Microbiota Transfer for Chronic Rhinosinusitis

NCT05454072 | Active Not Recruiting DMC

• 1 other identifier: H18-02263-A013
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic sinusitis (CRS) is a common inflammatory condition of the sinuses that affects up to 2.5% of the Canadian population, and is thought to be caused by bacterial infection, resistant biofilms, chronic inflammation and possibly an unhealthy population of sinus microbes (or microbiota). Symptoms include nasal obstruction and discharge, facial pain, loss of smell and sleep disturbance, which all strongly impact quality of life. CRS treatment involves nasal or oral steroids, repeated rounds of antibiotic, and sinus surgery. Despite maximal treatment, some recalcitrant patients suffer with CRS for years. The lack of new, effective therapies to treat CRS leads the investigators to test whether a SinoNasal Microbiota Transfer (SNMT) could trigger CRS recovery. SNMT is defined as the endoscopic transfer of a healthy sinus microbiota from a fully screened donor's sinus to a CRS patient's sinus(es). Similar to a fecal transplant used to treat Clostridioides difficile diarrhea, the sinonasal microbiota transfer may eliminate sinus pathogens and restore the sinus microbiota to a healthy state. SNMT will be combined with a one-time, high volume, high pressure "sinus power wash" pre-treatment to temporarily clear the way for the donor microbiota to establish itself. The investigators will conduct a proof-of-principle, randomized, double-blind, placebo-controlled trial of 80 subjects to test whether a sinus power wash plus SNMT improves clinical outcomes in CRS patients.

Conditions

Sinusitis, Chronic; Sinus Disease; Sinus Infection; Sinus Infection Chronic

Keywords

Microbiota Transplant; Chronic Rhinosinusitis

Outcome Measures

Primary Outcomes (1)

• Modified Lund-Kennedy (MLK) endoscopic scoring

  Change in endoscopic score, where points to each sinus are assigned based on discharge (0 - no discharge; 1 - clear discharge; 2 - purulent discharge), edema (0 - edema; 1 - mild edema; 2 - severe edema), and polyps (0 - no polyps; 1 - confined to the middle meatus; 2 - beyond the middle meatus) for a maximum of 6 points per side (12 total). A 1-point difference in the total MLK score is considered clinically meaningful since it signifies a change in either polyp size, edema severity, or type of discharge.

  Baseline to 45 days

Secondary Outcomes (5)

• Sinonasal Outcome Test (SNOT-22) questionnaire

  Baseline to 45 days, 90 days, 180 days

• Smell Test

  Baseline to 45 days, 90 days, 180 days

• Adverse and serious adverse events

  Baseline to any time until the end of the study period

• Microbiome analysis of patients and donor samples

  Baseline to 45 days, 90 days, 180 days

• Immune markers

  Baseline to 45 days, 90 days, 180 days

Study Arms (2)

Sinonasal Microbiota Transfer

EXPERIMENTAL

The transfer site for patients will be prepared by endoscopically removing any visible crusting, mucin, and purulent discharge from the sinuses and via manual high-volume (\>60 ml), high-pressure saline wash on day 0. The donor mucus sample will be homogenized using sterile, disposable rotor-stator homogenizer tips for 30 seconds and 5 ml of donor mucus will be instilled into the affected sinus cavity(ies) using a masked syringe under endoscopic visualization, with the recipient's head in a dependent position. Patients will remain in this position for 15 minutes to facilitate transfer.

Procedure: Sinonasal Microbiota Transfer

Sham Sinonasal Microbiota Transfer

SHAM COMPARATOR

Sterile saline will replace the SNMT donor mucus in the masked syringe and will be delivered in an identical manner to the SNMT intervention.

Procedure: Sham Sinonasal Microbiota Transfer

Interventions

Sinonasal Microbiota Transfer PROCEDURE

Pre-screened donor mucus, up to 15mL, will be transplanted into each diseased sinus via nasal lavage.

Sinonasal Microbiota Transfer

Sham Sinonasal Microbiota Transfer PROCEDURE

Saline, up to 15mL, will be transplanted into each diseased sinus via nasal lavage.

Sham Sinonasal Microbiota Transfer

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recalcitrant CRS patients
• Able to provide informed consent
• Diagnosed with CRS (with/without polyps) and have previously undergone functional endoscopic sinus surgery (Post-FESS)
• Continued to fail despite receiving "maximal and adequate medical treatment" This is defined as patients who:
• Have received topical nasal steroids in any form (Spray/ Rinse/ Atomized) for at least 3 months or at least one course of oral corticosteroids treatment (\>0.5 mg/kg for 2 weeks tapering dose);
• Had at least one course of antibiotic treatment either based on culture and sensitivity of nasal sinus secretions or as long-term low dose macrolide therapy (clarithromycin 500mg twice a day for 2 weeks then 250 mg once a day for 4 weeks) for at least one trial or have received a course of itraconazole 100mg twice daily for 6 weeks
• Have deteriorating SNOT-22 Scores (≥20) or do not improve after surgery and appropriate maximal medical management (MLK score ≥ 2, with at least 2 points on the discharge subdomain)

You may not qualify if:

• Diagnosed with sinonasal tumors
• Autoimmune diseases affecting the upper airway (e.g., systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis)
• Immune-compromised patients
• Impairment in mucociliary function (e.g., cystic fibrosis, Kartagener syndrome)
• Pregnant or planning to become pregnant or breastfeeding
• Severe underlying disease with anticipated survival less than 6 months
• Unable to tolerate SNMT for any reason
• years of age or older
• Able to provide informed consent, complete donor screening, and adhere to SNMT mucus collection and testing procedures
• If they are positive for any of the following: (i) from blood or mucus testing, human Immunodeficiency virus (HIV) I/II, hepatitis A IgM, hepatitis B surface antigen (HBsAg), hepatitis C, human T- lymphotropic virus (HTLV) I/II, methicillin-resistant Staphylococcus aureus, multidrug resistant bacteria, and/or SARS-CoV-2

Sponsors & Collaborators

• Amin Javer: lead

Study Sites (1)

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Related Publications (5)

• Lange B, Holst R, Thilsing T, Baelum J, Kjeldsen A. Quality of life and associated factors in persons with chronic rhinosinusitis in the general population: a prospective questionnaire and clinical cross-sectional study. Clin Otolaryngol. 2013 Dec;38(6):474-80. doi: 10.1111/coa.12189.

  PMID: 24131818 BACKGROUND

• Smith KA, Orlandi RR, Rudmik L. Cost of adult chronic rhinosinusitis: A systematic review. Laryngoscope. 2015 Jul;125(7):1547-56. doi: 10.1002/lary.25180. Epub 2015 Jan 30.

  PMID: 25640115 BACKGROUND

• Macdonald KI, McNally JD, Massoud E. The health and resource utilization of Canadians with chronic rhinosinusitis. Laryngoscope. 2009 Jan;119(1):184-9. doi: 10.1002/lary.20034.

  PMID: 19117310 BACKGROUND

• Baguley C, Brownlow A, Yeung K, Pratt E, Sacks R, Harvey R. The fate of chronic rhinosinusitis sufferers after maximal medical therapy. Int Forum Allergy Rhinol. 2014 Jul;4(7):525-32. doi: 10.1002/alr.21315. Epub 2014 Mar 7.

  PMID: 24610673 BACKGROUND

• Stein NR, Jafari A, DeConde AS. Revision rates and time to revision following endoscopic sinus surgery: A large database analysis. Laryngoscope. 2018 Jan;128(1):31-36. doi: 10.1002/lary.26741. Epub 2017 Jul 8.

  PMID: 28688189 BACKGROUND

MeSH Terms

Conditions

Sinusitis; Bronchiolitis Obliterans Syndrome; Paranasal Sinus Diseases

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Study Officials

• Amin Javer, MD

  University of British Columbia

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: July 7, 2022
• First Posted: July 12, 2022
• Study Start: June 15, 2022
• Primary Completion: April 14, 2024
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)