Effects of Substance P on Headache Induction in Healthy Individuals

Effects of Substance P on Headache Induction in Healthy Individuals: a Randomized Clinical Trial

Substance P is a signaling molecule that has been implicated in the pathogenesis of headache. This study aims to ascertain whether administration of substance P can induce headache in healthy adults.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Volunteers Only
• Intervention / Treatment: Drug: Substance P; Drug: Placebo

Detailed Description

Substance P is a vasoactive signaling molecule that belongs to the tachykinin family of peptides. It is expressed in multiple cells, including primary afferents of the trigeminal ganglion that innervate the meninges and its arteries. The best-known function of substance P is its role in pain transmission, and several lines of evidence has implicated substance P in the pathogenesis of headache. This study aims to ascertain whether intravenous infusion of substance P induces headache in healthy individuals who have no past or current history of primary or secondary headache disorder, except for infrequent episodic tension-type headache. For this purpose, we will conduct a randomized, double-blind, placebo-controlled, 2-way crossover trial.

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hakan Ashina, MD, PhD; Phone Number: +45 28 10 24 95; Email: haakan.ashina@regionh.dk
• Study Contact Backup: Name: Haidar Al-Khazali, MD; Phone Number: +45 41 59 84 94; Email: haidardk@hotmail.com

Study Locations

• Denmark
  • Glostrup, Denmark, 2600
    • Danish Headache Center, Copenhagen University Hospital - Rigshospitalet
    • Contact: Hakan Ashina, MD, PhD; Phone Number: +45 28 10 24 95; Email: haakan.ashina@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 18 to 65 years of age upon entry into screening
• A body weight of 50 to 100 kg
• Provision of informed consent prior to initiation of any study-specific activities/procedures.

Exclusion Criteria:

• Any history of a primary or secondary headache disorder, except for infrequent episodic tensiontype headache
• Any first-degree relatives with a history of a primary headache disorder, except for 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)
• Abnormalities on the electrocardiogram that, in the opinion of the site investigator, might pose a risk to the subject or impact the validity of the study results
• Daily use of any medication other than contraceptives
• Intake of any medication other than contraceptives within 48 hours of infusion start
• Intake of caffeine, nicotine, and alcohol within 12 hours of infusion start
• Headache of any intensity within 48 hours of infusion start

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

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 (1.5 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 Headache	The primary outcome is the difference in the incidence of headache* between substance P and placebo during the 12-hour observational period after infusion start. * The intensity of headache is rated by the subject on the 11-point numerical rating scale (0 being no headache, 10 being the worst imaginable headache).	12 hours

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dilation of the Superficial Temporal Artery	The difference in area under the curve for relative STA dilation between substance P and placebo from the start of infusion to 2 hours after the infusion.	2 hours
Blood Flow Velocity in the Middle Cerebral Artery	The difference in area under the curve for change in MCA mean blood flow velocity between substance P and placebo from the start of infusion to 2 hours after the infusion.	2 hours

Collaborators and Investigators

• Sponsor: Danish Headache Center

Study record dates

Study Major Dates

• Study Start (Estimated): October 14, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: October 6, 2024
• First Submitted That Met QC Criteria: October 6, 2024
• First Posted (Actual): October 8, 2024

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 11, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Headache
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Headache; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Substance P; Neurokinin A
• Other Study ID Numbers: H-23030963

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
• product manufactured in and exported from the U.S.: No