A Clinical Study to Investigate the Effect of a Partially Hydrolysed Infant Formula With Added Synbiotics on Gut Microbiota Composition and Clinical Effectiveness in Infants at High Risk of Developing Allergy

NCT ID: NCT03067714

Last Updated: 2021-12-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 855 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-30
• Study Completion Date: 2020-03-25

Brief Summary

With the rising prevalence of allergic diseases and the subsequent risk of developing other immune-related disorders, primary prevention of allergy has become a major priority. It is generally acknowledged that breastfeeding is one of the main pillars in allergy prevention. Infant formulas based on hydrolysed proteins have been developed to be used by infants at increased risk of developing allergy in case a mother is unable or chooses not to breastfeed her infant. It has recently been demonstrated that the gut microbiota composition and microbiota activity of infants receiving an infant formula based on partially hydrolysed proteins, supplemented with oligosaccharides, is more similar to breastfed infants than to infants receiving standard cow's milk formula, demonstrated by increased levels of bifidobacteria. However the interaction between microbial changes impacted by an hypoallergenic concept and its influence on early life immune development should be further explored. The aim of the present study is therefore to investigate the bifidogenic effect of a hypoallergenic formula supplemented with prebiotics and probiotics compared to standard infant formula in infants at increased risk of developing allergic disease. This study will secondary assess the effects of this concept on the development of allergic manifestations up to the age of 12 months, which will be verified in a separate clinical study MAESTRO as primary outcome. Furthermore, the effects on growth and safety will be studied.

Conditions

Immunity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Active product: partially hydrolysed formula + synbiotics

Group Type: EXPERIMENTAL

Infant formula with added synbiotics

Intervention Type: OTHER

Intervention group: Infant Formula / Follow-On formula with partially hydrolysed cow's milk protein supplemented with prebiotics and probiotics.

Control product: standard formula (intact protein)

Group Type: ACTIVE_COMPARATOR

Standard infant formula

Intervention Type: OTHER

Control group: Standard Infant Formula / Follow-On formula with intact cow's milk protein (only standard ingredients, without addition of pre- and probiotics).

Interventions

Infant formula with added synbiotics

Intervention group: Infant Formula / Follow-On formula with partially hydrolysed cow's milk protein supplemented with prebiotics and probiotics.

Intervention Type: OTHER

Standard infant formula

Control group: Standard Infant Formula / Follow-On formula with intact cow's milk protein (only standard ingredients, without addition of pre- and probiotics).

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Healthy term infants (gestational age ≥ 37 and ≤ 42 weeks) at high risk of developing allergy based on family history of allergy (*1).

2. Infants aged ≤ 16 weeks (max. 16 weeks + 0 days), preferably as soon as possible after birth.

3. Infants who start formula feeding within 16 weeks of age (infants of mothers who have chosen not to breastfeed or mothers who completely/partially cease breastfeeding before the subject's age of 16 weeks) (*2) OR Infants who are exclusively breastfed and whose mothers have the intention to exclusively breastfeed at least until their infant is 16 weeks of age (*2,3).

4. Written informed consent from one or both parents (according to local laws) and/or legal guardian.

1* Family history of allergy is defined as at least one first-degree relative (parent or full sibling) with self-reported historically doctor confirmed allergic disease (allergic rhinitis, asthma, food allergy, allergic eczema). In case of a self-reported historically non-doctor confirmed allergic disease, doctor confirmation must be done as part of the screening procedure according to local practice (e.g. skin prick test, IgE measurement).

Exclusion Criteria

3* Exclusive breast feeding. WHO definition: only breast milk and no other liquids or solids except for drops or syrups consisting of vitamins, mineral supplements or medicines [2]. In addition to the WHO definition, in this study water is allowed as well as formula feeding during the first 72 hours of life.

1. Consumption of any amount of infant formula based on intact protein before randomisation, except from consumption during the first 72 hours of life.

2. Consumption of any amount of infant formula with added probiotics and/or probiotic supplement before randomisation.

3. Existing allergic manifestations (e.g. allergic skin disorders, food allergy) before randomisation according to investigator's clinical assessment.

4. Established or suspected cows' milk allergy, lactose intolerance, galactosaemia, or in infants on a fibre-free diet.

5. Severe congenital abnormalities which could influence the subjects' growth (e.g. cystic fibrosis, bronchopulmonary dysplasia, tracheomalacia, tracheoesophageal fistula, major congenital heart disease, or any other condition according to investigator's clinical judgement).

6. Severe neonatal illnesses (e.g. respiratory distress syndrome, severe sepsis intraventricular hemorrhage, severe neonatal jaundice, necrotizing enterocolitis, persistent pulmonary hypertension of the newborn, or any other condition which required to be treated with intravenous and/or intramuscular antibiotics).

