Mechanisms of Smell Improvement With Dupilumab.

Mechanisms of Smell Improvement With Dupilumab

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 Overview

• Status: Completed
• Conditions: Chronic Rhinosinusitis With Nasal Polyps
• Intervention / Treatment: Drug: Dupilumab

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Virginia
    • Charlottesville, Virginia, United States, 22904
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; The treatment group will receive dupilumab at 300mg SC Q2weeks. The first dose will be administered via subcutaneous injection in clinic at baseline. Subjects will self-administer study drug (dupilumab 300 mg) subcutaneous every 2 weeks after initial dosing at visit 2.	Drug: Dupilumab; Monoclonal antibody blocking interleukin 4 and interleukin 13

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Volumetric Olfactory Cleft Opacification Based on CT.	Non-contrast sinus computed tomography (CT) scans were obtained at Baseline and Week 12. Volumetric analysis of the olfactory cleft was performed using previously described methods. Total olfactory cleft volume and air volume were measured to calculate percent olfactory cleft opacification as [1 - (air volume/total olfactory cleft volume)] × 100. Percent olfactory cleft opacification ranges from 0% to 100%, with higher values indicating greater olfactory cleft inflammation and disease severity and lower values indicating less inflammation and improvement.	Baseline and Week 12 (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.	3 months post-treatment
Change in Olfactory Cleft Mucus IL-13 Concentration	Olfactory cleft mucus samples were collected under endoscopic guidance at Baseline, Week 2, and Week 12. IL-13 concentrations were measured using a commercially available LegendPlex Th2 Cytometric Bead Array according to the manufacturer's instructions. The outcome reported here represents IL-13 concentration measured at Baseline and Week 12 to evaluate change after 3 months of dupilumab treatment.	Baseline and Week 12 (3 months post-treatment)
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
Change in Overall Polyp Score From Sinonasal Endoscopy	Overall Nasal Polyp Score (NPS) was assessed by sinonasal endoscopy. Polyps were graded separately in each nasal cavity on a scale from 0 to 4 and summed to calculate a total bilateral score ranging from 0 to 8. Higher scores indicate greater nasal polyp burden and more severe disease, while lower scores indicate less disease and improvement.	Baseline and Week 12 (3 months post-treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation Between Change in Olfactory Cleft Mucus IL-13 Level and Sniffin' Sticks TDI Score	Quantitative psychophysical olfactory testing was performed using the Sniffin' Sticks Test. This validated test assesses odor threshold (T), odor discrimination (D), and odor identification (I). Individual component scores are summed to generate a Total TDI Score that reflects overall olfactory function, with higher scores indicating better olfactory function. The correlation between olfactory cleft mucus IL-13 levels and change in Total TDI Score from Baseline to Week 12 was assessed using Spearman correlation.	Baseline and Week 12 (3 months post-treatment)
Correlation Between Change in IL13 Level and QOD-NS Score	Olfactory-specific quality of life was assessed using the Questionnaire of Olfactory Disorders - Negative Statements (QOD-NS), a validated patient-reported outcome measure of olfactory-specific quality of life. The QOD-NS total score ranges from 0 to 51, with higher scores indicating better olfactory-specific quality of life and lower scores indicating greater olfactory-related impairment. The correlation between change in olfactory cleft mucus IL-13 level and change in QOD-NS score from Baseline to Week 12 was assessed using Spearman correlation.	Baseline and Week 12 (3 months post-treatment)

Collaborators and Investigators

• Sponsor: Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2023
• Primary Completion (Actual): January 30, 2025
• Study Completion (Actual): January 30, 2025

Study Registration Dates

• First Submitted: February 15, 2023
• First Submitted That Met QC Criteria: July 25, 2023
• First Posted (Actual): July 28, 2023

Study Record Updates

• Last Update Posted (Actual): August 5, 2026
• Last Update Submitted That Met QC Criteria: July 10, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Chronic Rhinosinusitis; dupilumab; Nasal Polyps
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Respiratory Tract Diseases; Nose Diseases; Otorhinolaryngologic Diseases; Polyps; Pathological Conditions, Signs and Symptoms; Nasal Polyps; dupilumab
• Other Study ID Numbers: Pro00125142

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes