Effects of Substance P on Headache Induction in Healthy Individuals

NCT06632080 | Not Yet Recruiting

• 1 other identifier: H-23030963
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers Only

Keywords

Headache

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Headache Intensity Scores

  12 hours

Other Outcomes (2)

• Dilation of the Superficial Temporal Artery

  2 hours

• Blood Flow Velocity in the Middle Cerebral Artery

  2 hours

Study Arms (2)

Substance P

EXPERIMENTAL

Substance P will be administered by intravenous infusion.

Drug: Substance P

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Substance P DRUG

The participants will receive a continuous intravenous infusion of 20 mL of substance P (1.5 pmol/kg/min) over 20 minutes.

Substance P

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Danish Headache Center: lead

Study Sites (1)

Danish Headache Center, Copenhagen University Hospital - Rigshospitalet

Glostrup Municipality, 2600, Denmark

Location

Related Publications (1)

• Al-Khazali HM, Christensen RH, Gozalov E, Hakimzadeh Z, Melchior AG, Dominguez-Moreno R, Ashina M, Ashina H. Effects of substance P on headache induction and arterial dilation in healthy adults. Cephalalgia. 2025 May;45(5):3331024251336132. doi: 10.1177/03331024251336132. Epub 2025 May 14.

  PMID: 40369974 DERIVED

MeSH Terms

Conditions

Headache

Interventions

Substance P

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tachykinins; Kinins; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Neuropeptides; Oligopeptides; Proteins; Nerve Tissue Proteins; Autacoids; Inflammation Mediators; Biological Factors

Central Study Contacts

Hakan Ashina, MD, PhD

CONTACT

+45 28 10 24 95; haakan.ashina@regionh.dk

Haidar Al-Khazali, MD

CONTACT

+45 41 59 84 94; haidardk@hotmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Researcher

Model Details: The present trial has a randomized, double-blind, placebo-controlled, 2-way crossover design and will be conducted at a single site.

Study Record Dates

• First Submitted: October 6, 2024
• First Posted: October 8, 2024
• Study Start: October 14, 2024
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

DK (1)