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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04478409
Recruitment Status : Recruiting
First Posted : July 20, 2020
Last Update Posted : November 22, 2021
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Brief Summary:

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).


Condition or disease Intervention/treatment
Familial Mediterranean Fever MEFV Gene Mutation Biological: one additional blood sample during a planned blood test

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Study Type : Observational
Estimated Enrollment : 160 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Characterization of a Functional Test for Mediterranean Family Fever Screening - 2
Actual Study Start Date : July 21, 2021
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : June 2024


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
Healthy blood donor



Primary Outcome Measures :
  1. Quantification of interleukin-1β [ Time Frame: At inclusion ]

    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.



Biospecimen Retention:   Samples Without DNA

Sample will be code and sent to the laboratory within 24 hours (Inserm U1111, Lyon). For healthy subjects, research does not involve drawing additional blood from their blood donation.

There will be no long-term storage or establishment of biological collections. The monocytes will be extracted, selected and counted. The pyras inflammasome will then be activated and the interleukin-1β secretion will be measured by ELISA. Cell death will be quantified in real time by fluorimetry.

Validation on cellular models in vitro: immortalized monocytes will be invalidated for the MEFV gene by CrispR-Cas9 and different inducible variants of the MEFV gene will be expressed in MEFV knot out cells. These genetically modified cells will then undergo the tests for stimulation of the inflammatory Pyrine according to the same procedures as the monocytes of the patients.



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Ages Eligible for Study:   4 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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).
Criteria

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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04478409


Contacts
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Contact: Yvan Jamilloux, MD 26 73 26 36 ext +33 yvan.jamilloux@chu-lyon.fr

Locations
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France
Hôpital Femme-Mère-Enfant Not yet recruiting
Bron, France, 69677
Contact: Alexandre Belot, Pr    4 27 85 61 28 ext +33    alexandre.belot@chu-lyon.fr   
CH de Versailles - Hôpital André Mignot Not yet recruiting
Le Chesnay, France, 78157
Contact: Véronique Hentgen, MD    1 39 63 90 98 ext +33    vhentgen@ch-versailles.fr   
Hôpital Edouard Herriot Not yet recruiting
Lyon, France, 69008
Contact: Arnaud Hot, Pr    4 72 11 75 65 ext +33    arnaud.hot@chu-lyon.fr   
Hôpital de la Croix-Rousse Recruiting
Lyon, France, 69317
Contact: Yvan Jamilloux, MC/PH    26 73 26 36 ext +33    yvan.jamilloux@chu-lyon.fr   
CHU de Montpellier Not yet recruiting
Montpellier, France, 34295
Contact: Aurelia Carbasse, MD    4 67 33 67 33 ext +33    aurelia.carbasse@chu-montpellier.fr   
Service de Pédiatrie - CHU de Nîmes - Hôpital Carémeau Not yet recruiting
Nîmes, France, 30029
Contact: Tu Anh TRAN, MD       tu.anh.TRAN@chu-nimes.fr   
Principal Investigator: Tu Anh TRAN, MD         
Hôpital Tenon Not yet recruiting
Paris, France, 75020
Contact: Gilles Grateau, Pr    1 56 01 66 15 ext +33    gilles.grateau@aphp.fr   
Hôpital Lyon Sud Not yet recruiting
Pierre-Bénite, France, 69495
Contact: Isabelle Durieu, Pr    4 78 86 13 54 ext +33    Isabelle.durieu@chu-lyon.fr   
Sponsors and Collaborators
Hospices Civils de Lyon
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Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT04478409    
Other Study ID Numbers: 69HCL20_0236
First Posted: July 20, 2020    Key Record Dates
Last Update Posted: November 22, 2021
Last Verified: November 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hospices Civils de Lyon:
Familial Mediterranean fever
Interleukin-1β
MEFV gene mutation
innate immunity
Additional relevant MeSH terms:
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Brucellosis
Familial Mediterranean Fever
Hereditary Autoinflammatory Diseases
Fever
Body Temperature Changes
Gram-Negative Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Infections
Genetic Diseases, Inborn
Skin Diseases, Genetic
Skin Diseases