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RecruitingNCT06129552Updated Mar 22, 2024

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

An observational study in Chronic Rhinosinusitis With Nasal Polyps and Allergic Rhinitis, sponsored by Universitaire Ziekenhuizen KU Leuven. Recruiting at 1 site in Belgium. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-03-22.

Sponsored by Universitaire Ziekenhuizen KU Leuven · Observational

Study type
Observational
Model
Cohort
Time perspective
Cross-sectional
Enrollment
300
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the 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.
02

Conditions studied

  • Chronic Rhinosinusitis With Nasal Polyps
  • Allergic Rhinitis
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
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)

Inclusion criteria

  • Patients over the age of 18
  • Males and females

Exclusion criteria

Exclusion Criteria:

  • CRSwNP
  • AR
  • Smoker, or \< 1-year ex-smoker
  • Underlying systematic pathology (Morbus Wegener or Churg Strauss Syndrome for example)
04

Study design

Observational model
Cohort
Time perspective
Cross-sectional
Enrollment
300 participants (estimated)
Target follow-up
1 Day
Patient registry
Yes
Biospecimen retention
Samples with dna

Groups and cohorts

  • Healthy controls

    Procedure: Conchotomy, aesthetic nose surgery or functional endoscopic sinus operation

  • CRSwNP patients

    Procedure: Conchotomy, aesthetic nose surgery or functional endoscopic sinus operation

  • AR patients

    Procedure: Conchotomy, aesthetic nose surgery or functional endoscopic sinus operation

Interventions

  • ProcedureConchotomy, 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.

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 12-24 months

  2. 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.

    Time frame: 9-18 months

  3. 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).

    Time frame: 9-18 months

06

Study locations

1 of 1 sites recruiting
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT06129552
Lead sponsor
Universitaire Ziekenhuizen KU Leuven
Collaborators
Regeneron Pharmaceuticals
Responsible party
Sponsor
First posted
Nov 13, 2023
Start date
Dec 19, 2023
Primary completion
Oct 2027 (estimated)
Completion
Dec 2027 (estimated)
Last update
Mar 22, 2024

Study contacts

Peter Hellings, MD, PhD
Contact
peter.hellings@uzleuven.be
+32 16 33 23 42
Dominique Bullens, MD, PhD
Contact
dominique.bullens@uzleuven.be
+32 16 34 13 38

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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