Clinical trial NCT02888860: Innate Immunity Gene Polymorphisms and Yeast Colonization
Official title: Analysis of TLRs and Lectin Gene Polymorphisms. Impact on Yeast Colonization in Hospitalized Patients and on Adaptive Response Against Yeast Glycans
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Critical Illness
Keywords: genetic susceptibility
candida infection
colonization
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2016-09-05
Enrollment: 2200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Critically ill patients

Brief summary: It is proposed to carry out the study in three medical or surgical intensive care units (ICU) in the CHRU, Lille, and the CHU, Besançon. In all patients admitted to these ICU (see Figure 2), a corrected index of colonisation (CIC) will be determined and blood samples will be taken for genotyping of the lectins MBL, Dectin-1 and Galectin-3 and for serology. Over the duration of hospitalisation (on average 28 days) and weekly, fungal colonisation will be assessed in all patients (according to the CIC), and antibodies to yeast glycans will be determined by a simultaneous multiparametric analysis involving several families of natural or synthetic antigens, and the detection of circulating antigens (mannan and β-1,3 glucan).

Detailed description: Determination of the CIC:

The CIC will be determined on admission and then once a week during hospitalisation. This will be carried out on a fixed day for all patients; we will avoid determining the CIC any closer than 2 days apart. It is not planned in this study to modify the therapeutic strategy of the ICU services. The strains isolated will be stored in glycerol solution at -80°C. The specimens for genetic and serological analysis will be stored centrally in a local mycology laboratory.

Genotyping of lectin genes and TLRs:

Two tubes containing 6 ml of blood in EDTA will be taken from each patient for extraction of DNA

Serological study, detection of antibodies to yeast glycans:

10 ml of whole blood will be taken from each patient on the day of inclusion and over the duration of hospitalisation (maximum total quantity of 40 ml). This will be done on a fixed day for all patients; we will avoid sampling any closer than 2 days apart.

Functional tests on peripheral blood mononuclear cells (PBMCs) Taking into account the fact that the results of genotyping will not be available in real time and the need to work with freshly collected cells, a group size of 50 patients in group 2 (negative CIC over the duration of hospitalisation) and 50 patients in group 3 (negative CIC at admission but positive at hospital discharge) will be analysed.

Stimulation tests will be carried out in the presence of whole yeasts or yeast extracts on sub-populations of cells isolated from 20 ml of peripheral blood in EDTA.

Eligibility criteria: Inclusion Criteria:

* Male or female patients, ≥18 years of age, admitted to medical or surgical ICU for a duration of \>48 h, irrespective of their colonisation status.

Exclusion Criteria:

* -Patient (or their representative) who refuses to participate in the study or to undergo the procedures required for the investigations (mycological sampling in order to determine the CIC, blood sampling for genotyping of DNA and for serology)
* Previous antifungal treatment (in the 15 days preceding admission to the ICU).
* A CIC value based on an insufficient number of sampled sites (\<6).
* Neutropenic patients
* Patients who are receiving immunosuppressants (transplanted, grafted...)
* Patients who do not have universal cover or Social Security cover

Primary outcomes:
measure: Frequency of polymorphisms
timeFrame: From date of inclusion until the last day hospital stay (at once a week)
Secondary outcomes:
measure: Genotyping of lectin genes and toll-like-receptors (TLRs)
timeFrame: From date of inclusion until the last day hospital stay (at once a week)
measure: Colonization index
timeFrame: at admission and weekly for at least two weeks after.
measure: Functional tests on peripheral blood mononuclear cells (PBMC)
timeFrame: at admission and weekly for at least two weeks after.
Other outcomes:
Locations:
city: Lille
country: France
facility: CHRU de Lille
state: Nord
city: Arras
country: France
facility: Centre hospitalier
city: Boulogne-sur-Mer
country: France
facility: Centre hosptialier
city: Lens
country: France
facility: CH Schaffner
city: Lomme
country: France
facility: Hôpital Saint-Philibert
city: Roubaix
country: France
facility: CH Victor Provo
Study officials:
affiliation: CHRU de Lille
name: Daniel Mathieu, Prof
role: PRINCIPAL_INVESTIGATOR
References: