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To investigate whether administration of calcitonin gene-related peptide (CGRP) binding monoclonal antibodies eptinezumab prevents pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) induced migraine attacks in migraine without aura patients.
The aim of the present study is to investigate whether
- CGRP binding monoclonal antibodies eptinezumab prevents PACAP-38 induced migraine attacks in migraine without aura patients.
Clinical and basic research have established calcitonin gene-related peptide (CGRP) as central molecule in migraine pathophysiology, yet existing CGRP antagonizing therapies such as the CGRP and CGRP receptor binding monoclonal antibodies are only effective in 50-60% of migraine patients. PACAP-38 and CGRP colocalize in the trigeminovascular system, and both activate adenylate cyclase upon receptor binding which causes increased formation of cyclic AMP (cAMP). It is unknown if CGRP and PACAP-38 signaling pathways differ sufficiently for PACAP-38 to be an alternative treatment target to CGRP. Whether administration of CGRP binding monoclonal antibodies eptinezumab prevents PACAP-38 induced migraine attacks in migraine without aura patients is yet to be investigated.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Eptinezumab and PACAP-38 | Active Comparator | The participants will receive an intravenous infusion of eptinezumab (300 mg) over 30 minutes followed (2 hours later) by an intravenous infusion of PACAP-38 (10 pmol/kg/min) over 20 minutes. |
|
| Placebo and PACAP-38 | Placebo Comparator | The participants will receive an intravenous infusion of placebo (saline) over 30 minutes followed (2 hours later) by an intravenous infusion of PACAP-38 (10 pmol/kg/min) over 20 minutes. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Eptinezumab | Drug | Eptinezumab or ALD403 is a humanized anti-calcitonin gene-related peptide IgG1 monoclonal antibody that binds to calcitonin gene-related peptide (CGRP). It selectively binds human CGRP ligand to prevent activation of the CGRP receptor and blocks its binding to the receptor for the prevention of migraine. |
| Measure | Description | Time Frame |
|---|---|---|
| A subjective report of a migraine attack | The participants report whether they feel a migraine attack (Yes or no). | Time of reporting migraine attack is from the baseline to 24 hours after eptinezumab/placebo administration. |
| Measure | Description | Time Frame |
|---|---|---|
| Headache | Headache intensity will be recorded by numerical rating scale (NRS) from 0 to 10 (0, no headache; 1, a feeling of pressure; 10, worst imaginable headache). | Time of headache measurements is from from the baseline to 24 hours eptinezumab/placebo administration. |
| Changes in the superficial temporal artery (STA). |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Danish headache center | Glostrup Municipality | 2600 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40229719 | Derived | Al-Karagholi MA, Zhuang ZA, Beich S, Ashina H, Ashina M. PACAP38-induced migraine attacks are independent of CGRP signaling: a randomized controlled trial. J Headache Pain. 2025 Apr 14;26(1):79. doi: 10.1186/s10194-025-02022-2. |
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| ID | Term |
|---|---|
| D008881 | Migraine Disorders |
| D006261 | Headache |
| ID | Term |
|---|---|
| D051270 | Headache Disorders, Primary |
| D020773 | Headache Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C000628361 | eptinezumab |
| D051219 | Pituitary Adenylate Cyclase-Activating Polypeptide |
| ID | Term |
|---|---|
| D009414 | Nerve Growth Factors |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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Randomized, double-blind, placebo-controlled design in migraine without aura patients.
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|
| PACAP-38 | Drug | PACAP-38 is a naturally occurring peptide diffusely expressed throughout the body. The Danish Headache Center has used infusion of PACAP-38 for several years and the first time in 2007 where infusion of PACAP-38 triggered headaches and migraines in migraine patients. |
|
Diameter of the frontal branch of the superficial temporal artery (STA). Repeated measurements covering the diameter of STA before and after eptinezumab/placebo administration and PACAP-38 infusion measured by millimeters (mm). |
| Time of headache measurements is from from the baseline to 24 hours eptinezumab/placebo administration. |
| D009422 | Nervous System Diseases |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009479 | Neuropeptides |
| D011506 | Proteins |
| D009419 | Nerve Tissue Proteins |
| D001685 | Biological Factors |