TY - JOUR
T1 - Non-invasive vagus nerve stimulation (nVNS) for the preventive treatment of episodic migraine
T2 - The multicentre, double-blind, randomised, sham-controlled PREMIUM trial
AU - PREMIUM Study Group
AU - Diener, Hans-Christoph
AU - Goadsby, Peter J
AU - Ashina, Messoud
AU - Al-Karagholi, Mohammad Al-Mahdi
AU - Sinclair, Alexandra
AU - Mitsikostas, Dimos
AU - Magis, Delphine
AU - Pozo-Rosich, Patricia
AU - Sieira, Pablo Irimia
AU - Làinez, Miguel Ja
AU - Gaul, Charly
AU - Silver, Nicholas
AU - Hoffmann, Jan
AU - Marin, Juana
AU - Liebler, Eric
AU - Ferrari, Michel D
PY - 2019/10/1
Y1 - 2019/10/1
N2 - INTRODUCTION: Non-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.METHODS: 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 (6-8 hours apart).RESULTS: 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 = 165; baseline, 7.9 days) and 1.80 for sham (n = 167; baseline, 8.1 days) (p = 0.15). Results were similar across other outcomes. Upon observation of suboptimal adherence rates, post hoc analysis of patients with ≥ 67% adherence per month demonstrated significant differences between nVNS (n = 138) and sham (n = 140) for outcomes including reduction in migraine days (2.27 vs. 1.53; p = 0.043); 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.CONCLUSIONS: Preventive 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. Study identification and registration: PREMIUM; NCT02378844; https://clinicaltrials.gov/ct2/show/NCT02378844.
AB - INTRODUCTION: Non-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.METHODS: 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 (6-8 hours apart).RESULTS: 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 = 165; baseline, 7.9 days) and 1.80 for sham (n = 167; baseline, 8.1 days) (p = 0.15). Results were similar across other outcomes. Upon observation of suboptimal adherence rates, post hoc analysis of patients with ≥ 67% adherence per month demonstrated significant differences between nVNS (n = 138) and sham (n = 140) for outcomes including reduction in migraine days (2.27 vs. 1.53; p = 0.043); 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.CONCLUSIONS: Preventive 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. Study identification and registration: PREMIUM; NCT02378844; https://clinicaltrials.gov/ct2/show/NCT02378844.
KW - Neuromodulation
KW - RCT
KW - migraine prophylaxis
KW - non-pharmacologic treatment
KW - preventive therapy
KW - vagal activation
UR - http://www.scopus.com/inward/record.url?scp=85073125762&partnerID=8YFLogxK
U2 - 10.1177/0333102419876920
DO - 10.1177/0333102419876920
M3 - Article
C2 - 31522546
SN - 0333-1024
VL - 39
SP - 1475
EP - 1487
JO - Cephalalgia
JF - Cephalalgia
IS - 12
M1 - 333102419876920
ER -