The Involvement of ATP Sensitive Potassium Channel in Migraine Aura and Migraine Pain.

March 21, 2023 updated by: Mohammad Al-Mahdi Al-Karagholi, Danish Headache Center

Structural and Functional Cerebral Changes After Infusion of ATP Sensitive Potassium Channel Opener Levcromakalim.

The aim of the present study to investigate whether

  • Opening of KATP channels causes migraine pain by activation of meningeal nociceptors and ascending trigeminal nociceptive pathways.
  • Opening of KATP channels causes migraine aura by induction of CSD.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Migraine Pain The trigeminovascular system is the anatomical and physiological substrate of migraine pain. Nociceptive transmission originates from activation and sensitization of first-order trigeminovascular neurons. Their cell bodies are in the trigeminal ganglion, and their afferent fibers innervate the meninges and its vessels. Ascending nociceptive transmission from the trigeminal ganglion is projected to the brain stem, activating and sensitizing second-order trigeminovascular neurons, including those in the spinal trigeminal nucleus. This, in turn, activates and sensitizes third-order trigeminovascular neurons in the thalamus, which subsequently relay the nociceptive transmission to the somatosensory cortex and other cortical areas, ultimately resulting in migraine pain.

Although the biological underpinnings of migraine pain are incompletely understood, signaling pathways have been identified that are putatively responsible for the genesis of migraine pain. Recent human experimental data have implicated opening of KATP channels in migraine pathogenesis. In two randomized controlled trials, it was demonstrated that intravenous infusion of levcromakalim - an opener of KATP channels - induced migraine pain in people with migraine with and without aura.

- It remains unknown whether KATP channel opening causes migraine pain by activation of meningeal nociceptors and ascending trigeminal nociceptive pathways, as proposed during spontaneous migraine attacks.

Migraine Aura About one-third of people with migraine experience aura symptoms, which are characterized by reversible focal neurologic symptoms, typically comprising visual or hemisensory disturbances. The physiological substrate of the aura phase of migraine is thought to be cortical spreading depression (CSD), a self-propagating wave of depolarization across the cerebral cortex that disrupts ionic gradients and is followed by cerebral hypoperfusion. Recently, it was reported that intravenous infusion of levcromakalim - an opener of KATP channels - induced migraine aura in migraine with aura patients.

- It remains unknown whether KATP channel opening causes CSD which leads to migraine aura, as observed during spontaneous migraine attacks.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Migraine patients
  • 18-60 years.
  • 50-100 kg.
  • Women of childbearing potential must use adequate contraception.

Exclusion Criteria:

  • A history of serious somatic disease
  • 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Levcromakalim
Intravenous infusion of 1 mg levcromakalim followed by intravenous sumatriptan infusion.
Drug: Levcromakalim
Intravenous administration of levcromakalim or placebo over 20 minutes. After 3 hours from the administration of levcromakalim or placebo, participants will receive intravenous infusion of sumatriptan over 10 minutes.
Placebo Comparator: placebo (isotonic saline)
Intravenous infusion of placebo (isotonic saline) followed by intravenous sumatriptan infusion.
Drug: Levcromakalim
Intravenous administration of levcromakalim or placebo over 20 minutes. After 3 hours from the administration of levcromakalim or placebo, participants will receive intravenous infusion of sumatriptan over 10 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dynamic diffusion weighted image (DWI)
Time Frame: Before and after infusion of levcromakalim compared with before and after infusion of saline. Time of measurements is baseline, 20 minutes and 160 minutes after the infusion.
To measure transient diffusivity changes related to levcromakalim-induced CSD during the aura phase of migraine in subjects with migraine with aura.
Before and after infusion of levcromakalim compared with before and after infusion of saline. Time of measurements is baseline, 20 minutes and 160 minutes after the infusion.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Vascular imaging before sumatriptan
Time Frame: Before and after infusion of levcromakalim compared with before and after infusion of saline. Time of measurements is baseline, 20 minutes and 160 minutes after the infusion.
To investigate the diameter of middle meningeal arteries (MMA), superficial temporal arteries (STA) and middle cerebral arteries (MCA) measured by millimeters (mm).
Before and after infusion of levcromakalim compared with before and after infusion of saline. Time of measurements is baseline, 20 minutes and 160 minutes after the infusion.
Vascular imaging after sumatriptan
Time Frame: Before and after infusion of sumatriptan. Time of measurements is 200 minutes and 210 minutes after the infusion.
To investigate the diameter of middle meningeal arteries (MMA), superficial temporal arteries (STA) and middle cerebral arteries (MCA) measured by millimeters (mm).
Before and after infusion of sumatriptan. Time of measurements is 200 minutes and 210 minutes after the infusion.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Danish Headache Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2022

Primary Completion (Anticipated)

July 31, 2023

Study Completion (Anticipated)

July 31, 2023

Study Registration Dates

First Submitted

September 27, 2022

First Submitted That Met QC Criteria

September 29, 2022

First Posted (Actual)

October 4, 2022

Study Record Updates

Last Update Posted (Actual)

March 22, 2023

Last Update Submitted That Met QC Criteria

March 21, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-21028500

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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