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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05400616




Registration number
NCT05400616
Ethics application status
Date submitted
12/05/2022
Date registered
1/06/2022
Date last updated
7/12/2023

Titles & IDs
Public title
Nasal Microbiota Transfer Therapy in Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP)
Scientific title
Phase-II Randomized Control Trial of Nasal Microbiota Transplant Therapy in Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP)
Secondary ID [1] 0 0
University of Queensland
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Rhinosinusitis (Diagnosis) 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Microbiome Transplant
Treatment: Surgery - Placebo

Experimental: Intervention - For each nostril, the donated nasal wash sample is quiesced to 15 mls with saline Nasal Microbiota Transplant therapy.

Placebo Comparator: Control - For each nostril, 15 mls of saline will be used as the placebo therapy.


Treatment: Surgery: Microbiome Transplant
A raw microbiome, is collected from a donor without any sinonasal health problems, as a nasal lavage.

Treatment: Surgery: Placebo
Normal saline.
Intervention code [1] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Sino-Nasal Outcome Test (SNOT-22) - 22 Item Questionnaire
Timepoint [1] 0 0
Week 1 (Day 1) to Week 20
Secondary outcome [1] 0 0
Lund-Kennedy endoscopic assessment score
Timepoint [1] 0 0
Week 1 (Day 1) to Week 20
Secondary outcome [2] 0 0
Characterisation of nasal microbiome in study participants
Timepoint [2] 0 0
Week 1 (Day 1) to Week 20
Secondary outcome [3] 0 0
Characterisation of microbiome within effective donors as compared to ineffective donors
Timepoint [3] 0 0
Week 1 (Day 1) - Week 2 (Day 9)
Secondary outcome [4] 0 0
Adverse events of Participating Patients
Timepoint [4] 0 0
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).
Secondary outcome [5] 0 0
Cytokine level - Interleukin 5 or (IL-5)
Timepoint [5] 0 0
Week 1 (Day 1) to Week 20
Secondary outcome [6] 0 0
Cytokine level - Interleukin 13 (IL-13)
Timepoint [6] 0 0
Week 1 (Day 1) to Week 20
Secondary outcome [7] 0 0
Cytokine level - Interleukin 2 (IL-2)
Timepoint [7] 0 0
Week 1 (Day 1) to Week 20
Secondary outcome [8] 0 0
Cytokine level - Interleukin 6 (IL-6)
Timepoint [8] 0 0
Week 1 (Day 1) to Week 20
Secondary outcome [9] 0 0
Cytokine level - Interleukin 10 (IL-10)
Timepoint [9] 0 0
Week 1 (Day 1) to Week 20
Secondary outcome [10] 0 0
Cytokine level - Interferon gamma (IFN-?)
Timepoint [10] 0 0
Week 1 (Day 1) to Week 20
Secondary outcome [11] 0 0
Cytokine level - Interleukin 4 (IL-4)
Timepoint [11] 0 0
Week 1 (Day 1) to Week 20

Eligibility
Key inclusion criteria
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.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria (patient):

- 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:-

1. females must use contraceptive pill or Intra-uterine device (IUD) or similar and
condoms

2. 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.

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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/11/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2025
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [2] 0 0
University of Queensland - Brisbane
Recruitment hospital [3] 0 0
Monash Health - Melbourne
Recruitment postcode(s) [1] 0 0
4006 - Brisbane
Recruitment postcode(s) [2] 0 0
4680 - Brisbane
Recruitment postcode(s) [3] 0 0
- Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
The University of Queensland
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Royal Brisbane and Women's Hospital
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Monash Health
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Queensland University of Technology
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT05400616
Trial related presentations / publications
Marsh RL, Aho C, Beissbarth J, Bialasiewicz S, Binks M, Cervin A, Kirkham LS, Lemon KP, Slack MPE, Smith-Vaughan HC. Panel 4: Recent advances in understanding the natural history of the otitis media microbiome and its response to environmental pressures. Int J Pediatr Otorhinolaryngol. 2020 Mar;130 Suppl 1(Suppl 1):109836. doi: 10.1016/j.ijporl.2019.109836. Epub 2019 Dec 18.
Cho DY, Hunter RC, Ramakrishnan VR. The Microbiome and Chronic Rhinosinusitis. Immunol Allergy Clin North Am. 2020 May;40(2):251-263. doi: 10.1016/j.iac.2019.12.009. Epub 2020 Jan 16.
Psaltis AJ, Wormald PJ. Therapy of Sinonasal Microbiome in CRS: A Critical Approach. Curr Allergy Asthma Rep. 2017 Sep;17(9):59. doi: 10.1007/s11882-017-0726-x.
Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaert P, Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C, Jones N, Joos G, Kalogjera L, Kern B, Kowalski M, Price D, Riechelmann H, Schlosser R, Senior B, Thomas M, Toskala E, Voegels R, Wang de Y, Wormald PJ. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology. 2012 Mar;50(1):1-12. doi: 10.4193/Rhino12.000.
Mahdavinia M, Keshavarzian A, Tobin MC, Landay AL, Schleimer RP. A comprehensive review of the nasal microbiome in chronic rhinosinusitis (CRS). Clin Exp Allergy. 2016 Jan;46(1):21-41. doi: 10.1111/cea.12666.
Buckland JR, Thomas S, Harries PG. Can the Sino-nasal Outcome Test (SNOT-22) be used as a reliable outcome measure for successful septal surgery? Clin Otolaryngol Allied Sci. 2003 Feb;28(1):43-7. doi: 10.1046/j.1365-2273.2003.00663.x.
Rudmik L. Economics of Chronic Rhinosinusitis. Curr Allergy Asthma Rep. 2017 Apr;17(4):20. doi: 10.1007/s11882-017-0690-5.
Wagner Mackenzie B, Waite DW, Hoggard M, Douglas RG, Taylor MW, Biswas K. Bacterial community collapse: a meta-analysis of the sinonasal microbiota in chronic rhinosinusitis. Environ Microbiol. 2017 Jan;19(1):381-392. doi: 10.1111/1462-2920.13632. Epub 2017 Jan 18.
Public notes

Contacts
Principal investigator
Name 0 0
Anders Cervin, MD,FRACS
Address 0 0
University of Queensland/Royal Brisbane and Women's Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Anders Cervin, MD,FRACS
Address 0 0
Country 0 0
Phone 0 0
617 3497 3588
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05400616