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/NCT06037421</url>
    </required_header>
    <id_info>
      <org_study_id>2023-A01731-44</org_study_id>
      <nct_id>NCT06037421</nct_id>
    </id_info>
    <brief_title>Metagenomic Analysis of Bacterial Microbiota in Breast Milk</brief_title>
    <acronym>MIC-LAMA2</acronym>
    <official_title>Metagenomic Analysis of Bacterial Microbiota in Breast Milk</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Centre Hospitalier Sud Francilien</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Centre Hospitalier Sud Francilien</source>
    <oversight_info>
      <has_dmc>No</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 aim of this study is to determine the extent to which bacteria in the breast milk&#xD;
        microbiota represent an infectious risk for premature infants, by investigating whether they&#xD;
        possess virulence genes, and if so, whether these are expressed or repressed.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        There are still many unknowns about the exact bacterial composition of breast milk, and the&#xD;
        theoretical and real risks represented by its microbiota. In addition to determining the&#xD;
        Total Aerobic Flora (TAF) and the Staphylococcus aureus presence, the most commonly isolated&#xD;
        enterobacterales species identified by agar culture by the Prevention and Infection Control&#xD;
        department are also among those potentially found in diagnostic samples: Enterobacter&#xD;
        cloacae, Klebsiella pneumoniae, Klebsiella aerogenes, Klebsiella oxytoca and Escherichia&#xD;
        coli. However, it is not yet known whether these are identical strains or not. It is&#xD;
        therefore legitimate to ask whether there are any differences between the strains present in&#xD;
        the microbiota of breast milk and those responsible for newborn infections.&#xD;
  &#xD;
        Conventional methods for enumerating and identifying the bacteria making up the milk&#xD;
        microbiota are not standardized, which makes it difficult to draw up a precise, multicentric&#xD;
        inventory of its composition. It is therefore impossible to know whether exceeding a&#xD;
        threshold value defined by expert consensus represents a real danger for newborns who must&#xD;
        receive breast milk.&#xD;
  &#xD;
        At the Centre National de Recherche en Génomique Humaine (CNRGH), a metagenomic sequencing&#xD;
        approach makes it possible to study the microbiota using two complementary methodologies.&#xD;
        Either by sequencing the genomes of organisms (bacteria, viruses, fungi, etc.) present in the&#xD;
        environment to be analyzed (shotgun metagenomics), or by sequencing one or more genes&#xD;
        specific to each bacterial species (targeted metagenomics). The gene that codes for 16S&#xD;
        ribosomal RNA (rRNA) has sequence regions common to different bacterial species, as well as&#xD;
        variable regions that can be used to distinguish the bacteria present in a sample.&#xD;
  &#xD;
        A comparison of the composition of the bacterial microbiota in breast milk using conventional&#xD;
        agar culture methods and metagenomic analysis methods would enable us to make progress in&#xD;
        understanding its potential involvement in infectious pathologies in premature infants. It is&#xD;
        in this scientific and medical context that a collaborative project was initiated for the&#xD;
        first time between the departments of Neonatal Medicine and Intensive Care and of Prevention&#xD;
        and Infection Control, and the CNRGH. This was a pilot study with the aim of perpetuating&#xD;
        this collaboration, which combines scientific knowledge of the metagenome with the CNRGH's&#xD;
        high-performance technological tools, as well as potential applications in the medical&#xD;
        environment in the CHSF's care departments.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 15, 2023</start_date>
    <completion_date type="Anticipated">November 15, 2027</completion_date>
    <primary_completion_date type="Anticipated">November 15, 2027</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Assessing the potential pathogenic risk of certain bacteria in breast milk.</measure>
      <time_frame>at day 0</time_frame>
      <description>Presence of virulence genes in strains of bacteria with pathogenic potential (S. aureus, K. aerogenes, E. coli, K. pneumoniae, K. oxytoca, E. cloacae) in breast milk.</description>
    </primary_outcome>
    <other_outcome>
      <measure>Comparing the microbial ecologies of breast milk by bacterial culture and metagenomics.</measure>
      <time_frame>at day 0</time_frame>
      <description>Presence in breast milk of identical bacterial genera or species/strains between sequencing and bacterial culture.</description>
    </other_outcome>
    <other_outcome>
      <measure>If bacteria isolated from breast milk contain virulence genes, establish whether they are activated or repressed.</measure>
      <time_frame>at day 0</time_frame>
      <description>Production by bacteria isolated from breast milk of the mRNA and/or protein corresponding to the virulence gene(s) identified.</description>
    </other_outcome>
    <other_outcome>
      <measure>Establish whether strains of bacteria with pathogenic potential (S. aureus, K. aerogenes, E. coli, K. pneumoniae, K. oxytoca, E. cloacae) found in breast milk contain antibiotic resistance genes.</measure>
      <time_frame>at day 0</time_frame>
      <description>Presence of antibiotic resistance genes in strains of bacteria with pathogenic potential (S. aureus, K. aerogenes, E. coli, K. pneumoniae, K. oxytoca, E. cloacae) found in breast milk.</description>
    </other_outcome>
    <other_outcome>
      <measure>If so, establish whether these are activated or repressed.</measure>
      <time_frame>at day 0</time_frame>
      <description>Production by bacteria isolated from breast milk of the mRNA and/or protein corresponding to the antibiotic resistance gene.</description>
    </other_outcome>
    <other_outcome>
      <measure>Compare the microbial ecology of different ecosystems: intestinal, oral and cutaneous with that of breast milk, using bacterial culture and metagenomics.</measure>
      <time_frame>at day 0</time_frame>
      <description>Presence of common bacteria in different samples (child's stool and saliva + mother's stool, saliva, skin swab and milk).</description>
    </other_outcome>
    <other_outcome>
      <measure>Check maternal blood for the presence of essentially anaerobic bacteria such as bifidobacteria and/or mononuclear cells such as dendritic cells or macrophages, a potential reflection of the entero-mammary pathway.</measure>
      <time_frame>at day 0</time_frame>
      <description>Presence of mainly anaerobic bifidobacteria and/or mononuclear dendritic cells in maternal blood; biological marker of the entero-mammary tract.</description>
    </other_outcome>
    <enrollment type="Anticipated">120</enrollment>
    <condition>Bacteria in Breast Milk</condition>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Human breast milk sampling</intervention_name>
      <description>Human breast milk sampling</description>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Saddle sampling</intervention_name>
      <description>Saddle sampling</description>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Skin sampling</intervention_name>
      <description>Skin sampling</description>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Saliva sampling</intervention_name>
      <description>Saliva sampling</description>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>blood sampling</intervention_name>
      <description>blood sampling</description>
    </intervention>
    <biospec_retention>Samples Without DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Human breast milk samples, mother's stool samples, infant's stool samples, mother's saliva&#xD;
        samples, infant's saliva samples, mother's skin samples, mother's blood samples&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Mother-infant pairs whose newborn(s) are being cared for in the CHSF's Neonatal Medicine&#xD;
          and Intensive Care Unit.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Women of legal age who have given birth at the CHSF (or in another establishment) and&#xD;
               whose newborn(s) are being cared for in the CHSF's Neonatal Medicine and Intensive&#xD;
               Care Unit,&#xD;
  &#xD;
            -  Women wishing to give their milk to their child,&#xD;
  &#xD;
            -  Parents who have given their consent for the mother-child couple to take part in the&#xD;
               study.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Mother having received antibiotic therapy in the 3 months prior to delivery, except&#xD;
               for those who received injectable antibiotic prophylaxis during delivery.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>1 Hour</minimum_age>
      <maximum_age>N/A</maximum_age>
    </eligibility>
    <overall_contact>
      <last_name>Didier LECOINTE, PharmD</last_name>
      <phone>33 1 61 69 76 69</phone>
      <email>didier.lecointe@chsf.fr</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Caroline TOURTE</last_name>
      <phone>33 1 61 69 31 50</phone>
      <email>caroline.tourte@chsf.fr</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Centre Hospitalier Sud Francilien</name>
        <address>
          <city>Corbeil-Essonnes</city>
          <zip>91106</zip>
          <country>France</country>
        </address>
      </facility>
      <contact>
        <last_name>Didier LECOINTE, PharmD</last_name>
        <phone>33 1 61 69 76 69</phone>
        <email>didier.lecointe@chsf.fr</email>
      </contact>
      <contact_backup>
        <last_name>Benjalin QUERIN, Pharmacy intern</last_name>
        <email>benjamin.querin@chsf.fr</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>France</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 6, 2023</study_first_submitted>
    <study_first_submitted_qc>September 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 14, 2023</study_first_posted>
    <last_update_submitted>September 14, 2023</last_update_submitted>
    <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Bacterial</keyword>
    <keyword>newborn breast milk</keyword>
    <keyword>neonates</keyword>
    <keyword>infectious risk</keyword>
    <keyword>virulence genes</keyword>
    <keyword>agar culture methods</keyword>
    <keyword>shotgun metagenomics</keyword>
    <keyword>targeted metagenomics</keyword>
    <keyword>microbiota</keyword>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </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/NCT06037421
  org study id: 2023-A01731-44
  nct id: NCT06037421
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The aim of this study is to determine the extent to which bacteria in the breast milk
        microbiota represent an infectious risk for premature infants, by investigating whether they
        possess virulence genes, and if so, whether these are expressed or repressed.
  There are still many unknowns about the exact bacterial composition of breast milk, and the
        theoretical and real risks represented by its microbiota. In addition to determining the
        Total Aerobic Flora (TAF) and the Staphylococcus aureus presence, the most commonly isolated
        enterobacterales species identified by agar culture by the Prevention and Infection Control
        department are also among those potentially found in diagnostic samples: Enterobacter
        cloacae, Klebsiella pneumoniae, Klebsiella aerogenes, Klebsiella oxytoca and Escherichia
        coli. However, it is not yet known whether these are identical strains or not. It is
        therefore legitimate to ask whether there are any differences between the strains present in
        the microbiota of breast milk and those responsible for newborn infections.
  
        Conventional methods for enumerating and identifying the bacteria making up the milk
        microbiota are not standardized, which makes it difficult to draw up a precise, multicentric
        inventory of its composition. It is therefore impossible to know whether exceeding a
        threshold value defined by expert consensus represents a real danger for newborns who must
        receive breast milk.
  
        At the Centre National de Recherche en Génomique Humaine (CNRGH), a metagenomic sequencing
        approach makes it possible to study the microbiota using two complementary methodologies.
        Either by sequencing the genomes of organisms (bacteria, viruses, fungi, etc.) present in the
        environment to be analyzed (shotgun metagenomics), or by sequencing one or more genes
        specific to each bacterial species (targeted metagenomics). The gene that codes for 16S
        ribosomal RNA (rRNA) has sequence regions common to different bacterial species, as well as
        variable regions that can be used to distinguish the bacteria present in a sample.
  
        A comparison of the composition of the bacterial microbiota in breast milk using conventional
        agar culture methods and metagenomic analysis methods would enable us to make progress in
        understanding its potential involvement in infectious pathologies in premature infants. It is
        in this scientific and medical context that a collaborative project was initiated for the
        first time between the departments of Neonatal Medicine and Intensive Care and of Prevention
        and Infection Control, and the CNRGH. This was a pilot study with the aim of perpetuating
        this collaboration, which combines scientific knowledge of the metagenome with the CNRGH's
        high-performance technological tools, as well as potential applications in the medical
        environment in the CHSF's care departments.
  observational model: Cohort
  time perspective: Prospective
  measure: Assessing the potential pathogenic risk of certain bacteria in breast milk.
  time frame: at day 0
  description: Presence of virulence genes in strains of bacteria with pathogenic potential (S. aureus, K. aerogenes, E. coli, K. pneumoniae, K. oxytoca, E. cloacae) in breast milk.
  measure: Comparing the microbial ecologies of breast milk by bacterial culture and metagenomics.
  time frame: at day 0
  description: Presence in breast milk of identical bacterial genera or species/strains between sequencing and bacterial culture.
  measure: If bacteria isolated from breast milk contain virulence genes, establish whether they are activated or repressed.
  time frame: at day 0
  description: Production by bacteria isolated from breast milk of the mRNA and/or protein corresponding to the virulence gene(s) identified.
  measure: Establish whether strains of bacteria with pathogenic potential (S. aureus, K. aerogenes, E. coli, K. pneumoniae, K. oxytoca, E. cloacae) found in breast milk contain antibiotic resistance genes.
  time frame: at day 0
  description: Presence of antibiotic resistance genes in strains of bacteria with pathogenic potential (S. aureus, K. aerogenes, E. coli, K. pneumoniae, K. oxytoca, E. cloacae) found in breast milk.
  measure: If so, establish whether these are activated or repressed.
  time frame: at day 0
  description: Production by bacteria isolated from breast milk of the mRNA and/or protein corresponding to the antibiotic resistance gene.
  measure: Compare the microbial ecology of different ecosystems: intestinal, oral and cutaneous with that of breast milk, using bacterial culture and metagenomics.
  time frame: at day 0
  description: Presence of common bacteria in different samples (child's stool and saliva + mother's stool, saliva, skin swab and milk).
  measure: Check maternal blood for the presence of essentially anaerobic bacteria such as bifidobacteria and/or mononuclear cells such as dendritic cells or macrophages, a potential reflection of the entero-mammary pathway.
  time frame: at day 0
  description: Presence of mainly anaerobic bifidobacteria and/or mononuclear dendritic cells in maternal blood; biological marker of the entero-mammary tract.
  intervention type: Other
  intervention name: Human breast milk sampling
  description: Human breast milk sampling
  intervention type: Other
  intervention name: Saddle sampling
  description: Saddle sampling
  intervention type: Other
  intervention name: Skin sampling
  description: Skin sampling
  intervention type: Other
  intervention name: Saliva sampling
  description: Saliva sampling
  intervention type: Other
  intervention name: blood sampling
  description: blood sampling
  Human breast milk samples, mother's stool samples, infant's stool samples, mother's saliva
        samples, infant's saliva samples, mother's skin samples, mother's blood samples
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 1 Hour
  maximum age: N/A
  last name: Didier LECOINTE, PharmD
  phone: 33 1 61 69 76 69
  email: didier.lecointe@chsf.fr
  last name: Caroline TOURTE
  phone: 33 1 61 69 31 50
  email: caroline.tourte@chsf.fr
  facility: 
  contact: 
  contact backup: 
  country: France
  responsible party type: Sponsor
  sharing ipd: No