Innate Immunity Gene Polymorphisms and Yeast Colonization

NCT ID: NCT02888860

Last Updated: 2022-11-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 2200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-01-03
• Study Completion Date: 2021-01-03

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.

Conditions

Critical Illness

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Group 1

Patients with candidemia

No interventions assigned to this group

Group 2

Patients without colonization during follow up

No interventions assigned to this group

Group 3

Patients without colonization at admission, with subsequent colonization during hospitalization

No interventions assigned to this group

Group

Patients colonized at admission, and during the whole hospitalization

No interventions assigned to this group

Group 5

Patients who develop colonization during hospitalization and become negative at discharge

No interventions assigned to this group

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, France

OTHER_GOV

Sponsor Role: collaborator

University Hospital, Lille

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel Mathieu, Prof

Role: PRINCIPAL_INVESTIGATOR

CHRU de Lille

Locations

CHRU de Lille

Lille, Nord, France

Centre hospitalier

Arras, , France

Centre hosptialier

Boulogne-sur-Mer, , France

CH Schaffner

Lens, , France

Hôpital Saint-Philibert

Lomme, , France

CH Victor Provo

Roubaix, , France

Countries

France

Other Identifiers

2011_33

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2012-A00485-38

Identifier Type: OTHER

Identifier Source: secondary_id

2011_33

Identifier Type: -

Identifier Source: org_study_id