Droplet Digital PCR and PCR-free BIOSensors for the Detection of Resistance-associated SNPs in Pneumocystis Jirovecii (DDBIOS)

August 8, 2024 updated by: University Hospital, Brest
The main objective of the proposed research is to identify Pneumocystis jirovecii mutant strains on 4 genes encoding therapeutic targets such as dihydropteroate synthase (DHPS), dihydrofolate reductase (DHFR), cytochrome b (CYB), inosine-5'-monophosphate dehydrogenase (IMPDH) and therefore to assess the prevalence of potentially resistant strains in patients infected with P. jirovecii.

Study Overview

Status

Active, not recruiting

Conditions

Detailed Description

Pneumocystis jirovecii (P. jirovecii) is an opportunistic pathogenic fungus responsible for pulmonary infection or Pneumocystis pneumonia (PCP) in immunocompromised patients. There is currently no system for its in vitro culture. The diagnostic methods used are mainly based on molecular biology techniques which also allow the detection and analysis of single nucleotide polymorphisms (SNPs), particularly at the level of genes coding for the targets of molecules widely used in the prevention and treatment of PCP. These SNPs may represent missense mutations potentially associated with treatment resistance. They may result from exposure of patients to these treatments before the development of P. jirovecii infection. However, data concerning the prevalence of these mutations remains scarce, particularly in France. Methods for detecting these mutations based on PCR followed by DNA sequencing have limitations in terms of sensitivity. The evaluation of new, more sensitive and rapid tools for the detection and characterization of pathogens in this context is necessary.

The main objective of the proposed research is to identify P. jirovecii mutant strains on 4 genes encoding therapeutic targets such as dihydropteroate synthase (DHPS), dihydrofolate reductase (DHFR), cytochrome b (CYB), inosine-5'-monophosphate dehydrogenase (IMPDH) and therefore to assess the prevalence of potentially resistant strains in patients infected with P. jirovecii.

The secondary objectives are:

  • to determine the factors associated (e.g. exposure to treatments) with mutant P. jirovecii strains
  • to determine the impact of mutations on the effectiveness of anti-Pneumocystis treatment (e.g. favorable vs. unfavorable evolution of the infection)
  • to evaluate two methods - digital droplet PCR and biosensors without PCR - for the detection and characterization of mutations associated with resistance in Pneumocystis jirovecii

Study Type

Observational

Enrollment (Estimated)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Brest, France, 29609
        • CHU Brest

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients in whom P. jirovecii was detected in a pulmonary sample (bronchoalveolar lavage, sputum, bronchial aspiration, oropharyngeal rinse, nasopharyngeal sample) can be included in the study

Description

Inclusion Criteria:

  • Patients in whom P. jirovecii was detected in a pulmonary sample (bronchoalveolar lavage, sputum, bronchial aspiration, oropharyngeal rinse, nasopharyngeal sample)
  • No opposition
  • Patient affiliated to a social security system

Exclusion Criteria:

  • Patients under legal protection (guardianship, curatorship)
  • Refusal to participate

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Presence of specific strains of Pneumocystis jirovecii potentially resistant to treatments in patients infected with this fungus
Time Frame: at inclusion
Four genes encoding therapeutic targets such as dihydropteroate synthase (DHPS), dihydrofolate reductase (DHFR), cytochrome b (CYB), inosine-5'-monophosphate dehydrogenase (IMPDH) will be amplified and sequenced to detect single nucleotide polymorphisms (Single Nucleotide Polymorphism, SNP), in particular those potentially linked to resistance to anti-Pneumocystis treatments.
at inclusion

Secondary Outcome Measures

Outcome Measure
Time Frame
to determine the factors associated (e.g. exposure to treatments) with P. jirovecii mutant strains
Time Frame: at inclusion
at inclusion

Other Outcome Measures

Outcome Measure
Time Frame
to determine the impact of mutations on the effectiveness of anti-Pneumocystis treatment (e.g. favorable vs. unfavorable evolution of the infection)
Time Frame: 1 month and 3 month
1 month and 3 month
to evaluate two methods - digital droplet PCR and biosensors without PCR - for the detection and characterization of mutations associated with resistance in Pneumocystis jirovecii
Time Frame: at inclusion
at inclusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Brest

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

May 22, 2024

First Submitted That Met QC Criteria

May 22, 2024

First Posted (Actual)

May 29, 2024

Study Record Updates

Last Update Posted (Actual)

August 9, 2024

Last Update Submitted That Met QC Criteria

August 8, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 29BRC24.0085 - DDBIOS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All collected data that underlie results in a publication

IPD Sharing Time Frame

Data will be available beginning three years and ending fifteen years following the final study report completion

IPD Sharing Access Criteria

Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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