The Role of IL5 in Epithelial Cell Integrity

The goal of this laboratory study is the examine the effect of mepolizumab drug on the health and function of the cells lining the human nasal airways in vitro cell culture derived from patients with chronic rhinosinusitis with nasal polyposis. The main questions the study aims to study are:

1. To see what mepolizumab does to suppress inflammation of the human cells.
2. To see what mepolizumab does to maintain barrier integrity of epithelial cells

Study Overview

• Status: Recruiting
• Conditions: Chronic Rhinosinusitis (Diagnosis); Chronic Rhinosinusitis With Nasal Polyps
• Intervention / Treatment: Drug: Mepolizumab

Detailed Description

The investigators hypothesize that anti-IL5 treatment will promote epithelial cell function by inhibition of Type 1 and innate immune mediated inflammation and epithelial-mesenchymal transition resulting from IL5 induction.

Aim 1. To test the hypothesis that anti-IL5 therapy results in inhibition of epithelial cell dysfunction including epithelial derived inflammatory responses and barrier dysfunction, the investigators will examine the effect of in vitro anti-IL5 mepolizumab exposure of human primary nasal epithelial cells from chronic rhinosinusitis with nasal polyposis on Type 1, Type 2 and innate immune inflammatory markers, and markers of epithelial cell barrier function.

Aim 2. To examine the effect of mepolizumab to broadly modulate the expression of Type 2, Type 1, Type 3, and innate immune inflammatory gene responses in human nasal airway epithelial cells, the investigators will perform high throughput RNA sequencing on IL5 primed differentiated human primary nasal epithelial cells exposed to the presence and absence of mepolizumab in vitro cell culture which are derived from patients with chronic rhinosinusitis with nasal polyposis. These studies will provide an unbiased approach to identification of biomarkers resulting from anti-IL5 treatment.

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jean Kim, MD PhD; Phone Number: 410-550-2644; Email: jeankim@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins Hospital
      • Contact: Jean Kim, MD PhD; Phone Number: 410-550-0460; Email: jeankim@jhmi.edu
      • Contact: Hyun Lee, PhD; Phone Number: 410-550-2064; Email: hlee77@jhmi.edu
    • Baltimore, Maryland, United States, 21117
      • Recruiting
      • Johns Hopkins Bayview Medical Center
      • Contact: Jean Kim, MD PhD; Phone Number: 410-550-0460; Email: jeankim@jhmi.edu
      • Contact: Hyun Sil Lee, PhD; Phone Number: 410-550-2064; Email: hlee77@jhmi.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• (1) sinonasal inflammation for greater than 12 weeks which include at least 2 of the following symptoms: nasal obstruction/congestion, nasal discharge (anterior or posterior), facial pressure/pain, reduction of sense of smell.
• (2) confirmation of the clinical symptoms by: (2a) CT scan evidence of paranasal sinus mucosal inflammation, and/or (2b) endoscopic exam evidence of purulence from the sinuses or ostiomeatal complex; and
• (3) presence of nasal polyps seen on endoscopic exam or sinus CT scan.

Exclusion Criteria:

• 1. Children under the age of 18 will be excluded due to:

  1. possible confounding diagnosis of cystic fibrosis and other non-Type 2 inflammatory etiologies that commonly presents with nasal polyps in the pediatric population.
  2. lack of complete pneumatization of the majority of paranasal sinuses
• 2. pregnant or lactating females,
• 3. prisoners,
• 4. mentally disabled
• 5. persons unable to give informed consent will be contemplated for inclusion.
• 6. disease secondary to a clearly defined anatomic process, such as facial trauma, and obstruction due to sinonasal neoplasm.
• 7. exposure to oral or systemic IV glucocorticoids within 2 weeks of surgery
• 8. exposure to immunomodulatory biologics will be excluded. These include, but are not limited to systemic treatment with biologics omalizumab, dupilumab, mepolizumab, benralizumab, reslizumab, or rituximab.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mepolizumab treatment arm; Nasal epithelial cells will be exposed in vitro to mepolizumab in culture.	Drug: Mepolizumab; In vitro exposure of human nasal epithelial cells to mepolizumab; Other Names: Nucala
No Intervention: Control arm; Nasal epithelial cells will be exposed in vitro to media without mepolizumab in culture

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Type 1 inflammatory markers (ng/mL)	IL8 cytokine mRNA and protein expression	0 to 48 hours
Change in Type 2 inflammatory markers (ng/mL)	IL5 and thymic stromal lymphopoietin cytokine mRNA and protein expression	0 to 48 hours
Change in Innate immune inflammatory markers (ng/mL)	IL1 receptor mRNA and protein expression	0 to 48 hours
Change in epithelial barrier function protein expression (ng/mL)	E-cadherin	0 to 48 hours
Change in epithelial integrity markers (staining intensity units)	alpha-smooth muscle actin protein expression	0 to 48 hours

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Jean Kim, MD PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2023
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: May 12, 2023
• First Submitted That Met QC Criteria: May 30, 2023
• First Posted (Actual): June 9, 2023

Study Record Updates

• Last Update Posted (Actual): October 11, 2023
• Last Update Submitted That Met QC Criteria: October 9, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Paranasal Sinus Diseases; Nose Diseases; Polyps; Sinusitis; Nasal Polyps
• Other Study ID Numbers: IRB00363909

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.: No