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 - 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 - Irimia Sieira, Pablo

AU - Làinez, Miguel J.A.

AU - Gaul, Charly

AU - Silver, Nicholas

AU - Hoffmann, Jan

AU - Marin, Juana

AU - Liebler, Eric

AU - Ferrari, Michel D.

PY - 2019/10

Y1 - 2019/10

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 - migraine prophylaxis

KW - Neuromodulation

KW - non-pharmacologic treatment

KW - preventive therapy

KW - RCT

KW - vagal activation

U2 - 10.1177/0333102419876920

DO - 10.1177/0333102419876920

M3 - Journal article

C2 - 31522546

AN - SCOPUS:85073125762

VL - 39

SP - 1475

EP - 1487

JO - Cephalalgia

JF - Cephalalgia

SN - 0800-1952

IS - 12

ER -