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

Migraine Without Aura Clinical Trial

Official title:

Investigation of Vascular Inflammation in Migraine Without Aura Using Molecular Nano-imaging and Black Blood Imaging MRI

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02549898
• Other study ID #: H-15005669
• Status: Completed
• Phase: N/A
• Start date: August 2015
• Est. completion date: June 2018

Study information

• Verified date: July 2022
• Source: Danish Headache Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: June 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Headache
• Inflammation
• Migraine Disorders
• Migraine Headache
• Migraine Without Aura

Intervention

Drug:
• Feraheme
Feraheme is an USPIO agent, which will be applied as a contrast agent to visualize vascular inflammation in unilateral migraine without aura.
• Cilostazol
Cilostazol will be applied to provoke migraine attacks in migraineurs

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

Locations

Country	Name	City	State
Denmark	Rigshospitalet Glostrup	Glostrup

Sponsors (1)

Lead Sponsor	Collaborator
Danish Headache Center

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	34 hours
Primary	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.	6 hours
Primary	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.	34 hours
Primary	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.	36 hours
Primary	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.	7 hours
Primary	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.	36 hours