MigraineNCT02378844
A Randomized, Sham-controlled Study of gammaCore ® (nVNS) for Prevention of Episodic Migraine
A study testing gammaCore®-R in people with Migraine, run by ElectroCore INC at 22 sites in 8 countries.
Trial summary
A prospective, double-blind, randomized, sham-controlled, multicentre investigation. 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®-R
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 477 participants
- Where
- 22 sitesin 8 countries
- Study dates
- Jun 2015to 29 Aug 2018
- 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 between the ages of 18 and 75 years.
- Has been previously diagnosed with migraine (with or without aura) in accordance with the International Classification of Headache Disorders (ICHD)-3 Beta Classification criteria.
- Experience between 5 and 12 migraine days per month (over the last 4 months) with at least 2 of the migraines lasting more than 4 hours.
- Has age of onset of migraine less than 50 years old.
- Agrees not to use any migraine prevention treatments (including Botox injections) and/or medications (exclusive of medications taken for acute relief of migraine symptoms).
- Agrees to refrain from initiating or changing the type, dosage or frequency of any prophylactic medications for indications other than migraine that in the opinion of the clinician may interfere with the study objectives (e.g. antidepressant, anti convulsant, beta blockers, etc.).
- Agrees to use the gammaCore®-R 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.
- Is able to provide written Informed Consent.
Who cannot join
- Has a concomitant medical condition that will require oral or injectable steroids during the study.
- Has a history of any intracranial aneurysm, intracranial haemorrhage, brain tumour or significant head trauma.
- Has a structural abnormality at the gammaCore®-R treatment site (e.g lymphadenopathy previous surgery or abnormal anatomy).
- Has pain at the gammaCore®-R treatment site (e.g.dysesthesia, neuralgia and/or cervicalgia).
- 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
- Has know or suspected severe cardiac disease(e.g. symptomatic coronary artery disease, prior myocardial infarction, congestive heart failure (CHF)).
Show all 32Show fewer
- Has known or suspected severe cerebrovascular disease, (e.g. prior stroke or transient ischemic attack, symptomatic carotid artery disease, prior carotid endarterectomy or other vascular neck surgery).
- Has an abnormal baseline Electrocardiogram (ECG) e.g. second and third degree heart block, prolonged QT interval, atrial fibrillation, atrial flutter, history of ventricular tachycardia or ventricular fibrillation, or clinically significant premature ventricular contraction).
- 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, Sphenopalatine ganglion stimulator or Occipital nerve stimulator).
- Has been implanted with metal cervical spine hardware or has a metallic implant near the gammaCore®-R stimulation site.
- Has a known history of suspicion of secondary headache.
- Has a history of syncope (within the last five years).
- Has a history of seizures (within the last five years).
- Has a known or suspicion of substance abuse or addiction (within the last 5 years).
- 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 for headaches or other body pain.
- Currently takes prescription opioids greater than 2 days per month for headaches or body pain.
- Has taken medications for migraine prophylaxis in the previous 30 days.
- Has previous diagnosis of medication overuse headache (MoH) , which has reverted to episodic migraine within the last 6 months.
- Meets the ICHD-3 Beta Classification criteria for chronic migraine (> 15 headache days per month).
- Has failed an adequate trial (two months or greater) of at least 3 classes of a drug therapy for the prophylaxis of migraine .
- Has had surgery for migraine prevention.
- Has undergone nerve block (occipital or other) in the head or neck within the last 2 months.
- Has received Botox injections within the last 6 months.
- Is pregnant or thinking of becoming pregnant during the study period, or of childbearing years and is unwilling to use and accepted form of birth control.
- 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).
- Is a relative of or an employee of the investigator or the clinical study site.
- Has psychiatric or cognitive disorder and/or behavioural problems which in the opinion of the clinician may interfere with the study.
- Has previously used the gammaCore® device.
Trial locations and contacts
22 sites in 8 countries.
