Triggering migraine aura with CGRP

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

This trial will try giving calcitonin gene-related peptide (CGRP) to adults with migraine with aura to see if it triggers their aura.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 21 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Danish Headache Center (other)
• Locations: 1 site (Glostrup Municipality)
• Trial ID: NCT07021859 on ClinicalTrials.gov

What this trial studies

This randomized, double-blind, placebo-controlled trial gives calcitonin gene-related peptide (CGRP) or placebo to adults diagnosed with migraine with aura to determine whether CGRP provokes aura attacks. Eligible participants are 18–65 years old, have had migraine with aura for at least 12 months, and experience on average at least one aura day per month; they are monitored after administration for onset of aura. The placebo-controlled, blinded design aims to minimize nocebo effects and establish causality between peripheral CGRP administration and aura. Confirming this mechanism could change how clinicians think about CGRP-targeted therapies and the migraine–aura connection.

Who should consider this trial

Good fit: Adults aged 18–65 with a confirmed diagnosis of migraine with aura for ≥12 months who average at least one aura day per month and can attend visits at the study center are ideal candidates.

Not a fit: People without aura, those with other primary or secondary headache disorders outside the allowed diagnoses, or patients with serious comorbid conditions are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the results could help tailor or develop treatments to prevent aura and guide use of CGRP-targeting therapies for people with migraine with aura.

How similar studies have performed: Open-label reports have suggested CGRP can provoke aura, but randomized, placebo-controlled confirmation has been lacking.

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

Where this trial is running

Glostrup Municipality

• Rigshospitalet Glostrup — Glostrup Municipality, Denmark (RECRUITING)

Study contacts

• Study coordinator: Haidar Al-Khazali, MD

Conditions: Migraine Aura, Migraine With Aura, Migraine, Aura, Calcitonin gene-related peptide