{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T08:34:53Z","timestamp":1785227693363,"version":"3.55.0"},"reference-count":34,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2019,9,15]],"date-time":"2019-09-15T00:00:00Z","timestamp":1568505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"electroCore, Inc."}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cephalalgia"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Non-invasive vagus nerve stimulation (nVNS; gammaCore\u00ae) has the potential to prevent migraine days in patients with migraine on the basis of mechanistic rationale and pilot clinical data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This 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\u20138 hours apart).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 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\u2009=\u2009165; baseline, 7.9 days) and 1.80 for sham (n\u2009=\u2009167; baseline, 8.1 days) ( p\u2009=\u20090.15). Results were similar across other outcomes. Upon observation of suboptimal adherence rates, post hoc analysis of patients with\u2009\u2265\u200967% adherence per month demonstrated significant differences between nVNS (n\u2009=\u2009138) and sham (n\u2009=\u2009140) for outcomes including reduction in migraine days (2.27 vs. 1.53; p\u2009=\u20090.043); therapeutic gains were greater in patients with aura than in those without aura. Most nVNS device-related adverse events were mild and transient, with application site discomfort being the most common.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Preventive nVNS treatment in episodic migraine was not superior to sham stimulation in the ITT population. The \u201csham\u201d device inadvertently provided a level of active vagus nerve stimulation. Post hoc analysis showed significant effects of nVNS in treatment-adherent patients. Study identification and registration: PREMIUM; NCT02378844; https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02378844<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0333102419876920","type":"journal-article","created":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T00:30:21Z","timestamp":1568593821000},"page":"1475-1487","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":112,"title":["Non-invasive vagus nerve stimulation (nVNS) for the preventive treatment of episodic migraine: The multicentre, double-blind, randomised, sham-controlled PREMIUM trial"],"prefix":"10.1177","volume":"39","author":[{"given":"Hans-Christoph","family":"Diener","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3260-5904","authenticated-orcid":false,"given":"Peter 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Sieira","sequence":"additional","affiliation":[{"name":"Clinica Universidad de Navarra, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel JA","family":"L\u00e0inez","sequence":"additional","affiliation":[{"name":"Catholic University of Valencia, University Clinic Hospital, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charly","family":"Gaul","sequence":"additional","affiliation":[{"name":"Migraine and Headache Clinic, K\u00f6nigstein, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Silver","sequence":"additional","affiliation":[{"name":"The Walton Centre, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2103-9081","authenticated-orcid":false,"given":"Jan","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"NIHR-Wellcome Trust King's Clinical Research Facility, King's College London, London, 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