Clinical trial NCT06148194: Efficacy of Probiotics (LiveSpo Navax) in Preventing Respiratory Diseases in Children
Official title: Efficacy of Physiological Saline and Probiotics (LiveSpo Navax) in Preventing Respiratory Diseases in Children Aged 2-5, in Son Tay Province, Hanoi
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Respiratory Disease
Respiratory Infections in Children
Keywords: Acute respiratory infection
Prevention
Nasal-spraying probiotics
Bacillus spores
Children
Viruses
Bacterial co-infection
Lead sponsor: Anabio R&D
Sponsor class: INDUSTRY
Collaborators: name: Hanoi Medical University
First posted: 2023-11-28
Enrollment: 600
Sex: ALL
Minimum age (years): 2
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Blind, randomized, and controlled clinical trial
Primary purpose: PREVENTION

Brief summary: Acute respiratory infections are common diseases worldwide with the highest incidence and mortality rates, especially among children. Currently, the prevention of acute respiratory infections in children still faces certain limitations. Although there is a vaccine available for influenza, there are no vaccines yet for RSV and adenovirus in children, and influenza vaccination needs to be repeated annually to achieve optimal effectiveness. Therefore, maintaining respiratory and throat hygiene is essential for both treatment and prevention, ensuring respiratory health for children and reducing the risk of bacterial co-infections. In recent years, preventive strategies for respiratory inflammation have garnered increasing attention, with probiotics being shown to have the potential to support treatment and prevention \& reduce the risk of recurrent respiratory infections, thus decreasing reliance on antibiotics. Here, the investigators propose that direct nasal spraying of probiotics may be safe and effective in preventing respiratory diseases.

The aim of the study is to evaluate the effectiveness of two types of nasal- praying Bacillus probiotics including LiveSpo Navax (1 billion/mL x 30 mL B. subtilis and B. clausii) and LiveSpo Navax Kid (0.6 billion/mL x 30 mL B. subtilis and B. clausii) in preventing respiratory diseases. Study Population: The sample size is 600. Description of Sites: The study is conducted at preschools in Son Tay Province, Hanoi, Vietnam.

Description of Study Intervention: A total of 600 eligible children are randomly divided into three groups (n = 200/group each). Children in the Control group received 0.9% NaCl physiological saline twice daily (morning and afternoon), with 2 sprays in each nostril and 2 sprays in the throat each time (totally 6 sprays each time), continuously for four weeks. Children in the Probiotic 1 group receive LiveSpo Navax product, and children in the Probiotic 2 group receive LiveSpo Navax Kid, with the same dosage and frequency as the Control group.

Study Duration: 12 months.

Detailed description: Acute respiratory infections are common diseases worldwide with the highest incidence and mortality rates, especially among children. Vietnam is one of the 15 countries with the highest pneumonia rates in the world, with an estimated 2.9 million cases occurring annually. The age group most susceptible to acute respiratory infections is children under 5 years old, especially bronchiolitis, which often occurs in children under 2 years old. The incidence of acute respiratory infections varies with the seasons, with the highest prevalence of viral respiratory infections typically occurring during the winter and spring. In tropical regions, acute respiratory infections are more common during the rainy months, while in temperate regions, they are more prevalent during the winter months. Approximately 30-60% of outpatient visits for medical care are due to acute respiratory infections.

Currently, the prevention of acute respiratory infections in children still faces certain limitations. Although there is a vaccine available for influenza, there are no vaccines yet for RSV and adenovirus in children, and influenza vaccination needs to be repeated annually to achieve optimal effectiveness. Therefore, maintaining respiratory and throat hygiene is essential for both treatment and prevention, ensuring respiratory health for children and reducing the risk of bacterial co-infections. Here, the investigators propose that direct nasal spraying of probiotics may be a safe and effective method for preventing respiratory diseases.

The objective of this study is to investigate the safety and preventive effects of two types of nasal-spraying Bacillus probiotics: LiveSpo Navax (1 billion/mL x 30 mL B. subtilis and B. clausii) and LiveSpo Navax Kid (containing 0.6 billion/mL x 30 mL B. subtilis and B. clausii) in preventing respiratory diseases in healthy children attending preschools. The investigators will evaluate the preventive efficacy in terms of reducing the number of respiratory disease episodes and the number of courses of antibiotics in children after 2 weeks and 4 weeks of using LiveSpo Navax and LiveSpo Navax Kid.

