Clinical trial NCT02906085: Endothelin-1 as a Potential Trigger of Migraine Aura
Official title: Investigations of the Endogenous Vasoconstrictor and Neuromodulator Peptide Endothelin-1 as a Potential Trigger of Migraine Aura
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Migraine With Aura
Keywords: [C10.228.140.546.399.750.250]
Lead sponsor: Glostrup University Hospital, Copenhagen
Sponsor class: OTHER
First posted: 2016-09-19
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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

Primary outcomes:
measure: Occurrence of migraine aura
timeFrame: 0-24 hours
Secondary outcomes:
measure: Cerebral vasoconstriction: MR angiography
timeFrame: 0-30
measure: Change in cerebral blood flow: Phase contrast mapping
timeFrame: 0-30 minutes
measure: Change in cerebral blood flow: Arterial spin labeling
timeFrame: 0-30 minutes
Other outcomes:
Locations:
city: Glostrup
country: Denmark
facility: Danish Headache Center
Study officials:
References: