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

Region Skane

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Chronic Rhinosinusitis With Nasal Polyps; Chronic Rhinosinusitis Without Nasal Polyps

Treatments: Procedure: Sinonasal microbiome transplant procedure.; Other: Placebo saline transplant

Study type: Interventional

Funder types: Other

Identifiers

NCT07184684

Dnr 2024-03308-02

Details and patient eligibility

About

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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria (CRS-Patients):

• 2 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.

Exclusion Criteria (CRS-Patients):

• 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.

Inclusion Criteria (Donors):

• 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.

Exclusion Criteria (CRS-Patients):

• Chronic rhinosinusitis.
• Acute rhinosinusitis within the last two years.
• Nasal polyposis
• Antibiotic treatment within the last 3 months before the study start.
• On going or recent participation in another clinical trial.
• Findings in the pre study scan that makes the donor unsuitable.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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50 participants in 2 patient groups, including a placebo group

Microbiome transplant

Active Comparator group

Description:

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

Treatment:

Procedure: Sinonasal microbiome transplant procedure.

Placebo transplant

Placebo Comparator group

Description:

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

Treatment:

Other: Placebo saline transplant