Investigation of Vascular Inflammation in Migraine Using Molecular Nano-imaging and Black Blood Imaging MRI

NCT ID: NCT02549898

Last Updated: 2022-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2018-06-30

Brief 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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Vascular inflammation

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 ).

Group Type: EXPERIMENTAL

Feraheme

Intervention Type: DRUG

Feraheme is an USPIO agent, which will be applied as a contrast agent to visualize vascular inflammation in unilateral migraine without aura.

Cilostazol

Intervention Type: DRUG

Cilostazol will be applied to provoke migraine attacks in migraineurs

USPIO-MRI

Intervention Type: OTHER

USPIO-MRI scans will be performed in order to assess possible vascular inflammation associated with migraine attacks.

BBI-MRI

Intervention Type: OTHER

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.

Effect of sumatriptan

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).

Group Type: EXPERIMENTAL

Feraheme

Intervention Type: DRUG

Feraheme is an USPIO agent, which will be applied as a contrast agent to visualize vascular inflammation in unilateral migraine without aura.

Cilostazol

Intervention Type: DRUG

Cilostazol will be applied to provoke migraine attacks in migraineurs

USPIO-MRI

Intervention Type: OTHER

USPIO-MRI scans will be performed in order to assess possible vascular inflammation associated with migraine attacks.

BBI-MRI

Intervention Type: OTHER

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.

Pilot w/o cilostazol

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).

Group Type: EXPERIMENTAL

Feraheme

Intervention Type: DRUG

Feraheme is an USPIO agent, which will be applied as a contrast agent to visualize vascular inflammation in unilateral migraine without aura.

USPIO-MRI

Intervention Type: OTHER

USPIO-MRI scans will be performed in order to assess possible vascular inflammation associated with migraine attacks.

BBI-MRI

Intervention Type: OTHER

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.

Pilot w/ cilostazol

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).

Group Type: EXPERIMENTAL

Feraheme

Intervention Type: DRUG

Feraheme is an USPIO agent, which will be applied as a contrast agent to visualize vascular inflammation in unilateral migraine without aura.

Cilostazol

Intervention Type: DRUG

Cilostazol will be applied to provoke migraine attacks in migraineurs

USPIO-MRI

Intervention Type: OTHER

USPIO-MRI scans will be performed in order to assess possible vascular inflammation associated with migraine attacks.

BBI-MRI

Intervention Type: OTHER

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.

Interventions

Feraheme

Feraheme is an USPIO agent, which will be applied as a contrast agent to visualize vascular inflammation in unilateral migraine without aura.

Intervention Type: DRUG

Cilostazol

Cilostazol will be applied to provoke migraine attacks in migraineurs

Intervention Type: DRUG

USPIO-MRI

USPIO-MRI scans will be performed in order to assess possible vascular inflammation associated with migraine attacks.

Intervention Type: OTHER

BBI-MRI

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.

Intervention Type: OTHER

Other Intervention Names

Ferumoxytol; Pletal

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Danish Headache Center

OTHER

Sponsor Role: lead

Responsible Party

Sabrina Khan

Medical Doctor and PhD student

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sabrina Khan, MD

Role: PRINCIPAL_INVESTIGATOR

Danish Headache Center

Locations

Rigshospitalet Glostrup

Glostrup Municipality, , Denmark

Countries

Denmark

References

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.

Reference Type: DERIVED

PMID: 31104505 (View on PubMed)

Other Identifiers

H-15005669

Identifier Type: -

Identifier Source: org_study_id