Significant reduction in migraine days with Remote Electrical Neuromodulation (REN) for migraine prevention: A double-blind randomized sham-controlled clinical trial
Stewart Tepper1, Liron Rabany2, Robert Cowan3, Timothy Smith4, Brian Grosberg5, Brad Torphy6, Dagan Harris7, Maya Vizel8, Alon Ironi9, Alit Stark-Inbar8, Sandy Garas10, Andrew Blumenfeld11
1Geisel School of Medicine At Dartmouth, 2Theranica Bio-Electronics Ltd., 3Stanford Neurosciences Health Center, 4StudyMetrix Research, 5Hartford HealthCare Headache Center, 6Chicago Headache Center and Research Institute, 7Theranica BioElectronics Ltd, 8Theranica Bio-Electronics, 9Theranica, 10Theranica USA, 11The Los Angeles and San Diego Headache Centers

The aim of the present clinical trial was to evaluate the efficacy and safety of Remote Electrical Neuromodulation (REN), used every other day, for the prevention of migraine in a multi-center, randomized, double blind, placebo-controlled study.

Migraine affects over 1 billion people worldwide causing significant disability and a socioeconomic burden. Preventive treatment is key to managing migraine, but it is often underutilized. There is an unmet need for non-pharmacological migraine prevention that is both effective and well tolerated. REN, a non-pharmacological acute migraine treatment, was evaluated as a method of migraine prevention in patients with episodic and chronic migraine.
We conducted a prospective, randomized, double-blind, sham-controlled, multi-center trial, with 1:1 ratio. The study consisted of a four-week baseline observation phase, and an eight-week double-blind intervention phase in which subjects used either REN or a sham stimulation every other day. Throughout the study, subjects reported their symptoms daily, via an electronic diary.
Two hundred and forty-eight subjects were randomized (128 active, 120 placebo), of which 179 qualified for the 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 a mean change of -4.0±0.4 days (-1.3±0.4 in placebo, gain =-2.7, p=0.00002). The significance was maintained when analyzing the episodic (-3.2 vs -1.0; p=0.003) and chronic (-4.7 vs -1.6; p=0.001) migraine subgroups separately. A significant reduction in migraine days was also maintained in subjects using a preventative in addition to REN (-3.5 vs -1.5; p=0.03) and in those with no additional prophylaxis (-4.5 vs -1.5; p=0.00016). No serious device-related adverse events were reported in any group.
Applied every other day, REN is effective and safe for the prevention of migraine.