Healthy Volunteers Only
Conditions
Keywords
Headache
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.
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.
Interventions
DRUGSubstance P
The participants will receive a continuous intravenous infusion of 20 mL of substance P (1.5 pmol/kg/min) over 20 minutes.
DRUGPlacebo
The participants will receive a continuous intravenous infusion of 20 mL of placebo (isotonic saline) over 20 minutes.
Sponsors
Danish Headache Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
The present trial has a randomized, double-blind, placebo-controlled, 2-way crossover design and will be conducted at a single site.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Headache | 12 hours | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Headache Intensity Scores | 12 hours | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Dilation of the Superficial Temporal Artery | 2 hours | 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. |
| Blood Flow Velocity in the Middle Cerebral Artery | 2 hours | 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. |
Countries
Denmark
Contacts
Primary ContactHakan Ashina, MD, PhD
Backup ContactHaidar Al-Khazali, MD
Outcome results
None listed