Induction of Migraine Attacks With Aura Using Pituitary Adenylate Cyclase Activating Polypeptide-38

What Was Tested

This registered not phased trial tested PACAP for migraine.

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.

It had two arms (groups): Pituitary Adenylate Cyclase Activating Polypeptide-38 (PACAP-38) (experimental) and Placebo (placebo comparator).

PACAP-38 will be administered by intravenous infusion.

Placebo (isotonic saline) will be administered by intravenous infusion.

The registry classes the interventions as drug.

More on the Plan

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.

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.

To validate this effect, a randomized, double-blind, placebo-controlled trial is essential.

Its outcomes could inform future therapies targeting the migraine-aura connection.

Who Took Part

The registry lists 21 planned participants were the target.

It was open to people of any sex aged from 18 years up to 65 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Age 18 to 65 years of age upon entry into screening. ≥ 1 monthly day with aura that meets criteria as aura on average across the three months before screening. Provision of informed consent prior to initiation of any study-specific activities/procedures.

The full record lists 4 inclusion and 9 exclusion criteria; among the exclusions: the subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior; female subjects of childbearing potential with a positive pregnancy test during any study visit; intake of acute medications (e.g. analgesics, triptans) within 48 hours of infusion start.

How the Study Was Run

The set-up was randomized, crossover and quadruple-blind.

Because people in this PACAP study were split into groups at random, differences between the groups are less likely to reflect who happened to join each one.

In the crossover set-up each of the migraine participants took both PACAP and the comparison in turn, acting as their own control.

As a double-blind PACAP study, the assignments were hidden from both participants and investigators until the end.

Those kept unaware of assignments: participant, care provider, investigator and outcomes assessor.

It started in 2026-02-01 with completion listed for 2026-12-01.

Its stated primary purpose is basic science.

What Was Measured

Researchers chose this as the main measure: Incidence of migraine attacks with aura (time frame: 12 hours).

It also tracked 2 secondary outcomes, for example Incidence of migraine attacks without aura.

What This Means in Plain Language

Put simply, this is a not phased, randomized trial of PACAP in 21 people with migraine.

Its size is small, so on its own it can only give an early look.

Its status is not yet recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the PACAP compound page, Migraine research.