22 sites in 8 countries
Germany7 sites
Neurologische Klinik und Poliklinik, Charité Campus Mitte
Berlin, D-10117
Klinik für Neurologie, Universitätsklinikum Essen
Essen, D-45147
CTC, University Medical Center Hamburg-Eppendorf
Hamburg, D-20251
Migräne- und Kopfschmertzklinik Königstein
Königstein, D-61462
Klinik für Neurologie, Ludwig-Maximilliams-Universität, Klinikum Grosshadern
München, D-81377
Zentrum für Neurologie und Epileptologie, Hertie-Institut für Klinische Hirnforschung
Tübingen, 72076
DKD HELIOS Klinik Wiesbaden
Wiesbaden, D-65191
United Kingdom6 sites
Basildon University Hospital
Basildon, Essex, SS16 5NL
School of Clinical and Expermental Medicine
Birmingham, B15 2TT
Neurology Department, The Southern Hospital
Glasgow, G51 4TF
Neurology Department, Hull Royal Infirmary
Hull, HU3 2JZ
Neurology Department, The Walton Center
Liverpool, L9 7LJ
Neurology Department, King's College London
London, SE5 9PJ
Spain4 sites
Headache Unit, University Hospital Vall d'Hebron
Barcelona, 08035
Servicio de Neurologia, Hospital Ruber Internacional
Madrid, 28034
Servicio de Neurologia, Clinica Universidad de Navarra
Pamplona, ES-31008
Servicio de Neurologia, Hospital Clinico Universitario de Valencia
Valencia, ES-46010
Netherlands1 site
Neurology Department, Leiden University Center
Leiden, NL-2333 ZA
About this study
Official title: A Randomized, Multicentre, Double-blind, Parallel, Sham-controlled Study of gammaCore®, a Non-invasive Vagal Nerve Stimulator (nVNS), for Prevention of Episodic Migraine
A prospective, double-blind, randomized, sham-controlled, multicentre investigation.
Read the detailed description
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 observation for baseline 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.
The randomized period will be followed by a 24 week open label period, where the subjects in the sham treatment group will switch in treatment assignment and receive a gammaCore®-R and the gammaCore®-R will continue to receive an active treatment.
- Conditions
- Migraine
- Being tested
- gammaCore®-R, gammaCore®-R Sham
- 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®-RDevice
Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).
gammaCore®-R ShamDevice
Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side).
| Study group | Role | What they receive |
|---|---|---|
| gammaCore®-R | Active comparator | Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). Receives: Device: gammaCore®-R |
| gammaCore®-R Sham | Sham comparator | Subjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). Receives: Device: gammaCore®-R Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the Number of Migraine Days
Change in number of migraine days (as reported in subject diary), comparing the 4 week run-in period to the last 4 weeks in the randomized period.
Measured: last 4 weeks of the randomized/controlled period compared to the subject's own 4-week run-in period.
Secondary outcomes (9)
Number of Participants With 50% Responder Rate
The number of subjects with a reduction of 50% or more in number of migraine days (as reported in the subject diary) from the run-in period to the last 4 weeks of the double-blind period.
Measured: The last four weeks in the randomization period compared to the four week run-in period.
Mean Change in Number of Headache Days
The mean change in number of headache days (as reported in the subject diary) from the run-in period to the last 4 weeks of the double-blind period.
Measured: The last four weeks in the randomization period compared to the four week run-in period.
Change in Number of Acute Medication Days
The mean change in number of acute medication days (as reported in the subject diary) from the run-in period to the last 4 weeks of the double-blind period
Measured: The last four weeks in the randomization period compared to the four week run-in period.
Change in Headache Disability Using Headache Impact Test-6
Change in headache disability from the 4 week run-in period to the last 4 weeks of the randomized period as measured using the Headache Impact Test-6 (HIT-6). The HIT-6 measures the impact if a subject's headaches on their ability to function at work, at home and in social situations. Subjects are presented with 6 questions about ability to function and normal daily life and for each question they rate the impact of their headaches as 'never' (6 points) or 'rarely' (9 points) or 'sometimes' (10 points) or 'very often' (11 points) or 'always' (13 points). Minimum score = 36, maximum score = 78. A higher score indicates more impact.
