Characterization of Natural Killer Cells in Severe Asthma Patients in Comparison With Control Subjects

NCT06015256 | Recruiting

• 2 other identifiers: C21-752022-A00651- 42
• Study Type: interventional
• Target: 448
• Locations: 1 country
• Sites: 1

Brief Summary

Asthma is a common chronic bronchial disease affecting 300 million people worldwide. The disease can be severe when it is not managed properly or when it is not controlled by treatments. Asthma is characterized by bronchial inflammation, bronchial hyperreactivity and tissue remodeling. Symptoms include episodes of coughing, dyspnoea and wheezing in relation with bronchial obstruction. The evolution is marked by the occurrence of exacerbations (increase of symptoms), most often triggered by viral infections, mostly due to rhinoviruses. The treatment of asthma is based on inhaled corticosteroid therapy sometimes combined with other treatments that help control the majority of asthma. However, about 10% of patients suffer from persistent symptoms despite these treatments. Natural killer (NK) cells are important actors of the antiviral innate immune response and are present in high numbers in the lungs. However, their role in severe asthma and its virus-induced exacerbations is unknown. The purpose of this work is to characterize NK cells in severe asthma in order to identify molecules expressed differently from control subjects. The goal is to assess whether these molecules could be potential biomarkers of a severe asthma subtype, also known as the endotype, and/or be the molecular control for exacerbation. The advantage of identifying biomarkers for inflammatory diseases lies in their usefulness in establishing a correct diagnosis, monitoring the progress of the disease and the effectiveness of treatments. The secondary objectives are to characterize the activation of NK cells in response to in vitro rhinovirus infection of different types, in monoculture or in a model of interaction with a bronchial epithelium, and identify one or more molecules involved in the interaction between bronchial epithelial cells and NK cells.

Conditions

Asthma Acute

Outcome Measures

Primary Outcomes (1)

• Changes in expression of one or more molecules on the surface of NK cells

  Rationale for choice of primary endpoint: Our aim is to phenotype NK cells in different groups of severe asthma patients compared with control subjects, in order to identify at least one marker of disease discrimination on these cells. We are therefore looking for previously unknown changes in the expression of one or more molecules.

  day 1 to day 2555

Secondary Outcomes (2)

• Measurement of NK cell activation

  day 1 to day 2555

• Measurement of NK cell-induced epithelial cell activation and viability

  day 1 to day 2555

Study Arms (4)

Severe uncontrolled asthma in exacerbation

OTHER

Biological: blood sample

Severe uncontrolled asthma excluding exacerbation

OTHER

Biological: blood sample

Severe controlled asthma

OTHER

Biological: blood sample

Healthy volunteers (control group)

OTHER

Biological: blood sample

Interventions

blood sample BIOLOGICAL

Blood sample (56mL) taken in a heparin tube

Healthy volunteers (control group); Severe controlled asthma; Severe uncontrolled asthma excluding exacerbation; Severe uncontrolled asthma in exacerbation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cases asthma controlled, uncontrolled excluding exacerbation, uncontrolled asthma exacerbation, and healthy volunteers:
• Consent form read, understood, approved and signed before any study procedure
• Membership of a social security scheme or beneficiary of such a scheme
• Patient aged over 18
• Cases asthma controlled, uncontrolled excluding exacerbation, uncontrolled exacerbation:
• \- Diagnosis of severe asthma confirmed by a respirologist at an expert centre
• Case asthma controlled:
• \- Asthma control confirmed by a lung specialist from an expert centre
• Case uncontrolled asthma excluding exacerbation:
• \- Uncontrolled asthma confirmed by a lung specialist from an expert centre
• Case uncontrolled asthma with exacerbation:
• \- Current exacerbation

You may not qualify if:

• Cases asthma controlled, uncontrolled excluding exacerbation, uncontrolled asthma exacerbation, and healthy volunteers:
• Person subject to a legal protection measure
• Vulnerable population: minors, persons under guardianship or trusteeship or persons deprived of their rights to liberty by court order.
• women with a known pregnancy
• Inability or refusal to comply with research requirements
• Active or weaned smoker \> 15 PA
• Case patient with asthma:
• \- Coexistence of a chronic inflammatory disease other than asthma
• Case healthy volunteers:
• \- Coexistence of an inflammatory pathology
• Cases asthma: Pregnancy during follow-up Cases healthy volunteers: Total IgE level greater than 100 kU/L (measured on the study sample)

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (1)

Hôpital NORD - AP-HM, Clinique des bronches, de l'allergie et du sommeil

Marseille, 13915, France

RECRUITING

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Pascal Chanez, PU-PH

CONTACT

+334.91.96.58.64; pascal.chanez@univ-amu.fr

Catherine Duez, CRCN

CONTACT

+334.91.32.42.74; catherine.duez@inserm.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2023
• First Posted: August 29, 2023
• Study Start: September 7, 2023
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2030
• Last Updated: April 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)