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Lum-Iva-biota: Exploring the Respiratory Mycobiota and Microbiota Profile in French CF Patients Taking Lumacaftor-Ivacaftor (Lum-Iva-Biota)

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ClinicalTrials.gov Identifier: NCT03565692
Recruitment Status : Recruiting
First Posted : June 21, 2018
Last Update Posted : April 10, 2020
Sponsor:
Collaborator:
Societe Francaise de la Mucoviscidose
Information provided by (Responsible Party):
University Hospital, Bordeaux

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).


Condition or disease Intervention/treatment
Cystic Fibrosis Biological: the lung mycobiota and microbiota profile Biological: the gut mycobiota and microbiota profile

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Study Type : Observational
Estimated Enrollment : 250 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Lum-Iva-biota: Exploring the Respiratory Mycobiota and Microbiota Profile in French CF Patients Taking Lumacaftor-Ivacaftor
Actual Study Start Date : July 1, 2018
Estimated Primary Completion Date : February 28, 2023
Estimated Study Completion Date : February 28, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis
Drug Information available for: Ivacaftor

Group/Cohort Intervention/treatment
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 profile

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

Biological: the gut mycobiota and microbiota profile
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.




Primary Outcome Measures :
  1. Change of specific bacterial and/or fungal pathogens [ Time Frame: 18 months ]
    Measure by conventional methods (history of microbial culture and GM assay) and particularly by metagenomic analysis of pulmonary pro- and eukaryotic microbiota.


Secondary Outcome Measures :
  1. Forced expiratory volume in 1 second (FEV1) [ Time Frame: Day 1 ]
    Difference between the amount of air exhaled may be measured during the first second

  2. Forced expiratory volume (FEV1) [ Time Frame: 6 Months ]
    Difference between the amount of air exhaled may be measured during the first second

  3. Forced expiratory volume (FEV1) [ Time Frame: 12 Months ]
    Difference between the amount of air exhaled may be measured during the first second

  4. Change of specific bacterial and/or fungal pathogens [ Time Frame: 12 months ]
    Measure by conventional methods (history of microbial culture and GM assay) and particularly by metagenomic analysis of lung pro- and eukaryotic microbiota.

  5. Change of specific bacterial and/or fungal pathogens [ Time Frame: 12 months ]
    Measure by metagenomic analysis of gut pro- and eukaryotic microbiota.


Biospecimen Retention:   Samples Without DNA
Human sputum and stool specimen


Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-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.
Criteria

Inclusion Criteria:

  • CF Patient's ability to expectorate at inclusion time
  • 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.

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03565692


Contacts
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Contact: Laurence DELHAES, MD, PhD +335 56 79 56 67 laurence.delhaes@chu-bordeaux.fr

Locations
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France
CHU de Bordeaux - CRCM Recruiting
Bordeaux, France, 33000
Contact: Mickael FAYON, MD,PhD       mickael.fayon@chu-bordeaux.fr   
Principal Investigator: Mickael FAYON, MD,PhD         
Sub-Investigator: Patrick BERGER, MD,PhD         
Sub-Investigator: Raphael ENAUD, MD         
Centre Hospitalier Universitaire Grenoble Alpes Recruiting
Grenoble, France, 38000
Contact: Catherine Llerena, MD       CLlerena@chu-grenoble.fr   
Principal Investigator: Catherine Llerena, MD         
Sub-Investigator: Boubou Camara, MD         
CHRU de Lille Not yet recruiting
Lille, France, 69000
Contact: Nathalie Wizla, MD       nathalie.wizla@chru-lille.fr   
Principal Investigator: Nathalie Wizla, MD         
Sub-Investigator: Anne Prévotat, MD         
Hospices Civils de Lyon Not yet recruiting
Lyon, France, 69000
Contact: Philippe Reix, MD       philippe.reix@chu-lyon.fr   
Principal Investigator: Philippe Reix, MD         
Assistance publique Hôpitaux Marseille Recruiting
Marseille, France, 13000
Contact: Jean Christophe Dubus, MD,PhD       JeanChristophe.DUBUS@ap-hm.fr   
Principal Investigator: Jean Christophe Dubus, MD,PhD         
Assistance Publique Hôpitaux de paris Recruiting
Paris, France, 75000
Contact: Harriet Corvol, MD,PhD       harriet.corvol@aphp.fr   
Principal Investigator: Harriet Corvol, MD,PhD         
Sub-Investigator: Pierre-Regis BURGEL, MD         
Sub-Investigator: Isabelle Sermet-Gaudelus, MD,PhD         
Sub-Investigator: Michèle Gérardin Gérardin, MD         
Hôpital FOCH Recruiting
Suresnes, France, 92150
Contact: Dominique Grenet, MD       d.grenet@hopital-foch.org   
Principal Investigator: Dominique Grenet, MD         
CHU de Toulouse Recruiting
Toulouse, France, 31000
Contact: Marlène Murris-Espin, MD       murris.m@chu-toulouse.fr   
Contact: Murris-Espin         
Principal Investigator: Marlène Murris-Espin, MD         
Sponsors and Collaborators
University Hospital, Bordeaux
Societe Francaise de la Mucoviscidose
Investigators
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Principal Investigator: Laurence DELHAES, MD,PhD University Hospital, Bordeaux
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Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT03565692    
Other Study ID Numbers: CHUBX 2016/22
First Posted: June 21, 2018    Key Record Dates
Last Update Posted: April 10, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Bordeaux:
Microbiome
Microbiota
Mycobiota
Mycobiome
Deep-Sequencing
Cystic Fibrosis
Additional relevant MeSH terms:
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Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases