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The Role of IL5 in Epithelial Cell Integrity

Primary Purpose

Chronic Rhinosinusitis With Nasal Polyps, Chronic Rhinosinusitis (Diagnosis)

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Mepolizumab
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Chronic Rhinosinusitis With Nasal Polyps

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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: possible confounding diagnosis of cystic fibrosis and other non-Type 2 inflammatory etiologies that commonly presents with nasal polyps in the pediatric population. 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.

Sites / Locations

  • Johns Hopkins Bayview Medical CenterRecruiting
  • Johns Hopkins HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Mepolizumab treatment arm

Control arm

Arm Description

Nasal epithelial cells will be exposed in vitro to mepolizumab in culture.

Nasal epithelial cells will be exposed in vitro to media without mepolizumab in culture

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
May 12, 2023
Last Updated
October 9, 2023
Sponsor
Johns Hopkins University
Collaborators
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT05895929
Brief Title
The Role of IL5 in Epithelial Cell Integrity
Official Title
The Role of IL5 in Epithelial Cell Integrity
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 5, 2023 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
GlaxoSmithKline

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
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: To see what mepolizumab does to suppress inflammation of the human cells. To see what mepolizumab does to maintain barrier integrity of epithelial cells
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Rhinosinusitis With Nasal Polyps, Chronic Rhinosinusitis (Diagnosis)

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Nasal epithelial cells will be exposed to defined doses of mepolizumab in vitro culture (Arm 1) or control media without mepolizumab (Arm 2)
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
8 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Mepolizumab treatment arm
Arm Type
Experimental
Arm Description
Nasal epithelial cells will be exposed in vitro to mepolizumab in culture.
Arm Title
Control arm
Arm Type
No Intervention
Arm Description
Nasal epithelial cells will be exposed in vitro to media without mepolizumab in culture
Intervention Type
Drug
Intervention Name(s)
Mepolizumab
Other Intervention Name(s)
Nucala
Intervention Description
In vitro exposure of human nasal epithelial cells to mepolizumab
Primary Outcome Measure Information:
Title
Change in Type 1 inflammatory markers (ng/mL)
Description
IL8 cytokine mRNA and protein expression
Time Frame
0 to 48 hours
Title
Change in Type 2 inflammatory markers (ng/mL)
Description
IL5 and thymic stromal lymphopoietin cytokine mRNA and protein expression
Time Frame
0 to 48 hours
Title
Change in Innate immune inflammatory markers (ng/mL)
Description
IL1 receptor mRNA and protein expression
Time Frame
0 to 48 hours
Title
Change in epithelial barrier function protein expression (ng/mL)
Description
E-cadherin
Time Frame
0 to 48 hours
Title
Change in epithelial integrity markers (staining intensity units)
Description
alpha-smooth muscle actin protein expression
Time Frame
0 to 48 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: possible confounding diagnosis of cystic fibrosis and other non-Type 2 inflammatory etiologies that commonly presents with nasal polyps in the pediatric population. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jean Kim, MD PhD
Phone
410-550-2644
Email
jeankim@jhmi.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean Kim, MD PhD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins Bayview Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21117
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean Kim, MD PhD
Phone
410-550-0460
Email
jeankim@jhmi.edu
First Name & Middle Initial & Last Name & Degree
Hyun Sil Lee, PhD
Phone
410-550-2064
Email
hlee77@jhmi.edu
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean Kim, MD PhD
Phone
410-550-0460
Email
jeankim@jhmi.edu
First Name & Middle Initial & Last Name & Degree
Hyun Lee, PhD
Phone
410-550-2064
Email
hlee77@jhmi.edu

12. IPD Sharing Statement

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The Role of IL5 in Epithelial Cell Integrity

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