Mapping and Characterization of Alveolar Cells During Smoking and Chronic Obstructive Disease (CoStemCells)

To evaluate the regenerative capacities of mesenchymal cells composing the microenvironment of alveolar type 2 cells in a population of patients, undergoing thoracic surgery for suspected cancer, who are smokers with and without COPD compared to non-smokers patients

Study Overview

• Status: Recruiting
• Conditions: Chronic Obstructive Pulmonary Disease; Chronic Obstructive Lung Disease
• Intervention / Treatment: Other: Thoracic resection surgery

Detailed Description

Chronic obstructive pulmonary diseases (COPD) have a major public health impact, as evidenced by the 250 million patients affected by these diseases and the 50% 5-year mortality for severe stages of chronic obstructive pulmonary disease (COPD). One pathophysiological mechanism of COPD and emphysema is a depletion of alveolar progenitor cells inducing a loss of alveolar-reparation capacities after an aggression. The genesis of these alterations and the mechanisms involved remain unknown. Alveolar type 2 cells (AT2) are the alveolar epithelial progenitor cells. AT2 proliferate and differentiate into alveolar type 1 cells (AT1) which form the alveolar-capillary barrier, along with endothelial cells, through which respiratory gas exchanges take place. The proliferation and differentiation of AT2 into AT1 are under the control of mesenchymal cells and endothelial cells located in close proximity. Together these cells form the alveolar stem cell niche. The characteristics and interactions of the different cell populations have been well described during lung growth, in the normal adult lung or during pulmonary fibrosis; however, participants are poorly described during smoking exposure and chronic obstructive diseases.

• Study Type: Interventional
• Enrollment (Anticipated): 186
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: JUNG Camille, MD; Phone Number: +33 0145175000; Email: camille.jung@chiccreteil.fr

Study Locations

• France
  • Créteil, France, 94000
    • Recruiting
    • Rousseau-Bussac
    • Contact: Gaelle ROUSSEAU-BUSSAC, MD; Phone Number: +33 01 45 17 50 00; Email: Gaelle.RousseauBussac@chicreteil.fr
    • Sub-Investigator: LAURENT BOYER, MD
  • Paris, France, 75014
    • Active, not recruiting
    • Hôpital Cochin
  • Paris, France, 75015
    • Active, not recruiting
    • HEGP
  • Paris, France, 75020
    • Active, not recruiting
    • Hopital Tenon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18
2. Patient undergoing lung resection surgery (lobectomy, pneumonectomy, segmentectomy) for cancer or suspected cancer
3. Acceptance to participate in the protocol
4. Affiliated to a social security plan

Exclusion Criteria:

1. Chronic autoimmune disease
2. Patient under guardianship or curators
3. Neo-adjuvant chemotherapy
4. History of thoracic radiotherapy
5. Pregnant woman
6. Minor patient
7. Person not able to consent
8. Person deprived of liberty

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Thoracic resection surgery; Smokers (active or ex-smokers) and non-smokers with COPD and without COPD undergoing thoracic resection surgery	Other: Thoracic resection surgery; Patients undergoing thoracic resection surgery (pneumonectomy, lobectomy, segmentectomy) for cancer or suspected cancer, including smokers (active or ex-smokers) and non-smokers, with COPD and without COPD, and non-smoking patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of alveolar organoids	Comparison of the number of alveolar organoids formed 21 days after culture of fibroblasts with alveolar type II cells between smokers with and without COPD and non-smoking patients	through study completion, an average of 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibroblast proliferation capacity	Evaluated by their doubling time, number of cells collected compared to the number of cells seeded	through study completion, an average of 3 years
Differentiation into myofibroblasts	By immunofluorescence marking: number of alpha-smooth muscle actin (alpha-SMA) + cells compared to total cells	through study completion, an average of 3 years
Fibroblast migration capacity	Evaluated in Boyden chamber	through study completion, an average of 3 years
Modulated signaling pathways in isolated fibroblasts between groups	Evaluated by Ribonucleic acid (RNA) sequencing of fibroblasts	through study completion, an average of 3 years
Modulated signaling pathways in endothelial cells between groups	Evaluated byRibonucleic acid (RNA) sequencing of endothelial cells	through study completion, an average of 3 years
Evaluation of cytokines in fibroblasts supernatant	Evaluated by Luminex Assay	through study completion, an average of 3 years
Tumor progression	By studying the migration and invasion of tumor cells	through study completion, an average of 3 years
Identification of different cell types on total lung	Cell types composing the lung stem cell microenvironment measured by single cell analysis	through study completion, an average of 3 years
Severity of pulmonary emphysema,	Change of lung density assessed by computed tomography scan	At inclusion, every year, up to 5 years after surgery
Type of pulmonary emphysema	Assessed by computed tomography scan : [centro-lobular or pan-lobular, para-septal]	At inclusion, every year, up to 5 years after surgery
Research of pulmonary biomarkers	Searched according to the results obtained during cell cultures (immunohistochemistry, immunofluorescence)	through study completion, an average of 3 years
Identification of biomarkers in the pre and postoperative circulating blood	Evaluated in laboratory by metagenomic analysis of 16s Ribonucleic acid (RNA) of bacteria for cluster analysis that correlate with lung injury and could be prognostic markers	through study completion, an average of 3 years
Identification of biomarkers in the intestinal microbiota	Evaluated in laboratory by metagenomic analysis of 16s Ribonucleic acid (RNA) of bacteria for cluster analysis that correlate with lung injury and could be prognostic markers	through study completion, an average of 3 years
Measurement of Forced expiratory volume at one second (FEV1)	Determine the relationship between respiratory disease phenotype and exercise impact by measurement of Forced expiratory volume at one second (FEV1)	through study completion, an average of 3 years
Measurement of Forced Vital Capacity (FVC )	Determine the relationship between respiratory disease phenotype and exercise impact by measurement of Forced Vital Capacity (FVC )	through study completion, an average of 3 years
Measurement of pulmonary diffusion capacity of CO (DLCO)	Determine the relationship between respiratory disease phenotype and exercise impact by measurement of pulmonary diffusion capacity of CO (DLCO)	through study completion, an average of 3 years
Measurement of CO transfer coefficient (KCO)	Determine the relationship between respiratory disease phenotype and exercise impact by measurement of CO transfer coefficient (KCO)	through study completion, an average of 3 years

Collaborators and Investigators

• Sponsor: Centre Hospitalier Intercommunal Creteil

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 5, 2022
• Primary Completion (ANTICIPATED): October 31, 2025
• Study Completion (ANTICIPATED): October 5, 2030

Study Registration Dates

• First Submitted: November 4, 2021
• First Submitted That Met QC Criteria: January 26, 2022
• First Posted (ACTUAL): February 7, 2022

Study Record Updates

• Last Update Posted (ACTUAL): November 22, 2022
• Last Update Submitted That Met QC Criteria: November 21, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: CoStemCells

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No