Evaluation of Probiotic (L.Reuteri) Survival in Presence of Prebiotic Galacto-oligosaccharides

Study Overview
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Brief Summary
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This research study will compare the effect of test product #1 (containing a probiotic with the Galacto-OligoSaccharides fiber. GOS) and test product #2 (containing a probiotic without the GOS fiber) to understand how they can contribute to healthy digestion in toddlers between the age of 24 - 36 months. The hypothesis is that L. reuteri from TEST#1 will demonstrate an improved survival in the GIT of toddlers compared to that of TEST#2. This study is a single-centre, randomized, double-blind, comparator-controlled, parallel group study. The study will be conducted at the Clinical Innovation Lab (CIL) at Nestlé Research.

Official Title
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Evaluation of Probiotic (L.Reuteri) Survival in Presence of Prebiotic Galacto-oligosaccharides

Conditions
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Healthy

Intervention / Treatment
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* Other: TEST1
* Other: TEST 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Child is between 24 months to 36 months of age. Singleton, full-term gestational birth (≥ 37 completed weeks of gestation), with a birth weight of ≥ 2.5 kg and ≤ 4.5 kg. Healthy status based on medical history and physical examination Weight- for-age and height-for-age within normal range on local childhood growth chart. Written informed consent are obtained from both parents/legally authorized representative (LAR). Parents/legally authorized representative must be able to provide evidence of the parental authority and identity. Parents /legally authorized representative are of legal age of consent and must understand the informed consent and other study documents. Parents/legally authorized representative are willing and able to fulfill the requirements of the study protocol. Exclusion Criteria: Known or suspected cows' milk protein intolerance / allergy, or lactose intolerance, or significant food allergies that impact a normal diet. Prior to study participation, child has shown limited or no interest in drinking toddler milk. Chronic infectious, gastrointestinal, metabolic, or genetic disease, including any disease/condition that impacts feeding or growth. Use of systemic antibiotics or anti-mycotic medication in the 4 weeks preceding enrollment. Child is currently consuming or has consumed any formulas or taking any supplement containing L. reuteri in the past 3 months. Child is currently consuming or has consumed any formulas or taking any supplement containing GOS within the past 48 hrs prior to product in take, and who are not willing accept a temporary cessation of the consumption during the study period. Child is currently participating in another investigational clinical trial. Family or hierarchical relationships with the CIL team.

Ages Eligible for Study
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Minimum Age: 24 Months
Maximum Age: 36 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
Interventional Model Description: comparator-controlled
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TEST1<br> | Other: TEST1<br>* Toddler milk with preconditioned L. reuteri and containing GOS<br>|
| Experimental: TEST2<br> | Other: TEST 2<br>* Toddler milk with standard/non-preconditioned L. reuteri and not containing GOS.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Colony forming units of feces (CFU/g) | The primary end point is quantification of L. reuteri DSM 17938 in stool using quantitative polymerase chain reaction (qPCR). | Baseline (visit Day 0), Day 2, Day 3, Day4, Day 5, Day6 Day 7 and D21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut microbiota | Diversity and functionality will be evaluated on at least 8 stools samples using shotgun metagenomic sequencing. Structure and prevalence of microbiota and evaluation of taxa and function in the survival of the probiotic. | Between Day 0 and Day 21 | 
| Gastrointestinal (GI) tolerance and stooling patterns | Parent perceptions of GI symptoms and GI-related behaviors using Toddler Gut Comfort Questionnaire (GCQ) and stool frequency and consistency | Between Day 0 and Day 21 | 
| Assessment of dietary variety | Dietary variety assessed using a parent-reported Food Frequency Questionnaire (FFQ) | Between Day 0 and Day 21 | 
| Safety and tolerability | - Adverse events type, incidence, severity, and relationship to TEST1 and TEST2 products. | Between Day 0 and Day 21 |