Intestine-lung Axis of Cystic Fibrosis Patients Treated With the Combination Elexacaftor/Tezacaftor/Ivacaftor (KAF-BIOTA)

July 7, 2023 updated by: University Hospital, Bordeaux

Monitoring of the Intestine-lung Axis of Cystic Fibrosis Patients Treated With the Combination Elexacaftor/Tezacaftor/Ivacaftor: Study of the Pulmonary and Gut Microbiota and Inflammation

Cystic fibrosis is a systemic disease, which affects in particular the respiratory and digestive systems of patients, sites of chronic inflammation.

A new combination of elexacaftor/tezacaftor/ivacaftor has proven its efficacy for the treatment of patients aged 12 years and over with two F508del mutations or a so-called "minimal function" mutation associated with one F508del mutation. European marketing authorization was obtained in August 2020 and access in France should therefore arrive soon. Given that this treatment targets new mutations and that the efficacy seems greater than with LUM/IVA, it is important to assess its impact on the microbiota and the pulmonary and digestive inflammation of patients.

It is therefore a question of taking advantage of the experience of the Lum-Iva-Biota cohort, and the validated and operational sample circuit established in the various participating centers to set up a biological collection for the collection and storage of sputum and stools of patients during the first year of treatment with elexacaftor/tezacaftor/ivacaftor, in order to study the effect of treatment on the lung and digestive microbiota/mycobiota and inflammation.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Cystic fibrosis is a systemic disease, which affects in particular the respiratory and digestive systems of patients, sites of chronic inflammation. It has also been shown that in these patients, the pulmonary and intestinal microbiota were distinct from those of healthy subjects and that the progression of the disease was associated with alterations in these microbiota. In addition, numerous data suggest the existence of an "intestinal-lung axis" and therefore encourage studying these two organs in parallel and not separately.

The management of cystic fibrosis has been marked in recent years by the appearance of CFTR modulators, in particular the combination lumacaftor/ivacaftor (LUM/IVA) (for patients homozygous F508del). The criteria for evaluating the efficacy of these treatments are based on the change in FEV (forced expiratory volume in 1 second), the number of exacerbations, body mass index or quality of life. However, it is essential to be able to document the effect of these treatments on the lung and digestive microbiota and inflammation. Since 2016, we have set up the national "Lum-Iva-Biota" cohort and have been able to show that the effect of LUM/IVA on the pulmonary microbiota was more marked in patients not previously colonized with P. aeruginosa.

A new combination of elexacaftor/tezacaftor/ivacaftor has proven its efficacy for the treatment of patients aged 12 years and over with two F508del mutations or a so-called "minimal function" mutation associated with one F508del mutation. European marketing authorization was obtained in August 2020 and access in France should therefore arrive soon. Given that this treatment targets new mutations and that the efficacy seems greater than with LUM/IVA, it is important to assess its impact on the microbiota and the pulmonary and digestive inflammation of patients.

It is therefore a question of taking advantage of the experience of the Lum-Iva-Biota cohort, and the validated and operational sample circuit established in the various participating centers to set up a biological collection for the collection and storage of sputum and stools of patients during the first year of treatment with elexacaftor/tezacaftor/ivacaftor, in order to study the effect of treatment on the lung and digestive microbiota/mycobiota and inflammation.

Study Type

Interventional

Enrollment (Estimated)

253

Phase

  • Not Applicable

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • France
      • Bordeaux, France
        • Recruiting
        • CHU de Bordeaux - CRCM pédiatrique
        • Contact:
          • Raphaël ENAUD
      • Grenoble, France
        • Recruiting
        • CHU de Grenoble Alpes CRCM pédiatrique
        • Contact:
          • Catherine LLerena
      • Lille, France
        • Recruiting
        • CHRU de Lille CRCM Pédiatrique
        • Contact:
          • Nathalie Wizla
      • Limoges, France
        • Recruiting
        • CHU de Limoges CRCM Limousin
        • Contact:
          • Alexandra Masson-Rouchaud
      • Lyon, France
        • Recruiting
        • Hospices Civils de Lyon Service de pédiatrie, allergologie et mucoviscidose
        • Contact:
          • Philippe REIX
      • Marseille, France
        • Recruiting
        • AP-HM CRCM pédiatrique
        • Contact:
          • Jean-Christophe DUBUS
      • Montpellier, France
        • Recruiting
        • CHU de Montpellier
        • Contact:
          • Raphaël CHIRON
      • Nancy, France
        • Recruiting
        • CHU de NANCY
        • Contact:
          • Aurélie Tatopoulos
      • Nice, France
        • Recruiting
        • CHU de Nice
        • Contact:
          • Sylvie LEROY
      • Paris, France
        • Recruiting
        • AP-HP CRCM Robert debré
        • Contact:
          • Michèle GERARDIN
      • Paris, France
        • Recruiting
        • AP-PH Hopital Cochin service de pédiatrie
        • Contact:
          • Pierre-Régis BURGEL
      • Paris, France
        • Recruiting
        • APHP Hôpital Necker
        • Contact:
          • Isabelle Sermet Gaudelus
      • Roscoff, France
        • Recruiting
        • Fondation Ildys, Roscoff Centre Hélio Marin - Clinique "Mucoviscidose"
        • Contact:
          • Sophie RAMEL
      • Rouen, France
        • Recruiting
        • CHU de ROUEN
        • Contact:
          • Hélène Morisse Pradier
      • Toulouse, France
        • Recruiting
        • CHU de Toulouse
        • Contact:
          • Marie Mittaine

