Posttraumatic Headache
Conditions
Keywords
pain, adrenomedullin, posttraumatic headache
Brief summary
Adrenomedullin is a neuropeptide implicated in the pathogenesis of headache. This study investigates whether adrenomedullin induces headache with migraine-like features in people with persistent post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI).
Detailed description
Adrenomedullin is a potent vasoactive peptide that acts on the vascular smooth muscle and is known to induce vasodilation. It is endogenously expressed in the trigeminovascular system, a key anatomical substrate involved in headache pathogenesis. Evidence suggests that individuals with persistent post-traumatic headache (PTH) frequently experience headache with migraine-like symptoms. This study investigates whether intravenous infusion of adrenomedullin can provoke migraine-like headache in individuals with persistent PTH attributed to mild traumatic brain injury. To test this hypothesis, the investigators will carry out a randomized, double-blind, placebo-controlled, two-way crossover trial.
Interventions
DRUGAdrenomedullin
The participants will receive continuous intravenous infusion of 20 mL of 19.9 pmol/kg/min adrenomedullin 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
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 headache with migraine-like features or self-reported baseline headache that mimics the subjects' usual headache with migraine-like features
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of headache with migraine-like features | 12 hours | The difference in incidence of headache with migraine-like features between adrenomedullin 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 headache intensity scores between adrenomedullin and placebo during the 12-hour observational period after infusion start. |
Countries
Denmark
Contacts
Primary ContactHaidar Al-Khazali, MD
Backup ContactHakan Ashina, MD,PhD
Outcome results
None listed