Migraine Induction Properties of PACAP-38 After Eptinezumab in Migraine Without Aura Patients.

Danish Headache Center

Status: Completed

Conditions: Migraine

Treatments: Drug: Eptinezumab; Drug: PACAP-38

Study type: Interventional

Funder types: Other

Identifiers

NCT05635604

H22038923

Details and patient eligibility

About

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.

Full 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.

Enrollment: 38 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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38 participants in 2 patient groups, including a placebo group

Eptinezumab and PACAP-38

Active Comparator group

Description:

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.

Treatment:

Drug: Eptinezumab

Drug: PACAP-38

Placebo and PACAP-38

Placebo Comparator group

Description:

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.

Treatment:

Drug: PACAP-38