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

Cystic Fibrosis Clinical Trial

— KAF-BIOTA  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05937815
• Other study ID #: CHUBX 2021/14
• Status: Recruiting
• Phase: N/A
• Start date: September 13, 2021
• Est. completion date: September 13, 2024

Study information

• Verified date: July 2023
• Source: University Hospital, Bordeaux
• Contact: Aurore Capelli, PhD
• Phone: 0557820877
• Email: aurore.capelli[@]chu-bordeaux.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 253
• Est. completion date: September 13, 2024
• Est. primary completion date: September 13, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

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)

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Procedure:
• Sample collection
collection of sputum, stool and blood samples at baseline, 6 months and 1 year after baseline

Locations

Country	Name	City	State
France	CHU de Bordeaux - CRCM pédiatrique	Bordeaux
France	CHU de Grenoble Alpes CRCM pédiatrique	Grenoble
France	CHRU de Lille CRCM Pédiatrique	Lille
France	CHU de Limoges CRCM Limousin	Limoges
France	Hospices Civils de Lyon Service de pédiatrie, allergologie et mucoviscidose	Lyon
France	AP-HM CRCM pédiatrique	Marseille
France	CHU de Montpellier	Montpellier
France	CHU de Nancy	Nancy
France	CHU de Nice	Nice
France	AP-HP CRCM Robert debré	Paris
France	AP-PH Hopital Cochin service de pédiatrie	Paris
France	APHP Hopital Necker	Paris
France	Fondation Ildys, Roscoff Centre Hélio Marin - Clinique "Mucoviscidose"	Roscoff
France	CHU de Rouen	Rouen
France	CHU de Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	composition of the digestive bacterial microbiota	composition of the digestive, bacterial microbiota, at 12 months of treatment	12 months after baseline (treatment initiation)
Secondary	composition of the pulmonary bacterial microbiota	composition of the pulmonary bacterialmicrobiota, at 12 months of treatment	12 months after baseline (treatment initiation)
Secondary	composition of the pulmonary bacterial microbiota	composition of the pulmonary bacterialmicrobiota at baseline	at baseline (treatment initiation)
Secondary	composition of the digestive fungal microbiota	composition of the digestive fungal microbiota, at 12 months of treatment	12 months after baseline (treatment initiation)
Secondary	composition of the digestive fungal microbiota	composition of the digestive fungal microbiota at baseline	at baseline (treatment initiation)
Secondary	composition of the pulmonary fungal microbiota	composition of the pulmonary fungal microbiota, at 12 months of treatment	12 months after baseline (treatment initiation)
Secondary	composition of the pulmonary fungal microbiota	composition of the pulmonary fungal microbiota at baseline	at baseline (treatment initiation)
Secondary	composition of the digestive, bacterial microbiota	composition of the digestive, bacterial microbiota at baseline	at baseline (treatment initiation)