Measured: From four week run-in period to last four weeks in the randomization period
Number of Participants According to Grade on the Migraine Disability Assessment (MIDAS) Before and After Randomized Period
Migraine Disability Assessment (MIDAS) score from the end of run-in period to the end of randomized period. The MIDAS assessment measures the effect of headaches on a subject's daily functioning. It takes into account the past 3 months and is comprised of five questions. A lower score indicated less disability, a higher score indicates more disability. The scores are graded:
0-5, MIDAS Grade I, little disability 6-10, MIDAS Grade II, mild disability 11 to 20 MIDAS Grade III, moderate disability 21+ MIDAS Grade IV, severe disability
Measured: 3 months - end of run-in period to end of randomized period
Compare Changes in Quality of Life EuroQol Questionnaire 5 Dimensions and 5 Levels (EQ-5D-5L)
The descriptive system comprises five dimensions (5D): mobility, self-care, usual activities, pain/discomfort and anxiety/depression.
Each dimension has 5 levels (5L): no problems (1) , slight problems (2), moderate problems (3), severe problems (4) and extreme problems (5).
Minimum score is 5 (no problems) and maximum score is 25 (extreme problems)
An overall health question is asked using a visual analogue scale(VAS) from 0-100 where 0 is bad health and 100 good health
Measured: From four week run-in period to last four weeks in the randomization period
Change in Migraine Days in the Open Label Period (Adjusted ANCOVA)
Change in number of migraine days (as reported in subject diary) during the 6 month open label period compared to the baseline run-in period.
Measured: The 6 month open-label period compared to the four week run-in period
Number of Participants With Adverse Events
Adverse Effects were collected for all subjects for the duration of the study.
Measured: up to Week 36
Change in Headache Days in the Open Label Period
The mean change in number of headache days (as reported in the subject diary) during the open label period compared to the base-line run-in period
Measured: The 6 month open-label period compared to the four week run-in period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2015 (estimated)
- Study startJun 2015
- Primary completion1 Feb 2018
- Study completion29 Aug 2018
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 (1)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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 477 participants (actual)
Sponsor and investigators
- Lead sponsor
- ElectroCore INC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Hans-Christoph Diener, Professor, Principal investigator, Universtätsklinikum Essen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02378844
- Sponsor's protocol ID
- GM-11
- Status last verified
- Jul 2019
- First submitted
- 18 Feb 2015
- Last updated
- 19 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Results from the whole study will published but not individual participant data.
Publications
Diener HC, Goadsby PJ, Ashina M, Al-Karagholi MA, Sinclair A, Mitsikostas D, Magis D, Pozo-Rosich P, Irimia Sieira P, Lainez MJ, Gaul C, Silver N, Hoffmann J, Marin J, Liebler E, Ferrari MD. Non-invasive vagus nerve stimulation (nVNS) for the preventive treatment of episodic migraine: The multicentre, double-blind, randomised, sham-controlled PREMIUM trial. Cephalalgia. 2019 Oct;39(12):1475-1487. doi: 10.1177/0333102419876920. Epub 2019 Sep 15.
PubMed 31522546
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Multicentre, Double-blind, Parallel, Sham-controlled Study of gammaCore®, a Non-invasive Vagal Nerve Stimulator (nVNS), for Prevention of Episodic Migraine
- ClinicalTrials.gov ID
- NCT02378844
- Acronym / sponsor ID
- GM-11
- Conditions
- Migraine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 477 participants (actual)
- Lead sponsor
- ElectroCore INCIndustry (pharma, biotech, devices)
- Study start
- Jun 2015 (actual)
- Primary completion
- 1 Feb 2018 (actual)
- Study completion
- 29 Aug 2018 (actual)
- First posted
- 4 Mar 2015 (estimated)
- Results
- Posted 19 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A prospective, double-blind, randomized, sham-controlled, multicentre investigation.
Detailed description
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 observation for baseline 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.
The randomized period will be followed by a 24 week open label period, where the subjects in the sham treatment group will switch in treatment assignment and receive a gammaCore®-R and the gammaCore®-R will continue to receive an active treatment.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| gammaCore®-R | Active comparator | Device: gammaCore®-RSubjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). |
| gammaCore®-R Sham | Sham comparator | Device: gammaCore®-R ShamSubjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Is between the ages of 18 and 75 years.
