Microbiota Transfer for Chronic Sinusitis

(SNMT Trial)

Overseen By Amee Manges, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Amin Javer

Must be taking: Nasal steroids, Oral corticosteroids

Disqualifiers: Sinonasal tumors, Autoimmune diseases, Immune-compromised, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 46

Duration: 1 day

80 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the trial involves a new treatment, it's best to discuss your current medications with the trial team to ensure there are no conflicts.

What data supports the effectiveness of the treatment for chronic sinusitis?

Research shows that using beneficial bacteria like Lactococcus lactis W136 in nasal treatments can safely improve symptoms and quality of life for people with chronic sinusitis, suggesting that modifying the nasal microbiome might be a helpful approach. ^{1 2 3 4 5}

Is microbiota transfer safe for humans?

Microbiota transfer, often done as fecal microbiota transplantation (FMT), is generally considered safe and well-tolerated, even in high-risk patients. However, there have been serious adverse events linked to FMT products from stool banks that did not screen for multi-drug resistant organisms, so strict donor screening is important. ^{6 7 8 9 10}

How is Sinonasal Microbiota Transfer (SNMT) different from other treatments for chronic sinusitis?

Sinonasal Microbiota Transfer (SNMT) is unique because it involves transferring healthy bacteria directly to the nasal passages to restore balance in the sinus microbiome, unlike traditional treatments that often rely on antibiotics or surgery. This approach is similar to fecal microbiota transplants used for gut health, aiming to improve sinus health by modifying the bacterial community. ^{1 2 11 12 13}

Research Team

Amin Javer, MD

Principal Investigator

University of British Columbia

Eligibility Criteria

This trial is for adults with stubborn chronic sinusitis who've had sinus surgery and max medical treatment but still suffer. They must be able to consent and have a SNOT-22 Score ≥20 or no improvement post-surgery. Excluded are immune-compromised, those outside the US, with sinonasal tumors, certain infections/diseases, autoimmune diseases affecting airways, recent other respiratory conditions except common colds, active cancer history or specific risk factors.

Inclusion Criteria

People who have not responded well to treatment for cytokine release syndrome.

Able to provide informed consent, complete donor screening, and adhere to SNMT mucus collection and testing procedures (for donors)

I am 19 years old or older.

Exclusion Criteria

Living outside the US (for patients)

My doctor expects I have more than 6 months to live despite my severe illness.

I have been diagnosed with a tumor in my nasal passages.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a sinus power wash followed by either a SinoNasal Microbiota Transfer (SNMT) or a sham procedure

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including SNOT-22 questionnaire, smell test, and endoscopic scoring

6 months

Multiple visits (in-person) at 45, 90, and 180 days

Treatment Details

Interventions

• Sham Sinonasal Microbiota Transfer
• Sinonasal Microbiota Transfer

Trial Overview The study tests if transferring healthy sinus microbes from screened donors into patients' sinuses (SNMT) after a 'sinus power wash' can improve chronic sinusitis. It's a double-blind trial where half get real SNMT and half get sham transfers to compare outcomes.

Participant Groups

Group I: Sinonasal Microbiota Transfer Experimental Treatment 1 Intervention

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 II: Sham Sinonasal Microbiota Transfer Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Amin Javer

Lead Sponsor

Trials

2

Recruited

160+

Findings from Research

In a study of 35 subjects with surgically-opened maxillary sinuses, only about 24.5% of the sinus microbiota was stable over time, indicating that while some bacteria are consistently present, their abundance can vary significantly.

Certain bacteria, like Staphylococcus and Corynebacterium, were commonly found in both healthy and inflamed sinuses, while others like Janthinobacterium and Lactobacillus were more prevalent in healthy sinuses, suggesting that the composition of the sinus microbiota may play a role in chronic rhinosinusitis (CRS) pathogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temporal instability of the post-surgical maxillary sinus microbiota. Koutsourelakis, I., Halderman, A., Khalil, S., et al.[2018]

A pilot trial involving 24 patients with chronic rhinosinusitis showed that nasal irrigation with the probiotic Lactococcus lactis W136 was safe, with no major adverse events reported during the 14-day treatment period.

Patients experienced improvements in sinus symptoms and quality of life, suggesting that intranasal probiotics could be a promising treatment strategy for chronic rhinosinusitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal Application of Lactococcus lactis W136 Is Safe in Chronic Rhinosinusitis Patients With Previous Sinus Surgery. Endam, LM., Alromaih, S., Gonzalez, E., et al.[2021]

In a study of 22 patients with chronic sinusitis after radiotherapy, Staphylococcus aureus and Pseudomonas aeruginosa were the most commonly identified bacteria, indicating a shift in the microbiota post-treatment.

Next-generation gene sequencing revealed additional pathogens not detected by standard culture methods in 50% of patients, suggesting that this advanced technique could enhance the understanding and treatment of post-radiation sinusitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of Microbiota in Post Radiation Sinusitis. Stoddard, TJ., Varadarajan, VV., Dziegielewski, PT., et al.[2022]

A systematic review of 9 studies involving 244 patients with chronic rhinosinusitis (CRS) found that the sinonasal microbiome's composition may influence clinical outcomes, with specific bacteria like Corynebacterium linked to better surgical results.

However, the findings were inconsistent, with some bacteria like Escherichia associated with worse symptoms, indicating that more research is needed to clarify how different microbes affect CRS outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of the sinonasal bacterial microbiome with clinical outcomes in chronic rhinosinusitis: a systematic review. Wang, JC., Moore, CA., Epperson, MV., et al.[2022]

Current evidence does not strongly support the effectiveness of antibiotic therapy for chronic rhinosinusitis, as changes in the nasal microbiome after treatment are unpredictable and variable.

