Experimental Design and Randomization
headache
FRANKLIN
We conducted a double-blind, placebo-controlled, three-arm, crossover study. All enrolled participants came at the clinic on three different study days separated by at least 1 week where they were randomly allocated without restrictions to receive a continuous intravenous infusion of 20 mL levcromakalim (0.05 mg/min (50 mg/mL) (Sigma-Aldrich, Darmstadt, Germany)) or 20 mL placebo (isotonic saline) over 20 min, followed by oral administration of glibenclamide (10 mg oral tablet of Hexaglucon, Sandoz) or placebo (multivitamin pill) 80 min afterwards. The three study days were the following: infusion of levcromakalim followed by oral placebo (levcromakalim-placebo day), levcromakalim infusion followed by oral glibenclamide (levcromakalim-glibenclamide day), and infusion of placebo followed by oral placebo (placebo-placebo day) (Fig. Experimental design. Healthy participants (Participants arrived at the clinic non-fasting, at the same time on each study day (± 2 h). Participants were at least 48 h headache-free and were not allowed to consume coffee, tea, cocoa, alcohol, and tobacco 12 h prior to study onset. All female participants were tested for pregnancy on all study days. A venous catheter (BD VenflonVR, Franklin Lakes, NJ) was inserted into the left and right antecubital vein for drug (levcromakalim/placebo) and 20% glucose infusion. The infusion started using a time and volume-controlled infusion pump. Mean arterial blood pressure (MABP) and heart rate (HR) were continuously monitored and recorded at baseline (T0) and every 10 min after the start of the infusion (Fig. Experimental timeline. There was a 240-min in-hospital phase of the experiment and 8 h of outpatient headache diary. 