Clincosm LogoSign in Get a demo

IMPDH: Specific Genotypes/Phenotypes of Pneumocystis Jirovecii in Solid Organ Transplant Recipients: Potential Involvement of Mycophenolic Acid

Sponsor
University Hospital, Brest (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05452148
Collaborator
(none)
100
Enrollment
12
Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

To determine the presence of IMDPH mutants of Pneumocystis jirovecii in solid organ transplant recipient with prior exposition to mycophenolic acid.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    Mycophenolic acid (MPA) targets inosine 5'-monophosphate dehydrogenase (IMPDH) of human lymphocytes. It is used as an immunosuppressant to prevent rejection in solid organ transplant (SOT) recipients who are otherwise at risk for Pneumocystis pneumonia (PCP). We recently hypothesized that MPA exerts selective pressure on Pneumocystis given the in vitro antifungal activity of this drug on other fungi. In a single center study, we identified a missense mutation G1020A in the impdh gene, corresponding to an amino acid change Ala261Thr in IMPDH protein, among Pneumocystis isolates from MPA-treated SOT recipients. Considering that the IMPDH of MPA-resistant Candida albicans isolates harbors Thr at the analogous position, this mutation was considered to be a marker of Pneumocystis strain selection related to MPA exposure.

    The aim of this study is to strengthen these preliminary results with data from a large multicenter study.

    The study will be conducted in 26 centers in France. About one hundred patients with PCP will be enrolled. Pneumocystis isolates from SOT recipients exposed to MPA and from control patients (non-SOT recipients, not exposed to MPA) will be examined.The analysis of the impdh gene was combined with a multilocus sequence typing (MLST) method (mtLSUrRNA, cytochrome b and superoxide dismutase genes) characterized by a high discriminatory power.

    The expected results may show the presence of the G1020A mutation (Ala261Thr) in SOT recipients exposed to MPA and in none of the control patients not exposed to MPA. This mutation will be significantly associated with MPA exposure. It could also be associated with a specific multilocus genotype in SOT patients and none of the control patients.

    The study will confirm that the G1020A mutation (Ala261Thr) represents the signature of MPA exposure. The results of the analysis of the impdh gene combined with the MLST will highlight the selection under MPA pressure of specific strains of Pneumocystis, which circulate in the population of SOT recipients.

    Study Design

    Study Type:
    Observational
    Anticipated Enrollment :
    100 participants
    Observational Model:
    Case-Control
    Time Perspective:
    Retrospective
    Official Title:
    Emergence of Specific Genotypes/Phenotypes of Pneumocystis Jirovecii in Solid Organ Transplant Recipients: Potential Involvement of Mycophenolic Acid
    Anticipated Study Start Date :
    Jul 25, 2022
    Anticipated Primary Completion Date :
    Jul 25, 2023
    Anticipated Study Completion Date :
    Jul 25, 2023

    Outcome Measures

    Primary Outcome Measures

    1. Presence of Pneumocystis IMPDH gene mutant or not [At patient enrollment]

      The main biological parameter which will be measured will be the positive or negative result for the detection of Pneumocystis IMPDH gene mutant

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • = 18 years old with PCP diagnoses, organ transplant recipient or not, acceptation to participate

    Exclusion Criteria:
    • < 18 years old, no acceptation to participate

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • University Hospital, Brest

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University Hospital, Brest
    ClinicalTrials.gov Identifier:
    NCT05452148
    Other Study ID Numbers:
    • IMPDH ( 29BRC22.0106)
    First Posted:
    Jul 11, 2022
    Last Update Posted:
    Jul 11, 2022
    Last Verified:
    Jul 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by University Hospital, Brest
    Pneumocystis jirovecii
    IMPDH
    Genetic variant
    Additional relevant MeSH terms:
    Pneumonia, Pneumocystis

    Study Results

    No Results Posted as of Jul 11, 2022