A multicenter, prospective, single arm, open label, observational study of sTMS for migraine prevention (ESPOUSE Study)

Abstract

ObjectiveTo evaluate the efficacy and tolerability of single pulse transcranial magnetic stimulation (sTMS) for the preventive treatment of migraine.BackgroundsTMS was originally developed for the acute treatment of migraine with aura. Open label experience has suggested a preventive benefit. The objective of this trial was to evaluate the efficacy and tolerability of sTMS for migraine prevention.MethodsThe eNeura SpringTMS Post-Market Observational U.S. Study of Migraine (ESPOUSE) Study was a multicenter, prospective, open label, observational study. From December 2014 to March 2016, patients with migraine (n = 263) were consented to complete a 1-month baseline headache diary followed by 3 months of treatment. The treatment protocol consisted of preventive (four pulses twice daily) and acute (three pulses repeated up to three times for each attack) treatment. Patients reported daily headache status, medication use, and device use with a monthly headache diary. The primary endpoint, mean reduction of headache days compared to baseline, was measured over the 28-day period during weeks 9 to 12. The primary endpoint was compared to a statistically-derived placebo estimate (performance goal). Secondary endpoints included: 50% responder rate, acute headache medication consumption, HIT-6, and mean reduction in total headache days from baseline of any intensity.ResultsOf a total of 263 consented subjects, 229 completed a baseline diary, and 220 were found to be eligible based on the number of headache days. The device was assigned to 217 subjects (Safety Data Set) and 132 were included in the intention to treat Full Analysis Set. For the primary endpoint, there was a −2.75 ± 0.40 mean reduction of headache days from baseline (9.06 days) compared to the performance goal (−0.63 days) (p < 0.0001). The 50% responder rate of 46% (95% CI 37%, 56%) was also significantly higher (p < 0.0001) than the performance goal (20%). There was a reduction of −2.93 (5.24) days of acute medication use, headache impact measured by HIT-6, −3.1 (6.4) (p < 0.0001), and total headache days of any intensity −3.16 days (5.21) compared to the performance goal (−0.63 days) (p < 0.0001). The most common adverse events were lightheadedness (3.7%), tingling (3.2%), and tinnitus (3.2%). There were no serious adverse events.ConclusionsThis open label study suggests that sTMS may be an effective, well-tolerated treatment option for migraine prevention.Trial registration numberNCT02357381

The American Headache Society Position Statement On Integrating New Migraine Treatments Into Clinical Practice

“…78 Based on results demonstrating efficacy and safety in clinical trials, the United States Food and Drug Administration has cleared: 79,80 • Single-pulse transcranial magnetic stimulation for the acute and preventive treatment of migraine • Electrical trigeminal nerve stimulation for the acute and preventive treatment of migraine • Noninvasive vagus nerve stimulation for the acute treatment of migraine Patients who prefer nondrug therapies and those who have failed to respond to, have contraindications to, or poor tolerability with pharmacotherapy may be candidates for neuromodulation. These treatments modulate pain mechanisms involved in headache by stimulating the nervous system centrally or peripherally with an electric current or a magnetic field.…”

Transcranial Magnetic and Direct Current Stimulation (TMS/tDCS) for the Treatment of Headache: A Systematic Review

“…There were a total of 34 studies included in the descriptive synthesis. Of those, 22 were TMS (16 rTMS) and 12 were tDCS articles (Supplementary Materials – Study Characteristics Tables). A comparison of defining study parameters is outlined below.…”

“…Twelve TMS studies (9 rTMS, 2 sTMS, and 1 dTMS) were randomized trials. The remaining 10 were either non‐randomized controlled or prospective cohort/open label trials . Baseline duration among studies ranged from 1 day to 4 weeks, treatment duration varied from 1 day to 3 months, with 4 weeks being most common.…”

Challenges of differential placebo effects in contemporary medicine: The example of brain stimulation

“…As an interesting aside, more recent studies of TMS for migraine prevention have revealed that stimulation to occipital cortex may be quite efficacious and the eNeura TMS device has received FDA approval for this indication. 41,42 …”