment of Migraine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Migraine
Keywords: Migraine
Non-invasive vagus nerve stimulation
Vagus nerve stimulation
Vagal nerve stimulation
gammaCore
episodic migraine
Lead sponsor: ElectroCore INC
Sponsor class: INDUSTRY
First posted: 2016-02-19
Enrollment: 285
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a prospective, multi-centre, randomised, double-blind, sham-controlled investigation designed for comparison of two parallel treatment groups: gammaCore (active nVNS treatment) and a Sham device (control treatment), for the acute treatment of migraine attacks

Detailed description: Period 1: 4-week observational run-in period; no stimulation treatment. Subjects use standard of care (SoC) medication to treat their migraine attacks, according to their individual prescriptions.

Period 2: 4-week randomized/controlled period. After the run-in period, subjects are randomized (1:1) to receive either an nVNS device or a sham device to treat up to 5 migraine attacks.

Period 3: 4-week open-label (active treatment) period. After the randomized period, subjects continue to the open-label period where all subjects receive an active gammaCore device to treat up to 5 migraine attacks.

Eligibility criteria: Inclusion Criteria:

1. Is 18-75 years old.
2. Has been previously diagnosed with migraine (with or without aura) in accordance with the ICHD-3 Beta classification criteria.
3. Age of onset of migraines \< 50 years old.
4. Experiences between 3-8 migraine attacks per month of moderate or severe intensity, and less than 15 headache days per month over the last 6 months.
5. Is able to distinguish migraine headaches from other headaches (e.g. tension type headache).
6. Agrees to withhold usual acute migraine medications until 2 hours after stimulation treatment with the study device.
7. Agrees not to initiate new or change existing migraine prophylaxis medication for the duration of the study, or receive nerve blocks or injections.
8. Agrees not to initiate new or change existing prophylactic medication for indications other than migraine that in the opinion of the Investigator may interfere with the study objectives (e.g. antidepressant, anti-convulsant, beta blockers, etc).
9. Has internet/web access for web-based e-Diary completion.
10. Agrees to use the study device as intended, comply with all study requirements including treatment, follow-up visits, record required study data in the subject diary, and complete study self-assessment questionnaires.
11. Is able to provide written informed consent.

Exclusion Criteria:

1. Experiences ≥ 15 headache days per month, including migraine, tension type headache, medication overuse headache, and other types of headache as defined in the ICHD-3 Beta classification.
2. Has a known history or suspicion of secondary headache.
3. Has previous diagnosis of medication overuse headache (MoH), which has reverted to episodic migraine within the last 6 months.
4. Has had surgical intervention for migraine prevention.
5. Has had a cervical vagotomy.
6. Has a structural abnormality (e.g. lymphadenopathy, neoplasm, previous surgery or abnormal anatomy), or pain (e.g. dysesthesia, neuralgia and/or cervicalgia) at the stimulation treatment site.
7. Has other significant pain problem (e.g. cancer pain, fibromyalgia or other head or facial disorder) that in the opinion of the Investigator may confound the study assessments.
8. 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, sphenopalatine ganglion stimulator, or occipital nerve stimulator).
9. Has been implanted with metal cervical spine hardware or has a metallic implant near the stimulation treatment site.
10. Has failed an adequate trial (two months or greater) of at least 3 classes of a drug therapy for acute treatment of migraine.
11. Has initiated new, or changed existing medications for migraine prophylaxis in the previous 2 months.
12. Is using marijuana (including medical marijuana) for any indications, more than twice a month.
13. Currently takes simple analgesics or non-steroidal anti-inflammatory drugs (NSAIDS) greater than 15 days per month, or triptans, ergots or combined analgesics greater than 10 days per month.
14. Currently takes opioids greater than 2 days per month for headache relief or body pain.
15. Has undergone nerve block (occipital or other) in the head or neck within the last 2 months, or Botox injections within the last 6 months.
16. Has a concomitant medical condition that will require oral or injectable steroids during the study.
17. Has a history of intracranial aneurysm, intracranial haemorrhage, brain tumour or significant head trauma.
18. Has known or suspected severe cardiac disease (e.g. symptomatic coronary artery disease, prior myocardial infarction, congestive heart failure(CHF), cerebrovascular disease (e.g. prior stroke or transient ischemic attack symptomatic carotid artery disease, prior carotid endarterectomy or other vascular neck surgery), or uncontrolled high blood pressure (systolic \>160, diastolic \>100 after 3 repeated measurements within 24 hours).
19. Has a history of syncope or seizure (within the last 5 years).
20. Has a known history or suspicion of substance abuse or addiction (within the last 5 years).
21. Has psychiatric or cognitive disorder and/or behavioural problems which in the opinion of the clinician may interfere with the study.
22. 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, prisoner).
23. Is pregnant or thinking of becoming pregnant during the study period, or of childbearing years and is unwilling to use an accepted form of birth control.
24. Is a relative or employee of the Investigator or the clinical study site.
25. Is participating in any other therapeutic clinical investigation or has participated in a clinical trial in the preceding 30 days.
26. Has previously used the gammaCore device.

