An observational study in Rhinosinusitis Chronic and Microbiome, sponsored by Lallemand Pharma AG. Completed at 1 site in France. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2024-11-08.
Sponsored by Lallemand Pharma AG · Observational
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.
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.
330 studies on the registry are indexed under Rhinosinusitis; 55 are open to participants now.
This study's enrollment of 12 is below the median of 100 across 81 observational studies indexed under Rhinosinusitis.
Browse Rhinosinusitis studies →Lallemand Pharma AG is the lead sponsor of 10 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
The subjects will be recruited by the site among outpatients coming for routine consultation because of CRS.
Exclusion Criteria:
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
Comparaison of Alpha-diversity of Sino-nasal Microbiota Before and After Treatment (Visit 1 and Visit 2)
Comparaison of the values of alpha diversity of bacterial species assessed by the Shannon index at baseline and after the treatment period
Time frame: At baseline (V1) and at end of the 30-day treatment period (V2)
Impact of Healsea® Chronic on Quality of Life Assessed by the Sino-Nasal Outcome Test Score-22
Change of SNOT-22 total score at the end of the 30-day treatment period versus baseline . A change \>-9 is deemed clinically meaningful.
Time frame: End of treatment (Visit 2(V2)-Day 30) versus screening/inclusion (Visit 1(V1)-Day 1)
Patient Satisfaction Questionnaire (Usability)
To assess patient 's satisfaction regarding the medical device usability
Time frame: Visit 2(V2)-Day 30 (end of treatment)
Patient Satisfaction Questionnaire (Taste)
To assess patient 's satisfaction regarding the sensory perception (residual taste after spraying)
Time frame: Visit 2(V2)-Day 30 (end of treatment)
Patient Satisfaction Questionnaire (Efficacy)
To assess patient 's satisfaction regarding product efficacy for chronic Rhinosinusitis (Cleansing and Moistening of nasal mucosa)
Time frame: Visit 2(V2)-Day 30 (end of treatment)
Reporting of Adverse Events, Incidents and Expected Side Effects
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)
Time frame: During the intervention, up to 30 days
The subjects will be recruited by the site among outpatients coming for routine consultation because of CRS. The first patient was screened and enrolled on 12th December 2022, the last patient was screened and enrolled on 25th April 2023.
| Milestone | Healsea® Chronic: Hypertonic Seawater-Based Nasal Spray With Natural Symbiofilm® Extract |
|---|---|
| Started | 12 |
| Safety set | 12 |
| Full analysis set (fas) | 12 |
| Per protocol set (pp) | 3 |
| Completed | 12 |
| Not completed | 0 |
Comparaison of the values of alpha diversity of bacterial species assessed by the Shannon index at baseline and after the treatment period
| Shannon Index | Healsea® Chronic Baseline Value | Healsea® Chronic After 30-day Treatment |
|---|---|---|
| Comparaison of Alpha-diversity of Sino-nasal Microbiota Before and After Treatment (Visit 1 and Visit 2) | 2.041 ± 0.900 | 2.114 ± 1.041 |
Change of SNOT-22 total score at the end of the 30-day treatment period versus baseline . A change \>-9 is deemed clinically meaningful.
| score on a scale | Healsea Chronic Nasal Spray Baseline Value | Healsea® Chronic Nasal Spray After 30 Days |
|---|---|---|
| Absolute values of SNOT-22 total score | 59.3 ± 21.2 | 41.8 ± 25.5 |
| Change of SNOT-22 total score versus baseline | 0 ± 0 | -17.5 ± 17 |
To assess patient 's satisfaction regarding the medical device usability
| Participants | Healsea® Chronic: Hypertonic Seawater-Based Nasal Spray With Natural Symbiofilm® Extract |
|---|---|
| Missing | 0 |
| Not easy | 0 |
| Pretty easy | 0 |
| Easy | 0 |
| Very easy | 12 |
To assess patient 's satisfaction regarding the sensory perception (residual taste after spraying)
| Participants | Healsea® Chronic: Hypertonic Seawater-Based Nasal Spray With Natural Symbiofilm® Extract |
|---|---|
| Missing | 0 |
| Not pleasant | 0 |
| Neutral | 8 |
| Pleasant | 3 |
| Very pleasant | 1 |
To assess patient 's satisfaction regarding product efficacy for chronic Rhinosinusitis (Cleansing and Moistening of nasal mucosa)
| Participants | Healsea® Chronic: Hypertonic Seawater-Based Nasal Spray With Natural Symbiofilm® Extract |
|---|---|
| Missing | 0 |
| No improvement | 0 |
| Slight improvement | 2 |
| Moderate improvement | 6 |
| Very clear improvement | 4 |
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)
Results for this outcome have not been posted.
Collected over Adverse events/incidents were collected during the intervention and up to 30 days. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Healsea® Chronic: Hypertonic Seawater-Based Nasal Spray With Natural Symbiofilm® Extract | 0/12 (0%) | 0/12 (0%) | 2/12 (16.7%) |
| Event | Healsea® Chronic: Hypertonic Seawater-Based Nasal Spray With Natural Symbiofilm® Extract |
|---|---|
| Oropharyngeal painRespiratory, thoracic and mediastinal disorders | 2/12 |
| Mouth ulcerationGastrointestinal disorders | 1/12 |
| Palatal disorderGastrointestinal disorders | 1/12 |
| Age, Categorical(Participants) | Healsea® Chronic: Hypertonic Seawater-Based Nasal Spray With Natural Symbiofilm® Extract |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 10 |
| >=65 years | 2 |
| Age, Continuous(years) | Healsea® Chronic: Hypertonic Seawater-Based Nasal Spray With Natural Symbiofilm® Extract |
|---|---|
| Mean | 43.5 ± 13 |
| Sex: Female, Male(Participants) | Healsea® Chronic: Hypertonic Seawater-Based Nasal Spray With Natural Symbiofilm® Extract |
|---|---|
| Female | 11 |
| Male | 1 |
| Race (NIH/OMB)(Participants) | Healsea® Chronic: Hypertonic Seawater-Based Nasal Spray With Natural Symbiofilm® Extract |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 0 |
| More than one race | 0 |
| Unknown or Not Reported | 12 |
| Region of Enrollment(participants) | Healsea® Chronic: Hypertonic Seawater-Based Nasal Spray With Natural Symbiofilm® Extract |
|---|---|
| France | 12 |
| Baseline SNOT-22 (total)(score on a scale) | Healsea® Chronic: Hypertonic Seawater-Based Nasal Spray With Natural Symbiofilm® Extract |
|---|---|
| Mean | 59.3 ± 21.2 |
| α diversity(Shannon Index) | Healsea® Chronic: Hypertonic Seawater-Based Nasal Spray With Natural Symbiofilm® Extract |
|---|---|
| Mean | 2.041 ± 0.900 |
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Lallemand Pharma AG