Migraine HeadacheNCT02549898
Investigation of Vascular Inflammation in Migraine Using Molecular Nano-imaging and Black Blood Imaging MRI
A study testing Feraheme, Cilostazol and USPIO-MRI in people with Migraine Headache and Migraine Without Aura, run by Danish Headache Center at 1 site in Denmark.
Trial summary
The investigators aim to investigate inflammation of cranial and meningeal arteries during pharmacologically induced migraine attacks, using ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles and black blood imaging (BBI) MRI. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women only
- Conditions the study is for
- Migraine Headache, Migraine Without Aura
- What is being tested?
- Feraheme, Cilostazol and USPIO-MRI
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteDenmark
- Study dates
- Aug 2015to Jun 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 50 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Written informed consent
- Subject has migraine without aura according to criteria of the International Headache Society (IHS)
- Subject has unilateral migraine 70% of the time
- Migraine can be pharmacologically provoked in the subject using cilostazol.
- Subject is on birth control
- Subject has no other medical history
Who cannot join
- Subject suffers from bilateral migraine
- Subject suffers from migraine with aura
- Subject suffers from other primary headaches as specified by IHS criteria
- Pregnant or breast feeding subjects
- Subjects with contraindications for undergoing MRI scans
- Any known drug allergy
- Any signs or disorders of iron overload, including but not limited to hemosiderosis and porphyria cutanea tarda
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Investigation of Vascular Inflammation in Migraine Without Aura Using Molecular Nano-imaging and Black Blood Imaging MRI
The investigators aim to investigate inflammation of cranial and meningeal arteries during pharmacologically induced migraine attacks, using ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles and black blood imaging (BBI) MRI.
Read the detailed description
Migraine is the most common neurological disorder, ranked as the 7th most debilitating disease worldwide by the WHO. While much research has been and continues to be conducted to illuminate the enigma of migraine pathophysiology, key aspects still remain a conundrum. Specifically, the process of headache generation is perhaps the most complex and debated part of migraine pathophysiology. The vascular hypothesis of migraine has traditionally focused on the simple dilatation of cranial arteries. However, a possible contribution of perivascular pain sensitive structures should also be considered, as aseptic inflammation of the arterial walls and perivascular space may activate afferent nerve endings. Interestingly, giant cell arteritis caused by aseptic arterial wall inflammation may present clinically as localized headache with migraine-like features (i.e. throbbing pain, localized in the temporal region, and allodynia).
The primary trigeminal nociceptor is the first integral part of the headache-generating pathway. Animal models of migraine have suggested that activation and sensitization of perivascular trigeminal nociceptors caused by inflammatory substances may explain head pain in migraine. However, there is no human evidence to date to suggest perivascular and arterial wall inflammation as a source of pain in migraine.
The investigators hypothesize that unilateral migraine without aura is associated with ipsilateral inflammation of the cranial arteries and meninges. The investigators also suggest that sumatriptan inhibits this perivascular inflammation. To test the hypotheses the investigators will perform MRI scans on subjects with provoked migraine attacks, using two different methods to visualize perivascular inflammation: USPIO-MRI, using iron-oxide nanoparticles as contrast agent, and BBI MRI.
To pharmacologically induce migraine headache in the study subjects, the investigators will use the drug cilostazol, which is a phosphodiesterase 3 inhibitor.
- Conditions
- Migraine Headache, Migraine Without Aura
- Being tested
- Feraheme, Cilostazol, USPIO-MRI, BBI-MRI
- Medical subject headings
- Migraine Disorders, Migraine without Aura
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FerahemeDrug
Also called Ferumoxytol
Feraheme is an USPIO agent, which will be applied as a contrast agent to visualize vascular inflammation in unilateral migraine without aura.
CilostazolDrug
Also called Pletal
Cilostazol will be applied to provoke migraine attacks in migraineurs
USPIO-MRIOther
USPIO-MRI scans will be performed in order to assess possible vascular inflammation associated with migraine attacks.
