ISONAM: Impact of Symbiofilm On Nasal Microbiota

Sponsor

Lallemand Pharma AG (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05015530

Collaborator

(none)

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Rhinosinusitis Chronic Microbiome	Device: Healsea® Chronic, hypertonic seawater-based nasal spray supplemented with natural Symbiofilm® extract

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

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

20 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

Assessment of Sino-nasal Microbial Communities Changes in Adult Patients With Chronic Rhinosinusitis by 16 rRNA Gene Amplicon Sequencing Before and After 1-month Treatment Duration With Healsea® Chronic: an Exploratory Study

Anticipated Study Start Date :

Nov 1, 2022

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Test Medical Device Healsea Chronic nasal spray will be administered twice daily (1 puff, 1-2 sec) in each nostril during 30 days	Device: 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

Arm

Intervention/Treatment

Test Medical Device

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

Device: 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

Outcome Measures

Primary Outcome Measures

Modifications in microbial load and/or profile [Change in microbial species abundance and diversity at end of treatment (Visit 2(V2)-Day 30) versus screening/inclusion (Visit 1(V1)-Day 1)]
The microbial load will be evaluated by quantitative PCR and microbiome taxonomic profiling by 16S rRNA gene sequencing. Data obtained in patients before and after 1-month treatment with Healsea® Chronic will be compared using statistical analyses to assess changes in microbial species abundance and diversity. The analysis will also focus on typical sino-nasal pathogens (e.g. Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxell catarrhalis) at genus level, and if reachable, at species level.

Secondary Outcome Measures

Impact of Healsea® Chronic on quality of life assessed by the Sino-Nasal Outcome test score-22 [Change in quality of life of CRS patients using the SNOT-22 score at end of treatment (Visit 2(V2)-Day 30) versus screening/inclusion (Visit 1(V1)-Day 1)]
To measure the clinical performance of Healsea® Chronic, the quality of life of CRS patients will be assessed with the Sino-Nasal Outcome Test score-22 (SNOT-22). This questionnaire is a disease-specific, quality-of-life-related measure of sinonasal function. Patients should rate sino-nasal symptoms and their impact from 0 to 5 where 0 means that there is no complaint and 5 means that there are serious complaints.
Patient satisfaction questionnaire [Visit 2(V2)-Day 30 (end of treatment)]
To assess patient 's satisfaction regarding the medical device usability, its sensory perception and its efficacy for chronic Rhinosinusitis

Other Outcome Measures

Reporting of adverse events, incidents and expected side effects [During the intervention, up to 30 days]
Assessment of materiovigilance from the medical device (incidents, expected side effects) and reporting of adverse reactions related to the additional invasive procedure (swab of the nasal meatus)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female, aged 18 - 70 years
Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Diagnosed with CRS based on the diagnostic criteria of the EPOS guideline
Registered with a social security scheme or covered by such a regime