Clinical trial NCT05964465: Mechanisms of Smell Improvement With Dupilumab.
Official title: Mechanisms of Smell Improvement With Dupilumab
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Rhinosinusitis With Nasal Polyps
Keywords: Chronic Rhinosinusitis
Nasal Polyps
dupilumab
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
First posted: 2023-07-28
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in volumetric olfactory cleft opacification based on CT.
timeFrame: 3 months post-treatment
measure: Change in olfactory cleft endoscopy score based on nasalendoscopy.
timeFrame: 3 months post-treatment
measure: Change in olfactory cleft mucus cytokine levels
timeFrame: 3 months post-treatment
measure: Change in Lund-Kennedy endoscopy score.
timeFrame: 3 months post-treatment
measure: Change in overall polyp score from sinonasal endoscopy
timeFrame: 3 months post-treatment.
Secondary outcomes:
measure: Correlation between change in olfactory cleft mucus IL13 level and Sniffin Sticks TDI
timeFrame: 3 months post-treatment
measure: Correlation between change in IL13 level and QOD-NS score
timeFrame: 3 months post-treatment
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
References: