Selective Activation of the Adrenomedullin Receptors in Migraine

What Was Tested

In this not phased trial, researchers set out to test Adrenomedullin for migraine.

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.

It had two arms (groups): Adrenomedullin (experimental) and Placebo (placebo comparator).

The registry classes the interventions as drug and other.

More on the Plan

Adrenomedullin is an endogenous neuropeptide structurally related to CGRP that can activate both the adrenomedullin receptor and, to a lesser extent, the CGRP receptor.

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.

Who Took Part

Enrollment: 26 planned participants were the target.

It was open to people of any sex aged from 18 years up to 65 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Written informed consent has been obtained prior to the initiation of any study-specific procedures. Age ≥18 years at the time of screening.

The full record lists 3 inclusion and 10 exclusion criteria; among the exclusions: 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.

How the Study Was Run

It was run as a randomized, crossover and quadruple-blind study.

The migraine participants were allocated by chance, so the Adrenomedullin group and the comparison group should start out alike.

In the crossover set-up each of the migraine participants took both Adrenomedullin and the comparison in turn, acting as their own control.

As a double-blind Adrenomedullin study, the assignments were hidden from both participants and investigators until the end.

Those kept unaware of assignments: participant, care provider, investigator and outcomes assessor.

It started in 2026-03-12 with completion listed for 2027-03-10.

It ran at 1 site in Denmark.

Its stated primary purpose is basic science.

What Was Measured

Primary outcome: Incidence of migraine attacks (time frame: Assessed from baseline to 12 hours post-infusion of adrenomedullin or placebo).

What This Means in Plain Language

Put simply, this is a not phased, randomized trial of Adrenomedullin in 26 people with migraine.

Its size is small, so on its own it can only give an early look.

It is still recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Adrenomedullin compound page, Migraine research.