Migraine Induction Properties of PACAP-38 After Eptinezumab in Migraine Without Aura Patients.
- Registration Number
- NCT05635604
- Lead Sponsor
- Danish Headache Center
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 38
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Eptinezumab and PACAP-38 Eptinezumab 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. Eptinezumab and PACAP-38 PACAP-38 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 PACAP-38 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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).
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).
Trial Locations
- Locations (1)
Danish headache center
🇩🇰Glostrup, Denmark