<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02221687</url>
  </required_header>
  <id_info>
    <org_study_id>505564 - PEC10561</org_study_id>
    <nct_id>NCT02221687</nct_id>
  </id_info>
  <brief_title>The Combiotic-Study</brief_title>
  <acronym>GOLFIII</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>HiPP GmbH &amp; Co. Vertrieb KG</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Biofortis Mérieux NutriSciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>HiPP GmbH &amp; Co. Vertrieb KG</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to demonstrate that a synbiotic formula, fed for the&#xD;
      duration of the first year of life (infant and follow-on formula) reduces the incidence rate&#xD;
      of episodes of infectious diarrhea in infants during the first year of life compared to a&#xD;
      standard infant formula.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Recruitment of breastfed infants was very slow. Decision with PI (05/2018): Termination&#xD;
    (80/100); no implication on primary outcome. Predetermined number of breastfed infants (n=100)&#xD;
    was arbitray choice. Formula groups completed (460/460) 12/2017.&#xD;
  </why_stopped>
  <start_date type="Actual">August 2014</start_date>
  <completion_date type="Actual">April 2021</completion_date>
  <primary_completion_date type="Actual">April 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>(Cumulative) number of infectious diarrhea episodes per subject during the first year of life.</measure>
    <time_frame>one year</time_frame>
    <description>Difference between formula groups are evaluated via incidence rate based on number of subjects.&#xD;
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.&#xD;
Diarrhea episode is considered as ended as soon as 2 consecutive non-watery stools are observed or no stools are observed in 24 hours.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples</measure>
    <time_frame>4 months</time_frame>
    <description>Levels of total lactobacilli, Lactobacillus fermentum species (and if possible the strain CECT 5716 will be quantified too), total bifidobacteria, enterobacteriaceae, clostridium difficile</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples</measure>
    <time_frame>1 year</time_frame>
    <description>Levels of total lactobacilli, Lactobacillus fermentum species (and if possible the strain CECT 5716 will be quantified too), total bifidobacteria, enterobacteriaceae, clostridium difficile</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples</measure>
    <time_frame>2 years</time_frame>
    <description>Levels of total lactobacilli, Lactobacillus fermentum species (and if possible the strain CECT 5716 will be quantified too), total bifidobacteria, enterobacteriaceae, clostridium difficile</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples</measure>
    <time_frame>3 years</time_frame>
    <description>Levels of total lactobacilli, Lactobacillus fermentum species (and if possible the strain CECT 5716 will be quantified too), total bifidobacteria, enterobacteriaceae, clostridium difficile</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analysis of fecal microbiota by molecular analysis from frozen stools in diarrhea samples</measure>
    <time_frame>1 year</time_frame>
    <description>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);</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fecal pH and levels of short chain fatty acids (SCFA) in planned stool samples</measure>
    <time_frame>4 months</time_frame>
    <description>short chain fatty acids (SCFA): acetate, propionate, butyrate;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fecal pH and levels of short chain fatty acids (SCFA) in planned stool samples</measure>
    <time_frame>1 year</time_frame>
    <description>short chain fatty acids (SCFA): acetate, propionate, butyrate;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fecal pH and levels of short chain fatty acids (SCFA) in planned stool samples</measure>
    <time_frame>2 years</time_frame>
    <description>short chain fatty acids (SCFA): acetate, propionate, butyrate;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fecal pH and levels of short chain fatty acids (SCFA) in planned stool samples</measure>
    <time_frame>3 years</time_frame>
    <description>short chain fatty acids (SCFA): acetate, propionate, butyrate;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characteristics of bowel movements and stools</measure>
    <time_frame>4 months</time_frame>
    <description>- assessed through a 3-day diary filled in by parents&#xD;
average daily number of bowel movements;&#xD;
(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&#xD;
average daily incidence of loose or watery stools (category A, subscale 'consistency' on Bekkali scale);&#xD;
dominant stool color per visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characteristics of bowel movements and stools</measure>
    <time_frame>6 months</time_frame>
    <description>- assessed through a 3-day diary filled in by parents&#xD;
average daily number of bowel movements;&#xD;
(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&#xD;
average daily incidence of loose or watery stools (category A, subscale 'consistency' on Bekkali scale);&#xD;
dominant stool color per visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characteristics of bowel movements and stools</measure>
