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Eosinophils Endotypes in Chronic Airway Inflammatory Diseases (PLEIAD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04187976
Recruitment Status : Not yet recruiting
First Posted : December 5, 2019
Last Update Posted : December 5, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Lille

Brief Summary:

Asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) are frequently described as unified airway inflammatory diseases. Both heavily impacts quality of life with substantial productivity loss. They share the same pathophysiologic pattern based upon proTh2 immune response with blood eosinophils recruitment. Eosinophils are the major actor of persistent mucosal inflammation by promoting their own survival, by attracting other inflammatory cells and by producing cytotoxic proteins involved in mucosal remodeling.

Promising anti-Th2 therapeutic approaches (i.e.anti-IgE, anti-interleukin 5 (IL-5), anti-IL-4, anti-IL-13) are considered as effective alternative options to long-term corticosteroid treatment. Their advantage in recalcitrant CRSwNP is under consideration. Moreover, we still need to delineate the good responders to improve theirs indications.

The objective is to assess blood eosinophil immunophenotypes in asthma or CRSwNP. Flow cytometric expression of activation markers on eosinophil membrane will be compared with a group of healthy subjects. Innovative data on eosinophil involvement in airway diseases will be obtained. The major outcome will be to depict patients' endotypes for a better selection of immunotherapies.


Condition or disease
Eosinophilic Asthma Chronic Sinusitis Eosinophilic Rhinitis

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Study Type : Observational
Estimated Enrollment : 80 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Peripheral Eosinophils Phenotypes in Airway Inflammatory Diseases: Towards Proper Clustering and Therapeutic Targeting
Estimated Study Start Date : March 2020
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Group/Cohort
Patients with moderate to severe uncontrolled asthma
Patients with moderate to severe uncontrolled asthma defined on clinical assessment and spirometric criteria. Non controlled asthma is considered when ACQ score ≥ 1.5 or in case of acute exacerbation
Patients with recalcitrant CRSwNP requiring sinus surgery
The medical failure in CRSwNP is defined as persistent disease in spite of 3 courses of oral corticosteroid and double dose of local corticoid over 12 months
Patients with concomitant CRSwNP and uncontrolled asthma
Patients with concomitant CRSwNP and moderate to severe uncontrolled asthma
Healthy subjects
Patients without any airway inflammatory disease or atopy



Primary Outcome Measures :
  1. Percentage of blood eosinophils with expression of CD69 marker in patients with uncontrolled asthma alone, recalcitrant chronic rhinosinusitis with nasal polyps (CRSwNP) alone, uncontrolled asthma and recalcitrant CRSwNP and in healthy subjects. [ Time Frame: Baseline ]

    CD69 expression is measured with flow cytometry on blood eosinophils cell surface.

    The percentage of blood eosinophils positive for CD69 is compared between the four groups of patients (uncontrolled asthma alone, recalcitrant CRSwNP alone, uncontrolled asthma and recalcitrant CRSwNP and in healthy subjects)



Secondary Outcome Measures :
  1. Percentage of blood eosinophils with expression of HLADR marker in patients with uncontrolled asthma alone, recalcitrant CRSwNP alone, uncontrolled asthma and recalcitrant CRSwNP and in healthy subjects. [ Time Frame: baseline ]

    HLADR expression is measured with flow cytometry on blood eosinophils cell surface.

    The percentage of blood eosinophils positive for HLADR is compared between the four groups of patients (uncontrolled asthma alone, recalcitrant CRSwNP alone, uncontrolled asthma and recalcitrant CRSwNP and in healthy subjects)


  2. Percentage of activated blood eosinophils in patients with uncontrolled asthma alone, recalcitrant CRSwNP alone, uncontrolled asthma and recalcitrant CRSwNP and in healthy subjects. [ Time Frame: baseline ]
    Activated status of blood eosinophils is based on concomittant expression of biomarkers ( CD69, HLADR, CCR3) with flow cytometry. The percentage of activated blood eosinophils is compared between the four groups of patients (uncontrolled asthma alone, recalcitrant CRSwNP alone, uncontrolled asthma and recalcitrant CRSwNP and in healthy subjects).

  3. Comparison of the percentage of activated eosinophils in blood with the percentage of activated eosinophils in induced sputum in uncontrolled asthma (with or without CRSwNP). [ Time Frame: baseline ]
    Activated status of eosinophils in blood and in induced sputum is based on concomittant expression of biomarkers ( CD69, HLADR, CCR3) with flow cytometry.

  4. Comparison of the percentage of activated eosinophils in blood with the percentage of activated eosinophils in nasal polyps in CRSwNP patients (with or without uncontrolled asthma). [ Time Frame: baseline ]
    Activated status of eosinophils in blood and in nasal polyps is based on concomittant expression of biomarkers ( CD69, HLADR, CCR3) with flow cytometry.

  5. Comparison of qualitative transcriptomic profiles of blood eosinophils in patients with uncontrolled asthma alone, recalcitrant chronic rhinosinusitis with nasal polyps (CRSwNP) alone, uncontrolled asthma and recalcitrant CRSwNP. [ Time Frame: baseline ]

    Transcriptomic profiles will be compared between CRSwNP with or without uncontrolled asthma and between uncontrolled asthma with or without CRSwNP.

    A two-fold differential expression will be used for comparison.



Biospecimen Retention:   Samples With DNA
Eosinophils from blood samples,nasal polyps and induced sputum


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

All patients for the study will be targeted either during hospitalization in Pneumology for uncontrolled asthma patients, during ENT visit for scheduling of sinus surgery (recalcitrant CRSwNP).

The healthy subjects are going to be screened in the Clinical Investigation Center of the University Hospital of Lille. Subjects will be contacted by phone after selection in the database.

Criteria

Inclusion Criteria:

For all groups:

  • Social insured patient
  • Patient willing to comply with all procedures of the study and its duration
  • Provision of signed and dated informed consent form prior to any study specific procedure

For Group 1:

- Patients with moderate to severe uncontrolled asthma, confirmed by relevant clinical symptoms and proven variable airway obstruction, and assessed by an expert pulmonologist according to spirometry criteria (absolute and weighed Forced Expiratory Volume (FEV) and Forced Vital Capacity (FVC) before and after 2 test),(see CRF for details). Uncontrolled asthma will be defined by an ACQ score ≥ 1.5. or acute exacerbation

For Groups 2 and 3:

  • Patients with medically refractory bilateral sino-nasal polyposis requiring sinus surgery, according to an expert rhinologist. CRSwNP diagnosis is based on the presence of bilateral nasal polyps from both side of middle turbinates on nasoendoscopy and bilateral sinus opacification on CT scan. Briefly, CRSwNP is considered as refractory when symptoms are still not controlled after 3 courses of oral corticosteroid and double dose of nasal corticosteroid during the last 12 months
  • Patients with both uncontrolled asthma and recalcitrant CRSwNP with or without concomitant aspirin-exacerbated respiratory disease (AERD) (group 3)

For Group 4:

- Healthy subjects without any airway disease or any atopic status, as assessed by a questionnaire and a medical examination

Exclusion Criteria:

For all groups:

  • Patients with any other form of secondary CRSwNP (eg, cystic fibrosis, primary ciliary dyskinesia).
  • Patients with any form of secondary severe asthma (eg (non)eosinophilic granulomatosis with polyangiitis, allergic bronchopulmonary aspergillosis)
  • Patients taking or having taken systemic corticosteroid, leukotriene receptor antagonist, theophylline or long-term macrolide therapy within 1 month prior to sample collections, anti-immunoglobulin E therapy (omalizumab) anti-IL-5/5R or anti IL-4R/anti-IL13 therapies within 6 months before inclusion
  • Patients followed up for another inflammatory or auto-immune disease
  • Previous allogeneic bone marrow transplant
  • Patients with ongoing sub-cutaneous or sub-lingual anti-allergenic immunotherapies
  • Patients with active smoking or history of smoking > 10 packages-year for asthma patients
  • Pregnant, breastfeeding, or lactating women
  • Non-coverage by the social security insurance
  • Patient unable to receive informed information
  • Refusal to sign the consent form
  • Unwillingness or inability to follow the study procedures, in the opinion of the investigator
  • Person deprived of the liberty
  • Person benefiting from a system of legal protection (guardianship…)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04187976


Contacts
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Contact: Cécile Chenivesse, MD,PhD 03 20 44 59 48 ext +33 cecile.chenivesse@chru-lille.fr

Sponsors and Collaborators
University Hospital, Lille
Investigators
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Principal Investigator: Cécile Chenivess, MD,PhD University Hospital, Lille

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Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT04187976    
Other Study ID Numbers: 2018_81
2019-A01457-50 ( Other Identifier: ID-RCB number,ANSM )
First Posted: December 5, 2019    Key Record Dates
Last Update Posted: December 5, 2019
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Lille:
Eosinophil
asthma
chronic rhinosinusitis with nasal polyps
biotherapy
endotype
Additional relevant MeSH terms:
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Rhinitis
Sinusitis
Pulmonary Eosinophilia
Respiratory Tract Diseases
Lung Diseases
Nose Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Paranasal Sinus Diseases
Hypereosinophilic Syndrome
Eosinophilia
Leukocyte Disorders
Hematologic Diseases