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RecruitingNCT07059546Updated Jul 30, 2025

Hypersensitivity to Adrenomedullin in Post-Traumatic Headache

An interventional study of Adrenomedullin and Placebo in Posttraumatic Headache, sponsored by Danish Headache Center. Recruiting at 1 site in Denmark. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2025-07-30.

Sponsored by Danish Headache Center · Not applicable, Interventional, and Basic science

Phase
Not applicable
Study type
Interventional
Enrollment
21
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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).

Read the 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.

02

Conditions studied

  • Posttraumatic Headache

Keywords

  • pain
  • adrenomedullin
  • posttraumatic headache
03

In context

Post-Traumatic Headache

192 studies on the registry are indexed under Post-Traumatic Headache; 54 are open to participants now.

This study's planned enrollment of 21 is below the median of 44 across 169 interventional studies indexed under Post-Traumatic Headache.

Browse Post-Traumatic Headache studies →

Lead sponsor

Danish Headache Center is the lead sponsor of 129 studies on the registry; 15 are open to participants now.

Browse Danish Headache Center studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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 prior to initiation of any study-specific activities/procedures.

Exclusion criteria

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 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 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
Terms in these criteria, in plain language(3)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

05

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
21 participants (estimated)

Study arms

  • Experimental
    Adrenomedullin

    Adrenomedullin will be administered by intravenous infusion.

    Drug: Adrenomedullin

  • Placebo comparator
    Placebo

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

    Drug: Placebo

Interventions

  • DrugAdrenomedullin

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

  • DrugPlacebo

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

06

What researchers measure

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.

    Time frame: 12 hours

Secondary outcomes

  1. Headache Intensity Scores

    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.

    Time frame: 12 hours

07

Study locations

1 of 1 sites recruiting
08

References and documents

Individual participant data

Plan to share: Yes — Anonymized data not published within this article will be made available on reasonable request from any qualified investigator.

No publications or documents are linked to this record.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Start is estimated for Aug 2025; primary completion for May 2028, 33 months later.

Of 89 non-industry interventional studies with no phase under Post-Traumatic Headache, half reached primary completion within 11 months of starting (the median), counting those still running; a quarter within 5 and three quarters within 26. This study's planned 33 months is above that.

Counting every sponsor, half of 90 studies reached it within 12 months; a quarter within 5 and three quarters within 26.

How these figures are worked out, and which studies are left out of them.

Registered
Jul 1, 2025
First posted
Jul 10, 2025
StartEst.
Aug 1, 2025
Primary completionEst.
May 1, 2028
CompletionEst.
Dec 1, 2028
Last update
Jul 30, 2025
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jul 30, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT07059546
Lead sponsor
Danish Headache Center
Responsible party
Haidar Al-Khazali (Sub-Investigator, Rigshospitalet, Denmark) — Principal investigator
First posted
Jul 10, 2025
Start date
Aug 1, 2025 (estimated)
Primary completion
May 1, 2028 (estimated)
Completion
Dec 1, 2028 (estimated)
Last update
Jul 30, 2025

Study contacts

Haidar Al-Khazali, MD
Contact
haidardk@hotmail.com
+4541598494
Hakan Ashina, MD,PhD
Contact
haakan.ashina@regionh.dk
+4528102495

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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