Hypersensitivity to Adrenomedullin in Post-Traumatic Headache

NCT ID: NCT07059546

Last Updated: 2025-07-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-01
• Study Completion Date: 2028-12-01

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.

Conditions

Posttraumatic Headache

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Adrenomedullin

Adrenomedullin will be administered by intravenous infusion.

Group Type: EXPERIMENTAL

Adrenomedullin

Intervention Type: DRUG

The participants will receive continuous intravenous infusion of 20 mL of 19.9 pmol/kg/min adrenomedullin over 20 minutes.

Placebo

Placebo (isotonic saline) will be administered by intravenous infusion.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

The participants will receive a continuous intravenous infusion of 20 mL of placebo (isotonic saline) over 20 minutes.

Interventions

Adrenomedullin

The participants will receive continuous intravenous infusion of 20 mL of 19.9 pmol/kg/min adrenomedullin over 20 minutes.

Intervention Type: DRUG

Placebo

The participants will receive a continuous intravenous infusion of 20 mL of placebo (isotonic saline) over 20 minutes.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Danish Headache Center

OTHER

Sponsor Role: lead

Responsible Party

Haidar Al-Khazali

Sub-Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Rigshospitalet-Glostrup

Glostrup Municipality, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Haidar Al-Khazali, MD

Role: CONTACT

haidardk@hotmail.com

+4541598494

Hakan Ashina, MD,PhD

Role: CONTACT

haakan.ashina@regionh.dk

+4528102495

Facility Contacts

Haidar Al-Khazali, MD

Role: primary

haidardk@hotmail.com

+4541598494

Hakan Ashina, MD, PhD

Role: backup

haakan.ashina@regionh.dk

+4528102495

Other Identifiers

H-21067681

Identifier Type: -

Identifier Source: org_study_id