The Hemodynamics Effect of Glibenclamide on Levcromakalim Assessed by High Resolution Magnetic Resonance Angiography (MRA) Technique in a Randomized Double-blind Cross-over Placebo-controlled Study With Healthy Volunteers

Study Overview
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Brief Summary
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To investigate the effect of levcromakalim/placebo infusion on cranial arteries after glibenclamide administration.

Detailed Description
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15 healthy participants will randomly be allocated to receive levcromakalim or placebo on to different days before and after oral glibenclamide administration. The aim of the study is to investigate the effect of levcromakalim/placebo infusion on cranial arteries before and after glibenclamide administration. Repeated magnetic resonance angiography (MRA) measurements covering the middle meningeal artery (MMA), superficial temporal artery (STA) and middle cerebral artery (MCA) before and after glibenclamide administration and levcromakalim/placebo infusion.

Official Title
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The Hemodynamics Effect of Levcromakalim After Glibenclamide Administration Assessed by High Resolution MRA Technique in a Randomized, Double-blind, Cross-over and Placebo-controlled Study With Healthy Volunteers.

Conditions
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Hemodynamics of Cranial Arteries, Headache, Cerebral Blood Flow

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: Crossover Assignment
Interventional Model Description: Randomized, double-blind, cross-over, placebo-controlled design in healthy volunteers.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Glibenclamide and Levcromakalim<br>Participants will receive levcromakalim infusion after glibenclamide administration | Drug: Levcromakalim<br>* Intravenous infusion of levcromakalim or placebo for 20 minutes. To investigate the role of levcromakalim/placebo on cranial arteries in healthy volunteers after glibenclamide administration.<br>|
| Active Comparator: Glibenclamide and Saline<br>Participants will receive placebo infusion after glibenclamide administration | Drug: Saline<br>* Intravenous infusion of levcromakalim or placebo for 20 minutes. To investigate the role of levcromakalim/placebo on cranial arteries in healthy volunteers after glibenclamide administration.<br>|
| Sham Comparator: Placebo<br>Participants will receive placebo infusion after placebo administration. | Drug: Saline<br>* Intravenous infusion of levcromakalim or placebo for 20 minutes. To investigate the role of levcromakalim/placebo on cranial arteries in healthy volunteers after glibenclamide administration.<br>|
| Active Comparator: Levcromakalim and Glibenclamide<br>Participants will receive levcromakalim infusion before glibenclamide administration. | Drug: Levcromakalim<br>* Intravenous infusion of levcromakalim or placebo for 20 minutes. To investigate the role of levcromakalim/placebo on cranial arteries in healthy volunteers after glibenclamide administration.<br>|
| Active Comparator: Levcromakalim and Placebo<br>Participants will receive levcromakalim infusion before placebo administration. | Drug: Levcromakalim<br>* Intravenous infusion of levcromakalim or placebo for 20 minutes. To investigate the role of levcromakalim/placebo on cranial arteries in healthy volunteers after glibenclamide administration.<br>Drug: Saline<br>* Intravenous infusion of levcromakalim or placebo for 20 minutes. To investigate the role of levcromakalim/placebo on cranial arteries in healthy volunteers after glibenclamide administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the middle meningeal artery (MMA), superficiel temporal artery (STA) and middle cerebral artery (MCA) | Repeated MRA measurements covering the diameter of MMA , STA and MCA before and after glibenclamide administration and levcromakalim/placebo infusion measured by centimeter (cm) | Time of measurements is baseline, 1 hour after glibenclamide administration, 2 hour after glibenclamide administration, 20 minutes after levcromakalim infusion, 60 min after levcromakalim infusion | 
| Changes in Cerebral blood flow | Repeated MRA measurements covering the blood flow before and after glibenclamide administration and levcromakalim/placebo infusion measured by centimeter (cm)/minutes | Time of measurements is baseline, 1 hour after glibenclamide administration, 2 hour after glibenclamide administration, 20 minutes after levcromakalim infusion, 60 min after levcromakalim infusion | 
| Headache | Headache intensity will be recorded by numerical rating scale (NRS) from 0 to 10 (0, no headache; 1, a feeling of pressure; 10, worst imaginable headache). | Time of headache measurements is from before (-10 min) and after (12 hours) glibenclamide administration. |