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

NCT05400616 | Unknown DMC

• 1 other identifier: University of Queensland
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

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).

Conditions

Chronic Rhinosinusitis (Diagnosis)

Keywords

microbiota; transplant; paranasal sinuses; nasal lavage

Outcome Measures

Primary Outcomes (1)

• Sino-Nasal Outcome Test (SNOT-22) - 22 Item Questionnaire

  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.

  Week 1 (Day 1) to Week 20

Secondary Outcomes (11)

• Lund-Kennedy endoscopic assessment score

  Week 1 (Day 1) to Week 20

• Characterisation of nasal microbiome in study participants

  Week 1 (Day 1) to Week 20

• Characterisation of microbiome within effective donors as compared to ineffective donors

  Week 1 (Day 1) - Week 2 (Day 9)

• 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).

• Cytokine level - Interleukin 5 or (IL-5)

  Week 1 (Day 1) to Week 20

Study Arms (2)

Intervention

EXPERIMENTAL

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

Procedure: Microbiome Transplant

Control

PLACEBO COMPARATOR

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

Procedure: Placebo

Interventions

Microbiome Transplant PROCEDURE

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

Intervention

Placebo PROCEDURE

Normal saline.

Control

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Accepted as a donor by the patient.
• Signed informed consent to participate in the study.

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Queensland: lead
• Royal Brisbane and Women's Hospital: collaborator
• Monash Health: collaborator
• Queensland University of Technology: collaborator

Study Sites (3)

Royal Brisbane and Women's Hospital

Brisbane, Queensland, 4006, Australia

RECRUITING

University of Queensland

Brisbane, Queensland, 4680, Australia

NOT YET RECRUITING

Monash Health

Melbourne, Australia

NOT YET RECRUITING

Related Publications (8)

• 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.

  PMID: 31879084 BACKGROUND

• 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.

  PMID: 32278449 BACKGROUND

• 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.

  PMID: 28785927 BACKGROUND

• 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.

  PMID: 22469599 BACKGROUND

• 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.

  PMID: 26510171 BACKGROUND

• 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.

  PMID: 12580880 BACKGROUND

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

  PMID: 28337570 BACKGROUND

• 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.

  PMID: 27902866 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Disease

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Anders Cervin, MD,FRACS

  University of Queensland/Royal Brisbane and Women's Hospital

  STUDY DIRECTOR

Central Study Contacts

Anders Cervin, MD,FRACS

CONTACT

617 3497 3588; a.cervin@uq.edu.au

Diane Maresco-Pennisi, PhD

CONTACT

617 3346 6072; d.marescopennisi@uq.edu.au

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 12, 2022
• First Posted: June 1, 2022
• Study Start: November 10, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2025
• Last Updated: December 7, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3)