Does adrenomedullin trigger migraine-like headaches in people with persistent post-traumatic headache?
Hypersensitivity to Adrenomedullin in Post- Traumatic Headache: A Randomized Clinical Trial
This trial will test if a short intravenous infusion of the neuropeptide adrenomedullin can trigger migraine-like headaches in adults with long-standing post-traumatic headache after a single mild head injury.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 21 (estimated) |
| Ages | 18 Years to 65 Years |
| Sex | All |
| Sponsor | Danish Headache Center Academic / other |
| Locations | 1 site (Glostrup Municipality) |
| Trial ID | NCT07059546 on ClinicalTrials.gov |
What this trial studies
The trial uses a randomized, double-blind, placebo-controlled, two-way crossover design in which participants receive an intravenous infusion of adrenomedullin on one visit and placebo on another. Adults aged 18–65 with persistent post-traumatic headache for at least 12 months and an average of ≥4 headache days per month are eligible, provided they had a single mild traumatic brain injury and no prior primary headache disorder. Investigators will record whether the infusion provokes headache with migraine-like features and monitor vital signs and adverse events throughout each visit. The crossover design allows each participant to serve as their own control, improving sensitivity to detect a provocation effect.
Who should consider this trial
Good fit: Ideal candidates are adults 18–65 with a single mild traumatic brain injury, persistent post-traumatic headache for ≥12 months, and an average of at least 4 headache days per month, who can safely undergo an IV infusion and monitoring.
Not a fit: Patients with multiple head injuries, moderate or severe TBI, pre-existing primary headache disorders (other than infrequent tension-type headache), whiplash, prior craniotomy, or other significant comorbid conditions are unlikely to benefit or be eligible.
Why it matters
Potential benefit: If successful, the study could clarify a biological trigger for post-traumatic migraine-like headaches and point toward new targeted treatments or preventive strategies.
How similar studies have performed: Provocation studies with other neuropeptides (for example, CGRP and PACAP) have induced migraine-like attacks in susceptible people, but adrenomedullin provocation is a relatively novel approach with limited prior data.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Glostrup Municipality
- Rigshospitalet-Glostrup — Glostrup Municipality, Denmark (Recruiting)
Study contacts
- Study coordinator: Haidar Al-Khazali, MD
- Email: haidardk@hotmail.com
- Phone: +4541598494
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.