Toddler Milk Intervention Trial

Study Overview
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Brief Summary
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To assess growth of children (enrolled between 11.5 and 13.5 months) fed with two iso-energetic, young-child formulas with different protein content during the second year of life

Detailed Description
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This study is designed to investigate in a randomized double-blind parallel-group trial the growth and metabolic effects of different contributions of protein to total energy intakes in healthy children during the second year of life

Official Title
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Effects of Milk Protein Intake in Young Children on Early Growth and Later Obesity Risk: a Multicentre Randomized Clinical Trial

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: Young-child formula with low protein content
* Dietary Supplement: Young-child formula with protein content similar to that of cow's milk


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Having obtained his/her parents' (or his/her legally accepted representative [LAR's] written informed consent and having evidence of personally signed and dated informed consent document indicating that the child's parents/LAR have been informed of all pertinent aspects of the study Child was born full term (≥ 37 weeks of gestation) Age at enrollment: between 11.5 months and 13.5 months of age 2.5 kg ≤ birth weight ≤ 4.5 kg Born from a singleton pregnancy Child's parent(s)/LAR is of legal age of consent, has sufficient local language skills to complete the informed consent and other study documents, is able to be contacted directly by telephone throughout the study, and is willing and able to fulfill the requirements of the study protocol. Exclusion Criteria: Diagnosed disorder considered to interfere with nutrition or growth (e.g. malabsorptive disorders as short bowel syndrome, inflammatory bowel disease; neurological and congenital disorders that may delay growth as cerebral palsy, agenesis of the corpus callosum, spina bifida, Down Syndrome, Cri Du Chat; disorders that may lead to obesity: Prader willi syndrome, Angelman syndrome, etc.) Cows' milk allergy Lactose intolerance Participation in any other interventional clinical trial during the 4 weeks prior to enrollment Infant who is being breastfed at the time of enrollment Infant who does not usually drink 300ml of cow's and/or formula milk per day Institutionalized children Child or child's family who in the Investigator's judgment cannot be expected to comply with the protocol or study procedures

Ages Eligible for Study
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Minimum Age: 11 Months
Maximum Age: 13 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental formula<br>Young-child formula with low protein content | Dietary Supplement: Young-child formula with low protein content<br>* Young-child formula with low protein content<br>|
| Active Comparator: Control formula<br>Young-child formula with protein content similar to that of cow's milk | Dietary Supplement: Young-child formula with protein content similar to that of cow's milk<br>* Young-child formula with protein content similar to that of cow's milk<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMI-for-age z-score | WHO-growth standard | Age 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMI-for-age z-score |  | Age 72 months | 
| The percentage of overweight and obese children | CDC definition: Overweight above 85th to less than the 95th percentile and obese 95th percentile or greater and analyzed by the method of Peacock (Dichotomising continuous data while retaining statistical power using a distributional approach, Statistics in medicine, 2012). | Age 24 months | 
| The percentage of overweight and obese children |  | Age 72 months | 
| Growth parameters: Anthropometry: Weight, Length, Heel knee length, Mid-arm circumference, Waist circumference, Hip circumference (only 48 months and 72 months), Head circumference, Triceps skinfold, Subscapular skinfold |  | Age 12, 18, 24, 48 and 72 months | 
| Child's development: Parental rating of child development with Ages & Stages Questionnaires® |  | Age 24 and 48 months | 
| Body composition: air displacement plethysmography |  | at 24, 48 and 72 months of age | 
| Metabolic and endocrine markers: Blood and Urine markers | Blood: Complete blood count, Glucose, Creatinine, Ferritin (measured only at 24 months), 25-OH vitamin D (measured only at 24 months), Triglycerides, Total cholesterol, HDL- and LDL-cholesterol, Insulin, IGF-1, IGF-BP2, IGF-BP3, Leptin, Adiponectin, Ghrelin, Amino Acids, Serum albumin, Urea, C-reactive protein, Osteocalcin / Urine: Calcium, C-peptide, Creatinine, Urea nitrogen | Age 12, 24 and 72 months | 
| Metabolomic profile: Plasma and urine metabolic indicators of energy and protein metabolism (metabolomics with a focus on carnitines, amino acid catabolism, ketone bodies, Krebs cycle, and bacterial utilization of protein and carbohydrates) |  | Age 12, 18, 24, 48 and 72 months | 
| DNA methylation pattern: Methylation status of specific DNA regions (e.g. CpG sites) |  | Age 12, 24 and 72 months | 
| Blood pressure |  | Age 48 and 72 months | 
| Dietary intake: 24-hour recall |  | Age 12, 18, 24, 48 and 72 months |