Investigation of Vascular Inflammation in Migraine Using Molecular Nano-imaging and Black Blood Imaging MRI
Condition: Migraine Headache; Migraine Without Aura
MeSH terms: Migraine Disorders; Migraine without Aura; Inflammation; Headache
Study type: Interventional

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.
    

Intervention name(s): Feraheme; Cilostazol; USPIO-MRI; BBI-MRI
Intervention type(s): Drug; Drug; Other; Other
Intervention description(s): Feraheme is an USPIO agent, which will be applied as a contrast agent to visualize vascular inflammation in unilateral migraine without aura.; Cilostazol will be applied to provoke migraine attacks in migraineurs; USPIO-MRI scans will be performed in order to assess possible vascular inflammation associated with migraine attacks.; 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.
Other intervention name(s): Ferumoxytol; Pletal
Intervention MeSH terms: Cilostazol; Ferrosoferric Oxide
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other