Study of Probiotic Potential of Lactobacillus Strains in the Upper Respiratory Tract After Nasal Spray Application

Not Applicable

• Conditions: Sprays; Probiotics; Chronic Rhinosinusitis (Diagnosis); Healthy Volunteers; Nasal Disease
• Interventions: Other: Probiotic nasal spray; Other: Placebo nasal spray

• Registration Number: NCT03587545
• Lead Sponsor: University Hospital, Antwerp

Brief Summary

Probiotics are defined as "live micro-organisms that, when administered in adequate amounts, confer a health benefit to the host" (Hill et al, 2014). These microbes are generally applied in the gastrointestinal tract via fermented food products or capsules. In previous research, the investigators isolated bacterial strains with potential probiotic properties for the upper respiratory tract based on in vitro laboratory tests, in vivo mice experiments and genome sequencing.

In this study, the investigators want to deliver the Proof-of-Concept that the most promising isolated strain, Lactobacillus casei AMBR2 (LAMBR2) and the well-documented probiotic strain Lactobacillus rhamnosus GG (LGG) also have interesting properties in humans, i.e. that these strains are able to -temporarily- persist in the upper respiratory tract of healthy volunteers and CRS patients after daily nasal application via a nasal spray for 2 weeks. In addition, the investigators aim to explore whether the application of these strains has an impact on the nasopharyngeal microbiome via 16S rRNA amplicon sequencing and dedicated qPCR analysis.

Therefore, bacterial DNA from nasal swabs will be isolated via commercially available DNA extraction kits, followed by Illumina MiSeq sequencing in order to identify the bacterial species present in these samples. Furthermore, the concentration of the Lactobacillus and specific pathogens will be monitored via qPCR.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-06-01
• Study First Submitted: 2018-06-27
• Study First Submitted QC: 2018-07-13
• Study First Posted: 2018-07-16
• Primary Completion: 2018-10-10
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-07
• Last Update Posted: 2020-04-08
• Study Completion: 2021-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• CRS patient group: CRS diagnosed

Exclusion Criteria

• no patients with trisomy 21
• no pregnant women
• no breastfeeding women
• no acute or chronic airway infections (except for CRS patients in CRS patient group)
• no cancer
• no autoimmune diseases

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Healthy probiotic group LAMBR2	Probiotic nasal spray	Daily intake by healthy volunteers of 2 dosages of LAMBR2 spray during 2 weeks. Probiotic nasal spray.
Healthy placebo group	Placebo nasal spray	Daily intake by healthy volunteers of 2 dosages of placebo spray during 2 weeks. Placebo nasal spray.
CRS placebo group	Placebo nasal spray	Daily intake by CRS patients of 2 dosages of placebo spray during 2 weeks. Placebo nasal spray.
Healthy probiotic group LGG	Probiotic nasal spray	Daily intake by healthy volunteers of 2 dosages of LGG spray during 2 weeks. Probiotic nasal spray.
CRS probiotic group LGG	Probiotic nasal spray	Daily intake by CRS patients of 2 dosages of LGG spray during 2 weeks. Probiotic nasal spray.
CRS probiotic group LAMBR2	Probiotic nasal spray	Daily intake by CRS patients of 2 dosages of LAMBR2 spray during 2 weeks. Probiotic nasal spray.

Primary Outcome Measures

Name	Time	Method
Nasal persistence of lactobacilli	3 years	After DNA extraction of the biological samples, the relative and absolute concentration of the administered probiotics will be monitored via microbiome analysis and qPCR. This will give information about the capacity of the probiotics to colonize the nasopharynx.

Secondary Outcome Measures

Name	Time	Method
Therapeutic potential: chronic rhinosinusitis	3 years	Chronic rhinosinusitis symptoms will be evaluated before and after administration of the nasal spray. Participants should rate the complaints linked to CRS from 'not present' to 'serious'.
Microbiome differences	3 years	After Illumina MiSeq sequencing, bio-informatic tools will be used to cluster bacteria into amplicon sequence variants (ASVs). Based on these ASVs, the investigators will compare the composition of the bacteria in the sampled niches and compare this composition between patient with and without intake of probiotics. The investigators will specifically screen for ASVs that are over- or underrepresented in both populations. Furthermore, special attention will go to screen for the typical nasopharyngeal pathogens such as Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis... and also to beneficial microbes such as lactic acid bacteria.
Therapeutic potential: nasal hyperreactivity	3 years	Nasal hyperreactivity symptoms will be evaluated before and after administration of the nasal spray.
Therapeutic potential: SNOT-22 score	3 years	The investigators will investigate whether the nasal intake of probiotics has an effect on the quality of life of CRS patients. Patients should rate general nasopharyngeal complaints from 0 to 5 where 0 means that there is no complaint and 5 means that there are serious complaints.

Trial Locations

Locations (1)

Antwerp University Hospital; 🇧🇪 Edegem, Antwerp, Belgium