Evidence map›Paper›PMID 37231350›Full record

Trial reportThe journal of headache and pain2023

The effect of Lu AG09222 on PACAP38- and VIP-induced vasodilation, heart rate increase, and headache in healthy subjects: an interventional, randomized, double-blind, parallel-group, placebo-controlled study.

Nadja Bredo Rasmussen, Christina Deligianni, Casper Emil Christensen, William Kristian Karlsson, Haidar Muhsen Al-Khazali, Tom Van de Casteele, Charlotte Granhall, Faisal Mohammad Amin, Messoud Ashina

Erratum issued Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The journal of headache and pain, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04976309 (Interventional, Randomized, Double-blind, Parallel-group, Placebo-controlled Study Investigating the Effect of Lu AG09222 on PACAP38- and VIP-induced Vasodilation, Heart Rate Increase, and Headache in Healthy Subjects), which is not on this map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
5.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04976309 phase1completednot on this map

Interventional, Randomized, Double-blind, Parallel-group, Placebo-controlled Study Investigating the Effect of Lu AG09222 on PACAP38- and VIP-induced Vasodilation, Heart Rate Increase, and Headache in Healthy Subjects

TypeinterventionalSponsorH. Lundbeck A/SRan2021 to 2021Enrolled25ConditionsHealthyArmsLu AG09222, Placebo
3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Pooled it
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  16. Hallmarks of primary headache: part 1 - migraine.The journal of headache and pain · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Nadja Bredo RasmussenDepartment of Neurology, Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Valdemar Hansen Vej 5, DK-2600, Glostrup, Denmark.
Christina DeligianniDepartment of Neurology, Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Valdemar Hansen Vej 5, DK-2600, Glostrup, Denmark.
Casper Emil ChristensenDepartment of Neurology, Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Valdemar Hansen Vej 5, DK-2600, Glostrup, Denmark.
William Kristian KarlssonDepartment of Neurology, Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Valdemar Hansen Vej 5, DK-2600, Glostrup, Denmark.
Haidar Muhsen Al-KhazaliDepartment of Neurology, Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Valdemar Hansen Vej 5, DK-2600, Glostrup, Denmark.
Tom Van de CasteeleH. Lundbeck A/S, Ottiliavej 9, 2500, Valby, Denmark.
Charlotte GranhallH. Lundbeck A/S, Ottiliavej 9, 2500, Valby, Denmark.
Faisal Mohammad AminDepartment of Neurology, Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Valdemar Hansen Vej 5, DK-2600, Glostrup, Denmark.
Messoud AshinaDepartment of Neurology, Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Valdemar Hansen Vej 5, DK-2600, Glostrup, Denmark. ashina@dadlnet.dk.
University of Copenhagen · DKRigshospitalet · DKLundbeck (Denmark) · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPituitary adenylate cyclase-activating polypeptide (PACAP), structurally related to vasoactive intestinal peptide (VIP), is one of the important mediators in the pathogenesis of migraine and is known to dilate cranial arteries and induce headache and migraine. Our objective was to determine whether Lu AG09222-an investigational humanized monoclonal antibody directed against PACAP ligand-would inhibit the PACAP-signaling cascade by abolishing its vasodilatory and headache-inducing abilities.

methodsIn a randomized, double-blind, parallel-group, single-dose, placebo-controlled study of Lu AG09222, healthy volunteers aged 18-45 years without history of headache disorders were randomly allocated to three treatment sequences (1:2:2) on two experimental infusion visits with 9 ± 3 days' interval: placebo + saline + saline (n = 5), placebo + PACAP38 + VIP (n = 10), and Lu AG09222 + PACAP38 + VIP (n = 10). The primary outcome measure was area under the curve (AUC) of the change in superficial temporal artery (STA) diameter from 0 to 120 min after start of infusion of PACAP38. The study was conducted at the Danish Headache Center in Copenhagen, Denmark.

resultsIn participants who received Lu AG09222 + PACAP38 infusion, there was a significantly lower STA diameter (mean (SE) [95% CI] AUC ‒35.4 (4.32) [‒44.6, ‒26.3] mm × min; P < 0.0001) compared to participants who received placebo + PACAP38 infusion. Secondary and explorative analysis revealed that PACAP38 infusion induced an increase in facial blood flow, heart rate and mild headache, and indicated that these PACAP38-induced responses were inhibited by Lu AG09222.

conclusionsThis proof-of-mechanism study demonstrated that Lu AG09222 inhibited PACAP38-induced cephalic vasodilation and increases in heart rate, and reduced concomitant headache. Lu AG09222 may be a potential therapy against migraine and other PACAP-mediated diseases.

trial registrationClinicalTrials.gov: NCT04976309. Registration date: July 19, 2021.

Indexed as

Migraine DisordersPituitary Adenylate Cyclase-Activating PolypeptideAntibodies, Monoclonal, HumanizedDouble-Blind MethodHeadacheHealthy VolunteersHeart RateHumansVasoactive Intestinal PeptideVasodilationAntibodies, Monoclonal, HumanizedPituitary Adenylate Cyclase-Activating PolypeptideVasoactive Intestinal PeptideMigraineMigraine disordersMigraine treatmentMonoclonal antibodyPituitary adenylate cyclase-activating polypeptide

Identifiers

PMID37231350
PMCPMC10210362
OpenAlexW4378222474

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.