RCT of Non-Invasive Vagus Nerve Stimulation (nVNS) With gammaCore®, for the Acute Treatment of Migraine Attacks

NCT ID: NCT02686034

Last Updated: 2019-08-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 285 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2017-03-31

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.

Conditions

Migraine

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

gammaCore-S

Treatment of up to 5 migraine attacks with the Active gammaCore-S non-invasive vagus nerve stimulator device which delivers a mild electrical signal in the vicinity of the vagus nerve

Group Type: ACTIVE_COMPARATOR

gammaCore-S

Intervention Type: DEVICE

At onset of migraine pain, the subject self-administers a bilateral treatment with the gammaCore nVNS device (2 minutes on the right side, and 2 minutes on the left side). If their headache pain has not improved after 15 minutes, they administer another bilateral treatment. If they are not pain-free at 2 hours, they have the option to administer a third bilateral treatment, or take their usual rescue medication.

gammaCore-S Sham

Treatment of up to 5 migraine attacks with the Sham gammaCore-S non-invasive vagus nerve stimulator device which delivers a mild electrical signal in the vicinity of the vagus nerve

Group Type: SHAM_COMPARATOR

gammaCore-S Sham

Intervention Type: DEVICE

At onset of migraine pain, the subject self-administers a bilateral treatment with the gammaCore nVNS Sham device (2 minutes on the right side, and 2 minutes on the left side). If their headache pain has not improved after 15 minutes, they administer another bilateral treatment with the Sham device. If they are not pain-free at 2 hours, they have the option to administer a third bilateral treatment with the Sham device, or take their usual rescue medication.

Interventions

gammaCore-S

At onset of migraine pain, the subject self-administers a bilateral treatment with the gammaCore nVNS device (2 minutes on the right side, and 2 minutes on the left side). If their headache pain has not improved after 15 minutes, they administer another bilateral treatment. If they are not pain-free at 2 hours, they have the option to administer a third bilateral treatment, or take their usual rescue medication.

Intervention Type: DEVICE

gammaCore-S Sham

At onset of migraine pain, the subject self-administers a bilateral treatment with the gammaCore nVNS Sham device (2 minutes on the right side, and 2 minutes on the left side). If their headache pain has not improved after 15 minutes, they administer another bilateral treatment with the Sham device. If they are not pain-free at 2 hours, they have the option to administer a third bilateral treatment with the Sham device, or take their usual rescue medication.

Intervention Type: DEVICE

Other Intervention Names

nVNS; sham nVNS

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ElectroCore INC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cristina Tassorelli, MD, PhD

Role: STUDY_CHAIR

IRCSS "National Neurological Institute C. Mondino" Foundation

Locations

University Aldo Moro, Ospedale Pediatrico

Bari, , Italy

IRCCS Istituto delle Scienze Neurologiche di Bologna, Ospedale Bellaria

Bologna, , Italy

University Hospital of Careggi

Florence, , Italy

Fondazione IRCCS Istituto Neurologico C. Besta

Milan, , Italy

IRCSS "National Neurological Institute C. Mondino" Foundation

Pavia, , Italy

S. Maria della Misericordia Hospital

Perugia, , Italy

INM Neuromed IRCCS

Pozzilli, , Italy

IRCCS San Raffaele Pisana

Rome, , Italy

Sant'Andrea Hospital, Sapienza University of Rome

Rome, , Italy

University of Turin

Turin, , Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 30382909 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30340460 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29907608 (View on PubMed)

Other Identifiers

GM-16

Identifier Type: -

Identifier Source: org_study_id