- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02549898
Investigation of Vascular Inflammation in Migraine Using Molecular Nano-imaging and Black Blood Imaging MRI
Investigation of Vascular Inflammation in Migraine Without Aura Using Molecular Nano-imaging and Black Blood Imaging MRI
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Glostrup, Denmark, 2600
- Rigshospitalet Glostrup
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: OTHER
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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 ).
|
Feraheme is an USPIO agent, which will be applied as a contrast agent to visualize vascular inflammation in unilateral migraine without aura.
Other Names:
Cilostazol will be applied to provoke migraine attacks in migraineurs
Other Names:
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.
|
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).
|
Feraheme is an USPIO agent, which will be applied as a contrast agent to visualize vascular inflammation in unilateral migraine without aura.
Other Names:
Cilostazol will be applied to provoke migraine attacks in migraineurs
Other Names:
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.
|
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).
|
Feraheme is an USPIO agent, which will be applied as a contrast agent to visualize vascular inflammation in unilateral migraine without aura.
Other Names:
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.
|
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).
|
Feraheme is an USPIO agent, which will be applied as a contrast agent to visualize vascular inflammation in unilateral migraine without aura.
Other Names:
Cilostazol will be applied to provoke migraine attacks in migraineurs
Other Names:
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in USPIO uptake during attacks of unilateral migraine without aura compared to baseline
Time Frame: 34 hours
|
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.
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34 hours
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Change in arterial wall thickness during attacks of unilateral migraine without aura compared to baseline
Time Frame: 6 hours
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On the first study day, migraine is induced with cilostazol, and 4 hours after cilostazol ingestion, BBI-MRI is performed.
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6 hours
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Change in arterial circumference as a proxy measure for vascular inflammation during attacks of unilateral migraine without aura compared to baseline
Time Frame: 34 hours
|
On the first study day, migraine is induced with cilostazol, and at 4 hours and 28 hours after cilostazol ingestion, MR angiography is performed.
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34 hours
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Change in USPIO uptake during attacks of unilateral migraine without aura before and after sumatriptan
Time Frame: 36 hours
|
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
|
Change in arterial wall thickness during attacks of unilateral migraine without aura before and after sumatriptan
Time Frame: 7 hours
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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
|
Change in arterial circumference as a proxy measure for vascular inflammation during unilateral attacks of migraine without aura before and after sumatriptan
Time Frame: 36 hours
|
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.
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36 hours
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Sabrina Khan, MD, Danish Headache Center
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Pain
- Neurologic Manifestations
- Headache Disorders, Primary
- Headache Disorders
- Inflammation
- Migraine Disorders
- Headache
- Migraine without Aura
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Fibrinolytic Agents
- Fibrin Modulating Agents
- Platelet Aggregation Inhibitors
- Neuroprotective Agents
- Protective Agents
- Bronchodilator Agents
- Anti-Asthmatic Agents
- Respiratory System Agents
- Hematinics
- Phosphodiesterase Inhibitors
- Pharmaceutical Solutions
- Parenteral Nutrition Solutions
- Phosphodiesterase 3 Inhibitors
- Ferrosoferric Oxide
- Cilostazol
Other Study ID Numbers
- H-15005669
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