    <time_frame>9 months</time_frame>
    <description>- assessed through a 3-day diary filled in by parents&#xD;
average daily number of bowel movements;&#xD;
(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&#xD;
average daily incidence of loose or watery stools (category A, subscale 'consistency' on Bekkali scale);&#xD;
dominant stool color per visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characteristics of bowel movements and stools</measure>
    <time_frame>1 year</time_frame>
    <description>- assessed through a 3-day diary filled in by parents&#xD;
average daily number of bowel movements;&#xD;
(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&#xD;
average daily incidence of loose or watery stools (category A, subscale 'consistency' on Bekkali scale);&#xD;
dominant stool color per visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characteristics of bowel movements and stools</measure>
    <time_frame>2 years</time_frame>
    <description>- assessed through a 3-day diary filled in by parents&#xD;
average daily number of bowel movements;&#xD;
(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&#xD;
average daily incidence of loose or watery stools (category A, subscale 'consistency' on Bekkali scale);&#xD;
dominant stool color per visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characteristics of bowel movements and stools</measure>
    <time_frame>3 years</time_frame>
    <description>- assessed through a 3-day diary filled in by parents&#xD;
average daily number of bowel movements;&#xD;
(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&#xD;
average daily incidence of loose or watery stools (category A, subscale 'consistency' on Bekkali scale);&#xD;
dominant stool color per visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characteristics of bowel movements during diarrhea episodes</measure>
    <time_frame>1 year</time_frame>
    <description>- assessed through a diary filled in by parents during diarrhea episodes&#xD;
average daily number of bowel movements per diarrhea episode;&#xD;
average duration (number of days) of diarrhea episodes;&#xD;
total number of days with diarrhea, within the first year of age (between V1 and V5);&#xD;
(average daily) Infant Stool Form scores consistency (4-point scale), amount (4-point scale) and color (6 categories) per diarrhea episode.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of fecal IgA and fecal calprotectin in planned stool samples</measure>
    <time_frame>4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of fecal IgA and fecal calprotectin in planned stool samples</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of fecal IgA and fecal calprotectin in planned stool samples</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of fecal IgA and fecal calprotectin in planned stool samples</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number and duration of infectious diseases</measure>
    <time_frame>3 years</time_frame>
    <description>Especially: otitis media, infections of upper and lower respiratory tract and of urinary tract;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number and duration of fever episodes;</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number and duration of antibiotic treatment.</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infants growth measured by anthropometric measurements</measure>
    <time_frame>4 weeks</time_frame>
    <description>weight, size, head circumference;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infants growth measured by anthropometric measurements</measure>
    <time_frame>4 months</time_frame>
    <description>weight, size, head circumference;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infants growth measured by anthropometric measurements</measure>
    <time_frame>6 months</time_frame>
    <description>weight, size, head circumference;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infants growth measured by anthropometric measurements</measure>
    <time_frame>9 months</time_frame>
    <description>weight, size, head circumference;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infants growth measured by anthropometric measurements</measure>
    <time_frame>1 year</time_frame>
    <description>weight, size, head circumference;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infants growth measured by anthropometric measurements</measure>
    <time_frame>2 years</time_frame>
    <description>weight, size, head circumference;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infants growth measured by anthropometric measurements</measure>
    <time_frame>3 years</time_frame>
    <description>weight, size, head circumference;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Child's behavior</measure>
    <time_frame>4 months</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- Average sleep duration and crying duration per 24 hours;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Child's behavior</measure>
    <time_frame>6 months</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- Average sleep duration and crying duration per 24 hours;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Child's behavior</measure>
    <time_frame>9 months</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- Average sleep duration and crying duration per 24 hours;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Child's behavior</measure>
    <time_frame>1 year</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- Average sleep duration and crying duration per 24 hours;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Child's behavior</measure>
    <time_frame>2 years</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- Average sleep duration and crying duration per 24 hours;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Child's behavior</measure>
    <time_frame>3 years</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- Average sleep duration and crying duration per 24 hours;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minor gastrointestinal disorders (digestive tolerance)</measure>
    <time_frame>4 months</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- average daily vomiting, regurgitation/reflux, flatulence, constipation (according to WHO definition);</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minor gastrointestinal disorders (digestive tolerance)</measure>
    <time_frame>6 months</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- average daily vomiting, regurgitation/reflux, flatulence, constipation (according to WHO definition);</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minor gastrointestinal disorders (digestive tolerance)</measure>
    <time_frame>9 months</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- average daily vomiting, regurgitation/reflux, flatulence, constipation (according to WHO definition);</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minor gastrointestinal disorders (digestive tolerance)</measure>
    <time_frame>1 year</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- average daily vomiting, regurgitation/reflux, flatulence, constipation (according to WHO definition);</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minor gastrointestinal disorders (digestive tolerance)</measure>
    <time_frame>2 years</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- average daily vomiting, regurgitation/reflux, flatulence, constipation (according to WHO definition);</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minor gastrointestinal disorders (digestive tolerance)</measure>
    <time_frame>3 years</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- average daily vomiting, regurgitation/reflux, flatulence, constipation (according to WHO definition);</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Suitability for daily use</measure>
    <time_frame>4 months</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- average daily consumption: drinking amounts and formula acceptance;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Suitability for daily use</measure>
    <time_frame>6 months</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- average daily consumption: drinking amounts and formula acceptance;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Suitability for daily use</measure>
    <time_frame>9 months</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- average daily consumption: drinking amounts and formula acceptance;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Suitability for daily use</measure>
    <time_frame>1 year</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- average daily consumption: drinking amounts and formula acceptance;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Suitability for daily use</measure>
    <time_frame>2 years</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- average daily consumption: drinking amounts and formula acceptance;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Suitability for daily use</measure>
    <time_frame>3 years</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- average daily consumption: drinking amounts and formula acceptance;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events (AE)</measure>
    <time_frame>4 months</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- Number of events, number of subjects showing adverse events, intensity and relationship of AE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events (AE)</measure>
    <time_frame>6 months</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- Number of events, number of subjects showing adverse events, intensity and relationship of AE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events (AE)</measure>
    <time_frame>9 months</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- Number of events, number of subjects showing adverse events, intensity and relationship of AE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events (AE)</measure>
    <time_frame>1 year</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- Number of events, number of subjects showing adverse events, intensity and relationship of AE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events (AE)</measure>
    <time_frame>2 years</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- Number of events, number of subjects showing adverse events, intensity and relationship of AE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events (AE)</measure>
    <time_frame>3 years</time_frame>
    <description>Assessed through a 3-day diary filled in by parents&#xD;
