Mechanisms of Smell Improvement With Dupilumab.

Chronic Rhinosinusitis With Nasal Polyps Clinical Trial

Official title:

Mechanisms of Smell Improvement With Dupilumab

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05964465
• Other study ID #: Pro00125142
• Status: Recruiting
• Phase: Phase 4
• Start date: August 10, 2023
• Est. completion date: June 30, 2025

Study information

• Verified date: September 2023
• Source: Medical University of South Carolina
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study seeks to explore the mechanism through which dupilumab improves olfactory cleft inflammation in patients with chronic sinusitis with nasal polyps (CRSwNP). The investigators expect this study to provide convincing evidence that dupilumab improves clinical olfaction via direct reduction in olfactory cleft inflammation.

Description:

Post-marketed administration of dupilumab (FDA approved medication for CRSwNP) in patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) will result in significant improvement in objective measures of olfactory cleft inflammation and psychophysical olfaction. The investigators seek to explore the mechanism through which dupilumab improves olfactory cleft inflammation in patients with CRSwNP. The investigators also want to determine whether change in olfactory cleft inflammation correlates with improvement in olfaction (one of the cardinal symptoms of CRSwNP) at 3 months. The investigators hypothesize that after 3 months of treatment with dupilumab, non-inflammatory factors will explain a significant degree of variation in residual clinical olfaction. Additionally, the investigators want to explore the determinants of ongoing olfactory loss after 3 months of treatment with attention to non-inflammatory factors. The investigators expect this study to provide convincing evidence that dupilumab improves clinical olfaction via direct reduction in olfactory cleft inflammation. Specifically, the investigators expect to show that reduction in olfactory cleft inflammation is the result of reduction in IL13 levels in olfactory cleft mucus. Finally, the investigators expect to show that most of the variation in post-treatment olfaction can be explained by non-inflammatory measures that are independent of CRSwNP.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults =18 years of age
• Meet criteria for CRSwNP as defined by ICAR-21
• 2 out of 4 cardinal symptoms for =12 weeks
• Visible evidence of inflammation on endoscopy or imaging
• Bilateral visible nasal polyps =1 in each nasal cavity (0-4 scale each side)
• Olfaction score =1 (0-3 scale)
• Candidate for treatment with dupilumab for CRSwNP
• Elected to proceed with dupilumab for treatment of CRSwNP

Exclusion Criteria:

• Prior use of dupilumab
• Previous treatment with another biologic medication for CRSwNP or asthma within 6 months
• Any nasal or sinus surgery within the last 3 months
• Oral corticosteroid use within the last 1 month
• Current pregnancy, breast-feeding, or plan to become pregnant during next 3 months
• Presence of antrochoanal nasal polyps; acute rhinosinusitis; upper respiratory infection;
• Allergic granulomatous angiitis/eosinophilic granulomatosis with polyangiitis;
• Granulomatosis with polyangiitis; cystic fibrosis; Young syndrome;
• Kartagener syndrome; or dyskinetic cilia syndrome
• Poorly controlled asthma

Related Conditions & MeSH terms

• Chronic Rhinosinusitis With Nasal Polyps
• Nasal Polyps

Intervention

Drug:
• Dupilumab
Monoclonal antibody blocking interleukin 4 and interleukin 13

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia	Charlottesville	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of South Carolina

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in volumetric olfactory cleft opacification based on CT.	Non-contrast sinus computed tomography (CT) scans will be obtained at baseline and 3 month follow-up to provide 1mm cuts that can be formatted in coronal, sagittal, and axial planes. Volumetric analysis of the OC will be performed utilizing equally spaced coronal CT images per our previously described protocols. Total volume of the segmented 3-D olfactory cleft space will be calculated, as well as the volume of air within that space. The percent opacification will be defined as [1-(total volume of air/total volume of olfactory cleft)] multiplied by 100. Sinus opacification will be quantified using the Lund-Mackay CT scale.	3 months post-treatment
Primary	Change in olfactory cleft endoscopy score based on nasalendoscopy.	Subjects will have sinonasal endoscopy at baseline and every follow up visit. This procedure allows visual inspection of the sinus mucosal lining and grading of polyps, including the olfactory cleft. Results for each side will be recorded separately and combined for a final Olfactory Cleft Endoscopy Scale (OCES) that ranges from 0-20, with higher scores representing increased disease severity.	3 months post-treatment
Primary	Change in olfactory cleft mucus cytokine levels	Under endoscopic guidance, a 1 × 2-cm Leukosorb filter paper (Pall Scientific, Port Washington, NY) strip will be placed into the olfactory cleft of each side, and kept in place for 3 minutes, as described in earlier studies. This will be done at baseline, 2 weeks, and 3 months. Olfactory cleft mucus inflammatory cytokine levels will be detected using commercially available LegendPlex Th2 Cytometric Bead Array (BioLegend, San Diego, CA) following the manufacturer's recommended protocol. This panel will include IL4, IL13, IL5 cytokines (among others). The assay will be carried out according to manufacturers' instructions and as previously described. The samples will be read on a Guava easyCyte 8HT flow cytometer (EMD Millipore) and analysis performed with LegendPlex software. Total IgE will be quantified via ELISA (GenWay Biotech. Inc, San Diego, CA).	3 months post-treatment
Primary	Change in Lund-Kennedy endoscopy score.	Subjects will have sinonasal endoscopy at baseline and every follow up visit. This procedure allows visual inspection of the sinus mucosal lining and grading of polyps, including the olfactory cleft. Results for each side will be recorded separately and combined for a final Lund-Kennedy endoscopy score (LKES) that ranges from 0-20, with higher scores representing increased disease severity.	3 months post-treatment
Primary	Change in overall polyp score from sinonasal endoscopy	Overall polyp score on a 0-4 scale for each nostril (summed 0-8).	3 months post-treatment.
Secondary	Correlation between change in olfactory cleft mucus IL13 level and Sniffin Sticks TDI	Quantitative psychophysical olfactory testing will be performed using the "Sniffin' Sticks" test (Burghardt, Wedel, Germany). Testing will be performed by trained clinical research coordinators who routinely perform objective olfactory testing and will be done in a blinded fashion. This commercially available test battery measures odor threshold (OT), odor discrimination (OD) and odor identification (OI). The results will be combined for an overall TDI score. TDI will be correlated with OC IL13 levels.	3 months post-treatment
Secondary	Correlation between change in IL13 level and QOD-NS score	Olfactory-specific QOL will be assessed using the previously validated, short, modified version of the Questionnaire of Olfactory Disorders (QOD-NS) survey. This instrument was validated by Mattos and Soler and has been found to have criterion validity, internal consistency, and excellent reproducibility.	3 months post-treatment