BIOmarkers of MIGraine: a Proof of Concept Study Based on the Stratification of Responders to CGRP Monoclonal Antibodies

NCT04503083 | Completed

• 1 other identifier: BIOMIGA2020
• Study Type: observational
• Target: 243
• Locations: 3 countries
• Sites: 3

Brief Summary

Migraine is the 2nd most disabling neurological disease. It affects 14.7% of the population (children and adults) of whom 80% are female. In the European Union, the total annual cost of migraine is of 111 billion euros. If not adequately treated, migraine can evolve into the more severe chronic form (CM), defined by \>15 headache days/month, where burden and costs increase exponentially. Until very recently, available preventive treatments for migraine were non-specific, of limited efficacy and scarce tolerability. In 2018, monoclonal antibodies (mABs) against calcitonin gene-related peptide (CGRP) receptor have been approved. Since CGRP is one of the main modulators of the trigeminal system, mABs against CGRP are the first specific preventive treatment for migraine ever developed. They are highly effective in a subgroup of patients, well tolerated, but costly. In this frame, the main objective of BIOMIGA project is to identify predictive biomarkers of response to CGRP-mABs in patients with severe forms of migraine. To this end, the investigators will use an integrated hypothesis-based and data-driven, multidisciplinary approach that combines' omic testing in a deep-phenotyped migraine population and parallel fundamental research in a validated animal model of migraine. Three partners, Headache Science Centre, IRCCS C. Mondino Foundation, University of Pavia, Italy, Headache Research Group Vall d'Hebron Institute of Research, Barcelona, Spain and Institut für Systemische Neurowissenschaften, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany with an established long-standing and complementary expertise in neuroimaging, biochemical profiling and epigenetics in humans and in animal modeling of migraine will collaborate to achieve the Project's objective. The investigators expect important spin-offs to the improved management of migraine, both in terms of increased efficacy and cost saving, but also to understand CGRP-based mechanisms underlying migraine pathophysiology and to set the basis for a pathophysiologically driven classification. Healthcare providers and the pharmaceutical industry will be engaged once the biomarker(s) have been identified to optimize access to care and the use of resource, as well as to reduce disability and socio-economic impact of migraine.

Conditions

Migraine

Keywords

Migraine; Biomarkers; CGRP monoclonal Antibodies

Outcome Measures

Primary Outcomes (1)

• Biomarkers and CGRP-targeting mABs

  To identify a computational algorithm using a machine learning approach based on different types of biomarkers (demographic, clinical, psychological, cognitive, epigenetic, pharmacogenetic, biochemical and structural \& functional brain imaging) that is predictive of response to the class of the CGRP-targeting mABs.

  Day 0 and Week 12

Secondary Outcomes (6)

• Methylation levels

  Day 0 and Week 12

• Brain morphometric measures

  Day 0 and Week 12

• Pharmacogenetic, biochemical, clinical and psychological markers

  Day 0 and Week 12

• Methylation levels at the neuroanatomic and neurofunctional levels

  Day 0 and Week 12

• Morphometric measures

  Day 0 and Week 12

Study Arms (1)

Migraine patients

* Excellent responder, a patient who experiences a \>75% decrease of either the monthly number of migraine days or the monthly number of moderate/severe headache days during the last 4 weeks of treatment as compared to baseline; * Responder, a patient who experiences a \>50% decrease of either the monthly number of migraine days or the monthly number of moderate/severe headache days during the last 4 weeks of treatment as compared to baseline; * Non responder, a patient who experiences a decrease of either the monthly number of migraine days or the monthly number of moderate/severe headache days ranging from 26 to 49% during the last 4 weeks of treatment as compared to baseline; * Full non responder, a patient who experiences a \<25% decrease of either the monthly number of migraine days or the monthly number of moderate/severe headache days during the last 4 weeks of treatment as compared to baseline.

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Migraine patients and Healthy controls. The Health controls will be recruited among hospital staff and non-related acquaintances of the patients. All patients enrolled in the study will be treated with CGRP-targeting mABs according to the indications approved by their National regulatory bodies

You may qualify if:

• Migraine patients
• Adults between 25 and 55 years of age of both gender;
• European background;
• Patients diagnosed with high-frequency migraine (HFM) 8 or more migraine days days/month) or CM with or without aura (\>15 headache days migraine/month, of which 8 have migraine characteristics) according to the International Classification of Headache Disorders, 3rd edition, (ICHD-3);
• Females have to be postmenopausal for at least one year, surgically sterile or otherwise incapable of pregnancy, or using an acceptable method of birth control.
• Healthy controls
• Adults between 25 and 55 years of age of both genders;
• European background;
• Absence of any past or first-degree familial history of recurrent primary or secondary headache disorders.

You may not qualify if:

• For the clinical population:
• Headache on more than 25 days/month in the last 3 months;
• Medication overuse according to the ICHD-3 criteria.
• For the entire study population (migraine and healthy controls)
• Presence of any other significant medical condition (neurological disorders, severe psychiatric illness or cardiovascular disease);
• Evidence of drug, smoking or alcohol abuse or dependence within 12 months prior to V1, based on medical records or patient self-report. An alcohol consumption \>100mg/week will be considered an abuse;
• Pregnant or breastfeeding women;
• Women of childbearing potential, defined as all women physiologically capable of becoming pregnant who are not on contraception;
• Concomitant use of other migraine preventive drugs that may interfere with the endpoints of the study.

Sponsors & Collaborators

• IRCCS National Neurological Institute "C. Mondino" Foundation: lead
• Ministry of Health, Italy: collaborator

Study Sites (3)

Institut für Systemische Neurowissenschaften, Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20357, Germany

Location

Headache Science Center

Pavia, 27100, Italy

Location

Headache Research Group Vall d'Hebron Institute of Research

Barcelona, Catalonia, 8009, Spain

Location

Related Publications (17)

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Biospecimen

Retention: SAMPLES WITH DNA

Blood samples for DNA extraction for DNA methylation analysis and for CGRP-related polymorphisms, and for biochemical profiling

MeSH Terms

Conditions

Migraine Disorders

Condition Hierarchy (Ancestors)

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

Study Officials

• Cristina Tassorelli, Prof

  IRCCS Mondino Foundation, Pavia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2020
• First Posted: August 6, 2020
• Study Start: January 15, 2021
• Primary Completion: January 31, 2024
• Study Completion: January 31, 2024
• Last Updated: June 16, 2026

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); IT (1); DE (1)