Growth and Metabolic Biomarkers of Healthy Term Infants Fed Formulas With Staged Protein Concentrations Over the First Year of Life

Study Overview
=================
Brief Summary
-----------------
Growth and metabolic biomarkers of healthy term infants fed formulas with staged protein concentrations over the first year of life

Detailed Description
-----------------
The overall objective of this study is to assess growth and biomarkers of energy and protein metabolism in healthy term infants fed with two different study formula regimens from birth to 12 months of age and to follow up the infants to 4 years of age.

Official Title
-----------------
Growth and Metabolic Biomarkers of Healthy Term Infants Fed Formulas With Staged Protein Concentrations Over the First Year of Life

Conditions
-----------------
Healthy Term Infants

Intervention / Treatment
-----------------
* Dietary Supplement: Formula regimen 1
* Dietary Supplement: Formula regimen 2


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy infants will be enrolled in the study provided they meet the following inclusion criteria: Having obtained his/her parents' (or his/her legally accepted representative's [LAR's]) written informed consent and having evidence of personally signed and dated informed consent document indicating that the infant's parents/LAR have been informed of all pertinent aspects of the study. Age ≤ 7 days after birth (date of birth = Day 0) Full-term gestational birth (≥ 37 and ≤ 42 weeks) Born to mothers with pre-pregnancy body mass index (BMI) ≥ 18.5 and < 26 kg/m2 Born to mothers who independently elected, before study enrollment, not to breastfeed (not applicable for infants in the HM-fed comparator group) Weight ≥ 2'500 g and ≤ 4'200 g Infant's parent(s)/LAR is of legal age of consent, has sufficient command of French language to complete the informed consent and other study documents, and is willing and able to fulfill the requirements of the study protocol Infant's parent(s)/LAR is able to be contacted directly by telephone throughout the study Exclusion Criteria: Infants who exhibit one or more of the following criteria are excluded from enrollment in the study: Born to mothers with hormonal or metabolic disease (e.g. Type-1, Type-2, or gestational diabetes diagnosed according to standardized criteria) Born to mothers who smoked > 10 cigarettes per day during pregnancy Born to mothers who used illicit drugs (e.g. marijuana, cocaine, amphetamines, or heroin) or alcohol (> 3 alcoholic beverages per week) during pregnancy Cognitive or physical developmental disorders (e.g. malabsorptive disorders such as short bowel syndrome; neurological and congenital disorders that may delay growth such as cerebral palsy, agenesis of the corpus callosum, spina bifida, Down Syndrome, Cri Du Chat; disorders that may lead to obesity such as Prader willi syndrome, Angelman syndrome; other renal, hepatic, pancreatic, or cardiovascular disorders) Received radiation therapy (eg. scannography or interventional radiology) Participation in any other clinical trial prior to enrollment Infants or infant's family who in the Investigator's judgment cannot be expected to comply with the protocol or study procedures

Ages Eligible for Study
-----------------
Minimum Age: 0 Days
Maximum Age: 7 Days

