Mechanisms of Smell Improvement With Dupilumab.

Medical University of South Carolina60 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Chronic Rhinosinusitis With Nasal Polyps

Interventions

DupilumabDRUG

Monoclonal antibody blocking interleukin 4 and interleukin 13

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (2)

Medical University of South Carolina

Charleston, South Carolina, United States

University of Virginia

Charlottesville, Virginia, United States

Outcomes

Primary Outcomes

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.

Time frame: 3 months post-treatment

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.

Time frame: 3 months post-treatment

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).

Time frame: 3 months post-treatment

Change in Lund-Kennedy endoscopy score.

Data from ClinicalTrials.gov

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Secondary Outcomes

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.

Time frame: 3 months post-treatment

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.

Time frame: 3 months post-treatment