Basal Instincts: Towards Better Understanding of Basal Cell Function in Chronic Rhinosinusitis With Nasal Polyps

During this project, the investigators want to explore in vitro changes in basal cells and the crosstalk with residing immune cells as potential pathogenic mechanisms in CRSwNP vs healthy controls by using surgically resected patient samples.

Study Overview

• Status: Recruiting
• Conditions: Allergic Rhinitis; Chronic Rhinosinusitis With Nasal Polyps
• Intervention / Treatment: Procedure: Conchotomy, aesthetic nose surgery or functional endoscopic sinus operation

Detailed Description

The investigators want to use patient and healthy control samples to study/compare the following aspects in vitro:

1. Investigate differences in epithelial and basal cell functions and differentiation characteristics.
2. Characterize the differences in epithelial cell populations and gene expression patterns. Also include an AR subset, to see if changes are specific for CRSwNP or more general for type 2 inflammatory disease of the upper airways.
3. Investigate basal cell activation via different environmental triggers through TLR stimulation.
4. Look at the genetic imprinting of basal cells before and after being exposed to specific triggers.
5. Investigate whether the secreted proteins from basal cells are chemotactic for other cell populations.
6. Investigate the interaction between basal and regulatory T cells.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Peter Hellings, MD, PhD; Phone Number: +32 16 33 23 42; Email: peter.hellings@uzleuven.be
• Study Contact Backup: Name: Dominique Bullens, MD, PhD; Phone Number: +32 16 34 13 38; Email: dominique.bullens@uzleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • Peter Hellings
    • Contact: dominique bullens, MD PhD; Phone Number: +3216341338; Email: dominique.bullens@kuleuven.be
    • Contact: Daan Rodiers, MsC; Phone Number: +3216346165; Email: daan.rodiers@kuleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

CRSwNP patients:

Inclusion Criteria:

• Patients over the age of 18
• Males and females
• Patient with symptoms of chronic rhinosinusitis
• Presence of nasal polyps

Exclusion Criteria:

• AR
• Smoker, or < 1-year ex-smoker
• Patient with cystic fibrosis
• Only the presence of an antrochoanal polyp
• Underlying systematic pathology (Morbus Wegener or Churg Strauss Syndrome for example)

AR patients:

Inclusion criteria:

• Patients over the age of 18
• Males and females
• Patients with AR symptoms

Exclusion criteria:

• CRSwNP
• Smoker, or < 1-year ex-smoker
• Underlying systematic pathology (Morbus Wegener or Churg Strauss Syndrome for example)

Description

Inclusion Criteria:

• Patients over the age of 18
• Males and females

Exclusion Criteria:

• CRSwNP
• AR
• Smoker, or < 1-year ex-smoker
• Underlying systematic pathology (Morbus Wegener or Churg Strauss Syndrome for example)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy controls	Procedure: Conchotomy, aesthetic nose surgery or functional endoscopic sinus operation; Conchotomy involves the reduction or removal of hypertrophic nasal turbinates, aesthetic nose surgery is a surgical procedure that aims to enhance the appearance of the nose, while functional endoscopic sinus surgery is a minimally invasive procedure focused on treating sinus conditions by removing obstructions and improving sinus drainage.
CRSwNP patients	Procedure: Conchotomy, aesthetic nose surgery or functional endoscopic sinus operation; Conchotomy involves the reduction or removal of hypertrophic nasal turbinates, aesthetic nose surgery is a surgical procedure that aims to enhance the appearance of the nose, while functional endoscopic sinus surgery is a minimally invasive procedure focused on treating sinus conditions by removing obstructions and improving sinus drainage.
AR patients	Procedure: Conchotomy, aesthetic nose surgery or functional endoscopic sinus operation; Conchotomy involves the reduction or removal of hypertrophic nasal turbinates, aesthetic nose surgery is a surgical procedure that aims to enhance the appearance of the nose, while functional endoscopic sinus surgery is a minimally invasive procedure focused on treating sinus conditions by removing obstructions and improving sinus drainage.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional differences between epithelial/basal cells from CRSwNP samples in comparison to healthy controls assessed with functional assays.	Multiple techniques and functional assays will be used to fully investigate the functional differences between epithelial/basal cells isolated from healthy and CRSwNP samples. The differences in barrier composition will be assessed through TEER measurements (Ω × cm2) and FD4 permeability assays (ng/ml). Moreover, barrier composition is investigated by examining differences in membrane markers and junction expression through immunofluorescence and RT-qPCR. Finally, primary isolated cells will be used to assess protein levels through immunostainings, flow cytometry, and Western blots.	12-24 months
Characterization of differences in gene expression profiles and epithelial populations in/between CRSwNP and healthy controls assessed with different sequencing techniques.	To characterize differences in gene expression, or identify specific genes/cell populations that can contribute to CRSwNP, scRNA-sequencing will be performed, as well as bulk RNA sequencing. Depending on these results, specific triggers or receptors that can contribute to CRSwNP will be investigated by stimulation experiments. Besides, the effect on epigenetic imprinting before and after stimulation by performing ATAC-sequencing or DNA methylation profiling will be studied as well.	9-18 months
Changes and interactions in the basal and regulatory T-cell axis between healthy and CRSwNP-isolated cells will be studied through co-culture experiments.	The interaction between basal and regulatory T cells in relation to homeostasis and regeneration, and how this might change or contribute in/to CRSwNP will be investigated by co-culturing these cells. This will be assessed through the analysis of the supernatants using the Olink platform to investigate cytokines etc. Besides, there will be bulk RNA sequencing to look at changes in gene expression, as well as proliferation and growth assays to see the effect of T cells on basal cells and vice versa. To look at functional changes we can asses different functional assays and techniques (see outcome 1).	9-18 months

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2023
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: October 26, 2023
• First Submitted That Met QC Criteria: November 8, 2023
• First Posted (Actual): November 13, 2023

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Respiratory Hypersensitivity; Hypersensitivity; Paranasal Sinus Diseases; Nose Diseases; Sinusitis; Rhinitis; Rhinitis, Allergic; Nasal Polyps; Polyps; Rhinosinusitis
• Other Study ID Numbers: S67788

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No