Endothelin-1 as a Potential Trigger of Migraine Aura

NCT02906085 | Unknown DMC

• 1 other identifier: H-16022143
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Migraine With Aura

Keywords

[C10.228.140.546.399.750.250]

Outcome Measures

Primary Outcomes (1)

• Occurrence of migraine aura

  0-24 hours

Secondary Outcomes (3)

• Cerebral vasoconstriction: MR angiography

  0-30

• Change in cerebral blood flow: Phase contrast mapping

  0-30 minutes

• Change in cerebral blood flow: Arterial spin labeling

  0-30 minutes

Study Arms (2)

Endothelin-1

EXPERIMENTAL

Intravenous infusion of pharmaceutical grade human endothelin-1

Drug: Endothelin-1

Placebo

PLACEBO COMPARATOR

Intravenous infusion of placebo (isotonic saline)

Drug: Placebo

Interventions

Endothelin-1 DRUG

Endothelin-1

Placebo DRUG

Isotonic saline

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Glostrup University Hospital, Copenhagen: lead

Study Sites (1)

Danish Headache Center

Glostrup Municipality, 2600, Denmark

Location

MeSH Terms

Conditions

Migraine with Aura

Interventions

Endothelin-1

Condition Hierarchy (Ancestors)

Migraine Disorders; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Endothelins; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: September 3, 2016
• First Posted: September 19, 2016
• Study Start: October 1, 2016
• Primary Completion: May 1, 2018
• Study Completion: December 1, 2019
• Last Updated: December 12, 2019

Record last verified: 2019-12

Locations

DK (1)