Assessment of microRNAs Role in Familial Mediterranean Fever FMF Pathophysiology

NCT06033339 | Unknown

• 1 other identifier: RECHMPL22_0296 - UF 8310
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 4

Brief Summary

Familial Mediterranean Fever (FMF) genetic diagnosis is well established for homozygous patients. On the other hand, although heterozygous individuals are theoretically healthy carriers, 1/3 of them will develop clinical symptoms of FMF and could benefit from prophylactic treatment. This suggests that the disorder expression mechanisms are not fully elucidated to date. The preliminary results obtained at the Institute for Regenerative Medicine and Biotherapy (IRMB) suggest the involvement of an epigenetic mechanism in FMF pathogenesis, and our laboratory has strong arguments as to the involvement of microRNAs (in particular miR-326) which are negative regulators of gene expression. This study is exploratory and aims to validate the role of miRNAs in the clinical expression of FMF in patients, thus to explore the epigenetic mechanisms that may explain the variability of expression of this disorder.

Conditions

Familial Mediterranean Fever

Keywords

MEditerranean FeVer MEFV gene; micro ribonucleic acid miRNA

Outcome Measures

Primary Outcomes (2)

• miR-326 expression level quantification

  Analyze the expression levels (quantification) of miRNA miR-326 in blood monocytes within the 4 groups of individuals: homozygous, symptomatic heterozygous, asymptomatic heterozygous for MEFV and control subjects, in order to determine whether or not miR-326 influences the inflammatory response of monocytes.

  1 day (at enrollment)

• MEFV expression level quantification

  Analyze the expression levels (quantification) of MEFV gene in blood monocytes within the 4 groups of individuals: homozygous, symptomatic heterozygous, asymptomatic heterozygous for MEFV and control subjects

  1 day (at enrollment)

Secondary Outcomes (4)

• miR-326 expression level comparison

  1 day (at enrollment)

• MEFV expression level comparison

  1 day (at enrollment)

• Blood samples collection

  1 day (at enrollment)

• Expression levels of other candidate miRNAs targeting MEFV

  1 day (at enrollment)

Study Arms (1)

Blood Sampling

OTHER

Collection of 10 ml of blood on EDTA tube during: * Standard check-up visit as a part of the standard monitoring of the disorder for homozygous and symptomatic heterozygous patients * Specific study visit for asymptomatic heterozygous patients * Presurgery blood test for control subjects

Other: Blood sampling

Interventions

Blood sampling OTHER

Collection of 10 ml of blood on EDTA tubes per patient. Once collected, the blood tubes will be transported within 24 hours to the IRB (Biotherapy Research Institute) of Montpellier University Hospital, where the monocytes will be isolated by magnetic sorting on the basis of expression of surface marker CD14+, after a preliminary step of Ficoll. Monocytes will then be frozen in nitrogen at -196°C until use (biobank).Gain-of-function experiments will then be performed on monocytes by transfecting them with the microRNA of interest or control. The expression of the pyrin protein and its phosphorylation rate will be evaluated after induction by immunoprecipitation experiments followed by western blot. The activity of the pyrin inflammasome will also be studied by looking at pyroptosis and toxicity rate using LDH test. All these experiments will be carried out in the absence and in the presence of the microRNA in order to study its role in the pathophysiology of FMF.

Blood Sampling

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient aged ≥1 year
• Body weight ≥ 10kg
• Homozygous patients group: patients homozygous for MEFV (M694V, M694I, M680I, V726A)
• Symptomatic heterozygous patients group: patients heterozygous for the MEFV gene (M694V, M694I, M680I, V726A) meeting the Yalcinkaya criteria for FMF diagnosis (Fever lasting 6 to 72 hours with at least 3 attacks - Abdominal pain of 6 to 72 hours duration with at least 3 attacks - Chest pain of 6 to 72 hours duration with at least 3 attacks - Arthritis of 6 to 72 hours duration with at least 3 attacks- FMF Family History of FMF)
• Asymptomatic heterozygous patients group: patients heterozygous for the MEFV gene (M694V, M694I, M680I, V726A) who do not meet the Yalcinkaya criteria for FMF diagnosis
• Control subjects group: absence of identified auto-inflammatory disorder

You may not qualify if:

• Absence of collection of informed consent of participant or absence of informed consent of the legal representatives/guardians of pediatric participant
• Subjects not registered in Social Security system

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (4)

University Hospital of Nîmes

Nîmes, France

Location

Robert Debré University Hospital of Paris

Paris, France

Location

University Hospital of Paris Kremlin Bicêtre

Paris, France

Location

University Hospital of Toulouse

Toulouse, France

Location

MeSH Terms

Conditions

Familial Mediterranean Fever

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Eric JEZIORSKI, MD

  University Hospital, Montpellier

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna DEGUET, MD

CONTACT

0033669107224; a-deguet@chu-montpellier.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Among the 40 subjects to be enrolled: 10 are MEFV homozygous patients, 10 are symptomatic MEFV heterozygous patients, 10 are asymptomatic MEFV heterozygous patients and 10 are control subjects. All enrolled patients receive the same intervention (biological sample collection).

Study Record Dates

• First Submitted: September 5, 2023
• First Posted: September 13, 2023
• Study Start: October 2, 2023
• Primary Completion: October 2, 2025
• Study Completion: October 2, 2025
• Last Updated: September 14, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4)