Substance P-Induced Migraine Attacks Without Aura

Official title

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

Overview

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.

Interventions

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

Primary outcome measures

• Incidence of migraine attacks without aura [Time frame: 12 hours]

Secondary outcome measures (1)

• Headache intensity scores [Time frame: 12 hours]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Quadruple blind

Primary purpose

Basic science

Study locations

Denmark · 1 center

• Rigshospitalet Glostrup — Glostrup Municipality

Identifiers

NCT: NCT06959004 · H-23034165

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