- Number of events, number of subjects showing adverse events, intensity and relationship of AE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number and duration of fever episodes;</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number and duration of antibiotic treatment.</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number and duration of infectious diseases</measure>
    <time_frame>1 year</time_frame>
    <description>Especially: otitis media, infections of upper and lower respiratory tract and of urinary tract;</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Microbiota results</measure>
    <time_frame>1 year</time_frame>
    <description>Phyla and families of bacteria in planned stools using 16S taxonomical metasequencing compared to the control formula in a sub-group of 96 infants only</description>
  </other_outcome>
  <other_outcome>
    <measure>Urinary D-Lactate and creatinine</measure>
    <time_frame>4 weeks</time_frame>
    <description>To assess change in the urinary lactate and creatinine (in a subgroup of 96 infants only) via ratio after 3 months of consumption of the supplemented infant formula, compared to the control formula</description>
  </other_outcome>
  <other_outcome>
    <measure>Urinary D-Lactate and creatinine</measure>
    <time_frame>4 months</time_frame>
    <description>To assess change in the urinary lactate and creatinine (in a subgroup of 96 infants only) via ratio after 3 months of consumption of the supplemented infant formula, compared to the control formula</description>
  </other_outcome>
  <other_outcome>
    <measure>Microbiota results</measure>
    <time_frame>4 months</time_frame>
    <description>Phyla and families of bacteria in planned stools using 16S taxonomical metasequencing compared to the control formula in a sub-group of 96 infants only</description>
  </other_outcome>
  <other_outcome>
    <measure>Microbiota results</measure>
    <time_frame>2 years</time_frame>
    <description>Phyla and families of bacteria in planned stools using 16S taxonomical metasequencing compared to the control formula in a sub-group of 96 infants only</description>
  </other_outcome>
  <other_outcome>
    <measure>Microbiota results</measure>
    <time_frame>3 years</time_frame>
    <description>Phyla and families of bacteria in planned stools using 16S taxonomical metasequencing compared to the control formula in a sub-group of 96 infants only</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">540</enrollment>
  <condition>Healthy Term Infants</condition>
  <arm_group>
    <arm_group_label>Synbiotic formula</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Synbiotic formula : standard formula enriched with a prebiotic fiber and a probiotic strain&#xD;
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.&#xD;
Route : oral, ad libitum&#xD;
Duration of product intake:&#xD;
Synbiotic IF : 5 months of consumption (from the inclusion until 6 months completed of age)&#xD;
Synbiotic FoF: 6 months of consumption (from 6 to 12 months of age)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control formula</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Control formula : standard formula without pre and probiotic&#xD;
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.&#xD;
Route: oral, ad libitum&#xD;
Duration of product intake:&#xD;
Control IF : 5 months of consumption (from the inclusion until 6 months completed of age)&#xD;
Control FoF : 6 months of consumption (from 6 to 12 months of age)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Breast-fed group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>- Breast milk as exclusive feeding (no more than one formula meal per day), from birth until at least 4 months of age. Then, when the mother decides to stop breastfeeding, the infants can consume any formula on parent's choice respecting forbidden products list.&#xD;
Dose:&#xD;
Breast milk : on demand&#xD;
Route : oral, ad libitum&#xD;
Duration of product intake:&#xD;
Breast milk : at least 4 month (from birth until at least 4 months of age)</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Synbiotic formula</intervention_name>
    <description>Standard milk formula enriched with a prebiotic fiber and a probiotic strain</description>
    <arm_group_label>Synbiotic formula</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Control formula</intervention_name>
    <description>Standard milk formula without pre and probiotic</description>
    <arm_group_label>Control formula</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy term infants&#xD;
&#xD;
          -  Female or male gender&#xD;
&#xD;
          -  Gestational age between 37 and 41 weeks completed (= 41 weeks + 6 days)&#xD;
&#xD;
          -  Age at time of V1 visit : 4 +/- 7 days&#xD;
&#xD;
          -  Birth weight between 2500 ans 4200g, with regular weight gain (≥ 150g / week)&#xD;
&#xD;
          -  Two legal representatives (parent(s) / guardian(s)) who are capable of and willing to&#xD;
             comply with the protocol and have signed the informed consent in accordance with legal&#xD;
             requirements.&#xD;
&#xD;
          -  at least one of the legal representatives is affiliated to with a social security&#xD;
             scheme.&#xD;
&#xD;
        Additionnaly , criteria of inclusion in one of the formula-fed groups or in the breast-fed&#xD;
        group, respectively, are the following:&#xD;
&#xD;
          -  To be included in one of the formula arm, infants will have to be exclusively&#xD;
             formula-fed (no breast milk meal) at the time of V1 visit (randomization).&#xD;
&#xD;
        or&#xD;
&#xD;
          -  To be included in the breastfeeding arm, infants will have to be exclusively&#xD;
             breast-fed (no more than one formula meal per day) at V1 visit (randomization) and its&#xD;
             mother will have to be willing to pursue exclusive breastfeeding at least until the&#xD;
             infant will be 4-month old.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Intensive care during at least the first 14 days of life&#xD;
&#xD;
          -  Neonatal health problems, such as: respiratory distress, asphyxia, hypoglycemia,&#xD;
             sepsis, NEC (necrotizing enterocolitis),...&#xD;
&#xD;
          -  Clinical evidence of chronic illness or gastrointestinal disorders such as : GER&#xD;
             (Gastrooesophageal Reflux), gastroenteritis,...&#xD;
&#xD;
          -  Known metabolic disorders, such as diabetes, lactose intolerance,....&#xD;
&#xD;
          -  Known immune deficiency&#xD;
&#xD;
          -  Subjects recommended to receive formula with hydrolized protein (e.g. children with&#xD;
             allergy risk)&#xD;
&#xD;
          -  Subject under oral antibiotic treatment at V1 visit&#xD;
&#xD;
          -  Participation in another biomedical study&#xD;
&#xD;
          -  Whose legal representatives have psychological or linguistic incapability to sign the&#xD;
             informed consent form&#xD;
&#xD;
          -  Reasons to presume that parents are unable to meet the study plan requirements (e.g.&#xD;
             impossibility to contact study representatives in case of emergency, drug addiction&#xD;
             etc)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Weeks</minimum_age>
    <maximum_age>5 Weeks</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hugues Piloquet, Pediatrician</last_name>
    <role>Principal Investigator</role>
  </overall_official>
  <location>
    <facility>
      <name>Elie JABBOUR</name>
      <address>
        <city>Gemozac</city>
        <state>Charente-Maritime</state>
        <zip>17260</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christophe VIEL</name>
      <address>
        <city>La Rochelle</city>
        <state>Charente-Maritime</state>
        <zip>17000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>C.I.C Pédiatrique - C.H.U. de Grenoble - Hôpital Couple-Enfant</name>
      <address>
        <city>Grenoble</city>
        <state>Isère</state>
        <zip>38043</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>C.I.C pédiatrique - C.H.U. de Nantes - Hôpital Mère-Enfant</name>
      <address>
        <city>Nantes</city>
        <state>Loire-Atlantique</state>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alain PALOMBA</name>
      <address>
        <city>Angers</city>
        <state>Maine-et-Loire</state>
        <zip>49000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christophe RONDEAU</name>
      <address>
        <city>Angers</city>
        <state>Maine-et-Loire</state>
        <zip>49000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Damien GODIN</name>
      <address>
        <city>Angers</city>
        <state>Maine-et-Loire</state>
        <zip>49000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Daniel GOMBAUD</name>
      <address>
        <city>Angers</city>
        <state>Maine-et-Loire</state>
        <zip>49000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jean-François FOUCAULT</name>
      <address>
        <city>Angers</city>
        <state>Maine-et-Loire</state>
        <zip>49000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Michel LAMBERT</name>
      <address>
        <city>Angers</city>
        <state>Maine-et-Loire</state>
        <zip>49000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nolwenn RONCERAY</name>
      <address>
        <city>Angers</city>
        <state>Maine-et-Loire</state>
        <zip>49000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Philippe REMAUD</name>
      <address>
        <city>Angers</city>
        <state>Maine-et-Loire</state>
        <zip>49000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pierre-André FERRAND</name>
      <address>
        <city>Angers</city>
        <state>Maine-et-Loire</state>
        <zip>49000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanessa BERNAND</name>
      <address>
        <city>Angers</city>
        <state>Maine-et-Loire</state>
        <zip>49000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Francisco MARTINEZ-CORTES</name>
      <address>
        <city>Angers</city>
        <state>Maine-et-Loire</state>
        <zip>49100</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Damien GUILLON</name>
      <address>
        <city>Angers</city>
        <state>Maine-et-Loire</state>
        <zip>49120</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christine REGIMBART</name>
      <address>
        <city>Becon Les Granits</city>
        <state>Maine-et-Loire</state>
        <zip>49370</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Antoine LEPELLETIER</name>
      <address>
        <city>Montreuil</city>
        <state>Maine-et-Loire</state>
        <zip>49460</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Benoit DAGUZAN</name>
      <address>
        <city>Segre</city>
        <state>Maine-et-Loire</state>
        <zip>49500</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Didier NOURRY</name>
      <address>
