Clinical trial NCT02965326: Surrogate Markers of Response to New Therapies in Cystic Fibrosis Patients
Official title: Personalized Therapy of Cystic Fibrosis: Set-up of Response Markers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cystic Fibrosis
Lead sponsor: Hôpital Necker-Enfants Malades
Sponsor class: OTHER
Collaborators: name: Association Mucoviscidose-ABCF2
name: Vaincre la Mucoviscidose
First posted: 2016-11-16
Enrollment: 75
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to determine which biological marker, or association of biological markers, best predict clinical response of cystic fibrosis patients to CFTR modulators.

Detailed description: This study is based upon the hypothesis that clinical response of cystic fibrosis patients to CFTR modulators is correlated to in vitro responses to these drugs of epithelial cells derived from the patients, as assessed by CFTR-dependent Chloride secretion. Epithelial cells will be derived either from nasal or rectal epithelia, and consist both of cultured cells and organoids. The drugs tested will be Ivacaftor, or Lumacaftor/Ivacaftor, according to patient's treatment. Results of these assays will be compared with response to treatment at 6 and 12 months, assessed by clinical response and in vivo assay of CFTR function.

Eligibility criteria: Inclusion Criteria:

* Cystic fibrosis patients treated by CFTR modulators (Ivacaftor or the association Ivacaftor-Lumacaftor)
* Cystic fibrosis patients non treated by CFTR modulators
* Patients in whom cystic fibrosis diagnosis has been suspected, but excluded by physiological and genetic investigations

Exclusion Criteria:

* pregnant or lactating women
* contraindication to nasal swab
* contraindication to rectal biopsy

Primary outcomes:
measure: Forced Expiratory Volume in 1 second
timeFrame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
Secondary outcomes:
measure: Forced Vital Capacity
timeFrame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
measure: Forced Expiratory Flow 25-75
timeFrame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
measure: Residual Volume
timeFrame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
measure: elastase in sputum
timeFrame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
measure: calprotectin in sputum
timeFrame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
measure: IL-8 in sputum
timeFrame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
measure: Calprotectin in blood
timeFrame: initiation, 1 month, 3 Months, 6 months and every 6 months
measure: IL-8 in blood
timeFrame: initiation, 1 month, 3 Months, 6 months and every 6 months
measure: tumor necrosis factor in sputum
timeFrame: initiation, 1 month, 3 Months, 6 months and every 6 months
measure: liver function test in blood
timeFrame: initiation, 1 month, 3 Months, 6 months and every 6 months
measure: liver function test/SGPT in blood
timeFrame: initiation, 1 month, 3 Months, 6 months and every 6 months
measure: liver function test/bilirubin in blood
timeFrame: initiation, 1 month, 3 Months, 6 months and every 6 months
measure: liver function test, gammaGT in blood
timeFrame: initiation, 1 month, 3 Months, 6 months and every 6 months
measure: creatine phosphokinase in blood
timeFrame: initiation, 1 month, 3 Months, 6 months and every 6 months
measure: Amylase in blood
timeFrame: initiation, 1 month, 3 Months, 6 months and every 6 months
measure: Impedancemetry
timeFrame: initiation , 1 month, 3 Months, 6 months and every 6 months
measure: Dynamometry
timeFrame: initiation , 1 month, 3 Months, 6 months and every 6 months
measure: Sweat test
timeFrame: initiation ,1 month
measure: proteomics of sweat
timeFrame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
measure: metabolomics of sweat
timeFrame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
measure: proteomics of exhalate
timeFrame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months
measure: sputum bronchial microorganism colonization
timeFrame: initiation , 1 month, 3 Months, 6 months and every 6 months
measure: Lung MRI
timeFrame: initiation, at 1 year and every year
measure: osteodensitometry
timeFrame: initiation, 1 year, and every year
measure: fecal elastase
timeFrame: initiation, at 6 months and every year
measure: fecal calprotectin
timeFrame: initiation, at 6 months and every year
measure: Chest CT scan
timeFrame: initiation, 3 years and 5 years
measure: glycemic Holter
timeFrame: initiation, 1 year and every year
measure: abdominal ultrasonography
timeFrame: treatment initiation, 1 year and every year
measure: proton density fat fraction
timeFrame: treatment initiation, 1 year
measure: patient quality of life
timeFrame: initiation, 1 month, 6 months, 1 year and every 6 months
measure: CFTR activity in nasal cells/chloride
timeFrame: initiation of treatment and repeated if cell culture failure
measure: CFTR activity in nasal cells/bicarbonat
timeFrame: initiation of treatment and repeated if cell culture failure
measure: CFTR activity in intestinal epithelium/chloride
timeFrame: initiation of treatment and repeated of cell culture failure
measure: CFTR activity in intestinal epithelium/bicarbonate
timeFrame: initiation of treatment and repeated of cell culture failure
measure: sweat evaporimetry
timeFrame: initiation and 1 month
measure: Elasto MRI
timeFrame: initiation and 1 year
measure: Lung Clearance Index
timeFrame: initiation, 6 months, 1 year and every 6 months
measure: proteomics in blood
timeFrame: initiation, 7 days, 1 month, 6 months, 1 year and every year
measure: metabolomics in blood
timeFrame: initiation, 7 days, 1 month, 6 months, 1 year and every year
measure: proteomic in urine
timeFrame: initiation, 7 days, 1 month, 6 months, 1 year and every year
measure: metabolomics in urine
timeFrame: initiation, 7 days, 1 month, 6 months, 1 year and every year
measure: Exhaled air composition
timeFrame: initiation, 7 days, 1 month, 6 months, 1 year and every year
Other outcomes:
Locations:
city: Paris
country: France
facility: Necker Hospital
Study officials:
affiliation: APHP
name: Aleksander Edelman, phD
role: STUDY_DIRECTOR
References:
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citation: Boyle MP, Bell SC, Konstan MW, McColley SA, Rowe SM, Rietschel E, Huang X, Waltz D, Patel NR, Rodman D; VX09-809-102 study group. A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: a phase 2 randomised controlled trial. Lancet Respir Med. 2014 Jul;2(7):527-38. doi: 10.1016/S2213-2600(14)70132-8. Epub 2014 Jun 24.
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citation: Dekkers JF, Wiegerinck CL, de Jonge HR, Bronsveld I, Janssens HM, de Winter-de Groot KM, Brandsma AM, de Jong NW, Bijvelds MJ, Scholte BJ, Nieuwenhuis EE, van den Brink S, Clevers H, van der Ent CK, Middendorp S, Beekman JM. A functional CFTR assay using primary cystic fibrosis intestinal organoids. Nat Med. 2013 Jul;19(7):939-45. doi: 10.1038/nm.3201. Epub 2013 Jun 2.
citation: Pranke I, Hatton A, Masson A, Flament T, Le Bourgeois M, Chedevergne F, Bailly C, Urbach V, Hinzpeter A, Edelman A, Sermet-Gaudelus I. Might Brushed Nasal Cells Be a Surrogate for CFTR Modulator Clinical Response? Am J Respir Crit Care Med. 2019 Jan 1;199(1):123-126. doi: 10.1164/rccm.201808-1436LE. No abstract available.