Non-vascular ATP-sensitive potassium channel activation does not trigger migraine attacks: A randomized clinical trial.

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.