Sinonasal Microbiome Transplant as a Therapy for Chronic Rhinosinusitis (CRS).

NCT07184684 | Recruiting Phase 2

• 1 other identifier: Dnr 2024-03308-02
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Rhinosinusitis Without Nasal Polyps; Chronic Rhinosinusitis With Nasal Polyps

Outcome Measures

Primary Outcomes (1)

• Sino-nasal outcome test 22 (SNOT-22) (min 0 - max 110 higher being worse)

  Subjective symptom grading of the patients will be used to asses efficacy of the treatment and the duration of the treatment effect.

  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.

Secondary Outcomes (6)

• Endoscopy

  2 weeks before intervention, 3 months after intervention and as a follow up 1, 2 and 3 years after the study.

• 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.

• 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.

• Metabolomics

  2 weeks before intervention and 12 weeks after intervention and as a follow up 1, 2 and 3 years after the study.

• Inflammatory markers

  2 weeks before intervention, 12 weeks after intervention and as a follow up 1, 2 and 3 years after the study.

Study Arms (2)

Microbiome transplant

ACTIVE COMPARATOR

The study subject is examined before and after recieving 13 days of antibiotics followed by 5 concecutive days of microbiome transplant.

Procedure: Sinonasal microbiome transplant procedure.

Placebo transplant

PLACEBO COMPARATOR

The study subject is examined before and after recieving 13 days of antibiotics followed by 5 concecutive days of placebo (saline) transplant.

Other: Placebo saline transplant

Interventions

Sinonasal microbiome transplant procedure. PROCEDURE

A sinonasal microbiome transplant obtained from a healthy donor and administered as a nasal lavage once daily for five consecutive days.

Microbiome transplant

Placebo saline transplant OTHER

Placebo transplant containing saline administered as a nasala lavage once daily for five consecutive days.

Placebo transplant

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• Chronic rhinosinusitis.
• Acute rhinosinusitis within the last two years.
• Nasal polyposis
• Antibiotic treatment within the last 3 months before the study start.

Sponsors & Collaborators

• Region Skane: lead

Study Sites (1)

Departement of ORL

Helsingborg, 25187, Sweden

RECRUITING

Related Publications (16)

• Fokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsma S, Toppila-Salmi S, Bernal-Sprekelsen M, Mullol J, Alobid I, Terezinha Anselmo-Lima W, Bachert C, Baroody F, von Buchwald C, Cervin A, Cohen N, Constantinidis J, De Gabory L, Desrosiers M, Diamant Z, Douglas RG, Gevaert PH, Hafner A, Harvey RJ, Joos GF, Kalogjera L, Knill A, Kocks JH, Landis BN, Limpens J, Lebeer S, Lourenco O, Meco C, Matricardi PM, O'Mahony L, Philpott CM, Ryan D, Schlosser R, Senior B, Smith TL, Teeling T, Tomazic PV, Wang DY, Wang D, Zhang L, Agius AM, Ahlstrom-Emanuelsson C, Alabri R, Albu S, Alhabash S, Aleksic A, Aloulah M, Al-Qudah M, Alsaleh S, Baban MA, Baudoin T, Balvers T, Battaglia P, Bedoya JD, Beule A, Bofares KM, Braverman I, Brozek-Madry E, Richard B, Callejas C, Carrie S, Caulley L, Chussi D, de Corso E, Coste A, El Hadi U, Elfarouk A, Eloy PH, Farrokhi S, Felisati G, Ferrari MD, Fishchuk R, Grayson W, Goncalves PM, Grdinic B, Grgic V, Hamizan AW, Heinichen JV, Husain S, Ping TI, Ivaska J, Jakimovska F, Jovancevic L, Kakande E, Kamel R, Karpischenko S, Kariyawasam HH, Kawauchi H, Kjeldsen A, Klimek L, Krzeski A, Kopacheva Barsova G, Kim SW, Lal D, Letort JJ, Lopatin A, Mahdjoubi A, Mesbahi A, Netkovski J, Nyenbue Tshipukane D, Obando-Valverde A, Okano M, Onerci M, Ong YK, Orlandi R, Otori N, Ouennoughy K, Ozkan M, Peric A, Plzak J, Prokopakis E, Prepageran N, Psaltis A, Pugin B, Raftopulos M, Rombaux P, Riechelmann H, Sahtout S, Sarafoleanu CC, Searyoh K, Rhee CS, Shi J, Shkoukani M, Shukuryan AK, Sicak M, Smyth D, Sindvongs K, Soklic Kosak T, Stjarne P, Sutikno B, Steinsvag S, Tantilipikorn P, Thanaviratananich S, Tran T, Urbancic J, Valiulius A, Vasquez de Aparicio C, Vicheva D, Virkkula PM, Vicente G, Voegels R, Wagenmann MM, Wardani RS, Welge-Lussen A, Witterick I, Wright E, Zabolotniy D, Zsolt B, Zwetsloot CP. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020 Feb 20;58(Suppl S29):1-464. doi: 10.4193/Rhin20.600.

  PMID: 32077450 BACKGROUND

• Rudmik L, Smith TL. Quality of life in patients with chronic rhinosinusitis. Curr Allergy Asthma Rep. 2011 Jun;11(3):247-52. doi: 10.1007/s11882-010-0175-2.

  PMID: 21234819 BACKGROUND

• Wahid NW, Smith R, Clark A, Salam M, Philpott CM. The socioeconomic cost of chronic rhinosinusitis study. Rhinology. 2020 Apr 1;58(2):112-125. doi: 10.4193/Rhin19.424.

  PMID: 32172284 BACKGROUND

• McCormick JP, Thompson HM, Cho DY, Woodworth BA, Grayson JW. Phenotypes in Chronic Rhinosinusitis. Curr Allergy Asthma Rep. 2020 May 19;20(7):20. doi: 10.1007/s11882-020-00916-6.

  PMID: 32430653 BACKGROUND

• Kato A, Peters AT, Stevens WW, Schleimer RP, Tan BK, Kern RC. Endotypes of chronic rhinosinusitis: Relationships to disease phenotypes, pathogenesis, clinical findings, and treatment approaches. Allergy. 2022 Mar;77(3):812-826. doi: 10.1111/all.15074. Epub 2021 Sep 15.

  PMID: 34473358 BACKGROUND

• Stevens WW, Peters AT, Tan BK, Klingler AI, Poposki JA, Hulse KE, Grammer LC, Welch KC, Smith SS, Conley DB, Kern RC, Schleimer RP, Kato A. Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis. J Allergy Clin Immunol Pract. 2019 Nov-Dec;7(8):2812-2820.e3. doi: 10.1016/j.jaip.2019.05.009. Epub 2019 May 22.

  PMID: 31128376 BACKGROUND

• Foster KR, Schluter J, Coyte KZ, Rakoff-Nahoum S. The evolution of the host microbiome as an ecosystem on a leash. Nature. 2017 Aug 2;548(7665):43-51. doi: 10.1038/nature23292.

  PMID: 28770836 BACKGROUND

• Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014 Mar 27;157(1):121-41. doi: 10.1016/j.cell.2014.03.011.

  PMID: 24679531 BACKGROUND

• Martens K, Pugin B, De Boeck I, Spacova I, Steelant B, Seys SF, Lebeer S, Hellings PW. Probiotics for the airways: Potential to improve epithelial and immune homeostasis. Allergy. 2018 Oct;73(10):1954-1963. doi: 10.1111/all.13495. Epub 2018 Jun 28.

  PMID: 29869783 BACKGROUND

• Aggarwal N, Kitano S, Puah GRY, Kittelmann S, Hwang IY, Chang MW. Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies. Chem Rev. 2023 Jan 11;123(1):31-72. doi: 10.1021/acs.chemrev.2c00431. Epub 2022 Nov 1.

  PMID: 36317983 BACKGROUND

• Psaltis AJ, Mackenzie BW, Cope EK, Ramakrishnan VR. Unraveling the role of the microbiome in chronic rhinosinusitis. J Allergy Clin Immunol. 2022 May;149(5):1513-1521. doi: 10.1016/j.jaci.2022.02.022. Epub 2022 Mar 14.

  PMID: 35300985 BACKGROUND

• Paramasivan S, Bassiouni A, Shiffer A, Dillon MR, Cope EK, Cooksley C, Ramezanpour M, Moraitis S, Ali MJ, Bleier B, Callejas C, Cornet ME, Douglas RG, Dutra D, Georgalas C, Harvey RJ, Hwang PH, Luong AU, Schlosser RJ, Tantilipikorn P, Tewfik MA, Vreugde S, Wormald PJ, Caporaso JG, Psaltis AJ. The international sinonasal microbiome study: A multicentre, multinational characterization of sinonasal bacterial ecology. Allergy. 2020 Aug;75(8):2037-2049. doi: 10.1111/all.14276. Epub 2020 Mar 30.

  PMID: 32167574 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

• Wang ZK, Yang YS, Chen Y, Yuan J, Sun G, Peng LH. Intestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel disease. World J Gastroenterol. 2014 Oct 28;20(40):14805-20. doi: 10.3748/wjg.v20.i40.14805.

  PMID: 25356041 BACKGROUND

• Martensson A, Cervin-Hoberg C, Huygens F, Lindstedt M, Sakellariou C, Greiff L, Cervin A. Upper airway microbiome transplantation for patients with chronic rhinosinusitis. Int Forum Allergy Rhinol. 2023 Jun;13(6):979-988. doi: 10.1002/alr.23122. Epub 2023 Jan 1.

  PMID: 36515012 BACKGROUND

• Martensson A, Abolhalaj M, Lindstedt M, Martensson A, Olofsson TC, Vasquez A, Greiff L, Cervin A. Clinical efficacy of a topical lactic acid bacterial microbiome in chronic rhinosinusitis: A randomized controlled trial. Laryngoscope Investig Otolaryngol. 2017 Nov 8;2(6):410-416. doi: 10.1002/lio2.93. eCollection 2017 Dec.

  PMID: 29299516 BACKGROUND

Study Officials

• Anders Mårtensson, MD, PhD

  Region Skåne, Lund University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anders Mårtensson, MD, PhD

CONTACT

0424061000; anders.s.martensson@gmail.com

Frida Blixt, MD

CONTACT

0424061000; Frida.Blixt@skane.se

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 12, 2024
• First Posted: September 22, 2025
• Study Start: October 14, 2024
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2031
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)