xml: <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/NCT05973812</url>
    </required_header>
    <id_info>
      <org_study_id>SAFEBIF1</org_study_id>
      <nct_id>NCT05973812</nct_id>
    </id_info>
    <brief_title>Safety of Bifidobacterium Breve PS1 for Infants</brief_title>
    <official_title>Evaluation of the Safety of an Infant Formula Containing Bifidobacterium Breve PS1, a Strain Isolated From Human Milk, in a Pilot Trial.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Universidad Complutense de Madrid</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Hospital General Universitario Gregorio Marañon</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Gerencia de Atención Primaria, Madrid</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Universidad Complutense de Madrid</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The objective of this work was the characterization of the probiotic potential of&#xD;
        Bifidobacterium breve PS1, a strain originally isolated from human milk. Subsequently, its&#xD;
        safety and tolerance were evaluated in a trial including healthy, formula-fed 3-months-old&#xD;
        infants. A total of 187 infants were randomized into two groups: probiotic group (PG) and&#xD;
        control group (CG). Both groups received the same infant formula but, in the case of the PG,&#xD;
        it was supplemented with the strain. A total of 160 infants (80 per group) completed the&#xD;
        three months of intervention.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Introduction Some perinatal circumstances, such as the mode of birth, can alter the&#xD;
        composition of the infant gut microbiota. As an example, infants born by caesarean section&#xD;
        are prone to gut dysbiosis (including a depletion of bifidobacteria) in comparison with those&#xD;
        born by vaginal delivery, leading to an increased rate of gastrointestinal and respiratory&#xD;
        tract infections. Interestingly, breastfeeding can restore the Bifidobacterium population,&#xD;
        which in turn was associated with a decrease in the rate of various infections.&#xD;
  &#xD;
        Despite the important functions that bifidobacteria may play in the infant gut, some studies&#xD;
        have shown that these bacteria may be present at a low concentration or even ab-sent in some&#xD;
        infants. Some factors, including lack of breastfeeding, early weaning, maternal/infant&#xD;
        antibiotic therapy or HMO composition may select against bifidobacteria in the mother-infant&#xD;
        dyad. Therefore, there is a need for strategies to develop functional foods, including infant&#xD;
        formula, to provide bifidobacterial strains naturally present in human milk to infants who&#xD;
        may be deprived of such microbes. In this context, the objectives of this work were, first,&#xD;
        to characterize of the potential probiotic properties of a bifidobacterial strain isolated&#xD;
        from human milk and, subsequently, to test its safety and tolerance in a population of&#xD;
        3-months-old formula-fed infants&#xD;
  &#xD;
        Materials and Methods Study Design A randomized double-blinded controlled intervention study&#xD;
        with two study groups was carried out. Healthy, three month old infants, who due to their&#xD;
        mothers' choice were exclusively formula-fed from birth, were recruited into the study after&#xD;
        informed written consent was obtained from the parents. Investigators took special&#xD;
        precautions and care throughout their communication with the families in order to support and&#xD;
        protect, and not to discourage breastfeeding, and not to suggest bottle feeding to parents of&#xD;
        a breastfed baby. The exclusion criteria included history of mild or serious gastrointestinal&#xD;
        disorders (history of chronic diarrhea or constipation, gastroesophageal reflux),&#xD;
        gastrointestinal surgery, cow's milk protein allergy, metabolic disorders (diabetes, lactose&#xD;
        intolerance), immune deficiency, antibiotic prescription three-weeks prior to inclusion and&#xD;
        previous use of probiotic-containing formula. Exclusion criteria during the study were lack&#xD;
        of compliance with the study protocol, adverse events related to the consumption of the study&#xD;
        formula, not attending scheduled visits to the primary care center, and severe regurgitation&#xD;
        and/or colic that, according to pediatricians, needed prescription of a special formula.&#xD;
  &#xD;
        The protocol was approved by the Ethics Committee of the Hospital Clínico (Madrid, Spain)&#xD;
        (Reference 10/017-E).&#xD;
  &#xD;
        Sample size Sample size was estimated based on the primary outcome of average weight gain of&#xD;
        infants between baseline visit and visit 1 (180 ± 5 days of age). Based on previous&#xD;
        publications where growth was the primary outcome variable as part of a safety study, the&#xD;
        study was designed to have a power to detect a difference in weight gain equal to 0.5&#xD;
        standard deviations. Thus, at least 65 children would be needed in each formula group under&#xD;
        the assumption of non-inferiority (one-sided test), with a significance level of 2.5% and&#xD;
        power of 80%.&#xD;
  &#xD;
        Study Formula A total of 187 infants (3-month-old) were enrolled and randomized into two&#xD;
        study groups (probiotic group [PG] and control group [CG]), according to a randomization&#xD;
        generated by a computer program. Infants received one of the following formula: (a) CG: a&#xD;
        standard powdered infant formula (HiPP 1, 600 g) with a nutritional composition in accordance&#xD;
        with current EU regulations, and (b) PG: the same formula supplemented with B. breve PS1 at a&#xD;
