Characterization of a Functional Test for Mediterranean Family Fever Screening - 2 (DEPIST-FMF 2)

Familial Mediterranean fever (FMF) is the most common auto-inflammatory disease (prevalence: 1-5 / 10,000 inhabitants). It is caused by mutations in the MEFV gene, which encodes variants of the Pyrine inflammasome. Inflammasomes are protein complexes of the innate immunity that produce pro-inflammatory cytokines (interleukin-1β).

In vitro, our preliminary results demonstrated that the activation of the inflammatory pyrine (measured by the concentration of interleukin-1β) by kinase inhibitors is significantly increased in FMF patients compared to healthy subjects. Furthermore, a measurement of cell death gave significant results in differentiating the patients from the controls.

The performance of this functional has been tested, fast and simple diagnostic test on common mutations and wish to assess its characteristics for MEFV mutations.

The investigators hypothesize that this quick and simple functional test can serve as a diagnostic tool for FMF and can quantitatively discriminate against patients with different mutations (genotypes).

Study Overview

• Status: Recruiting
• Conditions: Familial Mediterranean Fever; MEFV Gene Mutation
• Intervention / Treatment: Biological: one additional blood sample during a planned blood test

• Study Type: Observational
• Enrollment (Estimated): 160

Contacts and Locations

• Study Contact: Name: Yvan Jamilloux, MD; Phone Number: +33 26 73 26 36; Email: yvan.jamilloux@chu-lyon.fr

Study Locations

• France
  • Bron, France, 69677
    • Recruiting
    • Hôpital Femme-Mère-Enfant
    • Contact: Alexandre Belot, Pr; Phone Number: +33 4 27 85 61 28; Email: alexandre.belot@chu-lyon.fr
  • Le Chesnay, France, 78157
    • Not yet recruiting
    • Ch de Versailles - Hopital Andre Mignot
    • Contact: Véronique Hentgen, MD; Phone Number: +33 1 39 63 90 98; Email: vhentgen@ch-versailles.fr
  • Lyon, France, 69317
    • Recruiting
    • Hopital De La Croix-Rousse
    • Contact: Yvan Jamilloux, MC/PH; Phone Number: +33 26 73 26 36; Email: yvan.jamilloux@chu-lyon.fr
  • Lyon, France, 69008
    • Not yet recruiting
    • Hôpital Edouard Herriot
    • Contact: Arnaud Hot, Pr; Phone Number: +33 4 72 11 75 65; Email: arnaud.hot@chu-lyon.fr
  • Montpellier, France, 34295
    • Not yet recruiting
    • CHU de Montpellier
    • Contact: Aurelia Carbasse, MD; Phone Number: +33 4 67 33 67 33; Email: aurelia.carbasse@chu-montpellier.fr
  • Nîmes, France, 30029
    • Not yet recruiting
    • Service de Pédiatrie - CHU de Nîmes - Hôpital Carémeau
    • Contact: Tu Anh TRAN, MD; Email: tu.anh.TRAN@chu-nimes.fr
    • Principal Investigator: Tu Anh TRAN, MD
  • Paris, France, 75020
    • Recruiting
    • Hôpital Tenon
    • Contact: Gilles Grateau, Pr; Phone Number: +33 1 56 01 66 15; Email: gilles.grateau@aphp.fr
  • Pierre-Bénite, France, 69495
    • Not yet recruiting
    • Hopital Lyon Sud
    • Contact: Isabelle Durieu, Pr; Phone Number: +33 4 78 86 13 54; Email: Isabelle.durieu@chu-lyon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

This study will involve 80 patients with Familial Mediterranean fever, presenting a previous genetic analysis finding at least one mutation of the MEFV gene, considered pathogenic or possibly pathogenic (60 heterozygotes or complex mutations and 20 homozygotes). The controls will be 80 healthy subjects (French national medical and scientific center (INSERM) and French blood bank (EFS) convention).

Description

Inclusion Criteria:

• Children 4 years of age or older or adults
• Having a clinical picture compatible with an FMF and a previous genetic analysis finding at least one mutation of the MEFV gene pathogenic or possibly pathogenic for the FMF group;
• Newly diagnosed or in the process of follow-up (with no time limit or evolutionary criteria);
• During specific or non-specific treatment of the disease or without treatment;
• For whom a blood test is planned as part of routine care;
• Whose informed non-opposition has been collected (or parental non-opposition in the case of a minor patient);

Exclusion Criteria:

• Person under legal protection or under the protection of justice or any other protective measures;
• Person out of state to express their consent;
• Person in emergency situation, vital or not;
• Known infections with HIV and / or HBV and / or HCV;

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Children or adult with Familial Mediterranean fever; Considering 5 clearly pathogenic (homozygous) genotypes, 15 possibly pathogenic genotypes (5 pathogenic mutations in the heterozygous state, 10 possibly pathogenic mutations in the homozygous or heterozygous state), a number of 80 patients will be necessary to cover the correlation analysis genotype / phenotype. The study does not change the usual course of care. Only an additional blood sample (4 ml for children under 12 and 10 ml for children 12 and over and adults) during a planned blood test is specific to research (no risk added). The benefit / risk balance therefore remains unchanged with regard to the usual care of patients.	Biological: one additional blood sample during a planned blood test; The study does not change the usual course of care. Only an additional blood sample (4 ml for children under 12 and 10 ml for children 12 and over and adults) during a planned blood test is specific to research (no risk added). The benefit / risk balance therefore remains unchanged with regard to the usual care of patients.
Healthy blood donor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantification of interleukin-1β	quantification of the capacity of the concentration of interleukin-1β measured in the supernatants of primary monocytes in response to kinase inhibitors, to discriminate between FMF subjects among themselves according to genotypes, and among control subjects (healthy subjects). All samples will be analysed in the INSERM Unit 1111 - CIRI Centre International de Recherche en Infectiologie - Lyon - Team Inflammasome, bacterial infections and autoinflammation.	At inclusion

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2021
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: July 16, 2020
• First Submitted That Met QC Criteria: July 16, 2020
• First Posted (Actual): July 20, 2020

Study Record Updates

• Last Update Posted (Actual): July 19, 2024
• Last Update Submitted That Met QC Criteria: July 18, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Familial Mediterranean fever; Interleukin-1β; MEFV gene mutation; innate immunity
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Genetic Diseases, Inborn; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Skin Diseases, Genetic; Body Temperature Changes; Fever; Brucellosis; Familial Mediterranean Fever; Hereditary Autoinflammatory Diseases
• Other Study ID Numbers: 69HCL20_0236

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No