Substance P-Induced Migraine Attacks Without Aura

June 1, 2025 updated by: Haidar Al-Khazali, Danish Headache Center

Substance P-Induced Migraine Attacks Without Aura: A Randomized Clinical Trial

Substance P is a neuropeptide implicated in the pathogenesis of headache. This study investigates whether its administration can trigger migraine attacks in individuals with migraine without aura.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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. Its most well-established role is in nociceptive signaling, and accumulating evidence implicates substance P in the pathogenesis of headache. 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.

Study Type

Interventional

Enrollment (Estimated)

21

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Denmark
      • Glostrup, Denmark, 2600
        • Recruiting
        • Rigshospitalet Glostrup
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Haidar Al-Khazali, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Any history of a primary or secondary headache disorder other than migraine without aura and infrequent episodic tension-type headache
  • Any history of moderate to severe traumatic brain injury
  • Any history of cardiovascular disease, including cerebrovascular diseases
  • Any history of pulmonary disease
  • Any other clinically significant disorders, conditions, or diseases that might impact the safety of the subject or interfere with the study's evaluation, procedures, or completion, aside from those mentioned above. This includes any relevant medical history or evidence that, in the opinion of the site investigator, might pose a risk to the subject or impact the validity of the study results
  • 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
  • Cardiovascular disease of any kind, including cerebrovascular diseases
  • Hypertension (systolic blood pressure of ≥150 mmHg and/or diastolic blood pressure of ≥100 mmHg) prior to the start of infusion on the experimental day
  • Hypotension (systolic blood pressure of ≤90 mmHg and/or diastolic blood pressure of ≤50 mmHg)
  • Daily use of any medication other than contraceptives
  • Intake of any medication other than contraceptives within 48 hours of infusion start
  • Headache of any intensity within 48 hours of infusion start
  • Migraine attack within 5 days of infusion start
  • Aura within 48 hours of infusion start

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Substance P
Substance P will be administered by intravenous infusion.
Drug: Substance P
The participants will receive a continuous intravenous infusion of 20 mL of substance P (4.0 pmol/kg/min) over 20 minutes.
Placebo Comparator: Placebo
Placebo (isotonic saline) will be administered by intravenous infusion.
Drug: Placebo
The participants will receive a continuous intravenous infusion of 20 mL of placebo (isotonic saline) over 20 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of migraine attacks without aura
Time Frame: 12 hours
The difference in the incidence of migraine attacks without aura between substance P and placebo during the 12-hour observational period after infusion start.
12 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Headache intensity scores
Time Frame: 12 hours
The secondary outcome is the difference in the area under the curve (AUC) for headache intensity scores between substance P and placebo during the 12-hour observational period after infusion start.
12 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Danish Headache Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 13, 2025

Primary Completion (Estimated)

May 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

May 5, 2025

First Submitted That Met QC Criteria

May 5, 2025

First Posted (Actual)

May 6, 2025

Study Record Updates

Last Update Posted (Estimated)

June 5, 2025

Last Update Submitted That Met QC Criteria

June 1, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-23034165

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Anonymized data not published within this article will be made available on reasonable request from any qualified investigator.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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