Induction of Migraine Attacks With Aura Using Calcitonin Gene-Related Peptide

Official title

Induction of Migraine Attacks With Aura Using Calcitonin Gene-Related Peptide: A Randomized Clinical Trial

Overview

Calcitonin gene-related peptide (CGRP) is a key neuropeptide in migraine pathophysiology and treatment. This study investigates whether CGRP administration can trigger aura in individuals with a diagnosis of migraine with aura.

Detailed description

Recent open-label findings show that calcitonin gene-related peptide (CGRP), a key player in migraine, can trigger aura attacks-despite its limited ability to cross the blood-brain barrier. This suggests CGRP might induce migraine aura via trigeminovascular activation, the same pathway involved in migraine headache. If confirmed, this could reshape treatment strategies for patients diagnosed with migraine with aura. To validate this effect and rule out nocebo influence, a randomized, double-blind, placebo-controlled trial is essential. Its outcomes could inform future therapies targeting the migraine-aura connection.

Interventions

• Drug Calcitonin-gene related peptide (CGRP)
  The participants will receive a continuous intravenous infusion of 1.5 μg/min of CGRP over 60 minutes.
• Drug Placebo
  The participants will receive a continuous intravenous infusion of 60 mL of placebo (isotonic saline) over 60 minutes.

Primary outcome measures

• Incidence of migraine attacks with aura [Time frame: 12 hours]

Secondary outcome measures (2)

• Incidence of migraine attacks without aura [Time frame: 12 hours]
• Headache intensity scores [Time frame: 12 hours]

Eligibility criteria

Inclusion criteria

• Age 18 to 65 years of age upon entry into screening
• History of migraine with aura for ≥ 12 months according to the International Classification of Headache Disorders 3rd Edition (ICHD-3) criteria
• ≥ 1 monthly day with aura that meets criteria as aura on average across the three months before screening
• Provision of informed consent prior to initiation of any study-specific activities/procedures.

Exclusion criteria

• Any history of a primary or secondary headache disorder other than migraine without aura, migraine with aura, chronic migraine, and episodic tension-type headache
• History or evidence of any other clinically significant disorder, condition, or disease (except for those outlined above) that, in the opinion of the site investigator, would pose a risk to subject safety or interfere with study evaluation, procedures or completion
• The subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior
• Female subjects of childbearing potential with a positive pregnancy test during any study visit
• Cardiovascular disease of any kind, including cerebrovascular diseases
• Hypertension (systolic blood pressure of ≥150 mmHg and/or diastolic blood pressure of ≥100 mmHg) prior to the start of infusion on the experimental day
• Hypotension (systolic blood pressure of ≤90 mmHg and/or diastolic blood pressure of ≤50 mmHg)
• Initiation, discontinuation, or change of dosing of prophylactic medications within 2 months prior to study inclusion
• Intake of acute medications (e.g. analgesics, triptans) within 48 hours of infusion start
• Headache of any intensity within 48 hours of infusion start
• Aura within 48 hours of infusion start

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Quadruple blind

Primary purpose

Basic science

Study locations

Denmark · 1 center

• Rigshospitalet Glostrup — Glostrup Municipality

Identifiers

NCT: NCT07021859 · H-23042433

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