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
- Are there results?
- Not yet: the study is under way
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
Show all 15Show fewer
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypersensitivity to Adrenomedullin in Post- Traumatic Headache: A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT07059546
- Acronym / sponsor ID
- H-21067681
- Conditions
- Posttraumatic Headache
- Keywords
- pain, adrenomedullin, posttraumatic headache
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- Danish Headache CenterUniversity, hospital or other
- Study start
- 1 Aug 2025 (estimated)
- Primary completion
- 1 May 2028 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 10 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This single-center trial applies a randomized, double-blind, placebo-controlled, two-way crossover design.
| Arm | Type | Receives |
|---|---|---|
| Adrenomedullin | Experimental | Drug: AdrenomedullinAdrenomedullin will be administered by intravenous infusion. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo (isotonic saline) will be administered by intravenous infusion. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (15 listed)
- > 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AdrenomedullinThe participants will receive continuous intravenous infusion of 20 mL of 19.9 pmol/kg/min adrenomedullin over 20 minutes. | Drug | Adrenomedullin |
| PlaceboThe participants will receive a continuous intravenous infusion of 20 mL of placebo (isotonic saline) over 20 minutes. | Drug | Placebo |
Primary outcome
Incidence of headache with migraine-like features
Time frame: 12 hours
The difference in incidence of headache with migraine-like features between adrenomedullin and placebo during the 12-hour observational period after infusion start.
1 secondary outcome
Headache Intensity Scores
Time frame: 12 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2025.
- Individual participant dataSharing planned: Yes. Anonymized data not published within this article will be made available on reasonable request from any qualified investigator.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Adrenomedullin in people with Posttraumatic Headache, run by Danish Headache Center at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Haidar Al-Khazali, MD (+4541598494, haidardk@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of headache with migraine-like features (time frame: 12 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2025.