Microbiota Transfer for Chronic Rhinosinusitis

Not Applicable

Recruiting

• Conditions: Sinusitis, Chronic; Sinus Infection Chronic; Sinus Disease; Sinus Infection
• Interventions: Procedure: Sinonasal Microbiota Transfer; Procedure: Sham Sinonasal Microbiota Transfer

• Registration Number: NCT05454072
• Lead Sponsor: Amin Javer

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.

Detailed Description

Chronic rhinosinusitis (CRS) is a common inflammatory condition of the paranasal sinuses. CRS patients experience persistent facial pain/pressure, nasal discharge, nasal obstruction, and loss of smell. Initial treatment includes topical and systemic steroids and (often multiple rounds of) antibiotics; however, two thirds of patients remain symptomatic despite medical therapy and require endoscopic sinus surgery. Direct medical and indirect social costs of CRS are substantial, with 57% of patients reporting absenteeism and poor health and 28% experiencing associated anxiety and depression. These hard-to-treat patients are classified as recalcitrant CRS (rCRS), have limited treatment options available, and are the focus of this trial.

CRS was thought to occur due to impaired sinus ventilation and drainage however new evidence suggests that sinus mucosal inflammation, driven in part by microbiota disruptions and pathogen carriage, is the etiological factor behind CRS. Type of inflammation varies and cannot be predicted based on clinical variables alone. Several studies show that the microbiome composition of CRS patients is less diverse compared to healthy subjects, suggesting that community-level disruptions, and not individual opportunistic pathogens, may contribute to persistent inflammation.

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 within 45 days compared to a sinus power wash and sham SNMT. The investigators will investigate the safety profile of SNMT and determine if SNMT-related CRS symptom improvement lasts up to 6 months. Finally, the investigators will investigate how SNMT contributes to CRS recovery, by tracking changes in the sinus microbiota and inflammation pre- and post-treatment. Results from our pilot study shows that SNMT produced CRS symptom improvement in 75% of patients. SNMT therapy may be a transformative strategy to address CRS, a chronic and debilitating illness.

Study Timeline

• Study Start: 2022-06-15
• Status Verified: 2022-07
• Study First Submitted: 2022-07-07
• Study First Submitted QC: 2022-07-07
• Study First Posted: 2022-07-12
• Last Update Submitted: 2022-07-15
• Last Update Posted: 2022-07-19
• Primary Completion: 2024-06
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sinonasal Microbiota Transfer	Sinonasal Microbiota Transfer	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.
Sham Sinonasal Microbiota Transfer	Sham Sinonasal Microbiota Transfer	Sterile saline will replace the SNMT donor mucus in the masked syringe and will be delivered in an identical manner to the SNMT intervention.

Primary Outcome Measures

Name	Time	Method
Modified Lund-Kennedy (MLK) endoscopic scoring	Baseline to 45 days	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.

Secondary Outcome Measures

Name	Time	Method
Sinonasal Outcome Test (SNOT-22) questionnaire	Baseline to 45 days, 90 days, 180 days	Disease specific quality of life improvement, which includes 22 questions that encompass 4 subdomains of CRS (nasal, sleep, otologic/facial pain, and emotional symptoms).
Smell Test	Baseline to 45 days, 90 days, 180 days	Smell test using Sniffin' Sticks (scores range from 0-48).
Microbiome analysis of patients and donor samples	Baseline to 45 days, 90 days, 180 days	Metagenome sequencing will be performed to construct metagenome-assembled genomes of CRS pathogens in donor and recipient mucus, to unambiguously describe strain-specific eradication or reinfection; determine donor sinus microbiota engraftment; detect evidence for (or not) resistance gene and resistant organism transfer via SNMT from donor to recipient; and investigate microbiome compositional and functional features associated with SNMT success or failure.
Adverse and serious adverse events	Baseline to any time until the end of the study period	The safety of SNMT will be examined by identifying any adverse events, including serious adverse events.
Immune markers	Baseline to 45 days, 90 days, 180 days	To assess immune activation and inflammation-related responses to SNMT CRS-specific structured histological analysis will be performed to detect a reduction in tissue eosinophilia and/or neutrophilia, mucosal ulceration, and squamous metaplasia; cytokine/chemokine testing to detect a decrease in inflammation; and antibody testing and blood work to measure sustained reductions in serum eosinophils and IgE levels

Trial Locations

Locations (1)

St. Paul's Hospital; 🇨🇦 Vancouver, British Columbia, Canada