NCT02549898

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
34

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Aug 2015

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 31, 2015

Completed
1 day until next milestone

Study Start

First participant enrolled

August 1, 2015

Completed
2 months until next milestone

First Posted

Study publicly available on registry

September 15, 2015

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2018

Completed
Last Updated

July 27, 2022

Status Verified

July 1, 2022

Enrollment Period

2.8 years

First QC Date

July 31, 2015

Last Update Submit

July 26, 2022

Conditions

Outcome Measures

Primary Outcomes (6)

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

Study Arms (4)

Vascular inflammation

EXPERIMENTAL

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: FerahemeDrug: CilostazolOther: USPIO-MRIOther: BBI-MRI

Effect of sumatriptan

EXPERIMENTAL

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: FerahemeDrug: CilostazolOther: USPIO-MRIOther: BBI-MRI

Pilot w/o cilostazol

EXPERIMENTAL

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: FerahemeOther: USPIO-MRIOther: BBI-MRI

Pilot w/ cilostazol

EXPERIMENTAL

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: FerahemeDrug: CilostazolOther: USPIO-MRIOther: BBI-MRI

Interventions

Feraheme is an USPIO agent, which will be applied as a contrast agent to visualize vascular inflammation in unilateral migraine without aura.

Also known as: Ferumoxytol
Effect of sumatriptanPilot w/ cilostazolPilot w/o cilostazolVascular inflammation

Cilostazol will be applied to provoke migraine attacks in migraineurs

Also known as: Pletal
Effect of sumatriptanPilot w/ cilostazolVascular inflammation

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

Effect of sumatriptanPilot w/ cilostazolPilot w/o cilostazolVascular inflammation
BBI-MRIOTHER

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.

Effect of sumatriptanPilot w/ cilostazolPilot w/o cilostazolVascular inflammation

Eligibility Criteria

Age18 Years - 50 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Rigshospitalet Glostrup

Glostrup Municipality, 2600, Denmark

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Migraine DisordersMigraine without Aura

Interventions

Ferrosoferric OxideCilostazol

Condition Hierarchy (Ancestors)

Headache Disorders, PrimaryHeadache DisordersBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

Ferric CompoundsIron CompoundsInorganic ChemicalsFerrous CompoundsMineralsTetrazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsQuinolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Study Officials

  • Sabrina Khan, MD

    Danish Headache Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
OTHER
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Medical Doctor and PhD student

Study Record Dates

First Submitted

July 31, 2015

First Posted

September 15, 2015

Study Start

August 1, 2015

Primary Completion

June 1, 2018

Study Completion

June 1, 2018

Last Updated

July 27, 2022

Record last verified: 2022-07

Locations