<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/NCT03752372</url>
  </required_header>
  <id_info>
    <org_study_id>HSCT microbiomte</org_study_id>
    <nct_id>NCT03752372</nct_id>
  </id_info>
  <brief_title>Microbiome Alterations in IL10RA-deficient Patients After HSCT</brief_title>
  <official_title>Longitudinal Development of Intestinal Microbiome in IL10RA-deficient Patients After Hematopoietic Stem Cell Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital of Fudan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Children's Hospital of Fudan University</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>
      To elucidate the longitudinal development of intestinal microbiota in patients with IL10RA&#xD;
      deficiency after hematopoietic stem cell transplantation (HSCT). The investigators planned to&#xD;
      collect fecal samples from IL10RA-deficient patients who received HSCT. Samples were&#xD;
      collected more than once every three days after engraftment in lamina flow ward and at least&#xD;
      once a week before discharge. Microbial DNA was extracted from the fecal samples. And all&#xD;
      analysis was based on the next generation sequencing data.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hematopoietic stem cell transplantation is considered the only curative therapy for patients&#xD;
      with interleukin-10 receptor-A(IL10RA) deficiency. The investigators aimed to collect the&#xD;
      fecal samples of these patients throughout the conditioning, transplantation until discharge,&#xD;
      providing a dense insight into the longitudinal development of intestinal microbiota.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    COVID-19&#xD;
  </why_stopped>
  <start_date type="Actual">October 1, 2017</start_date>
  <completion_date type="Actual">February 28, 2020</completion_date>
  <primary_completion_date type="Actual">February 28, 2020</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>Shannon indices</measure>
    <time_frame>during the hospitalization of each eligible patient, an average of 90 days per patient</time_frame>
    <description>Shannon index is a popular diversity index in the ecological literature; minimum score is zero, higher values represent a better outcome</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Simpson indices</measure>
    <time_frame>during the hospitalization of each eligible patient, an average of 90 days per patient</time_frame>
    <description>Simpson index in ecology is to measure the degree of concentration when individuals are classified into types; scale ranges [0,1]; lower values represent a better outcome</description>
  </primary_outcome>
  <primary_outcome>
    <measure>relative abundance of Proteobacteria</measure>
    <time_frame>during the hospitalization of each eligible patient, an average of 90 days per patient</time_frame>
    <description>describe the microbiome at the phylum level</description>
  </primary_outcome>
  <primary_outcome>
    <measure>relative abundance of Firmicutes</measure>
    <time_frame>during the hospitalization of each eligible patient, an average of 90 days per patient</time_frame>
    <description>describe the microbiome at the phylum level</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clostridium sensus_stricto_1</measure>
    <time_frame>during the hospitalization of each eligible patient, an average of 90 days per patient</time_frame>
    <description>describe the microbiome at the genus level</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Escherichia - Shigella</measure>
    <time_frame>during the hospitalization of each eligible patient, an average of 90 days per patient</time_frame>
    <description>describe the microbiome at the genus level</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>chimerism</measure>
    <time_frame>during the hospitalization of each eligible patient, an average of 90 days per patient</time_frame>
    <description>The level of chimerism of each patient will be reported as percentages [0,100%]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>manifestation of graft-versus-host disease</measure>
    <time_frame>during the hospitalization of each eligible patient, an average of 90 days per patient</time_frame>
    <description>describe the graft-versus-host disease happened to each patient</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sobs indices</measure>
    <time_frame>during the hospitalization of each eligible patient, an average of 90 days per patient</time_frame>
    <description>describe the the observed richness of each sample</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chao1 estimator</measure>
    <time_frame>during the hospitalization of each eligible patient, an average of 90 days per patient</time_frame>
    <description>describe the operational taxonomic unit(OTU) numbers of each sample</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>neutrophil cell count</measure>
    <time_frame>during the hospitalization of each eligible patient, an average of 90 days per patient</time_frame>
    <description>blood test results</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>platelet count</measure>
    <time_frame>during the hospitalization of each eligible patient, an average of 90 days per patient</time_frame>
    <description>blood test results</description>
  </secondary_outcome>
  <other_outcome>
    <measure>relative abundance of Clostridiales</measure>
    <time_frame>during the hospitalization of each eligible patient, an average of 90 days per patient</time_frame>
    <description>describe the microbiome at the order level</description>
  </other_outcome>
  <other_outcome>
    <measure>Shannoneven indices</measure>
    <time_frame>during the hospitalization of each eligible patient, an average of 90 days per patient</time_frame>
    <description>measure the community evenness, scale ranges [0,1]; higher values represent a better outcome</description>
  </other_outcome>
  <other_outcome>
    <measure>Simpsoneven indices</measure>
    <time_frame>during the hospitalization of each eligible patient, an average of 90 days per patient</time_frame>
    <description>measure community evenness, scale ranges [0,1]; higher values represent a better outcome</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">13</enrollment>
  <condition>Inflammatory Bowel Diseases</condition>
  <condition>Microbiota</condition>
  <arm_group>
    <arm_group_label>HSCT cohort</arm_group_label>
    <description>IL10RA-deficient patients who received hematopoietic stem cell transplantation</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>hematopoietic stem cell transplantation</intervention_name>
    <description>Reduced intensity conditioning(RIC) chemotherapy regimen before transplantation&#xD;
All patients were cared for in single rooms ventilated with a highly effective particulate air filtration system. All patients received intravenous immunoglobulin and antimicrobial prophylaxis, which included antiviral, antifungal, and Pneumocystis jirovecii prophylaxis with ganciclovir and micafungin, as per routine clinical practice before transplantation.&#xD;
Umbilical cord blood transplantation</description>
    <arm_group_label>HSCT cohort</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Fecal samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients who were diagnosed with IL10RA deficiency and who received the hematopoietic stem&#xD;
        cell transplantation in a tertiary hospital were enrolled.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  IL10RA gene mutations;&#xD;
&#xD;
          -  Eligible for hematopoietic stem cell transplantation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unwilling to participate.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Day</minimum_age>
    <maximum_age>6 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ying Huang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital of Fudan University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's hospital of Fudan university</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>201102</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <results_reference>
    <citation>Peng K, Qian X, Huang Z, Lu J, Wang Y, Zhou Y, Wang H, Wu B, Wang Y, Chen L, Zhai X, Huang Y. Umbilical Cord Blood Transplantation Corrects Very Early-Onset Inflammatory Bowel Disease in Chinese Patients With IL10RA-Associated Immune Deficiency. Inflamm Bowel Dis. 2018 Jun 8;24(7):1416-1427. doi: 10.1093/ibd/izy028.</citation>
    <PMID>29788474</PMID>
  </results_reference>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>November 19, 2018</study_first_submitted>
  <study_first_submitted_qc>November 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 26, 2018</study_first_posted>
  <last_update_submitted>August 10, 2020</last_update_submitted>
  <last_update_submitted_qc>August 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Children's Hospital of Fudan University</investigator_affiliation>
    <investigator_full_name>Ying HUANG</investigator_full_name>
    <investigator_title>The director of gastroenterology of Children's Hospital of Fudan University</investigator_title>
  </responsible_party>
  <keyword>interleukin 10 receptor alpha gene</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inflammatory Bowel Diseases</mesh_term>
  </condition_browse>
  <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/NCT03752372
org study id: HSCT microbiomte
nct id: NCT03752372
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To elucidate the longitudinal development of intestinal microbiota in patients with IL10RA
      deficiency after hematopoietic stem cell transplantation (HSCT). The investigators planned to
      collect fecal samples from IL10RA-deficient patients who received HSCT. Samples were
      collected more than once every three days after engraftment in lamina flow ward and at least
      once a week before discharge. Microbial DNA was extracted from the fecal samples. And all
      analysis was based on the next generation sequencing data.
