Mechanisms of Smell Improvement With Dupilumab
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Enrollment
- 60
- Locations
- 2
- Primary Endpoint
- Change in Volumetric Olfactory Cleft Opacification Based on CT.
Study Overview
Brief 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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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.
Intervention: Dupilumab (Drug)
Outcomes
Primary Outcomes
Change in Volumetric Olfactory Cleft Opacification Based on CT.
Time Frame: Baseline and Week 12 (3 months post-treatment)
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.
Change in Olfactory Cleft Endoscopy Score Based on Nasalendoscopy.
Time Frame: 3 months post-treatment
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.
Change in Olfactory Cleft Mucus IL-13 Concentration
Time Frame: Baseline and Week 12 (3 months post-treatment)
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.
Change in Lund-Kennedy Endoscopy Score.
Time Frame: 3 months post-treatment
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.
Change in Overall Polyp Score From Sinonasal Endoscopy
Time Frame: Baseline and Week 12 (3 months post-treatment)
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.
Secondary Outcomes
- Correlation Between Change in Olfactory Cleft Mucus IL-13 Level and Sniffin' Sticks TDI Score(Baseline and Week 12 (3 months post-treatment))
- Correlation Between Change in IL13 Level and QOD-NS Score(Baseline and Week 12 (3 months post-treatment))
Investigators
Shaun Nguyen
Professor and Director of Clinical Research
Medical University of South Carolina