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.

Study Overview

• Status: Completed
• Conditions: Headache; Dilatation of Cranial Arteries; MMA, STA and MCA
• Intervention / Treatment: Drug: Levcromakalim; Drug: Saline

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Glostrup
    • Copenhagen, Glostrup, Denmark, 2600
      • Danish Headache Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Danish Headache Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2018
• Primary Completion (Actual): August 15, 2018
• Study Completion (Actual): August 15, 2018

Study Registration Dates

• First Submitted: June 26, 2018
• First Submitted That Met QC Criteria: July 24, 2018
• First Posted (Actual): August 1, 2018

Study Record Updates

• Last Update Posted (Actual): July 5, 2022
• Last Update Submitted That Met QC Criteria: July 1, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Headache; Physiological Effects of Drugs; Antihypertensive Agents; Vasodilator Agents; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Cromakalim
• Other Study ID Numbers: Levcromakalim & MRI

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No