Posttraumatic HeadacheNCT07059546
Hypersensitivity to Adrenomedullin in Post-Traumatic Headache
A study testing Adrenomedullin in people with Posttraumatic Headache, run by Danish Headache Center at 1 site in Denmark.
Trial 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 more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Posttraumatic Headache
- What is being tested?
- Adrenomedullin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Aug 2025to 1 Dec 2028
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- > 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
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- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site, 1 recruiting
- Recruiting
Rigshospitalet-Glostrup
Glostrup Municipality, 2600
Haidar Al-Khazali, MD, +4541598494, haidardk@hotmail.com
Hakan Ashina, MD, PhD, +4528102495, haakan.ashina@regionh.dk
About this study
Official title: Hypersensitivity to Adrenomedullin in Post- Traumatic Headache: A Randomized Clinical Trial
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.
- Conditions
- Posttraumatic Headache
- Being tested
- Adrenomedullin, Placebo
- Keywords
- pain, adrenomedullin, posttraumatic headache
- Medical subject headings
- Post-Traumatic Headache, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdrenomedullinDrug
The participants will receive continuous intravenous infusion of 20 mL of 19.9 pmol/kg/min adrenomedullin over 20 minutes.
PlaceboDrug
The participants will receive a continuous intravenous infusion of 20 mL of placebo (isotonic saline) over 20 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Adrenomedullin | Experimental | Adrenomedullin will be administered by intravenous infusion. Receives: Drug: Adrenomedullin |
| Placebo | Placebo comparator | Placebo (isotonic saline) will be administered by intravenous infusion. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 12 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2025
- Study start1 Aug 2025 (estimated)
- Primary completion1 May 2028 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Posttraumatic HeadacheStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- This single-center trial applies a randomized, double-blind, placebo-controlled, two-way crossover design.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Danish Headache Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Haidar Al-Khazali, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07059546
- Sponsor's protocol ID
- H-21067681
- Status last verified
- Jun 2025
- First submitted
- 1 Jul 2025
- Last updated
- 30 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized data not published within this article will be made available on reasonable request from any qualified investigator.