Non-vascular ATP-sensitive potassium channel activation does not trigger migraine attacks: A randomized clinical trial
Lili Kokoti, Mohammad Al‐Mahdi Al‐Karagholi, Zixuan Alice Zhuang, Sarkhan Amirguliyev, Faisal Mohammad Amin, Messoud Ashina
Abstract
Objective To investigate the role of NN414, a selective K ATP channel opener for the Kir6.2/SUR1 channel subtype found in neurons and β-pancreatic cells, in inducing migraine attacks in individuals with migraine without aura. Methods Thirteen participants were randomly allocated to receive NN414 and placebo on two days separated by at least one week. The primary endpoint was the difference in the incidence of migraine attacks after NN414 compared with placebo. The secondary endpoints were the difference in the area under the curve for headache intensity scores, middle cerebral artery blood flow velocity (V MCA ), superficial temporal artery diameter, heart rate and mean arterial pressure. Results Twelve participants completed the study, with two (16.6%) reporting migraine attacks after NN414 compared to one (8.3%) after placebo (p = 0.53). The area under the curve for headache intensity, V MCA , superficial temporal artery diameter, heart rate and mean arterial pressure did not differ between NN414 and placebo (p > 0.05, all comparisons). Conclusion The lack of migraine induction upon activation of the Kir6.2/SUR1 channel subtype suggests it may not contribute to migraine pathogenesis. Our findings point to K ATP channel blockers that target the Kir6.1/SUR2B subtype, found in cerebral vasculature, as potential candidates for innovative antimigraine treatments. Registration number: NCT04744129