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

NCT ID: NCT05937815

Last Updated: 2023-07-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 253 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-13
• Study Completion Date: 2024-09-13

Brief Summary

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.

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.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

patients with cystic fibrosis

patients with cystic fibrosis before and one year after the start of treatment with elexacaftor/tezacaftor/ivacaftor

Group Type: EXPERIMENTAL

Sample collection

Intervention Type: PROCEDURE

collection of sputum, stool and blood samples at baseline, 6 months and 1 year after baseline

Interventions

Sample collection

collection of sputum, stool and blood samples at baseline, 6 months and 1 year after baseline

Intervention Type: PROCEDURE

Eligibility Criteria

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)

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Bordeaux

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Raphaël Enaud, MDPhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Bordeaux

Locations

CHU de Bordeaux - CRCM pédiatrique

Bordeaux, , France

Site Status: RECRUITING

CHU de Grenoble Alpes CRCM pédiatrique

Grenoble, , France

Site Status: RECRUITING

CHRU de Lille CRCM Pédiatrique

Lille, , France

Site Status: RECRUITING

CHU de Limoges CRCM Limousin

Limoges, , France

Site Status: RECRUITING

Hospices Civils de Lyon Service de pédiatrie, allergologie et mucoviscidose

Lyon, , France

Site Status: RECRUITING

AP-HM CRCM pédiatrique

Marseille, , France

Site Status: RECRUITING

CHU de Montpellier

Montpellier, , France

Site Status: RECRUITING

CHU de Nancy

Nancy, , France

Site Status: RECRUITING

CHU de Nice

Nice, , France

Site Status: RECRUITING

AP-HP CRCM Robert debré

Paris, , France

Site Status: RECRUITING

AP-PH Hopital Cochin service de pédiatrie

Paris, , France

Site Status: RECRUITING

APHP Hopital Necker

Paris, , France

Site Status: RECRUITING

Fondation Ildys, Roscoff Centre Hélio Marin - Clinique "Mucoviscidose"

Roscoff, , France

Site Status: RECRUITING

CHU de Rouen

Rouen, , France

Site Status: RECRUITING

CHU de Toulouse

Toulouse, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Aurore Capelli, PhD

Role: CONTACT

aurore.capelli@chu-bordeaux.fr

0557820877

Raphaël Enaud, MDPhD

Role: CONTACT

raphael.enaud@chu-bordeaux.fr

05 56 79 98 24

Facility Contacts

Raphaël ENAUD

Role: primary

Catherine LLerena

Role: primary

Nathalie Wizla

Role: primary

Alexandra Masson-Rouchaud

Role: primary

Philippe Reix

Role: primary

Jean-Christophe Dubus

Role: primary

Raphael CHIRON

Role: primary

Aurélie Tatopoulos

Role: primary

Sylvie Leroy

Role: primary

Michèle GERARDIN

Role: primary

Pierre-Régis BURGEL

Role: primary

Isabelle Sermet Gaudelus

Role: primary

Sophie RAMEL

Role: primary

Hélène Morisse Pradier

Role: primary

Marie Mittaine

Role: primary

Other Identifiers

CHUBX 2021/14

Identifier Type: -

Identifier Source: org_study_id