<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/NCT03752684</url>
  </required_header>
  <id_info>
    <org_study_id>IRB-131212001</org_study_id>
    <nct_id>NCT03752684</nct_id>
  </id_info>
  <brief_title>Oxalobacter Formigenes Colonization and Urinary Oxalate Excretion</brief_title>
  <official_title>Oxalobacter Formigenes Colonization and Oxalate Excretion in Calcium Oxalate Kidney Stone Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Alabama at Birmingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Alabama at Birmingham</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 purpose of this research study is to assess the efficacy of ingesting a small amount of&#xD;
      the harmless bacterium Oxalobacter formigenes in establishing residence in the guts of human&#xD;
      subjects and to determine whether this influences the oxalate passed in urine of healthy&#xD;
      volunteers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Adults that are not colonized with O. formigenes, have no history of stone disease and are in&#xD;
      good health as judged by their medical history, a complete metabolic profile of their serum,&#xD;
      and ranges of ions that influence stone formation in two 24-hour urine collections, will be&#xD;
      recruited from within the greater Birmingham area. Recruited subjects will be between the&#xD;
      ages of 18 to 65 years and with a BMI &gt;19 and &lt;32.&#xD;
&#xD;
      Subjects not colonized with O. formigenes will consume, firstly, a controlled diet containing&#xD;
      50 mg oxalate and 1000mg calcium (low oxalate/normal calcium diet), followed by a 250 mg&#xD;
      oxalate/400mg calcium controlled diet (moderately high oxalate/low calcium diet), with at&#xD;
      least a one week washout between each diet, and then repeat the same sequence of diets after&#xD;
      colonization with O.formigenes Group 1 strain OxCC13. Controlled diets will be prepared in&#xD;
      the Metabolic Kitchen of the UAB Clinical Research Unit (CRU). Sustainability of colonization&#xD;
      will be determined over time. Loss of colonization will be confirmed by having the subject&#xD;
      consume an oxalate-rich meal with subsequent testing for O. formigenes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 2, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Actual">April 27, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Evaluate urinary oxalate excretion before and after colonization with the oxalate degrading bacterium Oxalobacter formigenes</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Measurement of urinary oxalate by ion chromatography mass spectrometry</measure>
    <time_frame>1st 24 hour collection</time_frame>
    <description>1st 24 hour urine collection, started 24 hours after initiation of controlled diet</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Measurement of urinary oxalate by ion chromatography mass spectrometry</measure>
    <time_frame>2nd 24 hour collection</time_frame>
    <description>48 hours post diet</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Measurement of urinary oxalate by ion chromatography mass spectrometry</measure>
    <time_frame>3rd 24 hour collection</time_frame>
    <description>72 hours post diet</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Measurement of urinary oxalate by ion chromatography mass spectrometry</measure>
    <time_frame>4th 24 hour urine collection</time_frame>
    <description>96 hours post diet</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measurement of stool oxalate by ion chromatography mass spectrometry</measure>
    <time_frame>Stool collected 48-96 hours post diet</time_frame>
    <description>First bowel movement collected during days 2 through 4 of dietary control</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement of stool oxalate by ion chromatography mass spectrometry</measure>
    <time_frame>Stool collected 48-96 hours post diet</time_frame>
    <description>Second bowel movement collected during days 2 through 4 of dietary control</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement of stool oxalate by ion chromatography mass spectrometry</measure>
    <time_frame>Stool collected 48-96 hours post diet</time_frame>
    <description>Third bowel movement collected during days 2 through 4 of dietary control</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Calcium Oxalate Urolithiasis</condition>
  <arm_group>
    <arm_group_label>Low Oxalate Diet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects not colonized with Oxalobacter formigenes will be equilibrated to a low oxalate diet to determine baseline oxalate values in urine .&#xD;
Subjects will be colonized with Oxalobacter formigenes (Intervention). Following colonization with Oxalobacter formigenes, urinary oxalate will be measured to determine the impact of colonization.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Moderately high oxalate/low calcium diet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects not colonized with Oxalobacter formigenes will be equilibrated to a moderately high oxalate/ low calcium oxalate diet to enhance dietary oxalate absorption.&#xD;
Subjects will be colonized with Oxalobacter formigenes(Intervention). Following colonization with Oxalobacter formigenes, urinary oxalate will be measured to determine the impact of colonization.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Oxalobacter formigenes</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will ingest a live preparation of O.formigenes</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Low Oxalate Diet</intervention_name>
    <description>Subjects will be instructed to ingest a controlled diet low in oxalate</description>
    <arm_group_label>Low Oxalate Diet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Moderately high oxalate/low calcium diet</intervention_name>
    <description>Subjects will be instructed to ingest a controlled diet moderately high in oxalate</description>
    <arm_group_label>Moderately high oxalate/low calcium diet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Oxalobacter formigenes</intervention_name>
    <description>Subjects will ingest live preparation of O. formigenes</description>
    <arm_group_label>Oxalobacter formigenes</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Good health as judged from a medical history and reported medications&#xD;
&#xD;
          -  Not colonized with O. formigenes&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of any hepatic, renal, bowel or endocrine disease or any other condition that&#xD;
             may influence the absorption, transport or urinary excretion of ions, which will&#xD;
             compromise the interpretation of results&#xD;
&#xD;
          -  colonized with O. formigenes&#xD;
&#xD;
          -  abnormal urine chemistries or blood metabolic profiles&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John Knight, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Alabama at Birmingham</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>October 22, 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>July 17, 2023</last_update_submitted>
  <last_update_submitted_qc>July 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Alabama at Birmingham</investigator_affiliation>
    <investigator_full_name>John Knight</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Oxalobacter formigenes</keyword>
  <keyword>oxalate</keyword>
  <keyword>kidney stones</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urolithiasis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Calcium</mesh_term>
  </intervention_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/NCT03752684
org study id: IRB-131212001
nct id: NCT03752684
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this research study is to assess the efficacy of ingesting a small amount of
      the harmless bacterium Oxalobacter formigenes in establishing residence in the guts of human
      subjects and to determine whether this influences the oxalate passed in urine of healthy
      volunteers.
Adults that are not colonized with O. formigenes, have no history of stone disease and are in
      good health as judged by their medical history, a complete metabolic profile of their serum,
      and ranges of ions that influence stone formation in two 24-hour urine collections, will be
      recruited from within the greater Birmingham area. Recruited subjects will be between the
      ages of 18 to 65 years and with a BMI >19 and <32.

      Subjects not colonized with O. formigenes will consume, firstly, a controlled diet containing
      50 mg oxalate and 1000mg calcium (low oxalate/normal calcium diet), followed by a 250 mg
      oxalate/400mg calcium controlled diet (moderately high oxalate/low calcium diet), with at
      least a one week washout between each diet, and then repeat the same sequence of diets after
      colonization with O.formigenes Group 1 strain OxCC13. Controlled diets will be prepared in
      the Metabolic Kitchen of the UAB Clinical Research Unit (CRU). Sustainability of colonization
      will be determined over time. Loss of colonization will be confirmed by having the subject
      consume an oxalate-rich meal with subsequent testing for O. formigenes.
allocation: Non-Randomized
intervention model: Crossover Assignment
intervention model description: Evaluate urinary oxalate excretion before and after colonization with the oxalate degrading bacterium Oxalobacter formigenes
primary purpose: Basic Science
masking: None (Open Label)
measure: Measurement of urinary oxalate by ion chromatography mass spectrometry
time frame: 1st 24 hour collection
description: 1st 24 hour urine collection, started 24 hours after initiation of controlled diet
measure: Measurement of urinary oxalate by ion chromatography mass spectrometry
time frame: 2nd 24 hour collection
description: 48 hours post diet
measure: Measurement of urinary oxalate by ion chromatography mass spectrometry
time frame: 3rd 24 hour collection
description: 72 hours post diet
measure: Measurement of urinary oxalate by ion chromatography mass spectrometry
time frame: 4th 24 hour urine collection
description: 96 hours post diet
measure: Measurement of stool oxalate by ion chromatography mass spectrometry
time frame: Stool collected 48-96 hours post diet
description: First bowel movement collected during days 2 through 4 of dietary control
measure: Measurement of stool oxalate by ion chromatography mass spectrometry
time frame: Stool collected 48-96 hours post diet
description: Second bowel movement collected during days 2 through 4 of dietary control
measure: Measurement of stool oxalate by ion chromatography mass spectrometry
time frame: Stool collected 48-96 hours post diet
description: Third bowel movement collected during days 2 through 4 of dietary control
arm group label: Low Oxalate Diet
arm group type: Experimental
description: Subjects not colonized with Oxalobacter formigenes will be equilibrated to a low oxalate diet to determine baseline oxalate values in urine .
Subjects will be colonized with Oxalobacter formigenes (Intervention). Following colonization with Oxalobacter formigenes, urinary oxalate will be measured to determine the impact of colonization.
arm group label: Moderately high oxalate/low calcium diet
arm group type: Experimental
description: Subjects not colonized with Oxalobacter formigenes will be equilibrated to a moderately high oxalate/ low calcium oxalate diet to enhance dietary oxalate absorption.
Subjects will be colonized with Oxalobacter formigenes(Intervention). Following colonization with Oxalobacter formigenes, urinary oxalate will be measured to determine the impact of colonization.
arm group label: Oxalobacter formigenes
arm group type: Experimental
description: Subjects will ingest a live preparation of O.formigenes
intervention type: Other
intervention name: Low Oxalate Diet
description: Subjects will be instructed to ingest a controlled diet low in oxalate
arm group label: Low Oxalate Diet
intervention type: Other
intervention name: Moderately high oxalate/low calcium diet
description: Subjects will be instructed to ingest a controlled diet moderately high in oxalate
arm group label: Moderately high oxalate/low calcium diet
intervention type: Other
intervention name: Oxalobacter formigenes
description: Subjects will ingest live preparation of O. formigenes
arm group label: Oxalobacter formigenes
criteria: 
gender: All
minimum age: 19 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: John Knight, PhD
role: Principal Investigator
affiliation: University of Alabama at Birmingham
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Alabama at Birmingham
investigator full name: John Knight
investigator title: Associate Professor
mesh term: Urolithiasis
mesh term: Calcium
sharing ipd: No