The Effect of Levcromakalim Infusion on the Cranial Arteries Over Several Hours Using a High Resolution MRA Technique in a Randomized, Double-blind Placebo-controlled Design in Healthy Volunteers.

The Effect of Levcromakalim Infusion on the Cranial Arteries Over Several Hours Using a High Resolution MRA Technique in a Randomized, Double-blind Placebo-controlled Design in Healthy Volunteers.

The Effect of Levcromakalim Infusion on the Cranial Arteries Over Several Hours Using a High Resolution MRA Technique in a Randomized, Double-blind Placebo-controlled Design in Healthy Volunteers.

Healthy participants vill randomly be allocated in a 2:1 order to receive 1 mg levcromakalim or placebo (isotonic saline) for 20 min. The investigator here examine the effect of levcromakalim infusion on the MMA and the MCA circumference over several hours using a high resolution MRA technique in a randomized, double-blind placebo-controlled design in healthy volunteers. The investigator hypothesized that levcromakalim induces dilatation of cranial arteries.

Healthy participants vill randomly be allocated in a 2:1 order to receive 1 mg levcromakalim or placebo (isotonic saline) for 20 min. The investigator here examine the effect of levcromakalim infusion on the MMA and the MCA circumference over several hours using a high resolution MRA technique in a randomized, double-blind placebo-controlled design in healthy volunteers. The investigator hypothesized that levcromakalim induces dilatation of cranial arteries. MR imaging will be performed on a 3.0 Tesla Philips Achieva Scanner (Philips Medical Systems, Best, The Netherlands) using an eight-element phased-array receiver head coil. We will obtain repeated MRA measurements covering the MMA and MCA before and after levcromakalim/placebo infusion

18 participants will randomly be allocated in a 2:1 order to receive 1 mg levcromakalim or placebo (isotonic saline)

18 participants will randomly be allocated in a 2:1 order to receive 1 mg levcromakalim or placebo (isotonic saline)

Intravenous administration of levcromakalim or placebo for 20 minutes. To investigate the role of levcromakalim/placebo on cerebral hemodynamic in healthy volunteers.

Intravenous administration of levcromakalim or placebo for 20 minutes. To investigate the role of levcromakalim/placebo on cerebral hemodynamic in healthy volunteers.

The investigator will obtain repeated MRA measurements covering the diameter of MMA and MCA before and after levcromakalim/placebo infusion.

Before and after infusion of levcromakalim compared with before and after infusion of saline. Time of measurements is baseline, 20 min, 110 min, 200 min, 290 min and 350 min after the infusion.

Headache intensity will be recorded on a verbal rating scale (VRS) from 0 to 10 (0, no headache; 1, a feeling of pressure; 10, worst imaginable headache). Time of headache measurements is before (-10 min) and after infusion (+16 hours) of levcromakalim compared with before and after infusion of saline

Before (-10 min) and after infusion (+16 hours) of levcromakalim compared with before and after infusion of saline

Inclusion Criteria: Healthy volunteers of both sexes. 18-60 years. 50-100 kg. Women of childbearing potential must use adequate contraception. Exclusion Criteria: A history of serious somatic disease Migraine or any other type of headache (except episodic tension-type headache less than once a month) Daily intake of any medication except contraceptives Contraindications for MRI scan.

Al-Karagholi MA, Ghanizada H, Hansen JM, Skovgaard LT, Olesen J, Larsson HBW, Amin FM, Ashina M. Levcromakalim, an Adenosine Triphosphate-Sensitive Potassium Channel Opener, Dilates Extracerebral but not Cerebral Arteries. Headache. 2019 Oct;59(9):1468-1480. doi: 10.1111/head.13634. Epub 2019 Sep 18.