Migraine prevention by noninvasive electrical fastigial nucleus stimulation: a multi-center, randomized, double-blind, sham-controlled trial

Background: Migraine is a global disease with a high morbidity rate, and while there is medication for migraine prevention, it has many side effects. Thus there is a need to find a non-drug therapy to prevent migraine in patients with frequent attacks of migraine, severe pain, and poor drug control. Cortical spreading depression (CSD) is an important pathological mechanism behind migraine. Electrical fastigial nucleus stimulation (FNS) can reportedly inhibit the occurrence and propagation of CSD, and therefore can be used to prevent migraine. Methods/Design: This is a prospective, multi-center, randomized, double-blind, sham-controlled trial. It will be performed at Chengdu Second People′s Hospital, the Second Affiliated Hospital of Chongqing Medical University, Chongqing Fourth People′s Hospital, the First Affiliated Hospital of Chongqing Medical University, and Chongqing People′s Hospital, China. The approach is to randomly allocate 80 eligible migraine patients to undergo 3 months of either noninvasive electrical FNS (pulse width 90 μs, frequency 1.8 kHz, and output current 10 mA) or ineffective sham-stimulation (using the same stimulation equipment; pulse width 90 μs, frequency 10 kHz, and output current 0.18 mA). The primary outcomes are: change in monthly migraine days between the run-in month and 3 rd month of treatment, and percentage of patients having at least a 50% reduction of monthly migraine days in the 3 rd month of treatment. The secondary outcomes are: change between average monthly migraine days across 3 months of treatment and monthly migraine days in the 3 rd month of treatment, Visual Analogue Scale score in the 3 rd month of treatment, change in monthly anti-migraine drug use between the run-in month and 3 rd month of treatment, migraine disability assessment questionnaire score, accompanying symptoms, and adverse reactions. Discussion: In previous studies on electrical FNS for the treatment of various brain injuries, sample sizes have been small with inclusion of only a small number of institutions and non-rigorous trial protocols. Accordingly, the data obtained were not very reliable. In this study, we will validate the efficacy of electrical FNS in migraine prevention using a multi-center, randomized, double-blinded, controlled trial. Our findings will provide evidence for clinical application of this method. Trial registration: The trial protocol was registered at Chinese Clinical Trial Registry (www.chictr.org.cn) (registration number: ChiCTR-ICR-15006273) on 5 April 2015. Ethics: This trial was approved by the Ethics Committee of Chengdu Second People′s Hospital, China on 9 April 2015 (approval number: 2015010), and will be performed in accordance with the guidelines of the Declaration of Helsinki, formulated by the World Medical Association. Informed consent: Written informed consent will be obtained from participants or their guardians.