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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Migraine With Aura; Migraine Aura
• Intervention / Treatment: Drug: Calcitonin-gene related peptide (CGRP); Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Haidar Al-Khazali, MD; Phone Number: +4541598494; Email: haidardk@hotmail.com
• Study Contact Backup: Name: Hakan Ashina, MD, PhD; Phone Number: +4528102495; Email: haakan.ashina@regionh.dk

Study Locations

• Denmark
  • Glostrup, Denmark, 2600
    • Recruiting
    • Rigshospitalet Glostrup
    • Contact: Haidar Al-Khazali, MD; Phone Number: +4541598494; Email: haidardk@hotmail.com
    • Contact: Hakan Ashina, MD, PhD; Phone Number: +4528102495; Email: haakan.ashina@regionh.dk
    • Sub-Investigator: Haidar Al-Khazali, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo (isotonic saline) will be administered by intravenous infusion.	Drug: Placebo; The participants will receive a continuous intravenous infusion of 60 mL of placebo (isotonic saline) over 60 minutes.
Experimental: Calcitonin gene-related peptide (CGRP); CGRP will be administered by intravenous infusion.	Drug: Calcitonin-gene related peptide (CGRP); The participants will receive a continuous intravenous infusion of 1.5 μg/min of CGRP over 60 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of migraine attacks with aura	Difference in incidence of migraine attack with aura between CGRP and placebo during the 12-hour observational period after infusion start.	12 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of migraine attacks without aura	Difference in incidence of migraine headache between CGRP and placebo during the 12-hour observational period after infusion start.	12 hours
Headache intensity scores	Difference in area under the curve (AUC) for headache intensity scores between CGRP and placebo during the 12-hour observational period after infusion start.	12 hours

Collaborators and Investigators

• Sponsor: Danish Headache Center

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: June 6, 2025
• First Submitted That Met QC Criteria: June 6, 2025
• First Posted (Actual): June 15, 2025

Study Record Updates

• Last Update Posted (Actual): August 6, 2025
• Last Update Submitted That Met QC Criteria: August 3, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Migraine; Aura; Calcitonin gene-related peptide
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Migraine with Aura; Epilepsy; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Bone Density Conservation Agents; Vasodilator Agents; Calcitonin; Salmon calcitonin; Calcitonin Gene-Related Peptide; Katacalcin
• Other Study ID Numbers: H-23042433

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized data not published within this article will be made available on reasonable request from any qualified investigator.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No