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

Danish Headache Center

Status: Completed

Conditions: Migraine Headache; Migraine Without Aura

Treatments: Other: BBI-MRI; Drug: Cilostazol; Other: USPIO-MRI; Drug: Feraheme

Study type: Interventional

Funder types: Other

Identifiers

NCT02549898

H-15005669

Details and patient eligibility

About

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.

Full 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.

Enrollment: 34 patients

Sex: Female

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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34 participants in 4 patient groups

Vascular inflammation

Experimental group

Description:

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 ).

Treatment:

Drug: Feraheme

Other: USPIO-MRI

Other: BBI-MRI

Drug: Cilostazol

Effect of sumatriptan

Experimental group

Description:

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).

Treatment:

Drug: Feraheme

Other: USPIO-MRI

Other: BBI-MRI

Drug: Cilostazol

Pilot w/o cilostazol

Experimental group

Description:

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).

Treatment:

Drug: Feraheme

Other: USPIO-MRI

Other: BBI-MRI

Pilot w/ cilostazol

Experimental group

Description:

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).

Treatment:

Drug: Feraheme

Other: USPIO-MRI

Other: BBI-MRI

Drug: Cilostazol