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

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

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.

Study Overview

• Status: Unknown
• Conditions: Chronic Rhinosinusitis (Diagnosis); Probiotics; Healthy Volunteers; Nasal Disease; Sprays
• Intervention / Treatment: Other: Probiotic nasal spray; Other: Placebo nasal spray

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Antwerp
    • Edegem, Antwerp, Belgium, 2650
      • Antwerp University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy probiotic group LGG; Daily intake by healthy volunteers of 2 dosages of LGG spray during 2 weeks. Probiotic nasal spray.	Other: Probiotic nasal spray; Total daily nasal administration of 2*10^8 CFU of probiotic bacteria delivered via 2 servings.
Experimental: Healthy probiotic group LAMBR2; Daily intake by healthy volunteers of 2 dosages of LAMBR2 spray during 2 weeks. Probiotic nasal spray.	Other: Probiotic nasal spray; Total daily nasal administration of 2*10^8 CFU of probiotic bacteria delivered via 2 servings.
Placebo Comparator: Healthy placebo group; Daily intake by healthy volunteers of 2 dosages of placebo spray during 2 weeks. Placebo nasal spray.	Other: Placebo nasal spray; Two servings of nasal administration of placebo nasal spray (not containing probiotic bacteria)
Experimental: CRS probiotic group LGG; Daily intake by CRS patients of 2 dosages of LGG spray during 2 weeks. Probiotic nasal spray.	Other: Probiotic nasal spray; Total daily nasal administration of 2*10^8 CFU of probiotic bacteria delivered via 2 servings.
Experimental: CRS probiotic group LAMBR2; Daily intake by CRS patients of 2 dosages of LAMBR2 spray during 2 weeks. Probiotic nasal spray.	Other: Probiotic nasal spray; Total daily nasal administration of 2*10^8 CFU of probiotic bacteria delivered via 2 servings.
Placebo Comparator: CRS placebo group; Daily intake by CRS patients of 2 dosages of placebo spray during 2 weeks. Placebo nasal spray.	Other: Placebo nasal spray; Two servings of nasal administration of placebo nasal spray (not containing probiotic bacteria)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nasal persistence of lactobacilli	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.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiome differences	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.	3 years
Therapeutic potential: chronic rhinosinusitis	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'.	3 years
Therapeutic potential: nasal hyperreactivity	Nasal hyperreactivity symptoms will be evaluated before and after administration of the nasal spray.	3 years
Therapeutic potential: SNOT-22 score	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.	3 years

Collaborators and Investigators

• Sponsor: University Hospital, Antwerp
• Investigators: Principal Investigator: Sarah Lebeer, Universiteit Antwerpen

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Actual): October 10, 2018
• Study Completion (Anticipated): July 1, 2021

Study Registration Dates

• First Submitted: June 27, 2018
• First Submitted That Met QC Criteria: July 13, 2018
• First Posted (Actual): July 16, 2018

Study Record Updates

• Last Update Posted (Actual): April 8, 2020
• Last Update Submitted That Met QC Criteria: April 7, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Nose Diseases
• Other Study ID Numbers: B300201835709

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No