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

Danish Headache Center

Status: Enrolling

Conditions: Migraine With Aura; Migraine Aura

Treatments: Drug: Calcitonin-gene related peptide (CGRP); Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT07021859

H-23042433

Details and patient eligibility

About

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.

Full 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.

Enrollment: 21 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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21 participants in 2 patient groups, including a placebo group

Calcitonin gene-related peptide (CGRP)

Experimental group

Description:

CGRP will be administered by intravenous infusion.

Treatment:

Drug: Calcitonin-gene related peptide (CGRP)

Placebo

Placebo Comparator group

Description:

Placebo (isotonic saline) will be administered by intravenous infusion.

Treatment:

Drug: Placebo