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

Not Applicable

Completed

• Conditions: Healthy Term Infants
• Interventions: Dietary Supplement: Formula regimen 2; Dietary Supplement: Formula regimen 1

• Registration Number: NCT02646969
• Lead Sponsor: Société des Produits Nestlé (SPN)

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.

Study Timeline

• Study Start: 2015-10
• Study First Submitted: 2015-11-06
• Study First Submitted QC: 2016-01-04
• Study First Posted: 2016-01-06
• Primary Completion: 2022-07
• Study Completion: 2022-07
• Status Verified: 2023-01
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 691

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Formula regimen 2	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
Formula regimen 1	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

Primary Outcome Measures

Name	Time	Method
Growth velocity of formula regimen 1 and 2 versus WHO growth curve	0-6 months	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
Growth velocity (g/day) of formula regimen 1 and 2 versus a human milk (HM)-fed comparator group	0-6 months	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.

Secondary Outcome Measures

Name	Time	Method
Body Composition: Fat free mass density [kg/L] using PeaPod	1-6 months	Fat free mass density in kg/L will be assessed using PeaPod
Body Composition: Fat free mass [kg] using PeaPod	1-6 months	Fat free mass in kg will be assessed using PeaPod
Body Composition: Percentage fat mass using PeaPod	1-6 months	Percentage fat mass will be assessed using PeaPod
Assess the adverse events (AEs) among all study subjects	0-4 years	Assess the type, incidence, severity, seriousness, and relationship to study formulas of AEs among study subjects.
Growth velocity of formula regimen 1 and 2 versus WHO growth curve and versus a human milk (HM)-fed comparator group	0-3 months and 0-12 months	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.
Other growth parameters z-scores of formula regimen 1 and 2 versus WHO standards and versus a human milk (HM)-fed comparator group	6 and 12 months	Weight-for-length, weight-for-age, length-for-age, head circumference-for-age, and BMI-for-age z-scores
Body Composition: Body mass [kg] using PeaPod	1-6 months	Body mass in kg will be assessed using PeaPod
Assess and compare the child behavior in each group until 4 years of age	0-4 years	Neurodevelopment will be assessed by parental ratings of child development using validated measures Ages and Stages Questionnaire (ASQ)
Body Composition: Percentage fat free mass using PeaPod	1-6 months	Percentage fat free mass will be assessed using PeaPod
Assess and compare the neurodevelopment in each group until 4 years of age	0-4 years	Neurodevelopment will be assessed by tests of child development using validated Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV)
Body Composition: Body surface area [cm²] using PeaPod	1-6 months	Body surface area in cm² will be assessed using PeaPod
Body Composition: Body volume [L] using PeaPod	1-6 months	Body volume in L will be assessed using PeaPod
Compare metabolic biomarkers measures in each formula-fed group to the HM-fed group	0-4 years	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
Body Composition: Body density [kg/L] using PeaPod	1-6 months	Body density in kg/L will be assessed using PeaPod
Body Composition: Bone Mineral Density [g/cm²] using DEXA	0-3 years	Bone Mineral Density in g/cm² will be assessed using DEXA
Body Composition: Total mass [g] using DEXA	0-3 years	Total mass in g will be assessed using DEXA
Body Composition: Fat mass [kg] using PeaPod	1-6 months	Fat mass in kg will be assessed using PeaPod
Body Composition: Thoracic gas volume (L) using PeaPod	1-6 months	Thoracic gas volume in L will be assessed using PeaPod
Body Composition: Bone area [cm²] using DEXA	0-3 years	Bone area in cm² will be assessed using DEXA
Body Composition: Fat Free Mass [g] using DEXA	0-3 years	Fat Free Mass in g will be assessed using DEXA
Body Composition: Lean mass [g] using DEXA	0-3 years	Lean mass in g will be assessed using DEXA
Stool microbiota profile, and metabolomics endpoints in each group. Associations between microbiota and metabolomics profiles (serum, urine, and stool).	0-4 years	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.
Body Composition: Bone Mineral Content [g] using DEXA	0-3 years	Bone Mineral Content in g will be assessed using DEXA
Body Composition: Fat mass [g] using DEXA	0-3 years	Fat mass in g will be assessed using DEXA
Body Composition: Percentage fat using DEXA	0-3 years	Percentage fat will be assessed using DEXA

Trial Locations

Locations (9)

Hospices Civils de LYON - Hôpital Femme Mère Enfant de Bron; 🇫🇷 Bron, France

Hospices Civils de LYON - Hopital de La Croix Rousse; 🇫🇷 Lyon, France

Centre Hospitalier Régional Universitaire de Lille; 🇫🇷 Lille, France

Assistance Publique-Hôpitaux de Marseille, Hôpital de la Conception; 🇫🇷 Marseille, France

Centre Hospitalier du Belvédère; 🇫🇷 Mont-Saint-Aignan, France

CHU de Nancy - Hôpital Brabois; 🇫🇷 Nancy, France

Assistance Publique-Hôpitaux de Marseille, Hôpital NORD; 🇫🇷 Marseille, France

CHU - Hôpitaux de ROUEN; 🇫🇷 Rouen, France

CHU Pellegrin; 🇫🇷 Bordeaux, France