BBI-MRIOther
Black blood MRI scans will be performed in order to asses changes in vessel wall thickness due to possible vascular inflammation associated with migraine attacks.
| Study group | Role | What they receive |
|---|---|---|
| Vascular inflammation | Experimental | Subjects with habitual unilateral migraine without aura, undergo a baseline MRI scan, undergo pharmacological induction of a migraine attack, and subsequently are MRI scanned prior to (BBI-MRI) and after Feraheme infusion (USPIO-MRI ). Receives: Drug: Feraheme; Drug: Cilostazol; Other: USPIO-MRI; Other: BBI-MRI |
| Effect of sumatriptan | Experimental | Subjects with habitual unilateral migraine without aura, undergo a baseline MRI scan and then undergo pharmacological induction of a migraine attack. Sumatriptan is given and subjects subsequently undergo MRI scans prior to (BBI-MRI) and after Feraheme infusion (USPIO-MRI). Receives: Drug: Feraheme; Drug: Cilostazol; Other: USPIO-MRI; Other: BBI-MRI |
| Pilot w/o cilostazol | Experimental | Subjects without habitual unilateral migraine without aura undergo a baseline MRI scan. Subjects are then MRI scanned prior to (BBI-MRI) and after Feraheme infusion (USPIO-MRI). Receives: Drug: Feraheme; Other: USPIO-MRI; Other: BBI-MRI |
| Pilot w/ cilostazol | Experimental | Subjects without habitual unilateral migraine without aura undergo a baseline MRI scan and then receive cilostazol. Subjects are then MRI scanned prior (BBI-MRI) to and after Feraheme infusion (USPIO-MRI). Receives: Drug: Feraheme; Drug: Cilostazol; Other: USPIO-MRI; Other: BBI-MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in USPIO uptake during attacks of unilateral migraine without aura compared to baseline
On the first study day, migraine is induced with cilostazol, and intravenous infusion of Feraheme (USPIO) is delivered. On the second study day, USPIO-MRI is performed.
Measured: 34 hours
Change in arterial wall thickness during attacks of unilateral migraine without aura compared to baseline
On the first study day, migraine is induced with cilostazol, and 4 hours after cilostazol ingestion, BBI-MRI is performed.
Measured: 6 hours
Change in arterial circumference as a proxy measure for vascular inflammation during attacks of unilateral migraine without aura compared to baseline
On the first study day, migraine is induced with cilostazol, and at 4 hours and 28 hours after cilostazol ingestion, MR angiography is performed.
Measured: 34 hours
Change in USPIO uptake during attacks of unilateral migraine without aura before and after sumatriptan
On the first study day, migraine is induced with cilostazol and subsequently treated with sumatriptan. Intravenous infusion of Feraheme (USPIO) is delivered, and on the second study day, USPIO-MRI is performed.
Measured: 36 hours
Change in arterial wall thickness during attacks of unilateral migraine without aura before and after sumatriptan
On the first study day, migraine is induced with cilostazol, and 4 hours after cilostazol ingestion, BBI-MRI is performed. Subjects are treated with sumatriptan, and BBI-MRI is repeated.
Measured: 7 hours
Change in arterial circumference as a proxy measure for vascular inflammation during unilateral attacks of migraine without aura before and after sumatriptan
On the first study day, migraine is induced with cilostazol, and 4 hours after cilostazol, MR angiography is performed. Subjects are treated with sumatriptan, and MR angiography is repeated. 28 hours after cilostazol ingestion, MR angiography is performed again.
Measured: 36 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2015 (estimated)
- Study startAug 2015
- Primary completionJun 2018
- Study completionJun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Migraine 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Danish Headache Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sabrina Khan, Danish Headache Center
- Investigators
- Sabrina Khan, MD, Principal investigator, Danish Headache Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02549898
- Sponsor's protocol ID
- H-15005669
- Status last verified
- Jul 2022
- First submitted
- 31 Jul 2015
- Last updated
- 27 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Khan S, Amin FM, Fliedner FP, Christensen CE, Tolnai D, Younis S, Olinger ACR, Birgens H, Daldrup-Link H, Kjaer A, Larsson HBW, Lindberg U, Ashina M. Investigating macrophage-mediated inflammation in migraine using ultrasmall superparamagnetic iron oxide-enhanced 3T magnetic resonance imaging. Cephalalgia. 2019 Oct;39(11):1407-1420. doi: 10.1177/0333102419848122. Epub 2019 May 19.
