<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/NCT04435470</url>
  </required_header>
  <id_info>
    <org_study_id>BIOUCIP</org_study_id>
    <secondary_id>PI18/01334</secondary_id>
    <nct_id>NCT04435470</nct_id>
  </id_info>
  <brief_title>Epidemiological Study of the Microbiota in Critically Ill Children</brief_title>
  <acronym>BIOUCIP</acronym>
  <official_title>Epidemiological Study of the Microbiota in Critically Ill Children and Its Relationship With Clinical Complications and Inflammation Biomarkers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidad de Granada</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hospital Materno-Infantil Torrecárdenas de Almería</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Materno-Infantil de Málaga</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Complejo Hospitalario Universitario de Santiago</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital Virgen de las Nieves</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universidad de Granada</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>
      Objectives: To study the composition of the microbiota in critically ill children, and to&#xD;
      know the relationship of its microbiota with clinical complications and inflammation&#xD;
      biomarkers.&#xD;
&#xD;
      Design: Multicenter observational and prospective study including 100 critically ill children&#xD;
      admitted in three pediatric intensive care units with a prediction of more than 5 days of&#xD;
      stay and 50 healthy children. Clinical parameters and rectal, fecal, blood and respiratory&#xD;
      samples will be collected at admission and at pediatric intensive care units discharge. The&#xD;
      microbiota and inflammation biomarkers and metabolomic will be analyzed.&#xD;
&#xD;
      Analysis of results: Description an evolution of the microbiota throughout the time,&#xD;
      intestinal and respiratory, and the influence of clinical and therapeutic factors will be&#xD;
      analyzed. The composition of microbiota will be compared with a cohort of healthy children&#xD;
      and between the different types of pediatric intensive care units. The correlation of the&#xD;
      microbiota with the markers of inflammation, metabolomics and the development of infectious&#xD;
      complications and multiorgan failure will be analyzed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      AIM: The present study is an observational clinical study aimed to study the intestinal&#xD;
      microbiota composition of critically ill children in paediatric intensive care unit and its&#xD;
      relationship with clinical complications and inflammatory biomarkers.&#xD;
&#xD;
      DESIGN: This study is a multicentre, observational and prospective study including 100&#xD;
      critically ill children admitted in three paediatric intensive care units (Hospital&#xD;
      Materno-Infantil Torrecárdenas de Almería, y en el Hospital Materno-Infantil Carlos Haya de&#xD;
      Málaga and Complejo Hospitalario Universitario de Santiago) This study is a multicentre,&#xD;
      observational and prospective study conducted by members of the Department of Biochemistry&#xD;
      and Molecular Biology II, Nutrition and Food Technology Institute &quot;José Mataix&quot; of the&#xD;
      University of Granada research group in collaboration with the Hospital Materno-Infantil&#xD;
      Torrecárdenas from Almería, the Hospital Materno-Infantil Carlos Haya from Málaga and&#xD;
      Complejo Hospitalario Universitario from Santiago de Compostela pediatric intensive care&#xD;
      units and primary care unit of the University Hospital Virgen de las Nieves from Granada as&#xD;
      recruitment centres.&#xD;
&#xD;
      This trial will include 100 critically ill children admitted from the three different&#xD;
      pediatric intensive care units with an expected hospitalization time of more than 5 days. In&#xD;
      addition, 50 healthy children will be recruited from a primary care centre as controls.&#xD;
      Faecal and respiratory system (oropharynx) samples will be collected from ill and healthy&#xD;
      children, while blood samples will be harvested only from critically ill children at the time&#xD;
      of admission to the pediatric intensive care units as well as at the day of discharge. Sample&#xD;
      aliquots will be sent to the Department of Biochemistry and Molecular Biology II, University&#xD;
      of Granada for further analysis.&#xD;
&#xD;
      Study population The study population will comprise 50 healthy children aged between 1 month&#xD;
      and 16 years, recruited in a paediatric primary care center from Granada, and 100 critically&#xD;
      ill children admitted to the pediatric intensive care units aged between 1 month and 16&#xD;
      years. 50 patients will be recruited at the pediatric intensive care units of Hospital&#xD;
      Materno-Infantil Torrecárdenas from Almería, the Hospital Materno-Infantil Carlos Haya from&#xD;
      Málaga and Complejo Hospitalario Universitario from Santiago de Compostela. Only those&#xD;
      children who satisfy all inclusion and none of exclusion criteria will be included in the&#xD;
      study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 1, 2020</start_date>
  <completion_date type="Anticipated">July 2023</completion_date>
  <primary_completion_date type="Anticipated">February 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>To identify intestinal and respiratory microbiota and if their changes are related with digestive and infectious complications</measure>
    <time_frame>At admission and through study completion, at least 5 days</time_frame>
    <description>To analyse the intestinal and respiratory microbiota in critically ill children admitted to the pediatric intensive care unit through massive sequencing, and evaluate if their changes are related with the appearance of digestive and infectious complications and the development of multiorgan failure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To compare intestinal and respiratory microbiota of critically ill children with a cohort of healthy children</measure>
    <time_frame>Samples will be taken at admission to pediatric intensive care unit and a single sample witl be taken from healthy controls</time_frame>
    <description>To compare intestinal and respiratory microbiota of critically ill children when admitted to the pediatric intensive care unit with a cohort of healthy children</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To study the clinical factors influencing the changes in the intestinal microbiota during admission to the pediatric intensive care unit</measure>
    <time_frame>At admission and through study completion, at least 5 days</time_frame>
    <description>To study the clinical factors and influencing the changes in the intestinal microbiota during admission to the pediatric intensive care unit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare the changes of the microbiota according to the type of critical patients and the type of pediatric intensive care unit</measure>
    <time_frame>At admission and through study completion, at least 5 days</time_frame>
    <description>To compare the changes in the composition of intestinal and respiratory microbiota according to the type of critical patients and the type of pediatric intensive care unit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess the relationship between changes in the intestinal microbiota and the frequency and severity of digestive complications</measure>
    <time_frame>At admission and through study completion, at least 5 days</time_frame>
    <description>To assess the relationship between the composition of the intestinal microbiota and the frequency and severity of digestive complications (diarrhea, constipation and tolerance of enteral nutrition) in critical ill children admitted to the pediatric intensive care unit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To study the relationship between changes in the intestinal and respiratory microbiota and the frequency and severity of nosocomial infection</measure>
    <time_frame>At admission and through study completion, at least 5 days</time_frame>
    <description>To study the relationship between the composition of intestinal and respiratory microbiota and the frequency and severity of nosocomial infection in critically ill children admitted to the pediatric intensive care unit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To study the relationship between changes in the intestinal and respiratory microbiota and the development of multiorgan failure</measure>
    <time_frame>At admission and through study completion, at least 5 days</time_frame>
    <description>To study the relationship between the intestinal and respiratory microbiota and the development of multiorgan failure in critical ill children admitted to the pediatric intensive care unit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine changes in the serum levels of lipopolysaccharide and lipopolysaccharide binding protein and to evaluate their relationship with intestinal and respiratory microbiota</measure>
    <time_frame>At admission and through study completion, at least 5 days</time_frame>
    <description>To determine the serum levels of lipopolysaccharide (LPS) and lipopolysacchaide binding protein (LPB) in critical ill children admitted to the pediatric intensive care unit, and to evaluate their relationship with intestinal and respiratory microbiota, the evolution during admission and the relationship with clinical complications</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To analyse the relationship between changes in the intestinal and respiratory microbiota plasma sort chain fatty acids and bile acids</measure>
    <time_frame>At admission and through study completion, at least 5 days</time_frame>
    <description>To analyse the relationship between the intestinal and respiratory microbiota and the metabolomic profile, especially short chain fatty acids (SCFA) and bile acids, in critical ill children admitted to the pediatric intensive care unit, the evolution during admission and the relationship with clinical complications</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To analyse the relationship between changes in microbiota and inflammatory biomarkers</measure>
    <time_frame>At admission and through study completion, at least 5 days</time_frame>
    <description>To analyse the relationship between microbiota and inflammatory biomarkers in critical ill children admitted to the pediatric intensive care unit, the evolution during admission and the relationship with clinical complications</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess the influence of the type of nutrition during admission and changes of intestinal microbiota</measure>
    <time_frame>At admission and through study completion, at least 5 days</time_frame>
    <description>To assess whether the type of nutrition, enteral or parenteral, of critical ill children during admision to pediatric intensive care unit and to evaluate their influences with the composition of the intestinal microbiota, and the relationship with clinical complications</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Critical Illness</condition>
  <condition>Child, Only</condition>
  <condition>Intensive Care Unit</condition>
  <arm_group>
    <arm_group_label>Critical ill children</arm_group_label>
    <description>Critial ill children admited in pediatric intensive care units 1-16 years old</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <description>Healthy children 1-16 years old</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Plasma Feces Saliva&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Critical ill children admited to pediatric intensive care unit, with a hospitalization time&#xD;
        expectancy more than 5 days Control subjects will be healthy children&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  admission to pediatric intensive care unit&#xD;
&#xD;
          -  hospitalization time expectancy more than 5 days&#xD;
&#xD;
          -  age between 1 month and 16 years&#xD;
&#xD;
          -  informed consent signed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  hospitalization time expectancy less than 5 days&#xD;
&#xD;
          -  no signed informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Month</minimum_age>
    <maximum_age>16 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>MARÍA DOLORES MESA GARCÍA, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universidad de Granada</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>MARÍA DOLORES MESA GARCÍA, PhD</last_name>
    <phone>958246187</phone>
    <email>mdmesa@ugr.es</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>JOSE MALDONADO, PhD</last_name>
    <phone>958242334</phone>
    <email>jmaldon@ugr.es</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>María Dolores Mesa García</name>
      <address>
        <city>Armilla</city>
        <state>Granada</state>
        <zip>18071</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>MARÍA DOLORES MESA GARCÍA</last_name>
      <phone>958246187</phone>
      <email>mdmesa@ugr.es</email>
    </contact>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>March 2, 2022</last_update_submitted>
  <last_update_submitted_qc>March 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 17, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universidad de Granada</investigator_affiliation>
    <investigator_full_name>María Dolores Mesa García</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>microbiota</keyword>
  <keyword>inflammation</keyword>
  <keyword>metabolomic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Study Protocol</ipd_description>
  </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/NCT04435470
org study id: BIOUCIP
secondary id: PI18/01334
nct id: NCT04435470
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Objectives: To study the composition of the microbiota in critically ill children, and to
      know the relationship of its microbiota with clinical complications and inflammation
      biomarkers.

      Design: Multicenter observational and prospective study including 100 critically ill children
      admitted in three pediatric intensive care units with a prediction of more than 5 days of
      stay and 50 healthy children. Clinical parameters and rectal, fecal, blood and respiratory
      samples will be collected at admission and at pediatric intensive care units discharge. The
      microbiota and inflammation biomarkers and metabolomic will be analyzed.

      Analysis of results: Description an evolution of the microbiota throughout the time,
      intestinal and respiratory, and the influence of clinical and therapeutic factors will be
      analyzed. The composition of microbiota will be compared with a cohort of healthy children
      and between the different types of pediatric intensive care units. The correlation of the
      microbiota with the markers of inflammation, metabolomics and the development of infectious
      complications and multiorgan failure will be analyzed.
AIM: The present study is an observational clinical study aimed to study the intestinal
      microbiota composition of critically ill children in paediatric intensive care unit and its
      relationship with clinical complications and inflammatory biomarkers.

      DESIGN: This study is a multicentre, observational and prospective study including 100
      critically ill children admitted in three paediatric intensive care units (Hospital
      Materno-Infantil Torrecárdenas de Almería, y en el Hospital Materno-Infantil Carlos Haya de
      Málaga and Complejo Hospitalario Universitario de Santiago) This study is a multicentre,
      observational and prospective study conducted by members of the Department of Biochemistry
      and Molecular Biology II, Nutrition and Food Technology Institute "José Mataix" of the
      University of Granada research group in collaboration with the Hospital Materno-Infantil
      Torrecárdenas from Almería, the Hospital Materno-Infantil Carlos Haya from Málaga and
      Complejo Hospitalario Universitario from Santiago de Compostela pediatric intensive care
      units and primary care unit of the University Hospital Virgen de las Nieves from Granada as
      recruitment centres.

      This trial will include 100 critically ill children admitted from the three different
      pediatric intensive care units with an expected hospitalization time of more than 5 days. In
      addition, 50 healthy children will be recruited from a primary care centre as controls.
      Faecal and respiratory system (oropharynx) samples will be collected from ill and healthy
      children, while blood samples will be harvested only from critically ill children at the time
      of admission to the pediatric intensive care units as well as at the day of discharge. Sample
      aliquots will be sent to the Department of Biochemistry and Molecular Biology II, University
      of Granada for further analysis.

      Study population The study population will comprise 50 healthy children aged between 1 month
      and 16 years, recruited in a paediatric primary care center from Granada, and 100 critically
      ill children admitted to the pediatric intensive care units aged between 1 month and 16
      years. 50 patients will be recruited at the pediatric intensive care units of Hospital
      Materno-Infantil Torrecárdenas from Almería, the Hospital Materno-Infantil Carlos Haya from
      Málaga and Complejo Hospitalario Universitario from Santiago de Compostela. Only those
      children who satisfy all inclusion and none of exclusion criteria will be included in the
      study.
observational model: Case-Control
time perspective: Prospective
measure: To identify intestinal and respiratory microbiota and if their changes are related with digestive and infectious complications
time frame: At admission and through study completion, at least 5 days
description: To analyse the intestinal and respiratory microbiota in critically ill children admitted to the pediatric intensive care unit through massive sequencing, and evaluate if their changes are related with the appearance of digestive and infectious complications and the development of multiorgan failure.
measure: To compare intestinal and respiratory microbiota of critically ill children with a cohort of healthy children
time frame: Samples will be taken at admission to pediatric intensive care unit and a single sample witl be taken from healthy controls
description: To compare intestinal and respiratory microbiota of critically ill children when admitted to the pediatric intensive care unit with a cohort of healthy children
measure: To study the clinical factors influencing the changes in the intestinal microbiota during admission to the pediatric intensive care unit
time frame: At admission and through study completion, at least 5 days
description: To study the clinical factors and influencing the changes in the intestinal microbiota during admission to the pediatric intensive care unit
measure: To compare the changes of the microbiota according to the type of critical patients and the type of pediatric intensive care unit
time frame: At admission and through study completion, at least 5 days
description: To compare the changes in the composition of intestinal and respiratory microbiota according to the type of critical patients and the type of pediatric intensive care unit
measure: To assess the relationship between changes in the intestinal microbiota and the frequency and severity of digestive complications
time frame: At admission and through study completion, at least 5 days
description: To assess the relationship between the composition of the intestinal microbiota and the frequency and severity of digestive complications (diarrhea, constipation and tolerance of enteral nutrition) in critical ill children admitted to the pediatric intensive care unit
measure: To study the relationship between changes in the intestinal and respiratory microbiota and the frequency and severity of nosocomial infection
time frame: At admission and through study completion, at least 5 days
description: To study the relationship between the composition of intestinal and respiratory microbiota and the frequency and severity of nosocomial infection in critically ill children admitted to the pediatric intensive care unit
measure: To study the relationship between changes in the intestinal and respiratory microbiota and the development of multiorgan failure
time frame: At admission and through study completion, at least 5 days
description: To study the relationship between the intestinal and respiratory microbiota and the development of multiorgan failure in critical ill children admitted to the pediatric intensive care unit
measure: To determine changes in the serum levels of lipopolysaccharide and lipopolysaccharide binding protein and to evaluate their relationship with intestinal and respiratory microbiota
time frame: At admission and through study completion, at least 5 days
description: To determine the serum levels of lipopolysaccharide (LPS) and lipopolysacchaide binding protein (LPB) in critical ill children admitted to the pediatric intensive care unit, and to evaluate their relationship with intestinal and respiratory microbiota, the evolution during admission and the relationship with clinical complications
measure: To analyse the relationship between changes in the intestinal and respiratory microbiota plasma sort chain fatty acids and bile acids
time frame: At admission and through study completion, at least 5 days
description: To analyse the relationship between the intestinal and respiratory microbiota and the metabolomic profile, especially short chain fatty acids (SCFA) and bile acids, in critical ill children admitted to the pediatric intensive care unit, the evolution during admission and the relationship with clinical complications
measure: To analyse the relationship between changes in microbiota and inflammatory biomarkers
time frame: At admission and through study completion, at least 5 days
description: To analyse the relationship between microbiota and inflammatory biomarkers in critical ill children admitted to the pediatric intensive care unit, the evolution during admission and the relationship with clinical complications
measure: To assess the influence of the type of nutrition during admission and changes of intestinal microbiota
time frame: At admission and through study completion, at least 5 days
description: To assess whether the type of nutrition, enteral or parenteral, of critical ill children during admision to pediatric intensive care unit and to evaluate their influences with the composition of the intestinal microbiota, and the relationship with clinical complications
arm group label: Critical ill children
description: Critial ill children admited in pediatric intensive care units 1-16 years old
arm group label: Control
description: Healthy children 1-16 years old
Plasma Feces Saliva
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 1 Month
maximum age: 16 Years
healthy volunteers: No
last name: MARÍA DOLORES MESA GARCÍA, PhD
role: Principal Investigator
affiliation: Universidad de Granada
last name: MARÍA DOLORES MESA GARCÍA, PhD
phone: 958246187
email: mdmesa@ugr.es
last name: JOSE MALDONADO, PhD
phone: 958242334
email: jmaldon@ugr.es
facility: 
status: Recruiting
contact: 
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Universidad de Granada
investigator full name: María Dolores Mesa García
investigator title: Associate Professor
mesh term: Critical Illness
sharing ipd: No
ipd description: Study Protocol