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

NCT03067714 | Completed Phase 3 DMC

• 1 other identifier: EBB15BL89847
• Study Type: interventional
• Target: 855
• Locations: 13 countries
• Sites: 59

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

Outcome Measures

Primary Outcomes (1)

• Faecel levels of Bifidobacteria

  Levels of Bifidobacteria at 17 weeks of age - stool sample

  17 weeks

Secondary Outcomes (2)

• Faecal levels of Bifidobacteria and adult-like bacterial cluster

  52 weeks

• IgE-mediated allergic manifestations

  52 weeks

Study Arms (2)

Active product: partially hydrolysed formula + synbiotics

EXPERIMENTAL

Other: Infant formula with added synbiotics

Control product: standard formula (intact protein)

ACTIVE COMPARATOR

Other: Standard infant formula

Interventions

Infant formula with added synbiotics OTHER

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

Active product: partially hydrolysed formula + synbiotics

Standard infant formula OTHER

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

Control product: standard formula (intact protein)

Eligibility Criteria

• Age: Up to 16 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Healthy term infants (gestational age ≥ 37 and ≤ 42 weeks) at high risk of developing allergy based on family history of allergy (\*1).
• Infants aged ≤ 16 weeks (max. 16 weeks + 0 days), preferably as soon as possible after birth.
• 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).
• Written informed consent from one or both parents (according to local laws) and/or legal guardian.
• \* 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).

You may not qualify if:

• \* 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.
• Consumption of any amount of infant formula based on intact protein before randomisation, except from consumption during the first 72 hours of life.
• Consumption of any amount of infant formula with added probiotics and/or probiotic supplement before randomisation.
• Existing allergic manifestations (e.g. allergic skin disorders, food allergy) before randomisation according to investigator's clinical assessment.
• Established or suspected cows' milk allergy, lactose intolerance, galactosaemia, or in infants on a fibre-free diet.
• 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).
• 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).
• Known underlying disease predisposing to infection (e.g. HIV, viral hepatitis B, and C, auto-immune diabetes, immune deficiency).
• Severe renal failure and hepatic failure according to investigator's clinical judgement.
• 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
• Participation in other studies involving investigational or marketed products concomitantly or within two weeks prior to screening visit.

Sponsors & Collaborators

• Nutricia Research: lead

Study Sites (59)

Algemeen Stedelijk Ziekenhuis

Aalst, Belgium

Location

Cliniques universitaires Saint-Luc

Brussels, Belgium

Location

Universitair Ziekenhuis Brussel

Brussels, Belgium

Location

Centre Hospitalier Régional de Namur

Namur, Belgium

Location

MUDr. Daniel Drazan, prakticky lekar pro deti a dorost

Prague, Czechia

Location

MUDr. Jitka Fabianova

Prague, Czechia

Location

Prakticky lekar pro deti a dorost

Prague, Czechia

Location

Ustav pro peci o matku a dite

Prague, Czechia

Location

Nemocnice Strakonice, a.s.

Strakonice, Czechia

Location

Charité Universitätsmedizin Berlin

Berlin, Germany

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Prince of Wales Hospital

Shatin, Hong Kong

Location

Dr. Kenessey Albert Korhaz-Rendelointezet

Balassagyarmat, Hungary

Location

Pestszentimrei Gyermekrendelő / Elitance Duo Kft.

Budapest, Hungary

Location

Rózsavölgyi Gyermekháziorvosi Rendelő / CEBA Egészségügyi Bt.

Budapest, Hungary

Location

Gyermekorvosi Rendelő

Debrecen, Hungary

Location

Futurenest Kft.

Miskolc, Hungary

Location

Prehospital Med Kft

Miskolc, Hungary

Location

Kanizsai Dorottya Korhaz

Nagykanizsa, Hungary

Location

Házi Gyermekorvosi Rendelő /Babadoki Kft.

Szeged, Hungary

Location

Hillel Yaffe Medical center

Hadera, Israel

Location

Rambam Health Care Campus

Haifa, Israel

Location

Meir Medical Center

Kfar Saba, Israel

Location

Schneider Children's Medical

Petah Tikva, Israel

Location

Kaplan Medical Center

Rehovot, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

Ospdale Maggiore Policlinico, Fondazione IRCCS Ca' Granda

Milan, Italy

Location

IRCCS Policlinico San Matteo, Università degli studi di Pavi

Pavia, Italy

Location

UOC Allergologia, Osp. Pediatrico Bambino Gesù, IRCCS;

Roma, Italy

Location

Amphia Ziekenhuis

Breda, North Brabant, 4819 EV, Netherlands

Location

VU University Medical Center

Amsterdam, Netherlands

Location

PT&R

Beek, Netherlands

Location

Deventer Ziekenhuis

Deventer, Netherlands

Location

EB UtrechtResearch BV

Utrecht, Netherlands

Location

Kandang Kerbau Women's and Children's Hospital

Singapore, Singapore

Location

National University Hospital

Singapore, Singapore

Location

PEGYS s.r.o.

Dolný Kubín, Slovakia

Location

Juvenalia, s.r.o.

Dunajská Streda, Slovakia

Location

GASTREN, spol. s.r.o.

Košice, Slovakia

Location

PEDMAN s.r.o.

Martin, Slovakia

Location

Univerzitna nemocnica Martin

Martin, Slovakia

Location

Fakultna nemocnica Nitra

Nitra, Slovakia

Location

GASTOL s.r.o.

Prešov, Slovakia

Location

Fakultna nemocnica Trencin

Trenčín, Slovakia

Location

Ambulancia vseobecneho lekara pre deti a dorast

Zlaté Moravce, Slovakia

Location

Hospital HLA Inmaculada Servicio de Pediatría

Granada, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, Spain

Location

Hospital Materno Infantil La Paz

Madrid, Spain

Location

Hospital Sant Joan de Deu

Manresa, Spain

Location

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, Spain

Location

Instituto Hispalense de Pediatría

Seville, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, Spain

Location

China Medical University Hospital

Taichung, Taiwan

Location

LinKou Chang Gung Memorial Hospital

Taoyuan District, Taiwan

Location

Royal London Hospital

London, United Kingdom

Location

University College Hospital

London, United Kingdom

Location

Central Manchester University Hospitals NHS Foundation Trust

Manchester, United Kingdom

Location

The Newcastle Hospitals NHS Foundation Trust

Newcastle, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, United Kingdom

Location

MeSH Terms

Interventions

Infant Formula

Intervention Hierarchy (Ancestors)

Milk Substitutes; Beverages; Diet, Food, and Nutrition; Physiological Phenomena; Food, Formulated; Foods, Specialized; Food; Infant Food; Food and Beverages

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2017
• First Posted: March 1, 2017
• Study Start: March 30, 2017
• Primary Completion: March 25, 2020
• Study Completion: March 25, 2020
• Last Updated: December 8, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

IL (6); BE (4); TW (2); NL (5); ES (7); HK (2); SG (2); SL (9); CZ (5); IT (3); HU (8); DE (1); GB (5)