Hypersensitivity to Adrenomedullin in Post-Traumatic Headache

Not Applicable

Recruiting

• Conditions: Posttraumatic Headache
• Interventions: Drug: Adrenomedullin; Drug: Placebo

• Registration Number: NCT07059546
• Lead Sponsor: Danish Headache Center

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.

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-07-01
• Study First Submitted QC: 2025-07-01
• Study First Posted: 2025-07-10
• Last Update Submitted: 2025-07-28
• Last Update Posted: 2025-07-30
• Study Start: 2025-08-01
• Primary Completion: 2028-05-01
• Study Completion: 2028-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 21

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Adrenomedullin	Adrenomedullin	Adrenomedullin will be administered by intravenous infusion.
Placebo	Placebo	Placebo (isotonic saline) will be administered by intravenous infusion.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Rigshospitalet-Glostrup; 🇩🇰 Glostrup, Denmark