Clinical trial NCT05635604: Migraine Induction Properties of PACAP-38 After Eptinezumab in Migraine Without Aura Patients.
Official title: Molecular Stratification of Signaling Pathways Underlying Migraine Pathophysiology.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Migraine
Keywords: Headache
Vascular effect
Lead sponsor: Danish Headache Center
Sponsor class: OTHER
First posted: 2022-12-02
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled design in migraine without aura patients.
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: A subjective report of a migraine attack
timeFrame: Time of reporting migraine attack is from the baseline to 24 hours after eptinezumab/placebo administration.
Secondary outcomes:
measure: Headache
timeFrame: Time of headache measurements is from from the baseline to 24 hours eptinezumab/placebo administration.
measure: Changes in the superficial temporal artery (STA).
timeFrame: Time of headache measurements is from from the baseline to 24 hours eptinezumab/placebo administration.
Other outcomes:
Locations:
city: Glostrup
country: Denmark
facility: Danish headache center
Study officials:
References: