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

NCT05635604 | Completed DMC

• 1 other identifier: H22038923
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

Migraine

Keywords

Headache; Vascular effect

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (2)

• Headache

  Time of headache measurements is from from the baseline to 24 hours eptinezumab/placebo administration.

• Changes in the superficial temporal artery (STA).

  Time of headache measurements is from from the baseline to 24 hours eptinezumab/placebo administration.

Study Arms (2)

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.

Drug: Eptinezumab; Drug: PACAP-38

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.

Drug: PACAP-38

Interventions

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.

Eptinezumab and PACAP-38

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.

Eptinezumab and PACAP-38; Placebo and PACAP-38

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers of both sexes.
• years.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Danish Headache Center: lead

Study Sites (1)

Danish headache center

Glostrup Municipality, 2600, Denmark

Location

Related Publications (1)

• 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.

  PMID: 40229719 DERIVED

MeSH Terms

Conditions

Migraine Disorders; Headache

Interventions

eptinezumab; Pituitary Adenylate Cyclase-Activating Polypeptide

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nerve Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Neuropeptides; Proteins; Nerve Tissue Proteins; Biological Factors

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study investigator

Model Details: Randomized, double-blind, placebo-controlled design in migraine without aura patients.

Study Record Dates

• First Submitted: November 15, 2022
• First Posted: December 2, 2022
• Study Start: March 1, 2023
• Primary Completion: August 4, 2023
• Study Completion: August 4, 2023
• Last Updated: December 4, 2023

Record last verified: 2023-11

Locations

DK (1)