Substance P-Induced Migraine Attacks Without Aura

NCT ID: NCT06959004

Last Updated: 2025-06-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-13
• Study Completion Date: 2026-12-01

Brief Summary

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.

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.

Conditions

Migraine

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Substance P

Substance P will be administered by intravenous infusion.

Group Type: EXPERIMENTAL

Substance P

Intervention Type: DRUG

The participants will receive a continuous intravenous infusion of 20 mL of substance P (4.0 pmol/kg/min) over 20 minutes.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

The participants will receive a continuous intravenous infusion of 20 mL of placebo (isotonic saline) over 20 minutes.

Interventions

Substance P

The participants will receive a continuous intravenous infusion of 20 mL of substance P (4.0 pmol/kg/min) over 20 minutes.

Intervention Type: DRUG

Placebo

The participants will receive a continuous intravenous infusion of 20 mL of placebo (isotonic saline) over 20 minutes.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Danish Headache Center

OTHER

Sponsor Role: lead

Responsible Party

Haidar Al-Khazali

Sub-Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Rigshospitalet Glostrup

Glostrup Municipality, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Haidar Al-Khazali, MD

Role: CONTACT

haidardk@hotmail.com

+4541598494

Hakan Ashina, MD, PhD

Role: CONTACT

haakan.ashina@regionh.dk

+4528102495

Facility Contacts

Haidar Al-Khazali, MD

Role: primary

haidardk@hotmail.com

41598494

Hakan Ashina, MD, PhD

Role: backup

haakan.ashina@regionh.dk

+4528102495

Other Identifiers

H-23034165

Identifier Type: -

Identifier Source: org_study_id