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

NCT03122795 | Completed

• 1 other identifier: Snortransplantationsstudie1
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic rhinosinusitis (CRS) is a disease associated with impaired quality of life and substantial societal costs. Though sometimes co-appearing with other conditions, such as asthma, allergy, and nasal polyps, many cases present without co-morbidities. Micro-biological diagnostic procedures are frequently undertaken, but the results are often inconclusive. Nevertheless, antibiotics are usually prescribed, but invariably with limited and temporary success. Accordingly, there is a need for new treatments for CRS. Recent studies indicate that the sinuses are colonized by a commensal microbiome of bacteria and that damage to this natural microbiome, by pathogens or antibiotics, may cause an imbalance that may promote CRS. Therefore, treatments that restore the commensal microbiome may offer an alternative to current protocols. Arguably, as suggested by studies on patients with intestinal infections (next paragraph), one such possibility may be to transfer a "normal microbiome" to patients with CRS. A disrupted microbiome is linked to intestinal clostridium difficile infections. Probiotic restitution therapy may be effective even in cases recalcitrant to antibiotic treatment. However, a key to effective probiotic restitution is selecting the bacteria that facilitate regrowth of normal microbiome. As an answer to this, researchers have chosen to simply transplant the entire microbiome from a healthy donor. In the case of clostridium difficile infection in the form of faecal transplants. In this study, we will examine the possibility to treat patients with chronic rhinosinusitis without polyps (CRSsNP) with complete sinonasal microbiomes obtained from healthy donors. Our analysis will focus on symptoms and signs of disease as well as on nasal inflammatory and microbiological indices.

Conditions

Chronic Rhinosinusitis (Diagnosis)

Outcome Measures

Primary Outcomes (1)

• SNOT-22

  Change of burden of disease as measured by the SNOT-22 (22 item sinonasal outcome test) questionnaire in patients

  Day 1 to day 106

Secondary Outcomes (4)

• Lund Kennedy endoscopy score

  Day 1 to day 106

• Subjective symptom score

  Day 1 to 106.

• Inflammatory burden

  Day 1 to day 106

• Microflora

  Day 1 to day 106

Study Arms (1)

Microbiome transplant

EXPERIMENTAL

The only arm of the study. Patients suffering from CRSsNP gets microbiome transplants from donors without any sinonasal health problems.

Procedure: Microbiome transplant

Interventions

Microbiome transplant PROCEDURE

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

Microbiome transplant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• nasal symptoms: 1 of which must be nasal obstruction or discoloured discharge.
• Sinusitis verified by endoscopy or CT-scan.
• Duration \> 12 weeks.
• Previous surgery with patent ostia to the diseased sinuses.
• Signed informed consent to participate in the study.
• No history of sinonasal or lower airway disease within 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:

• Nasal polyposis.
• Antibiotic treatment within the last 4 weeks.
• On-going or recent participation in another clinical trial.
• Any medication that may affect the results in an unpredictable manner.
• Immune deficiency.
• Allergy to amoxicillin or clavulanate potassium and clarithromycin.
• Pregnancy or breastfeeding.
• Chronic rhinosinusitis.
• Acute rhinosinusitis within the last two years.
• Nasal polyposis.
• Asthma.
• Antibiotic treatment within the last 4 weeks.
• On-going or recent participation in another clinical trial.
• Findings in the pre-study pathogen scan that makes the donor unsuitable.
• Pregnancy or breastfeeding.

Sponsors & Collaborators

• Region Skane: lead

Study Sites (1)

Departement of ORL

Helsingborg, 25187, Sweden

Location

Related Publications (12)

• 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

• Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012 Jun 13;486(7402):207-14. doi: 10.1038/nature11234.

  PMID: 22699609 BACKGROUND

• Abreu NA, Nagalingam NA, Song Y, Roediger FC, Pletcher SD, Goldberg AN, Lynch SV. Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum enrichment mediates rhinosinusitis. Sci Transl Med. 2012 Sep 12;4(151):151ra124. doi: 10.1126/scitranslmed.3003783.

  PMID: 22972842 BACKGROUND

• van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, Keller JJ. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15. doi: 10.1056/NEJMoa1205037. Epub 2013 Jan 16.

  PMID: 23323867 BACKGROUND

• Nagalingam NA, Cope EK, Lynch SV. Probiotic strategies for treatment of respiratory diseases. Trends Microbiol. 2013 Sep;21(9):485-92. doi: 10.1016/j.tim.2013.04.008. Epub 2013 May 23.

  PMID: 23707554 BACKGROUND

• Cope EK, Lynch SV. Novel microbiome-based therapeutics for chronic rhinosinusitis. Curr Allergy Asthma Rep. 2015 Mar;15(3):504. doi: 10.1007/s11882-014-0504-y.

  PMID: 25777787 BACKGROUND

• Hopkins C, Gillett S, Slack R, Lund VJ, Browne JP. Psychometric validity of the 22-item Sinonasal Outcome Test. Clin Otolaryngol. 2009 Oct;34(5):447-54. doi: 10.1111/j.1749-4486.2009.01995.x.

  PMID: 19793277 BACKGROUND

• Lund VJ, Kennedy DW. Staging for rhinosinusitis. Otolaryngol Head Neck Surg. 1997 Sep;117(3 Pt 2):S35-40. doi: 10.1016/S0194-59989770005-6.

  PMID: 9334786 BACKGROUND

• Greiff L, Andersson M, Persson CG. Nasal secretions and exudations : collection and approaches to analysis. Methods Mol Med. 2001;56:61-73. doi: 10.1385/1-59259-151-5:61.

  PMID: 21336890 BACKGROUND

• Greiff L, Pipkorn U, Alkner U, Persson CG. The 'nasal pool' device applies controlled concentrations of solutes on human nasal airway mucosa and samples its surface exudations/secretions. Clin Exp Allergy. 1990 May;20(3):253-9. doi: 10.1111/j.1365-2222.1990.tb02680.x.

  PMID: 2364306 BACKGROUND

• Morgan XC, Huttenhower C. Chapter 12: Human microbiome analysis. PLoS Comput Biol. 2012;8(12):e1002808. doi: 10.1371/journal.pcbi.1002808. Epub 2012 Dec 27.

  PMID: 23300406 BACKGROUND

• Sahlstrand-Johnson P, Ohlsson B, Von Buchwald C, Jannert M, Ahlner-Elmqvist M. A multi-centre study on quality of life and absenteeism in patients with CRS referred for endoscopic surgery. Rhinology. 2011 Oct;49(4):420-8. doi: 10.4193/Rhino11.101.

  PMID: 21991567 BACKGROUND

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 Mårtensson, MD

  Region Skåne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients and donors who meet the inclusion criteria will be recruited and inclueded and put through the study in a cumulative fashion.

Study Record Dates

• First Submitted: April 18, 2017
• First Posted: April 21, 2017
• Study Start: May 15, 2017
• Primary Completion: December 17, 2018
• Study Completion: December 31, 2018
• Last Updated: January 11, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)