HeadacheNCT05565001
The Involvement of ATP Sensitive Potassium Channel in Migraine Aura and Migraine Pain.
A study testing Levcromakalim in people with Headache and Migraine With Aura, run by Danish Headache Center at 1 site in Denmark.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Headache, Migraine With Aura, Migraine Without Aura
- What is being tested?
- Levcromakalim
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Sep 2022to 31 Jul 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Migraine patients
- 18-60 years.
- 50-100 kg.
- Women of childbearing potential must use adequate contraception.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
Danish headache center
Copenhagen, Glostrup, 2600
Mohammad Al-Mahdi A Al-Karagholi, +4531191647, mahdi.alkaragholi@gmail.com
About this study
Official title: 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.
Read the 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.
- Conditions
- Headache, Migraine With Aura, Migraine Without Aura
- Being tested
- Levcromakalim
- Medical subject headings
- Headache, Migraine with Aura, Migraine without Aura
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevcromakalimDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Levcromakalim | Active comparator | Intravenous infusion of 1 mg levcromakalim followed by intravenous sumatriptan infusion. Receives: Drug: Levcromakalim |
| placebo (isotonic saline) | Placebo comparator | Intravenous infusion of placebo (isotonic saline) followed by intravenous sumatriptan infusion. Receives: Drug: Levcromakalim |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dynamic diffusion weighted image (DWI)
To measure transient diffusivity changes related to levcromakalim-induced CSD during the aura phase of migraine in subjects with migraine with aura.
Measured: 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 outcomes (2)
Vascular imaging before sumatriptan
To investigate the diameter of middle meningeal arteries (MMA), superficial temporal arteries (STA) and middle cerebral arteries (MCA) measured by millimeters (mm).
Measured: 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
To investigate the diameter of middle meningeal arteries (MMA), superficial temporal arteries (STA) and middle cerebral arteries (MCA) measured by millimeters (mm).
Measured: Before and after infusion of sumatriptan. Time of measurements is 200 minutes and 210 minutes after the infusion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2022
- Study start1 Sep 2022
- Primary completion31 Jul 2023 (estimated)
- Study completion31 Jul 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HeadacheStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Danish Headache Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohammad Al-Mahdi Al-Karagholi, Danish Headache Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05565001
- Sponsor's protocol ID
- H-21028500
- Status last verified
- Mar 2023
- First submitted
- 27 Sep 2022
- Last updated
- 22 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Structural and Functional Cerebral Changes After Infusion of ATP Sensitive Potassium Channel Opener Levcromakalim.
- ClinicalTrials.gov ID
- NCT05565001
- Acronym / sponsor ID
- H-21028500
- Conditions
- Headache, Migraine With Aura, Migraine Without Aura
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Danish Headache CenterUniversity, hospital or other
- Study start
- 1 Sep 2022 (actual)
- Primary completion
- 31 Jul 2023 (estimated)
- Study completion
- 31 Jul 2023 (estimated)
- First posted
- 4 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Levcromakalim | Active comparator | Drug: LevcromakalimIntravenous infusion of 1 mg levcromakalim followed by intravenous sumatriptan infusion. |
| placebo (isotonic saline) | Placebo comparator | Drug: LevcromakalimIntravenous infusion of placebo (isotonic saline) followed by intravenous sumatriptan infusion. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Migraine patients
- 18-60 years.
- 50-100 kg.
- Women of childbearing potential must use adequate contraception.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevcromakalimIntravenous 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. | Drug | Levcromakalim, placebo (isotonic saline) |
Primary outcome
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.
2 secondary outcomes
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.
Vascular imaging after sumatriptan
Time frame: Before and after infusion of sumatriptan. Time of measurements is 200 minutes and 210 minutes after the infusion.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Levcromakalim in people with Headache and Migraine With Aura, run by Danish Headache Center at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mohammad Al-Mahdi Al-Karagholi (00 45 31 19 16 47, mahdi.alkaragholi@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2023.