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.
Neurology. 2021 May 18;96(20):e2488-e2499. doi: 10.1212/WNL.0000000000011930. Epub 2021 Apr 7.
To determine whether the IV infusion of adrenomedullin, a potent vasodilator belonging to calcitonin family of peptides, provokes attacks of migraine in patients.
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 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 (AUC hours) for the headache intensity score and AUC for mean arterial blood pressure (MAP), flushing, and heart rate (HR).
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 ( 0.039). We found that patients reported in a period of 0 to 12 hours stronger headache intensity after adrenomedullin compared to placebo infusion ( 0.035). AUC value for HR and flushing ( < 0.05) was significant and for MAP ( = 0.502) remained unchanged. Common reported adverse events were facial flushing, heat sensation, and palpitation ( < 0.001).
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.
ClinicalTrials.gov Identifier: NCT04111484.
确定属于降钙素基因相关肽家族的强效血管舒张肽肾上腺髓质素（adrenomedullin）静脉输注是否会引发偏头痛患者的偏头痛发作。
20 名无先兆偏头痛患者参加了一项安慰剂对照、双盲临床研究。采用随机交叉设计，患者接受静脉输注人肾上腺髓质素（19.9pmol/kg/min）或安慰剂（生理盐水），通过自动静脉输注泵（20 分钟）给药。患者在 2 个研究日中参加，洗脱期至少为 7 天。该研究的主要结局为偏头痛发作的发生率（0-12 小时）的差异，次要结局为头痛强度评分的曲线下面积（AUC 小时）和平均动脉血压（MAP）、潮红和心率（HR）的 AUC。
11 名（55%）无先兆偏头痛患者在肾上腺髓质素输注后符合偏头痛发作标准，而仅 3 名患者（15%）在安慰剂输注后报告发作（0.039）。我们发现，与安慰剂输注相比，患者在 0 至 12 小时报告的头痛强度更强（0.035）。HR 和潮红的 AUC 值（<0.05）有显著差异，而 MAP（=0.502）保持不变。常见的不良反应报告为面部潮红、发热感和心悸（<0.001）。
我们的数据提示肾上腺髓质素参与偏头痛的发病机制。这表明肾上腺髓质素或其受体是治疗偏头痛的新的治疗靶点。然而，我们不能排除肾上腺髓质素可能通过经典的降钙素基因相关肽受体起作用的可能性。
ClinicalTrials.gov 标识符：NCT04111484。
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