Migraine Aura, Migraine With Aura
Conditions
Keywords
Migraine, Aura, Calcitonin gene-related peptide
Brief summary
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
DRUGCalcitonin-gene related peptide (CGRP)
The participants will receive a continuous intravenous infusion of 1.5 μg/min of CGRP over 60 minutes.
DRUGPlacebo
The participants will receive a continuous intravenous infusion of 60 mL of placebo (isotonic saline) over 60 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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of migraine attacks with aura | 12 hours | Difference in incidence of migraine attack with aura between CGRP and placebo during the 12-hour observational period after infusion start. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of migraine attacks without aura | 12 hours | Difference in incidence of migraine headache between CGRP and placebo during the 12-hour observational period after infusion start. |
| Headache intensity scores | 12 hours | Difference in area under the curve (AUC) for headache intensity scores between CGRP and placebo during the 12-hour observational period after infusion start. |
Countries
Denmark
Contacts
Primary ContactHaidar Al-Khazali, MD
Backup ContactHakan Ashina, MD, PhD
Outcome results
None listed