<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/NCT03010735</url>
  </required_header>
  <id_info>
    <org_study_id>CAUPCKD-02</org_study_id>
    <nct_id>NCT03010735</nct_id>
  </id_info>
  <brief_title>Effects of Probiotics on the Patients With End Stage Renal Disease (ESRD)</brief_title>
  <official_title>Effects of Probiotics on Metabolism of Uremic Toxin in Patients With End Stage Renal Disease (ESRD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>China Agricultural University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Peking University Aerospace Centre Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>General Hospital of Chinese Armed Police Forces</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Beijing Anzhen Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Beijing Biostats Technology Co. Ltd.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Beijing Heyiyuan Biotech Co. Ltd.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>China Agricultural University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate the effects of oral administration of probiotics&#xD;
      on the metabolism of uremic toxins, in the patients with End Stage Renal Disease (ESRD). One&#xD;
      hundred and fifty hemodialysis patients are recruited, and a Double Blind Randomized Parallel&#xD;
      Controlled Trial was performed.The microbiota-derived uremic toxin, such as indoxyl sulfate&#xD;
      and p-cresol sulfate, are measured as Primary Outcome. The Fecal microbiome, fecal&#xD;
      metabolites, blood metabolites, defecation, Gastrointestinal Symptoms The Kidney Disease&#xD;
      Quality of Life and The Occurrence of Cardiovascular Event are also assessed.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2015</start_date>
  <completion_date type="Actual">December 2017</completion_date>
  <primary_completion_date type="Actual">February 2017</primary_completion_date>
  <phase>Phase 2/Phase 3</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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in Microbiota-derived uremic toxin</measure>
    <time_frame>6 months</time_frame>
    <description>follow up the patients at Month 0, 3, 6</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in Fecal Microbiome</measure>
    <time_frame>6 months</time_frame>
    <description>follow up the patients at Month 0, 3, 6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Fecal metabolites</measure>
    <time_frame>6 months</time_frame>
    <description>follow up the patients at Month 0, 3, 6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Blood metabolites</measure>
    <time_frame>6 months</time_frame>
    <description>follow up the patients at Month 0, 3, 6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Defecation questionnaire</measure>
    <time_frame>6 months</time_frame>
    <description>follow up the patients at Month 0, 3, 6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gastrointestinal Symptoms</measure>
    <time_frame>6 months</time_frame>
    <description>follow up the patients at Month 0, 3, 6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Kidney Disease Quality of Life</measure>
    <time_frame>6 months</time_frame>
    <description>follow up the patients at Month 0, 3, 6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Occurrence of Cardiovascular Event</measure>
    <time_frame>6 month follow-up</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">150</enrollment>
  <condition>Kidney Failure, Chronic</condition>
  <arm_group>
    <arm_group_label>Probiotics</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The patient take two chewing tablet per day, which contain 4.0E+10 CFU of probiotics.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The patient take two placebo chewing tablet per day.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>probiotics</intervention_name>
    <description>Daily take 4.0E+10 CFU of probiotics</description>
    <arm_group_label>Probiotics</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age over 18 years old&#xD;
&#xD;
          -  Patients who diagnosed as ESRD with hemodialysis&#xD;
&#xD;
          -  Fixed hemodialysis cycle (average 3 times a week)&#xD;
&#xD;
          -  Agree to take the products to be studied during the study period, and no longer take&#xD;
             other fermented dairy products (live lactic acid bacteria drinks, cheese, yogurt,&#xD;
             probiotic products, etc.)&#xD;
&#xD;
          -  Agree to sign the informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Taking antibiotics or antifungal drugs within 30 days before the study&#xD;
&#xD;
          -  Have serious allergic reaction to skim milk powder&#xD;
&#xD;
          -  Researcher are not sure whether the subjects are willing or able to complete the study&#xD;
&#xD;
          -  Subject participated in other research projects within two months before the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fazheng Ren, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>China Agricultural Universtiy</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beijing Anzhen Hospital</name>
      <address>
        <city>Beijing</city>
        <zip>100029</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>General Hospital of Chinese Armed Police Forces</name>
      <address>
        <city>Beijing</city>
        <zip>100039</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peking University Aerospace Centre Hospital</name>
      <address>
        <city>Beijing</city>
        <zip>100049</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Vaziri ND, Wong J, Pahl M, Piceno YM, Yuan J, DeSantis TZ, Ni Z, Nguyen TH, Andersen GL. Chronic kidney disease alters intestinal microbial flora. Kidney Int. 2013 Feb;83(2):308-15. doi: 10.1038/ki.2012.345. Epub 2012 Sep 19.</citation>
    <PMID>22992469</PMID>
  </reference>
  <reference>
    <citation>Poesen R, Windey K, Neven E, Kuypers D, De Preter V, Augustijns P, D'Haese P, Evenepoel P, Verbeke K, Meijers B. The Influence of CKD on Colonic Microbial Metabolism. J Am Soc Nephrol. 2016 May;27(5):1389-99. doi: 10.1681/ASN.2015030279. Epub 2015 Sep 23.</citation>
    <PMID>26400570</PMID>
  </reference>
  <reference>
    <citation>Koppe L, Mafra D, Fouque D. Probiotics and chronic kidney disease. Kidney Int. 2015 Nov;88(5):958-66. doi: 10.1038/ki.2015.255. Epub 2015 Sep 16.</citation>
    <PMID>26376131</PMID>
  </reference>
  <reference>
    <citation>Anders HJ, Andersen K, Stecher B. The intestinal microbiota, a leaky gut, and abnormal immunity in kidney disease. Kidney Int. 2013 Jun;83(6):1010-6. doi: 10.1038/ki.2012.440. Epub 2013 Jan 16.</citation>
    <PMID>23325079</PMID>
  </reference>
  <reference>
    <citation>Ramezani A, Raj DS. The gut microbiome, kidney disease, and targeted interventions. J Am Soc Nephrol. 2014 Apr;25(4):657-70. doi: 10.1681/ASN.2013080905. Epub 2013 Nov 14.</citation>
    <PMID>24231662</PMID>
  </reference>
  <reference>
    <citation>Poesen R, Claes K, Evenepoel P, de Loor H, Augustijns P, Kuypers D, Meijers B. Microbiota-Derived Phenylacetylglutamine Associates with Overall Mortality and Cardiovascular Disease in Patients with CKD. J Am Soc Nephrol. 2016 Nov;27(11):3479-3487. doi: 10.1681/ASN.2015121302. Epub 2016 May 26.</citation>
    <PMID>27230658</PMID>
  </reference>
  <reference>
    <citation>Meyer TW, Hostetter TH. Uremia. N Engl J Med. 2007 Sep 27;357(13):1316-25. doi: 10.1056/NEJMra071313. No abstract available.</citation>
    <PMID>17898101</PMID>
  </reference>
  <reference>
    <citation>Aronov PA, Luo FJ, Plummer NS, Quan Z, Holmes S, Hostetter TH, Meyer TW. Colonic contribution to uremic solutes. J Am Soc Nephrol. 2011 Sep;22(9):1769-76. doi: 10.1681/ASN.2010121220. Epub 2011 Jul 22.</citation>
    <PMID>21784895</PMID>
  </reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>December 28, 2016</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <last_update_submitted>October 20, 2020</last_update_submitted>
  <last_update_submitted_qc>October 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>China Agricultural University</investigator_affiliation>
    <investigator_full_name>Fazheng Ren</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Kidney Failure, Chronic</keyword>
  <keyword>Probiotics</keyword>
  <keyword>Uremic toxins</keyword>
  <keyword>Gastrointestinal Microbiome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Failure, Chronic</mesh_term>
    <mesh_term>Renal Insufficiency</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/NCT03010735
org study id: CAUPCKD-02
nct id: NCT03010735
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to investigate the effects of oral administration of probiotics
      on the metabolism of uremic toxins, in the patients with End Stage Renal Disease (ESRD). One
      hundred and fifty hemodialysis patients are recruited, and a Double Blind Randomized Parallel
      Controlled Trial was performed.The microbiota-derived uremic toxin, such as indoxyl sulfate
      and p-cresol sulfate, are measured as Primary Outcome. The Fecal microbiome, fecal
      metabolites, blood metabolites, defecation, Gastrointestinal Symptoms The Kidney Disease
      Quality of Life and The Occurrence of Cardiovascular Event are also assessed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Changes in Microbiota-derived uremic toxin
time frame: 6 months
description: follow up the patients at Month 0, 3, 6
measure: Changes in Fecal Microbiome
time frame: 6 months
description: follow up the patients at Month 0, 3, 6
measure: Changes in Fecal metabolites
time frame: 6 months
description: follow up the patients at Month 0, 3, 6
measure: Changes in Blood metabolites
time frame: 6 months
description: follow up the patients at Month 0, 3, 6
measure: Defecation questionnaire
time frame: 6 months
description: follow up the patients at Month 0, 3, 6
measure: Gastrointestinal Symptoms
time frame: 6 months
description: follow up the patients at Month 0, 3, 6
measure: The Kidney Disease Quality of Life
time frame: 6 months
description: follow up the patients at Month 0, 3, 6
measure: The Occurrence of Cardiovascular Event
time frame: 6 month follow-up
arm group label: Probiotics
arm group type: Active Comparator
description: The patient take two chewing tablet per day, which contain 4.0E+10 CFU of probiotics.
arm group label: Placebo
arm group type: Placebo Comparator
description: The patient take two placebo chewing tablet per day.
intervention type: Dietary Supplement
intervention name: probiotics
description: Daily take 4.0E+10 CFU of probiotics
arm group label: Probiotics
intervention type: Dietary Supplement
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Fazheng Ren, PhD
role: Principal Investigator
affiliation: China Agricultural Universtiy
facility: 
facility: 
facility: 
country: China
citation: Vaziri ND, Wong J, Pahl M, Piceno YM, Yuan J, DeSantis TZ, Ni Z, Nguyen TH, Andersen GL. Chronic kidney disease alters intestinal microbial flora. Kidney Int. 2013 Feb;83(2):308-15. doi: 10.1038/ki.2012.345. Epub 2012 Sep 19.
PMID: 22992469
citation: Poesen R, Windey K, Neven E, Kuypers D, De Preter V, Augustijns P, D'Haese P, Evenepoel P, Verbeke K, Meijers B. The Influence of CKD on Colonic Microbial Metabolism. J Am Soc Nephrol. 2016 May;27(5):1389-99. doi: 10.1681/ASN.2015030279. Epub 2015 Sep 23.
PMID: 26400570
citation: Koppe L, Mafra D, Fouque D. Probiotics and chronic kidney disease. Kidney Int. 2015 Nov;88(5):958-66. doi: 10.1038/ki.2015.255. Epub 2015 Sep 16.
PMID: 26376131
citation: Anders HJ, Andersen K, Stecher B. The intestinal microbiota, a leaky gut, and abnormal immunity in kidney disease. Kidney Int. 2013 Jun;83(6):1010-6. doi: 10.1038/ki.2012.440. Epub 2013 Jan 16.
PMID: 23325079
citation: Ramezani A, Raj DS. The gut microbiome, kidney disease, and targeted interventions. J Am Soc Nephrol. 2014 Apr;25(4):657-70. doi: 10.1681/ASN.2013080905. Epub 2013 Nov 14.
PMID: 24231662
citation: Poesen R, Claes K, Evenepoel P, de Loor H, Augustijns P, Kuypers D, Meijers B. Microbiota-Derived Phenylacetylglutamine Associates with Overall Mortality and Cardiovascular Disease in Patients with CKD. J Am Soc Nephrol. 2016 Nov;27(11):3479-3487. doi: 10.1681/ASN.2015121302. Epub 2016 May 26.
PMID: 27230658
citation: Meyer TW, Hostetter TH. Uremia. N Engl J Med. 2007 Sep 27;357(13):1316-25. doi: 10.1056/NEJMra071313. No abstract available.
PMID: 17898101
citation: Aronov PA, Luo FJ, Plummer NS, Quan Z, Holmes S, Hostetter TH, Meyer TW. Colonic contribution to uremic solutes. J Am Soc Nephrol. 2011 Sep;22(9):1769-76. doi: 10.1681/ASN.2010121220. Epub 2011 Jul 22.
PMID: 21784895
responsible party type: Principal Investigator
investigator affiliation: China Agricultural University
investigator full name: Fazheng Ren
investigator title: Professor
mesh term: Kidney Failure, Chronic
mesh term: Renal Insufficiency
sharing ipd: No