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Formula regimen 1<br>Product Control from enrollment to transition phase 1 (blinded administration), followed by open label administration for 2 months. Product Test 2 from transition phase 2 to 1 year old (open label) Commercial follow up formula from 1 year old | Dietary Supplement: Formula regimen 1<br> <br> |
| Active Comparator: Formula regimen 2<br>Product Test 1 from enrollment to transition phase 1 (blinded administration) Product Control for 2 months(open label) Product Test 2 from transition phase 2 to 1 year old (open label) Commercial follow up formula from 1 year old | Dietary Supplement: Formula regimen 2<br> <br> |
| No Intervention: Reference group<br>Infants fed HM exclusively through at least 4 months of age. Once breastfeeding is over and if wished Infant will receive Product test 2 until 1 year old followed by the commercial follow-up formula | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth velocity of formula regimen 1 and 2 versus WHO growth curve | Compare weight gain velocity (g/day) of each formula-fed group from enrollment to 6 months of age and compare to the World Health Organization (WHO) standards | 0-6 months | 
| Growth velocity (g/day) of formula regimen 1 and 2 versus a human milk (HM)-fed comparator group | Assess the growth velocity of each formula-fed group from enrollment to 6 months of age and compare to growth velocity of a human milk (HM)-fed comparator group. | 0-6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth velocity of formula regimen 1 and 2 versus WHO growth curve and versus a human milk (HM)-fed comparator group | Assess the growth velocity of each formula-fed group from enrollment to 3 months, and from enrollment to 12 months, and compare to both WHO standards and to the HM-fed comparator group. | 0-3 months and 0-12 months | 
| Other growth parameters z-scores of formula regimen 1 and 2 versus WHO standards and versus a human milk (HM)-fed comparator group | Weight-for-length, weight-for-age, length-for-age, head circumference-for-age, and BMI-for-age z-scores | 6 and 12 months | 
| Compare metabolic biomarkers measures in each formula-fed group to the HM-fed group | Assess and compare metabolic biomarkers in each formula-fed group to the HM-fed group. Here is the list of metabolic biomarkers that will be measured: free and total IGF-1, IGF-binding protein 2, IGF-binding protein 3, C-peptide, insulin, glucose, leptin, adiponectin, ghrelin in all subjects and complete amino acid profile in subset | 0-4 years | 
| Assess the adverse events (AEs) among all study subjects | Assess the type, incidence, severity, seriousness, and relationship to study formulas of AEs among study subjects. | 0-4 years | 
| Assess and compare the child behavior in each group until 4 years of age | Neurodevelopment will be assessed by parental ratings of child development using validated measures Ages and Stages Questionnaire (ASQ) | 0-4 years | 
| Assess and compare the neurodevelopment in each group until 4 years of age | Neurodevelopment will be assessed by tests of child development using validated Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV) | 0-4 years | 
| Body Composition: Body density [kg/L] using PeaPod | Body density in kg/L will be assessed using PeaPod | 1-6 months | 
| Body Composition: Body mass [kg] using PeaPod | Body mass in kg will be assessed using PeaPod | 1-6 months | 
| Body Composition: Body surface area [cm²] using PeaPod | Body surface area in cm² will be assessed using PeaPod | 1-6 months | 
| Body Composition: Body volume [L] using PeaPod | Body volume in L will be assessed using PeaPod | 1-6 months | 
| Body Composition: Fat free mass [kg] using PeaPod | Fat free mass in kg will be assessed using PeaPod | 1-6 months | 
| Body Composition: Fat free mass density [kg/L] using PeaPod | Fat free mass density in kg/L will be assessed using PeaPod | 1-6 months | 
| Body Composition: Fat mass [kg] using PeaPod | Fat mass in kg will be assessed using PeaPod | 1-6 months | 
| Body Composition: Percentage fat free mass using PeaPod | Percentage fat free mass will be assessed using PeaPod | 1-6 months | 
| Body Composition: Percentage fat mass using PeaPod | Percentage fat mass will be assessed using PeaPod | 1-6 months | 
| Body Composition: Thoracic gas volume (L) using PeaPod | Thoracic gas volume in L will be assessed using PeaPod | 1-6 months | 
| Body Composition: Bone area [cm²] using DEXA | Bone area in cm² will be assessed using DEXA | 0-3 years | 
| Body Composition: Bone Mineral Content [g] using DEXA | Bone Mineral Content in g will be assessed using DEXA | 0-3 years | 
| Body Composition: Bone Mineral Density [g/cm²] using DEXA | Bone Mineral Density in g/cm² will be assessed using DEXA | 0-3 years | 
| Body Composition: Fat Free Mass [g] using DEXA | Fat Free Mass in g will be assessed using DEXA | 0-3 years | 
| Body Composition: Fat mass [g] using DEXA | Fat mass in g will be assessed using DEXA | 0-3 years | 
| Body Composition: Lean mass [g] using DEXA | Lean mass in g will be assessed using DEXA | 0-3 years | 
| Body Composition: Percentage fat using DEXA | Percentage fat will be assessed using DEXA | 0-3 years | 
| Body Composition: Total mass [g] using DEXA | Total mass in g will be assessed using DEXA | 0-3 years | 
| Stool microbiota profile, and metabolomics endpoints in each group. Associations between microbiota and metabolomics profiles (serum, urine, and stool). | Stool microbiota profile (including proportion of fecal bifidobacteria and other bacterial species that may influence energy homeostasis), and metabolomics profile (metabolite sets related to energy recovery and protein and lipid metabolism assessed in blood, urine, and stool samples) in a subset. | 0-4 years |