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

This study is currently recruiting participants.
Verified October 2017 by Sabrina Khan, Danish Headache Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT02549898
First Posted: September 15, 2015
Last Update Posted: October 27, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Sabrina Khan, Danish Headache Center
  Purpose
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.

Condition Intervention
Migraine Headache Migraine Without Aura Drug: Feraheme Drug: Cilostazol Other: USPIO-MRI Other: BBI-MRI

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Investigation of Vascular Inflammation in Migraine Without Aura Using Molecular Nano-imaging and Black Blood Imaging MRI

Resource links provided by NLM:


Further study details as provided by Sabrina Khan, Danish Headache Center:

Primary Outcome Measures:
  • USPIO uptake during attacks of unilateral migraine without aura [ Time Frame: 2 days ]
    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.

  • Arterial wall thickness during attacks of unilateral migraine without aura [ Time Frame: 1 day ]
    On the first study day, migraine is induced with cilostazol, and 4 hours after cilostazol ingestion, BBI-MRI is performed.

  • Arterial circumference as a proxy measure for vascular inflammation [ Time Frame: 2 days ]
    On the first study day, migraine is induced with cilostazol, and at 4 hours and 1 day after cilostazol ingestion, MR angiography is performed.

  • USPIO uptake during attacks of unilateral migraine without aura before and after sumatriptan [ Time Frame: 2 days ]
    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.

  • Arterial wall thickness during attacks of unilateral migraine without aura before and after sumatriptan [ Time Frame: 1 day ]
    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.

  • Arterial circumference as a proxy measure for vascular inflammation before and after sumatriptan [ Time Frame: 2 days ]
    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. 1 day after cilostazol ingestion, MR angiography is performed again..


Estimated Enrollment: 42
Study Start Date: August 2015
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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 ).
Drug: Feraheme
Feraheme is an USPIO agent, which will be applied as a contrast agent to visualize vascular inflammation in unilateral migraine without aura.
Other Name: Ferumoxytol
Drug: Cilostazol
Cilostazol will be applied to provoke migraine attacks in migraineurs
Other Name: Pletal
Other: USPIO-MRI
USPIO-MRI scans will be performed in order to assess possible vascular inflammation associated with migraine attacks.
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.
Experimental: 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).
Drug: Feraheme
Feraheme is an USPIO agent, which will be applied as a contrast agent to visualize vascular inflammation in unilateral migraine without aura.
Other Name: Ferumoxytol
Drug: Cilostazol
Cilostazol will be applied to provoke migraine attacks in migraineurs
Other Name: Pletal
Other: USPIO-MRI
USPIO-MRI scans will be performed in order to assess possible vascular inflammation associated with migraine attacks.
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.
Experimental: 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).
Drug: Feraheme
Feraheme is an USPIO agent, which will be applied as a contrast agent to visualize vascular inflammation in unilateral migraine without aura.
Other Name: Ferumoxytol
Other: USPIO-MRI
USPIO-MRI scans will be performed in order to assess possible vascular inflammation associated with migraine attacks.
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.
Experimental: 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).
Drug: Feraheme
Feraheme is an USPIO agent, which will be applied as a contrast agent to visualize vascular inflammation in unilateral migraine without aura.
Other Name: Ferumoxytol
Drug: Cilostazol
Cilostazol will be applied to provoke migraine attacks in migraineurs
Other Name: Pletal
Other: USPIO-MRI
USPIO-MRI scans will be performed in order to assess possible vascular inflammation associated with migraine attacks.
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.

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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02549898


Contacts
Contact: Sabrina Khan, MD 004538633066 sabrina.khan@regionh.dk

Locations
Denmark
Rigshospitalet Glostrup Recruiting
Glostrup, Denmark, 2600
Contact: Sabrina Khan, MD    4538633066    sabrina.khan@regionh.dk   
Sponsors and Collaborators
Danish Headache Center
Investigators
Principal Investigator: Sabrina Khan, MD Danish Headache Center
  More Information

Responsible Party: Sabrina Khan, Medical Doctor and PhD student, Danish Headache Center
ClinicalTrials.gov Identifier: NCT02549898     History of Changes
Other Study ID Numbers: H-15005669
First Submitted: July 31, 2015
First Posted: September 15, 2015
Last Update Posted: October 27, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Inflammation
Migraine Disorders
Headache
Migraine without Aura
Pathologic Processes
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Pain
Neurologic Manifestations
Signs and Symptoms
Cilostazol
Sumatriptan
Ferrosoferric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Vasodilator Agents
Neuroprotective Agents
Protective Agents
Phosphodiesterase 3 Inhibitors