Substance P-Induced Migraine Attacks Without Aura

What Was Tested

This registered not phased trial tested Substance P for migraine.

This study investigates whether its administration can trigger migraine attacks in individuals with migraine without aura.

It had two arms (groups): Substance P (experimental) and Placebo (placebo comparator).

Substance P 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

Substance P is a vasoactive neuropeptide of the tachykinin family, expressed in various cell types, including primary afferents of the trigeminal ganglion that innervate the meninges and associated vasculature.

This study investigates whether intravenous infusion of substance P can induce migraine attacks in individuals with a history of migraine without aura.

To test this, the investigators will conduct a randomized, double-blind, placebo-controlled, two-way crossover trial.

Who Took Part

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. A body weight of 50 to 100 kg. History of migraine without aura for ≥12 months and in accordance with ICHD-3. Between 1-5 monthly migraine days without aura on average across the 3 months prior to screening.

The full record lists 4 inclusion and 15 exclusion criteria; among the exclusions: any history of moderate to severe traumatic brain injury; any history of cardiovascular disease, including cerebrovascular diseases; any history of pulmonary disease.

How the Study Was Run

It was run as a randomized, crossover and quadruple-blind study.

Random assignment meant chance, not the researchers, decided who got Substance P and who got the comparison, which limits bias.

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

Blinding on both sides kept the migraine participants and researchers unaware of who received Substance P.

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

It started in 2025-05-13 with completion listed for 2026-05-01.

It ran at 1 site in Denmark.

Its stated primary purpose is basic science.

What Was Measured

Primary outcome: Incidence of migraine attacks without aura (time frame: 12 hours).

What This Means in Plain Language

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

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

It is still recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Substance P compound page, Migraine research.