Clinical trial NCT05937815: Intestine-lung Axis of Cystic Fibrosis Patients Treated With the Combination Elexacaftor/Tezacaftor/Ivacaftor
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cystic Fibrosis
Keywords: elexacaftor/tezacaftor/ivacaftor
lung and digestive microbiota and inflammation
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2023-07-10
Enrollment: 253
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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)

Primary outcomes:
measure: composition of the digestive bacterial microbiota
timeFrame: 12 months after baseline (treatment initiation)
Secondary outcomes:
measure: composition of the pulmonary bacterial microbiota
timeFrame: 12 months after baseline (treatment initiation)
measure: composition of the pulmonary bacterial microbiota
timeFrame: at baseline (treatment initiation)
measure: composition of the digestive fungal microbiota
timeFrame: 12 months after baseline (treatment initiation)
measure: composition of the digestive fungal microbiota
timeFrame: at baseline (treatment initiation)
measure: composition of the pulmonary fungal microbiota
timeFrame: 12 months after baseline (treatment initiation)
measure: composition of the pulmonary fungal microbiota
timeFrame: at baseline (treatment initiation)
measure: composition of the digestive, bacterial microbiota
timeFrame: at baseline (treatment initiation)
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux - CRCM pédiatrique
city: Grenoble
country: France
facility: CHU de Grenoble Alpes CRCM pédiatrique
city: Lille
country: France
facility: CHRU de Lille CRCM Pédiatrique
city: Limoges
country: France
facility: CHU de Limoges CRCM Limousin
city: Lyon
country: France
facility: Hospices Civils de Lyon Service de pédiatrie, allergologie et mucoviscidose
city: Marseille
country: France
facility: AP-HM CRCM pédiatrique
city: Montpellier
country: France
facility: CHU de Montpellier
city: Nancy
country: France
facility: CHU de Nancy
city: Nice
country: France
facility: CHU de Nice
city: Paris
country: France
facility: AP-HP CRCM Robert debré
city: Paris
country: France
facility: AP-PH Hopital Cochin service de pédiatrie
city: Paris
country: France
facility: APHP Hopital Necker
city: Roscoff
country: France
facility: Fondation Ildys, Roscoff Centre Hélio Marin - Clinique "Mucoviscidose"
city: Rouen
country: France
facility: CHU de Rouen
city: Toulouse
country: France
facility: CHU de Toulouse
Study officials:
affiliation: University Hospital, Bordeaux
name: Raphaël Enaud, MDPhD
role: PRINCIPAL_INVESTIGATOR
References: