Chronic Rhinosinusitis (Diagnosis)
Conditions
Keywords
microbiota, transplant, paranasal sinuses, nasal lavage
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).
Interventions
PROCEDUREMicrobiome Transplant
A raw microbiome, is collected from a donor without any sinonasal health problems, as a nasal lavage.
PROCEDUREPlacebo
Normal saline.
Sponsors
Royal Brisbane and Women's Hospital
Monash Health
Queensland University of Technology
The University of Queensland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
A biostatistician, not involved in assignment or care of the trial participants, will generate the randomisation sequence with a computerised random number generator. A research assistant, not involved in any other aspect of this study, will place the assigned treatments into sealed envelopes. Participants (Patients and donors) will be blinded from knowing if they are in the intervention group or the control group. The nurse and doctors attending to the participants will also be blinded. A member of the study team who will prepare the Nasal Microbiota Transplant therapy will not be masked. The person doing the analysis will be masked.
Intervention model description
Eligible patient participants will be randomly assigned to intervention or control group (1:1 ratio) as per a computer-generated randomisation schedule using permuted blocks of random sizes. The block sizes will not be disclosed, to ensure concealment. Both groups will receive two weeks of antibiotic treatment between recruitment and allocation to a study arm. The study team will work with each patient participant to find a suitable donor. Some patient participants will prefer a donor that is known to them other patients will prefer a donor that is an unknown volunteer. Potential donors who consent to participating in this study will be screened and be classified as donor-participants in the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
(patient): * 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 Inclusion criteria (donor): * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 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 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). |
| 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. |
| 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). |
| 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). |
| 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). |
Countries
Australia
Contacts
Primary ContactAnders Cervin, MD,FRACS
Backup ContactDiane Maresco-Pennisi, PhD
Outcome results
None listed