A Clinical Study to Investigate the Effects of an Infant Formula Containing Partially Hydrolysed Proteins on Growth, Safety and Tolerance in Healthy Term Infants

Study Overview
=================
Brief Summary
-----------------
It is universally accepted that the best nutrition for a new-born infant is breast milk. Breast milk provides a complete set of nutrients to support growth and development of children in early life, including components that have a beneficial effect on gut health and the body's ability to defend itself against infectious organisms and other invaders (immune system).However, it may occur that a mother is unable to breastfeed her child, or chooses not to breastfeed. In such cases, an infant formula inspired by breast milk is the best alternative. Research is done to optimize milk formula for infants. One of these formulas contains 'partially hydrolyzed' proteins instead of intact proteins, meaning the proteins in this formula are broken down into smaller pieces. These smaller pieces of protein make the milk more suitable for consumption by infants at risk of developing cow's milk allergy. These types of partially hydrolyzed protein formulas have been on the market for several years, in particular for children with a family risk of allergy. So far, no safety related issues have been reported. It is also known that weight gain of infants receiving partially hydrolyzed proteins in general is appropriate according to the World Health Organisation growth standards. The main purpose of the TENUTO study is to demonstrate that infants who receive a specific partially hydrolyzed protein infant formula for the first 4 months of life have a similar weight gain compared to infants receiving standard infant formula with intact proteins. A group of infants who receive breast milk only is also included for comparison.

Official Title
-----------------
A Randomized, Controlled, Double Blind, Parallel Group, Multi-country Study to Investigate the Effects of an Infant Formula Containing Partially Hydrolysed Proteins on Growth, Safety and Tolerance in Healthy Term Infants

Conditions
-----------------
Growth

Intervention / Treatment
-----------------
* Other: Infant Formula with prebiotics
* Other: Standard Infant Formula


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy term infants (gestational age ≥ 37 weeks + 0 days and ≤ 41 weeks + 6 days); Infants' age at enrolment ≤ 14 days; Birth weight within normal range for gestational age and sex (10th to 90th percentile according to the WHO Child Growth Standards - or local growth standards if available); Head circumference at inclusion within normal range for age and sex (within 2 SD curves according to WHO Child Growth Standards - or local growth standards if available); Infant formula arms: infants who are exclusively formula fed by time of randomisation with a maximum infants' age of 14 days (infants of mothers who choose not to breastfeed or mothers who cease breastfeeding for any reason before the infant is 14 days of age); OR Breastfeeding reference arm: infants who are exclusively breastfed and whose mothers are intending to exclusively breastfeed their infant at least until the infant is 17 weeks of age; 6 Written informed consent from parent(s) and/or legal guardian(s) aged ≥ 18 years. Exclusion Criteria: Infants of pregnant women/mothers: who are currently participating or will participate in any other (clinical) study involving investigational or marketed products during pregnancy and/or lactation; known to have a significant medical condition (including during pregnancy) that might interfere with the study or known to affect intra-uterine growth (e.g. placenta previa, pre-eclampsia, eclampsia, gestational diabetes requiring insulin or oral medication), as per investigator's clinical judgement; Infants of parents: who are incapable to comply with study protocol or Investigator's uncertainty about the willingness or ability of the parents to comply with the protocol requirements; Infants: who have to be fed with a special diet other than standard (non-hydrolysed) cow's milk based infant formula known to have current or previous illnesses/conditions which could interfere with the study or its outcome parameters, such as gastrointestinal malformations, congenital metabolic disorders, immune deficiency or major surgery, as per investigator's clinical judgement; with any history of, or current participation in any other study involving investigational or marketed products.

Ages Eligible for Study
-----------------
Maximum Age: 14 Days

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active product: partially hydrolysed proteins<br>Partially hydrolysed whey protein based infant formula containing prebiotics. | Other: Infant Formula with prebiotics<br>* Intervention group: Partially hydrolysed whey protein based infant formula containing prebiotics.<br>|
| Active Comparator: Control product: standard formula (intact protein)<br>Intact cow's milk protein based infant formula containing prebiotics. | Other: Standard Infant Formula<br>* Control group: Intact cow's milk protein based infant formula containing prebiotics<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight gain | Weight gain in grams per day from baseline until 17 weeks of age | 17 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length | Gain in Recumbent length (mm/day) | 17 weeks | 
| Head circumference | Gain in Head circumference (mm/day) | 17 weeks | 
| Mid-upper arm circumference | Gain in Mid-upper arm circumference (mm/day) | 17 weeks | 
| Anthropometric measures | Z scores of anthropometric parameters | 17 weeks | 
| Albumin level | Albumin in blood (g/L) | 17 weeks | 
| Calcium level | Calcium in blood (mmol/l) | 17 weeks | 
| Phosphorus level | Phosphorus in blood (mmol/l) | 17 weeks | 
| Iron level | Iron (µmol/l) in blood | 17 weeks | 
| Magnesium level | Magnesium (mmol/l) in blood | 17 weeks | 
| Nitrogen level | Blood urea nitrogen (mmol/l) | 17 weeks | 
| Number of subjects with adverse events | Adverse events (by System/Organ Class and Preferred term according the MedDRA ) will be reported as number of subjects with at least one adverse event | 17 weeks | 
| Number of adverse events | Number of adverse events (by System/Organ Class and Preferred term according the MedDRA) | 17 weeks | 
| Concomitant medications | All concomitant medications (according to WHO-DDE) will be summarised in individual data listing | 17 weeks | 
| Regurgitation | Regurgitation nr of occurrences per week | 4, 8, 13 and 17 weeks | 
| Vomiting | Vomiting nr of occurrences per week | 4, 8, 13 and 17 weeks | 
| Diarrhoea | Number of infants with diarrhoea (definition adapted from WHO definition based on number of watery stools per day) | 4, 8, 13 and 17 weeks | 
| Constipation | Number of infants with constipation (definition adapted from Rome II criteria based on number of defecations and consistency per week) | 4, 8, 13 and 17 weeks |