Effect of Levcromakalim in Individuals With Migraine Pretreated With Erenumab

NCT ID: NCT05889442

Last Updated: 2023-10-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-09
• Study Completion Date: 2023-06-12

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Levcromakalim

Group Type: EXPERIMENTAL

Levcromakalim

Intervention Type: DRUG

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

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Continuous intravenous infusion of 20 mL isotonic saline over 20 minutes

Interventions

Levcromakalim

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

Intervention Type: DRUG

Placebo

Continuous intravenous infusion of 20 mL isotonic saline over 20 minutes

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Danish Headache Center

OTHER

Sponsor Role: lead

Responsible Party

Messoud Ashina, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Danish Headache Center

Copenhagen, , Denmark

Countries

Denmark

References

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.

Reference Type: DERIVED

PMID: 38181724 (View on PubMed)

Other Identifiers

H-22031695

Identifier Type: -

Identifier Source: org_study_id