Selective Activation of the Adrenomedullin Receptors in Migraine

NCT07451769 | Not Yet Recruiting DMC

• 1 other identifier: 118122
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Adrenomedullin is a neuropeptide implicated in the pathogenesis of migraine. This study investigates whether its administration, after pre-treatment with erenumab (a CGRP-receptor blocking monoclonal antibody), can trigger migraine attacks in individuals with migraine without aura.

Conditions

Migraine; Brain Diseases; Adrenomedullin; Pain; Peptides; Neuropeptides; Signs and Symptoms; Central Nervous System Diseases

Keywords

Migraine Disorders; Adrenomedulin; Pain

Outcome Measures

Primary Outcomes (1)

• Incidence of migraine attacks

  Incidence of migraine attacks, defined by either: I. Headache fulfilling criteria C and D for migraine without aura according to ICHD-3 2 * Criterion C: At least two of the following: * Unilateral location * Pulsating quality * Moderate to severe pain intensity (≥4 on an 11-point numerical rating scale) * Aggravation by cough (in-hospital setting) or avoidance of routine physical activity (out-hospital setting) * Criterion D: At least one of the following: * Nausea and/or vomiting * Photophobia and phonophobia OR II. Headache that mimics the participant's usual spontaneous migraine attacks and is treated with acute migraine (rescue) medication.

  Assessed from baseline to 12 hours post-infusion of adrenomedullin or placebo

Secondary Outcomes (1)

• Headache intensity

  Assessed from baseline to 12 hours post-infusion of adrenomedullin or placebo

Study Arms (2)

Adrenomedullin

EXPERIMENTAL

Drug: Adrenomedullin

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

Adrenomedullin DRUG

Continous intravenous infusion of 20 mL (19.9 pmol/kg/min) adrenomedulin over 20 minutes

Adrenomedullin

Placebo OTHER

Continous intravenous infusion of 20 mL isotonic saline over 20 minutes

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent has been obtained prior to the initiation of any study-specific procedures.
• Age ≥18 years at the time of screening.
• History of migraine without aura for at least 12 months prior to screening, with a frequency of 1-5 migraine attacks per month, based on medical records and/or patient self-report, and diagnosed in accordance with the ICHD-3 criteria.

You may not qualify if:

• History of any other primary headache disorder, except for tension-type headache with \<5 headache days per month, based on ICHD-3 classification.
• History of any secondary headache disorder, per ICHD-3 criteria, prior to screening.
• Use of prophylactic migraine medication within 30 days or within 5 plasma half-lives (whichever is longer) prior to screening.
• Previous use of any therapies targeting the CGRP signaling pathway, including anti-CGRP ligand monoclonal antibodies, anti-CGRP receptor monoclonal antibodies, or small molecule CGRP receptor antagonists.
• Known risk of self-harm or harm to others, including a history of suicidal behavior.
• Any clinically significant disorder, condition, or disease (other than those permitted in the protocol) that, in the opinion of the investigator, could compromise participant safety or interfere with study procedures or data integrity.
• Positive urine pregnancy test at screening or on Day 1 in female participants of childbearing potential.
• Pregnancy or breastfeeding, or plans to become pregnant or breastfeed during the study period.
• Evidence of current pregnancy or breastfeeding based on self-report or medical records.
• Inability or unwillingness to complete all protocol-required visits and procedures, or concerns regarding protocol adherence, as judged by the investigator.

Sponsors & Collaborators

• Danish Headache Center: lead

Study Sites (1)

Danish Headache Center

Glostrup Municipality, 2600, Denmark

Location

Related Publications (15)

• Do TP, Younis S, Ashina M. Erenumab [Internet]. 2021. p. 121-9.Available from: https://link.springer.com/10.1007/978-3-030-69032-8_9

  BACKGROUND

• Goadsby PJ, Reuter U, Hallstrom Y, Broessner G, Bonner JH, Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA. A Controlled Trial of Erenumab for Episodic Migraine. N Engl J Med. 2017 Nov 30;377(22):2123-2132. doi: 10.1056/NEJMoa1705848.

  PMID: 29171821 BACKGROUND

• de Hoon J, Van Hecken A, Vandermeulen C, Yan L, Smith B, Chen JS, Bautista E, Hamilton L, Waksman J, Vu T, Vargas G. Phase I, Randomized, Double-blind, Placebo-controlled, Single-dose, and Multiple-dose Studies of Erenumab in Healthy Subjects and Patients With Migraine. Clin Pharmacol Ther. 2018 May;103(5):815-825. doi: 10.1002/cpt.799. Epub 2017 Oct 24.

  PMID: 28736918 BACKGROUND

• Giamberardino MA, Affaitati G, Costantini R, Cipollone F, Martelletti P. Calcitonin gene-related peptide receptor as a novel target for the management of people with episodic migraine: current evidence and safety profile of erenumab. J Pain Res. 2017 Dec 8;10:2751-2760. doi: 10.2147/JPR.S128143. eCollection 2017.

