Effects of levcromakalim in patients with migraine aura without headache: An experimental study

Abstract

Background/Hypothesis Levcromakalim has previously been shown to induce attacks of migraine with aura in certain individuals. In this study, we tested the migraine-inducing effect of levcromakalim in a cohort of participants with migraine aura without headache. Methods In a double-blind, randomized, placebo-controlled cross-over study, eight adult participants with migraine with aura received intravenous infusions of levcromakalim and saline. Headache, aura and associated symptoms were evaluated for 24 h following administration of the study drug. The primary endpoint was occurrence of migraine-like attacks with or without aura in the 24-h observation period. Results Five participants (62.5%) developed migraine of any type following levcromakalim compared with three participants (37.5%) following placebo. No participants developed aura following levcromakalim. Conclusion/Interpretation Our findings suggest that the aura-inducing effect of levcromakalim is likely not based on direct induction of cortical spreading depression but may involve activation of the trigeminovascular system. This hypothesis should be further explored in future studies. ClinicalTrials.gov identifier NCT04905654