There is a need for further research on how oral antibiotics affect the sinonasal microbiome, particularly regarding the distribution of drug concentrations and their efficacy at different sites in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring antibiotic levels and their relationship with the microbiome in chronic rhinosinusitis. Siu, J., Tingle, MD., Douglas, RG.[2021]

Fecal microbiota transplantation (FMT) showed significant long-term efficacy in reducing IBS symptoms, with response rates of 69.1% and 77.8% for the 30g and 60g treatment groups, respectively, at 2 years, and 64.9% and 71.8% at 3 years, compared to only 26.3% in the placebo group.

No long-term adverse events were reported, indicating that FMT is a safe intervention for IBS, with improvements in quality of life and a decrease in dysbiosis index observed in the treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. El-Salhy, M., Winkel, R., Casen, C., et al.[2022]

Fecal microbiota transplantation (FMT) is a generally safe and well-tolerated procedure for treating recurrent Clostridioides difficile infections, even in high-risk patients, with most short-term risks being mild and related to delivery methods.

Recent concerns have emerged regarding serious adverse events linked to FMT products from stool banks that do not screen for multi-drug resistant organisms, highlighting the need for improved safety protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation: Is It Safe? Park, SY., Seo, GS.[2021]

Faecal microbiota transplantation (FMT) has shown effectiveness in inducing clinical remission in inflammatory bowel disease (IBD), with 36% of ulcerative colitis (UC) patients and 50.5% of Crohn's disease (CD) patients achieving remission based on a systematic review of 53 studies involving 555 patients.

The study found that the likelihood of achieving remission in UC improved with more FMT infusions and lower gastrointestinal tract administration, although most adverse events were mild and transient, indicating a generally safe profile for FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. Paramsothy, S., Paramsothy, R., Rubin, DT., et al.[2022]

A systematic review of 8 randomized trials involving 472 IBS patients found that fecal microbiota transfer (FMT) did not significantly improve overall IBS symptom severity compared to placebo, indicating limited efficacy of FMT for IBS treatment.

While the oral route of FMT showed some initial improvement in response rates, this did not translate into a significant reduction in symptom severity, and the benefits appeared to diminish over time, suggesting that alternative bacterial-based treatments may be more effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of fecal microbiota transplant in irritable bowel syndrome: An update based on meta-analysis of randomized control trials. Abdelghafar, YA., AbdelQadir, YH., Motawea, KR., et al.[2022]

Solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients face a higher risk of infections due to immunosuppression and antibiotic use, which can lead to gut microbiota imbalances.

Emerging therapies like fecal microbiota transplantation and precision probiotics show promise in restoring gut health and potentially improving outcomes for HSCT and SOT recipients with dysbiosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The gut microbiota in transplant patients. Chong, PP., Koh, AY.[2021]

Patients with chronic sinusitis showed significantly lower levels of beneficial gut bacteria, such as Bifidobacterium spp. and Akkermansia muciniphila, which are important for gut health and have anti-inflammatory properties.

The study suggests that analyzing gut microbiota could lead to personalized prebiotic and probiotic treatments to improve mucosal immunity in chronic sinusitis patients, although further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alteration of indicator gut microbiota in patients with chronic sinusitis. Michalik, M., Podbielska-Kubera, A., Basińska, AM., et al.[2023]

Recent advancements in DNA sequencing technology have enhanced our understanding of the human microbiome, revealing the significant role of bacterial communities in the pathogenesis of chronic sinusitis.

This review highlights three key aspects: the composition of nasal bacterial communities, their relationship with inflammatory responses, and the interactions between bacteria and the host, suggesting a complex interplay that contributes to chronic sinusitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of nasal microbiome in chronic sinusitis]. Wang, L., Chen, F., Yang, L., et al.[2023]

Patients with chronic rhinosinusitis (CRS) have significantly reduced bacterial diversity in their sinus microbiota compared to healthy individuals, indicating a potential link between microbiota composition and CRS.

The study identified Corynebacterium tuberculostearicum as a pathogenic species associated with CRS, while Lactobacillus sakei was found to be a potentially protective bacterium that could help prevent infections, suggesting new avenues for therapeutic interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum enrichment mediates rhinosinusitis. Abreu, NA., Nagalingam, NA., Song, Y., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Temporal instability of the post-surgical maxillary sinus microbiota. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Intranasal Application of Lactococcus lactis W136 Is Safe in Chronic Rhinosinusitis Patients With Previous Sinus Surgery. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Detection of Microbiota in Post Radiation Sinusitis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Association of the sinonasal bacterial microbiome with clinical outcomes in chronic rhinosinusitis: a systematic review. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Measuring antibiotic levels and their relationship with the microbiome in chronic rhinosinusitis. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. [2022]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation: Is It Safe? [2021]

8. England pubmed.ncbi.nlm.nih.gov

Faecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of fecal microbiota transplant in irritable bowel syndrome: An update based on meta-analysis of randomized control trials. [2022]

10. England pubmed.ncbi.nlm.nih.gov

The gut microbiota in transplant patients. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Alteration of indicator gut microbiota in patients with chronic sinusitis. [2023]

12. China pubmed.ncbi.nlm.nih.gov

[Role of nasal microbiome in chronic sinusitis]. [2023]

13. United States pubmed.ncbi.nlm.nih.gov

Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum enrichment mediates rhinosinusitis. [2022]