title: Chronic migraine headache prevention with noninvasive vagus nerve stimulation: The EVENT study.
abstract: OBJECTIVE
  To evaluate the feasibility, safety, and tolerability of noninvasive vagus nerve stimulation (nVNS) for the prevention of chronic migraine (CM) attacks.
  
  
  METHODS
  In this first prospective, multicenter, double-blind, sham-controlled pilot study of nVNS in CM prophylaxis, adults with CM (≥15 headache d/mo) entered the baseline phase (1 month) and were subsequently randomized to nVNS or sham treatment (2 months) before receiving open-label nVNS treatment (6 months). The primary endpoints were safety and tolerability. Efficacy endpoints in the intent-to-treat population included change in the number of headache days per 28 days and acute medication use.
  
  
  RESULTS
  Fifty-nine participants (mean age, 39.2 years; mean headache frequency, 21.5 d/mo) were enrolled. During the randomized phase, tolerability was similar for nVNS (n = 30) and sham treatment (n = 29). Most adverse events were mild/moderate and transient. Mean changes in the number of headache days were -1.4 (nVNS) and -0.2 (sham) (Δ = 1.2; p = 0.56). Twenty-seven participants completed the open-label phase. For the 15 completers initially assigned to nVNS, the mean change from baseline in headache days after 8 months of treatment was -7.9 (95% confidence interval -11.9 to -3.8; p < 0.01).
  
  
  CONCLUSIONS
  Therapy with nVNS was well-tolerated with no safety issues. Persistent prophylactic use may reduce the number of headache days in CM; larger sham-controlled studies are needed.
  
  
  BACKGROUND
  NCT01667250.
  
  
  METHODS
  This study provides Class II evidence that for patients with CM, nVNS is safe, is well-tolerated, and did not significantly change the number of headache days. This pilot study lacked the precision to exclude important safety issues or benefits of nVNS.
authors.affiliation: From Jefferson Headache Center (S.D.S.), Philadelphia, PA; Carolina Headache Institute (A.H.C.), Chapel Hill, NC; Montefiore Headache Center and Albert Einstein College of Medicine (R.B.L.), Bronx, NY; Hartford HealthCare Headache Center (B.M.G.), West Hartford, CT; Clinvest Headache Care Center (R.K.C.), Springfield, MO; MedLogix Communications, LLC (S.D.), Schaumburg, IL; electroCore, LLC (K.A.S., E.J.L.), Basking Ridge, NJ; NAMSA (C.M.), Minneapolis, MN; University of California San Francisco (P.J.G.); King's College London (P.J.G.), UK; and Michigan Headache and Neurological Institute (J.R.S.), Ann Arbor. B.M.G. was affiliated with Montefiore Headache Center, Bronx, NY, at the time of study completion. stephen.silberstein@jefferson.edu.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Silberstein
authors.affiliation: From Jefferson Headache Center (S.D.S.), Philadelphia, PA; Carolina Headache Institute (A.H.C.), Chapel Hill, NC; Montefiore Headache Center and Albert Einstein College of Medicine (R.B.L.), Bronx, NY; Hartford HealthCare Headache Center (B.M.G.), West Hartford, CT; Clinvest Headache Care Center (R.K.C.), Springfield, MO; MedLogix Communications, LLC (S.D.), Schaumburg, IL; electroCore, LLC (K.A.S., E.J.L.), Basking Ridge, NJ; NAMSA (C.M.), Minneapolis, MN; University of California San Francisco (P.J.G.); King's College London (P.J.G.), UK; and Michigan Headache and Neurological Institute (J.R.S.), Ann Arbor. B.M.G. was affiliated with Montefiore Headache Center, Bronx, NY, at the time of study completion.
authors.forename: Anne H
authors.initials: AH
authors.lastname: Calhoun
authors.affiliation: From Jefferson Headache Center (S.D.S.), Philadelphia, PA; Carolina Headache Institute (A.H.C.), Chapel Hill, NC; Montefiore Headache Center and Albert Einstein College of Medicine (R.B.L.), Bronx, NY; Hartford HealthCare Headache Center (B.M.G.), West Hartford, CT; Clinvest Headache Care Center (R.K.C.), Springfield, MO; MedLogix Communications, LLC (S.D.), Schaumburg, IL; electroCore, LLC (K.A.S., E.J.L.), Basking Ridge, NJ; NAMSA (C.M.), Minneapolis, MN; University of California San Francisco (P.J.G.); King's College London (P.J.G.), UK; and Michigan Headache and Neurological Institute (J.R.S.), Ann Arbor. B.M.G. was affiliated with Montefiore Headache Center, Bronx, NY, at the time of study completion.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Lipton
authors.affiliation: From Jefferson Headache Center (S.D.S.), Philadelphia, PA; Carolina Headache Institute (A.H.C.), Chapel Hill, NC; Montefiore Headache Center and Albert Einstein College of Medicine (R.B.L.), Bronx, NY; Hartford HealthCare Headache Center (B.M.G.), West Hartford, CT; Clinvest Headache Care Center (R.K.C.), Springfield, MO; MedLogix Communications, LLC (S.D.), Schaumburg, IL; electroCore, LLC (K.A.S., E.J.L.), Basking Ridge, NJ; NAMSA (C.M.), Minneapolis, MN; University of California San Francisco (P.J.G.); King's College London (P.J.G.), UK; and Michigan Headache and Neurological Institute (J.R.S.), Ann Arbor. B.M.G. was affiliated with Montefiore Headache Center, Bronx, NY, at the time of study completion.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Grosberg
authors.affiliation: From Jefferson Headache Center (S.D.S.), Philadelphia, PA; Carolina Headache Institute (A.H.C.), Chapel Hill, NC; Montefiore Headache Center and Albert Einstein College of Medicine (R.B.L.), Bronx, NY; Hartford HealthCare Headache Center (B.M.G.), West Hartford, CT; Clinvest Headache Care Center (R.K.C.), Springfield, MO; MedLogix Communications, LLC (S.D.), Schaumburg, IL; electroCore, LLC (K.A.S., E.J.L.), Basking Ridge, NJ; NAMSA (C.M.), Minneapolis, MN; University of California San Francisco (P.J.G.); King's College London (P.J.G.), UK; and Michigan Headache and Neurological Institute (J.R.S.), Ann Arbor. B.M.G. was affiliated with Montefiore Headache Center, Bronx, NY, at the time of study completion.
authors.forename: Roger K
authors.initials: RK
authors.lastname: Cady
authors.affiliation: From Jefferson Headache Center (S.D.S.), Philadelphia, PA; Carolina Headache Institute (A.H.C.), Chapel Hill, NC; Montefiore Headache Center and Albert Einstein College of Medicine (R.B.L.), Bronx, NY; Hartford HealthCare Headache Center (B.M.G.), West Hartford, CT; Clinvest Headache Care Center (R.K.C.), Springfield, MO; MedLogix Communications, LLC (S.D.), Schaumburg, IL; electroCore, LLC (K.A.S., E.J.L.), Basking Ridge, NJ; NAMSA (C.M.), Minneapolis, MN; University of California San Francisco (P.J.G.); King's College London (P.J.G.), UK; and Michigan Headache and Neurological Institute (J.R.S.), Ann Arbor. B.M.G. was affiliated with Montefiore Headache Center, Bronx, NY, at the time of study completion.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dorlas
authors.affiliation: From Jefferson Headache Center (S.D.S.), Philadelphia, PA; Carolina Headache Institute (A.H.C.), Chapel Hill, NC; Montefiore Headache Center and Albert Einstein College of Medicine (R.B.L.), Bronx, NY; Hartford HealthCare Headache Center (B.M.G.), West Hartford, CT; Clinvest Headache Care Center (R.K.C.), Springfield, MO; MedLogix Communications, LLC (S.D.), Schaumburg, IL; electroCore, LLC (K.A.S., E.J.L.), Basking Ridge, NJ; NAMSA (C.M.), Minneapolis, MN; University of California San Francisco (P.J.G.); King's College London (P.J.G.), UK; and Michigan Headache and Neurological Institute (J.R.S.), Ann Arbor. B.M.G. was affiliated with Montefiore Headache Center, Bronx, NY, at the time of study completion.
authors.forename: Kristy A
authors.initials: KA
authors.lastname: Simmons
authors.affiliation: From Jefferson Headache Center (S.D.S.), Philadelphia, PA; Carolina Headache Institute (A.H.C.), Chapel Hill, NC; Montefiore Headache Center and Albert Einstein College of Medicine (R.B.L.), Bronx, NY; Hartford HealthCare Headache Center (B.M.G.), West Hartford, CT; Clinvest Headache Care Center (R.K.C.), Springfield, MO; MedLogix Communications, LLC (S.D.), Schaumburg, IL; electroCore, LLC (K.A.S., E.J.L.), Basking Ridge, NJ; NAMSA (C.M.), Minneapolis, MN; University of California San Francisco (P.J.G.); King's College London (P.J.G.), UK; and Michigan Headache and Neurological Institute (J.R.S.), Ann Arbor. B.M.G. was affiliated with Montefiore Headache Center, Bronx, NY, at the time of study completion.
authors.forename: Chris
authors.initials: C
authors.lastname: Mullin
authors.affiliation: From Jefferson Headache Center (S.D.S.), Philadelphia, PA; Carolina Headache Institute (A.H.C.), Chapel Hill, NC; Montefiore Headache Center and Albert Einstein College of Medicine (R.B.L.), Bronx, NY; Hartford HealthCare Headache Center (B.M.G.), West Hartford, CT; Clinvest Headache Care Center (R.K.C.), Springfield, MO; MedLogix Communications, LLC (S.D.), Schaumburg, IL; electroCore, LLC (K.A.S., E.J.L.), Basking Ridge, NJ; NAMSA (C.M.), Minneapolis, MN; University of California San Francisco (P.J.G.); King's College London (P.J.G.), UK; and Michigan Headache and Neurological Institute (J.R.S.), Ann Arbor. B.M.G. was affiliated with Montefiore Headache Center, Bronx, NY, at the time of study completion.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Liebler
authors.affiliation: From Jefferson Headache Center (S.D.S.), Philadelphia, PA; Carolina Headache Institute (A.H.C.), Chapel Hill, NC; Montefiore Headache Center and Albert Einstein College of Medicine (R.B.L.), Bronx, NY; Hartford HealthCare Headache Center (B.M.G.), West Hartford, CT; Clinvest Headache Care Center (R.K.C.), Springfield, MO; MedLogix Communications, LLC (S.D.), Schaumburg, IL; electroCore, LLC (K.A.S., E.J.L.), Basking Ridge, NJ; NAMSA (C.M.), Minneapolis, MN; University of California San Francisco (P.J.G.); King's College London (P.J.G.), UK; and Michigan Headache and Neurological Institute (J.R.S.), Ann Arbor. B.M.G. was affiliated with Montefiore Headache Center, Bronx, NY, at the time of study completion.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goadsby
authors.forename: Joel R
authors.initials: JR
authors.lastname: Saper
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D020773:Headache Disorders / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000517:prevention & control*; D010865:Pilot Projects; D016896:Treatment Outcome; D055536:Vagus Nerve Stimulation / Q000009:adverse effects; D055815:Young Adult