        concentration dose of 107 cfu/g of formula. B. breve PS1 was produced in the facilities of&#xD;
        Biopolis (Valencia, Spain). Both formulas were consumed by the infants until the age of 6&#xD;
        months (3 months' intervention period).&#xD;
  &#xD;
        The concentration of the probiotic in the formula was analyzed and confirmed before and at&#xD;
        the end of the study. The original HiPP infant formula was purchased and prepared for the&#xD;
        appropriate use in a double-blind intervention trial. Therefore, the formula pow-der was&#xD;
        transferred to plain white undistinguishable tins and a subset was supplemented with the&#xD;
        strain PS1.&#xD;
  &#xD;
        Preparation of both formulae were performed in a clean room provided of a aseptic pack-age&#xD;
        device in the facilities of the Dpt. of Galenic Pharmacy and Food Technology of the&#xD;
        Complutense University of Madrid. All study personnel (pediatricians and researchers) as well&#xD;
        as parents were kept blinded throughout the entire study period. The group assignment was&#xD;
        only revealed upon completion of the statistical analysis. The pediatricians prescribed the&#xD;
        amounts of formula per day to be administered to the infants following ESPGHAN guidelines.&#xD;
  &#xD;
        Study outcomes Infants were scheduled to receive two clinical evaluations during the&#xD;
        intervention period: at baseline (3 months of age) and at the end of the study (6 months of&#xD;
        age). The primary outcome of the trial was average weight gain between baseline evaluation&#xD;
        and 6 months of age. Secondary outcomes included average length and head circumference gain,&#xD;
        ad-verse events associated with formula consumption, fecal bifidobacteria levels, and fecal&#xD;
        concentration of short-chain fatty acids (SCFA).&#xD;
  &#xD;
        Fecal sample collection and analysis Fecal samples were collected from the diaper at both&#xD;
        study visits. Each fecal sample from each participant and sampling time was aliquoted in four&#xD;
        parts, preserved at -20 °C and processed within 1 week. Three aliquots were used to evaluate&#xD;
        the defined study parameters, and the remaining fourth aliquot was stored at -80 °C.&#xD;
  &#xD;
        Bifidobacterial quantification in feces was performed by plating decimal dilutions of the&#xD;
        samples on MRS plates supplemented with L-cysteine (0.5 g/L) (MRS-Cys) agar plates, which&#xD;
        were incubated anaerobically (85% nitrogen, 10% hydrogen, 5% carbon dioxide) in an anaerobic&#xD;
        workstation (MINI-MACS; DW Scientific, Shipley, United Kingdom) for 72 h at 37ºC. The&#xD;
        enumeration included the colonies that corresponded to Gram-positive catalase-negative and&#xD;
        F6PPK-positive. The detection and quantification of B. breve DNA in the fecal samples was&#xD;
        performed by real-time quantitative PCR as previously described.&#xD;
  &#xD;
        For short chain fatty acids (SCFA) quantification, fecal samples were homogenized with 150 mM&#xD;
        NaHCO3 (pH 7.8) (1:5, wt/v) in an argon atmosphere. Samples were incubated for fermentation&#xD;
        during 24 h at 37°C and stored at -80 °C until the extraction. The extraction of SCFA was&#xD;
        performed by gas chromatography.&#xD;
  &#xD;
        Statistical Analysis The quantitative data were expressed descriptively as the mean and&#xD;
        standard deviation (SD). When not normally distributed, the data were presented as the median&#xD;
        and inter-quartile range (IQR).&#xD;
  &#xD;
        Anthropometric measurement data were summarized using the mean and standard deviation (SD),&#xD;
        while intestinal bacterial counts were summarized by median and inter-quartile range (IQR).&#xD;
        In addition, anthropometric measurements were converted to age and gender standardized&#xD;
        z-scores using the methodology recommended by the WHO and implemented in the R package anthro&#xD;
        version 1.0.0. Next, the student's t-test was used to compare means by treatment group of the&#xD;
        z scores for weight, length and head circumference at the 6-month time point. Intestinal&#xD;
        bacterial counts were compared using the Mann-Whitney-U non-parametric test. The tests were&#xD;
        performed at the two-sided 5% significance level and the 95% confidence intervals were&#xD;
        obtained for the estimates. For all the comparisons, differences were considered significant&#xD;
        at p&lt; 0.05. The statistical analyses were conducted using R version 4.2.1&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">December 12, 2012</start_date>
    <completion_date type="Actual">March 12, 2015</completion_date>
    <primary_completion_date type="Actual">July 29, 2014</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>
      <intervention_model_description>Infants were classified into 2 groups. All infants in the probiotic group consumed an infant formula containing a freeze-dried probiotic (7 log10 CFU of B. breve PS1 per gram of formula). All infants in the control group consumed the same formula but without probiotic supplementation.</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Triple (Participant, Care Provider, Investigator)</masking>
      <masking_description>Only one person of the research team (statistician) knew the correspondence between each reference (one reference per each subject) and the arm (probiotic or control). The codes were blinded for the participant, the care provider and the investigator.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Weight gain</measure>
      <time_frame>3 months</time_frame>
      <description>Measurement of weight gain (kg)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Length</measure>
      <time_frame>3 months</time_frame>
      <description>Measurement of length (cm)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Head circumference</measure>
      <time_frame>3 months</time_frame>
      <description>Measurement of head circumference (cm)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Modification of the fecal microbiota</measure>
      <time_frame>3 months</time_frame>
      <description>Variation in the concentration of bifidobacteria in fecal samples</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Modification of the fecal concentration of short-chain fatty acids</measure>
      <time_frame>3 months</time_frame>
      <description>Variation in the concentration of butyrate, propionate and acetate in the fecal samples</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Actual">80</enrollment>
    <condition>Infant Development</condition>
    <condition>Safety Issues</condition>
    <arm_group>
      <arm_group_label>Probiotic group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>All infants (3-months-old) in the probiotic group consumed an infant formula supplemented with a freeze-dried probiotic (7 log10 colony-forming units [CFU] of B. breve PS1 per gram of formula) for 3 months.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_type>Sham Comparator</arm_group_type>
      <description>All infants (3-months-old) in the control group consumed the same infant formula but without probiotic supplementation.</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Infant formula supplemented with Bifidobacterium breve PS1</intervention_name>
      <description>Feeding with an infant formula containing 7 log10 cfu of the strain per gram of formula.</description>
      <arm_group_label>Probiotic group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Infant formula NOT supplemented with Bifidobacterium breve PS1</intervention_name>
      <description>Feeding with the same infant formula but without supplementation with the B. breve strain</description>
      <arm_group_label>Control group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Healthy 3-months-old infants&#xD;
  &#xD;
            -  Formula-fed infants from birth&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History of mild or serious gastrointestinal disorders (history of chronic diarrhea or&#xD;
               constipation, gastroesophageal reflux)&#xD;
  &#xD;
            -  Gastrointestinal surgery&#xD;
  &#xD;
            -  Cow's milk protein allergy&#xD;
  &#xD;
            -  Metabolic disorders (diabetes, lactose intolerance)&#xD;
  &#xD;
            -  Immune deficiency&#xD;
  &#xD;
            -  Antibiotic prescription three-weeks prior to inclusion&#xD;
  &#xD;
            -  Previous use of probiotic-containing formula.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>3 Months</minimum_age>
      <maximum_age>3 Months</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Juan M Rodríguez, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Universidad Complutense de Madrid</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Hospital Gregorio Marañón</name>
        <address>
          <city>Madrid</city>
          <zip>28007</zip>
          <country>Spain</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Universidad Complutense de Madrid</name>
        <address>
          <city>Madrid</city>
          <zip>28040</zip>
          <country>Spain</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Centro de Atención Primaria Silvano</name>
        <address>
          <city>Madrid</city>
          <zip>28043</zip>
          <country>Spain</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Spain</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 16, 2023</study_first_submitted>
    <study_first_submitted_qc>July 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 3, 2023</study_first_posted>
    <last_update_submitted>July 25, 2023</last_update_submitted>
    <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 3, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Universidad Complutense de Madrid</investigator_affiliation>
      <investigator_full_name>Juan M. Rodríguez</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>IPD will be available to other researchers once the study is published.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_time_frame>All the data will be available to other researchers once the study is published.</ipd_time_frame>
      <ipd_access_criteria>Data will be available after the publication of the study in an open access journal. They will be provided on request.</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05973812
  org study id: SAFEBIF1
  nct id: NCT05973812
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The objective of this work was the characterization of the probiotic potential of
        Bifidobacterium breve PS1, a strain originally isolated from human milk. Subsequently, its
        safety and tolerance were evaluated in a trial including healthy, formula-fed 3-months-old
        infants. A total of 187 infants were randomized into two groups: probiotic group (PG) and
        control group (CG). Both groups received the same infant formula but, in the case of the PG,
        it was supplemented with the strain. A total of 160 infants (80 per group) completed the
        three months of intervention.
  Introduction Some perinatal circumstances, such as the mode of birth, can alter the
        composition of the infant gut microbiota. As an example, infants born by caesarean section
        are prone to gut dysbiosis (including a depletion of bifidobacteria) in comparison with those
        born by vaginal delivery, leading to an increased rate of gastrointestinal and respiratory
        tract infections. Interestingly, breastfeeding can restore the Bifidobacterium population,
        which in turn was associated with a decrease in the rate of various infections.
  
        Despite the important functions that bifidobacteria may play in the infant gut, some studies
        have shown that these bacteria may be present at a low concentration or even ab-sent in some
        infants. Some factors, including lack of breastfeeding, early weaning, maternal/infant
        antibiotic therapy or HMO composition may select against bifidobacteria in the mother-infant
        dyad. Therefore, there is a need for strategies to develop functional foods, including infant
        formula, to provide bifidobacterial strains naturally present in human milk to infants who
        may be deprived of such microbes. In this context, the objectives of this work were, first,
        to characterize of the potential probiotic properties of a bifidobacterial strain isolated
        from human milk and, subsequently, to test its safety and tolerance in a population of
        3-months-old formula-fed infants
  
        Materials and Methods Study Design A randomized double-blinded controlled intervention study
        with two study groups was carried out. Healthy, three month old infants, who due to their
        mothers' choice were exclusively formula-fed from birth, were recruited into the study after
        informed written consent was obtained from the parents. Investigators took special
        precautions and care throughout their communication with the families in order to support and
        protect, and not to discourage breastfeeding, and not to suggest bottle feeding to parents of
        a breastfed baby. The exclusion criteria included history of mild or serious gastrointestinal
        disorders (history of chronic diarrhea or constipation, gastroesophageal reflux),
        gastrointestinal surgery, cow's milk protein allergy, metabolic disorders (diabetes, lactose
        intolerance), immune deficiency, antibiotic prescription three-weeks prior to inclusion and
        previous use of probiotic-containing formula. Exclusion criteria during the study were lack
        of compliance with the study protocol, adverse events related to the consumption of the study
        formula, not attending scheduled visits to the primary care center, and severe regurgitation
        and/or colic that, according to pediatricians, needed prescription of a special formula.
  
        The protocol was approved by the Ethics Committee of the Hospital Clínico (Madrid, Spain)
        (Reference 10/017-E).
  
        Sample size Sample size was estimated based on the primary outcome of average weight gain of
        infants between baseline visit and visit 1 (180 ± 5 days of age). Based on previous
        publications where growth was the primary outcome variable as part of a safety study, the
        study was designed to have a power to detect a difference in weight gain equal to 0.5
        standard deviations. Thus, at least 65 children would be needed in each formula group under
        the assumption of non-inferiority (one-sided test), with a significance level of 2.5% and
        power of 80%.
  
        Study Formula A total of 187 infants (3-month-old) were enrolled and randomized into two
        study groups (probiotic group [PG] and control group [CG]), according to a randomization
        generated by a computer program. Infants received one of the following formula: (a) CG: a
        standard powdered infant formula (HiPP 1, 600 g) with a nutritional composition in accordance
        with current EU regulations, and (b) PG: the same formula supplemented with B. breve PS1 at a
        concentration dose of 107 cfu/g of formula. B. breve PS1 was produced in the facilities of
        Biopolis (Valencia, Spain). Both formulas were consumed by the infants until the age of 6
        months (3 months' intervention period).
  
        The concentration of the probiotic in the formula was analyzed and confirmed before and at
        the end of the study. The original HiPP infant formula was purchased and prepared for the
        appropriate use in a double-blind intervention trial. Therefore, the formula pow-der was
        transferred to plain white undistinguishable tins and a subset was supplemented with the
        strain PS1.
  
        Preparation of both formulae were performed in a clean room provided of a aseptic pack-age
        device in the facilities of the Dpt. of Galenic Pharmacy and Food Technology of the
        Complutense University of Madrid. All study personnel (pediatricians and researchers) as well
        as parents were kept blinded throughout the entire study period. The group assignment was
        only revealed upon completion of the statistical analysis. The pediatricians prescribed the
        amounts of formula per day to be administered to the infants following ESPGHAN guidelines.
  
        Study outcomes Infants were scheduled to receive two clinical evaluations during the
        intervention period: at baseline (3 months of age) and at the end of the study (6 months of
        age). The primary outcome of the trial was average weight gain between baseline evaluation
        and 6 months of age. Secondary outcomes included average length and head circumference gain,
        ad-verse events associated with formula consumption, fecal bifidobacteria levels, and fecal
        concentration of short-chain fatty acids (SCFA).
  
        Fecal sample collection and analysis Fecal samples were collected from the diaper at both
        study visits. Each fecal sample from each participant and sampling time was aliquoted in four
        parts, preserved at -20 °C and processed within 1 week. Three aliquots were used to evaluate
        the defined study parameters, and the remaining fourth aliquot was stored at -80 °C.
  
        Bifidobacterial quantification in feces was performed by plating decimal dilutions of the
        samples on MRS plates supplemented with L-cysteine (0.5 g/L) (MRS-Cys) agar plates, which
        were incubated anaerobically (85% nitrogen, 10% hydrogen, 5% carbon dioxide) in an anaerobic
        workstation (MINI-MACS; DW Scientific, Shipley, United Kingdom) for 72 h at 37ºC. The
        enumeration included the colonies that corresponded to Gram-positive catalase-negative and
        F6PPK-positive. The detection and quantification of B. breve DNA in the fecal samples was
        performed by real-time quantitative PCR as previously described.
  
