Objective To assess the efficacy and safety of a remote electrical neuromodulation (REN) device for the acute treatment of migraine. Background There is a significant unmet need for novel effective well‐tolerated acute migraine treatments. REN is a novel acute migraine treatment that stimulates upper arm peripheral nerves to induce conditioned pain modulation – an endogenous analgesic mechanism in which conditioning stimulation inhibits pain in remote body regions. A recent pilot study showed that REN can significantly reduce headache. We have conducted a randomized, double‐blind, sham‐controlled study to further evaluate the efficacy and safety of REN for the acute treatment of migraine. Methods This was a randomized, double‐blind, sham‐controlled, multicenter study conducted at 7 sites in the United States and 5 sites in Israel. Two hundred and fifty‐two adults meeting the International Classification of Headache Disorders criteria for migraine with 2‐8 migraine headaches per month were randomized in a 1:1 ratio to active or sham stimulation. A smartphone‐controlled wireless device was applied for 30‐45 minutes on the upper arm within 1 hour of attack onset; electrical stimulation was at a perceptible but non‐painful intensity level. Migraine pain levels were recorded at baseline, 2, and 48 hours post‐treatment. Most bothersome symptoms (MBS) were also recorded. The primary efficacy endpoint was the proportion of participants achieving pain relief at 2 hours post‐treatment (improvement from severe or moderate pain to mild or none, or from mild pain to none). Relief of MBS and pain‐free at 2 hours were key secondary endpoints. Results Active stimulation was more effective than sham stimulation in achieving pain relief (66.7% [66/99] vs 38.8% [40/103]; therapeutic gain of 27.9% [CI95%, 15.6‐40.2]; P < .0001), pain‐free (37.4% vs 18.4%, P = .003), and MBS relief (46.3% vs 22.2%, P = .0008) at 2 hours post‐treatment. The pain relief and pain‐free superiority of the active treatment was sustained 48 hours post‐treatment. The incidence of device‐related adverse events was low and similar between treatment groups (4.8% [6/126] vs 2.4% [3/126], P = .499). Conclusions REN provides superior clinically meaningful relief of migraine pain and MBS compared to placebo, offering a safe and effective non‐pharmacological alternative for acute migraine treatment.

This study provides Class III evidence that for patients with an acute migraine headache, remote nonpainful electrical stimulation on the upper arm skin reduces migraine pain.

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.

BackgroundThere is a significant unmet need for new, effective and well tolerated acute migraine treatments. A recent study has demonstrated that a novel remote electrical neuromodulation (REN) treatment provides superior clinically meaningful pain relief with a low rate of device-related adverse events. The results reported herein compare the efficacy of REN with current standard of care in the acute treatments of migraine.MethodsWe performed a post-hoc analysis on a subgroup of participants with migraine from a randomized, double-blind, parallel-group, sham-controlled, multicenter study on acute care. The original study included a 2–4 weeks run-in phase, in which migraine attacks were treated according to patient preference (i.e., usual care) and reported in an electronic diary; next, participants entered a double-blind treatment phase in which they treated the attacks with an active or sham device. The efficacy of REN was compared to the efficacy of usual care or pharmacological treatments in the run-in phase in a within-subject design that included participants who treated at least one attack with the active REN device and reported pain intensity at 2 h post-treatment.ResultsOf the 252 patients randomized, there were 99 participants available for analysis. At 2 h post-treatment, pain relief was achieved in 66.7% of the participants using REN versus 52.5% participants with usual care (p < 0.05). Pain relief at 2 h in at least one of two attacks was achieved by 84.4% of participants versus 68.9% in usual care (p < 0.05). REN and usual care were similarly effective for pain-free status at 2 h. The results also demonstrate the non-inferiority of REN compared with acute pharmacological treatments and its non-dependency on preventive medication use.ConclusionREN is an effective acute treatment for migraine with non-inferior efficacy compared to current acute migraine therapies. Together with a very favorable safety profile, these findings suggest that REN may offer a promising alternative for the acute treatment of migraine and could be considered first line treatment in some patients.Trial registrationClinicalTrials.gov NCT03361423. Registered 18 November 2017.

Introduction: Remote electrical neuromodulation (REN) is a novel acute treatment of migraine. Upper arm peripheral nerves are stimulated to induce conditioned pain modulation (CPM)-an endogenous analgesic mechanism in which conditioning stimulation inhibits pain in remote body regions. The REN device (Nerivio Ò , Theranica Bio-Electronics LTD., Israel) is FDA-authorized for acute treatment of migraine in adults who do not have chronic migraine. The current study assessed Digital Features To view digital features for this article go to