Mapping and Characterization of Alveolar Cells During Smoking and Chronic Obstructive Disease

Chronic Obstructive Pulmonary Disease Clinical Trial

— CoStemCells  

Official title:

Mapping and Characterization of Alveolar Cells During Smoking and Chronic Obstructive Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05227547
• Other study ID #: CoStemCells
• Status: Recruiting
• Phase: N/A
• Start date: October 5, 2022
• Est. completion date: October 5, 2030

Study information

• Verified date: November 2022
• Source: Centre Hospitalier Intercommunal Creteil
• Contact: JUNG Camille, MD
• Phone: 0145175000
• Email: camille.jung[@]chiccreteil.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 186
• Est. completion date: October 5, 2030
• Est. primary completion date: October 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Obstructive Lung Disease
• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

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.

Locations

Country	Name	City	State
France	Rousseau-Bussac	Créteil
France	HEGP	Paris
France	Hopital Cochin	Paris
France	Hopital Tenon	Paris

Sponsors (3)

Lead Sponsor	Collaborator
Centre Hospitalier Intercommunal Creteil	Henri Mondor University Hospital, Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Fibroblast migration capacity	Evaluated in Boyden chamber	through study completion, an average of 3 years
Secondary	Modulated signaling pathways in isolated fibroblasts between groups	Evaluated by Ribonucleic acid (RNA) sequencing of fibroblasts	through study completion, an average of 3 years
Secondary	Modulated signaling pathways in endothelial cells between groups	Evaluated byRibonucleic acid (RNA) sequencing of endothelial cells	through study completion, an average of 3 years
Secondary	Evaluation of cytokines in fibroblasts supernatant	Evaluated by Luminex Assay	through study completion, an average of 3 years
Secondary	Tumor progression	By studying the migration and invasion of tumor cells	through study completion, an average of 3 years
Secondary	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
Secondary	Severity of pulmonary emphysema,	Change of lung density assessed by computed tomography scan	At inclusion, every year, up to 5 years after surgery
Secondary	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
Secondary	Research of pulmonary biomarkers	Searched according to the results obtained during cell cultures (immunohistochemistry, immunofluorescence)	through study completion, an average of 3 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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