  PMID: 29263689 BACKGROUND

• Meeran K, O'Shea D, Upton PD, Small CJ, Ghatei MA, Byfield PH, Bloom SR. Circulating adrenomedullin does not regulate systemic blood pressure but increases plasma prolactin after intravenous infusion in humans: a pharmacokinetic study. J Clin Endocrinol Metab. 1997 Jan;82(1):95-100. doi: 10.1210/jcem.82.1.3656.

  PMID: 8989240 BACKGROUND

• Ashina M, Hansen JM, A Dunga BO, Olesen J. Human models of migraine - short-term pain for long-term gain. Nat Rev Neurol. 2017 Dec;13(12):713-724. doi: 10.1038/nrneurol.2017.137. Epub 2017 Oct 6.

  PMID: 28984313 BACKGROUND

• Hay DL, Garelja ML, Poyner DR, Walker CS. Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR Review 25. Br J Pharmacol. 2018 Jan;175(1):3-17. doi: 10.1111/bph.14075. Epub 2017 Nov 28.

  PMID: 29059473 BACKGROUND

• Ghanizada H, Al-Karagholi MA, Arngrim N, Morch-Rasmussen M, Walker CS, Hay DL, Ashina M. Effect of Adrenomedullin on Migraine-Like Attacks in Patients With Migraine: A Randomized Crossover Study. Neurology. 2021 May 18;96(20):e2488-e2499. doi: 10.1212/WNL.0000000000011930. Epub 2021 Apr 7.

  PMID: 33827963 BACKGROUND

• Shi L, Lehto SG, Zhu DX, Sun H, Zhang J, Smith BP, Immke DC, Wild KD, Xu C. Pharmacologic Characterization of AMG 334, a Potent and Selective Human Monoclonal Antibody against the Calcitonin Gene-Related Peptide Receptor. J Pharmacol Exp Ther. 2016 Jan;356(1):223-31. doi: 10.1124/jpet.115.227793. Epub 2015 Nov 11.

  PMID: 26559125 BACKGROUND

• Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF; AMPP Advisory Group. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007 Jan 30;68(5):343-9. doi: 10.1212/01.wnl.0000252808.97649.21.

  PMID: 17261680 BACKGROUND

• Steiner TJ, Jensen R, Katsarava Z, Linde M, MacGregor EA, Osipova V, Paemeleire K, Olesen J, Peters M, Martelletti P. Aids to management of headache disorders in primary care (2nd edition) : on behalf of the European Headache Federation and Lifting The Burden: the Global Campaign against Headache. J Headache Pain. 2019 May 21;20(1):57. doi: 10.1186/s10194-018-0899-2.

  PMID: 31113373 BACKGROUND

• Stovner LJ, Andree C. Prevalence of headache in Europe: a review for the Eurolight project. J Headache Pain. 2010 Aug;11(4):289-99. doi: 10.1007/s10194-010-0217-0. Epub 2010 May 16.

  PMID: 20473702 BACKGROUND

• Robbins MS, Lipton RB. The epidemiology of primary headache disorders. Semin Neurol. 2010 Apr;30(2):107-19. doi: 10.1055/s-0030-1249220. Epub 2010 Mar 29.

  PMID: 20352581 BACKGROUND

• Ashina M, Terwindt GM, Al-Karagholi MA, de Boer I, Lee MJ, Hay DL, Schulte LH, Hadjikhani N, Sinclair AJ, Ashina H, Schwedt TJ, Goadsby PJ. Migraine: disease characterisation, biomarkers, and precision medicine. Lancet. 2021 Apr 17;397(10283):1496-1504. doi: 10.1016/S0140-6736(20)32162-0. Epub 2021 Mar 25.

  PMID: 33773610 BACKGROUND

• Ashina M. Migraine. N Engl J Med. 2020 Nov 5;383(19):1866-1876. doi: 10.1056/NEJMra1915327. No abstract available.

  PMID: 33211930 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Migraine Disorders; Brain Diseases; Central Nervous System Diseases; Pain; Signs and Symptoms

Interventions

Adrenomedullin

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Nervous System Diseases; Neurologic Manifestations; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Central Study Contacts

Annette Maria Ellekaer Fuchs, PhD Fellow

CONTACT

+4526232421; annette.maria.ellekaer.fuchs@regionh.dk

Hakan Ashina, Ass. Professor

CONTACT

+4528102495; haakan.ashina@regionh.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: This single-center trial applies a randomized, double-blind, placebo-controlled, two-way crossover design

Study Record Dates

• First Submitted: February 28, 2026
• First Posted: March 5, 2026
• Study Start: March 10, 2026
• Primary Completion (Estimated): March 10, 2027
• Study Completion (Estimated): December 20, 2032
• Last Updated: March 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

DK (1)