Nasal Microbiota Transfer Therapy in Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP)
- Conditions
- Chronic Rhinosinusitis (Diagnosis)
- Interventions
- Procedure: Microbiome TransplantProcedure: Placebo
- Registration Number
- NCT05400616
- Lead Sponsor
- The University of Queensland
- Brief Summary
Chronic Rhinosinusitis (CRS) is a chronic inflammatory condition of the nasal passage and paranasal sinuses that places significant burden on affected patients and global healthcare systems.
Current treatments for CRS such as long-term antibiotics, anti-inflammatory drugs, and surgery often reduce symptoms and signs of disease temporarily, however long-term results are much less satisfactory.
Recently, the theory of a damaged microbiome (dysbiosis) as a cause or promoting factor behind CRS has gained increasing evidence from the scientific community.
A condition of the gut with microbial dysbiosis (c.difficile) has previously employed microbiota transplant treatment with great success in long-term health outcomes. Such treatments are shown to repopulate bacterial microenvironment and restore protective commensal bacterial load.
A pilot study conducted by this study team trialed a novel intervention of a Nasal Microbiota Transplant in a small group of participants. Preliminary results suggested significantly improved CRS symptoms after treatment with a healthy donor microbiota transplant, compared to the pre-transplant baseline. The addition of a randomized-control trial with inclusion of a placebo group is the next step.
In this study, investigators aim to perform a two-arm, double-blinded, phase II randomized controlled clinical trial in order to assess the efficacy of a Nasal Microbiota Transplant against a placebo in a cohort of CRS patients without Nasal Polyps (CRSsNP).
- Detailed Description
Current treatments for CRS such as long-term antibiotics, anti-inflammatory drugs, and surgery often reduce symptoms and signs of disease temporarily, however long-term results are much less satisfactory.
A microbiota therapy, as an alternative treatment to antibiotics, has the potential of improving outcomes for CRS patients long-term, whilst reducing the use of antibiotics in the community.
Several attempts of studies to define the role of microbiota of the nose and paranasal sinuses in health and disease have not yet been able to achieve a universal consensus. This is in part due to the significant inter-individual microbiota variation and complexity within humans. Such challenges have also limited the use of probiotic assemblages of one or a combination of few bacterial species in treatment of CRS.
The data derived from this study will add to our understanding of the role of the microbiome in the airways and its role in interfering with respiratory pathogens and host immunity. This is likely to have implications for CRS microbiome-based therapies, and also other potentially related respiratory conditions such as asthma, and chronic obstructive pulmonary disease (COPD).
In this study, investigators will recruit patients suffering from chronic rhinosinusitis without polyps (CRSsNP) and healthy participants that do not have a history of sinonasal disease. The sinus microbiome transplants will occur over a 2 week period, with regular follow up for up to 6-months post intervention. Main outcomes include change in disease severity, symptom severity, inflammatory changes, and microbial composition across the study period. Successful results from this trial may pave the way for a novel therapeutic for CRS patients.
This study has received ethics approval from the Royal Brisbane and Women's Health Human Resource and Ethics Committee (RBWH HREC).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
Not provided
Exclusion criteria (patient):
-
Aged <18 or >80 years
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Allergy to amoxicillin or clavulanate potassium and Clarithromycin.
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Excessive Nasal polyposis
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Antibiotic treatment in the last 4 weeks
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Patients with a history supporting a diagnosis of immune deficiency will be tested (Immunoglobulin A (IgA), Immunoglobulin M (IgM), Immunoglobulin G (IgG) and IgG subclasses, MBL) and /or are immunocompromised due to disease and / or medication ( e.g., insulin dependent diabetes mellitis, systemic corticosteroids)
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Patients who live with someone who is severly immunocompromised.
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Patients with cystic fibrosis or ciliary dyskinesia
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Patients who have been on an active investigational therapy within 2 months of screening
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Patients who have clinically significant laboratory abnormalities
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Patients who are pregnant, breast feeding or planning to become pregnant during the study
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Patients who are not willing to use a double barrier method of contraception during the study that is:-
- females must use contraceptive pill or Intra-uterine device (IUD) or similar and condoms
- males must use condoms and spermicidal gel
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Patients currently on any medication that may affect the results in an unpredictable manner
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The patient does not agree to comply with or is unable to meet all study requirements for the duration of the study period
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Patients deemed by the investigator to be unsuitable for participation in the study
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Patients who have had Coronavirus-19 (COVID-19) within the last month.
Exclusion criteria (donor):
- Findings in the prestudy pathogen scan that makes the donor unsuitable. Prestudy pathogen scan: Prior to first donation, the donors will be tested for HIV, Human T-lymphotropic virus 1 and 2, Hepatitis B and C, Syphilis, Tuberculosis, Herpes Simplex (HSV 1 and 2), Varicella Zoster (VZV), Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Methicillin-resistant Staphylococcus aureus (MRSA) and a standard panel for sinonasal pathogens (Pneumococci, H. Influenza, Beta-streptococci and M. Catarrhalis).
- Donors who have had COVID-19 within the last 2 months.
