Clinical trial NCT06188871: Early-onset Dupilumab Effects in CRSwNP
Official title: Early Changes in Type 2 Inflammatory Cytokines, Respiratory Oscillometry, and Sinonasal Microbiome With Dupilumab Treatment for Chronic Rhinosinusitis With Nasal Polyps
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Chronic Rhinosinusitis With Nasal Polyps
Lead sponsor: University of Rochester
Sponsor class: OTHER
First posted: 2024-01-03
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: While it is known that Dupilumab has profound effects in patients with CRSwNP, these are often seen months later after treatment initiation; however, in practice, patients often endorse feeling significantly better within days of their first injection. No studies have investigated the molecular basis for such an acute change. This study proposes that specific cytokine changes in phenotype in addition to microbiome and oscillometry effects play a synergistic role in producing this effect.

Detailed description: This is a single center, prospective, controlled pilot study investigating the acute-onset changes across multiple parameters from immunology to microbiome and pulmonary physiology in patients with CRSwNP after receiving initial doses of dupilumab therapy. In total, eligible participants will be enrolled in the study for a total of 3 weeks, during which they will receive two injections of 300 mg of dupilumab. There will be a total of 8 study visits with the 1st visit being a 1-month pre-intervention baseline allowing each patient to serve as independent controls. The next seven visits will be at the following time points: Day of the 1st injection, 24-hrs after the first injection, 48 hrs after the first injection, one week after the first injection, two weeks after the first injection prior to receiving the second injection, 24hrs after receiving the 2nd injection and the 3-week timepoint (1 week after the second injection). At each visit, patients will be screened for side effects and nasal endoscopy will be performed as well as collection of nasal secretions via sinus packings that are placed in both nares for five minutes. The packings will subsequently be removed and per the collection protocol will undergo centrifugation, aliquoting and storage in a -80 freezer for future cytokine analysis via ELISA assays for various cytokine markers of type 2 inflammation, neutrophil activity, and mucin type. At specific visits, additional measures will be collected including Staph Aureus swabs for qPCR and cell culture, SNOT-22 surveys and smell testing, and oscillometry.

Eligibility criteria: Inclusion Criteria:

* Patients age 18+
* who in normal clinical practice would be a candidate for dupilumab.
* with a diagnosis of CRSwNP including
* at least 2 of the following symptoms on screening:

  * nasal blockade/obstruction/congestion or nasal discharge;
  * facial pain/pressure;
  * reduction or loss of smell

Exclusion Criteria:

* \> 80 years of age
* prior history of immunotherapy use (including prior participation in dupilumab or other clinical trials)
* Treatment with systemic corticosteroids, monoclonal antibodies, immunosuppressive treatments or anti-IgE therapy during the past two months prior to trial participation.
* CRS without polyps or another non-nasal polyposis condition
* Patients with conditions/concomitant diseases making them ineligible for evaluation of the primary efficacy endpoint such as: acute sinusitis/nasal infection or upper respiratory infection at day of screening or in the two weeks prior to screening, Churg-Strauss syndrome, Young's syndrome, Kartagener's syndrome or dyskinetic ciliary syndromes, concomitant cystic fibrosis, CT scan suggestive of allergic fungal rhinosinusitis
* Patients with comorbid asthma if they had a recent asthma exacerbation requiring systemic (oral and/or parenteral) steroid treatment or hospitalization for \>24h for treatment of asthma, within 3 months prior to screening or are on a dose of greater than 1000 ug fluticasone or an equivalent inhaled corticosteroid.

Primary outcomes:
measure: Mean change in concentration of IgE (IU/mL)
timeFrame: 3 weeks post baseline
Secondary outcomes:
measure: Mean change in concentration of type II inflammatory markers contributing to sinonasal inflammation (ng/mL)
timeFrame: 3 weeks post baseline
measure: Mean change in concentration of markers of neutrophil activity contributing to sinonasal inflammation (ng/mL)
timeFrame: 3 weeks post baseline
measure: Mean change in concentration of markers of mucin type contributing to sinonasal inflammation (ng/mL)
timeFrame: 3 weeks post baseline
measure: Mean change in active Staph Aureus collected via nasal swabs
timeFrame: 3 weeks
Other outcomes:
measure: Mean change in SNOT-22 score
timeFrame: 3 weeks
measure: Mean change in UPSIT score
timeFrame: 3 weeks
measure: Mean change in oscillometry data R5-R20 (frequency-dependent resistance heterogeneity between 5 and 20 Hz)
timeFrame: 3 weeks
measure: Mean change in oscillometry X5 (reactance at 5 Hz)
timeFrame: 3 weeks
measure: Mean change in oscillometry AX (area under the reactance curve)
timeFrame: 3 weeks
Locations:
city: Rochester
country: United States
facility: University of Rochester Department of Otolaryngology Head and Neck Surgery
state: New York
Study officials:
affiliation: University of Rochester
name: Li-Xing Man, MSc, MD, MPA
role: PRINCIPAL_INVESTIGATOR
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