Hypersensitivity to Adrenomedullin in Post-Traumatic Headache

NCT07059546 | Recruiting

• 1 other identifier: H-21067681
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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).

Conditions

Posttraumatic Headache

Keywords

pain; adrenomedullin; posttraumatic headache

Outcome Measures

Primary Outcomes (1)

• Incidence of headache with migraine-like features

  The difference in incidence of headache with migraine-like features between adrenomedullin and placebo during the 12-hour observational period after infusion start.

  12 hours

Secondary Outcomes (1)

• Headache Intensity Scores

  12 hours

Study Arms (2)

Adrenomedullin

EXPERIMENTAL

Adrenomedullin will be administered by intravenous infusion.

Drug: Adrenomedullin

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Adrenomedullin DRUG

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

Adrenomedullin

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \> 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)
• 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

Sponsors & Collaborators

• Danish Headache Center: lead

Study Sites (1)

Rigshospitalet-Glostrup

Glostrup Municipality, 2600, Denmark

RECRUITING

MeSH Terms

Conditions

Post-Traumatic Headache; Pain

Interventions

Adrenomedullin

Condition Hierarchy (Ancestors)

Headache Disorders, Secondary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Central Study Contacts

Haidar Al-Khazali, MD

CONTACT

+4541598494; haidardk@hotmail.com

Hakan Ashina, MD,PhD

CONTACT

+4528102495; haakan.ashina@regionh.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sub-Investigator

Model Details: This single-center trial applies a randomized, double-blind, placebo-controlled, two-way crossover design.

Study Record Dates

• First Submitted: July 1, 2025
• First Posted: July 10, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 30, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

DK (1)