Effect of Levcromakalim in Individuals With Migraine Pretreated With Erenumab

NCT05889442 | Completed

• 1 other identifier: H-22031695
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

An outstanding scientific question, that merits further investigation, is whether dilation of intracranial arteries is implicated in the pathogenesis of cephalic pain in migraine. Here, we hypothesize that experimentally-induced dilation of intracranial arteries using intravenous infusion of levcromakalim (a potent vasodilator) induces cephalic pain with migraine-like features in people with migraine, who prior to the infusion are administered erenumab (anti-calcitonin gene-related peptide (CGRP) receptor monoclonal antibody).

Conditions

Migraine Without Aura

Outcome Measures

Primary Outcomes (1)

• Incidence of migraine attack

  Difference in incidence of migraine attack (0 to 12 hours) between levcromakalim and placebo. A migraine attack is defined as an attack fulfilling either (i) or (ii): (i)\* Headache fulfilling criteria C and D for migraine without aura according to the International Headache Society criteria: C. Headache has at least two of the following characteristics: unilateral location pulsating quality moderate or severe pain intensity (moderate to severe pain intensity is considered ≥4 on verbal rating scale) aggravation by cough (in-hospital phase) or causing avoidance of routine physical activity (out-hospital phase) D. During headache at least one of the following: nausea and/or vomiting photophobia and phonophobia (ii) Headache described as mimicking the patient's usual migraine attack and treated with acute migraine medication (rescue medication).

  12 hours

Secondary Outcomes (3)

• Incidence of headache

  12 hours

• Intensity of headache

  12 hours

• Diameter of superficial temporal artery

  1 hour

Study Arms (2)

Levcromakalim

EXPERIMENTAL

Drug: Levcromakalim

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

Levcromakalim DRUG

Continuous intravenous infusion of 20 mL levcromakalim (0.05 mg/min (50 μg/ mL) over 20 minutes

Levcromakalim

Placebo OTHER

Continuous intravenous infusion of 20 mL isotonic saline over 20 minutes

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has provided informed consent prior to initiation of any study-specific activities/procedures.
• Age ≥18 years upon entry into screening.
• History of migraine without aura for ≥12 months with a frequency of 1-5 migraine attacks per month before screening according to the International Headache Society (IHS) Classification ICHD-3 (Headache Classification Committee of the International Headache Society, 2018), based on medical records and/or patient self-report.

You may not qualify if:

• History of any primary headache disorder other than migraine without aura, or tension-type headache with a frequency of ≥5 headache days per month before screening according to the International Headache Society (IHS) Classification ICHD-3 (Headache Classification Committee of the International Headache Society, 2018), based on medical records and/or patient self-report.
• History of any secondary headache disorder before screening according to the International Headache Society (IHS) Classification ICHD-3 (Headache Classification Committee of the International Headache Society, 2018) based on medical records and/or patient self-report.
• Intake of prophylactic migraine medication within ≤30 days or 5 plasma half-lives (whichever is longer) prior to screening.
• Prior intake of therapies targeting the CGRP signaling pathway, including anti-CGRP ligand monoclonal antibodies, anti-CGRP receptor monoclonal antibodies, and small molecule CGRP receptor antagonists.
• The participant is at risk of self-harm or harm to others as evidenced by past suicidal behavior.
• History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the investigator will pose a risk to participant safety or interfere with the study evaluation, procedures or completion.
• Female participants of childbearing potential with a positive pregnancy test assessed at screening or day 1 by a urine pregnancy test.
• Female participants who are pregnant or breastfeeding or plan to become pregnant or breastfeed during participation in the study.
• Evidence of current pregnancy or breastfeeding per participant self-report or medical records.
• Participants likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participants' and investigator's knowledge.

Sponsors & Collaborators

• Danish Headache Center: lead
• Novartis: collaborator

Study Sites (1)

Danish Headache Center

Copenhagen, 2600, Denmark

Location

Related Publications (1)

• Raffaelli B, Do TP, Chaudhry BA, Amin FM, Ashina H, Snellman J, Maio-Twofoot T, Ashina M. Activation of ATP-sensitive potassium channels triggers migraine attacks independent of calcitonin gene-related peptide receptors: a randomized placebo-controlled trial. Cephalalgia. 2024 Jan;44(1):3331024231222916. doi: 10.1177/03331024231222916.

  PMID: 38181724 DERIVED

MeSH Terms

Conditions

Migraine without Aura

Interventions

Cromakalim

Condition Hierarchy (Ancestors)

Migraine Disorders; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 25, 2023
• First Posted: June 5, 2023
• Study Start: March 9, 2023
• Primary Completion: June 12, 2023
• Study Completion: June 12, 2023
• Last Updated: October 24, 2023

Record last verified: 2023-10

Locations

DK (1)