Hypersensitivity to Adrenomedullin in Post-Traumatic Headache

Danish Headache Center

Status: Enrolling

Conditions: Posttraumatic Headache

Treatments: Drug: Placebo; Drug: Adrenomedullin

Study type: Interventional

Funder types: Other

Identifiers

NCT07059546

H-21067681

Details and patient eligibility

About

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).

Full 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.

Enrollment: 21 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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21 participants in 2 patient groups, including a placebo group

Adrenomedullin

Experimental group

Description:

Adrenomedullin will be administered by intravenous infusion.

Treatment:

Drug: Adrenomedullin

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo