Amino Acids, Peptides, and Proteins, Amylin, Brain Diseases, Central Nervous System Diseases, Headache Disorders, Headache Disorders, Secondary, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Nervous System Diseases, Neurologic Manifestations, Pain, Pathological Conditions, Signs and Symptoms, Peptide Hormones, Peptides, Post-Traumatic Headache, Pramlintide, Signs and Symptoms
Conditions
Keywords
Post-traumatic headache, Pain, Amylin
Brief summary
Pramlintide is a peptide analogue of human amylin which is a vasoactive substance involved in the pathogenesis of headache. This study investigates whether pramlintide induces migraine-like headache in people with persistent post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI).
Detailed description
Amylin is a vasodilator released from nerve fibers within the trigeminovascular system, which is considered a key anatomical and physiological substrate in the pathogenesis of migraine and persistent post-traumatic headache (PTH). Persistent PTH attributed to mild traumatic brain injury frequently presents with migraine attacks, suggesting shared underlying mechanisms with migraine. This study aims to determine whether intravenous infusion of pramlintide, an analogue of amylin, can induce migraine-like headache in individuals with persistent post-traumatic headache. To test this hypothesis, we will conduct a randomized, double-blind, placebo-controlled, two-way crossover study.
Interventions
DRUGAmylin
The participants will receive continuous intravenous infusion of 6 μg/min of pramlintide (amylin) over 20 minutes.
DRUGPlacebo
The participants will receive 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
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 * History of persistent headache attributed to mild traumatic injury to the head for ≥ 12 months and in accordance with the International Classification of Headache Disorders, 3rd Edition (ICHD-3) * ≥ 4 monthly headache days on average across the 3 months prior to screening * Provision of informed consent prior to initiation of any study-specific activities/procedures
Exclusion criteria
* \> 1 mild traumatic injury to the head * History of any primary or secondary headache disorder prior to mild traumatic injury to the head (except for infrequent episodic tension-type headache) * History of moderate or severe injury to the head * History of whiplash injury * History of craniotomy * History or evidence of any other clinically significant disorder, condition or disease (except for those outlined above) than, in the opinion of the site investigator, would pose a risk to subject safety or interfere with study evaluation, procedures or completion * 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) * Initiation, discontinuation, or change of dosing of prophylactic medications within 2 months prior to study inclusion * Intake of acute medications (e.g. analgesics, triptans) within 48 hours of infusion start * Baseline headache intensity of \>3 on an 11-point numeric rating scale (0 being no headache, 10 being the worst imaginable headache) * Baseline migraine-like headache or self-reported baseline headache that mimics the subjects' usual migraine-like headache
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of migraine-like headache | 12 hours | Difference in incidence of migraine-like headache (0 to 12 hours) between pramlintide and placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Headache Intensity Scores | 12 hours | Difference in area under the curve (AUC) for headache intensity scores (0 to 12 hours) between pramlintide and placebo. |
Countries
Denmark
Contacts
Primary ContactHaidar Al-Khazali, MD, PhD
Backup ContactHakan Ashina, MD, PhD
Outcome results
None listed