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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Migraine
• Intervention / Treatment: Diagnostic test: Nociceptive Blink Reflex

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.

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

Study Locations

• Germany
  • Greifswald, Germany, 17475
    • Recruiting
    • University Medicine Greifswald
    • Principal Investigator: Robert Fleischmann, MD
    • Contact: Robert Fleischmann, MD; Phone Number: -6725 +49383486; Email: robert.fleischmann@uni-greifswald.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients will be recruited through the outpatient headache department and through public adverstisement. Patients are consecutively recruited and inclusion/exclusion criteria are minimzied to avoid selection bias.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

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

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

Collaborators and Investigators

• Sponsor: University Medicine Greifswald

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2023
• Primary Completion (Anticipated): May 30, 2023
• Study Completion (Anticipated): July 30, 2023

Study Registration Dates

• First Submitted: March 3, 2023
• First Submitted That Met QC Criteria: March 3, 2023
• First Posted (Actual): March 14, 2023

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 3, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: BB 040/22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD can be shared upon reasonable request. Data protection regulation preclude public sharing of data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No