Effect of Probiotics on the Digestibility and Immunity in Infants

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of the probiotic product on the GI tract flora composition.

Official Title
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Effect of Probiotics on the Digestibility and Immunity in Infants

Conditions
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Gastrointestinal Tract Flora Composition

Intervention / Treatment
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* Drug: Biostime probiotics sachet children's formula
* Drug: Biostime probiotics sachet children's formula（placebo）


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy infants; Single birth; Gestational age ≥ 37 weeks (=non-preterm infant, WHO); Birth weight: > 2500g Appropriate weight between P20-P80 in accordance with the weight percentile standards of the children ages 0 to 6 years in Shanghai urban areas at inclusion visit ; Aged > 4 months and < 6 months; Infants being exclusively formula-fed(no breast milk meal) at inclusion visit; No suffering of gastrointestinal diseases within 1 month (CCDC recommendations); Parents agreeing to use one of the recommended infant formulas (no probiotic, if with prebiotics, exclude it when there is GOS over 2g/100g or FOS inside); Consent form signed by at least one of the parents or by the legal tutor properly informed of the study; Parents able to understand the protocol requirements and to fill out the infants' diary. Exclusion Criteria: Congenital illness or malformation; Significant pre-natal and/or post-natal disease; Mothers with metabolic or chronic diseases; Infants with allergic constitution and sensitive to the probiotics (CCDC recommendations); Infants with serious diseases, such as cardiovascular, cerebrovascular, liver, kidney and hematopoietic system diseases and internal secretion diseases, and those with mental disorder (CCDC recommendations); Infants administering other drugs during the administering of the study products, thus impossible to judge the efficacy or influencing the judgment of results (CCDC recommendations); Infants known to have current or previous illnesses/conditions or intervention which could interfere with the study (impacting tolerance and/or growth), such as gastrointestinal malformations, chronic diarrhoea, malabsorptive syndrome, malnutrition, congenital immunodeficiency, or major surgery, as per investigator's clinical judgment; Infant under oral antibiotic treatment at V1 visit and within the 4 weeks before V1 Infants who used any medication or nutritional supplements (including probiotics, prebiotics etc, except for infant formula) in the 4 weeks preceding study start; Infants who have ever consumed the test product; Infants who have medical conditions for which a special diet other than standard (non hydrolyzed) cow's milk-based infant formula is required (such as cow's milk allergy, soy protein allergy, fish protein allergy, egg protein allergy, lactose intolerance, galactosemia); Currently participating or having participated in another clinical trial during the last month. Infants whose legal representatives have psychological or linguistic incapability to sign the informed consent form Reasons to presume that parents are unable to meet the study plan requirements (e.g. impossibility to contact study representatives in case of emergency, drug addiction etc.)

Ages Eligible for Study
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Minimum Age: 4 Months
Maximum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Probiotics<br>Biostime probiotics sachet children's formula, 1.5g/d/sachet, administrated during the consumption of the first feeding-bottle of the day. Duration: 4 weeks | Drug: Biostime probiotics sachet children's formula<br>* Biostime probiotics sachet children's formula,1.5g Oral Single dose<br>|
| Placebo Comparator: Probiotics simulation<br>Biostime probiotics sachet children's formula（placebo）, 1.5g/d/sachet, administrated during the consumption of the first feeding-bottle of the day. Duration: 4 weeks | Drug: Biostime probiotics sachet children's formula（placebo）<br>* Biostime probiotics sachet children's formula（placebo）,1.5g Oral Single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Achieving the modulatory effect on the GI tract flora composition after the intervention. | GI tract flora include Bifidobacterium, Lactobacillus, Clostridium perfringens, Enterococcus, Enterobacter, Bacteroides. Modulatory effect of GI tract flora composition was defined as two definitions. The first definition is that Lactobacillus and/or Bifidobacterium increases significantly, Clostridium perfringens decreases or has no change and Enterococcus, Enterobacter, Bacteroides has no obvious change. The other is that Lactobacillus and/or Bifidobacterium increases significantly, Clostridium perfringens decreases or has no change, Enterobacter and/or Enterococcus, Bacteroides increases significantly, but the amplification less than Lactobacillus/Bifidobacterium. | From Baseline to week 4 | 
| Change of Lactobacillus helveticuspopulations in stool |  | From Baseline to week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| average daily number of stools |  | From Baseline to week 4 | 
| Aaverage daily Infant Stool Form scores consistency |  | From Baseline to week 4 | 
| Average weekly Infant Stool Form scores amount |  | From Baseline to week 4 | 
| Average weekly Infant Stool Form scores color |  | From Baseline to week 4 | 
| Average daily number of crying episodes |  | From Baseline to week 4 | 
| Average daily duration of crying episodes |  | From Baseline to week 4 | 
| sIgA antibody levels in stool |  | From Baseline to week 4 | 
| sIgA antibody levels in saliva |  | From Baseline to week 4 | 
| change in infant weight |  | From Baseline to week 4 | 
| change in infant length |  | From Baseline to week 4 | 
| change in infant head circumference |  | From Baseline to week 4 | 
| The number of AE and SAE |  | From Baseline to week 4 |