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

Growth and metabolic biomarkers of healthy term infants fed formulas with staged protein concentrations over the first year of life

Study Overview

• Status: Completed
• Conditions: Healthy Term Infants
• Intervention / Treatment: Dietary supplement: Formula regimen 1; Dietary supplement: Formula regimen 2

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.

• Study Type: Interventional
• Enrollment (Actual): 691
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33000
    • CHU Pellegrin
  • Bron, France, 69500
    • Hospices Civils de LYON - Hôpital Femme Mère Enfant de Bron
  • Lille, France, 59037
    • Centre Hospitalier Regional Universitaire de Lille
  • Lyon, France, 69229
    • Hospices Civils de Lyon - Hôpital de la Croix Rousse
  • Marseille, France, 13000
    • Assistance Publique-Hôpitaux de Marseille, Hôpital de la Conception
  • Marseille, France, 13000
    • Assistance Publique-Hôpitaux de Marseille, Hôpital NORD
  • Mont-Saint-Aignan, France, 76130
    • Centre Hospitalier du Belvédère
  • Nancy, France, 54511
    • CHU de Nancy - Hôpital Brabois
  • Rouen, France, 76031
    • CHU - Hôpitaux de Rouen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 1 week (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Healthy infants will be enrolled in the study provided they meet the following inclusion criteria:

1. 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.
2. Age ≤ 7 days after birth (date of birth = Day 0)
3. Full-term gestational birth (≥ 37 and ≤ 42 weeks)
4. Born to mothers with pre-pregnancy body mass index (BMI) ≥ 18.5 and < 26 kg/m2
5. Born to mothers who independently elected, before study enrollment, not to breastfeed (not applicable for infants in the HM-fed comparator group)
6. Weight ≥ 2'500 g and ≤ 4'200 g
7. 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
8. 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:

1. Born to mothers with hormonal or metabolic disease (e.g. Type-1, Type-2, or gestational diabetes diagnosed according to standardized criteria)
2. Born to mothers who smoked > 10 cigarettes per day during pregnancy
3. Born to mothers who used illicit drugs (e.g. marijuana, cocaine, amphetamines, or heroin) or alcohol (> 3 alcoholic beverages per week) during pregnancy
4. 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)
5. Received radiation therapy (eg. scannography or interventional radiology)
6. Participation in any other clinical trial prior to enrollment
7. Infants or infant's family who in the Investigator's judgment cannot be expected to comply with the protocol or study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Formula regimen 1; 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
Active Comparator: Formula regimen 2; 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
No Intervention: Reference group; 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

Collaborators and Investigators

• Sponsor: Société des Produits Nestlé (SPN)
• Investigators: Study Chair: Sebastien Paoli, MSc, Nestlé Research

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): July 1, 2022
• Study Completion (Actual): July 1, 2022

Study Registration Dates

• First Submitted: November 6, 2015
• First Submitted That Met QC Criteria: January 4, 2016
• First Posted (Estimated): January 6, 2016

Study Record Updates

• Last Update Posted (Actual): May 15, 2025
• Last Update Submitted That Met QC Criteria: May 12, 2025
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 13.13.INF