Searching for Novel Biological Phenotypes in Migraine Patients Resistant to Treatments

NCT06562413 | Recruiting

• 1 other identifier: SPHERA-functional
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators aim to define the neurofunctional phenotype of migraine patients who did not respond to at least 3 preventive treatments, including monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) pathway (NON-responders). Primary aim will be to assess and compare changes in functional resting-state connectivity at baseline and after three months of mAbs treatment between patients who will achieve a reduction of monthly migraine days \>/= than 50% (namely Responders) and those who will not (namely Responders). The 2 groups will undergo a neurofunctional profile by means of High Density-electroencephalogram (HD-EEG) and functional-magnetic resonance imaging (fMRI).

Conditions

Migraine Disorders; Chronic Migraine; Episodic Migraine

Keywords

migraine; anti CGRP mABs; calcitonin gene related peptide; HD EEG; functional MRI; brain connectivity

Outcome Measures

Primary Outcomes (2)

• RSN-FC assessed through HD-EEG

  Resting state functional connectivity assessed through HD-EEG (continuous variable, without unit of measurement)

  Baseline (T0), and three months of mAbs treatment (T1)

• RSN-FC assessed through MRI

  Resting state functional connectivity assessed through MRI (continuous variable, without unit of measurement)

  Baseline (T0)

Secondary Outcomes (2)

• Comparison between baseline RSN-FC assessed through HD-EEG

  Baseline (T0)

• Comparison between baseline RSN-FC assessed through MRI

  Baseline (T0)

Study Arms (2)

Responders

Patients with high frequency episodic or chronic migraine undergoing treatment with monoclonal antibodies directed against calcitonin gene related peptide pathway (mAbs) who obtained a reduction in monthly migraine days equal or higher than 50% compared to pre-treatment values.

Drug: MAbs

NON-Responders

Patients with high frequency episodic or chronic migraine undergoing mAbs treatment who obtained a reduction in monthly migraine days \< 50% compared to pre-treatment values.

Drug: MAbs

Interventions

MAbs DRUG

Monthly or quarterly mAbs administration

Also known as: Monoclonal antibody targeting the CGRP pathway (ligand or receptor) (mAbs)

NON-Responders; Responders

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Subjects with chronic and high frequency episodic migraine attending the outpatient clinic of the Headache Science \& Neurorehabilitation Unit of the IRCCS Mondino Foundation (Pavia, Italy) and the Neurology Department of the University of L'Aquila (Avezzano, Italy).

You may qualify if:

• male and female patients aged 18 to 75 years
• diagnosis of episodic migraine or chronic migraine according to ICHD-3 criteria
• for episodic migraine: 8-14 monthly migraine days in the previous 3 months
• diagnosis of resistant migraine, defined by having failed at least 3 classes of migraine preventatives and suffer from at least 8 debilitating monthly headache days for at least 3 consecutive months
• patients naive to CGRP targeting treatments

You may not qualify if:

• history of major psychiatric or other neurological conditions
• diagnosis of other primary or secondary headache disorders (only sporadic tension-type headache is allowed if the patients can clearly differentiate between the 2 types of headaches)
• changes in ongoing preventive treatment (if any) in the previous 3 months
• clinically significant medical conditions
• chronic pain conditions
• alcohol and/or drug abuse
• pregnancy or lactation

Sponsors & Collaborators

• IRCCS National Neurological Institute "C. Mondino" Foundation: lead
• University of L'Aquila: collaborator

Study Sites (1)

Headache Science & Neurorehabilitation Unit

Pavia, 27100, Italy

RECRUITING

Related Publications (6)

• Mantini D, Franciotti R, Romani GL, Pizzella V. Improving MEG source localizations: an automated method for complete artifact removal based on independent component analysis. Neuroimage. 2008 Mar 1;40(1):160-73. doi: 10.1016/j.neuroimage.2007.11.022. Epub 2007 Dec 3.

  PMID: 18155928 BACKGROUND

• Gao W, Walther A, Wekenborg M, Penz M, Kirschbaum C. Determination of endocannabinoids and N-acylethanolamines in human hair with LC-MS/MS and their relation to symptoms of depression, burnout, and anxiety. Talanta. 2020 Sep 1;217:121006. doi: 10.1016/j.talanta.2020.121006. Epub 2020 Apr 9.

  PMID: 32498885 BACKGROUND

• Fuertig R, Ceci A, Camus SM, Bezard E, Luippold AH, Hengerer B. LC-MS/MS-based quantification of kynurenine metabolites, tryptophan, monoamines and neopterin in plasma, cerebrospinal fluid and brain. Bioanalysis. 2016 Sep;8(18):1903-17. doi: 10.4155/bio-2016-0111. Epub 2016 Aug 15.

  PMID: 27524289 BACKGROUND

• Curto M, Lionetto L, Negro A, Capi M, Fazio F, Giamberardino MA, Simmaco M, Nicoletti F, Martelletti P. Altered kynurenine pathway metabolites in serum of chronic migraine patients. J Headache Pain. 2015;17:47. doi: 10.1186/s10194-016-0638-5. Epub 2016 Apr 29.

  PMID: 27130315 BACKGROUND

• Greco R, Demartini C, Zanaboni AM, Tumelero E, Icco R, Sances G, Allena M, Tassorelli C. Peripheral changes of endocannabinoid system components in episodic and chronic migraine patients: A pilot study. Cephalalgia. 2021 Feb;41(2):185-196. doi: 10.1177/0333102420949201. Epub 2020 Sep 23.

  PMID: 32967434 BACKGROUND

• De Icco R, Greco R, Demartini C, Vergobbi P, Zanaboni A, Tumelero E, Reggiani A, Realini N, Sances G, Grillo V, Allena M, Tassorelli C. Spinal nociceptive sensitization and plasma palmitoylethanolamide levels during experimentally induced migraine attacks. Pain. 2021 Sep 1;162(9):2376-2385. doi: 10.1097/j.pain.0000000000002223.

  PMID: 33587406 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood

MeSH Terms

Conditions

Migraine Disorders

Interventions

Ligands

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Laboratory Chemicals; Specialty Uses of Chemicals; Chemical Actions and Uses

Central Study Contacts

Roberto De Icco

CONTACT

00390382380425; roberto.deicco@mondino.it

Cinzia Fattore

CONTACT

00390382380385; cinzia.fattore@mondino.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2024
• First Posted: August 20, 2024
• Study Start: May 10, 2023
• Primary Completion: February 1, 2026
• Study Completion: May 1, 2026
• Last Updated: August 20, 2024

Record last verified: 2024-08

Locations

IT (1)