The Combiotic-Study
- Conditions
- Healthy Term Infants
- Interventions
- Dietary Supplement: Control formulaDietary Supplement: Synbiotic formula
- Registration Number
- NCT02221687
- Lead Sponsor
- HiPP GmbH & Co. Vertrieb KG
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 540
- 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.
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control formula Control formula Control formula : standard formula without pre and probiotic Dose : variable number of powder scoops, adapted to the infant's age and weight, and addition of the defined amount of water according to the Dose and Drinking Amount table. Route: oral, ad libitum Duration of product intake: * Control IF : 5 months of consumption (from the inclusion until 6 months completed of age) * Control FoF : 6 months of consumption (from 6 to 12 months of age) Synbiotic formula Synbiotic formula Synbiotic formula : standard formula enriched with a prebiotic fiber and a probiotic strain Dose : variable number of powder scoops, adapted to the infant's age and weight, and addition of the defined amount of water, according to the Dose and Drinking Amount table. Route : oral, ad libitum Duration of product intake: * Synbiotic IF : 5 months of consumption (from the inclusion until 6 months completed of age) * Synbiotic FoF: 6 months of consumption (from 6 to 12 months of age)
- Primary Outcome Measures
Name Time Method (Cumulative) number of infectious diarrhea episodes per subject during the first year of life. one year Difference between formula groups are evaluated via incidence rate based on number of subjects.
In formula-fed infants, diarrhea is defined as three or more loose or watery stools in 24 hours with or without fever or vomiting (according to WHO and ESPGHAN definition). For breast-fed infants, a change in stool consistency versus previous stool consistency is more indicative of diarrhea than stool number.
Diarrhea episode is considered as ended as soon as 2 consecutive non-watery stools are observed or no stools are observed in 24 hours.
- Secondary Outcome Measures
Name Time Method Number and duration of antibiotic treatment. 1 year Suitability for daily use 3 years Assessed through a 3-day diary filled in by parents
- average daily consumption: drinking amounts and formula acceptance;Levels of fecal IgA and fecal calprotectin in planned stool samples 3 years Adverse events (AE) 3 years Assessed through a 3-day diary filled in by parents
- Number of events, number of subjects showing adverse events, intensity and relationship of AE.Fecal pH and levels of short chain fatty acids (SCFA) in planned stool samples 3 years short chain fatty acids (SCFA): acetate, propionate, butyrate;
Characteristics of bowel movements during diarrhea episodes 1 year - assessed through a diary filled in by parents during diarrhea episodes
* average daily number of bowel movements per diarrhea episode;
* average duration (number of days) of diarrhea episodes;
* total number of days with diarrhea, within the first year of age (between V1 and V5);
* (average daily) Infant Stool Form scores consistency (4-point scale), amount (4-point scale) and color (6 categories) per diarrhea episode.Infants growth measured by anthropometric measurements 3 years weight, size, head circumference;
Child's behavior 3 years Assessed through a 3-day diary filled in by parents
- Average sleep duration and crying duration per 24 hours;Minor gastrointestinal disorders (digestive tolerance) 3 years Assessed through a 3-day diary filled in by parents
- average daily vomiting, regurgitation/reflux, flatulence, constipation (according to WHO definition);Analysis of fecal microbiota by molecular analysis from frozen stools in diarrhea samples 1 year levels of potential pathogens causing diarrhea including rotavirus, norovirus, Salmonella enterica, Campylobacter jejuni, Clostridium difficile, Clostridium perfringens, Escherichia coli (potential pathogenic bacteria will be screened only in case of negative testing for viruses on sample collected within 72 hours after beginning of the diarrhea episode);
Characteristics of bowel movements and stools 3 years - assessed through a 3-day diary filled in by parents
* average daily number of bowel movements;
* (average daily) Infant Stool Form scores consistency (4-point scale), amount (4-point scale) and color (6 categories) (using the validated scale for preterm and term infants proposed by Bekkali N, et al., 2009), and especially
* average daily incidence of loose or watery stools (category A, subscale 'consistency' on Bekkali scale);
* dominant stool color per visitNumber and duration of infectious diseases 1 year Especially: otitis media, infections of upper and lower respiratory tract and of urinary tract;
Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples 3 years Levels of total lactobacilli, Lactobacillus fermentum species (and if possible the strain CECT 5716 will be quantified too), total bifidobacteria, enterobacteriaceae, clostridium difficile
Number and duration of fever episodes; 1 year
Trial Locations
- Locations (25)
C.I.C pédiatrique - C.H.U. de Nantes - Hôpital Mère-Enfant
🇫🇷Nantes, Loire-Atlantique, France
Alain BATY
🇫🇷Laval, Mayenne, France
Christian DUROY
🇫🇷Laval, Mayenne, France
François RICHARD
🇫🇷Laval, Mayenne, France
Patrick ROBERT
🇫🇷Laval, Mayenne, France
Michel LAMBERT
🇫🇷Angers, Maine-et-Loire, France
Christine REGIMBART
🇫🇷Becon Les Granits, Maine-et-Loire, France
Daniel GOMBAUD
🇫🇷Angers, Maine-et-Loire, France
Pierre-André FERRAND
🇫🇷Angers, Maine-et-Loire, France
Damien GUILLON
🇫🇷Angers, Maine-et-Loire, France
Antoine LEPELLETIER
🇫🇷Montreuil, Maine-et-Loire, France
Alain PALOMBA
🇫🇷Angers, Maine-et-Loire, France
Philippe REMAUD
🇫🇷Angers, Maine-et-Loire, France
Vanessa BERNAND
🇫🇷Angers, Maine-et-Loire, France
Benoit DAGUZAN
🇫🇷Segre, Maine-et-Loire, France
Damien GODIN
🇫🇷Angers, Maine-et-Loire, France
Nolwenn RONCERAY
🇫🇷Angers, Maine-et-Loire, France
Philippe IGIGABEL
🇫🇷Tierce, Maine-et-Loire, France
Elie JABBOUR
🇫🇷Gemozac, Charente-Maritime, France
Christophe VIEL
🇫🇷La Rochelle, Charente-Maritime, France
C.I.C Pédiatrique - C.H.U. de Grenoble - Hôpital Couple-Enfant
🇫🇷Grenoble, Isère, France
Christophe RONDEAU
🇫🇷Angers, Maine-et-Loire, France
Jean-François FOUCAULT
🇫🇷Angers, Maine-et-Loire, France
Francisco MARTINEZ-CORTES
🇫🇷Angers, Maine-et-Loire, France
Didier NOURRY
🇫🇷Tierce, Maine-et-Loire, France