Markers of Pulmonary Dysbiosis Associated With Exacerbation in Patients Followed for Cystic Fibrosis (DYSBIOSE-CF)

March 17, 2020 updated by: University Hospital, Grenoble

The aim objective is to identify markers of bacterial, viral and fungal pulmonary dysbiosis, associated with the occurrence of exacerbation in patients followed for cystic fibrosis.

The primary endpoint is the association between a modification of at least 10% of the relative abundance of a bacterial phylum (Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, Fusobacteria) or fungal (ascomycetes / hemiascomycetes, basidiomycetes, zygomycetes), or viral, and the occurrence of exacerbations over a period of 12 months.

Study Overview

Status

Unknown

Conditions

Detailed Description

Therapeutic advances and the organization of care within the "CRCM" have led to an overall improvement in the management of cystic fibrosis. The protein therapies that have marked this progression only target certain genes and concern a small number of patients. The morbidity, mortality and social cost of cystic fibrosis are still considerable. Exacerbations modulate the prognosis of the disease.

We are interested in dysbiosis, which is the association of an imbalance in the composition and functions of commensal complex microbial communities and an alteration of the immune response of the host. It is involved in the development of chronic pulmonary pathologies such as cystic fibrosis Pulmonary microbiota and host responses mutually influence each other, and evidence suggests that changes in microbiota-host interactions play a major role in the evolution of chronic respiratory diseases. The response of the host may be partially measured by protein markers of inflammation or metabolites regulating inflammation (tryptophan metabolites).

Most microbiome studies focus on the bacterial microbiota, while other microorganisms such as fungi and viruses represent an important cofactor in the degradation of respiratory function. Viral dysbiosis probably plays a role in the appearance of exacerbation.

Among the few studies incorporating fungal risk, very few have considered the role of Pneumocystis jirovecii (PCJ). This non-culturable species was found in 12.5% of patients with cystic fibrosis and possibly associated with exacerbations. We will prospectively follow a cohort of cystic fibrosis patients by collecting clinical and microbiological data on various samples (exhaled air condensate (EAC), sputum and serum) on a quarterly basis and during episodes of exacerbations.

Our project will verify the hypothesis of a correlation between the microbiota, inflammation, and the production of metabolites regulating inflammation (dysbiosis), but also to determine what is the initial biological process leading to the exacerbation: dysbiosis induced by variation of the microbiota or dysbiosis induced by modification of host defense systems. In addition, unlike studies in this area, we will be interested in the bacterial, viral and fungal microbiota.

Study Type

Observational

Enrollment (Anticipated)

30

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
      • Grenoble, France
        • Recruiting
        • University Hospital Grenoble
        • Contact:
          • Boubou Camara

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

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients followed for cystic fibrosis are followed in "CRCM". The selection of patients will be done by the various investigating physicians during consultations, day hospitals or admission to the hospital for differents reasons. This research protocol fits as much as possible in the context of routine care, particularly with respect to the rhythmicity of the various visits

Description

Inclusion Criteria:

  • Patients with cystic fibrosis
  • Patient agreeing to participate in the study
  • Patient with at least 2 exacerbations in the year prior to inclusion (2 antimicrobial treatments at home or in hospital during the last 12 months)
  • Patient or legal guardian of the patient able to read and understand the procedure and able to express his / her consent for the study protocol
  • Stable patients, away from exacerbation (at 4 weeks from the beginning of exacerbation, found to be resolved by the investigator)
  • Patient affiliated to the social security scheme

Exclusion Criteria:

  • Patients who can not read
  • Patients opposing the use of their medical data
  • Unstable patients, less than one month from the beginning of the exacerbation
  • Pregnant or lactating women
  • Adult patient under curatorship or tutorship, person deprived of liberty
  • Patient awaiting transplant or non-invasive ventilation in chronic
  • Patient can not be contacted in case of emergency

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

  • Observational Models: Other
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification of markers of bacterial fungal and viral dysbiosis associated with the occurrence of exacerbation in patients followed for cystic fibrosis.
Time Frame: One year
Association between a modification of at least 10% of the relative abundance of a bacterial phylum (Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, Fusobacteria) or fungal (ascomycetes / hemiascomycetes, basidiomycetes, zygomycetes), or viral and the occurrence of exacerbations over a period of 12 months.
One year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of the influence of the modification of the relative abundance of different bacterial, viral and fungal taxa, on the occurrence of exacerbations
Time Frame: One year
Association between a change of at least 10% in the relative abundance of a bacterial or fungal taxum, and the occurrence of exacerbations over a 12-month period
One year
Evaluation of the influence of the global biodiversity of the bacterial and fungal pulmonary microbiome on the occurrence of exacerbations.
Time Frame: One year
Association between a modification of two indices (Faith's Phylogenetic Diversity and Shannon's B H index) and the occurrence of exacerbations over a 12-month period
One year
Association between markers of respiratory function and the relative abundance of different bacterial, viral and fungal phyla and taxa
Time Frame: One year
Correlation between FEV1 on the one hand, and changes in the relative abundance of bacterial, viral and fungal phyla and taxa on the other hand
One year
Evaluation of the link between an increase in inflammatory markers and the occurrence of exacerbations
Time Frame: One year
Association between serum concentrations of serum inflammatory cytokines and the occurrence of exacerbations over a period of 12 months
One year
Association between markers of respiratory function and serum inflammatory markers
Time Frame: One year
Correlation between FEV 1 and CV on the one hand, and different serum inflammatory serum cytokines
One year
Comparison of two types of sputum samples versus expired air condensate to evaluate the pulmonary microbiome in patients with cystic fibrosis
Time Frame: One year
Comparison of relative abundance of phyla of interest in sputum vs exhaled air condensate
One year
Evaluation of the interactions between the different taxa of the pulmonary microbiome of patients with cystic fibrosis
Time Frame: One year
Network co-occurrence (network interference) of the relative abundance of different bacterial and fungal taxa
One year
Evaluation of the impact of treatments administered during exacerbations on the pulmonary microbiome, in particular on changes in the relative abundance and diversity of different bacterial, viral and fungal taxa
Time Frame: One year
Comparison of the relative abundance of the phyla of interest and the diversity of the microbiome (Faith's Phylogenetic Diversity and Shannon B H index) in the presence or absence of antimicrobial and anti-inflammatory steroid treatments
One year

Collaborators and Investigators

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

Sponsor

University Hospital, Grenoble

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)

October 2, 2018

Primary Completion (Anticipated)

September 1, 2021

Study Completion (Anticipated)

December 1, 2021

Study Registration Dates

First Submitted

June 14, 2018

First Submitted That Met QC Criteria

June 14, 2018

First Posted (Actual)

June 26, 2018

Study Record Updates

Last Update Posted (Actual)

March 18, 2020

Last Update Submitted That Met QC Criteria

March 17, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 38RC17.317

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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