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

Immunity Clinical Trial

— TEMPO  

Official title:

A Randomised, Double-blind, Controlled, Parallel-group, Multi-country 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03067714
• Other study ID #: EBB15BL89847
• Status: Completed
• Phase: Phase 3
• Start date: March 30, 2017
• Est. completion date: March 25, 2020

Study information

• Verified date: December 2021
• Source: Nutricia Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 855
• Est. completion date: March 25, 2020
• Est. primary completion date: March 25, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 16 Weeks

Eligibility

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). 2* Subjects whose mother intents to switch to formula feeding before the subject's age of 16 weeks but in the end still exclusively breastfeed, will be included in the breastfed reference group. The other way around, subjects whose mother intents to exclusively breastfeed for at least 16 weeks, but in the end decides to switch to formula earlier, will be included in the randomised groups. All these subjects should meet all other in-/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.

• Exclusion Criteria:

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.

Related Conditions & MeSH terms

• Hypersensitivity
• Immunity

Intervention

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

Locations

Country	Name	City	State
Belgium	Algemeen Stedelijk Ziekenhuis	Aalst
Belgium	Cliniques universitaires Saint-Luc	Brussels
Belgium	Universitair Ziekenhuis Brussel	Brussels
Belgium	Centre Hospitalier Régional de Namur	Namur
Czechia	MUDr. Daniel Drazan, prakticky lekar pro deti a dorost	Praha
Czechia	MUDr. Jitka Fabianova	Praha
Czechia	Prakticky lekar pro deti a dorost	Praha
Czechia	Ustav pro peci o matku a dite	Praha
Czechia	Nemocnice Strakonice, a.s.	Strakonice
Germany	Charité Universitätsmedizin Berlin	Berlin
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Prince of Wales Hospital	Shatin
Hungary	Dr. Kenessey Albert Korhaz-Rendelointezet	Balassagyarmat
Hungary	Pestszentimrei Gyermekrendelo / Elitance Duo Kft.	Budapest
Hungary	Rózsavölgyi Gyermekháziorvosi Rendelo / CEBA Egészségügyi Bt.	Budapest
Hungary	Gyermekorvosi Rendelo	Debrecen
Hungary	Futurenest Kft.	Miskolc
Hungary	Prehospital Med Kft	Miskolc
Hungary	Kanizsai Dorottya Korhaz	Nagykanizsa
Hungary	Házi Gyermekorvosi Rendelo /Babadoki Kft.	Szeged
Israel	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	Re?ovot
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Ospdale Maggiore Policlinico, Fondazione IRCCS Ca' Granda	Milano
Italy	IRCCS Policlinico San Matteo, Università degli studi di Pavi	Pavia
Italy	UOC Allergologia, Osp. Pediatrico Bambino Gesù, IRCCS;	Roma
Netherlands	VU University Medical Center	Amsterdam
Netherlands	PT&R	Beek
Netherlands	Amphia Ziekenhuis	Breda	Brabant
Netherlands	Deventer Ziekenhuis	Deventer
Netherlands	EB UtrechtResearch BV	Utrecht
Singapore	Kandang Kerbau Women's and Children's Hospital	Singapore
Singapore	National University Hospital	Singapore
Slovakia	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	Trencín
Slovakia	Ambulancia vseobecneho lekara pre deti a dorast	Zlaté Moravce
Spain	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	Sevilla
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Taiwan	China Medical University Hospital	Taichung
Taiwan	LinKou Chang Gung Memorial Hospital	Taoyuan
United Kingdom	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

Sponsors (1)

Lead Sponsor	Collaborator
Nutricia Research

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Faecel levels of Bifidobacteria	Levels of Bifidobacteria at 17 weeks of age - stool sample	17 weeks
Secondary	Faecal levels of Bifidobacteria and adult-like bacterial cluster	Levels of Bifidobacteria and adult-like bacterial cluster up to 52 weeks of age - stool sample	52 weeks
Secondary	IgE-mediated allergic manifestations	IgE-mediated allergic manifestations up to 52 weeks of age - blood sample	52 weeks