MigraineNCT05635604
Migraine Induction Properties of PACAP-38 After Eptinezumab in Migraine Without Aura Patients.
A study testing Eptinezumab and PACAP-38 in people with Migraine, run by Danish Headache Center at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Migraine
- What is being tested?
- Eptinezumab and PACAP-38
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Mar 2023to 4 Aug 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Migraine
- Being tested
- Eptinezumab, PACAP-38
- Keywords
- Headache, Vascular effect
- Medical subject headings
- Migraine Disorders, Headache
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EptinezumabDrug
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.
PACAP-38Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: PACAP-38 |
What is being measured
The primary outcome is the main question the study is designed to answer.
A subjective report of a migraine attack
The participants report whether they feel a migraine attack (Yes or no).
Measured: Time of reporting migraine attack is from the baseline to 24 hours after eptinezumab/placebo administration.
Secondary outcomes (2)
Headache
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).
Measured: Time of headache measurements is from from the baseline to 24 hours eptinezumab/placebo administration.
Changes in the superficial temporal artery (STA).
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).
Measured: Time of headache measurements is from from the baseline to 24 hours eptinezumab/placebo administration.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2022
- Study start1 Mar 2023
- Primary completion4 Aug 2023
- Study completion4 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MigraineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, double-blind, placebo-controlled design in migraine without aura patients.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Danish Headache Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohammad Al-Mahdi Al-Karagholi, Danish Headache Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05635604
- Sponsor's protocol ID
- H22038923
- Status last verified
- Nov 2023
- First submitted
- 15 Nov 2022
- Last updated
- 4 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 40229719
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Stratification of Signaling Pathways Underlying Migraine Pathophysiology.
- ClinicalTrials.gov ID
- NCT05635604
- Acronym / sponsor ID
- H22038923
- Conditions
- Migraine
- Keywords
- Headache, Vascular effect
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Danish Headache CenterUniversity, hospital or other
- Study start
- 1 Mar 2023 (actual)
- Primary completion
- 4 Aug 2023 (actual)
- Study completion
- 4 Aug 2023 (actual)
- First posted
- 2 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, double-blind, placebo-controlled design in migraine without aura patients.
| Arm | Type | Receives |
|---|---|---|
| Eptinezumab and PACAP-38 | Active comparator | Drug: Eptinezumab, Drug: PACAP-38The 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 | Placebo comparator | Drug: PACAP-38The 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EptinezumabEptinezumab 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 | Eptinezumab and PACAP-38 |
| PACAP-38PACAP-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. | Drug | Eptinezumab and PACAP-38, Placebo and PACAP-38 |
Primary outcome
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).
2 secondary outcomes
Headache
Time frame: 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2023.
- Derived from this study: PubMed 40229719Al-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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Eptinezumab and PACAP-38 in people with Migraine, run by Danish Headache Center at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05635604, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2023.