Study of the Involvement of IL-17 / IL-22 Pathway in Bacterial Exacerbations of COPD

Pulmonary Disease, Chronic Obstructive Clinical Trial

— COPD1722  

Official title:

Study of the Involvement of IL-17 / IL-22 Pathway in Bacterial Exacerbations of COPD

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02655302
• Other study ID #: 2013_76
• Secondary ID: 2015-A00190-49
• Status: Recruiting
• Phase: N/A
• Start date: July 4, 2018
• Est. completion date: July 2028

Study information

• Verified date: January 2023
• Source: University Hospital, Lille
• Contact: Nathalie Bautin, MD
• Phone: 320444318
• Email: nathalie.bautin[@]chru-lille.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Chronic obstructive pulmonary disease (COPD) is a worldwide chronic inflammatory disease of the airways linked to environmental exposure. The chronic course of COPD is often interrupted by acute exacerbations which have a major impact on the morbidity and mortality of COPD patients. A bacterial etiology for these exacerbations is common (almost 50%). Moreover, airway bacterial colonization linked to an increased susceptibility is observed in COPD patients. Effective Th17 immune response is needed to develop a good response against bacteria. Thus, this study aims to demonstrate that there is a defective IL-17/ IL-22 response to bacteria in COPD leading to airway bacterial colonization and infection.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: July 2028
• Est. primary completion date: July 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Diagnosed COPD according GOLD guidelines
• Current or ex-smoker (at least 10 pack-years)
• Hospitalized for COPD exacerbation

Exclusion Criteria:

• Asthma or Cystic fibrosis
• No other chronic lung disease
• Solid Tumor unhealed or not considered in remission
• Inhaled drug consumption
• Women of childbearing potential without effective contraception
• Pregnant or breastfeeding women
• Incapable of consent
• Lack of social security coverage

Related Conditions & MeSH terms

• Bacterial Infections
• Pulmonary Disease, Chronic Obstructive

Intervention

Other:
• Sample collecting
Collect sputum, blood and nasopharyngeal swab during the exacerbation and at steady state 8 to 16 weeks later.
• Lung function measure
Measure lung function and follow it during 4 years

Locations

Country	Name	City	State
France	University hospital of Lille	Lille
France	Roubaix hospital	Roubaix
France	Seclin hospital	Seclin
France	Tourcoing hospital	Tourcoing

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Lille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measure cytokines by ELISA	Compare the delta of IL-17 and IL-22 cytokines between exacerbation and steady-state in the sputum,between the two groups of patients.	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Secondary	Compare the delta of IL-17 and IL-22 cytokines between exacerbation and steady-state in the blood.	Measure cytokines by ELISA in the blood at exacerbation and at steady-state. Compare the delta of these cytokines between the two groups of patients.	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Secondary	Identify IL-17 and IL-22 producing cells in the blood	Identify by flow cytometry, IL-17 and/or IL-22 positive immune cell types in the blood.	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Secondary	Identify IL-17 and IL-22 producing cells in the sputum	Identify by flow cytometry, IL-17 and/or IL-22 positive immune cell types in the sputum.	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Secondary	Quantification of immune cell types in the blood	Quantify by flow cytometry different immune cells in the blood: monocytes, macrophages, B and T cells, innate lymphocytes.	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Secondary	Quantification of immune cell types in the sputum	Quantify by flow cytometry different immune cells in the sputum: monocytes, macrophages, B and T cells, innate lymphocytes.	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Secondary	Quantification of pro-inflammatory cytokines in blood	Quantify by ELISA Th1 (IL-12, IFN gamma), Th2 (IL-4, IL-5), Th17 (IL-1 beta, IL-6, IL-23, TGF beta), regulatory (IL-10) and pro-inflammatory cytokines (IL-8) in the blood.	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Secondary	Quantification of pro-inflammatory cytokines in sputum	Quantify by ELISA Th1 (IL-12, IFN gamma), Th2 (IL-4, IL-5), Th17 (IL-1 beta, IL-6, IL-23, TGF beta), regulatory (IL-10) and pro-inflammatory cytokines (IL-8) in the sputum.	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Secondary	Identify pathogens linked to the exacerbation	Research of classical bacteria and fungi by usual microbial cultures from sputum and of respiratory virus and non conventional bacteria (Mycoplasma, Legionella, Bordetella pertussis and parapertussis and Chlamydophila pneumoniae) by PCR on nasopharyngeal swab.	At inclusion (exacerbation)
Secondary	Identify persistent pathogens at steady-state	Research of classical bacteria and fungi by usual microbial cultures from sputum and of respiratory virus and non conventional bacteria (Mycoplasma, Legionella, Bordetella pertussis and parapertussis and Chlamydophila pneumoniae) by PCR on nasopharyngeal swab.	Between 8 to 16 weeks (steady-state)
Secondary	Compare sputum microbiota between exacerbation and steady-state	Metagenomic analysis on sputum	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Secondary	Compare oxidative stress in the blood between exacerbation and steady-state	Quantification by ELISA in the blood of oxidative stress markers (isoprostane, superoxyde dismutase, 3-nitrotyrosine, peroxyde, catalase).	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Secondary	Quantification of oxidative stress in exhaled condensates	Quantification by ELISA of nitrite species in exhaled condensates.	At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Secondary	Describe exacerbation phenotype	Collect respiratory symptoms, received treatments and hospitalization duration.	At inclusion (exacerbation)
Secondary	Describe environmental exposure	Collect informations on the patient's occupation, occupational exposures and smoking.	At inclusion (exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years
Secondary	Describe COPD clinical phenotype	Collect morphological informations, history of exacerbations	At inclusion (exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years
Secondary	Describe COPD radiological phenotype	Realization of a chest CT scan if not performed during the 2 previous years.	Between 8 to 16 weeks (steady-state)
Secondary	Quantify Quality of Life	Realization of the COPD Assessment Test (CAT), a quality of life questionnaire.	At inclusion (exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years
Secondary	Describe COPD treatments	Collect informations on treatments related to COPD including inhaled treatments, influenza and pneumococcal vaccinations, oxygen therapy and respiratory rehabilitation.	At inclusion (exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years
Secondary	Measure static lung function	Test the lung function with spirometry and plethysmography repeated annually to measure the decline of respiratory function.	Between 8 to 16 weeks (steady-state) and annually for 4 years
Secondary	Measure airway resistances	Measure resistances with the forced oscillation technique.	Between 8 to 16 weeks (steady-state) and at 2 and 4 years
Secondary	Measure exercise tolerance	Perform a 6-minute walk-test.	At inclusion (end of the hospitalization for exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years
Secondary	Analysis exercise tolerance	Perform a cardiopulmonary exercise test on a bicycle.	Between 8 to 16 weeks (steady-state) and at 2 and 4 years