Evidence map›Paper›PMID 31522546›Full record

Trial reportCephalalgia : an international journal of headache2019

Non-invasive vagus nerve stimulation (nVNS) for the preventive treatment of episodic migraine: The multicentre, double-blind, randomised, sham-controlled PREMIUM trial.

Hans-Christoph Diener, Peter J Goadsby, Messoud Ashina, Mohammad Al-Mahdi Al-Karagholi, Alexandra Sinclair, Dimos Mitsikostas, Delphine Magis, Patricia Pozo-Rosich, Pablo Irimia Sieira, Miguel Ja Làinez and 6 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cephalalgia : an international journal of headache, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06277063 (Noninvasive Vagus Nerve Stimulation for the Prevention and Treatment of Primary Headache), which is not on this map. Cited by 59 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 9 pooled it
8.7field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06277063 narecruitingnot on this mapstarted 2024, after this paper: background citation

Noninvasive Vagus Nerve Stimulation for the Prevention and Treatment of Primary Headache: a Single-arm Single-center Clinical Trial.

TypeinterventionalSponsorNanfang Hospital, Southern Medical UniversityRan2024 to 2026Enrolled15ConditionsPrimary Headache, Migraine in Adolescence, Migraine in Children, Cluster HeadacheArmsTranscutaneous auricular vagus nerve stimulation
3 · Its place in the literature

Who cites it

59 citing papers in PubMed, 9 syntheses or guidelines pooled it, 119 citations in OpenAlex.

  1. Pooled it
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  10. Trial
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  14. Stimulating discussion: neuromodulation for migraine in pregnancy.Current opinion in obstetrics & gynecology · 2026
    Article
  15. Review
  16. Review
  17. Non-pharmacological approaches for migraine management: a mini-review.Frontiers in pain research (Lausanne, Switzerland) · 2026
    Review
  18. Review
  19. Review
  20. Non-Invasive Neuromodulation in the Treatment of Headache.Current neurology and neuroscience reports · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 12 institutions in 7 countries.

Hans-Christoph DienerFaculty of Medicine, University Duisburg-Essen, Essen, Germany.
Peter J GoadsbyNIHR-Wellcome Trust King's Clinical Research Facility, King's College London, London, UK.ORCID https://orcid.org/0000-0003-3260-5904
Messoud AshinaDanish Headache Center, Rigshospitalet Glostrup, University of Copenhagen, Copenhagen, Denmark.
Mohammad Al-Mahdi Al-KaragholiDanish Headache Center, Rigshospitalet Glostrup, University of Copenhagen, Copenhagen, Denmark.ORCID https://orcid.org/0000-0003-1118-9665
Alexandra SinclairMetabolic Neurology, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
Dimos Mitsikostas1st Neurology Department, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Delphine MagisNeurology Department and Pain Clinic, CHR East Belgium, Liège, Belgium.ORCID https://orcid.org/0000-0002-4392-9413
Patricia Pozo-RosichHeadache Unit, Neurology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Pablo Irimia SieiraClinica Universidad de Navarra, Pamplona, Spain.
Miguel Ja LàinezCatholic University of Valencia, University Clinic Hospital, Valencia, Spain.
Charly GaulMigraine and Headache Clinic, Königstein, Germany.
Nicholas SilverThe Walton Centre, Liverpool, UK.
Jan HoffmannNIHR-Wellcome Trust King's Clinical Research Facility, King's College London, London, UK.ORCID https://orcid.org/0000-0002-2103-9081
Juana MarinNIHR-Wellcome Trust King's Clinical Research Facility, King's College London, London, UK.
Eric LieblerelectroCore, Inc., Basking Ridge, New Jersey, USA.
Michel D FerrariLeiden University Medical Center, Leiden, The Netherlands.
King's College London · GBUniversity of Copenhagen · DKCentre Hospitalier Chrétien · BEClinica Universidad de Navarra · ESLeiden University Medical Center · NLMigräne Klinik Königstein · DENational and Kapodistrian University of Athens · GRUniversitat Autònoma de Barcelona · ESUniversitat de València · ESUniversity of Birmingham · GBUniversity of Duisburg-Essen · DEUniversity of Liverpool · GB

Funding

Medical Research Council MR/K015184/1
6 · The paper itself

Abstract

introductionNon-invasive vagus nerve stimulation (nVNS; gammaCore®) has the potential to prevent migraine days in patients with migraine on the basis of mechanistic rationale and pilot clinical data.

methodsThis multicentre study included a 4-week run-in period, a 12-week double-blind period of randomised treatment with nVNS or sham, and a 24-week open-label period of nVNS. Patients were to administer two 120-second stimulations bilaterally to the neck three times daily (6-8 hours apart).

resultsOf 477 enrolled patients, 332 comprised the intent-to-treat (ITT) population. Mean reductions in migraine days per month (primary outcome) were 2.26 for nVNS (n = 165; baseline, 7.9 days) and 1.80 for sham (n = 167; baseline, 8.1 days) (

conclusionsPreventive nVNS treatment in episodic migraine was not superior to sham stimulation in the ITT population. The "sham" device inadvertently provided a level of active vagus nerve stimulation. Post hoc analysis showed significant effects of nVNS in treatment-adherent patients.

Indexed as

AdultDouble-Blind MethodFemaleHumansMaleMiddle AgedMigraine DisordersTreatment OutcomeVagus Nerve Stimulationmigraine prophylaxisNeuromodulationnon-pharmacologic treatmentpreventive therapyRCTvagal activation

Identifiers

PMID31522546
PMCPMC6791025
OpenAlexW2974905654

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.