- If the donor is positive for Herpes Simplex, CMV or EBV they will be considered unsuitable as a donor for a patient negative for the same pathogen. If the donor is positive for any other pathogen they will be considered unsuitable as a donor entirely.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intervention Microbiome Transplant For each nostril, the donated nasal wash sample is quiesced to 15 mls with saline Nasal Microbiota Transplant therapy. Control Placebo For each nostril, 15 mls of saline will be used as the placebo therapy.
- Primary Outcome Measures
Name Time Method Sino-Nasal Outcome Test (SNOT-22) - 22 Item Questionnaire Week 1 (Day 1) to Week 20 Change of burden of disease as measured by the SNOT-22 (22 item sinonasal outcome test) questionnaire in patients. Each item graded 0-5.
Minimum score 0, Maximum 105 Interpretation: Higher score indicates poorer disease control.
- Secondary Outcome Measures
Name Time Method Cytokine level - Interleukin 2 (IL-2) Week 1 (Day 1) to Week 20 Change of lL-2 in nasal secretion/swab markers across duration of study. Each cytokine will be quantified using a highly sensitive immunoassay which will use biotinylated antibodies specific to each cytokine to bind the cytokine molecules in the sample.
Interactions measured on a flow cytometer and compared against its relevant standard. this will result in a measure of the total concentration of the cytokine in the sample (pg/ml).Characterisation of microbiome within effective donors as compared to ineffective donors Week 1 (Day 1) - Week 2 (Day 9) Analysis of microbes (bacterial strains, viruses and fungi), and human cell types within donor specimens.
Adverse events of Participating Patients From the day participating patients give signed consent (2-4 weeks before baseline) until the day of their End of study visit (Up to 33 weeks). Any adverse event
Cytokine level - Interleukin 13 (IL-13) Week 1 (Day 1) to Week 20 Change of lL-13 in nasal secretion/swab markers across duration of study. Each cytokine will be quantified using a highly sensitive immunoassay which will use biotinylated antibodies specific to each cytokine to bind the cytokine molecules in the sample.
Interactions measured on a flow cytometer and compared against its relevant standard. this will result in a measure of the total concentration of the cytokine in the sample (pg/ml).Cytokine level - Interleukin 4 (IL-4) Week 1 (Day 1) to Week 20 Change of IL-4 in nasal secretion/swab markers across duration of study.Each cytokine will be quantified using a highly sensitive immunoassay which will use biotinylated antibodies specific to each cytokine to bind the cytokine molecules in the sample.
Interactions measured on a flow cytometer and compared against its relevant standard. this will result in a measure of the total concentration of the cytokine in the sample (pg/ml).Lund-Kennedy endoscopic assessment score Week 1 (Day 1) to Week 20 Change of grading of disease severity using the Lund-Kennedy endoscopy score based on clinical assessment of the middle meatus. 4-item criteria, with score of 0-2 Minimum score: 0, Maximum 8 Interpretation: Higher score indicates a higher degree of disease severity based on clinical assessment.
Characterisation of nasal microbiome in study participants Week 1 (Day 1) to Week 20 Change in nasal microbiome associated with clinical outcomes such as decrease in presence, absence or abundance of bacterial pathogens.
Cytokine level - Interleukin 5 or (IL-5) Week 1 (Day 1) to Week 20 Change of lL-5 in nasal secretion/swab markers across duration of study. Each cytokine will be quantified using a highly sensitive immunoassay which will use biotinylated antibodies specific to each cytokine to bind the cytokine molecules in the sample. Interactions measured on a flow cytometer and compared against its relevant standard. this will result in a measure of the total concentration of the cytokine in the sample (pg/ml).
Cytokine level - Interleukin 6 (IL-6) Week 1 (Day 1) to Week 20 Change of lL-6 in nasal secretion/swab markers across duration of study.Each cytokine will be quantified using a highly sensitive immunoassay which will use biotinylated antibodies specific to each cytokine to bind the cytokine molecules in the sample.
Interactions measured on a flow cytometer and compared against its relevant standard. this will result in a measure of the total concentration of the cytokine in the sample (pg/ml).Cytokine level - Interleukin 10 (IL-10) Week 1 (Day 1) to Week 20 Change of lL-10 in nasal secretion/swab markers across duration of study.Each cytokine will be quantified using a highly sensitive immunoassay which will use biotinylated antibodies specific to each cytokine to bind the cytokine molecules in the sample.
Interactions measured on a flow cytometer and compared against its relevant standard. this will result in a measure of the total concentration of the cytokine in the sample (pg/ml).Cytokine level - Interferon gamma (IFN-γ) Week 1 (Day 1) to Week 20 Change of IFN-Y in nasal secretion/swab markers across duration of study.Each cytokine will be quantified using a highly sensitive immunoassay which will use biotinylated antibodies specific to each cytokine to bind the cytokine molecules in the sample.
Interactions measured on a flow cytometer and compared against its relevant standard. this will result in a measure of the total concentration of the cytokine in the sample (pg/ml).
Trial Locations
- Locations (3)
Royal Brisbane and Women's Hospital
🇦🇺Brisbane, Queensland, Australia
University of Queensland
🇦🇺Brisbane, Queensland, Australia
Monash Health
🇦🇺Melbourne, Australia