        <city>Tierce</city>
        <state>Maine-et-Loire</state>
        <zip>49125</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Philippe IGIGABEL</name>
      <address>
        <city>Tierce</city>
        <state>Maine-et-Loire</state>
        <zip>49125</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alain BATY</name>
      <address>
        <city>Laval</city>
        <state>Mayenne</state>
        <zip>53000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christian DUROY</name>
      <address>
        <city>Laval</city>
        <state>Mayenne</state>
        <zip>53000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>François RICHARD</name>
      <address>
        <city>Laval</city>
        <state>Mayenne</state>
        <zip>53000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Patrick ROBERT</name>
      <address>
        <city>Laval</city>
        <state>Mayenne</state>
        <zip>53000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>January 4, 2022</last_update_submitted>
  <last_update_submitted_qc>January 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>synbiotic formula</keyword>
  <keyword>infant formula</keyword>
  <keyword>diarrhea</keyword>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02221687
org study id: 505564 - PEC10561
nct id: NCT02221687
lead sponsor: 
collaborator: 
has dmc: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Investigator)
measure: (Cumulative) number of infectious diarrhea episodes per subject during the first year of life.
time frame: one year
description: 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.
measure: Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples
time frame: 4 months
description: Levels of total lactobacilli, Lactobacillus fermentum species (and if possible the strain CECT 5716 will be quantified too), total bifidobacteria, enterobacteriaceae, clostridium difficile
measure: Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples
time frame: 1 year
description: Levels of total lactobacilli, Lactobacillus fermentum species (and if possible the strain CECT 5716 will be quantified too), total bifidobacteria, enterobacteriaceae, clostridium difficile
measure: Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples
time frame: 2 years
description: Levels of total lactobacilli, Lactobacillus fermentum species (and if possible the strain CECT 5716 will be quantified too), total bifidobacteria, enterobacteriaceae, clostridium difficile
measure: Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples
time frame: 3 years
description: Levels of total lactobacilli, Lactobacillus fermentum species (and if possible the strain CECT 5716 will be quantified too), total bifidobacteria, enterobacteriaceae, clostridium difficile
measure: Analysis of fecal microbiota by molecular analysis from frozen stools in diarrhea samples
time frame: 1 year
description: 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);
measure: Fecal pH and levels of short chain fatty acids (SCFA) in planned stool samples
time frame: 4 months
description: short chain fatty acids (SCFA): acetate, propionate, butyrate;
measure: Fecal pH and levels of short chain fatty acids (SCFA) in planned stool samples
time frame: 1 year
description: short chain fatty acids (SCFA): acetate, propionate, butyrate;
measure: Fecal pH and levels of short chain fatty acids (SCFA) in planned stool samples
time frame: 2 years
description: short chain fatty acids (SCFA): acetate, propionate, butyrate;
measure: Fecal pH and levels of short chain fatty acids (SCFA) in planned stool samples
time frame: 3 years
description: short chain fatty acids (SCFA): acetate, propionate, butyrate;
measure: Characteristics of bowel movements and stools
time frame: 4 months
description: - 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 visit
measure: Characteristics of bowel movements and stools
time frame: 6 months
description: - 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 visit
measure: Characteristics of bowel movements and stools
time frame: 9 months
description: - 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 visit
measure: Characteristics of bowel movements and stools
time frame: 1 year
description: - 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 visit
measure: Characteristics of bowel movements and stools
time frame: 2 years
description: - 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 visit
measure: Characteristics of bowel movements and stools
time frame: 3 years
description: - 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 visit
measure: Characteristics of bowel movements during diarrhea episodes
time frame: 1 year
description: - 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.
measure: Levels of fecal IgA and fecal calprotectin in planned stool samples
time frame: 4 months
measure: Levels of fecal IgA and fecal calprotectin in planned stool samples
time frame: 1 year
measure: Levels of fecal IgA and fecal calprotectin in planned stool samples
time frame: 2 years
measure: Levels of fecal IgA and fecal calprotectin in planned stool samples
time frame: 3 years
measure: Number and duration of infectious diseases
time frame: 3 years
description: Especially: otitis media, infections of upper and lower respiratory tract and of urinary tract;
measure: Number and duration of fever episodes;
time frame: 3 years
measure: Number and duration of antibiotic treatment.
time frame: 3 years
measure: Infants growth measured by anthropometric measurements
time frame: 4 weeks
description: weight, size, head circumference;
measure: Infants growth measured by anthropometric measurements
time frame: 4 months
description: weight, size, head circumference;
measure: Infants growth measured by anthropometric measurements
time frame: 6 months
description: weight, size, head circumference;
measure: Infants growth measured by anthropometric measurements
time frame: 9 months
description: weight, size, head circumference;
measure: Infants growth measured by anthropometric measurements
time frame: 1 year
description: weight, size, head circumference;
measure: Infants growth measured by anthropometric measurements
time frame: 2 years
description: weight, size, head circumference;
measure: Infants growth measured by anthropometric measurements
time frame: 3 years
description: weight, size, head circumference;
measure: Child's behavior
time frame: 4 months
description: Assessed through a 3-day diary filled in by parents
- Average sleep duration and crying duration per 24 hours;
measure: Child's behavior
time frame: 6 months
description: Assessed through a 3-day diary filled in by parents
- Average sleep duration and crying duration per 24 hours;
measure: Child's behavior
time frame: 9 months
description: Assessed through a 3-day diary filled in by parents
- Average sleep duration and crying duration per 24 hours;
measure: Child's behavior
time frame: 1 year
description: Assessed through a 3-day diary filled in by parents
- Average sleep duration and crying duration per 24 hours;
measure: Child's behavior
time frame: 2 years
description: Assessed through a 3-day diary filled in by parents
- Average sleep duration and crying duration per 24 hours;
measure: Child's behavior
time frame: 3 years
description: Assessed through a 3-day diary filled in by parents
- Average sleep duration and crying duration per 24 hours;
measure: Minor gastrointestinal disorders (digestive tolerance)
time frame: 4 months
description: Assessed through a 3-day diary filled in by parents
- average daily vomiting, regurgitation/reflux, flatulence, constipation (according to WHO definition);
measure: Minor gastrointestinal disorders (digestive tolerance)
time frame: 6 months
description: Assessed through a 3-day diary filled in by parents
- average daily vomiting, regurgitation/reflux, flatulence, constipation (according to WHO definition);
measure: Minor gastrointestinal disorders (digestive tolerance)
time frame: 9 months
description: Assessed through a 3-day diary filled in by parents
- average daily vomiting, regurgitation/reflux, flatulence, constipation (according to WHO definition);
measure: Minor gastrointestinal disorders (digestive tolerance)
time frame: 1 year
description: Assessed through a 3-day diary filled in by parents
- average daily vomiting, regurgitation/reflux, flatulence, constipation (according to WHO definition);
measure: Minor gastrointestinal disorders (digestive tolerance)
time frame: 2 years
description: Assessed through a 3-day diary filled in by parents
- average daily vomiting, regurgitation/reflux, flatulence, constipation (according to WHO definition);
measure: Minor gastrointestinal disorders (digestive tolerance)
time frame: 3 years
description: Assessed through a 3-day diary filled in by parents
- average daily vomiting, regurgitation/reflux, flatulence, constipation (according to WHO definition);
measure: Suitability for daily use
time frame: 4 months
description: Assessed through a 3-day diary filled in by parents
- average daily consumption: drinking amounts and formula acceptance;
measure: Suitability for daily use
time frame: 6 months
description: Assessed through a 3-day diary filled in by parents
- average daily consumption: drinking amounts and formula acceptance;
measure: Suitability for daily use
time frame: 9 months
description: Assessed through a 3-day diary filled in by parents
- average daily consumption: drinking amounts and formula acceptance;
measure: Suitability for daily use
time frame: 1 year
description: Assessed through a 3-day diary filled in by parents
- average daily consumption: drinking amounts and formula acceptance;
measure: Suitability for daily use
time frame: 2 years
description: Assessed through a 3-day diary filled in by parents
- average daily consumption: drinking amounts and formula acceptance;
measure: Suitability for daily use
time frame: 3 years
description: Assessed through a 3-day diary filled in by parents
- average daily consumption: drinking amounts and formula acceptance;
measure: Adverse events (AE)
time frame: 4 months
description: Assessed through a 3-day diary filled in by parents
- Number of events, number of subjects showing adverse events, intensity and relationship of AE.
