Viral and Epigenetic Influences in CRSwNP

NCT05857228 | Active Not Recruiting

• 1 other identifier: 08.149
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Background/rationale While multiple disorders feature a Type 2 (T2) inflammation, triggers for T2 remains unknown. In Chronic Rhinosinusitis with Nasal Polyposis CRSwNP), a classic Type 2 disorder, dysfunction of the epithelial barrier is suggested by loss of epithelial cell differentiation, impaired response to wounding, and impairment of innate defense mechanisms. After unsuccessful attempts to describe T2 disorders solely by host genetic or environmental factors, the role of epigenetics in the modification of innate immune response and epithelial integrity appears an important unexplored mechanism for a novel appreciation of T2 disease. In addition, the investigators explore the possibility that these changes may be induced by viral pathogens. This concept has been supported by the recent observation that SARS-CoV-2 viral reduction measures resulted in a reduction of the frequency of respiratory viruses and a concomitant reduction in chronic airway disease, suggesting a role for viruses in T2 disease. Hypothesis The investigators believe T2 chronic rhinosinusitis (CRSwNP) involves epigenetic mechanisms where external factors, possibly viruses, contribute to disease via epigenetic manipulation and/or chronic viral infection. Objectives The investigators aim to identify epigenetic signatures associated with T2 CRS and explore the contribution of viruses. Method A robust methylation profiling with extensive coverage will be used for epigenome-wide association studies in T2 CRS patients assessing healthy subjects, CRS patients in remission, and diseased patients undergoing surgery. Moreover, advanced transcriptomic and metagenomic methods will identify gene expression profiles and viruses. This proposal also includes a cross-sectional study of patients undergoing surgery to assess transcriptomic patterns and epigenetics at the single-cell level. Expected outcome The investigators expect to identify epigenetic biomarkers and implicate several pathogenic viruses to open new targets for novel therapies.

Conditions

Chronic Rhinosinusitis (Diagnosis)

Keywords

CRSwNP; Epigenetic; Virus; Infection; Microbiome

Outcome Measures

Primary Outcomes (1)

• Identification of epigenetic biomarkers and pathogenic viruses

  The investigators expect to identify viruses and epigenetic markers associated with CRS. Viruses will be identified using bulk sequencing of collected tissue. Viruses will be considered "present" only if they are seen on at least 5 reads in sequencing. These identified viruses will be considered as associated with disease or healthy states assessed only when they are seen in at least 25% of tissue samples for the given condition. Association with disease will be defined as a higher proportion of candidate virus in diseased as opposed to healthy conditions. Epigenetic markers will be identified by comparing methylation profiles across the whole genome between active CRSwNP disease with disease in remission. Machine learning techniques will be used to identify putative sequences of epigenetic biomarkers associated with active disease or presence of an identified viral pathogen.

  12 months

Study Arms (4)

Primary epithelial cells

Population: The investigators will use frozen dissociated cells from our biobank in earliest possible format (P0 or P1) to preserve original viruses and epigenetic marks. Polyp samples from T2 CRSwNP will be selected according to clinical phenotype together with blood test and histology.

Patients in remission of CRSwNP

Population: Perfect sinus cavity outcome after ESS under continued intranasal corticosteroids (INCS) or dupilumab.

Effect of sinus surgery on the sinus virome

Population: Patients undergoing ESS for CRSwNP, including at least 30% of subjects with aspirin sensitivity.

Procedure: Endoscopic sinus surgery (ESS)

Healthy volonteers

Population: Participants with no sino-nasal symptoms and normal sense of smell as assessed by UPSIT-40 testing.

Interventions

Endoscopic sinus surgery (ESS) PROCEDURE

Endoscopic sinus surgery for removal of nasal polyps and sinus tissue.

Effect of sinus surgery on the sinus virome

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

* T2 CRSwNP patients with favorable evolution * T2 CRSwNP patients undergoing ESS * Healthy volonteers with no nasal symptoms and documented normal sense of smell

You may qualify if:

• T2 CRSwNP patients with favorable evolution
• T2 CRSwNP patients undergoing ESS
• Healthy volonteers with no nasal symptoms and documented normal sense of smell

You may not qualify if:

• Cystic fibrosis
• Primary immunodefisciencies

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): lead

Study Sites (1)

CHUM

Montreal, Quebec, H2X 3E4, Canada

Location

Related Publications (3)

• North ML, Ellis AK. The role of epigenetics in the developmental origins of allergic disease. Ann Allergy Asthma Immunol. 2011 May;106(5):355-61; quiz 362. doi: 10.1016/j.anai.2011.02.008. Epub 2011 Mar 16.

  PMID: 21530865 BACKGROUND

• Linden D, Guo-Parke H, Coyle PV, Fairley D, McAuley DF, Taggart CC, Kidney J. Respiratory viral infection: a potential "missing link" in the pathogenesis of COPD. Eur Respir Rev. 2019 Mar 14;28(151):180063. doi: 10.1183/16000617.0063-2018. Print 2019 Mar 31.

  PMID: 30872396 BACKGROUND

• Mikhail I, Grayson MH. Asthma and viral infections: An intricate relationship. Ann Allergy Asthma Immunol. 2019 Oct;123(4):352-358. doi: 10.1016/j.anai.2019.06.020. Epub 2019 Jul 2.

  PMID: 31276807 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples, nasal biopsies and/or nasal brushings

MeSH Terms

Conditions

Disease; Virus Diseases; Infections

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Martin Y. Desrosiers, MD

  Centre hospitalier de l'Université de Montréal (CHUM)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2023
• First Posted: May 12, 2023
• Study Start: May 18, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)