Impact of Symbiofilm On Nasal Microbiota

NCT ID: NCT05015530

Last Updated: 2024-11-08

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 12 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-12-12
• Study Completion Date: 2023-05-19

Brief Summary

Healsea® chronic is CE marked medical device indicated in adults for the treatment of nasal symptoms of chronic rhinosinusitis. This is an hypertonic seawater-based nasal spray supplemented with natural Symbiofilm® extract (0.2%) isolated from marine bacteria. In vitro, Symbiofilm® inhibits at early stage biofilm formation from bacteria found to be more prevalent and abundant in CRS patients (e.g. Staphylococcus aureus, Pseudomonas aeruginosa). This exploratory study is designed with aim to determine if the antibiofilm properties of Symbiofilm® may modify sino-nasal microbiota, impacting α and/ or β diversities.

Detailed Description

Chronic rhinosinusitis (CRS) is an inflammation of the nose and paranasal sinuses and is characterized by two or more symptoms, one of which should be either nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip), lasting for 12 weeks or longer. In addition, facial pain or pressure and a reduction in the sense of smell can occur. The condition can occur with or without nasal polyps.

Chronic rhinosinusitis (CRS) is a significant health problem and affects 5-12% of the general population.

The physiopathology of CRS is poorly understood with multiple environmental, host and microbial factors being implicated. Putative pathological factors include changes in the microbiota, imbalance of the local or systemic immune system, allergens, toxins and genetic predisposition.

A dysbiosis mechanism has been proposed as modulating inflammation in diseased sinuses. This hypothesis suggests that externally influenced changes in the nasal microbiome can result in dysbiosis, i.e. a shift from a "normal" or "healthy" microbial community structure and that this shift may be responsible for the initiation or maintenance of CRS. For example, the disruption of the commensal biofilm during a viral upper respiratory tract infection can create a niche for pathogenic species to grow. Despite many contradictory statements in the different studies some common trends emerge. Less diversity in the microbial community rather than an increased overall bacterial load seems to characterize CRS compared to the healthy state with no consensus about specific genera indicative of disease. However, anaerobes and S. aureus are found to be significantly more prevalent and abundant in CRS versus healthy controls. Bacterial biofilm is detected on the sinus mucosa in up to 80% of CRS patients and its presence does not imply that it is causing mucosal inflammation. However, in the context of CRS, there are several possible mechanisms by which biofilms may be pro-inflammatory including the release of planktonic organisms and the release of superantigens, which can cause ciliary dysfunction and inhibition of ciliary clearance. Bacterial biofilms are likely a key modulator of the refractory nature of CRS.

Although clinical evidence from well-designed trials is scarce, European Guidelines for chronic rhinosinusitis recommend daily nasal saline irrigation for reduction of the severity of symptoms of CRS. A recent Cochrane analysis has concluded that daily nasal irrigation with hypertonic saline solution is more effective than placebo to improve patient symptoms. The exact mechanisms by which nasal irrigation works are not known. However, most of the experts agree that it is primarily a mechanical intervention leading to direct cleansing of the nasal mucosa. Nevertheless, the efficacy of such solution remains moderate.

Healsea® Chronic is a CE marked medical device indicated in adults for the treatment of nasal symptoms of chronic rhinosinusitis. This is a seawater-based nasal spray supplemented with a natural Symbiofilm® extract (0.02%) isolated from marine bacteria. The nasal solution is hypertonic (NaCl 2.2%). Symbiofilm® is a marine postbiotic comprising active exopolysaccharides with emulsifying properties and in vitro antibiofilm activity. Antibiofilm properties have been demonstrated with the colorimetric microtiter plate assay. In this model, a significant inhibition of biofilm formation by Staphylococcus aureus and Haemophilus influenzae are observed. Detachment properties from human nasal epithelial cells of Staphylococcus aureus and Pseudomonas aeruginosa has also been demonstrated in vitro, suggesting an inhibition of biofilm formation at early stage in this model. Symbiofilm® has no bacteriostatic nor bactericidal activities.

To date, properly designed studies to evaluate the effect of topical therapies on microbiome are scarce so no definite conclusion can be made. In one study, use of saline irrigation with or without budesonideDCI used was not associated with significantly distinct microbiota composition among either controls or post-operative CRS patients with polyp.

This exploratory study is designed with aim to determine if the antibiofilm properties of Symbiofilm® may modify sino-nasal microbiota, impacting α and/ or β diversities. To this end middle meatus swab specimen will be taken from CRS patients before and after treatment with Healsea® Chronic. Bacteria colonization will be assessed using quantitative PCR and 16S rRNA gene sequencing.

Improvement of nasal symptoms and quality of life will be assessed with the Sino-Nasal Outcome Test score-22 (SNOT-22). Post-market vigilance of Healsea® Chronic and vigilance of study procedures will be assessed throughout the study.

Conditions

Rhinosinusitis Chronic; Microbiome

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

Test Medical Device

Healsea Chronic nasal spray will be administered twice daily (1 puff, 1-2 sec) in each nostril during 30 days

Healsea® Chronic, hypertonic seawater-based nasal spray supplemented with natural Symbiofilm® extract

Intervention Type: DEVICE

Healsea® Chronic nasal spray will be administered twice daily (1 puff, 1-2 sec) in each nostril during 30 days

Interventions

Healsea® Chronic, hypertonic seawater-based nasal spray supplemented with natural Symbiofilm® extract

Healsea® Chronic nasal spray will be administered twice daily (1 puff, 1-2 sec) in each nostril during 30 days

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Male or female, aged 18 - 70 years

2. Provision of signed and dated informed consent form

3. Stated willingness to comply with all study procedures and availability for the duration of the study

4. Diagnosed with CRS based on the diagnostic criteria of the EPOS guideline

5. Registered with a social security scheme or covered by such a regime

Exclusion Criteria

1. Antibiotics or oral corticosteroids intake in the month prior to the study

2. Endoscopic sinus surgery in the past 6 months

3. Cystic fibrosis

4. Wegener's granulomatosis

5. Immunodeficiency

6. Defective access to middle meatus

7. Lidocaine allergy

8. Known hypersensitivity/allergy to any component of the test device

9. Pregnant/Lactating female or absence of efficient contraception

10. Under tutorship or guardianship

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lallemand Pharma AG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pr Guillaume de Bonnecaze, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Otorhinolaryngology , University Hospital of Toulouse (Larrey), France

Locations

Larrey Hospital

Toulouse, , France

Countries

France

References

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Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

LPH-2102

Identifier Type: -

Identifier Source: org_study_id