MigraineNCT02686034
RCT of Non-Invasive Vagus Nerve Stimulation (nVNS) With gammaCore®, for the Acute Treatment of Migraine Attacks
A study testing gammaCore-S in people with Migraine, run by ElectroCore INC at 10 sites in Italy.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Migraine
- What is being tested?
- gammaCore-S
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 285 participants
- Where
- 10 sitesItaly
- Study dates
- Jan 2016to Mar 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Is 18-75 years old.
- Has been previously diagnosed with migraine (with or without aura) in accordance with the ICHD-3 Beta classification criteria.
- Age of onset of migraines < 50 years old.
- 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.
- Is able to distinguish migraine headaches from other headaches (e.g. tension type headache).
- Agrees to withhold usual acute migraine medications until 2 hours after stimulation treatment with the study device.
Show all 11Show fewer
- Agrees not to initiate new or change existing migraine prophylaxis medication for the duration of the study, or receive nerve blocks or injections.
- 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).
- Has internet/web access for web-based e-Diary completion.
- 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.
- Is able to provide written informed consent.
Who cannot join
- 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.
- Has a known history or suspicion of secondary headache.
- Has previous diagnosis of medication overuse headache (MoH), which has reverted to episodic migraine within the last 6 months.
- Has had surgical intervention for migraine prevention.
- Has had a cervical vagotomy.
- 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.
Show all 26Show fewer
- 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.
- 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).
- Has been implanted with metal cervical spine hardware or has a metallic implant near the stimulation treatment site.
- Has failed an adequate trial (two months or greater) of at least 3 classes of a drug therapy for acute treatment of migraine.
- Has initiated new, or changed existing medications for migraine prophylaxis in the previous 2 months.
- Is using marijuana (including medical marijuana) for any indications, more than twice a month.
- 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.
- Currently takes opioids greater than 2 days per month for headache relief or body pain.
- 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.
- Has a concomitant medical condition that will require oral or injectable steroids during the study.
- Has a history of intracranial aneurysm, intracranial haemorrhage, brain tumour or significant head trauma.
- 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).
- Has a history of syncope or seizure (within the last 5 years).
- Has a known history or suspicion of substance abuse or addiction (within the last 5 years).
- Has psychiatric or cognitive disorder and/or behavioural problems which in the opinion of the clinician may interfere with the study.
- 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).
- 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.
- Is a relative or employee of the Investigator or the clinical study site.
- Is participating in any other therapeutic clinical investigation or has participated in a clinical trial in the preceding 30 days.
- Has previously used the gammaCore device.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Italy10 sites
University Aldo Moro, Ospedale Pediatrico
Bari
IRCCS Istituto delle Scienze Neurologiche di Bologna, Ospedale Bellaria
Bologna
University Hospital of Careggi
Florence
Fondazione IRCCS Istituto Neurologico C. Besta
Milan
IRCSS "National Neurological Institute C. Mondino" Foundation
Pavia
S. Maria della Misericordia Hospital
Perugia
INM Neuromed IRCCS
Pozzilli
IRCCS San Raffaele Pisana
Rome
Sant'Andrea Hospital, Sapienza University of Rome
Rome
University of Turin
Turin
About this study
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
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
Read the 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
- Being tested
- gammaCore-S, gammaCore-S Sham
- Keywords
- Migraine, Non-invasive vagus nerve stimulation, Vagus nerve stimulation, Vagal nerve stimulation, gammaCore, episodic migraine
- Medical subject headings
- Migraine Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gammaCore-SDevice
Also called nVNS
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 ShamDevice
Also called sham nVNS
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.
| Study group | Role | What they receive |
|---|---|---|
| gammaCore-S | Active comparator | 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 Receives: Device: gammaCore-S |
| gammaCore-S Sham | Sham comparator | 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 Receives: Device: gammaCore-S Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Response - No Pain
The primary objective is to compare the treatment response for nVNS and Sham therapies at two hours post-treatment, for the first treated migraine attack during study Period 2. Treatment response is defined as no pain at 2 hours post-treatment and no rescue medication use by 2 hours post-treatment.
Measured: 2 hours post-treatment
Secondary outcomes (4)
Number of Participants With Absence of Nausea/Vomiting, Photophobia, Phonophobia
Presence or absence of nausea/vomiting, photophobia and phonophobia for nVNS and sham therapies for the first treated migraine attack at 120 minutes during study Period 2.
Measured: 2 hours post-treatment study - period 2 (each study period was 4 weeks)
Number of Participants With Treatment Response - No Pain or Mild Pain
Response to treatment was assessed by the subjects using the 4 point headache scale, where 0 = No pain, 1 = Mild pain, 2 = Moderate pain and 3 = severe pain.
