Amino Acids, Peptides, and Proteins, Amylin, Brain Diseases, Central Nervous System Diseases, Headache, Headache Disorders, Headache Disorders, Primary, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Migraine Disorders, Nervous System Diseases, Neurologic Manifestations, Pain, Pathological Conditions, Signs and Symptoms, Peptide Hormones, Peptides, Pramlintide, Signs and Symptoms
Conditions
Keywords
Migraine, Headache, Pain, Amylin
Brief summary
Pramlintide is a peptide analogue of human amylin which is a vasoactive signaling molecule involved in the pathogenesis of migraine. This study investigates whether pramlintide induces migraine attacks without aura in people with migraine without aura.
Detailed description
Amylin is a vasoactive substance that acts on vascular smooth muscle and can cause vasodilation. It is naturally present in the trigeminovascular system, an important structure involved in headache development. Recent studies indicate that intravenous infusion of pramlintide, an amylin analogue, can trigger migraine attacks in people with migraine. This study aims to determine whether intravenous pramlintide can induce migraine attacks without aura in individuals who experience migraine without aura. To test this, the investigators will conduct a randomized, double-blind, placebo-controlled, two-way crossover trial.
Interventions
DRUGPlacebo
The participants will receive continuous intravenous infusion of 20 mL of placebo (isotonic saline) over 20 minutes.
DRUGAmylin
The participants will receive continuous intravenous infusion of 20 mL (6 μg/min) of pramlintide (amylin) 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
This single-center trial applies a randomized, double-blind, placebo-controlled, two-way crossover design.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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 * Provision of informed consent prior to initiation of any study-specific activities/procedures
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) * 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 * Migraine attack within 48 hours of infusion start * Aura within 48 hours of infusion start
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of migraine attacks without aura | 12 hours | The difference in the incidence of migraine attacks without aura between pramlintide and placebo during the 12-hour observational period after infusion start. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Headache intensity scores | 12 hours | The secondary outcome is the difference in the area under the curve (AUC) for median headache intensity scores between pramlintide and placebo during the 12-hour observational period after infusion start. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Superficial temporal artery dilation | 2 hours | The difference in AUC for relative superficial temporal artery (STA) dilation between pramlintide and placebo from the start of infusion to 2 hours after the infusion. |
| Middle cerebral artery blood flow velocity | 2 hours | The difference in AUC for change in middle cerebral artery (MCA) mean blood flow velocity between pramlintide and placebo from the start of infusion to 2 hours after the infusion. |
Countries
Denmark
Contacts
Primary ContactHaidar Al-Khazali, MD, PhD
Backup ContactHakan Ashina, MD, PhD
Outcome results
None listed