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Endothelin-1 as a Potential Trigger of Migraine Aura

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ClinicalTrials.gov Identifier: NCT02906085
Recruitment Status : Not yet recruiting
First Posted : September 19, 2016
Last Update Posted : September 19, 2016
Sponsor:
Information provided by (Responsible Party):

Study Description
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
Migraine With Aura Drug: Endothelin-1 Drug: Placebo

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 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
Study Start Date : October 2016
Estimated Primary Completion Date : October 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Migraine
U.S. FDA Resources

Arms and Interventions

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


Outcome Measures

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

Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. 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)

  4. 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.

  5. 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.


Eligibility Criteria

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

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
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): NCT02906085


Locations
Denmark
Danish Headache Center Recruiting
Glostrup, Denmark, 2600
Contact: Anders Hougaard, MD    +4538632713    andhou05@glo.regionh.dk   
Principal Investigator: Anders Hougaard, MD         
Sponsors and Collaborators
Glostrup University Hospital, Copenhagen
More Information

Responsible Party: Anders Hougaard, MD, PhD, Glostrup University Hospital, Copenhagen
ClinicalTrials.gov Identifier: NCT02906085     History of Changes
Other Study ID Numbers: H-16022143
First Posted: September 19, 2016    Key Record Dates
Last Update Posted: September 19, 2016
Last Verified: September 2016

Keywords provided by Anders Hougaard, Glostrup University Hospital, Copenhagen:
[C10.228.140.546.399.750.250]

Additional relevant MeSH terms:
Migraine Disorders
Migraine with Aura
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases