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Study of the Involvement of IL-17 / IL-22 Pathway in Bacterial Exacerbations of COPD (COPD1722)

Primary Purpose

Pulmonary Disease, Chronic Obstructive, Bacterial Infections

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Sample collecting
Lung function measure
Sponsored by
University Hospital, Lille
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Pulmonary Disease, Chronic Obstructive focused on measuring Interleukin-17, Interleukin-22, Microbiota, Exacerbations, Immunity, Mucosal

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University hospital of LilleRecruiting
  • Roubaix hospitalRecruiting
  • Seclin hospital
  • Tourcoing hospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Bacterial exacerbations

Non-bacterial exacerbations

Arm Description

Patients with at least 10^7 UFC/ml bacteria in their sputum during their first COPD exacerbation.

Patients without detected bacteria or below 10^7 UFC/ml in sputum during their first COPD exacerbation.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.
Compare sputum microbiota between exacerbation and steady-state
Metagenomic analysis on sputum
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).
Quantification of oxidative stress in exhaled condensates
Quantification by ELISA of nitrite species in exhaled condensates.
Describe exacerbation phenotype
Collect respiratory symptoms, received treatments and hospitalization duration.
Describe environmental exposure
Collect informations on the patient's occupation, occupational exposures and smoking.
Describe COPD clinical phenotype
Collect morphological informations, history of exacerbations
Describe COPD radiological phenotype
Realization of a chest CT scan if not performed during the 2 previous years.
Quantify Quality of Life
Realization of the COPD Assessment Test (CAT), a quality of life questionnaire.
Describe COPD treatments
Collect informations on treatments related to COPD including inhaled treatments, influenza and pneumococcal vaccinations, oxygen therapy and respiratory rehabilitation.
Measure static lung function
Test the lung function with spirometry and plethysmography repeated annually to measure the decline of respiratory function.
Measure airway resistances
Measure resistances with the forced oscillation technique.
Measure exercise tolerance
Perform a 6-minute walk-test.
Analysis exercise tolerance
Perform a cardiopulmonary exercise test on a bicycle.

Full Information

First Posted
December 3, 2015
Last Updated
January 26, 2023
Sponsor
University Hospital, Lille
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1. Study Identification

Unique Protocol Identification Number
NCT02655302
Brief Title
Study of the Involvement of IL-17 / IL-22 Pathway in Bacterial Exacerbations of COPD
Acronym
COPD1722
Official Title
Study of the Involvement of IL-17 / IL-22 Pathway in Bacterial Exacerbations of COPD
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 4, 2018 (Actual)
Primary Completion Date
July 2028 (Anticipated)
Study Completion Date
July 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Lille

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Disease, Chronic Obstructive, Bacterial Infections
Keywords
Interleukin-17, Interleukin-22, Microbiota, Exacerbations, Immunity, Mucosal

