<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/NCT03296631</url>
  </required_header>
  <id_info>
    <org_study_id>2016-097</org_study_id>
    <secondary_id>ID RCB number : 2017-A00750-53</secondary_id>
    <nct_id>NCT03296631</nct_id>
  </id_info>
  <brief_title>Phages Dynamics and Influences During Human Gut Microbiome Establishment</brief_title>
  <acronym>METAKIDS</acronym>
  <official_title>Phages Dynamics and Influences During Human Gut Microbiome Establishment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut Pasteur</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>City of Orsay</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Institut Pasteur</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>
      Microbial communities are key components of human environment. Consequently, human gut&#xD;
      microbiome have been extensively studied providing a better understanding of the relations&#xD;
      between bacterial populations and host physiology. However, a typical analysis tends to elude&#xD;
      the complexity of the mixes in term of species, strains, as well as extra-chromosomal DNA&#xD;
      molecules such as and phages. MetaKids project aims at bringing, at an unprecedented&#xD;
      resolution, a new view of those populations and the internal relationships during human gut&#xD;
      establishment, a crucial step with long-term impacts on host health. This project relies on&#xD;
      the ability of Meta3C, a newly technique developed in the lab, to identify the bacterial host&#xD;
      genomes of the different phages the investigators will detect thanks to the physical&#xD;
      collision these molecules experience. Given the role that human gut phages may play in&#xD;
      shaping the development of host microbiomes, their potential for application is of great&#xD;
      interest.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Over the last decade, the role of microorganisms residing in human intestines has been&#xD;
      intensively studied. The intestinal microbiome includes bacteria, viruses, fungi and archaea.&#xD;
      The importance of microbiome to human health is highlighted by the observation that dysbiotic&#xD;
      shifts in these microbial communities have been associated with numerous human diseases,&#xD;
      including obesity, inflammatory bowel disorders, autoimmune disease or gastrointestinal&#xD;
      cancer. It is also clearly established that some of these microorganisms interact with the&#xD;
      immune system and contribute to its development. The intestinal microbiome is established&#xD;
      soon after birth, and its composition changes over the next several years toward a&#xD;
      stereotypical 'adult-like' bacterial community structure. Epidemiological studies have&#xD;
      demonstrated the importance of this period for a long-term health. It also has been shown&#xD;
      that this process can be influenced by multiple interacting factors such as nutrition,&#xD;
      antibiotic use and others environmental factors. Much less is known on the viral part of&#xD;
      human microbiome. Most of them are phages (phageome) that are known to modulate microbial&#xD;
      population through predation or transfer of genetic information between bacteria, and are&#xD;
      likely to have important effects on intestinal microbiome establishment and, consequently,&#xD;
      human physiology. MetaKids project aims at understanding how the gut phageome develops during&#xD;
      the early human life and how it influences the composition of the bacterial microbiome. The&#xD;
      investigators will carry a longitudinal study of 15-20 infants from 3-9 months till age 24-30&#xD;
      months. By combining latest metagenomic methods, will be investigated: 1) the composition,&#xD;
      evolution and dynamic of the phageome and bacterial microbiome over this critical period; 2)&#xD;
      the interactions between phages and bacteria and their relationships; and 3) the impact of&#xD;
      environmental factors, like vaccinations or antibiotics treatment on the phages populations.&#xD;
      The project is based on the combination of innovative recent metagenomic techniques developed&#xD;
      in the lab. DNA is an ubiquitous and stable molecule that can be used as a marker of&#xD;
      &quot;compartmentalization&quot; at cellular and population levels, providing important information&#xD;
      regarding the genomic structure of a mix of species. Therefore, by combining approaches like&#xD;
      purification of virales particles and 3C related methods, the investigators propose to&#xD;
      characterize infant gut microbiome establishment and decipher the relationships between the&#xD;
      different genomic entities present during this period. This project will bring crucial data&#xD;
      on the role of phages during early life of human intestinal tract. Intervention to&#xD;
      modify/control intestinal population is a dynamic field and MetaKids project will bring new&#xD;
      perspectives for this research area.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The Pi has estimated that he has received sufficiently biological samples and associated data.&#xD;
    it's no longer worth following up.&#xD;
  </why_stopped>
  <start_date type="Actual">September 5, 2017</start_date>
  <completion_date type="Actual">December 31, 2018</completion_date>
  <primary_completion_date type="Actual">December 31, 2018</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>Characterization of phages and bacteria genomes during infant gut development.</measure>
    <time_frame>3 years</time_frame>
    <description>Genomic reconstruction and characterization of the different genomes (phages, bacteria, yeast) present in the human gut during the three first years of life. This outcomes will provide a large catalog of DNA sequences.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Characterization of phages and bacteria abundance and variations during infant gut development</measure>
    <time_frame>3 years</time_frame>
    <description>Characterization of the variation of the different species present in human gut during the 3 first years of life. This outcomes will provide access to the dynamics of the different species present during this period and possibility to correlate them with environmental variation (dietary, age)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Characterization of phages-bacteria interactions</measure>
    <time_frame>3 years</time_frame>
    <description>Phages are the major predator of bacteria but their role during human gut establishment remains poorly characterized. This catalog of interactions will allow to understand the role of the phages during human gut development</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Characterization of phages and bacteria variations in response to environmental perturbations during infant gut development</measure>
    <time_frame>2 to 3 weeks</time_frame>
    <description>Characterization of the small variations of the different species present in human gut during the 3 first years of life in response to environmental perturbations. This outcome will provide access to the dynamics of the different species present during this period and possibility to correlate them with environmental perturbations (antibiotic, vaccine, illness).</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">19</enrollment>
  <condition>Human Gut Microbiome Development</condition>
  <arm_group>
    <arm_group_label>children</arm_group_label>
    <description>Enrollment of 15 to 20 children (&lt; 9 months old) at the early beginning of their entry in nursery (crèche) between August and November 2017.&#xD;
This cohort will be followed during a maximum period of 36 months . Diapers with fresh stools will be collected once a week per child and then frozen.&#xD;
Spontaneous personal day care informations given by the parents to the nurses and recorded in each child's daily logbook will be collected for the research. No specific interviews will be conducted.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>collection of diapers with fresh stools</intervention_name>
    <description>collection of diapers with fresh stools</description>
    <arm_group_label>children</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      fresh stools in diapers. Genomic DNA will be extracted from feces but no human genetic&#xD;
      analysis will be realized.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Children being in age to attend in a nursery day care structure of the town of Orsay&#xD;
        (France) and aged less than 9 months.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Child attending at least 4 days a week one of the two municipal municipal nursery&#xD;
             (crèches) in the town of Orsay (91, France);&#xD;
&#xD;
          2. Aged less than 9 months at the time of entry to the crèche (August-October 2017);&#xD;
&#xD;
          3. Parent (s) / legal representative not opposed to the child's participation in the&#xD;
             research;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Toilet training;&#xD;
&#xD;
          -  Prematurity;&#xD;
&#xD;
          -  Participation in clinical research requiring the use of a drug.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Weeks</minimum_age>
    <maximum_age>9 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Martial Marbouty</last_name>
    <role>Study Director</role>
    <affiliation>Institut Pasteur / CNRS</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Crèche du Parc</name>
      <address>
        <city>Orsay</city>
        <state>Essonne</state>
        <zip>91400</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Crèche La Farandole</name>
      <address>
        <city>Orsay</city>
        <state>Essonne</state>
        <zip>91400</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>August 1, 2017</study_first_submitted>
  <study_first_submitted_qc>September 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 28, 2017</study_first_posted>
  <last_update_submitted>July 12, 2019</last_update_submitted>
  <last_update_submitted_qc>July 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 16, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>microbiome</keyword>
  <keyword>gut</keyword>
  <keyword>infant gut</keyword>
  <keyword>phages</keyword>
  <keyword>phages-bacteria interactions</keyword>
  <keyword>microbiome development</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03296631
org study id: 2016-097
secondary id: ID RCB number : 2017-A00750-53
nct id: NCT03296631
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Microbial communities are key components of human environment. Consequently, human gut
      microbiome have been extensively studied providing a better understanding of the relations
      between bacterial populations and host physiology. However, a typical analysis tends to elude
      the complexity of the mixes in term of species, strains, as well as extra-chromosomal DNA
      molecules such as and phages. MetaKids project aims at bringing, at an unprecedented
      resolution, a new view of those populations and the internal relationships during human gut
      establishment, a crucial step with long-term impacts on host health. This project relies on
      the ability of Meta3C, a newly technique developed in the lab, to identify the bacterial host
      genomes of the different phages the investigators will detect thanks to the physical
      collision these molecules experience. Given the role that human gut phages may play in
      shaping the development of host microbiomes, their potential for application is of great
      interest.
Over the last decade, the role of microorganisms residing in human intestines has been
      intensively studied. The intestinal microbiome includes bacteria, viruses, fungi and archaea.
      The importance of microbiome to human health is highlighted by the observation that dysbiotic
      shifts in these microbial communities have been associated with numerous human diseases,
      including obesity, inflammatory bowel disorders, autoimmune disease or gastrointestinal
      cancer. It is also clearly established that some of these microorganisms interact with the
      immune system and contribute to its development. The intestinal microbiome is established
      soon after birth, and its composition changes over the next several years toward a
      stereotypical 'adult-like' bacterial community structure. Epidemiological studies have
      demonstrated the importance of this period for a long-term health. It also has been shown
      that this process can be influenced by multiple interacting factors such as nutrition,
      antibiotic use and others environmental factors. Much less is known on the viral part of
      human microbiome. Most of them are phages (phageome) that are known to modulate microbial
      population through predation or transfer of genetic information between bacteria, and are
      likely to have important effects on intestinal microbiome establishment and, consequently,
      human physiology. MetaKids project aims at understanding how the gut phageome develops during
      the early human life and how it influences the composition of the bacterial microbiome. The
      investigators will carry a longitudinal study of 15-20 infants from 3-9 months till age 24-30
      months. By combining latest metagenomic methods, will be investigated: 1) the composition,
      evolution and dynamic of the phageome and bacterial microbiome over this critical period; 2)
      the interactions between phages and bacteria and their relationships; and 3) the impact of
      environmental factors, like vaccinations or antibiotics treatment on the phages populations.
      The project is based on the combination of innovative recent metagenomic techniques developed
      in the lab. DNA is an ubiquitous and stable molecule that can be used as a marker of
      "compartmentalization" at cellular and population levels, providing important information
      regarding the genomic structure of a mix of species. Therefore, by combining approaches like
      purification of virales particles and 3C related methods, the investigators propose to
      characterize infant gut microbiome establishment and decipher the relationships between the
      different genomic entities present during this period. This project will bring crucial data
      on the role of phages during early life of human intestinal tract. Intervention to
      modify/control intestinal population is a dynamic field and MetaKids project will bring new
      perspectives for this research area.
observational model: Cohort
time perspective: Prospective
measure: Characterization of phages and bacteria genomes during infant gut development.
time frame: 3 years
description: Genomic reconstruction and characterization of the different genomes (phages, bacteria, yeast) present in the human gut during the three first years of life. This outcomes will provide a large catalog of DNA sequences.
measure: Characterization of phages and bacteria abundance and variations during infant gut development
time frame: 3 years
description: Characterization of the variation of the different species present in human gut during the 3 first years of life. This outcomes will provide access to the dynamics of the different species present during this period and possibility to correlate them with environmental variation (dietary, age)
measure: Characterization of phages-bacteria interactions
time frame: 3 years
description: Phages are the major predator of bacteria but their role during human gut establishment remains poorly characterized. This catalog of interactions will allow to understand the role of the phages during human gut development
measure: Characterization of phages and bacteria variations in response to environmental perturbations during infant gut development
time frame: 2 to 3 weeks
description: Characterization of the small variations of the different species present in human gut during the 3 first years of life in response to environmental perturbations. This outcome will provide access to the dynamics of the different species present during this period and possibility to correlate them with environmental perturbations (antibiotic, vaccine, illness).
arm group label: children
description: Enrollment of 15 to 20 children (< 9 months old) at the early beginning of their entry in nursery (crèche) between August and November 2017.
This cohort will be followed during a maximum period of 36 months . Diapers with fresh stools will be collected once a week per child and then frozen.
Spontaneous personal day care informations given by the parents to the nurses and recorded in each child's daily logbook will be collected for the research. No specific interviews will be conducted.
intervention type: Other
intervention name: collection of diapers with fresh stools
description: collection of diapers with fresh stools
arm group label: children
fresh stools in diapers. Genomic DNA will be extracted from feces but no human genetic
      analysis will be realized.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 10 Weeks
maximum age: 9 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Martial Marbouty
role: Study Director
affiliation: Institut Pasteur / CNRS
facility: 
facility: 
country: France
responsible party type: Sponsor
sharing ipd: No