Microbiota Transfer for Chronic Rhinosinusitis

NCT ID: NCT05454072

Last Updated: 2022-07-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-15
• Study Completion Date: 2025-06-30

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Sinonasal Microbiota Transfer

Intervention Type: PROCEDURE

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

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.

Group Type: SHAM_COMPARATOR

Sham Sinonasal Microbiota Transfer

Intervention Type: PROCEDURE

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

Interventions

Sinonasal Microbiota Transfer

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

Intervention Type: PROCEDURE

Sham Sinonasal Microbiota Transfer

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

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 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)

• 19 years of age or older
• Able to provide informed consent, complete donor screening, and adhere to SNMT mucus collection and testing procedures

Exclusion Criteria

• 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

• 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
• A history of sinonasal or lower airway disease within the last 2 years other than the common cold; diagnosed with CRS; diagnosed with acute rhinosinusitis within the last six months; asthma; and/or clinical findings of sinonasal disease at the inclusion visit and immunodeficiency; any history of active cancer, or risk factors for acquisition of HIV, syphilis, hepatitis A, hepatitis B, hepatitis C, prion, or relevant neurological disease, receipt of blood transfusion from a country other than Canada in the preceding 6 months, any type of antibiotic treatment or any systemic immunosuppressive agents in the 3 months prior to the donation, or any current or previous medical or psychosocial condition or behaviours, which in the opinion of the investigator, may pose a risk to the recipient or the donor

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Amin Javer

OTHER

Sponsor Role: lead

Responsible Party

Amin Javer

Clinical Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Amin Javer, MD

Role: STUDY_DIRECTOR

University of British Columbia

Locations

St. Paul's Hospital

Vancouver, British Columbia, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Amin Javer, MD

Role: CONTACT

sinusdoc@me.com

(604) 806-9926

Amee Manges, PhD

Role: CONTACT

amee.manges@ubc.ca

(604) 822-9203

Facility Contacts

Amin Javer, MD

Role: primary

sinusdoc@me.com

(604) 806-9926

Amee Manges, PhD

Role: backup

amee.manges@ubc.ca

(604) 822-9203

References

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.

Reference Type: BACKGROUND

PMID: 24131818 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25640115 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19117310 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24610673 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28688189 (View on PubMed)

Other Identifiers

H18-02263-A013

Identifier Type: -

Identifier Source: org_study_id