Selective Activation of the Adrenomedullin Receptors in Migraine

March 5, 2026 updated by: Håkan Ashina, Danish Headache Center

Selective Activation of the Adrenomedullin Receptors in Migraine: A Randomized, Double-Blind, Placebo-Controlled Crossover Study

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

To isolate adrenomedullin receptor-mediated effects, participants will receive the monoclonal antibody erenumab prior to adrenomedullin administration in order to block CGRP receptor activation.

This study therefore aims to determine whether selective activation of adrenomedullin receptors - isolated from confounding CGRP receptor activation - can induce migraine-relevant physiological responses.

Study Type

Interventional

Enrollment (Estimated)

26

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Denmark
      • Glostrup Municipality, Denmark, 2600
        • Danish Headache Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Written informed consent has been obtained prior to the initiation of any study-specific procedures.
  2. Age ≥18 years at the time of screening.
  3. 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.

Exclusion Criteria:

  1. History of any other primary headache disorder, except for tension-type headache with <5 headache days per month, based on ICHD-3 classification.
  2. History of any secondary headache disorder, per ICHD-3 criteria, prior to screening.
  3. Use of prophylactic migraine medication within 30 days or within 5 plasma half-lives (whichever is longer) prior to screening.
  4. 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.
  5. Known risk of self-harm or harm to others, including a history of suicidal behavior.
  6. 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.
  7. Positive urine pregnancy test at screening or on Day 1 in female participants of childbearing potential.
  8. Pregnancy or breastfeeding, or plans to become pregnant or breastfeed during the study period.
  9. Evidence of current pregnancy or breastfeeding based on self-report or medical records.
  10. Inability or unwillingness to complete all protocol-required visits and procedures, or concerns regarding protocol adherence, as judged by the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Other: Placebo
Continous intravenous infusion of 20 mL isotonic saline over 20 minutes
Experimental: Adrenomedullin
Drug: Adrenomedullin
Continous intravenous infusion of 20 mL (19.9 pmol/kg/min) adrenomedulin over 20 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of migraine attacks
Time Frame: Assessed from baseline to 12 hours post-infusion of adrenomedullin or placebo

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Headache intensity
Time Frame: Assessed from baseline to 12 hours post-infusion of adrenomedullin or placebo

Headache intensity, assessed using a numerical rating scale (NRS) from 0 to 10:

  • 0 = No headache
  • 10 = Worst headache imaginable
Assessed from baseline to 12 hours post-infusion of adrenomedullin or placebo

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Danish Headache Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 10, 2026

Primary Completion (Estimated)

March 10, 2027

Study Completion (Estimated)

December 20, 2032

Study Registration Dates

First Submitted

February 28, 2026

First Submitted That Met QC Criteria

February 28, 2026

First Posted (Actual)

March 5, 2026

Study Record Updates

Last Update Posted (Actual)

March 9, 2026

Last Update Submitted That Met QC Criteria

March 5, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 118122

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Anonymized data not published within this article will be made available on reasonable request from any qualified investigator

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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