Clinical Trial: Endothelin-1 as a Potential Trigger of Migraine Aura

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Investigations of the Endogenous Vasoconstrictor and Neuromodulator Peptide Endothelin-1 as a Potential Trigger of Migraine Aura

Brief Summary:

One third of migraine patients experience aura, i.e. dramatic, transient neurological symptoms, most often in the form of visual disturbances, that usually appear before the onset of migraine headache. The likely underlying mechanism of aura is known as cortical spreading depression, a wave of changes in electrical activity that slowly spreads in the outermost layer of the brain. It is currently not known what causes the aura to initiate in patients or what the relationship is between aura and migraine headache, e.g. if treatment targeted at aura mechanisms will prevent subsequent headache. Due to the short-lasting and unpredictable nature of aura, the only possible approach for systematic investigations is to experimentally trigger aura, but currently no method for aura-triggering is available.

The overall goal of the proposed project is to reveal the earliest mechanisms of the migraine attack by investigating the initiating factors of aura in the migraine brain.

Current animal evidence indicates that infusion of endothelin-1 (ET-1), a naturally occurring signaling molecule released from blood vessels, is safe and very likely to trigger migraine aura in patients.

In this project the investigators aim to study the effects of ET-1 on the human brain, to investigate aura-inducing effects of ET-1 in patients and to develop a safe and reliable method for the experimental induction of migraine aura using ET-1.


Detailed Summary:
Sponsor: Glostrup University Hospital, Copenhagen

Current Primary Outcome: Occurrence of migraine aura [ Time Frame: 0-24 hours ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Cerebral vasoconstriction: transcranial doppler [ Time Frame: 0-30 min ]
    Blood flow velocity (cm/s), an indirect measure of arterial diameter, of the middle cerebral artery measured before and after intervention using transcranial doppler ultrasound (in all subjects).
  • Cerebral vasoconstriction: MR angiography [ Time Frame: 0-30 ]
    Time of flight arteriography using 3 tesla MRI (6 healthy subjects). Arterial diameters and circumferences (mm) will be measured from the resulting angiography images. This type of investigation will be carried out in 6 healthy subjects only.
  • Change in cerebral blood flow: Phase contrast mapping [ Time Frame: 0-30 minutes ]
    Cerebral blood flow (perfusion, ml/100 g/min) measured before and after intervention using MRI phase contrast mapping (measure of global brain perfusion)
  • Change in cerebral blood flow: Phase contrast mapping [ Time Frame: 0-30 minutes ]
    Regional cerebral blood flow (perfusion, ml/100g/min) measured before and after intervention using MRI pseudo-continous arterial spin labelling at 3 tesla. This type of investigation will be carried out in 6 healthy subjects only.
  • Peripheral artery constriction [ Time Frame: 0-30 min ]
    Diameters (mm) of the radial and superficial temporal artery before and after intervention measured using DermaScan (C) transdermal ultrasound in all subjects.


Original Secondary Outcome: Same as current

Information By: Glostrup University Hospital, Copenhagen

Dates:
Date Received: September 3, 2016
Date Started: October 2016
Date Completion:
Last Updated: September 14, 2016
Last Verified: September 2016