Migraine
Conditions
Keywords
Headache, Vascular effect
Brief summary
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.
Detailed description
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.
Interventions
DRUGEptinezumab
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.
DRUGPACAP-38
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.
Sponsors
Danish Headache Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, double-blind, placebo-controlled design in migraine without aura patients.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Healthy volunteers of both sexes. * 18-60 years. * 50-100 kg. * Women of childbearing potential must use adequate contraception * History of migraine without aura for ≥ 12 months according to the International Classification of Headache Disorders 3rd Edition (ICHD-3) criteria. * No migraine preventive treatment.
Exclusion criteria
* A history of serious somatic disease * \> 50 years of age at migraine onset. * History of any other primary headaches disorder (except ≤ 5 monthly days with tension- type headache). * Daily intake of any medication except contraceptives
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| A subjective report of a migraine attack | Time of reporting migraine attack is from the baseline to 24 hours after eptinezumab/placebo administration. | The participants report whether they feel a migraine attack (Yes or no). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in the superficial temporal artery (STA). | Time of headache measurements is from from the baseline to 24 hours eptinezumab/placebo administration. | 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). |
| Headache | Time of headache measurements is from from the baseline to 24 hours eptinezumab/placebo administration. | 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). |
Countries
Denmark
Outcome results
None listed