Results show count of participants with a response of no pain (score = 0) or mild pain (score = 1) on the 4-point headache pain scale for the nVNS and sham therapies at 2 hours post-treatment and no rescue medication use by 2 hours post-treatment for the first treated migraine attack during study Period 2.
Measured: 2 hours post-treatment
Number of Participants With Treatment Response no Pain or Mild Pain at 24 and 48 Hours.
Response to treatment was assessed by the subjects using the 4 point headache scale, where 0 = No pain, 1 = Mild pain, 2 = Moderate pain and 3 = severe pain.
Results show count of participants with a response of no pain or mild pain on the 4-point headache pain scale at 24, and 48 hours post-treatment (and no rescue medication use) for nVNS and sham therapies for the first treated migraine attack during study Period 2.
Measured: 24 and 48 hours post-treatment
Number of Migraine Attacks With Treatment Response 'No Pain' in Study Period 2 All Attacks
Response to treatment was assessed by the subjects using the 4 point headache scale, where 0 = No pain, 1 = Mild pain, 2 = Moderate pain and 3 = severe pain.
Results show % Treatment response 'No pain' for the nVNS and sham therapies at 30, 60 and 120 minutes calculated for all treated attacks during study Period 2.
Measured: 30, 60, 120 minutes; Study Period 2 (each study period was 4 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2016 (estimated)
- Study startJan 2016
- Primary completionDec 2016
- Study completionMar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for MigraineStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 285 participants (actual)
Sponsor and investigators
- Lead sponsor
- ElectroCore INC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Cristina Tassorelli, MD, PhD, Study chair, IRCSS "National Neurological Institute C. Mondino" Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02686034
- Sponsor's protocol ID
- GM-16
- Status last verified
- Jun 2019
- First submitted
- 15 Feb 2016
- Last updated
- 2 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 30382909Grazzi 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.
PubMed 30340460Tassorelli 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.
PubMed 29907608
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02686034
- Acronym / sponsor ID
- GM-16
- Conditions
- Migraine
- Keywords
- Migraine, Non-invasive vagus nerve stimulation, Vagus nerve stimulation, Vagal nerve stimulation, gammaCore, episodic migraine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 285 participants (actual)
- Lead sponsor
- ElectroCore INCIndustry (pharma, biotech, devices)
- Study start
- Jan 2016 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 19 Feb 2016 (estimated)
- Results
- Posted 2 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| gammaCore-S | Active comparator | Device: gammaCore-STreatment 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 |
| gammaCore-S Sham | Sham comparator | Device: gammaCore-S ShamTreatment 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Is 18-75 years old.
- Has been previously diagnosed with migraine (with or without aura) in accordance with the ICHD-3 Beta classification criteria.
- Age of onset of migraines < 50 years old.
- 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.
- Is able to distinguish migraine headaches from other headaches (e.g. tension type headache).
Key exclusion criteria (26 listed)
- 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.
- Has a known history or suspicion of secondary headache.
- Has previous diagnosis of medication overuse headache (MoH), which has reverted to episodic migraine within the last 6 months.
- Has had surgical intervention for migraine prevention.
- Has had a cervical vagotomy.
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-SAlso: nVNSAt 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. | Device | gammaCore-S |
| gammaCore-S ShamAlso: sham nVNSAt 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. | Device | gammaCore-S Sham |
Primary outcome
Number of Participants With Treatment Response - No Pain
Time frame: 2 hours post-treatment
The primary objective is to compare the treatment response for nVNS and Sham therapies at two hours post-treatment, for the first treated migraine attack during study Period 2. Treatment response is defined as no pain at 2 hours post-treatment and no rescue medication use by 2 hours post-treatment.
4 secondary outcomes
Number of Participants With Absence of Nausea/Vomiting, Photophobia, Phonophobia
Time frame: 2 hours post-treatment study - period 2 (each study period was 4 weeks)
Number of Participants With Treatment Response - No Pain or Mild Pain
Time frame: 2 hours post-treatment
Number of Participants With Treatment Response no Pain or Mild Pain at 24 and 48 Hours.
Time frame: 24 and 48 hours post-treatment
Number of Migraine Attacks With Treatment Response 'No Pain' in Study Period 2 All Attacks
Time frame: 30, 60, 120 minutes; Study Period 2 (each study period was 4 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30382909Martelletti 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.
- Derived from this study: PubMed 30340460Grazzi 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.
- Derived from this study: PubMed 29907608Tassorelli 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.
- 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.
Cristina Tassorelli, MD, PhD study chair
IRCSS "National Neurological Institute C. Mondino" Foundation
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing gammaCore-S in people with Migraine, run by ElectroCore INC at 10 sites in Italy.
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 11 inclusion and 26 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 2 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Italy. 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?
Yes. Results are posted in the registry (first posted 2 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Treatment Response - No Pain (time frame: 2 hours post-treatment). 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 NCT02686034, which also lists 3 linked publications.
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 2 Aug 2019.