Plasma Levels of CGRP and Expression of Specific microRNAs in Blood Cells of Episodic and Chronic Migraine Subjects

NCT04473976 | Completed

• 1 other identifier: CGRP-microRNA2020
• Study Type: observational
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

Migraine can manifest with an episodic or chronic pattern in a continuum of disease severity. Multiple factors are associated to the transformation of the pattern form episodic to chronic. Of these, the most consistently reported is the overuse of medications (MO) for the acute treatment of attacks. Knowledge of the mechanisms through which MO facilitates the transformation of episodic migraine (EM) into chronic migraine (CM) is very limited. In order insights into these mechanisms, the present study was aimed at identifying possible peripheral biomarkers associated to the 2 forms of migraine and to the presence of MO. The investigators evaluated CGRP plasma levels and the expression of miR-34a-5p and miR-382-5p in peripheral blood mononuclear cells of subjects with episodic migraine (EM, n=27) and CM-MO (n=28). CM-MO group was also tested 2 months after an in-hospital detoxification protocol.

Conditions

Migraine

Keywords

Migraine; CGRP; MicroRNA; Overuse of medications

Outcome Measures

Primary Outcomes (2)

• Plasma levels of CGRP

  In order to identify individual or a panel of potential biomarkers of migraine subtypes

  Day 0 at the enrolment

• Expression of miRNAs in PBMCs

  In order to identify individual or a panel of potential biomarkers of migraine subtypes

  Day 0 at the enrolment

Secondary Outcomes (2)

• Changes in CGRP levels

  Day1 - Two months after Day 0

• Changes in miRNAs levels

  Day 1 - Two months after Day 0

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Twenty-seven subjects with EM and 28 subjects with CM-MO were consecutively enrolled among patients attending the outpatient clinics of the Headache Science Centre of the IRCCS Mondino Foundation of Pavia (Italy).

You may qualify if:

• diagnosis of migraine without aura according to The International Classification Headache Disorders 3rd edition (ICHD-3) criteria;
• documented history of EM for at least 10 years before enrollment;
• negative life-time history of CM.

You may not qualify if:

• headache or headache with migraine features and mild intensity (less than 4 on 0 to 10 visual analogue scale) in the 24 hours before blood sampling;
• intake of acute anti-migraine medications in the 24 hours before blood sampling.
• diagnosis of CM and MO according to ICHD-3 criteria;
• documented pattern of stable CM in the 5 years prior to enrollment, without any remission period. This latter point was verified with a high degree of confidence combining the information obtained from the patients' history with their medical records, including their headache diaries.
• headache or headache with migraine features and mild intensity (less than 4 on 0 to 10 visual analogue scale) in the 24 hours before blood sampling;
• intake of acute anti-migraine medications in the 24 hours before blood sampling.

Sponsors & Collaborators

• IRCCS National Neurological Institute "C. Mondino" Foundation: lead
• University of Pavia: collaborator

Study Sites (1)

Headache Science Center

Pavia, 27100, Italy

Location

Related Publications (26)

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  PMID: 30806518 BACKGROUND

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  PMID: 31635478 BACKGROUND

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• Tassorelli C, Jensen R, Allena M, De Icco R, Sances G, Katsarava Z, Lainez M, Leston J, Fadic R, Spadafora S, Pagani M, Nappi G; the COMOESTAS Consortium. A consensus protocol for the management of medication-overuse headache: Evaluation in a multicentric, multinational study. Cephalalgia. 2014 Aug;34(9):645-655. doi: 10.1177/0333102414521508. Epub 2014 Feb 20.

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  PMID: 23565591 BACKGROUND

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  PMID: 21467931 BACKGROUND

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  PMID: 23431023 BACKGROUND

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  PMID: 20373344 BACKGROUND

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  PMID: 30484333 BACKGROUND

• Deng T, Yang L, Zheng Z, Li Y, Ren W, Wu C, Guo L. Calcitonin gene-related peptide induces IL-6 expression in RAW264.7 macrophages mediated by mmu_circRNA_007893. Mol Med Rep. 2017 Dec;16(6):9367-9374. doi: 10.3892/mmr.2017.7779. Epub 2017 Oct 12.

  PMID: 29039515 BACKGROUND

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  PMID: 28056747 BACKGROUND

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  PMID: 29932027 BACKGROUND

• Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. doi: 10.1177/0333102417738202. No abstract available.

  PMID: 29368949 BACKGROUND

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• Tassorelli C, Diener HC, Dodick DW, Silberstein SD, Lipton RB, Ashina M, Becker WJ, Ferrari MD, Goadsby PJ, Pozo-Rosich P, Wang SJ; International Headache Society Clinical Trials Standing Committee. Guidelines of the International Headache Society for controlled trials of preventive treatment of chronic migraine in adults. Cephalalgia. 2018 Apr;38(5):815-832. doi: 10.1177/0333102418758283. Epub 2018 Mar 4.

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• Greco R, De Icco R, Demartini C, Zanaboni AM, Tumelero E, Sances G, Allena M, Tassorelli C. Plasma levels of CGRP and expression of specific microRNAs in blood cells of episodic and chronic migraine subjects: towards the identification of a panel of peripheral biomarkers of migraine? J Headache Pain. 2020 Oct 16;21(1):122. doi: 10.1186/s10194-020-01189-0.

  PMID: 33066724 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples from the cubital vein of each patient was put into a 5 ml lavender tube. Plasma samples were prepared by centrifugation and then stored at -80°C. Plasma CGRP levels were measured using a commercial enzyme-linked immuno-sorbent assay kit. The miRNAs expression was evaluated by real-time reverse transcription (RT) Polymerase Chain Reaction (PCR) in peripheral blood mononuclear cell (PBMCs). PBMCs were isolated immediately after blood collection. Blood samples were collected within ethylenediamine tetra-acetic acid (EDTA) containing tube and diluted in 1:1 ratio with Phosphate Buffer Saline (PBS). Then, diluted blood samples were slowly loaded into Ficoll separating solution (15 ml) (Sigma) and centrifuged at 800 g for 30 min at room temperature. PBMCs accumulated as the middle white monolayer, were washed twice in sterile PBS at 300 g for 15 min. After washing, PBMCs pellet was resuspended in trizol and stored at -80 °C until use.

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: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2020
• First Posted: July 16, 2020
• Study Start: December 15, 2017
• Primary Completion: April 15, 2019
• Study Completion: June 15, 2019
• Last Updated: July 20, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)