Effect of Adrenomedullin on Migraine-like Attacks in Patients With Migraine: A Randomized Crossover Study

Hashmat Ghanizada, Mohammad Al-Mahdi Al-Karagholi, Nanna Arngrim, Mette Mørch-Rasmussen, Christopher S Walker, Debbie L Hay, Messoud Ashina


ObjectiveTo determine whether the intravenous infusion of adrenomedullin, a potent vasodilator belonging to calcitonin family of peptides, provokes attacks of migraine in patients.MethodsTwenty migraine without aura patients participated in a placebo-controlled and double-blinded clinical study. In a randomized and crossover design the patients received an intravenous infusion of human adrenomedullin (19.9 picomole/kg/min) or placebo (saline) administrated via an automated intravenous pump (20 minutes). The patients participated in two study days with washout period of minimum of seven days. The primary outcome of the study was predefined as a difference in migraine incidence (0-12 h) and the secondary outcome were the headache intensity score's area under curve (AUC0-12 h) and the (AUC 0-90 min) for MAP, flushing and HR.ResultsEleven migraine without aura patients (55%) fulfilled migraine attacks criteria after adrenomedullin infusion in comparison to only three patients reported attack (15%) after placebo (P= 0.039). We found that patients reported in a period of (0-12 hours) stronger headache intensity after adrenomedullin in comparison to placebo infusion (P= 0.035). AUC0-90 min for HR and, flushing (P < 0.05) were significant and MAP (P = 0.502) remain unchanged. Common adverse events reported were facial flushing, heat sensation and palpitation (P <0.001)ConclusionOur data implicate adrenomedullin in migraine pathogenesis. This suggests that adrenomedullin and/or its receptors are novel therapeutic targets for the treatment of migraine. However, we cannot discount for the possibility that adrenomedullin may be acting through the canonical CGRP receptor.

Udgave nummer20
Sider (fra-til)e2488-e2499
StatusUdgivet - 18 maj 2021


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