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Bacterial exacerbations
Arm Type
Other
Arm Description
Patients with at least 10^7 UFC/ml bacteria in their sputum during their first COPD exacerbation.
Arm Title
Non-bacterial exacerbations
Arm Type
Other
Arm Description
Patients without detected bacteria or below 10^7 UFC/ml in sputum during their first COPD exacerbation.
Intervention Type
Other
Intervention Name(s)
Sample collecting
Intervention Description
Collect sputum, blood and nasopharyngeal swab during the exacerbation and at steady state 8 to 16 weeks later.
Intervention Type
Other
Intervention Name(s)
Lung function measure
Intervention Description
Measure lung function and follow it during 4 years
Primary Outcome Measure Information:
Title
Measure cytokines by ELISA
Description
Compare the delta of IL-17 and IL-22 cytokines between exacerbation and steady-state in the sputum,between the two groups of patients.
Time Frame
At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Secondary Outcome Measure Information:
Title
Compare the delta of IL-17 and IL-22 cytokines between exacerbation and steady-state in the blood.
Description
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.
Time Frame
At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Title
Identify IL-17 and IL-22 producing cells in the blood
Description
Identify by flow cytometry, IL-17 and/or IL-22 positive immune cell types in the blood.
Time Frame
At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Title
Identify IL-17 and IL-22 producing cells in the sputum
Description
Identify by flow cytometry, IL-17 and/or IL-22 positive immune cell types in the sputum.
Time Frame
At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Title
Quantification of immune cell types in the blood
Description
Quantify by flow cytometry different immune cells in the blood: monocytes, macrophages, B and T cells, innate lymphocytes.
Time Frame
At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Title
Quantification of immune cell types in the sputum
Description
Quantify by flow cytometry different immune cells in the sputum: monocytes, macrophages, B and T cells, innate lymphocytes.
Time Frame
At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Title
Quantification of pro-inflammatory cytokines in blood
Description
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.
Time Frame
At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Title
Quantification of pro-inflammatory cytokines in sputum
Description
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.
Time Frame
At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Title
Identify pathogens linked to the exacerbation
Description
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.
Time Frame
At inclusion (exacerbation)
Title
Identify persistent pathogens at steady-state
Description
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.
Time Frame
Between 8 to 16 weeks (steady-state)
Title
Compare sputum microbiota between exacerbation and steady-state
Description
Metagenomic analysis on sputum
Time Frame
At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Title
Compare oxidative stress in the blood between exacerbation and steady-state
Description
Quantification by ELISA in the blood of oxidative stress markers (isoprostane, superoxyde dismutase, 3-nitrotyrosine, peroxyde, catalase).
Time Frame
At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Title
Quantification of oxidative stress in exhaled condensates
Description
Quantification by ELISA of nitrite species in exhaled condensates.
Time Frame
At inclusion (exacerbation) and between 8 to 16 weeks (steady-state)
Title
Describe exacerbation phenotype
Description
Collect respiratory symptoms, received treatments and hospitalization duration.
Time Frame
At inclusion (exacerbation)
Title
Describe environmental exposure
Description
Collect informations on the patient's occupation, occupational exposures and smoking.
Time Frame
At inclusion (exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years
Title
Describe COPD clinical phenotype
Description
Collect morphological informations, history of exacerbations
Time Frame
At inclusion (exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years
Title
Describe COPD radiological phenotype
Description
Realization of a chest CT scan if not performed during the 2 previous years.
Time Frame
Between 8 to 16 weeks (steady-state)
Title
Quantify Quality of Life
Description
Realization of the COPD Assessment Test (CAT), a quality of life questionnaire.
Time Frame
At inclusion (exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years
Title
Describe COPD treatments
Description
Collect informations on treatments related to COPD including inhaled treatments, influenza and pneumococcal vaccinations, oxygen therapy and respiratory rehabilitation.
Time Frame
At inclusion (exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years
Title
Measure static lung function
Description
Test the lung function with spirometry and plethysmography repeated annually to measure the decline of respiratory function.
Time Frame
Between 8 to 16 weeks (steady-state) and annually for 4 years
Title
Measure airway resistances
Description
Measure resistances with the forced oscillation technique.
Time Frame
Between 8 to 16 weeks (steady-state) and at 2 and 4 years
Title
Measure exercise tolerance
Description
Perform a 6-minute walk-test.
Time Frame
At inclusion (end of the hospitalization for exacerbation), between 8 to 16 weeks (steady-state) and annually for 4 years
Title
Analysis exercise tolerance
Description
Perform a cardiopulmonary exercise test on a bicycle.
Time Frame
Between 8 to 16 weeks (steady-state) and at 2 and 4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nathalie Bautin, MD
Phone
320444318
Ext
+33
Email
nathalie.bautin@chru-lille.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Olivier Le Rouzic, MD
Phone
320444318
Ext
+33
Email
olivier.lerouzic@chru-lille.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nathalie Bautin, MD
Organizational Affiliation
University Hospital, Lille
Official's Role
Principal Investigator
Facility Information:
Facility Name
University hospital of Lille
City
Lille
ZIP/Postal Code
59037
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nathalie Bautin, MD
Email
nathalie.bautin@chru-lille.fr
First Name & Middle Initial & Last Name & Degree
Olivier Le Rouzic, MD
Email
olivier.lerouzic@chru-lille.fr
First Name & Middle Initial & Last Name & Degree
Nathalie Bautin, MD
First Name & Middle Initial & Last Name & Degree
Olivier Le Rouzic, MD
First Name & Middle Initial & Last Name & Degree
Thierry Perez, MD
First Name & Middle Initial & Last Name & Degree
Jean-François Bervar, MD
Facility Name
Roubaix hospital
City
Roubaix
ZIP/Postal Code
59100
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olivier Le Rouzic, MD
Email
olivier.lerouzic@chru-lille.fr
First Name & Middle Initial & Last Name & Degree
Nicolas Just, MD
Facility Name
Seclin hospital
City
Seclin
ZIP/Postal Code
59113
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olivier Le Rouzic, MD
Email
olivier.lerouzic@chru-lille.fr
First Name & Middle Initial & Last Name & Degree
Julie Delourme, MD
First Name & Middle Initial & Last Name & Degree
Cyrielle Jardin, MD
Facility Name
Tourcoing hospital
City
Tourcoing
ZIP/Postal Code
59200
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olivier Le Rouzic, MD
Email
olivier.lerouzic@chru-lille.fr
First Name & Middle Initial & Last Name & Degree
Laurence Thirard, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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