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Nasal Microbiota Transfer Therapy in Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP)

RECRUITING

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).

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Study details:

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).

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  • Diagnosis of Chronic Rhinosinusitis as defined by the presence of 2 or more major sinonasal symptoms (nasal blockage, nasal discharge, loss of smell, and facial pain/ fullness) for a minimum of 12 weeks
  • Endoscopic confirmation of middle meatus inflammation or presence of mucopurulence, and /or CT confirmation of paranasal sinus inflammation.
  • Previous nasal surgery with patent ostia to the diseased ethmoids and maxillary sinuses
  • Signed written informed consent
  • No history of sinonasal or lower airway disease for the last 2 years other than the common cold.
  • No clinical findings of sinonasal disease at the inclusion visit.
  • Accepted as a donor by the patient.
  • Signed informed consent to participate in the study.
  • Exclusion criteria

  • Aged <18 or >80 years
  • Allergy to amoxicillin or clavulanate potassium and Clarithromycin.
  • Excessive Nasal polyposis
  • Antibiotic treatment in the last 4 weeks
  • 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)
  • Patients who live with someone who is severly immunocompromised.
  • Patients with cystic fibrosis or ciliary dyskinesia
  • Patients who have been on an active investigational therapy within 2 months of screening
  • Patients who have clinically significant laboratory abnormalities
  • Patients who are pregnant, breast feeding or planning to become pregnant during the study
  • 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
  • Patients currently on any medication that may affect the results in an unpredictable manner
  • The patient does not agree to comply with or is unable to meet all study requirements for the duration of the study period
  • Patients deemed by the investigator to be unsuitable for participation in the study
  • Patients who have had Coronavirus-19 (COVID-19) within the last month.
  • 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.
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    Eligibility

    Age eligible for study : 18 and older

    Healthy volunteers accepted : Yes

    Gender eligible for study: All

    Things to know

    Study dates

    Study start: 2022-11-10

    Primary completion: 2024-12-01

    Study completion finish: 2025-12-01

    study type

    Study type

    TREATMENT

    phase

    Phase

      NA

    trial

    Trial ID

    NCT05400616

    Intervention or treatment

    PROCEDURE: Microbiome Transplant

    PROCEDURE: Placebo

    Conditions

    • Chronic Rhinosinusitis (Diagnosis)
    Image related to Chronic Rhinosinusitis (Diagnosis)
    • Condition: Chronic Rhinosinusitis (Diagnosis)

    • PROCEDURE: Microbiome Transplant and other drugs

    • Brisbane, Queensland, Australia and more

    • Sponsor: The University of Queensland

    Find a site

    Closest Location:

    Royal Brisbane and Women's Hospital

    Research sites nearby

    Select from list below to view details:

    • Royal Brisbane and Women's Hospital

      Brisbane, Queensland, Australia

    • Monash Health

      Melbourne, Not Specified, Australia

    • University of Queensland

      Brisbane, Queensland, Australia

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    Study Plan

    This section provides details of the study plan, including how the study is designed and what the study is measuring.

    How is the study designed?

    Participant Group/ArmIntervention/Treatment
    EXPERIMENTAL: Intervention
    • For each nostril, the donated nasal wash sample is quiesced to 15 mls with saline Nasal Microbiota Transplant therapy.
    PROCEDURE: Microbiome Transplant
    • A raw microbiome, is collected from a donor without any sinonasal health problems, as a nasal lavage.
    PLACEBO_COMPARATOR: Control
    • For each nostril, 15 mls of saline will be used as the placebo therapy.
    PROCEDURE: Placebo
    • Normal saline.

    What is the study measuring?

    Primary outcome

    Primary Outcome MeasurePrimary Outcome DescriptionPrimary Outcome Time Frame
    Sino-Nasal Outcome Test (SNOT-22) - 22 Item QuestionnaireChange 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.Week 1 (Day 1) to Week 20

    Secondary outcome

    Secondary Outcome MeasureSecondary Outcome DescriptionSecondary Outcome Time Frame
    Lund-Kennedy endoscopic assessment scoreChange 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.Week 1 (Day 1) to Week 20
    Characterisation of nasal microbiome in study participantsChange in nasal microbiome associated with clinical outcomes such as decrease in presence, absence or abundance of bacterial pathogens.Week 1 (Day 1) to Week 20
    Characterisation of microbiome within effective donors as compared to ineffective donorsAnalysis of microbes (bacterial strains, viruses and fungi), and human cell types within donor specimens.Week 1 (Day 1) - Week 2 (Day 9)
    Adverse events of Participating PatientsAny adverse eventFrom 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).
    Cytokine level - Interleukin 5 or (IL-5)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).Week 1 (Day 1) to Week 20
    Cytokine level - Interleukin 13 (IL-13)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).Week 1 (Day 1) to Week 20
    Cytokine level - Interleukin 2 (IL-2)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).Week 1 (Day 1) to Week 20
    Cytokine level - Interleukin 6 (IL-6)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).Week 1 (Day 1) to Week 20
    Cytokine level - Interleukin 10 (IL-10)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).Week 1 (Day 1) to Week 20
    Cytokine level - Interferon gamma (IFN-γ)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).Week 1 (Day 1) to Week 20
    Cytokine level - Interleukin 4 (IL-4)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).Week 1 (Day 1) to Week 20

    Frequently Asked Questions

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    References

    Clinical Trials Gov: Nasal Microbiota Transfer Therapy in Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP)

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