Modeling Bronchial Epithelium Modifications Associated With COPD Using iPS

NCT03181204 | Completed

• 2 other identifiers: 97912017-A00252-51
• Study Type: observational
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Disease, Chronic Obstructive; Smoking

Outcome Measures

Primary Outcomes (2)

• functional bronchial epithelium from iPS?

  Was a functional bronchial epithelium obtained from the patient's induced pluripotent stem cells from blood or fibroblasts? (yes/no)

  Day 0 + culture (cross-sectional study)

• functional bronchial epithelium from HBEC-ALI?

  Was a functional bronchial epithelium obtained from the patient's bronchial biopsy: human bronchial epithelial cell culture on an air-liquid-interface? (yes/no)

  Day 0 + culture (cross-sectional study)

Study Arms (2)

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

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

Procedure: Bronchial biopsy; Procedure: Skin biopsy; Procedure: Blood sample

Interventions

Bronchial biopsy PROCEDURE

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.

Patients likely to develop COPD; Patients not likely to develop COPD

Skin biopsy PROCEDURE

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.

Patients likely to develop COPD; Patients not likely to develop COPD

Blood sample PROCEDURE

The blood sample will be taken at the end of the cutaneous biospy, approximately 20 ml of blood will be collected.

Patients likely to develop COPD; Patients not likely to develop COPD

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

• 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
• Smoking \>10 pack-years, ongoing or weaned
• 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
• 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
• Smoking \>40 pack-years, ongoing or weaned
• 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

You may not qualify if:

• 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
• 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
• 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.

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (1)

Centre Hospitalier Universitaire de Montpellier

Montpellier, 34295, France

Location

Related Publications (2)

• Ahmed E, Fieldes M, Mianne J, Bourguignon C, Nasri A, Vachier I, Assou S, Bourdin A, De Vos J. Generation of four severe early-onset chronic obstructive pulmonary disease (COPD) patient-derived induced pluripotent stem cell lines from peripheral blood mononuclear cells. Stem Cell Res. 2021 Oct;56:102550. doi: 10.1016/j.scr.2021.102550. Epub 2021 Sep 27.

  PMID: 34624616 RESULT

• Fieldes M, Ahmed E, Bourguignon C, Mianne J, Vernisse C, Fort A, Vachier I, Bourdin A, Assou S, De Vos J. [Modelling the bronchial epithelium in chronic obstructive pulmonary disease using human induced pluripotential stem cells]. Rev Mal Respir. 2020 Mar;37(3):197-200. doi: 10.1016/j.rmr.2020.02.003. Epub 2020 Mar 4. French.

  PMID: 32146059 RESULT

Related Links

• INVECCO on the Open Science Framework

Biospecimen

Retention: SAMPLES WITHOUT DNA

This study will general cell cultures.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Smoking

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Arnaud Bourdin, MD, PhD

  University Hospital, Montpellier

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2017
• First Posted: June 8, 2017
• Study Start: August 7, 2017
• Primary Completion: March 9, 2022
• Study Completion: March 9, 2022
• Last Updated: September 8, 2023

Record last verified: 2023-09

Locations

FR (1)