        For short chain fatty acids (SCFA) quantification, fecal samples were homogenized with 150 mM
        NaHCO3 (pH 7.8) (1:5, wt/v) in an argon atmosphere. Samples were incubated for fermentation
        during 24 h at 37°C and stored at -80 °C until the extraction. The extraction of SCFA was
        performed by gas chromatography.
  
        Statistical Analysis The quantitative data were expressed descriptively as the mean and
        standard deviation (SD). When not normally distributed, the data were presented as the median
        and inter-quartile range (IQR).
  
        Anthropometric measurement data were summarized using the mean and standard deviation (SD),
        while intestinal bacterial counts were summarized by median and inter-quartile range (IQR).
        In addition, anthropometric measurements were converted to age and gender standardized
        z-scores using the methodology recommended by the WHO and implemented in the R package anthro
        version 1.0.0. Next, the student's t-test was used to compare means by treatment group of the
        z scores for weight, length and head circumference at the 6-month time point. Intestinal
        bacterial counts were compared using the Mann-Whitney-U non-parametric test. The tests were
        performed at the two-sided 5% significance level and the 95% confidence intervals were
        obtained for the estimates. For all the comparisons, differences were considered significant
        at p< 0.05. The statistical analyses were conducted using R version 4.2.1
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Infants were classified into 2 groups. All infants in the probiotic group consumed an infant formula containing a freeze-dried probiotic (7 log10 CFU of B. breve PS1 per gram of formula). All infants in the control group consumed the same formula but without probiotic supplementation.
  primary purpose: Basic Science
  masking: Triple (Participant, Care Provider, Investigator)
  masking description: Only one person of the research team (statistician) knew the correspondence between each reference (one reference per each subject) and the arm (probiotic or control). The codes were blinded for the participant, the care provider and the investigator.
  measure: Weight gain
  time frame: 3 months
  description: Measurement of weight gain (kg)
  measure: Length
  time frame: 3 months
  description: Measurement of length (cm)
  measure: Head circumference
  time frame: 3 months
  description: Measurement of head circumference (cm)
  measure: Modification of the fecal microbiota
  time frame: 3 months
  description: Variation in the concentration of bifidobacteria in fecal samples
  measure: Modification of the fecal concentration of short-chain fatty acids
  time frame: 3 months
  description: Variation in the concentration of butyrate, propionate and acetate in the fecal samples
  arm group label: Probiotic group
  arm group type: Experimental
  description: All infants (3-months-old) in the probiotic group consumed an infant formula supplemented with a freeze-dried probiotic (7 log10 colony-forming units [CFU] of B. breve PS1 per gram of formula) for 3 months.
  arm group label: Control group
  arm group type: Sham Comparator
  description: All infants (3-months-old) in the control group consumed the same infant formula but without probiotic supplementation.
  intervention type: Dietary Supplement
  intervention name: Infant formula supplemented with Bifidobacterium breve PS1
  description: Feeding with an infant formula containing 7 log10 cfu of the strain per gram of formula.
  arm group label: Probiotic group
  intervention type: Dietary Supplement
  intervention name: Infant formula NOT supplemented with Bifidobacterium breve PS1
  description: Feeding with the same infant formula but without supplementation with the B. breve strain
  arm group label: Control group
  criteria: 
  gender: All
  minimum age: 3 Months
  maximum age: 3 Months
  healthy volunteers: Accepts Healthy Volunteers
  last name: Juan M Rodríguez, PhD
  role: Principal Investigator
  affiliation: Universidad Complutense de Madrid
  facility: 
  facility: 
  facility: 
  country: Spain
  responsible party type: Principal Investigator
  investigator affiliation: Universidad Complutense de Madrid
  investigator full name: Juan M. Rodríguez
  investigator title: Professor
  sharing ipd: Yes
  ipd description: IPD will be available to other researchers once the study is published.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Informed Consent Form (ICF)
  ipd time frame: All the data will be available to other researchers once the study is published.
  ipd access criteria: Data will be available after the publication of the study in an open access journal. They will be provided on request.