Effects of Probiotic Against Respiratory & Gastrointestinal Illnesses in Children

Study Overview
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Brief Summary
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This project aims to study the benefits of probiotics namely Bifidobacterium lactis subsp. infantis B8762 in treatment of respiratory and gastrointestinal illnesses in children, which are found common among pre-school children in Malaysia aged below 7-years old.

Detailed Description
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Respiratory and gastrointestinal illnesses are the most common acute diseases in children where no virtually effective treatments or prophylaxes are available for these infections. Probiotics on the other hand have gained increasing evidences as an effective therapy in preventing respiratory and gastrointestinal illnesses. While the precise mechanisms of using probiotics are largely unknown, speculations include: probiotics compete against pathogens; increase the barrier function in respiratory epithelium; immuno-stimulatory effects by enhancing cellular immunity with increased activity of natural killer cells and macrophages in airways and gut. Hence, probiotics may offer safe means of reducing the risk of respiratory and gastrointestinal illnesses, antibiotic use, and the risk of recurrent infections, thereby represent a simple, safe, effective, available and affordable method for preventing respiratory and gastrointestinal infections in children. Among the various types of probiotics, Bifidobacterium is one of the best-known probiotic genus in the world, and it is widely applied in the dairy industry as a probiotic. Evidences from more than 100 scientific publications based on in vitro, in vivo, and clinical studies and long consumption history support the safety and health benefits of Bifidobacterium strains. The ingestion of yogurt fortified with B. longum reduced harmful bacteria such as Enterobacteriaceae, Streptococcus and C. perfringens, while at the same time alter the microbiota gut profile of volunteers with a significant increase of beneficial microbes Bifidobacterium and Lactobacillus species. Additionally, putrefactive substances in the intestinal environment were also reduced in the presence of the probiotic supplement. Such findings suggest that Bifidobacterium strains are safe and could be used further to evaluate its effect in preventing diarrhea and/or respiratory-related illness prevalence in young children. Probiotic (Bifidobacterium lactis subsp. infantis B8762) adheres to probiotic properties such as excellent tolerance to gastric acid, intestinal fluid and bile salt of the digestive system. Both probiotic and placebo products are manufactured under an ISO9001, ISO22000 and HACCP conditions. All products do not contain any animal-origin ingredients. The probiotic product contains probiotic and carrier while placebo contains only carrier. Sachets of products containing probiotic and placebo appear as light yellow powder. Both probiotic and placebo products are kept at storage temperature range below 30oC according to the condition recommended by the manufacturer. A total number of 120 pre-school children with respiratory diseases aged below 7-years old will be recruited for this study.

Official Title
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Effects of Probiotic Against Respiratory & Gastrointestinal Illnesses in Children

Conditions
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Respiratory Tract Infections

Intervention / Treatment
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* Dietary Supplement: Probiotic
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: preschool children (<7 years old), and having respiratory and/or gastrointestinal diseases symptoms. Willing to commit throughout the experiment Exclusion Criteria: Long term medication due to certain severe illness (6 months or more) Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 84 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic<br>Intervention consists of daily administration of excipient plus Bifidobacterium lactis subsp. infantis B8762 at 0.5x10 log colony forming unit (CFU)/day administered daily for 4-weeks | Dietary Supplement: Probiotic<br>* Oral administration of Bifidobacterium lactis subsp. infantis B8762 at 0.5x10 log colony forming unit (CFU)/day for 4-weeks<br>* Other names: Bifidobacterium lactis subsp. infantis B8762;|
| Placebo Comparator: Placebo<br>Intervention consists of daily administration of 2g/sachet of excipient administered daily for 4-weeks | Dietary Supplement: Placebo<br>* Intervention consists of daily administration of 2g/sachet of excipient administered daily for 4-weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of respiratory illnesses in children with respiratory tract infections upon administration of probiotic for 4-weeks | Changes in duration of respiratory illnesses in children compared between probiotic and placebo after 4-weeks | 4-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical respiratory symptoms frequency in children with respiratory tract infections upon administration of probiotic as assessed using the Monthly Health Questionnaire (as used in ClinicalTrials.gov (identifier number NCT02434042). | Changes in frequency of respiratory illnesses symptoms from children on probiotic or placebo after 4-weeks, via the use of questionnaire. | 4-weeks | 
| Clinical gastrointestinal symptoms in children with respiratory tract infections upon administration of probiotic as assessed using the Monthly Gastrointestinal Questionnaire as used in ClinicalTrials.gov (identifier number NCT02434042). | Differences in duration and frequency of gastrointestinal symptoms of children upon administration of probiotic compared to placebo | 4-weeks | 
| Microbiota profiles of saliva and fecal samples in children with respiratory tract infections upon administration of probiotic as assessed via pyrosequencing | Differences in microbiota abundance of saliva and fecal sample in children with respiratory tract infections upon administration o probiotic compared to placebo | 4-weeks | 
| Concentrations of proteins in saliva samples in children with respiratory tract infections upon administration of probiotic as assessed via biochemical tests | Differences in concentrations of proteins such as interleukins (IL-10, IL-4, IL-6, Tumour Necrosis Factor-alpha, Interferon gamma) in saliva (ug/mL) samples in children with with respiratory tract infections upon administration of probiotic compared to placebo | 4-weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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probiotic, respiratory tract infections, Bifidobacterium, children