Hematopoietic stem cell transplantation is considered the only curative therapy for patients
      with interleukin-10 receptor-A(IL10RA) deficiency. The investigators aimed to collect the
      fecal samples of these patients throughout the conditioning, transplantation until discharge,
      providing a dense insight into the longitudinal development of intestinal microbiota.
observational model: Cohort
time perspective: Prospective
measure: Shannon indices
time frame: during the hospitalization of each eligible patient, an average of 90 days per patient
description: Shannon index is a popular diversity index in the ecological literature; minimum score is zero, higher values represent a better outcome
measure: Simpson indices
time frame: during the hospitalization of each eligible patient, an average of 90 days per patient
description: Simpson index in ecology is to measure the degree of concentration when individuals are classified into types; scale ranges [0,1]; lower values represent a better outcome
measure: relative abundance of Proteobacteria
time frame: during the hospitalization of each eligible patient, an average of 90 days per patient
description: describe the microbiome at the phylum level
measure: relative abundance of Firmicutes
time frame: during the hospitalization of each eligible patient, an average of 90 days per patient
description: describe the microbiome at the phylum level
measure: Clostridium sensus_stricto_1
time frame: during the hospitalization of each eligible patient, an average of 90 days per patient
description: describe the microbiome at the genus level
measure: Escherichia - Shigella
time frame: during the hospitalization of each eligible patient, an average of 90 days per patient
description: describe the microbiome at the genus level
measure: chimerism
time frame: during the hospitalization of each eligible patient, an average of 90 days per patient
description: The level of chimerism of each patient will be reported as percentages [0,100%]
measure: manifestation of graft-versus-host disease
time frame: during the hospitalization of each eligible patient, an average of 90 days per patient
description: describe the graft-versus-host disease happened to each patient
measure: Sobs indices
time frame: during the hospitalization of each eligible patient, an average of 90 days per patient
description: describe the the observed richness of each sample
measure: Chao1 estimator
time frame: during the hospitalization of each eligible patient, an average of 90 days per patient
description: describe the operational taxonomic unit(OTU) numbers of each sample
measure: neutrophil cell count
time frame: during the hospitalization of each eligible patient, an average of 90 days per patient
description: blood test results
measure: platelet count
time frame: during the hospitalization of each eligible patient, an average of 90 days per patient
description: blood test results
measure: relative abundance of Clostridiales
time frame: during the hospitalization of each eligible patient, an average of 90 days per patient
description: describe the microbiome at the order level
measure: Shannoneven indices
time frame: during the hospitalization of each eligible patient, an average of 90 days per patient
description: measure the community evenness, scale ranges [0,1]; higher values represent a better outcome
measure: Simpsoneven indices
time frame: during the hospitalization of each eligible patient, an average of 90 days per patient
description: measure community evenness, scale ranges [0,1]; higher values represent a better outcome
arm group label: HSCT cohort
description: IL10RA-deficient patients who received hematopoietic stem cell transplantation
intervention type: Procedure
intervention name: hematopoietic stem cell transplantation
description: Reduced intensity conditioning(RIC) chemotherapy regimen before transplantation
All patients were cared for in single rooms ventilated with a highly effective particulate air filtration system. All patients received intravenous immunoglobulin and antimicrobial prophylaxis, which included antiviral, antifungal, and Pneumocystis jirovecii prophylaxis with ganciclovir and micafungin, as per routine clinical practice before transplantation.
Umbilical cord blood transplantation
arm group label: HSCT cohort
Fecal samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 1 Day
maximum age: 6 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ying Huang, MD
role: Principal Investigator
affiliation: Children's Hospital of Fudan University
facility: 
country: China
citation: Peng K, Qian X, Huang Z, Lu J, Wang Y, Zhou Y, Wang H, Wu B, Wang Y, Chen L, Zhai X, Huang Y. Umbilical Cord Blood Transplantation Corrects Very Early-Onset Inflammatory Bowel Disease in Chinese Patients With IL10RA-Associated Immune Deficiency. Inflamm Bowel Dis. 2018 Jun 8;24(7):1416-1427. doi: 10.1093/ibd/izy028.
PMID: 29788474
responsible party type: Principal Investigator
investigator affiliation: Children's Hospital of Fudan University
investigator full name: Ying HUANG
investigator title: The director of gastroenterology of Children's Hospital of Fudan University
mesh term: Inflammatory Bowel Diseases
sharing ipd: No