Clinical trial NCT02549898: Investigation of Vascular Inflammation in Migraine Using Molecular Nano-imaging and Black Blood Imaging MRI
Official title: Investigation of Vascular Inflammation in Migraine Without Aura Using Molecular Nano-imaging and Black Blood Imaging MRI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Migraine Headache
Migraine Without Aura
Lead sponsor: Danish Headache Center
Sponsor class: OTHER
First posted: 2015-09-15
Enrollment: 34
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Change in USPIO uptake during attacks of unilateral migraine without aura compared to baseline
timeFrame: 34 hours
measure: Change in arterial wall thickness during attacks of unilateral migraine without aura compared to baseline
timeFrame: 6 hours
measure: Change in arterial circumference as a proxy measure for vascular inflammation during attacks of unilateral migraine without aura compared to baseline
timeFrame: 34 hours
measure: Change in USPIO uptake during attacks of unilateral migraine without aura before and after sumatriptan
timeFrame: 36 hours
measure: Change in arterial wall thickness during attacks of unilateral migraine without aura before and after sumatriptan
timeFrame: 7 hours
measure: Change in arterial circumference as a proxy measure for vascular inflammation during unilateral attacks of migraine without aura before and after sumatriptan
timeFrame: 36 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Glostrup
country: Denmark
facility: Rigshospitalet Glostrup
Study officials:
affiliation: Danish Headache Center
name: Sabrina Khan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.