A Diagnostic Test for Familial Mediterranean Fever (DEPIST-FMF)

Assessment of a Functional Test to Detect Familial Mediterranean Fever

Familial Mediterranean Fever (FMF) is the most common auto-inflammatory disease (prevalence: 1-5 / 10,000 inhabitants). It is due to mutations of the MEFV gene, encoding variants of the Pyrin inflammasome. Inflammasomes are protein complexes of innate immunity producing pro-inflammatory cytokines (interleukin-1β).

In vitro, preliminary results demonstrated that activation of the Pyrin inflammasome (measured by interleukin-1β concentration) by kinase inhibitors is significantly increased in FMF patients compared to subjects with a similar clinical picture, and healthy controls. In addition, a measure of cell death yielded significant results in differentiating patients from controls.

The investigators hypothesize that this fast and simple functional test can serve as a diagnostic tool for FMF.

Study Overview

• Status: Completed
• Conditions: Familial Mediterranean Fever
• Intervention / Treatment: Other: In vitro functional test; Other: In vitro functional test

• Study Type: Observational
• Enrollment (Actual): 107

Contacts and Locations

Study Locations

• France
  • Bron, France, 69500
    • Service de néphrologie et rhumatologie pédiatrique, Hôpital Femme Mère Enfant
  • Lyon, France, 69004
    • Unité Inserm U1111 & Service de Médecine Interne, Hôpital de la Croix-Rousse
  • Lyon, France, 69437
    • Service de Médecine Interne, Pavillon O - Hopital Edouard Herriot
  • Pierre-Bénite, France, 69495
    • Service de Médecine Interne et pathologies vasculaires, Batiment 1B, Centre Hospitalier Lyon Sud

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with Familial Mediterranean Fever, patients controls with similar symptoms and healthy subjects who donated their blood to the French Blood Establishment.

Description

Inclusion Criteria:

• Clinical picture compatible with an Familial Mediterranean Fever and an earlier genetic analysis finding a mutation of the MEFV gene;
• Newly diagnosed or undergoing follow-up (without criteria of delay or evolutionary stage);
• In the course of specific or non-specific treatment of the disease or without treatment;
• For whom a blood test is planned as part of the routine care;
• Of whom the informed non-opposition has been collected (parental authorization in the case of a minor patient);

Exclusion Criteria:

• patient under legal protection or under safeguard of justice or any other measures of protection (guardianship, curatorship);
• Person unable to express his consent;
• Person in emergency situation, vital or not;
• Infection known to 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

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Familial Mediterranean Fever (patients); Patients with previously confirmed Familial Mediterranean Fever (based on clinical criteria)	Other: In vitro functional test; Measurement of interleukin-1beta secretion by monocytes and measurement of cell death upon Pyrin inflammasome activation by kinase inhibitor on an additional blood sample (4 ml for children under 12 and 10 ml for children 12 years and older and adults) during a sample for patient care.; Other: In vitro functional test; Measurement of interleukin-1beta secretion by monocytes and measurement of cell death upon Pyrin inflammasome activation by kinase inhibitor on samples from healthy subjects who donated their blood to the French Blood Establishment.
Control group (patients); Patients with symptoms similar to that of Familial Mediterranean Fever (e.g. Behcet disease, Crohn, sepsis..) but without confirmed Familial Mediterranean Fever.	Other: In vitro functional test; Measurement of interleukin-1beta secretion by monocytes and measurement of cell death upon Pyrin inflammasome activation by kinase inhibitor on an additional blood sample (4 ml for children under 12 and 10 ml for children 12 years and older and adults) during a sample for patient care.; Other: In vitro functional test; Measurement of interleukin-1beta secretion by monocytes and measurement of cell death upon Pyrin inflammasome activation by kinase inhibitor on samples from healthy subjects who donated their blood to the French Blood Establishment.
Healthy donors; Patients without symptoms (anonymous blood donors)	Other: In vitro functional test; Measurement of interleukin-1beta secretion by monocytes and measurement of cell death upon Pyrin inflammasome activation by kinase inhibitor on an additional blood sample (4 ml for children under 12 and 10 ml for children 12 years and older and adults) during a sample for patient care.; Other: In vitro functional test; Measurement of interleukin-1beta secretion by monocytes and measurement of cell death upon Pyrin inflammasome activation by kinase inhibitor on samples from healthy subjects who donated their blood to the French Blood Establishment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in interleukin-1bβ levels	Quantification of the capacity of interleukin-1β concentration measured in primary monocyte supernatants in response to kinase inhibitors, to discriminate Familial Mediterranean Fever subjects from control subjects (healthy subjects and subjects with symptoms similar to those of Familial Mediterranean Fever). Analysis have to be performed Less than 48 hours after blood sampling (only one sampling).	Less than 48 hours

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2018
• Primary Completion (Actual): December 15, 2020
• Study Completion (Actual): December 15, 2020

Study Registration Dates

• First Submitted: November 14, 2018
• First Submitted That Met QC Criteria: November 19, 2018
• First Posted (Actual): November 20, 2018

Study Record Updates

• Last Update Posted (Actual): June 8, 2021
• Last Update Submitted That Met QC Criteria: June 7, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• 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: 69HCL17_0710

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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