Effect of Vasoactive Intestinal Polypeptide on Development of Migraine Headaches: A Randomized Clinical Trial.

Autor:	Pellesi L; Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Al-Karagholi MA; Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., De Icco R; Headache Science & Neurorehabilitation Center, Istituto di Ricovero e Cura a Carattere Scientifico Mondino Foundation, Pavia, Italy.; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy., Coskun H; Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Elbahi FA; Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Lopez-Lopez C; Novartis Pharma AG, Basel, Switzerland., Snellman J; Novartis Pharma AG, Basel, Switzerland., Hannibal J; Department of Clinical Biochemistry, Bispebjerg Frederiksberg Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark., Amin FM; Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Ashina M; Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	JAMA network open [JAMA Netw Open] 2021 Aug 02; Vol. 4 (8), pp. e2118543. Date of Electronic Publication: 2021 Aug 02.
DOI:	10.1001/jamanetworkopen.2021.18543
Abstrakt:	Importance: Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptides (PACAPs) are structurally and functionally related, yet different in their migraine-inducing properties. It remains unclear whether the lack of migraine induction can be attributed to the only transient vasodilatory response after a 20-minute infusion of VIP. Objective: To determine whether a 2-hour infusion of VIP would provoke migraine attacks. Design, Setting, and Participants: A randomized, double-blind, placebo-controlled, crossover study was conducted between May and September 2020 at the Danish Headache Center in Copenhagen, Denmark. Patients were eligible for inclusion if they were ages 18 to 40 years, weighed between 50 and 90 kg, had a diagnosis of migraine without aura as defined by the International Classification of Headache Disorders, and had a migraine frequency of 1 to 6 attacks per month. Interventions: Patients were randomly allocated to receive a 2-hour infusion of VIP or placebo on 2 different days. Main Outcomes and Measures: The primary end point was the difference in incidence of experimentally induced migraine attacks during the observational period (0-12 hours) between VIP and placebo. Results: Twenty-one patients (17 [81%] women and 4 [19%] men; mean [range] age, 25.9 [19-40] years) were recruited in the study. Fifteen patients (71%; 95% CI, 48%-89%) developed migraine attacks after VIP compared with 1 patient (5%; 95% CI, 0%-24%) who developed a migraine attack after placebo (P < .001). The VIP-induced migraine attacks mimicked patients' spontaneous attacks. The area under the curve (AUC) of headache intensity scores (0-12 hours), as well as the AUC of the superficial temporal artery diameter (0-180 minute) were significantly greater after VIP compared with placebo (AUC0-12h, P = .003; AUC0-180min, P < .001). Conclusions and Relevance: A 2-hour infusion of VIP caused migraine attacks, suggesting an important role of VIP in migraine pathophysiology. VIP and its receptors could be potential targets for novel migraine drugs. Trial Registration: ClinicalTrials.gov Identifier: NCT04260035.
Databáze:	MEDLINE
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