Activation of ATP-sensitive potassium channels triggers migraine attacks independent of calcitonin gene-related peptide receptors: a randomized placebo-controlled trial.

Bianca Raffaelli, Josefin Snellman, Håkan Ashina, Basit Ali Chaudhry, Faisal Mohammad Amin, Messoud Ashina, Thien Phu Do, Tina Maio-Twofoot

Journal: Cephalalgia : an international journal of headache 2024;44(1):3331024231222916

PMID: 38181724

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Abstract

BACKGROUND

The present study aimed to investigate whether levcromakalim, a K channel opener, induces migraine attacks in people with migraine pre-treated with erenumab, a monoclonal CGRP receptor antibody.

METHODS

In this double-blind, placebo-controlled, two-way cross-over study, adults with migraine without aura received a subcutaneous injection of 140 mg of erenumab on day 1. Subsequently, they were randomized to receive a 20-minute infusion of 0.05 mg/ml levcromakalim or placebo on two experimental days separated by at least one week (between days 8 and 21). The primary endpoint was the difference in the incidence of migraine attacks between levcromakalim and placebo during the 12-hour post-infusion period.

RESULTS

In total, 16 participants completed the study. During the 12-hour observation period, 14 (88%) of 16 participants experienced migraine attacks after levcromakalim, compared to two (12%) after placebo ( < 0.001). The area under the curve for median headache intensity was greater after levcromakalim than placebo ( < 0.001). Levcromakalim elicited dilation of the superficial temporal artery during the first hour after infusion, a response absent following placebo ( < 0.001).

CONCLUSIONS

The induction of migraine attacks via opening of K channels appears independent of CGRP receptor activation. ClinicalTrials.gov, Identifier NCT05889442.

Address: Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.; Department of Neurology, Charité Universitätsmedizin Berlin, corporate member of Freie Universitä Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; Clinician Scientist Program, Berlin Institute of Health at Charité (BIH), Berlin, Germany.; Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.; Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Brain and Spinal Cord Injury, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.; Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Brain and Spinal Cord Injury, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.; Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Novartis Pharma AG, Basel, Switzerland.

DOI: 10.1177/03331024231222916

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MeSH Terms: Adult, Humans, KATP Channels, Receptors, Calcitonin Gene-Related Peptide, Cromakalim, Cross-Over Studies, Migraine Disorders, Antibodies, Monoclonal, Adenosine Triphosphate