A randomized, double-blind, and controlled clinical trial will be conducted. Parents of the will be required to provide various information about their children, including their full names, sex, ages, respiratory infection history, and history of antibiotic use... After obtaining informed consent, 600 children will be randomly assigned to three groups (n = 200/group): the control group (referred to as the "Control" group) will receive 0.9% NaCl physiological saline, the experimental group 1 (referred to as the "Probiotic 1" group) will receive the probiotic LiveSpo Navax product, and the experimental group 2 (referred to as the "Probiotic 2" group) will receive the probiotic LiveSpo Navax Kid. Children will be provided with coded nasal sprays in blinded samples to ensure the objectivity of the study. Clinical examinations and monitoring will be conducted after 2 weeks and 4 weeks of the experiment. Nasopharyngeal samples will be collected at the same time as the clinical examinations to assess the presence of probiotic spores in the children's nasal mucosa. During the trial, children's typical clinical symptoms of respiratory tract infections are monitored, including runny nose, stuffy nose, sneezing, sore throat, cough, and fatigue. Data is collected on the number of cold or illness episodes, the average duration of each illness episode, the number of days absent from school, and medication history after 2 weeks and 4 weeks of participating in the study. The children's health conditions are observed by caregivers, and the information is recorded in medical records. During this study, parents or caregivers are asked to refrain from giving their children other probiotics, whether via nasal spray or oral administration, and to avoid cleaning their children's noses with other 0.9% NaCl physiological saline sprayers. Data collection and statistical analysis will involve collecting individual medical records and systematically organizing the children's information into a dataset.

The prevention efficacy of LiveSpo Navax product (Probiotic 1 group) and LiveSpo Navax Kid (Probiotic 2 group) is evaluated and compared to 0.9% NaCl physiological saline (Control group) based on the following clinical and survey criteria: (i) reduction in the percentage (%) of children with respiratory infections; (ii) reduction in the number of colds, illnesses, or respiratory tract infections in children; (iii) reduction in the duration of medication usage and the number of medication episodes in the treatment of respiratory diseases. Tabular analysis is performed on dichotomous variables using the χ2 test or Fisher's exact test when the expected value of any cell is below five. Continuous variables are compared using either the t-test or the Mann-Whitney test when the data is not normally distributed. Statistical and graphical analyses are conducted using GraphPad Prism v8.4.3 software (GraphPad Software, CA, USA). The significance level for all analyses is set at p \< 0.05.

Detection of B. subtilis ANA4 and B. clausii ANA39 in nasopharyngeal samples was conducted at 2 weeks and 4 weeks using real-time PCR with SYBR Green following the ISO 17025:2017 guidelines. This testing was performed at the Spobiotic Research Center.

Eligibility criteria: Inclusion Criteria:

* Children (male/female) aged from 2 to 5 years, currently attending a preschool.
* Parents of the pediatric agree to participate in the study, explain, and sign the research consent form.

Exclusion Criteria:

* Children with a history of nasal reconstructive surgery, nasal ulcers, or nasal polyps.
* Children with a history of congenital immunodeficiency or infectious diseases (e.g., HIV).
* Children who regularly use products that may affect the research outcomes (e.g., immunosuppressive/immunostimulant drugs, pain relievers/anti-inflammatory drugs, anti-cough/expectorant drugs, antihistamines, or other probiotics) within 4 weeks before the start of the study.
* Children with co-morbidities that affect cognition and perception.

Primary outcomes:
measure: Percentage of children with respiratory infections
timeFrame: Days 0, 14, and 28
measure: Incidence of medication intakes (%)
timeFrame: Weeks 1-2 and 3-4
Secondary outcomes:
measure: The number of episodes of children with cold/illness/respiratory tract infections.
timeFrame: 2 weeks and 4 weeks
measure: Duration of illness
timeFrame: 2 weeks and 4 weeks
measure: Duration of school absence
timeFrame: 2 weeks and 4 weeks
measure: Duration of respiratory tract disease treatment
timeFrame: 2 weeks and 4 weeks
measure: Duration of treatment for respiratory tract diseases with each type of medication
timeFrame: 2 weeks and 4 weeks
measure: Percentage (%) of children infected with viral and bacterial infections
timeFrame: Days 0, 14, and 28
Other outcomes:
measure: Changes in the nasal microbiome in children at day 28 compared to day 0.
timeFrame: Days 0 and 28
measure: Changes in pro/anti-inflammatory cytokine levels in nasopharyngeal samples at days 0, 14, and 28
timeFrame: Day 0, 14, and 28
Locations:
city: Hanoi
country: Vietnam
facility: Son Tay Province, Hanoi
Study officials:
affiliation: Hanoi Medical University
name: Thu TH Nguyen, Assoc. Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Spobio Research Center, Anabio R&D
name: Anh TV Nguyen, Assoc. Prof.
role: PRINCIPAL_INVESTIGATOR
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