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.

• ClinicalTrials.gov Identifier: NCT03609008
• Recruitment Status: Completed
• First Posted: August 1, 2018
• Last Update Posted: March 21, 2019
• Sponsor: Danish Headache Center
• Information provided by (Responsible Party): Mohammad Al-Mahdi Al-Karagholi, Danish Headache Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Dilatation of Cranial Arteries; MMA, STA and MCA; Headache	Drug: Levcromakalim; Drug: Saline	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, double-blind placebo-controlled study with healthy volunteers.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: 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.
• Actual Study Start Date: June 26, 2018
• Actual Primary Completion Date: August 15, 2018
• Actual Study Completion Date: August 15, 2018

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Change is assessed of cranaial arteries; MMA, STA and MCA [ Time Frame: 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. ]
   The investigator will obtain repeated MRA measurements covering the diameter of MMA and MCA before and after levcromakalim/placebo infusion.

Secondary Outcome Measures :

1. Headache [ Time Frame: Before (-10 min) and after infusion (+16 hours) of levcromakalim compared with before and after infusion of saline ]

   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Denmark

Danish headache center

Copenhagen, Glostrup, Denmark, 2600

Sponsors and Collaborators

Danish Headache Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Mohammad Al-Mahdi Al-Karagholi, MD, PhD student, Danish Headache Center
• ClinicalTrials.gov Identifier: NCT03609008
• Other Study ID Numbers: Levcromakalim & MRI
• First Posted: August 1, 2018
• Last Update Posted: March 21, 2019
• Last Verified: August 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Headache; Pain; Neurologic Manifestations; Cromakalim; Antihypertensive Agents; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Parasympatholytics; Vasodilator Agents