measure: Adverse events (AE)
time frame: 6 months
description: Assessed through a 3-day diary filled in by parents
- Number of events, number of subjects showing adverse events, intensity and relationship of AE.
measure: Adverse events (AE)
time frame: 9 months
description: Assessed through a 3-day diary filled in by parents
- Number of events, number of subjects showing adverse events, intensity and relationship of AE.
measure: Adverse events (AE)
time frame: 1 year
description: Assessed through a 3-day diary filled in by parents
- Number of events, number of subjects showing adverse events, intensity and relationship of AE.
measure: Adverse events (AE)
time frame: 2 years
description: Assessed through a 3-day diary filled in by parents
- Number of events, number of subjects showing adverse events, intensity and relationship of AE.
measure: Adverse events (AE)
time frame: 3 years
description: Assessed through a 3-day diary filled in by parents
- Number of events, number of subjects showing adverse events, intensity and relationship of AE.
measure: Number and duration of fever episodes;
time frame: 1 year
measure: Number and duration of antibiotic treatment.
time frame: 1 year
measure: Number and duration of infectious diseases
time frame: 1 year
description: Especially: otitis media, infections of upper and lower respiratory tract and of urinary tract;
measure: Microbiota results
time frame: 1 year
description: Phyla and families of bacteria in planned stools using 16S taxonomical metasequencing compared to the control formula in a sub-group of 96 infants only
measure: Urinary D-Lactate and creatinine
time frame: 4 weeks
description: To assess change in the urinary lactate and creatinine (in a subgroup of 96 infants only) via ratio after 3 months of consumption of the supplemented infant formula, compared to the control formula
measure: Urinary D-Lactate and creatinine
time frame: 4 months
description: To assess change in the urinary lactate and creatinine (in a subgroup of 96 infants only) via ratio after 3 months of consumption of the supplemented infant formula, compared to the control formula
measure: Microbiota results
time frame: 4 months
description: Phyla and families of bacteria in planned stools using 16S taxonomical metasequencing compared to the control formula in a sub-group of 96 infants only
measure: Microbiota results
time frame: 2 years
description: Phyla and families of bacteria in planned stools using 16S taxonomical metasequencing compared to the control formula in a sub-group of 96 infants only
measure: Microbiota results
time frame: 3 years
description: Phyla and families of bacteria in planned stools using 16S taxonomical metasequencing compared to the control formula in a sub-group of 96 infants only
arm group label: Synbiotic formula
arm group type: Experimental
description: 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)
arm group label: Control formula
arm group type: Placebo Comparator
description: 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)
arm group label: Breast-fed group
arm group type: No Intervention
description: - Breast milk as exclusive feeding (no more than one formula meal per day), from birth until at least 4 months of age. Then, when the mother decides to stop breastfeeding, the infants can consume any formula on parent's choice respecting forbidden products list.
Dose:
Breast milk : on demand
Route : oral, ad libitum
Duration of product intake:
Breast milk : at least 4 month (from birth until at least 4 months of age)
intervention type: Dietary Supplement
intervention name: Synbiotic formula
description: Standard milk formula enriched with a prebiotic fiber and a probiotic strain
arm group label: Synbiotic formula
intervention type: Dietary Supplement
intervention name: Control formula
description: Standard milk formula without pre and probiotic
arm group label: Control formula
criteria: 
gender: All
minimum age: 3 Weeks
maximum age: 5 Weeks
healthy volunteers: Accepts Healthy Volunteers
last name: Hugues Piloquet, Pediatrician
role: Principal Investigator
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor