Ignite Creation Date:
2026-03-26 @ 3:17 PM
Ignite Modification Date:
2026-03-31 @ 9:10 AM
Study NCT ID:
NCT07451769
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-03-09
First Post:
2026-02-28
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Selective Activation of the Adrenomedullin Receptors in Migraine
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D008881', 'term': 'Migraine Disorders'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D010146', 'term': 'Pain'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}], 'ancestors': [{'id': 'D051270', 'term': 'Headache Disorders, Primary'}, {'id': 'D020773', 'term': 'Headache Disorders'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D053607', 'term': 'Adrenomedullin'}], 'ancestors': [{'id': 'D036361', 'term': 'Peptide Hormones'}, {'id': 'D006728', 'term': 'Hormones'}, {'id': 'D006730', 'term': 'Hormones, Hormone Substitutes, and Hormone Antagonists'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'This single-center trial applies a randomized, double-blind, placebo-controlled, two-way crossover design'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 26}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-03-10', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-01', 'completionDateStruct': {'date': '2032-12-20', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-03-05', 'studyFirstSubmitDate': '2026-02-28', 'studyFirstSubmitQcDate': '2026-02-28', 'lastUpdatePostDateStruct': {'date': '2026-03-09', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-03-05', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-03-10', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Incidence of migraine attacks', 'timeFrame': 'Assessed from baseline to 12 hours post-infusion of adrenomedullin or placebo', 'description': "Incidence of migraine attacks, defined by either:\n\nI. Headache fulfilling criteria C and D for migraine without aura according to ICHD-3 2\n\n* Criterion C: At least two of the following:\n\n * Unilateral location\n * Pulsating quality\n * Moderate to severe pain intensity (≥4 on an 11-point numerical rating scale)\n * Aggravation by cough (in-hospital setting) or avoidance of routine physical activity (out-hospital setting)\n* Criterion D: At least one of the following:\n\n * Nausea and/or vomiting\n * Photophobia and phonophobia OR II. Headache that mimics the participant's usual spontaneous migraine attacks and is treated with acute migraine (rescue) medication."}], 'secondaryOutcomes': [{'measure': 'Headache intensity', 'timeFrame': 'Assessed from baseline to 12 hours post-infusion of adrenomedullin or placebo', 'description': 'Headache intensity, assessed using a numerical rating scale (NRS) from 0 to 10:\n\n* 0 = No headache\n* 10 = Worst headache imaginable'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Migraine Disorders', 'Adrenomedulin', 'Pain'], 'conditions': ['Migraine', 'Brain Diseases', 'Central Nervous System Diseases', 'Adrenomedullin', 'Pain', 'Peptides', 'Neuropeptides', 'Signs and Symptoms']}, 'referencesModule': {'references': [{'type': 'BACKGROUND', 'citation': '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'}, {'pmid': '29171821', 'type': 'BACKGROUND', 'citation': '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': '28736918', 'type': 'BACKGROUND', 'citation': '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': '29263689', 'type': 'BACKGROUND', 'citation': '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': '8989240', 'type': 'BACKGROUND', 'citation': "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': '28984313', 'type': 'BACKGROUND', 'citation': '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': '29059473', 'type': 'BACKGROUND', 'citation': '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': '33827963', 'type': 'BACKGROUND', 'citation': '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': '26559125', 'type': 'BACKGROUND', 'citation': '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': '17261680', 'type': 'BACKGROUND', 'citation': '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': '31113373', 'type': 'BACKGROUND', 'citation': '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': '20473702', 'type': 'BACKGROUND', 'citation': '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': '20352581', 'type': 'BACKGROUND', 'citation': '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': '33773610', 'type': 'BACKGROUND', 'citation': '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': '33211930', 'type': 'BACKGROUND', 'citation': 'Ashina M. Migraine. N Engl J Med. 2020 Nov 5;383(19):1866-1876. doi: 10.1056/NEJMra1915327. No abstract available.'}], 'seeAlsoLinks': [{'url': 'https://www.regionh.dk/til-fagfolk/forskning-og-innovation/de-regionale-videnskabsetiske-komiteer/sider/default.aspx', 'label': 'Related Info'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': 'Adrenomedullin is an endogenous neuropeptide structurally related to CGRP that can activate both the adrenomedullin receptor and, to a lesser extent, the CGRP receptor. Prior human provocation studies have shown that administration of adrenomedullin can elicit migraine attacks in people with migraine. Because adrenomedullin lacks receptor selectivity, physiological responses observed after its administration might represent a composite of adrenomedullin-receptor activation and potential off-target activation of the CGRP receptor. The extent to which selective activation of the adrenomedullin receptor alone can provoke migraine-relevant responses remains unknown.\n\nTo isolate adrenomedullin receptor-mediated effects, participants will receive the monoclonal antibody erenumab prior to adrenomedullin administration in order to block CGRP receptor activation.\n\nThis study therefore aims to determine whether selective activation of adrenomedullin receptors - isolated from confounding CGRP receptor activation - can induce migraine-relevant physiological responses.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Written informed consent has been obtained prior to the initiation of any study-specific procedures.\n2. Age ≥18 years at the time of screening.\n3. 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.\n\nExclusion Criteria:\n\n1. History of any other primary headache disorder, except for tension-type headache with \\<5 headache days per month, based on ICHD-3 classification.\n2. History of any secondary headache disorder, per ICHD-3 criteria, prior to screening.\n3. Use of prophylactic migraine medication within 30 days or within 5 plasma half-lives (whichever is longer) prior to screening.\n4. 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.\n5. Known risk of self-harm or harm to others, including a history of suicidal behavior.\n6. 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.\n7. Positive urine pregnancy test at screening or on Day 1 in female participants of childbearing potential.\n8. Pregnancy or breastfeeding, or plans to become pregnant or breastfeed during the study period.\n9. Evidence of current pregnancy or breastfeeding based on self-report or medical records.\n10. Inability or unwillingness to complete all protocol-required visits and procedures, or concerns regarding protocol adherence, as judged by the investigator.'}, 'identificationModule': {'nctId': 'NCT07451769', 'briefTitle': 'Selective Activation of the Adrenomedullin Receptors in Migraine', 'organization': {'class': 'OTHER', 'fullName': 'Danish Headache Center'}, 'officialTitle': 'Selective Activation of the Adrenomedullin Receptors in Migraine: A Randomized, Double-Blind, Placebo-Controlled Crossover Study', 'orgStudyIdInfo': {'id': '118122'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Adrenomedullin', 'interventionNames': ['Drug: Adrenomedullin']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'interventionNames': ['Other: Placebo']}], 'interventions': [{'name': 'Adrenomedullin', 'type': 'DRUG', 'description': 'Continous intravenous infusion of 20 mL (19.9 pmol/kg/min) adrenomedulin over 20 minutes', 'armGroupLabels': ['Adrenomedullin']}, {'name': 'Placebo', 'type': 'OTHER', 'description': 'Continous intravenous infusion of 20 mL isotonic saline over 20 minutes', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '2600', 'city': 'Glostrup Municipality', 'country': 'Denmark', 'facility': 'Danish Headache Center', 'geoPoint': {'lat': 55.6666, 'lon': 12.40377}}], 'centralContacts': [{'name': 'Annette Maria Ellekaer Fuchs, PhD Fellow', 'role': 'CONTACT', 'email': 'annette.maria.ellekaer.fuchs@regionh.dk', 'phone': '+4526232421'}, {'name': 'Hakan Ashina, Ass. Professor', 'role': 'CONTACT', 'email': 'haakan.ashina@regionh.dk', 'phone': '+4528102495'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'YES', 'description': 'Anonymized data not published within this article will be made available on reasonable request from any qualified investigator'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Danish Headache Center', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Associate Professor', 'investigatorFullName': 'Håkan Ashina', 'investigatorAffiliation': 'Danish Headache Center'}}}}