Primary outcomes:
measure: Number of Participants With Treatment Response - No Pain
timeFrame: 2 hours post-treatment
Secondary outcomes:
measure: Number of Participants With Absence of Nausea/Vomiting, Photophobia, Phonophobia
timeFrame: 2 hours post-treatment study - period 2 (each study period was 4 weeks)
measure: Number of Participants With Treatment Response - No Pain or Mild Pain
timeFrame: 2 hours post-treatment
measure: Number of Participants With Treatment Response no Pain or Mild Pain at 24 and 48 Hours.
timeFrame: 24 and 48 hours post-treatment
measure: Number of Migraine Attacks With Treatment Response 'No Pain' in Study Period 2 All Attacks
timeFrame: 30, 60, 120 minutes; Study Period 2 (each study period was 4 weeks)
Other outcomes:
measure: Number of Migraine Attacks With Treatment Response 'No Pain' in Study Period 3
timeFrame: 30, 60, 120 minutes; Period 3 (each study period was 4 weeks)
measure: Number of Migraine Attacks With Treatment Response no Pain or Mild Pain
timeFrame: 30, 60, 120 minutes; Study Periods 2 and 3 (each study period was 4 weeks)
measure: Number of Migraine Attacks With Absence of Nausea, Vomiting, Photophobia and Phonophobia
timeFrame: Study Periods 2 and 3 (each study period was 4 weeks)
measure: Number of Attacks With Sustained Treatment Response
timeFrame: 24 and 48 hours; Study Periods 2 and 3 (each study period was 4 weeks)
measure: Number of Subjects With Consistency of Response
timeFrame: Study Periods 2 and 3 (each study period was 4 weeks)
measure: Quality of Life Measured by EuroQol-5D-5L (EQ-5D-5L)
timeFrame: End of each study period (each study period was 4 weeks)
measure: Bang Blinding Index Scores
timeFrame: Study Period 2 (4 weeks)
measure: Subject Satisfaction
timeFrame: End of Study Periods 2 and 3 (each study period was 4 weeks long)
measure: Mean Change in Pain Score From Baseline to 120 Minutes
timeFrame: 120 minutes, Study Period 2 (each study period was 4 weeks long)
measure: Ease of Use
timeFrame: End of Study Periods 2 and 3 (each study period was 4 weeks long)
measure: Quality of Life Measured by Headache Impact Test (HIT-6)
timeFrame: End of each study period (each study period was 4 weeks)
Locations:
city: Bari
country: Italy
facility: University Aldo Moro, Ospedale Pediatrico
city: Bologna
country: Italy
facility: IRCCS Istituto delle Scienze Neurologiche di Bologna, Ospedale Bellaria
city: Florence
country: Italy
facility: University Hospital of Careggi
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Neurologico C. Besta
city: Pavia
country: Italy
facility: IRCSS "National Neurological Institute C. Mondino" Foundation
city: Perugia
country: Italy
facility: S. Maria della Misericordia Hospital
city: Pozzilli
country: Italy
facility: INM Neuromed IRCCS
city: Rome
country: Italy
facility: IRCCS San Raffaele Pisana
city: Rome
country: Italy
facility: Sant'Andrea Hospital, Sapienza University of Rome
city: Turin
country: Italy
facility: University of Turin
Study officials:
affiliation: IRCSS "National Neurological Institute C. Mondino" Foundation
name: Cristina Tassorelli, MD, PhD
role: STUDY_CHAIR
References:
citation: Martelletti P, Barbanti P, Grazzi L, Pierangeli G, Rainero I, Geppetti P, Ambrosini A, Sarchielli P, Tassorelli C, Liebler E, de Tommaso M; PRESTO Study Group. Consistent effects of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: additional findings from the randomized, sham-controlled, double-blind PRESTO trial. J Headache Pain. 2018 Nov 1;19(1):101. doi: 10.1186/s10194-018-0929-0.
citation: Grazzi L, Tassorelli C, de Tommaso M, Pierangeli G, Martelletti P, Rainero I, Geppetti P, Ambrosini A, Sarchielli P, Liebler E, Barbanti P; PRESTO Study Group. Practical and clinical utility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: a post hoc analysis of the randomized, sham-controlled, double-blind PRESTO trial. J Headache Pain. 2018 Oct 19;19(1):98. doi: 10.1186/s10194-018-0928-1.
citation: Tassorelli C, Grazzi L, de Tommaso M, Pierangeli G, Martelletti P, Rainero I, Dorlas S, Geppetti P, Ambrosini A, Sarchielli P, Liebler E, Barbanti P; PRESTO Study Group. Noninvasive vagus nerve stimulation as acute therapy for migraine: The randomized PRESTO study. Neurology. 2018 Jul 24;91(4):e364-e373. doi: 10.1212/WNL.0000000000005857. Epub 2018 Jun 15.