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Endothelin-1 as a Potential Trigger of Migraine Aura

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. Read our disclaimer for details. Identifier: NCT02906085
Recruitment Status : Active, not recruiting
First Posted : September 19, 2016
Last Update Posted : December 12, 2019
Information provided by (Responsible Party):
Anders Hougaard, Glostrup University Hospital, Copenhagen

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.

Condition or disease Intervention/treatment Phase
Migraine With Aura Drug: Endothelin-1 Drug: Placebo Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Investigations of the Endogenous Vasoconstrictor and Neuromodulator Peptide Endothelin-1 as a Potential Trigger of Migraine Aura
Actual Study Start Date : October 2016
Actual Primary Completion Date : May 2018
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Migraine

Arm Intervention/treatment
Experimental: Endothelin-1
Intravenous infusion of pharmaceutical grade human endothelin-1
Drug: Endothelin-1
Placebo Comparator: Placebo
Intravenous infusion of placebo (isotonic saline)
Drug: Placebo
Isotonic saline

Primary Outcome Measures :
  1. Occurrence of migraine aura [ Time Frame: 0-24 hours ]

Secondary Outcome Measures :
  1. Cerebral vasoconstriction: MR angiography [ Time Frame: 0-30 ]
    Time of flight arteriography using 3 tesla MRI (healthy subjects). Arterial diameters and circumferences (mm) will be measured from the resulting angiography images. This type of investigation will be carried out in healthy subjects only.

  2. 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). This type of investigation will be carried out in healthy subjects only.

  3. Change in cerebral blood flow: Arterial spin labeling [ 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 healthy subjects only.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Age between 18 and 40 years
  • Diagnosis of migraine with typical aura (patient group only)
  • Attacks of migraine with aura at least once per month on average (patient group only)
  • No history or family history of migraine (healthy subject group only)
  • Use of safe contraception (women of fertile age only)

Exclusion Criteria:

  • Tension-type headache more than one day per month on average
  • Any other primary headache disorder
  • Daily intake of medication
  • Daily smoking during the past 5 years
  • Pregnant or breastfeeding women
  • Hypertension on the experimental day (systolic BP>150 mmHg or diastolic BP> 100 mmHg)
  • History of any cardiovascular disease including cerebrovascular disease
  • History of diabetes or hypercholesterolemia
  • ECG changes suggestive of ischemia
  • Contraindications of MRI

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 identifier (NCT number): NCT02906085

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Danish Headache Center
Glostrup, Denmark, 2600
Sponsors and Collaborators
Glostrup University Hospital, Copenhagen
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Responsible Party: Anders Hougaard, MD, PhD, Glostrup University Hospital, Copenhagen Identifier: NCT02906085    
Other Study ID Numbers: H-16022143
First Posted: September 19, 2016    Key Record Dates
Last Update Posted: December 12, 2019
Last Verified: December 2019
Keywords provided by Anders Hougaard, Glostrup University Hospital, Copenhagen:
Additional relevant MeSH terms:
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Migraine Disorders
Migraine with Aura
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases