NCT03565692

Brief Summary

n2015, VERTEX company - producing already KALYDECO (IVACAFTOR, VX-770) potentiator molecule that is recommended for the treatment of CF patients aged ≥ 6 y, with CFTR mutation altering the channel regulation (class III mutations) as G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549Nou S549R) -was allowed by the Federal Drug Administration (FDA) and European Medicines Agency (EMEA) for producing and using ivacaftor combination (such as lumacaftor/ ivacaftor initially, and more recently tezacaftor/ivacaftor, tezacaftor/ivacaftor/VX-659, tezacaftor/ivacaftor/VX-445 and tezacaftor/ivacaftor/VX-152) in clinical trials for patient with cystic fibrosis, according to age and mutation eligibility criteria. Since 2016, the French patients homozygous for the p.Phe508del mutation and older than 12 years are able to be treated with the association LUMACAFTOR-IVACAFTOR and this French authorization is being extended for 6-11 years old children (while the European Commission has already granted an extension of the Marketing Authorization for lumacaftor/ivacaftor to include 6-11 years old children with cystic fibrosis since January 2018). Patients treated by lumacaftor/ivacaftor (or other ivacaftor new combinations) are closely monitored according to criteria established by the working group "New Therapeutic Approaches" of the French Society Cystic fibrosis. This study is a phase IV observational trial for a period of 1 year. In this context, the team aims at initiating a comprehensive monitoring of the lung and gut mycobiota and microbiota evolution under LUMACAFTOR-IVACAFTOR (or other ivacaftor combinations) treatment. This project is directly linked to the monitoring of cystic fibrosis patients who begin treatment with LUMACAFTOR-IVACAFTOR (or other ivacaftor combinations) in France. The pro- and eukaryotic microbiota analysis is based on the secondary use of sputum and stool samples associated with several clinical data of CF patients under ivacaftor combinations and follow-up during the 1st year of therapy. According to the French law, Lum-Iva-Biota project is a non-interventional study. It aims at demonstrating that changes in the hydration of secretions at the pulmonary and intestinal levels related to LUMACAFTOR-IVACAFTOR therapy (or other new generation of ivacaftor combinations) promote a change in the lung and gut mycobiota and microbiota profiles which may achieve the characteristics of the "healthy type" (in terms of composition, richness and diversity).

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
250

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Jul 2018

Longer than P75 for all trials

Geographic Reach
1 country

8 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 31, 2018

Completed
21 days until next milestone

First Posted

Study publicly available on registry

June 21, 2018

Completed
10 days until next milestone

Study Start

First participant enrolled

July 1, 2018

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 28, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2023

Completed
Last Updated

April 10, 2020

Status Verified

April 1, 2020

Enrollment Period

4.7 years

First QC Date

May 31, 2018

Last Update Submit

April 9, 2020

Conditions

Cystic Fibrosis

Keywords

MicrobiomeMicrobiotaMycobiotaMycobiomeDeep-SequencingCystic Fibrosis

Outcome Measures

Primary Outcomes (1)

  • Change of specific bacterial and/or fungal pathogens

    Measure by conventional methods (history of microbial culture and GM assay) and particularly by metagenomic analysis of pulmonary pro- and eukaryotic microbiota.

    18 months

Secondary Outcomes (5)

  • Forced expiratory volume in 1 second (FEV1)

    Day 1

  • Forced expiratory volume (FEV1)

    6 Months

  • Forced expiratory volume (FEV1)

    12 Months

  • Change of specific bacterial and/or fungal pathogens

    12 months

  • Change of specific bacterial and/or fungal pathogens

    12 months

Study Arms (1)

Patients treated by LUMACAFTOR-IVACAFTOR

Patients treated by LUMACAFTOR-IVACAFTOR (or other ivacaftor combinations) Patients over 6 years who are currently able to benefit from LUMACAFTOR-IVACAFTOR (or other ivacaftor combinations) according the mutation eligibility criteria and for whom conventional microbiological analysis of sputum samples and stool will be collected during their follow-up after the treatment onset.

Biological: the lung mycobiota and microbiota profileBiological: the gut mycobiota and microbiota profile

Interventions

the lung mycobiota and microbiota profileBIOLOGICAL

All sputum samples will follow regarding mycological and metagenomic analyses as summarized : * Pre-analytical treatment combining pre-treatment with mucolytic agent and sonication action * Separation of the pellet and supernatant, stored at -20 ° C until testing * Galactomannan (GM) Assay on each sputum supernatant to correlate with Aspergillus colonization history * Targeted metagenomics of bacterial communities (based on 16S amplification) and of fungal community (based on ITS2 amplification) * Bioinformatic analysis of metagenomics raw data, correlation with bioclinical data of each patient, statistical analysis, and characterization of phenomena of co-evolution/co-exclusion according to evolutionary ecology concepts. * Pseudomonas aeruginosa load measured by qPCR

Patients treated by LUMACAFTOR-IVACAFTOR
the gut mycobiota and microbiota profileBIOLOGICAL

All stool samples will follow regarding mycological and metagenomic analyses as summarized : - Separation of the pellet and supernatant, stored at -20 ° C until testing - Targeted metagenomics of bacterial communities (based on 16S amplification) and of fungal community (based on ITS2 amplification) - Bioinformatic analysis of metagenomics raw data, correlation with bioclinical data of each patient, statistical analysis, and characterization of phenomena of co-evolution/co-exclusion according to evolutionary ecology concepts. - Measurement of inflammation.

Patients treated by LUMACAFTOR-IVACAFTOR

Eligibility Criteria

Age2 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

French patients with cystic fibrosis who start a treatment with an ivacaftor combination (lumacaftor/ivacaftor or new other combination) according to the age and mutations criteria in effect in France and monitored according to criteria established by the working group "New Therapeutic Approaches" of the French Society Cystic fibrosis.

You may qualify if:

  • CF patient treated with an ivacaftor combination (lumacaftor/ivacaftor or new generation combination) for a period of at least 1 year and managed by the National working group "New therapeutic approaches" under the National CF Observatory and who haven't expressed a non-opposition to the secondary use of their sputum and stool samples in the context on Lum-Iva-biota project.

You may not qualify if:

  • CF patient who stop ivacaftor combination treatment.
  • CF patient who doesn't want to participate anymore to Lum-Iva-Biota

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

CHU de Bordeaux - CRCM

Bordeaux, 33000, France

RECRUITING

Centre Hospitalier Universitaire Grenoble Alpes

Grenoble, 38000, France

RECRUITING

CHRU de Lille

Lille, 69000, France

NOT YET RECRUITING

Hospices Civils de Lyon

Lyon, 69000, France

NOT YET RECRUITING

Assistance publique Hôpitaux Marseille

Marseille, 13000, France

RECRUITING

Assistance Publique Hôpitaux de paris

Paris, 75000, France

RECRUITING

Hôpital FOCH

Suresnes, 92150, France

RECRUITING

CHU de Toulouse

Toulouse, 31000, France

RECRUITING

Related Publications (1)

  • Enaud R, Lussac-Sorton F, Charpentier E, Velo-Suarez L, Guiraud J, Bui S, Fayon M, Schaeverbeke T, Nikolski M; LumIvaBiota Study Group; Burgel PR, Hery-Arnaud G, Delhaes L. Effects of Lumacaftor-Ivacaftor on Airway Microbiota-Mycobiota and Inflammation in Patients with Cystic Fibrosis Appear To Be Linked to Pseudomonas aeruginosa Chronic Colonization. Microbiol Spectr. 2023 Mar 27;11(2):e0225122. doi: 10.1128/spectrum.02251-22. Online ahead of print.

    PMID: 36971560DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Human sputum and stool specimen

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic DiseasesDigestive System DiseasesLung DiseasesRespiratory Tract DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesInfant, Newborn, Diseases

Study Officials

  • Laurence DELHAES, MD,PhD

    University Hospital, Bordeaux

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Laurence DELHAES, MD, PhD

CONTACT

+335 56 79 56 67laurence.delhaes@chu-bordeaux.fr

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
RETROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 31, 2018

First Posted

June 21, 2018

Study Start

July 1, 2018

Primary Completion

February 28, 2023

Study Completion

February 28, 2023

Last Updated

April 10, 2020

Record last verified: 2020-04

Data Sharing

IPD Sharing
Will not share

Locations

FR(8)