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

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ClinicalTrials.gov Identifier: NCT04503083
Recruitment Status : Recruiting
First Posted : August 6, 2020
Last Update Posted : April 29, 2021
Sponsor:
Collaborator:
Ministry of Health, Italy
Information provided by (Responsible Party):
IRCCS National Neurological Institute "C. Mondino" Foundation

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.


Condition or disease
Migraine

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Study Type : Observational
Estimated Enrollment : 219 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Multidisciplinary Approach to the Identification of BIOmarkers of MIGraine: a Proof of Concept Study Based on the Stratification of Responders to CGRP Monoclonal Antibodies
Actual Study Start Date : January 15, 2021
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : March 1, 2023

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Migraine
MedlinePlus related topics: Migraine

Group/Cohort
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.



Primary Outcome Measures :
  1. Biomarkers and CGRP-targeting mABs [ Time Frame: Day 0 and Week 12 ]
    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.


Secondary Outcome Measures :
  1. Methylation levels [ Time Frame: Day 0 and Week 12 ]
    Difference in methylation levels in migraine subjects as compared to healthy controls

  2. Brain morphometric measures [ Time Frame: Day 0 and Week 12 ]
    Differences in brain morphometric measures between migraine patients and healthy controls at the neuroanatomic and neurofunctional levels

  3. Pharmacogenetic, biochemical, clinical and psychological markers [ Time Frame: Day 0 and Week 12 ]
    Differences in pharmacogenetic, biochemical, clinical and psychological markers between migraine patients and healthy controls

  4. Methylation levels at the neuroanatomic and neurofunctional levels [ Time Frame: Day 0 and Week 12 ]
    Difference in methylation levels in migraine subjects between migraine patients and healthy controls at the neuroanatomic and neurofunctional levels

  5. Morphometric measures [ Time Frame: Day 0 and Week 12 ]
    Differences in brain morphometric measures between migraine subjects who are responder and those who are non responders to CGRP-targeting mABs

  6. Pharmacogenetic, biochemical, clinical and psychological markers in responder and non responders [ Time Frame: Day 0 and Week 12 ]
    Differences in pharmacogenetic, biochemical, clinical and psychological between migraine subjects who are responder and those who are non responders to CGRP-targeting mABs


Biospecimen Retention:   Samples With DNA
Blood samples for DNA extraction for DNA methylation analysis and for CGRP-related polymorphisms, and for biochemical profiling


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   25 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04503083


Contacts
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Contact: Cristina Tassorelli, MD 0039 382 380390 cristina.tassorelli@mondino.it
Contact: Cinzia Fattore, MD 0039 382385 cinzia.fattore@mondino.it