PubMed 31104505
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of Vascular Inflammation in Migraine Without Aura Using Molecular Nano-imaging and Black Blood Imaging MRI
- ClinicalTrials.gov ID
- NCT02549898
- Acronym / sponsor ID
- H-15005669
- Conditions
- Migraine Headache, Migraine Without Aura
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Danish Headache CenterUniversity, hospital or other
- Study start
- Aug 2015
- Primary completion
- Jun 2018 (actual)
- Study completion
- Jun 2018 (actual)
- First posted
- 15 Sep 2015 (estimated)
- 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.
The investigators aim to investigate inflammation of cranial and meningeal arteries during pharmacologically induced migraine attacks, using ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles and black blood imaging (BBI) MRI.
Detailed description
Migraine is the most common neurological disorder, ranked as the 7th most debilitating disease worldwide by the WHO. While much research has been and continues to be conducted to illuminate the enigma of migraine pathophysiology, key aspects still remain a conundrum. Specifically, the process of headache generation is perhaps the most complex and debated part of migraine pathophysiology. The vascular hypothesis of migraine has traditionally focused on the simple dilatation of cranial arteries. However, a possible contribution of perivascular pain sensitive structures should also be considered, as aseptic inflammation of the arterial walls and perivascular space may activate afferent nerve endings. Interestingly, giant cell arteritis caused by aseptic arterial wall inflammation may present clinically as localized headache with migraine-like features (i.e. throbbing pain, localized in the temporal region, and allodynia).
The primary trigeminal nociceptor is the first integral part of the headache-generating pathway. Animal models of migraine have suggested that activation and sensitization of perivascular trigeminal nociceptors caused by inflammatory substances may explain head pain in migraine. However, there is no human evidence to date to suggest perivascular and arterial wall inflammation as a source of pain in migraine.
The investigators hypothesize that unilateral migraine without aura is associated with ipsilateral inflammation of the cranial arteries and meninges. The investigators also suggest that sumatriptan inhibits this perivascular inflammation. To test the hypotheses the investigators will perform MRI scans on subjects with provoked migraine attacks, using two different methods to visualize perivascular inflammation: USPIO-MRI, using iron-oxide nanoparticles as contrast agent, and BBI MRI.
To pharmacologically induce migraine headache in the study subjects, the investigators will use the drug cilostazol, which is a phosphodiesterase 3 inhibitor.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Vascular inflammation | Experimental | Drug: Feraheme, Drug: Cilostazol, Other: USPIO-MRI, Other: BBI-MRISubjects with habitual unilateral migraine without aura, undergo a baseline MRI scan, undergo pharmacological induction of a migraine attack, and subsequently are MRI scanned prior to (BBI-MRI) and after Feraheme infusion (USPIO-MRI ). |
| Effect of sumatriptan | Experimental | Drug: Feraheme, Drug: Cilostazol, Other: USPIO-MRI, Other: BBI-MRISubjects with habitual unilateral migraine without aura, undergo a baseline MRI scan and then undergo pharmacological induction of a migraine attack. Sumatriptan is given and subjects subsequently undergo MRI scans prior to (BBI-MRI) and after Feraheme infusion (USPIO-MRI). |
| Pilot w/o cilostazol | Experimental | Drug: Feraheme, Other: USPIO-MRI, Other: BBI-MRISubjects without habitual unilateral migraine without aura undergo a baseline MRI scan. Subjects are then MRI scanned prior to (BBI-MRI) and after Feraheme infusion (USPIO-MRI). |
| Pilot w/ cilostazol | Experimental | Drug: Feraheme, Drug: Cilostazol, Other: USPIO-MRI, Other: BBI-MRISubjects without habitual unilateral migraine without aura undergo a baseline MRI scan and then receive cilostazol. Subjects are then MRI scanned prior (BBI-MRI) to and after Feraheme infusion (USPIO-MRI). |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Written informed consent
- Subject has migraine without aura according to criteria of the International Headache Society (IHS)
- Subject has unilateral migraine 70% of the time
- Migraine can be pharmacologically provoked in the subject using cilostazol.
