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.

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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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.

Conditions
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Dilatation of Cranial Arteries; MMA, STA and MCA, Headache

Intervention / Treatment
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* Drug: Levcromakalim
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind placebo-controlled study with healthy volunteers.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Levcromakalim<br>18 participants will randomly be allocated in a 2:1 order to receive 1 mg levcromakalim or placebo (isotonic saline) | Drug: Levcromakalim<br>* Intravenous administration of levcromakalim or placebo for 20 minutes. To investigate the role of levcromakalim/placebo on cerebral hemodynamic in healthy volunteers.<br>|
| Placebo Comparator: Saline<br>18 participants will randomly be allocated in a 2:1 order to receive 1 mg levcromakalim or placebo (isotonic saline) | Drug: Saline<br>* Intravenous administration of levcromakalim or placebo for 20 minutes. To investigate the role of levcromakalim/placebo on cerebral hemodynamic in healthy volunteers.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change is assessed of cranaial arteries; MMA, STA and MCA | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Headache | 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 |