Chronic Rhinosinusitis With Nasal Polyps, Chronic Rhinosinusitis Without Nasal Polyps
Conditions
Brief summary
Chronic rhinosinusitis (CRS) is a disease associated with impaired quality of life and substantial societal costs. Much is still uncertain regarding the underlying etiology of the disease. Current treatment protocols are based on observed effects rather than a mechanistic understanding of the disease and thus patients often report unsatisfactory symptom reduction despite treatment with maximal medical therapy and even surgery. CRS is subgrouped phenotypically based on whether or not polyps are observed. Recently an endotypical differentiation reflecting the underlying inflammatory profile has been recommended as well, especially for research. Increasing interest in the role of the commensal microbiome inflammatory diseases has followed a growing understanding of its profound impact on the human immune system. Current research indicates that instability and dysfunction of the microbiome is linked to inflammatory disease rather than compositional differences. Previous research has shown that microbiome transplants are effective in restoring the commensal microbiome and reducing inflammation in gastrointestinal disease and in a previous pilot study the investigators showed that sinonasal microbiome transplants are feasible and were associated with reduced symptoms in chronic rhinosinusitis without nasal polyps (CRSsNP). This study will examine if the positive effect on patients symptoms observed in a previous pilot study are sustained in a placebo controlled, blinded study. In addition to this the study will also examine any differences in microbiome structure, stability, and function between patients with CRS and healthy donors as well as any correlation to disease phenotype or inflammatory endotype.
Interventions
PROCEDURESinonasal microbiome transplant procedure.
A sinonasal microbiome transplant obtained from a healthy donor and administered as a nasal lavage once daily for five consecutive days.
OTHERPlacebo saline transplant
Placebo transplant containing saline administered as a nasala lavage once daily for five consecutive days.
Sponsors
Region Skane
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
All participants will run through the study twice with a 7 month wash-out in between. Once the participant will run through the microbiome translant arm and once through the placebo arm.. Participants and investigators will be blinded to the if the participant gets microbiome transplantation or placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
(CRS-Patients): * 2 nasal symptoms, 1 of which must be nasal obstruction or discolored discharge. * Sinusitis verified by endoscopy or CT scan * Duration \> 12 weeks. * Signed informed consent to participate in the study.
Exclusion criteria
(CRS-Patients): * Antibiotic treatment in the last 3 months before study start. * Ongoing or recent participation in another clinical trial. * Any medication that might affect the results in an unpredictable manner. * Treatment with monoclonal antibodies (biologics). * Immunodeficiency other than low grade MBL deficiency. * Pregnancy or breastfeeding * Severe anatomical abnormalities. * SNOT 22 \< 20. Inclusion Criteria (Donors): * No history of sinonasal or lower airway disease within the last two years other than the common cold. * 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 22 (SNOT-22) (min 0 - max 110 higher being worse) | 14 days before intervention, on the first day of intervention, 2 and 3 months after intervention and as a follow up 1, 2 and 3 years after the study. | Subjective symptom grading of the patients will be used to asses efficacy of the treatment and the duration of the treatment effect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Nasal Symptom Score. (min 0 - max 9) | 14 days before intervention, daily during the five days of intervention, 2 and 3 months after intervention and as a follow up 1, 2 and 3 years after the study. | The TNSS scale will be used to measure nasal symptoms of donors and patients especially during the transplant procedure to evaluate the tolerability of the procedure. |
| Metagenomics | 6 and 2 weeks before intervention, 8 and 12 weeks after intervention and as a follow up twice with 4 weeks apart 1, 2 and 3 years after the study. | Microbiological samples will be collected from both donors and patients to assess whether the microbiota differ in patients with CRS compared to healthy subjects regarding composition, abundance, diversity, and stability. Further we will examine the effect of the microbiome transplant procedure on the recipients microbiota. |
| Endoscopy | 2 weeks before intervention, 3 months after intervention and as a follow up 1, 2 and 3 years after the study. | Patients will be documented using video endoscopy for later, blinded grading. |
| Inflammatory markers | 2 weeks before intervention, 12 weeks after intervention and as a follow up 1, 2 and 3 years after the study. | Biopsies from the nasal mucosa will be collected from both donors and patients and analysed for inflammatory endotypes and to assess the effect of the microbiome transplant procedure in the patients. |
| Adverse events | Entire study duration. Total study duration is 1 year and 5 months for the study and 3 years of follow up. | Any adverse events reported by the patients will be recorded. |
| Metabolomics | 2 weeks before intervention and 12 weeks after intervention and as a follow up 1, 2 and 3 years after the study. | Metabolomics samples will be collected from both donors and patients to assess if the microbiome activity differ in patients with CRS compared to healthy subjects and if this activity is affected by the microbiome transplant procedure. |
Countries
Sweden
Contacts
Primary ContactAnders Mårtensson, MD, PhD
Backup ContactFrida Blixt, MD
Outcome results
None listed