Remote Electrical Neuromodulation for Acute Treatment of Migraine in Adolescents

Andrew D. Hershey MD, PhD, FAAN, FAHS; Tamar Lin PhD; Yaron Gruper MSc; Dagan Harris PhD; Alon Ironi MSEE; Thomas Berk MD; Christina L. Szperka MD, MSCE; Frank Berenson MD, FAHS

Disclosures

Headache. 2021;61(2):310-317. 

In This Article

Abstract and Introduction

Abstract

Objectives: Migraine is a common disabling neurological disorder. Current acute treatments for migraine in adolescents are mostly pharmacological and may have limited effectiveness, can cause side effects, and may lead to medication overuse. There is an unmet need for effective and well-tolerated treatments. Remote electrical neuromodulation (REN) is a novel acute treatment of migraine that stimulates upper arm peripheral nerves to induce conditioned pain modulation (CPM)—an endogenous analgesic mechanism. The REN device (Nerivio®, Theranica Bio-Electronics Ltd., Israel) is a FDA-authorized device for acute treatment of migraine in adults. This study assessed the efficacy and safety of REN in adolescents with migraine.

Design and Methods: This was an open-label, single-arm, multicenter study in adolescents (ages 12–17 years) with migraine. Participants underwent a 4-week run-in phase. Eligible participants continued to an 8-week treatment phase with the device. Pain severity, associated symptoms, and functional disability were recorded at treatment initiation, and 2 and 24 hours post-treatment. The primary endpoints of this study were related to the safety and tolerability of REN. The secondary endpoints were related to device efficacy and included the proportion of participants who achieved pain relief at 2 hours post-treatment and the proportion of participants who achieved pain freedom at 2 hours. The presented results reflect an interim analysis with subsequent stopping of the rest of the study.

Results: Sixty participants were enrolled for the study; of these, 14 failed to meet the run-in criteria and 1 was lost to follow-up. Forty-five participants performed at least one treatment, of which 39 participants completed a test treatment with REN. One device-related adverse event (2%) was reported in which a temporary feeling of pain in the arm was felt. Pain relief and pain-free at 2 hours were achieved by 71% (28/39) and 35% (14/39) participants, respectively. At 2 hours, 69% (23/33) participants experienced improvement in functional ability.

Conclusions: REN may offer a safe and effective non-pharmacological alternative for acute treatment in adolescents.

Introduction

Migraine is one of the most prevalent and disabling diseases worldwide, affecting approximately 9% of children and adolescents.[1] The prevalence of migraine increases with age, particularly during adolescence.[2] Migraine in adolescents has been associated with missed school days,[3] poorer performance in school,[4] negative effect on peer and social interactions, and negative impact on quality of life.[5]

The majority of current migraine acute treatments for adolescents are pharmacological.[6] These treatments may not always be effective,[7] they can cause side effects, and their overuse may lead to medication overuse headache[8,9] and migraine chronification.[10] Thus, there is a great unmet need for alternative acute migraine treatments that are both effective and well tolerated to improve the health and quality of life of adolescents with migraines.

Noninvasive neuromodulation devices represent an emerging field in the acute treatment of migraine. Remote electrical neuromodulation (REN)[11–15] is a non-pharmacological, noninvasive, acute migraine treatment that stimulates upper arm peripheral nerves to induce conditioned pain modulation—an endogenous analgesic mechanism in which a conditioning stimulation inhibits pain in remote body regions.[16] The REN device (Nerivio®, Theranica Bio-Electronics Ltd., Israel) is a wireless, wearable, battery-operated stimulation unit controlled by a smartphone software application. The device is applied for 45 minutes to the lateral upper arm and mainly stimulates small skin nerves.

The safety and efficacy of REN have been previously assessed for migraine in a randomized, double-blind, sham-controlled multicenter study conducted on adults aged 18 years and above.[12] This study demonstrated that REN provides superior clinically meaningful relief of migraine pain and most bothersome symptom (MBS) compared to placebo (pain relief: 66.7% vs. 38.8%), offering a safe and effective non-pharmacological alternative for acute migraine treatment. The aim of this study was to evaluate the safety and efficacy of REN for acute treatment of migraine in adolescents. We hypothesized that the safety of the REN device in adolescents will be favorable and similar to that observed in adults.

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