- Subject is on birth control
Key exclusion criteria (7 listed)
- Subject suffers from bilateral migraine
- Subject suffers from migraine with aura
- Subject suffers from other primary headaches as specified by IHS criteria
- Pregnant or breast feeding subjects
- Subjects with contraindications for undergoing MRI scans
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 |
|---|---|---|
| FerahemeAlso: FerumoxytolFeraheme is an USPIO agent, which will be applied as a contrast agent to visualize vascular inflammation in unilateral migraine without aura. | Drug | Effect of sumatriptan, Pilot w/ cilostazol, Pilot w/o cilostazol, Vascular inflammation |
| CilostazolAlso: PletalCilostazol will be applied to provoke migraine attacks in migraineurs | Drug | Effect of sumatriptan, Pilot w/ cilostazol, Vascular inflammation |
| USPIO-MRIUSPIO-MRI scans will be performed in order to assess possible vascular inflammation associated with migraine attacks. | Other | Effect of sumatriptan, Pilot w/ cilostazol, Pilot w/o cilostazol, Vascular inflammation |
| BBI-MRIBlack blood MRI scans will be performed in order to asses changes in vessel wall thickness due to possible vascular inflammation associated with migraine attacks. | Other | Effect of sumatriptan, Pilot w/ cilostazol, Pilot w/o cilostazol, Vascular inflammation |
Primary outcome
Change in USPIO uptake during attacks of unilateral migraine without aura compared to baseline
Time frame: 34 hours
On the first study day, migraine is induced with cilostazol, and intravenous infusion of Feraheme (USPIO) is delivered. On the second study day, USPIO-MRI is performed.
Change in arterial wall thickness during attacks of unilateral migraine without aura compared to baseline
Time frame: 6 hours
On the first study day, migraine is induced with cilostazol, and 4 hours after cilostazol ingestion, BBI-MRI is performed.
Change in arterial circumference as a proxy measure for vascular inflammation during attacks of unilateral migraine without aura compared to baseline
Time frame: 34 hours
On the first study day, migraine is induced with cilostazol, and at 4 hours and 28 hours after cilostazol ingestion, MR angiography is performed.
Change in USPIO uptake during attacks of unilateral migraine without aura before and after sumatriptan
Time frame: 36 hours
On the first study day, migraine is induced with cilostazol and subsequently treated with sumatriptan. Intravenous infusion of Feraheme (USPIO) is delivered, and on the second study day, USPIO-MRI is performed.
Change in arterial wall thickness during attacks of unilateral migraine without aura before and after sumatriptan
Time frame: 7 hours
On the first study day, migraine is induced with cilostazol, and 4 hours after cilostazol ingestion, BBI-MRI is performed. Subjects are treated with sumatriptan, and BBI-MRI is repeated.
Change in arterial circumference as a proxy measure for vascular inflammation during unilateral attacks of migraine without aura before and after sumatriptan
Time frame: 36 hours
On the first study day, migraine is induced with cilostazol, and 4 hours after cilostazol, MR angiography is performed. Subjects are treated with sumatriptan, and MR angiography is repeated. 28 hours after cilostazol ingestion, MR angiography is performed again.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2022.
- Derived from this study: PubMed 31104505Khan S, Amin FM, Fliedner FP, Christensen CE, Tolnai D, Younis S, Olinger ACR, Birgens H, Daldrup-Link H, Kjaer A, Larsson HBW, Lindberg U, Ashina M. Investigating macrophage-mediated inflammation in migraine using ultrasmall superparamagnetic iron oxide-enhanced 3T magnetic resonance imaging. Cephalalgia. 2019 Oct;39(11):1407-1420. doi: 10.1177/0333102419848122. Epub 2019 May 19.
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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. This study is not recruiting at the moment.
Sabrina Khan, MD principal investigator
Danish Headache Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Feraheme, Cilostazol and USPIO-MRI in people with Migraine Headache and Migraine Without Aura, 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 6 inclusion and 7 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: finished, as of the sponsor's last update on 27 Jul 2022. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in USPIO uptake during attacks of unilateral migraine without aura compared to baseline (time frame: 34 hours). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02549898, which also lists 1 linked publication.
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 27 Jul 2022.