Acute migraine therapy with external trigeminal neurostimulation (ACME): A randomized controlled trial

Abstract

ObjectiveTo assess the safety and efficacy of external trigeminal nerve stimulation for acute pain relief during migraine attacks with or without aura via a sham-controlled trial.MethodsThis was a double-blind, randomized, sham-controlled study conducted across three headache centers in the United States. Adult patients who were experiencing an acute migraine attack with or without aura were recruited on site and randomly assigned 1:1 to receive either verum or sham external trigeminal nerve stimulation treatment (CEFALY Technology) for 1 hour. Pain intensity was scored using a visual analogue scale (0 = no pain to 10 = maximum pain). The primary outcome measure was the mean change in pain intensity at 1 hour compared to baseline.ResultsA total of 109 participants were screened between February 1, 2016 and March 31, 2017. Of these, 106 patients were randomized and included in the intention-to-treat analysis (verum: n = 52; sham: n = 54). The primary outcome measure was significantly more reduced in the verum group than in the sham group: −3.46 ± 2.32 versus −1.78 ± 1.89 (p < 0.0001), or −59% versus −30% (p < 0.0001). With regards to migraine subgroups, there was a significant difference in pain reduction between verum and sham for ‘migraine without aura’ attacks: mean visual analogue scale reduction at 1 hour was −3.3 ± 2.4 for the verum group versus −1.7 ± 1.9 for the sham group (p = 0.0006). For ‘migraine with aura’ attacks, pain reduction was numerically greater for verum versus sham, but did not reach significance: mean visual analogue scale reduction at 1 hour was −4.3 ± 1.8 for the verum group versus −2.6 ± 1.9 for the sham group (p = 0.060). No serious adverse events were reported and five minor adverse events occurred in the verum group.ConclusionOne-hour treatment with external trigeminal nerve stimulation resulted in significant headache pain relief compared to sham stimulation and was well tolerated, suggesting it may be a safe and effective acute treatment for migraine attacks.Study protocolClinicalTrials.gov Identifier: NCT02590939.

Remote Electrical Neuromodulation (REN) Relieves Acute Migraine: A Randomized, Double‐Blind, Placebo‐Controlled, Multicenter Trial

“…In fact, the study on nVNS for acute treatment of migraine did not meet its primary endpoint of pain free at 2 hours post‐treatment (therapeutic gain of 10.7%), which was successfully achieved in the current study, with a therapeutic gain of 19.0%. The therapeutic gain of pain free at 2 hours in the current study was also higher than the therapeutic gain of 10% reported for external trigeminal nerve stimulation . To compare the efficacy of REN to that of triptans, we analyzed the pain relief and pain‐free responses at 2 hours post‐treatment in attacks with moderate or severe baseline pain intensity.…”

Neuromodulation for the Acute and Preventive Therapy of Migraine and Cluster Headache

“…There has been a single randomized, sham‐controlled, double‐blind study looking at the use of STNS for the acute treatment of migraine . This study, called the ACME trial (acute migraine therapy with external trigeminal neurostimulation) recruited 106 patients from 3 medical centers, all of whom had migraine, and randomized them 1:1 to receive either true or sham stimulation at migraine onset.…”

“…There has been a single randomized, sham-controlled, double-blind study looking at the use of STNS for the acute treatment of migraine. 6 This study, called the ACME trial (acute migraine therapy with external trigeminal neurostimulation) recruited 106 patients from 3 medical centers, all of whom had migraine, and randomized them 1:1 to receive either true or sham stimulation at migraine onset. Subjects were told to treat their attack with their assigned device for 1 hour, and the primary outcome was the mean change in pain intensity (using the 1-10 visual analog scale) at 1 hour compared to baseline.…”

Development of a Prospective Real‐World Data Clinical Registry of Children and Adolescents With Migraine

“…2 In addition to causing significant pain, migraine causes children and adolescents to miss school, negatively affects school performance, leads to high health care costs for affected families, and has profound economic impact. [6][7][8][9][10][11][12][13] Pediatric studies are now getting underway to meet regulatory requirements. 4,5 Recently developed novel therapeutics, including drugs, biologics, and neuromodulation devices, are safe and welltolerated in adults.…”

“…4,5 Recently developed novel therapeutics, including drugs, biologics, and neuromodulation devices, are safe and welltolerated in adults. [6][7][8][9][10][11][12][13] Pediatric studies are now getting underway to meet regulatory requirements. Both the US Food and Drug Administration (FDA) and the European Medicines Agency require pediatric studies in order to assess safety, pharmacokinetics, and efficacy in children.…”