Locations
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Germany
Institut für Systemische Neurowissenschaften, Universitätsklinikum Hamburg-Eppendorf Not yet recruiting
Hamburg, Germany, 20357
Contact: Arne May, MD       a.may@uke.uni-hamburg.de   
Italy
Headache Science Center Recruiting
Pavia, Italy, 27100
Contact: Cristina Tassorelli, MD    0382380390    cristina.tassorelli@mondino.it   
Contact: Daniele Martinelli, MD    0382 380390    daniele.martinelli@mondino.it   
Spain
Headache Research Group Vall d'Hebron Institute of Research Not yet recruiting
Barcelona, Cataluna, Spain, 8009
Contact: Patricia Pozo-Rosich, MD       ppozorosich@yahoo.com   
Sponsors and Collaborators
IRCCS National Neurological Institute "C. Mondino" Foundation
Ministry of Health, Italy
Investigators
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Principal Investigator: Cristina Tassorelli, Prof IRCCS Mondino Foundation, Pavia
Publications:
Brainstorm Consortium, Anttila V, Bulik-Sullivan B, Finucane HK, Walters RK, Bras J, Duncan L, Escott-Price V, Falcone GJ, Gormley P, Malik R, Patsopoulos NA, Ripke S, Wei Z, Yu D, Lee PH, Turley P, Grenier-Boley B, Chouraki V, Kamatani Y, Berr C, Letenneur L, Hannequin D, Amouyel P, Boland A, Deleuze JF, Duron E, Vardarajan BN, Reitz C, Goate AM, Huentelman MJ, Kamboh MI, Larson EB, Rogaeva E, St George-Hyslop P, Hakonarson H, Kukull WA, Farrer LA, Barnes LL, Beach TG, Demirci FY, Head E, Hulette CM, Jicha GA, Kauwe JSK, Kaye JA, Leverenz JB, Levey AI, Lieberman AP, Pankratz VS, Poon WW, Quinn JF, Saykin AJ, Schneider LS, Smith AG, Sonnen JA, Stern RA, Van Deerlin VM, Van Eldik LJ, Harold D, Russo G, Rubinsztein DC, Bayer A, Tsolaki M, Proitsi P, Fox NC, Hampel H, Owen MJ, Mead S, Passmore P, Morgan K, Nöthen MM, Rossor M, Lupton MK, Hoffmann P, Kornhuber J, Lawlor B, McQuillin A, Al-Chalabi A, Bis JC, Ruiz A, Boada M, Seshadri S, Beiser A, Rice K, van der Lee SJ, De Jager PL, 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Privitera M, Radtke R, Ruppert AK, Sander T, Schachter S, Schankin C, Scheffer I, Schoch S, Sisodiya SM, Smith P, Sperling M, Striano P, Surges R, Thomas GN, Visscher F, Whelan CD, Zara F, Heinzen EL, Marson A, Becker F, Stroink H, Zimprich F, Gasser T, Gibbs R, Heutink P, Martinez M, Morris HR, Sharma M, Ryten M, Mok KY, Pulit S, Bevan S, Holliday E, Attia J, Battey T, Boncoraglio G, Thijs V, Chen WM, Mitchell B, Rothwell P, Sharma P, Sudlow C, Vicente A, Markus H, Kourkoulis C, Pera J, Raffeld M, Silliman S, Boraska Perica V, Thornton LM, Huckins LM, William Rayner N, Lewis CM, Gratacos M, Rybakowski F, Keski-Rahkonen A, Raevuori A, Hudson JI, Reichborn-Kjennerud T, Monteleone P, Karwautz A, Mannik K, Baker JH, O'Toole JK, Trace SE, Davis OSP, Helder SG, Ehrlich S, Herpertz-Dahlmann B, Danner UN, van Elburg AA, Clementi M, Forzan M, Docampo E, Lissowska J, Hauser J, Tortorella A, Maj M, Gonidakis F, Tziouvas K, Papezova H, Yilmaz Z, Wagner G, Cohen-Woods S, Herms S, Julià A, Rabionet R, Dick DM, Ripatti S, Andreassen OA, Espeseth T, Lundervold AJ, Steen VM, Pinto D, Scherer SW, Aschauer H, Schosser A, Alfredsson L, Padyukov L, Halmi KA, Mitchell J, Strober M, Bergen AW, Kaye W, Szatkiewicz JP, Cormand B, Ramos-Quiroga JA, Sánchez-Mora C, Ribasés M, Casas M, Hervas A, Arranz MJ, Haavik J, Zayats T, Johansson S, Williams N, Dempfle A, Rothenberger A, Kuntsi J, Oades RD, Banaschewski T, Franke B, Buitelaar JK, Arias Vasquez A, Doyle AE, Reif A, Lesch KP, Freitag C, Rivero O, Palmason H, Romanos M, Langley K, Rietschel M, Witt SH, Dalsgaard S, Børglum AD, Waldman I, Wilmot B, Molly N, Bau CHD, Crosbie J, Schachar R, Loo SK, McGough JJ, Grevet EH, Medland SE, Robinson E, Weiss LA, Bacchelli E, Bailey A, Bal V, Battaglia A, Betancur C, Bolton P, Cantor R, Celestino-Soper P, Dawson G, De Rubeis S, Duque F, Green A, Klauck SM, Leboyer M, Levitt P, Maestrini E, Mane S, De-Luca DM, Parr J, Regan R, Reichenberg A, Sandin S, Vorstman J, Wassink T, Wijsman E, Cook E, Santangelo S, Delorme R, Rogé B, Magalhaes T, Arking D, Schulze TG, Thompson RC, Strohmaier J, Matthews K, Melle I, Morris D, Blackwood D, McIntosh A, Bergen SE, Schalling M, Jamain S, Maaser A, Fischer SB, Reinbold CS, Fullerton JM, Guzman-Parra J, Mayoral F, Schofield PR, Cichon S, Mühleisen TW, Degenhardt F, Schumacher J, Bauer M, Mitchell PB, Gershon ES, Rice J, Potash JB, Zandi PP, Craddock N, Ferrier IN, Alda M, Rouleau GA, Turecki G, Ophoff R, Pato C, Anjorin A, Stahl E, Leber M, Czerski PM, Cruceanu C, Jones IR, Posthuma D, Andlauer TFM, Forstner AJ, Streit F, Baune BT, Air T, Sinnamon G, Wray NR, MacIntyre DJ, Porteous D, Homuth G, Rivera M, Grove J, Middeldorp CM, Hickie I, Pergadia M, Mehta D, Smit JH, Jansen R, de Geus E, Dunn E, Li QS, Nauck M, Schoevers RA, Beekman AT, Knowles JA, Viktorin A, Arnold P, Barr CL, Bedoya-Berrio G, Bienvenu OJ, Brentani H, Burton C, Camarena B, Cappi C, Cath D, Cavallini M, Cusi D, Darrow S, Denys D, Derks EM, Dietrich A, Fernandez T, Figee M, Freimer 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Responsible Party: IRCCS National Neurological Institute "C. Mondino" Foundation
ClinicalTrials.gov Identifier: NCT04503083    
Other Study ID Numbers: BIOMIGA2020
First Posted: August 6, 2020    Key Record Dates
Last Update Posted: April 29, 2021
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by IRCCS National Neurological Institute "C. Mondino" Foundation:
Migraine
Biomarkers
CGRP monoclonal Antibodies
Additional relevant MeSH terms:
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Migraine Disorders
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases