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

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

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.

Study Overview

• Status: Completed
• Conditions: Growth
• Intervention / Treatment: Other: Infant Formula with prebiotics; Other: Standard Infant Formula

• Study Type: Interventional
• Enrollment (Actual): 380
• Phase: Phase 2

Contacts and Locations

Study Locations

• Finland
  • Turku, Finland
    • University of Turku Children's Allergy and Asthma Clinic
• France
  • Lille, France
    • Groupement des Hôpitaux de l'Institut Catholique de Lille
  • Lyon, France
    • Hospices Civils de Lyon
• Germany
  • Berlin, Germany
    • Vivantes Klinik für Geburtsmedizin, Klinikum Neukölln
  • Bramsche, Germany
    • Paediatric Practice
• Netherlands
  • Apeldoorn, Netherlands
    • Gelre Ziekenhuizen
• Poland
  • Białystok, Poland
    • Poliklinika Ginekologiczno-Poloznicza Sp. z o.o. Sp.k
  • Kraków, Poland
    • Specjalistyczna Poradnia Medyczna Przylądek Zdrowia
  • Poznań, Poland
    • POLMED / Instytut Mikroekologii
  • Rzeszów, Poland
    • Korczowski Bartosz, Gabinet Lekarski
  • Siemianowice Śląskie, Poland
    • NZLA Michalkowice Jarosz i partnerzy Spolka Lekarska
• Spain
  • Barcelona, Spain
    • Hospital Quirónsalud Barcelona
  • Elche, Spain
    • Hospital General Universitario de Elche
  • Reus, Spain
    • Hospital Universitari Sant Joan de Reus (IISPV)
  • Tarragona, Spain
    • Hospital Universitari de Tarragona Joan XXIII

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 weeks (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy term infants (gestational age ≥ 37 weeks + 0 days and ≤ 41 weeks + 6 days);
2. Infants' age at enrolment ≤ 14 days;
3. 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);
4. 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);
5. 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:

1. who are currently participating or will participate in any other (clinical) study involving investigational or marketed products during pregnancy and/or lactation;

2. 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:

3. 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:

4. who have to be fed with a special diet other than standard (non-hydrolysed) cow's milk based infant formula
5. 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;
6. with any history of, or current participation in any other study involving investigational or marketed products.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Nutricia Research

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2017
• Primary Completion (Actual): October 26, 2018
• Study Completion (Actual): November 12, 2018

Study Registration Dates

• First Submitted: February 3, 2017
• First Submitted That Met QC Criteria: February 22, 2017
• First Posted (Actual): February 23, 2017

Study Record Updates

• Last Update Posted (Actual): January 14, 2019
• Last Update Submitted That Met QC Criteria: January 11, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: EBB15BL89832

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No