Endothelin-1 as a Potential Trigger of Migraine Aura

December 10, 2019 updated by: Anders Hougaard, Glostrup University Hospital, Copenhagen

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Glostrup, Denmark, 2600
        • Danish Headache Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Occurrence of migraine aura
Time Frame: 0-24 hours
0-24 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
0-30
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.
0-30 minutes
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.
0-30 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Glostrup University Hospital, Copenhagen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2016

Primary Completion (Actual)

May 1, 2018

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

September 3, 2016

First Submitted That Met QC Criteria

September 14, 2016

First Posted (Estimate)

September 19, 2016

Study Record Updates

Last Update Posted (Actual)

December 12, 2019

Last Update Submitted That Met QC Criteria

December 10, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-16022143

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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