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

Sponsor

Danish Headache Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05635604

Collaborator

(none)

Enrollment

Location

Arms

7.9

Anticipated Duration (Months)

4.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: Eptinezumab Drug: PACAP-38	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

38 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Other

Official Title:

Molecular Stratification of Signaling Pathways Underlying Migraine Pathophysiology.

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Jul 30, 2023

Anticipated Study Completion Date :

Jul 30, 2023

Arms and Interventions

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.

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

Outcome Measures

Primary Outcome Measures

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

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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Danish headache center	Glostrup		Denmark	2600

Sponsors and Collaborators

Danish Headache Center

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Mohammad Al-Mahdi Al-Karagholi, Study investigator, Danish Headache Center

ClinicalTrials.gov Identifier:

NCT05635604

Other Study ID Numbers:

H22038923

First Posted:

Dec 2, 2022

Last Update Posted:

Dec 5, 2022

Last Verified:

Dec 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Mohammad Al-Mahdi Al-Karagholi, Study investigator, Danish Headache Center

Headache

Vascular effect

Additional relevant MeSH terms:

Migraine Disorders

Pituitary Adenylate Cyclase-Activating Polypeptide

Study Results

No Results Posted as of Dec 5, 2022