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

NCT ID: NCT05565001

Last Updated: 2023-03-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-01

Study Completion Date

2023-07-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Headache Migraine With Aura Migraine Without Aura

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

OTHER

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Levcromakalim

Intravenous infusion of 1 mg levcromakalim followed by intravenous sumatriptan infusion.

Group Type ACTIVE_COMPARATOR

Levcromakalim

Intervention Type DRUG

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 (isotonic saline)

Intravenous infusion of placebo (isotonic saline) followed by intravenous sumatriptan infusion.

Group Type PLACEBO_COMPARATOR

Levcromakalim

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Danish Headache Center

OTHER

Sponsor Role lead

Responsible Party

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Mohammad Al-Mahdi Al-Karagholi

Study investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Danish headache center

Copenhagen, Glostrup, Denmark

Site Status RECRUITING

Countries

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Denmark

Central Contacts

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Mohammad Al-Mahdi Al-Karagholi

Role: CONTACT

00 45 31 19 16 47

Facility Contacts

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Mohammad Al-Mahdi A Al-Karagholi

Role: primary

+4531191647

Other Identifiers

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H-21028500

Identifier Type: -

Identifier Source: org_study_id

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