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

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • To have cystic fibrosis (sweat test > 60 mmol/l);
  • Carrier of at least one DeltaF508 mutation;
  • Be followed in the current care by a participant in the CRCM study;
  • Start treatment with elexacaftor/tezacaftor/ivacaftor in routine care, according to the indications in the Marketing Authorization at the time of inclusion;
  • Be of the age specified in the marketing authorization in force;
  • Person affiliated or beneficiary of a social security scheme;
  • Consent obtained by the patient (for adult patients) or the holders of parental authority (for minor patients) before any examination required by the research and oral and/or written consent by the participant (depending on his or her age) .
  • Patient agreeing to take part in cohort follow-up studies of patients treated with elexacaftor/tezacaftor/ivacaftor, included in the French cystic fibrosis register (cf. Study by Pr BURGEL and/or MODUL CF).

Exclusion Criteria:

  • Start of treatment with elexacaftor/tezacaftor/ivacaftor as part of a therapeutic trial.
  • Patient already on CFTR modulator (including lumacaftor/ivacaftor)
  • Vulnerable people (pregnant woman, person under guardianship/curators)

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

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: patients with cystic fibrosis
patients with cystic fibrosis before and one year after the start of treatment with elexacaftor/tezacaftor/ivacaftor
Procedure: Sample collection
collection of sputum, stool and blood samples at baseline, 6 months and 1 year after baseline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
composition of the digestive bacterial microbiota
Time Frame: 12 months after baseline (treatment initiation)
composition of the digestive, bacterial microbiota, at 12 months of treatment
12 months after baseline (treatment initiation)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
composition of the pulmonary bacterial microbiota
Time Frame: 12 months after baseline (treatment initiation)
composition of the pulmonary bacterialmicrobiota, at 12 months of treatment
12 months after baseline (treatment initiation)
composition of the pulmonary bacterial microbiota
Time Frame: at baseline (treatment initiation)
composition of the pulmonary bacterialmicrobiota at baseline
at baseline (treatment initiation)
composition of the digestive fungal microbiota
Time Frame: 12 months after baseline (treatment initiation)
composition of the digestive fungal microbiota, at 12 months of treatment
12 months after baseline (treatment initiation)
composition of the digestive fungal microbiota
Time Frame: at baseline (treatment initiation)
composition of the digestive fungal microbiota at baseline
at baseline (treatment initiation)
composition of the pulmonary fungal microbiota
Time Frame: 12 months after baseline (treatment initiation)
composition of the pulmonary fungal microbiota, at 12 months of treatment
12 months after baseline (treatment initiation)
composition of the pulmonary fungal microbiota
Time Frame: at baseline (treatment initiation)
composition of the pulmonary fungal microbiota at baseline
at baseline (treatment initiation)
composition of the digestive, bacterial microbiota
Time Frame: at baseline (treatment initiation)
composition of the digestive, bacterial microbiota at baseline
at baseline (treatment initiation)

Collaborators and Investigators

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

Sponsor

University Hospital, Bordeaux

Investigators

  • Principal Investigator: Raphaël Enaud, MDPhD, University Hospital, Bordeaux

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)

September 13, 2021

Primary Completion (Estimated)

September 13, 2023

Study Completion (Estimated)

September 13, 2024

Study Registration Dates

First Submitted

June 27, 2023

First Submitted That Met QC Criteria

July 7, 2023

First Posted (Actual)

July 10, 2023

Study Record Updates

Last Update Posted (Actual)

July 10, 2023

Last Update Submitted That Met QC Criteria

July 7, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUBX 2021/14

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.

Clinical Trials on Cystic Fibrosis

Clinical Trials on Sample collection

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Hungary

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe