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Modeling Bronchial Epithelium Modifications Associated With COPD Using iPS (INVECCO)

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ClinicalTrials.gov Identifier: NCT03181204
Recruitment Status : Recruiting
First Posted : June 8, 2017
Last Update Posted : September 13, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Montpellier

Tracking Information
First Submitted Date June 6, 2017
First Posted Date June 8, 2017
Last Update Posted Date September 13, 2019
Actual Study Start Date August 7, 2017
Estimated Primary Completion Date August 7, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 6, 2017)
  • functional bronchial epithelium from iPS? [ Time Frame: Day 0 + culture (cross-sectional study) ]
    Was a functional bronchial epithelium obtained from the patient's induced pluripotent stem cells from blood or fibroblasts? (yes/no)
  • functional bronchial epithelium from HBEC-ALI? [ Time Frame: Day 0 + culture (cross-sectional study) ]
    Was a functional bronchial epithelium obtained from the patient's bronchial biopsy: human bronchial epithelial cell culture on an air-liquid-interface? (yes/no)
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT03181204 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Modeling Bronchial Epithelium Modifications Associated With COPD Using iPS
Official Title Modeling Bronchial Epithelia Modifications Associated With Chronic Obstructive Pulmonary Disease (COPD) Using Induced Pluripotent Stemcells (iPS)
Brief Summary

The primary objective of this study is to to verify the feasibility of obtaining and comparing two epithelia in two populations based on the following experiments:

  • Differentiation of an Induced Pluripotent Stem cell (iPS) clone derived from cutaneous biopsy in a population of heavy smokers (plus patients with chronic obstructive pulmonary disease) in order to obtain differentiated bronchial epithelia in vitro.
  • For each of these same patients, generation of bronchial epithelium in vitro from bronchial biopsy using human bronchial epithelial cells (HBECs) in air-liquid interface (ALI) cultures.
Detailed Description

Secondary objectives:

  • Confrontation of the two models of in vitro generation of bronchial epithelium by iPS and ALI in order to validate our model of study of the human bronchial epithelium COPD generated by the iPS.
  • Inducing a "COPD-like" epithelial phenotype by exposing the bronchial epithelia generated from the iPS to a source of in vitro toxin (tobacco) and studying its effects by transcriptomic analysis via high-throughput sequencing (NGS) at key steps during the model.
  • Demonstrate the feasibility of obtaining iPS from peripheral blood sampling.
Study Type Observational
Study Design Observational Model: Other
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
This study will general cell cultures.
Sampling Method Non-Probability Sample
Study Population This study includes patients with chronic obstructive pulmonary disease, as well as patients without chronic obstructive pulmonary disease, but who are heavy smokers.
Condition
  • Pulmonary Disease, Chronic Obstructive
  • Smoking
Intervention
  • Procedure: Bronchial biopsy
    The bronchial biopsy is part of this study's inclusion criteria and is required during routine care for the patient. Bronchial fibroscopy is performed under general or local anesthesia. Biopsies are performed using forceps and according to current recommendations. One biopsy will be fixed immediately in RCL2 medium while the others (between 3 and 6) will be kept in isotonic saline and rapidly prepared for air-liquid-interface (ALI) cell culture.
  • Procedure: Skin biopsy
    The skin biopsy will be performed after local anesthesia by hypodermic injection of a 1% Xylocaine solution. A single sample of a skin fragment about 3 mm in diameter will be necessary.
  • Procedure: Blood sample
    The blood sample will be taken at the end of the cutaneous biospy, approximately 20 ml of blood will be collected.
Study Groups/Cohorts
  • Patients likely to develop COPD

    Patients in this group are relatively light smokers who have developed chronic obstructive lung disease (COPD).

    Intervention: Bronchial biopsy

    Intervention: Skin biopsy

    Intervention: Blood sample

    Interventions:
    • Procedure: Bronchial biopsy
    • Procedure: Skin biopsy
    • Procedure: Blood sample
  • Patients not likely to develop COPD

    Patients in this group are heavy smokers who have no signs of chronic obstructive lung disease (COPD).

    Intervention: Bronchial biopsy

    Intervention: Skin biopsy

    Intervention: Blood sample

    Interventions:
    • Procedure: Bronchial biopsy
    • Procedure: Skin biopsy
    • Procedure: Blood sample
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: June 6, 2017)
16
Original Estimated Enrollment Same as current
Estimated Study Completion Date August 7, 2020
Estimated Primary Completion Date August 7, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria for COPD patients:

  • The patient has given his/her signed, informed consent
  • Forced expiratory volume in 1 second / forced vital capacity < 0.7 [FEV1/FVC < 0.7]
  • FEV1 < 50% of predicted value
  • Exclusion of other respiratory pathologies, based on anamnesis, computed tomography and complementary respiratory function tests and transthoracic ultrasound,
  • Smoking >10 pack-years, ongoing or weaned
  • Absence of exacerbation or intercurrent infectious episode for at least 4 weeks at time of inclusion
  • Medical indication for a bronchial fibroscopy (indication validated by the physician in charge of the patient and the study investigating physician): pulmonary peripheral nodule exploration with computed tomography, interventional endoscopy for emphysema reduction, removal of foreign bodies, other indications.
  • Absence of contraindications for bronchial biopsy (left to physician's discretion): not limited to: regular intake of anticoagulants or anti-platelet aggregation, hemostasis abnormalities

Inclusion Criteria for smokers:

  • The patient has given his/her signed, informed consent
  • Forced expiratory volume in 1 second / forced vital capacity > 0.7 [FEV1/FVC > 0.7]
  • FEV1 > 80% of predicted value
  • Exclusion of other respiratory pathologies, based on anamnesis, computed tomography (absence of extensive emphysema lesions defined by the presence of less than <5% relative surface area occupied by densities less than 910 UH (measured on millimeter cuts)) and respiratory function tests (Residual Volume <120%, Diffusion Capacity for Carbon Monoxide > 60% and Total Pulmonary Capacity> 120%) and transthoracic ultrasound (normal),
  • Smoking >40 pack-years, ongoing or weaned
  • Absence of exacerbation or intercurrent infectious episode for at least 4 weeks at time of inclusion
  • Medical indication for a bronchial fibroscopy (indication validated by the physician in charge of the patient and the study investigating physician): pulmonary peripheral nodule exploration with computed tomography, interventional endoscopy for emphysema reduction, removal of foreign bodies, other indications.
  • Absence of contraindications for bronchial biopsy (left to physician's discretion): not limited to: regular intake of anticoagulants or anti-platelet aggregation, hemostasis abnormalities

Exclusion Criteria:

  • Contra-indication for bronchial fibroscopy and cutaneous biopsy
  • Deficiency in α-1 antitrypsin
  • Significant bronchiectasis on chest computed tomography scan
  • Colonization of the airways by Pseudomonas Aeroginosa or Aspergillus
  • Chemotherapy or other cytotoxic treatments in the last 12 months
  • Systemic corticotherapy in the 4 weeks prior to inclusion
  • Long-term antibiotic treatment, notably by macrolides
  • Any other treatment that may affect the bronchial epithelium, this being left to the discretion of the investigating physician
  • Consumer of illicit drugs or alcohol
  • Participant in an exclusion period determined by a previous study
  • Subject not affiliated with, or not beneficiary of, a social security plan.
  • Pregnant or nursing women according to Article L1121-5 of the Public Health Code.
  • Vulnerable persons according to Article L1121-6 of the Public Health Code
  • An adult who is protected or incapable of giving consent in accordance with Article L1121-8 of the Public Health Code
  • Subject deprived of freedom by judicial or administrative decision.
  • Those patients for whom two epithelia cultures (1 from bronchial biopsy ("ALI") and 1 from fibroblast reprogrammation of redifferentiated iPS ("iALI")) were not obtained will be excluded (post-inclusion).
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Arnaud Bourdin, MD,PhD +33.(0)4.67.33.61.26 a-bourdin@chu-montpellier.fr
Listed Location Countries France
Removed Location Countries  
 
Administrative Information
NCT Number NCT03181204
Other Study ID Numbers 9791
2017-A00252-51 ( Other Identifier: RCB number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party University Hospital, Montpellier
Study Sponsor University Hospital, Montpellier
Collaborators Not Provided
Investigators
Study Director: Arnaud Bourdin, MD, PhD University Hospital, Montpellier
PRS Account University Hospital, Montpellier
Verification Date September 2019