Adrenomedullin, Brain Diseases, Central Nervous System Diseases, Migraine, Neuropeptides, Pain, Peptides, Signs and Symptoms
Conditions
Keywords
Migraine Disorders, Adrenomedulin, Pain
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.
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.
Interventions
DRUGAdrenomedullin
Continous intravenous infusion of 20 mL (19.9 pmol/kg/min) adrenomedulin over 20 minutes
OTHERPlacebo
Continous intravenous infusion of 20 mL isotonic saline over 20 minutes
Sponsors
Danish Headache Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This single-center trial applies a randomized, double-blind, placebo-controlled, two-way crossover design
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of migraine attacks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Headache intensity | 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 |
Countries
Denmark
Contacts
CONTACTAnnette Maria Ellekaer Fuchs, PhD Fellow
CONTACTHakan Ashina, Ass. Professor
Outcome results
None listed