Clinical trial NCT05227547: Mapping and Characterization of Alveolar Cells During Smoking and Chronic Obstructive Disease
Official title: Mapping and Characterization of Alveolar Cells During Smoking and Chronic Obstructive Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Chronic Obstructive Lung Disease
Chronic Obstructive Pulmonary Disease
Lead sponsor: Centre Hospitalier Intercommunal Creteil
Sponsor class: OTHER
Collaborators: name: Henri Mondor University Hospital
name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2022-02-07
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of alveolar organoids
timeFrame: through study completion, an average of 3 years
Secondary outcomes:
measure: Fibroblast proliferation capacity
timeFrame: through study completion, an average of 3 years
measure: Differentiation into myofibroblasts
timeFrame: through study completion, an average of 3 years
measure: Fibroblast migration capacity
timeFrame: through study completion, an average of 3 years
measure: Modulated signaling pathways in isolated fibroblasts between groups
timeFrame: through study completion, an average of 3 years
measure: Modulated signaling pathways in endothelial cells between groups
timeFrame: through study completion, an average of 3 years
measure: Evaluation of cytokines in fibroblasts supernatant
timeFrame: through study completion, an average of 3 years
measure: Tumor progression
timeFrame: through study completion, an average of 3 years
measure: Identification of different cell types on total lung
timeFrame: through study completion, an average of 3 years
measure: Severity of pulmonary emphysema,
timeFrame: At inclusion, every year, up to 5 years after surgery
measure: Type of pulmonary emphysema
timeFrame: At inclusion, every year, up to 5 years after surgery
measure: Research of pulmonary biomarkers
timeFrame: through study completion, an average of 3 years
measure: Identification of biomarkers in the pre and postoperative circulating blood
timeFrame: through study completion, an average of 3 years
measure: Identification of biomarkers in the intestinal microbiota
timeFrame: through study completion, an average of 3 years
measure: Measurement of Forced expiratory volume at one second (FEV1)
timeFrame: through study completion, an average of 3 years
measure: Measurement of Forced Vital Capacity (FVC )
timeFrame: through study completion, an average of 3 years
measure: Measurement of pulmonary diffusion capacity of CO (DLCO)
timeFrame: through study completion, an average of 3 years
measure: Measurement of CO transfer coefficient (KCO)
timeFrame: through study completion, an average of 3 years
Other outcomes:
Locations:
city: Créteil
country: France
facility: Rousseau-Bussac
city: Paris
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: HEGP
city: Paris
country: France
facility: Hopital Tenon
Study officials:
References: