Stimulation-evoked Calcitonin Gene-Related Peptide (CGRP) as Biomarker of Migraine

Study Overview
=================
Brief Summary
-----------------
This study aims to improve the management migraine by providing a more profound understanding of the interactions of pain disinhibition on the brain stem level and calcitonin gene-related peptide as a main mediator in the generation of migraine headaches. For this purpose, this observational study investigates established neurophysiological and blood biomarkers parameters in association with the clinical phenotype.

Detailed Description
-----------------
The study's focus is the investigation of mechanisms that are directly related to the pain generation in migraine. In this context, the primary endpoint is an enhancement of trigeminal stimulation evoked calcitonin gene-related peptide (CGRP). The stimulation is normalized using an established protocol to elicit the nociceptive blink reflex, which is a brain stem reflex to study the trigemino-spinal system. We expect CGRP levels to rise more in patients affected by migraine as compared to controls, based on the observation that painful stimulation elicits migraine attacks. Furthermore, baseline CGRP levels and their association with markers of brainstem excitability are probed.

Official Title
-----------------
Calcitonin Gene-Related Peptide (CGRP) and Neurophysiological Biomarkers of Migraine

Conditions
-----------------
Migraine

Intervention / Treatment
-----------------
* Diagnostic Test: Nociceptive Blink Reflex


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Migraine according to ICHD-3 criteria (cases) No headaches or tension-type headache frequency <1x/year (controls) Exclusion Criteria: other chronic pain disorder

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Migraine<br>Patients suffering from migraine based on ICHD-3 criteria | Diagnostic Test: Nociceptive Blink Reflex<br>* Noxious trigeminal electrical stimulation at different interstimulus intervals using 1.5x the pain threshold in order to provoke a release of trigeminal CGRP<br>|
| Controls<br>Patients free of headaches or not suffering from headaches with a frequency that exceeds 1x/year | Diagnostic Test: Nociceptive Blink Reflex<br>* Noxious trigeminal electrical stimulation at different interstimulus intervals using 1.5x the pain threshold in order to provoke a release of trigeminal CGRP<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma levels of Calcitonin Gene-Related Peptide | Plasma levels of Calcitonin Gene-Related Peptide from samples taken from the cubital vein following nociceptive trigeminal stimulation | cross-sectional, once after stimulation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lacrimal fluid levels of Calcitonin Gene-Related Peptide | Lacrimal fluid levels of Calcitonin Gene-Related Peptide from samples taken from the outer angle of the eye following nociceptive trigeminal stimulation | cross-sectional, once after stimulation | 
| Habituation of the nociceptive blink reflex in correlation with plasma levels of Calcitonin Gene-Related Peptide | Explore the correlation of the amplitude of the R2 component of the nociceptive blink reflex with baseline plasma levels of Calcitonin Gene-Related Peptide | cross-sectional, once before stimulation | 
| Habituation of the nociceptive blink reflex in correlation with lacrimal fluid levels of Calcitonin Gene-Related Peptide | Explore the correlation of the amplitude of the R2 component of the nociceptive blink reflex with baseline lacrimal fluid levels of Calcitonin Gene-Related Peptide | cross-sectional, once before stimulation |