Chronic Rhinosinusitis With Nasal Polyps
Conditions
Keywords
Chronic Rhinosinusitis, Nasal Polyps, dupilumab
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.
Interventions
DRUGDupilumab
Monoclonal antibody blocking interleukin 4 and interleukin 13
Sponsors
Medical University of South Carolina
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Volumetric Olfactory Cleft Opacification Based on CT. | 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. | 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 | 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. | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between Change in Olfactory Cleft Mucus IL-13 Level and Sniffin' Sticks TDI Score | Baseline and Week 12 (3 months post-treatment) | 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. |
| Correlation Between Change in IL13 Level and QOD-NS Score | Baseline and Week 12 (3 months post-treatment) | 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. |
Countries
United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 53.4 years STANDARD_DEVIATION 17.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 59 |
| other Total, other adverse events | 12 / 59 |
| serious Total, serious adverse events | 1 / 59 |
Outcome results
None listed