Clinical trial NCT06398873: Effect of Dupilumab on Nasal Epithelial Barrier Function in Patients With CRSwNP
Official title: Effect of Dupilumab on Nasal Epithelial Barrier Function in Patients With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) - an Exploratory Pilot Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Chronic Rhinosinusitis With Nasal Polyps
Chronic Rhinosinusitis Without Nasal Polyps
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2024-05-03
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with chronic rhinosinusitis with and without nasal polyps

Brief summary: The investigators aim to investigate two major so far unresolved topics in CRSwNP research: (1) Thorough functional and molecular characterisation of barrier function in patients suffering from CRSsNP and CRSwNP and (2) effect of dupilumab treatment on barrier function in polyp patients. This will be achieved in patient-derived samples by employing measurement of barrier function in primary cell cultures in combination with a mass cytometry based imaging approach, transcriptomic analysis as well as cytokine and microbiome data of individual patients.

Detailed description: Primary objective 1: Characterization of differences in barrier function of the nasal epithelium in patients suffering from CRSsNP, CRSwNP with and without asthma or N-ERD (in absence of therapy with monoclonal antibodies). T Primary objective 2: Effect of dupilumab treatment on barrier function of the nasal epithelium in patients suffering from CRSwNP with and without asthma or N-ERD.

Eligibility criteria: Inclusion Criteria:

* 18-99 years of age
* Willingness to participate in the study
* Suffer from chronic rhinosinusitis defined as in EPOS 2020 criteria, see main text
* Group 1 (n=20, CRSsNP): Absence of nasal polyps
* Group 2 (N=60, CRSwNP): Presence of nasal polyps as confirmed by endoscopy or CT and planned therapy with dupilumab
* Presence or absence of non-steroidal anti-inflammatory drug (NSAID)-Exacerbated Respiratory Disease (N-ERD)
* Patients with a history of treatment with monoclonal antibodies will only be included if at least a washout period of 6 months has passed

Exclusion Criteria:

* Pregnancy (as determined by ß-HCG test) or breast feeding
* Patients with severe anatomic variations or deviations that do not allow access to all areas in the nasal cavity
* Patients with cystic fibrosis or primary ciliary dyskinesia
* Patients with permanent immunosuppression
* A mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
* Patients with clinically meaningful comorbidity as determined by the evaluating committee
* Patients with a history of exacerbation of chronic rhinosinusitis 4 weeks prior to the screening visit
* Intake of a burst of systemic corticosteroids for the treatment of CRS 4 weeks prior to the screening visit

Primary outcomes:
measure: Barrier function in CRSsNP and CRSwNP
timeFrame: 1 Visit (baseline)
measure: Barrier function in CRSwNP with Dupilumab
timeFrame: 3 Visits (baseline, 3 months, 6 months)
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
Study officials:
References:
citation: Bachert C, Han JK, Desrosiers M, Hellings PW, Amin N, Lee SE, Mullol J, Greos LS, Bosso JV, Laidlaw TM, Cervin AU, Maspero JF, Hopkins C, Olze H, Canonica GW, Paggiaro P, Cho SH, Fokkens WJ, Fujieda S, Zhang M, Lu X, Fan C, Draikiwicz S, Kamat SA, Khan A, Pirozzi G, Patel N, Graham NMH, Ruddy M, Staudinger H, Weinreich D, Stahl N, Yancopoulos GD, Mannent LP. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet. 2019 Nov 2;394(10209):1638-1650. doi: 10.1016/S0140-6736(19)31881-1. Epub 2019 Sep 19.
citation: Schneider S, Poglitsch K, Morgenstern C, Quint T, Gangl K, Sinz C, Bartosik T, Campion NJ, Liu DT, Landegger LD, Tu A, Stanek V, Rocha-Hasler M, Bangert C, Eckl-Dorna J. Dupilumab increases aspirin tolerance in NSAID-exacerbated respiratory disease. Eur Respir J. 2023 Mar 16;61(3):2201335. doi: 10.1183/13993003.01335-2022. Print 2023 Mar.