Immunological Mechanisms Underlying Mucosal IgE Responses

NCT06234761 | Recruiting

• 1 other identifier: ONZ-2023-0280
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Background / rationale: Type 2 inflammation is driving several chronic diseases in the airway. On one hand allergic rhinitis (AR) and allergic asthma (AA) are driven by allergen expose, while on the other hand eosinophilic Type 2 inflammation with late onset eosinophilic asthma (LOA) and chronic rhinosinusitis with nasal polyps (CRSwNP) are of non-allergic ethiology. For late onset type2 asthma, many risk factors have been defined, but clear insights into disease ethiology are currently lacking. Given the quintessential role of IgE in disease ethiology of both diseases, understanding the molecular immunological mechanisms underlying mucosal IgE responses is essential to understand disease ethiology. Hypothesis: Distinct mechanisms drive local IgE production in AA and LOA Overall objectives: Elucidate the potential drivers of and immunological pathways leading to local IgE production in AA and LOA, and understand how dupilumab acts on these mechanisms. Methods: A unique combination of state-of-the-art methods will be applied, including single-cell RNA sequencing and receptor profiling, proteomics, determination of the microbial composition, recombinant antibody screening and disease modelling in cell cultures. Expected results: The investigators expect for the first time to discern the drivers of local IgE production in LOA and uncover the immunological pathways leading to local IgE production in AA and LOA. Moreover, the investigators will obtain insights into the role of Dupilumab in modulation mechanisms. Impact: If successful, these insights will answer a long standing, unresolved question in type 2 disease and might aid in the development of novel directed therapeutics for AA and LOA.

Conditions

Pathophysiology

Outcome Measures

Primary Outcomes (3)

• Understanding the mechanisms of allergic and non-allergic IgE B cell differentiation

  Investigate the difference IgE B cell differentiation in nasal polyp tissue and nasal tissue from allergic patients

  1 year

• Elucidating the drivers of non-allergic IgE B cell responses

  Identify the possible compounds that regulate IgE B cell responses

  2 years

• Elucidating epithelial instruction in CRSwNP and allergic rhinitis to IgE B cells

  Elucidating the role of epithelial cells in CRSwNP IgE class switch recombination compared to allergic rhinitis

  2 years

Study Arms (1)

patients with nasal polyposis

Patients with nasal polyposis will be treated with dupilumab following the clinical care path available in the hospital

Drug: Dupilumab

Interventions

Dupilumab DRUG

Patient who start to take dupilumab will be followed. This study is only observational

patients with nasal polyposis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

patients with nasal polyposis and with or without asthma

You may qualify if:

• patients with nasal polyposis -

You may not qualify if:

• patients treated in the last 2 months with systemic corticosteroids

Sponsors & Collaborators

• University Hospital, Ghent: lead
• Sanofi: collaborator

Study Sites (1)

University Hospital Gent

Ghent, 9000, Belgium

RECRUITING

Related Links

• Cluster analysis and clinical phenotypes
• Omalizumab and nasal polyposis
• IgE B cell responses
• Extrafollicular B cells

Biospecimen

Retention: SAMPLES WITH DNA

tissue and blood samples of patients with nasal polyposis

MeSH Terms

Interventions

dupilumab

Central Study Contacts

Philippe Gevaert, PHD

CONTACT

003293322332; philippe.gevaert@ugent.be

Lara Derycke, pHD

CONTACT

003293321246; lara.derycke@ugent.be

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2024
• First Posted: January 31, 2024
• Study Start: January 2, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)