7. Known underlying disease predisposing to infection (e.g. HIV, viral hepatitis B, and C, auto-immune diabetes, immune deficiency).

8. Severe renal failure and hepatic failure according to investigator's clinical judgement.

9. Incapability of the parents to comply with study protocol or investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements

10. Participation in other studies involving investigational or marketed products concomitantly or within two weeks prior to screening visit.

• Maximum Eligible Age: 16 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Nutricia Research

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Algemeen Stedelijk Ziekenhuis

Aalst, , Belgium

Cliniques universitaires Saint-Luc

Brussels, , Belgium

Universitair Ziekenhuis Brussel

Brussels, , Belgium

Centre Hospitalier Régional de Namur

Namur, , Belgium

MUDr. Daniel Drazan, prakticky lekar pro deti a dorost

Prague, , Czechia

MUDr. Jitka Fabianova

Prague, , Czechia

Prakticky lekar pro deti a dorost

Prague, , Czechia

Ustav pro peci o matku a dite

Prague, , Czechia

Nemocnice Strakonice, a.s.

Strakonice, , Czechia

Charité Universitätsmedizin Berlin

Berlin, , Germany

Queen Mary Hospital

Hong Kong, , Hong Kong

Prince of Wales Hospital

Shatin, , Hong Kong

Dr. Kenessey Albert Korhaz-Rendelointezet

Balassagyarmat, , Hungary

Pestszentimrei Gyermekrendelő / Elitance Duo Kft.

Budapest, , Hungary

Rózsavölgyi Gyermekháziorvosi Rendelő / CEBA Egészségügyi Bt.

Budapest, , Hungary

Gyermekorvosi Rendelő

Debrecen, , Hungary

Futurenest Kft.

Miskolc, , Hungary

Prehospital Med Kft

Miskolc, , Hungary

Kanizsai Dorottya Korhaz

Nagykanizsa, , Hungary

Házi Gyermekorvosi Rendelő /Babadoki Kft.

Szeged, , Hungary

Hillel Yaffe Medical center

Hadera, , Israel

Rambam Health Care Campus

Haifa, , Israel

Meir Medical Center

Kfar Saba, , Israel

Schneider Children's Medical

Petah Tikva, , Israel

Kaplan Medical Center

Rehovot, , Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Ospdale Maggiore Policlinico, Fondazione IRCCS Ca' Granda

Milan, , Italy

IRCCS Policlinico San Matteo, Università degli studi di Pavi

Pavia, , Italy

UOC Allergologia, Osp. Pediatrico Bambino Gesù, IRCCS;

Roma, , Italy

Amphia Ziekenhuis

Breda, North Brabant, Netherlands

VU University Medical Center

Amsterdam, , Netherlands

PT&R

Beek, , Netherlands

Deventer Ziekenhuis

Deventer, , Netherlands

EB UtrechtResearch BV

Utrecht, , Netherlands

Kandang Kerbau Women's and Children's Hospital

Singapore, , Singapore

National University Hospital

Singapore, , Singapore

PEGYS s.r.o.

Dolný Kubín, , Slovakia

Juvenalia, s.r.o.

Dunajská Streda, , Slovakia

GASTREN, spol. s.r.o.

Košice, , Slovakia

PEDMAN s.r.o.

Martin, , Slovakia

Univerzitna nemocnica Martin

Martin, , Slovakia

Fakultna nemocnica Nitra

Nitra, , Slovakia

GASTOL s.r.o.

Prešov, , Slovakia

Fakultna nemocnica Trencin

Trenčín, , Slovakia

Ambulancia vseobecneho lekara pre deti a dorast

Zlaté Moravce, , Slovakia

Hospital HLA Inmaculada Servicio de Pediatría

Granada, , Spain

Hospital Universitario Virgen de las Nieves

Granada, , Spain

Hospital Materno Infantil La Paz

Madrid, , Spain

Hospital Sant Joan de Deu

Manresa, , Spain

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, , Spain

Instituto Hispalense de Pediatría

Seville, , Spain

Hospital Universitari i Politecnic La Fe

Valencia, , Spain

China Medical University Hospital

Taichung, , Taiwan

LinKou Chang Gung Memorial Hospital

Taoyuan District, , Taiwan

Royal London Hospital

London, , United Kingdom

University College Hospital

London, , United Kingdom

Central Manchester University Hospitals NHS Foundation Trust

Manchester, , United Kingdom

The Newcastle Hospitals NHS Foundation Trust

Newcastle, , United Kingdom

University Hospital Southampton NHS Foundation Trust

Southampton, , United Kingdom

Countries

Belgium; Czechia; Germany; Hong Kong; Hungary; Israel; Italy; Netherlands; Singapore; Slovakia; Spain; Taiwan; United Kingdom

Other Identifiers

EBB15BL89847

Identifier Type: -

Identifier Source: org_study_id