Clinical trial NCT02221687: The Combiotic-Study
Official title: Evaluation of the Efficacy and Safety of an Infant Formula Containing Synbiotics and Its Effects on the Incidence of Infectious Diseases in the Infant Gut : a Double-blind, Randomized, Controlled Interventional Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Healthy Term Infants
Keywords: synbiotic formula
infant formula
diarrhea
Lead sponsor: HiPP GmbH & Co. Vertrieb KG
Sponsor class: INDUSTRY
Collaborators: name: Biofortis Mérieux NutriSciences
First posted: 2014-08-20
Enrollment: 540
Sex: ALL
Minimum age (years): 3
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The primary objective of this study is to demonstrate that a synbiotic formula, fed for the duration of the first year of life (infant and follow-on formula) reduces the incidence rate of episodes of infectious diarrhea in infants during the first year of life compared to a standard infant formula.


Eligibility criteria: Inclusion Criteria:

* Healthy term infants
* Female or male gender
* Gestational age between 37 and 41 weeks completed (= 41 weeks + 6 days)
* Age at time of V1 visit : 4 +/- 7 days
* Birth weight between 2500 ans 4200g, with regular weight gain (≥ 150g / week)
* Two legal representatives (parent(s) / guardian(s)) who are capable of and willing to comply with the protocol and have signed the informed consent in accordance with legal requirements.
* at least one of the legal representatives is affiliated to with a social security scheme.

Additionnaly , criteria of inclusion in one of the formula-fed groups or in the breast-fed group, respectively, are the following:

* To be included in one of the formula arm, infants will have to be exclusively formula-fed (no breast milk meal) at the time of V1 visit (randomization).

or

* To be included in the breastfeeding arm, infants will have to be exclusively breast-fed (no more than one formula meal per day) at V1 visit (randomization) and its mother will have to be willing to pursue exclusive breastfeeding at least until the infant will be 4-month old.

Exclusion Criteria:

* Intensive care during at least the first 14 days of life
* Neonatal health problems, such as: respiratory distress, asphyxia, hypoglycemia, sepsis, NEC (necrotizing enterocolitis),...
* Clinical evidence of chronic illness or gastrointestinal disorders such as : GER (Gastrooesophageal Reflux), gastroenteritis,...
* Known metabolic disorders, such as diabetes, lactose intolerance,....
* Known immune deficiency
* Subjects recommended to receive formula with hydrolized protein (e.g. children with allergy risk)
* Subject under oral antibiotic treatment at V1 visit
* Participation in another biomedical study
* Whose legal representatives have psychological or linguistic incapability to sign the informed consent form
* Reasons to presume that parents are unable to meet the study plan requirements (e.g. impossibility to contact study representatives in case of emergency, drug addiction etc)

Primary outcomes:
measure: (Cumulative) number of infectious diarrhea episodes per subject during the first year of life.
timeFrame: one year
Secondary outcomes:
measure: Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples
timeFrame: 4 months
measure: Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples
timeFrame: 1 year
measure: Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples
timeFrame: 2 years
measure: Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples
timeFrame: 3 years
measure: Analysis of fecal microbiota by molecular analysis from frozen stools in diarrhea samples
timeFrame: 1 year
measure: Fecal pH and levels of short chain fatty acids (SCFA) in planned stool samples
timeFrame: 4 months
measure: Fecal pH and levels of short chain fatty acids (SCFA) in planned stool samples
timeFrame: 1 year
measure: Fecal pH and levels of short chain fatty acids (SCFA) in planned stool samples
timeFrame: 2 years
measure: Fecal pH and levels of short chain fatty acids (SCFA) in planned stool samples
timeFrame: 3 years
measure: Characteristics of bowel movements and stools
timeFrame: 4 months
measure: Characteristics of bowel movements and stools
timeFrame: 6 months
measure: Characteristics of bowel movements and stools
timeFrame: 9 months
measure: Characteristics of bowel movements and stools
timeFrame: 1 year
measure: Characteristics of bowel movements and stools
timeFrame: 2 years
measure: Characteristics of bowel movements and stools
timeFrame: 3 years
measure: Characteristics of bowel movements during diarrhea episodes
timeFrame: 1 year
measure: Levels of fecal IgA and fecal calprotectin in planned stool samples
timeFrame: 4 months
measure: Levels of fecal IgA and fecal calprotectin in planned stool samples
timeFrame: 1 year
measure: Levels of fecal IgA and fecal calprotectin in planned stool samples
timeFrame: 2 years
measure: Levels of fecal IgA and fecal calprotectin in planned stool samples
timeFrame: 3 years
measure: Number and duration of infectious diseases
timeFrame: 3 years
measure: Number and duration of fever episodes;
timeFrame: 3 years
measure: Number and duration of antibiotic treatment.
timeFrame: 3 years
measure: Infants growth measured by anthropometric measurements
timeFrame: 4 weeks
measure: Infants growth measured by anthropometric measurements
timeFrame: 4 months
measure: Infants growth measured by anthropometric measurements
timeFrame: 6 months
measure: Infants growth measured by anthropometric measurements
timeFrame: 9 months
measure: Infants growth measured by anthropometric measurements
timeFrame: 1 year
measure: Infants growth measured by anthropometric measurements
timeFrame: 2 years
measure: Infants growth measured by anthropometric measurements
timeFrame: 3 years
measure: Child's behavior
timeFrame: 4 months
measure: Child's behavior
timeFrame: 6 months
measure: Child's behavior
timeFrame: 9 months
measure: Child's behavior
timeFrame: 1 year
measure: Child's behavior
timeFrame: 2 years
measure: Child's behavior
timeFrame: 3 years
measure: Minor gastrointestinal disorders (digestive tolerance)
timeFrame: 4 months
measure: Minor gastrointestinal disorders (digestive tolerance)
timeFrame: 6 months
measure: Minor gastrointestinal disorders (digestive tolerance)
timeFrame: 9 months
measure: Minor gastrointestinal disorders (digestive tolerance)
timeFrame: 1 year
measure: Minor gastrointestinal disorders (digestive tolerance)
timeFrame: 2 years
measure: Minor gastrointestinal disorders (digestive tolerance)
timeFrame: 3 years
measure: Suitability for daily use
timeFrame: 4 months
measure: Suitability for daily use
timeFrame: 6 months
measure: Suitability for daily use
timeFrame: 9 months
measure: Suitability for daily use
timeFrame: 1 year
measure: Suitability for daily use
timeFrame: 2 years
measure: Suitability for daily use
timeFrame: 3 years
measure: Adverse events (AE)
timeFrame: 4 months
measure: Adverse events (AE)
timeFrame: 6 months
measure: Adverse events (AE)
timeFrame: 9 months
measure: Adverse events (AE)
timeFrame: 1 year
measure: Adverse events (AE)
timeFrame: 2 years
measure: Adverse events (AE)
timeFrame: 3 years
measure: Number and duration of fever episodes;
timeFrame: 1 year
measure: Number and duration of antibiotic treatment.
timeFrame: 1 year
measure: Number and duration of infectious diseases
timeFrame: 1 year
Other outcomes:
measure: Microbiota results
timeFrame: 1 year
measure: Urinary D-Lactate and creatinine
timeFrame: 4 weeks
measure: Urinary D-Lactate and creatinine
timeFrame: 4 months
measure: Microbiota results
timeFrame: 4 months
measure: Microbiota results
timeFrame: 2 years
measure: Microbiota results
timeFrame: 3 years
Locations:
city: Gemozac
country: France
facility: Elie JABBOUR
state: Charente-Maritime
city: La Rochelle
country: France
facility: Christophe VIEL
state: Charente-Maritime
city: Grenoble
country: France
facility: C.I.C Pédiatrique - C.H.U. de Grenoble - Hôpital Couple-Enfant
state: Isère
city: Nantes
country: France
facility: C.I.C pédiatrique - C.H.U. de Nantes - Hôpital Mère-Enfant
state: Loire-Atlantique
city: Angers
country: France
facility: Alain PALOMBA
state: Maine-et-Loire
city: Angers
country: France
facility: Christophe RONDEAU
state: Maine-et-Loire
city: Angers
country: France
facility: Damien GODIN
state: Maine-et-Loire
city: Angers
country: France
facility: Daniel GOMBAUD
state: Maine-et-Loire
city: Angers
country: France
facility: Jean-François FOUCAULT
state: Maine-et-Loire
city: Angers
country: France
facility: Michel LAMBERT
state: Maine-et-Loire
city: Angers
country: France
facility: Nolwenn RONCERAY
state: Maine-et-Loire
city: Angers
country: France
facility: Philippe REMAUD
state: Maine-et-Loire
city: Angers
country: France
facility: Pierre-André FERRAND
state: Maine-et-Loire
city: Angers
country: France
facility: Vanessa BERNAND
state: Maine-et-Loire
city: Angers
country: France
facility: Francisco MARTINEZ-CORTES
state: Maine-et-Loire
city: Angers
country: France
facility: Damien GUILLON
state: Maine-et-Loire
city: Becon Les Granits
country: France
facility: Christine REGIMBART
state: Maine-et-Loire
city: Montreuil
country: France
facility: Antoine LEPELLETIER
state: Maine-et-Loire
city: Segre
country: France
facility: Benoit DAGUZAN
state: Maine-et-Loire
city: Tierce
country: France
facility: Didier NOURRY
state: Maine-et-Loire
city: Tierce
country: France
facility: Philippe IGIGABEL
state: Maine-et-Loire
city: Laval
country: France
facility: Alain BATY
state: Mayenne
city: Laval
country: France
facility: Christian DUROY
state: Mayenne
city: Laval
country: France
facility: François RICHARD
state: Mayenne
city: Laval
country: France
facility: Patrick ROBERT
state: Mayenne
Study officials:
name: Hugues Piloquet, Pediatrician
role: PRINCIPAL_INVESTIGATOR
References: