Evaluation of Toddler Milk Containing L.Reuteri, Galacto-oligosaccharides and Palm-Oil Free Fat Blend

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effects of experimental growing up milk (EXPL) as compared to traditional children's fortified milk (CTRL) fed for 6 months on bone mass index.

Detailed Description
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A randomized, double-blind controlled clinical trial was chosen to study the effects of toddler milk containing L. reuteri and GOS (4g/L) and a low sn-1, -3 fat blend when compared to a control formula. There is an additional unblinded habitual intake reference group (REF) for real-world comparison (including 58% non-dairy drinkers according to observational data).

Official Title
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Evaluation of Toddler Milk Containing L.Reuteri, Galacto-oligosaccharides and Palm-Oil Free Fat Blend On Bone Metabolism Among Healthy Toddlers

Conditions
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Toddlers Bone Metabolism

Intervention / Treatment
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* Other: Traditional cow's milk
* Other: Experimental milk
* Other: Habitual diet


Participation Criteria
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Eligibility Criteria
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All subjects must comply with all the following criteria: Written informed consent has been obtained from the parent(s)/legally acceptable representative (LAR). Singleton, full-term gestational birth (≥ 37 completed weeks of gestation), with a birth weight of ≥ 2.5 kg and ≤ 4.5 kg. Child is between 24 months ±1 week to 36 months ±1 week. Child is not currently consuming nor has consumed any formulas or taking any supplements with pre- or probiotics at enrolment or in the past month. Child's parent(s)/guardian is of legal age of consent, must understand the informed consent and other study documents, and is willing and able to fulfill the requirements of the study protocol. All subjects presenting one or more of the following criteria are excluded from participation in the study: Chronic infectious, metabolic, genetic illness or other disease including any condition that impacts feeding or growth. History of bone, malabsorption, metabolic, congenital or chromosomal abnormality known to affect feeding or growth. Use of systemic antibiotics or anti-mycotic medication in the 4 weeks preceding enrollment. Known or suspected cows' milk protein intolerance / allergy, or lactose intolerance, or severe food allergies that impact diet. Current breast milk feeding in place of all other milk, and/or milk alternatives. Clinical signs of severe micronutrient deficiencies. Parents not willing / not able to comply with the requirements of study protocol. Child's participation in another interventional clinical trial.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 3 Years

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Traditional children's fortified cow's milk<br> | Other: Traditional cow's milk<br>* Fortified cow's milk<br>|
| Experimental: New toddler milk with synbiotics and fat blend<br> | Other: Experimental milk<br>* Milk with synbiotics and fat blend<br>|
| Other: Toddlers consuming habitual diet<br> | Other: Habitual diet<br>* Habitual diet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Speed of sound (SOS) | Speed of sound (SOS) using a quantitative ultrasound methods measured by Pediatric Sunlight 9000 device | Day 1, Day 90, Day 180 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GI tolerance and stooling patterns | Stool patterns including stool frequency will be recorded retrospectively via 24-hour GI Symptom and Behavior Recall | Day 1 | 
| GI tolerance and stooling patterns | Stool patterns including stool consistency will be recorded retrospectively via 24-hour GI Symptom and Behavior Recall | Day 1 | 
| GI tolerance and stooling patterns | Stool patterns including stool frequency will be recorded using 3-day GI Symptom and Behavior diary | Day 90, Day 180 | 
| GI tolerance and stooling patterns | Stool patterns including stool consistency will be recorded using 3-day GI Symptom and Behavior diary | Day 90, Day 180 | 
| GI tolerance and stooling patterns | Parent perceptions of GI symptoms using parent-reported questionnaire Toddler Gut Comfort Questionnaire (GCQ) using VAS from 1-Never to 6-Always with higher scores indicating increasing GI burden. | Day 1, Day 90, Day 180 | 
| GI tolerance and stooling patterns | Parent perceptions of GI-related behaviors using parent-reported questionnaire Toddler Gut Comfort Questionnaire (GCQ) using VAS from 1-Never to 6-Always with higher scores indicating increasing GI burden. | Day 1, Day 90, Day 180 | 
| Stool analyses | Excretion of fecal calcium fatty acid soaps | Day 1, Day 180 | 
| Stool analyses | Measurement of stool calcium content | Day 1, Day 180 | 
| Serum vitamin D | Measured by serum 25[OH]D concentration requiring 1mL of whole blood sample. | Day 1, Day 180 | 
| Urine and Blood bone turnover markers | Bone accretion markers in urinary [C-terminal cross-linked telopeptides of type I collagen (CTX) | Day 1, Day 180 (EXPL and CTRL groups only) | 
| Urine and Blood bone turnover markers | serum procollagen type I N-terminal propeptide (PINP) | Day 1, Day 180 (EXPL and CTRL groups only | 
| Gut microbiota | Gut microbiota analyzed for microbiome composition and diversity using next generation shotgun metagenomics sequencing, requiring 3g of stool sample. | Day 1, Day 180 | 
| Stool analyses | Determination of fecal short chain fatty acids (SCFAs) | Day 1, Day 180 | 
| Stool analyses | Fecal pH and metabolism. | Day 1, Day 180 | 
| Stool analyses | Fecal markers of gut health | Day 1, Day 180 | 
| Physical strength | Hand grip test (Jamar hand dynamometer) tailored for toddlers will be used as previously described Bohannon et al Pediatric Physical Therapy 2017. | Day 1, Day 180 | 
| Vitamin B | serum vitamin B concentration requiring 2 mL of whole blood sample. | Day 1, Day 180 | 
| Dietary intake patterns | Intake patterns are assessed using parent-reported questionnaire Child Eating Behavior Questionnaire including variety of food groups consumed as well as behaviors rated from Never to Always. | Day 1, Day 180 | 
| Child quality of life using validated ITQOL SF-47 questionnaire | assessed using the parent-reported questionnaires | Day 1, Day 180 | 
| Outdoor Playtime | Assessed using parent-reported questionnaire on Outdoor Playtime recording number of hours child spent outside. | Day 1 and Day 180 | 
| Child temperament | Children's Behavior Questionnaire (very short form), consisting of 36 questions and 3 scales on child temperament domains Surgency, Negative Affect and Effort Control with each question ranging 1-extremely untrue to 7- extremely true of parent observing various behaviors. | Day 1, Day 180 |