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

November 30, 2023 updated by: Mohammad Al-Mahdi Al-Karagholi, Danish Headache Center

Molecular Stratification of Signaling Pathways Underlying Migraine Pathophysiology.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

38

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Glostrup, Denmark, 2600
        • Danish Headache Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Eptinezumab and 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.
Drug: Eptinezumab
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.
Drug: PACAP-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.
Placebo Comparator: Placebo and 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.
Drug: PACAP-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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
A subjective report of a migraine attack
Time Frame: 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).
Time of reporting migraine attack is from the baseline to 24 hours after eptinezumab/placebo administration.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Headache
Time Frame: 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).
Time of headache measurements is from from the baseline to 24 hours eptinezumab/placebo administration.
Changes in the superficial temporal artery (STA).
Time Frame: 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).
Time of headache measurements is from from the baseline to 24 hours eptinezumab/placebo administration.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Danish Headache Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2023

Primary Completion (Actual)

August 4, 2023

Study Completion (Actual)

August 4, 2023

Study Registration Dates

First Submitted

November 15, 2022

First Submitted That Met QC Criteria

November 22, 2022

First Posted (Actual)

December 2, 2022

Study Record Updates

Last Update Posted (Estimated)

December 4, 2023

Last Update Submitted That Met QC Criteria

November 30, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H22038923

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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