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

NCT ID: NCT05400616

Last Updated: 2023-12-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-10

Study Completion Date

2025-12-31

Brief Summary

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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

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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).

Conditions

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Chronic Rhinosinusitis (Diagnosis)

Keywords

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microbiota transplant paranasal sinuses nasal lavage

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
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.

Study Groups

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Intervention

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

Group Type EXPERIMENTAL

Microbiome Transplant

Intervention Type PROCEDURE

A raw microbiome, is collected from a donor without any sinonasal health problems, as a nasal lavage.

Control

For each nostril, 15 mls of saline will be used as the placebo therapy.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type PROCEDURE

Normal saline.

Interventions

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Microbiome Transplant

A raw microbiome, is collected from a donor without any sinonasal health problems, as a nasal lavage.

Intervention Type PROCEDURE

Placebo

Normal saline.

Intervention Type PROCEDURE

Eligibility Criteria

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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:-

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.


* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Royal Brisbane and Women's Hospital

OTHER_GOV

Sponsor Role collaborator

Monash Health

OTHER

Sponsor Role collaborator

Queensland University of Technology

OTHER

Sponsor Role collaborator

The University of Queensland

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Anders Cervin, MD,FRACS

Role: STUDY_DIRECTOR

University of Queensland/Royal Brisbane and Women's Hospital

Locations

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Royal Brisbane and Women's Hospital

Brisbane, Queensland, Australia

Site Status RECRUITING

University of Queensland

Brisbane, Queensland, Australia

Site Status NOT_YET_RECRUITING

Monash Health

Melbourne, , Australia

Site Status NOT_YET_RECRUITING

Countries

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Australia

Central Contacts

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Anders Cervin, MD,FRACS

Role: CONTACT

Phone: 617 3497 3588

Email: [email protected]

Diane Maresco-Pennisi, PhD

Role: CONTACT

Phone: 617 3346 6072

Email: [email protected]

Facility Contacts

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Abigail Walker, MD,FRACS

Role: primary

Diane Maresco-Pennisi, PhD

Role: primary

JoAnne Rimmer, MD,FRACS

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 31879084 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32278449 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28785927 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22469599 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26510171 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12580880 (View on PubMed)

Rudmik L. Economics of Chronic Rhinosinusitis. Curr Allergy Asthma Rep. 2017 Apr;17(4):20. doi: 10.1007/s11882-017-0690-5.

Reference Type BACKGROUND
PMID: 28337570 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27902866 (View on PubMed)

Related Links

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https://clinicaltrials.gov/ct2/show/NCT03122795

Sinonasal Microbiome Transplant as a Therapy for Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP) - pilot study

Other Identifiers

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University of Queensland

Identifier Type: -

Identifier Source: org_study_id