Hashmat Ghanizada1, Mohammad Al-Mahdi Al-Karagholi1, Nanna Arngrim1, Mette Mørch-Rasmussen1, Christopher S Walker1, Debbie L Hay1, Messoud Ashina2. 1. From the Danish Headache Center and Department of Neurology (H.G., M.A.-M.A.-K., N.A., M.M.-R., M.A.), Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; School of Biological Sciences and Centre for Brain Research (C.S.W., D.L.H.), University of Auckland; and Department of Pharmacology and Toxicology (D.L.H.), University of Otago, Dunedin, New Zealand. 2. From the Danish Headache Center and Department of Neurology (H.G., M.A.-M.A.-K., N.A., M.M.-R., M.A.), Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; School of Biological Sciences and Centre for Brain Research (C.S.W., D.L.H.), University of Auckland; and Department of Pharmacology and Toxicology (D.L.H.), University of Otago, Dunedin, New Zealand. Ashina@dadlnet.dk.
Abstract
OBJECTIVE: To determine whether the IV infusion of adrenomedullin, a potent vasodilator belonging to calcitonin family of peptides, provokes attacks of migraine in patients. METHODS:Twenty patients with migraine without aura participated in aplacebo-controlled and double-blind clinical study. In a randomized crossover design, the patients received an IV infusion of human adrenomedullin (19.9 pmol/kg/min) or placebo (saline) administrated via an automated IV pump (20 minutes). The patients participated in 2 study days with a washout period of minimum of 7 days. The primary outcome of the study was predefined as a difference in migraine incidence (0-12 hours), and the secondary outcomes were the area under curve (AUC0-12 hours) for the headache intensity score and AUC0-90 minutes for mean arterial blood pressure (MAP), flushing, and heart rate (HR). RESULTS:Eleven patients with migraine without aura (55%) fulfilledmigraine attacks criteria after adrenomedullin infusion compared to only 3 patients who reported attack (15%) after placebo (p = 0.039). We found that patients reported in a period of 0 to 12 hours stronger headache intensity after adrenomedullin compared to placebo infusion (p = 0.035). AUC0-90 minutes value for HR and flushing (p < 0.05) was significant and for MAP (p = 0.502) remained unchanged. Common reported adverse events were facial flushing, heat sensation, and palpitation (p < 0.001). CONCLUSION: Our data implicate adrenomedullin in migraine pathogenesis. This suggests that adrenomedullin or its receptors are novel therapeutic targets for the treatment of migraine. However, we cannot discount the possibility that adrenomedullin may be acting through the canonical calcitonin gene-related peptide receptor. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT04111484.
RCT Entities:
OBJECTIVE: To determine whether the IV infusion of adrenomedullin, a potent vasodilator belonging to calcitonin family of peptides, provokes attacks of migraine in patients. METHODS: Twenty patients with migraine without aura participated in a placebo-controlled and double-blind clinical study. In a randomized crossover design, the patients received an IV infusion of humanadrenomedullin (19.9 pmol/kg/min) or placebo (saline) administrated via an automated IV pump (20 minutes). The patients participated in 2 study days with a washout period of minimum of 7 days. The primary outcome of the study was predefined as a difference in migraine incidence (0-12 hours), and the secondary outcomes were the area under curve (AUC0-12 hours) for the headache intensity score and AUC0-90 minutes for mean arterial blood pressure (MAP), flushing, and heart rate (HR). RESULTS: Eleven patients with migraine without aura (55%) fulfilled migraine attacks criteria after adrenomedullin infusion compared to only 3 patients who reported attack (15%) after placebo (p = 0.039). We found that patients reported in a period of 0 to 12 hours stronger headache intensity after adrenomedullin compared to placebo infusion (p = 0.035). AUC0-90 minutes value for HR and flushing (p < 0.05) was significant and for MAP (p = 0.502) remained unchanged. Common reported adverse events were facial flushing, heat sensation, and palpitation (p < 0.001). CONCLUSION: Our data implicate adrenomedullin in migraine pathogenesis. This suggests that adrenomedullin or its receptors are novel therapeutic targets for the treatment of migraine. However, we cannot discount the possibility that adrenomedullin may be acting through the canonical calcitonin gene-related peptide receptor. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT04111484.
Authors: Håkan Ashina; Afrim Iljazi; Haidar M Al-Khazali; Thien Phu Do; Anna K Eigenbrodt; Eigil L Larsen; Amalie M Andersen; Kevin J Hansen; Karoline B Bräuner; Basit Ali Chaudhry; Casper E Christensen; Faisal Mohammad Amin; Henrik W Schytz Journal: J Headache Pain Date: 2022-10-17 Impact factor: 8.588
Authors: Michael L Garelja; Rebekah L Bower; Margaret A Brimble; Shanan Chand; Paul W R Harris; Muhammad Aqfan Jamaluddin; Jakeb Petersen; Andrew Siow; Christopher S Walker; Debbie L Hay Journal: Br J Pharmacol Date: 2021-10-15 Impact factor: 8.739