An interventional study of Pituitary Adenylate Cyclase Activating Polypeptide-38 (PACAP-38) and Placebo in Migraine With Aura and Migraine Aura, sponsored by Danish Headache Center. Not yet recruiting. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-01-15.
Sponsored by Danish Headache Center · Not applicable, Interventional, and Basic science
Pituitary Adenylate Cyclase Activating Polypeptide-38 (PACAP-38) is a key neuropeptide in migraine pathophysiology and treatment. This study investigates whether PACAP-38 administration can trigger aura in individuals with a diagnosis of migraine with aura.
In a series of studies, pharmacological triggers of migraine headache were able to induce aura as well migraine headache. Recent open-label findings show that calcitonin gene-related peptide (CGRP) can trigger aura attacks-despite its limited ability to cross the blood-brain barrier. This suggests CGRP might induce migraine aura via trigeminovascular activation, the same pathway involved in migraine headache. To further explore this concept, it is fundamental to examine whether other migraine-inducing signaling molecules that pass the BBB to a minimal degree, such as PACAP-38, are able to induce aura as well. If PACAP-38 is able to induce aura, the anti-PACAP monoclonal antibody may provide a promising therapeutic option for preventing migraine with aura.
To validate this effect, a randomized, double-blind, placebo-controlled trial is essential. Its outcomes could inform future therapies targeting the migraine-aura connection.
114 studies on the registry are indexed under Migraine with Aura; 22 are open to participants now.
This study's planned enrollment of 21 is below the median of 89 across 86 interventional studies indexed under Migraine with Aura.
Browse Migraine with Aura studies →Danish Headache Center is the lead sponsor of 129 studies on the registry; 15 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
PACAP-38 will be administered by intravenous infusion.
Drug: Pituitary Adenylate Cyclase Activating Polypeptide-38 (PACAP-38)
Placebo (isotonic saline) will be administered by intravenous infusion.
Drug: Placebo
The participants will receive a continuous intravenous infusion of 10 pmol/kg/min PACAP-38 over 20 min
The participants will receive a continuous intravenous infusion of 20 mL of placebo (isotonic saline) over 20 minutes.
Incidence of migraine attacks with aura
Difference in incidence of migraine attack with aura between PACAP-38 and placebo during the 12-hour observational period after infusion start. Experimentally induced migraine aura is defined as aura that meet Criteria B and C of 1.2 Migraine with Aura in ICHD-3.
Time frame: 12 hours
Incidence of migraine attacks without aura
Difference in incidence of migraine pain (headache) between PACAP-38 and placebo during the 12-hour observational period after infusion start. Experimentally induced migraine pain is defined as headache that meet Criteria C and D of 1.1. Migraine without Aura in ICHD-3 as well as resembles the subject's usual migraine attack or is treated with an acute headache medication.
Time frame: 12 hours
Headache intensity scores
Difference in area under the curve (AUC) for headache intensity scores between PACAP-38 and placebo during the 12-hour observational period after infusion start. The intensity of headache is rated by the subject on the 11-point numerical rating scale (0 being no headache, 10 being the worst imaginable headache).
Time frame: 12 hours
No study locations are listed for this record.
Plan to share: Yes — Anonymized data not published within this article will be made available on reasonable request from any qualified investigator.
No publications or documents are linked to this record.
This study is not yet recruiting, as verified in Jan 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Pituitary Adenylate Cyclase-Activating Polypeptide