Evaluation of Eosinophil Phenotype in COPD Patients

COPD Clinical Trial

— V-FEO  

Official title:

Pilot Study for Evaluation of Eosinophils Phenotype and Activation Status in COPD Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04494308
• Other study ID #: RP 06/18
• Status: Recruiting
• Start date: March 19, 2019
• Est. completion date: July 2025

Study information

• Verified date: June 2023
• Source: IRCCS San Raffaele Roma
• Contact: Vittorio Cardaci, MD
• Phone: +39 0666052336
• Email: vittorio.cardaci[@]sanraffaele.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a pilot non pharmacological observational study. Aim of the study is to analyze the immunophenotype of circulating eosinophils in chronic obstructive pulmonary disease (COPD) patients, and to correlate results with clinical status of patients (stable versus exacerbated patients, response to therapy). In about 30% of COPD patients there is an increase in the number of circulating eosinophils, which associates with an increased risk for exacerbation. However, no data is available on the role of eosinophils in this disease, on their activation status and their response to chemotactic factors. By multicolor flow cytometry the investigators will analyze membrane molecules and intracellular cytokines associated to chemotaxis, degranulation and inflammation. The study will enroll 30 patients (15 stable and 15 with exacerbation). Results will be analyzed taking into account clinical status,disease progression and response to treatment.

Description:

In about 30% of COPD patients there is an increased number of circulating eosinophils. On their membrane, eosinophils express several molecules, also related to their physiology, namely major histocompatibility complex (MHC) class II, needed for antigen presentation; CCR3, receptor for a variety of chemokines, including eotaxin (CCL11), eotaxin-3 (CCL26), monocyte chemotactict protein (MCP)-3 (CCL7), MCP-4 (CCL13), and RANTES (CCL5); cluster of differentiation (CD)125, which binds IL-5 and stimulates eosinophils proliferation; CD63, a marker that is upregulated after eosinophils degranulation; and CD294 (CRTH2) which is the prostaglandin D2 receptor, and is associated to allergy and inflammation . The hypothesis for the present trial is that different clinical phenotypes of COPD patients could be associated to different activation statuses of eosinophils, that can be evaluated analyzing by flow cytometry the membrane expression of the above mentioned molecules. In particular, the investigators hypothesize that membrane molecules may be modulated in different stages of the diseases, and may change after medical and rehabilitative therapies. The investigators will analyze phenotype of eosinophils from blood samples of patients with COPD, admitted to the hospital after an episode of exacerbation, or for routine controls. In this way, the association between a particular pattern of molecules expressed on eosinophils membrane and the severity of COPD will be defined. Moreover, for hospitalized patients, eosinophils phenotype also on discharge day will be analyzed. In this way the effect of therapies on eosinophils activation will be assessed. Clinical status of patients will be assessed by standard tests such as St George Respiratory Questionnaire (SGRQ), BODE index, COPD Assessment Test (CAT), Six min. Walking Test (6'WT), Pulmonary Function Tests (PFT). Eosinophils phenotype and in vitro cytokines production will be analyzed by multicolor flow cytometry. To minimize the effect of manipulation, staining of membrane molecules will be performed on whole blood samples, followed by lysis of erythrocytes. The following molecules will be analyzed: CD45, CD16, CD15, CD63, CCR3, CD125, CD294, Siglec-8. After in vitro stimulation with lipopolysaccharide (LPS) or CCL11, the production of interleukine (IL)-4, TGFbeta and IL-2 will be analyzed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: July 2025
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• COPD
• percentage of eosinophils >0%
• episode of exacerbation in the previous 10 days (for exacerbated cohort)
• no exacerbation in the previous 3 months (for stable cohort)

Exclusion Criteria:

• percentage of eosinophils =0%
• history of allergic diseases
• patients that are currently enrolled in other clinical trials involving new drugs or treatments

Related Conditions & MeSH terms

• COPD
• COPD Exacerbation
• Pulmonary Disease, Chronic Obstructive

Intervention

Other:
• biomarker identification
flow cytometric analysis of eosinophils membrane molecules

Locations

Country	Name	City	State
Italy	IRCCS San Raffaele Pisana	Roma	RM

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS San Raffaele Roma

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Association of eosinophils phenotype with clinical status in COPD patients	We expect to identify different patterns of expression of molecules on eosinophils membrane that are associated with different clinical phenotypes of COPD patients. We will also associate eosinophils phenotype to the response to medical and rehabilitation therapy. The definition of these patterns will provide a diagnostic tool to rapidly identify patients that will benefit from a specific therapy	one year