A Randomized, Double-blinded, Placebo-controlled Trial of Idebenone in the Prevention of Episodic Migraine

One-hundred-and-eighty subjects will be recruited for a placebo-controlled, double-blinded study of idebenone (90 mg/day, 270 mg/day) versus placebo. One-hundred-and-eighty subjects will be recruited based on past research and an expected 20% dropout rate. A dose of 90mg or 270 mg is based on large number of reports at study initiation in Leber's hereditary optic neuropathy that demonstrated the safety of 900mg/day. Subjects are 18 to 65 years old, inclusive, who meet the International Classification of Headache Disorder- III (ICHD-III) for episodic migraine with or without aura, no over consumption of acute anti-migraine medication, no other prophylactic medication (washout 3 months), no serious organic or psychiatric disease, who are recommended to start prophylactic therapy (two to eight attacks per month). Written informed consent is obtained. The process of patients through the trial phases follows the CONSORT flow chart.

Idebenone and placebo were provided by Qilu Pharmaceutical Company Limited, China. Placebo consisted of the same ingredients as verum-instead idebenone, they classify as fit for human consumption in the China and without any known effect on migraine.

The design of this double-blind, randomized, placebo-controlled trial followed the IHS Committee on Clinical Trials in Migraine guidelines, 8 current EU guidelines on Good Clinical Practice, and the Declaration of Helsinki. It was approved by Neurology Department, the Second Affiliated Hospital, School of Medicine, Zhejiang University. This study is supported by the following funding sources: the Zhejiang Provincial Natural Science Foundation of China (Grant No. LY19H090025, Grant No. LQ15H090003), the National Natural Science Foundation of China (Grant No. 81101157). The study is also supported by Qilu Pharmaceutical Company Limited, China (http://www.qilu-pharma.com); the use of idebenone in migraine, is patent pending in the China. Dr. Kaiming Liu do not receive honoraria from the sponsor of the study.

Exclusion criteria includes subjects who previously failed idebenone therapy for migraine prophylaxis, those who previously discontinued idebenone due to adverse events, those who are taking idebenone or had taken idebenone within 14 days prior to enrollment, and subjects with continuous headaches. Subjects will be equally randomized to be treated with 90 mg/day idebenone, 270 mg/day idebenone, or placebo for 3 months.

At the first visit, patients will receive placebo for a 1-month base-line. At the second visit, they will be randomized to be treated with 90 mg/day idebenone, 270 mg/day idebenone, or placebo for next 3 months if they have presented at least one migraine attack.