Remote electrical neuromodulation for migraine prevention: A double‐blind, randomized, placebo‐controlled clinical trial

Abstract

Objective: To assess the clinical efficacy of remote electrical neuromodulation (REN), used every other day, for the prevention of migraine.Background: Preventive treatment is key to managing migraine, but it is often underutilized. REN, a non-pharmacological acute treatment for migraine, was evaluated as a method of migraine prevention in patients with episodic and chronic migraine. Methods: We conducted a prospective, randomized, double-blind, placebo-controlled, multi-center trial, with 1:1 ratio. The study consisted of a 4- week baseline observation phase, and an 8- week double -blind intervention phase in which participants used either REN or a placebo stimulation every other day. Throughout the study, participants reported their symptoms daily, via an electronic diary.Results: Two hundred forty- eight participants were randomized (128 active, 120 pla-cebo), of which 179 qualified for the modified intention- to- treat (mITT) analysis (95 active; 84 placebo). REN was superior to placebo in the primary endpoint, change in mean number of migraine days per month from baseline, with mean reduction of 4.0 +/- SD of 4.0 days (1.3 +/- 4.0 in placebo, therapeutic gain = 2.7 [confidence interval -3.9 to -1.5], p < 0.001). The significance was maintained when analyzing the episodic (-3.2 +/- 3.4 vs. -1.0 +/- 3.6, p = 0.003) and chronic (-4.7 +/- 4.4 vs. -1.6 +/- 4.4, p = 0.001) migraine subgroups separately. REN was also superior to placebo in reduction of mod-erate/severe headache days (3.8 +/- 3.9 vs. 2.2 +/- 3.6, p = 0.005), reduction of head-ache days of all severities (4.5 +/- 4.1 vs. 1.8 +/- 4.6, p < 0.001), percentage of patients achieving 50% reduction in moderate/severe headache days (51.6% [49/95] vs. 35.7% [30/84], p = 0.033), and reduction in days of acute medication intake (3.5 +/- 4.1 vs. 1.4 +/- 4.3, p = 0.001). Similar results were obtained in the ITT analysis. No serious device-related adverse events were reported in any group.Conclusion: Applied every other day, REN is effective and safe for the prevention of migraine.