Biochemical Profiling of Migraine Patients

NCT06549270 | Recruiting

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

Brief Summary

Aim of the study was to assess a potential dysfunction of the endocannabidiome system (eCBome) in migraine patients. Migraine patients who will undergo preventive therapy with monoclonal antibodies directed against the calcitonin gene related peptide (mAbs) will be evaluated through a deep phenotyping of peripheral neurochemical biomarkers (eCBome, neuropeptides, cytokines and kynurenine levels, and microRNAs expression). Primary aim is to assess baseline differences among those patients who achieved a reduction of monthly migraine days \>/= 50% after three months of tretament (namely Responders) and those who did not (namely Non-responders).

Conditions

Migraine Disorders; Chronic Migraine; Episodic Migraine

Keywords

migraine; anti CGRP mABs; calcitonin gene related peptide; endocannabinoid system

Outcome Measures

Primary Outcomes (2)

• Gene expression of FAAH

  Baseline differences in gene expression of fatty acid amide hydrolase (FAAH) in peripheral blood mononuclear cells (PBMC) (continuous variable)

  Baseline (T0) - three months of mAbs treatment (T1)

• Gene expression of MAGL

  Gene expression of Monoacylglycerol lipase (MAGL) in peripheral blood mononuclear cells (PBMC) (continuous variable)

  Baseline (T0) - three months of mAbs treatment (T1)

Secondary Outcomes (7)

• Gene expression of catalyzing enzymes (DAGL, NAPE, NAAA)

  Baseline (T0) - three months of mAbs treatment (T1)

• Plasma levels of AEA, 2-AG, PEA, OEA

  Baseline (T0) - three months of mAbs treatment (T1)

• Plasma levels of CGRP, PACAP and VIP

  Baseline (T0) - three months of mAbs treatment (T1)

• Gene expression of miR-382-5p, miR-34a, miR-30a and miR-155

  Baseline (T0) - three months of mAbs treatment (T1)

• Plasma levels of IL-1beta, TNF-alpha, IL-4 and IL-10

  Baseline (T0) - three months of mAbs treatment (T1)

Study Arms (2)

Responders

Patients with high frequency episodic migraine (HFEM) or chronic migraine (CM) 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% after three months of treatment compared to pre-treatment values.

Drug: MAbs

Non-Responders

Patients with HFEM or CM undergoing mAbs treatment who obtained a reduction in monthly migraine days \< 50% after three months of treatment 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 or 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: i) having failed at least 3 classes of migraine preventatives and ii) suffering 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 (4)

• 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

• 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 WITHOUT 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: 3 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2024
• First Posted: August 12, 2024
• Study Start: May 10, 2023
• Primary Completion: February 1, 2026
• Study Completion: May 1, 2026
• Last Updated: September 5, 2024

Record last verified: 2024-09

Locations

IT (1)