title: Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): A randomised controlled study.
abstract: BACKGROUND
  Chronic cluster headache (CH) is a debilitating disorder for which few well-controlled studies demon.strate effectiveness of available therapies. Non-invasive vagus nerve stimulation (nVNS) was examined as adjunctive prophylactic treatment of chronic CH.
  
  
  METHODS
  PREVA was a prospective, open-label, randomised study that compared adjunctive prophylactic nVNS (n = 48) with standard of care (SoC) alone (control (n = 49)). A two-week baseline phase was followed by a four-week randomised phase (SoC plus nVNS vs control) and a four-week extension phase (SoC plus nVNS). The primary end point was the reduction in the mean number of CH attacks per week. Response rate, abortive medication use and safety/tolerability were also assessed.
  
  
  RESULTS
  During the randomised phase, individuals in the intent-to-treat population treated with SoC plus nVNS (n = 45) had a significantly greater reduction in the number of attacks per week vs controls (n = 48) (-5.9 vs -2.1, respectively) for a mean therapeutic gain of 3.9 fewer attacks per week (95% CI: 0.5, 7.2; p = 0.02). Higher ≥50% response rates were also observed with SoC plus nVNS (40% (18/45)) vs controls (8.3% (4/48); p < 0.001). No serious treatment-related adverse events occurred.
  
  
  CONCLUSIONS
  Adjunctive prophylactic nVNS is a well-tolerated novel treatment for chronic CH, offering clinical benefits beyond those with SoC.
authors.affiliation: Migraine and Headache Clinic, Königstein, Germany c.gaul@migraene-klinik.de.
authors.forename: Charly
authors.initials: C
authors.lastname: Gaul
authors.affiliation: Department of Neurology, University Hospital-Essen, Essen, Germany.
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Diener
authors.affiliation: Walton Centre for Neurology and Neurosurgery, Liverpool, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Silver
authors.affiliation: Liège University, Liège, Belgium.
authors.forename: Delphine
authors.initials: D
authors.lastname: Magis
authors.affiliation: Department of Neurology, Charité University Hospital, Berlin, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Reuter
authors.affiliation: electroCore GMBH, Gothenburg, Sweden.
authors.forename: Annelie
authors.initials: A
authors.lastname: Andersson
authors.affiliation: electroCore, LLC, Basking Ridge, NJ, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Liebler
authors.affiliation: Ludwig Maximilian University of Munich, Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Straube
mesh_terms: D000328:Adult; D003027:Cluster Headache / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055536:Vagus Nerve Stimulation / Q000379:methods*
keywords: Neuromodulation; adjunctive prophylaxis; cluster headache; vagus nerve