- Has been previously diagnosed with migraine (with or without aura) in accordance with the International Classification of Headache Disorders (ICHD)-3 Beta Classification criteria.
- Experience between 5 and 12 migraine days per month (over the last 4 months) with at least 2 of the migraines lasting more than 4 hours.
- Has age of onset of migraine less than 50 years old.
- Agrees not to use any migraine prevention treatments (including Botox injections) and/or medications (exclusive of medications taken for acute relief of migraine symptoms).
Key exclusion criteria (32 listed)
- Has a concomitant medical condition that will require oral or injectable steroids during the study.
- Has a history of any intracranial aneurysm, intracranial haemorrhage, brain tumour or significant head trauma.
- Has a structural abnormality at the gammaCore®-R treatment site (e.g lymphadenopathy previous surgery or abnormal anatomy).
- Has pain at the gammaCore®-R treatment site (e.g.dysesthesia, neuralgia and/or cervicalgia).
- 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
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®-RSubjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). | Device | gammaCore®-R |
| gammaCore®-R ShamSubjects will be instructed to treat three times per day, 2 consecutive bilateral stimulations, upon waking, six to eight hours following the first daily treatment, and six to eight hours following the second daily treatment (one stimulation on the right side immediately followed by a second stimulation on the left side). | Device | gammaCore®-R Sham |
Primary outcome
Change in the Number of Migraine Days
Time frame: last 4 weeks of the randomized/controlled period compared to the subject's own 4-week run-in period.
Change in number of migraine days (as reported in subject diary), comparing the 4 week run-in period to the last 4 weeks in the randomized period.
9 secondary outcomes
Number of Participants With 50% Responder Rate
Time frame: The last four weeks in the randomization period compared to the four week run-in period.
Mean Change in Number of Headache Days
Time frame: The last four weeks in the randomization period compared to the four week run-in period.
Change in Number of Acute Medication Days
Time frame: The last four weeks in the randomization period compared to the four week run-in period.
Change in Headache Disability Using Headache Impact Test-6
Time frame: From four week run-in period to last four weeks in the randomization period
Number of Participants According to Grade on the Migraine Disability Assessment (MIDAS) Before and After Randomized Period
Time frame: 3 months - end of run-in period to end of randomized period
Compare Changes in Quality of Life EuroQol Questionnaire 5 Dimensions and 5 Levels (EQ-5D-5L)
Time frame: From four week run-in period to last four weeks in the randomization period
Change in Migraine Days in the Open Label Period (Adjusted ANCOVA)
Time frame: The 6 month open-label period compared to the four week run-in period
Number of Participants With Adverse Events
Time frame: up to Week 36
Change in Headache Days in the Open Label Period
Time frame: The 6 month open-label period compared to the four week run-in period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31522546Diener HC, Goadsby PJ, Ashina M, Al-Karagholi MA, Sinclair A, Mitsikostas D, Magis D, Pozo-Rosich P, Irimia Sieira P, Lainez MJ, Gaul C, Silver N, Hoffmann J, Marin J, Liebler E, Ferrari MD. Non-invasive vagus nerve stimulation (nVNS) for the preventive treatment of episodic migraine: The multicentre, double-blind, randomised, sham-controlled PREMIUM trial. Cephalalgia. 2019 Oct;39(12):1475-1487. doi: 10.1177/0333102419876920. Epub 2019 Sep 15.
- Individual participant dataSharing planned: No. Results from the whole study will published but not individual participant data.
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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.
Hans-Christoph Diener, Professor principal investigator
Universtätsklinikum Essen
22 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing gammaCore®-R in people with Migraine, run by ElectroCore INC at 22 sites in 8 countries.
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 8 inclusion and 32 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 19 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 22 sites in Germany, United Kingdom, Spain, Belgium, Denmark and 3 more countries. 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 19 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?
Change in the Number of Migraine Days (time frame: last 4 weeks of the randomized/controlled period compared to the subject's own 4-week run-in period.). 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 NCT02378844, which also lists 1 linked publication.
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 19 Aug 2019.