<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/NCT04437225</url>
  </required_header>
  <id_info>
    <org_study_id>IRB-160505004</org_study_id>
    <nct_id>NCT04437225</nct_id>
  </id_info>
  <brief_title>Renal Metabolism of Glycolate to Oxalate</brief_title>
  <official_title>Renal Metabolism of Glycolate to Oxalate</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>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will determine the contribution of glycolate metabolism to urinary oxalate&#xD;
      excretion in healthy subjects, using carbon 13 isotope glycolate tracer technique and a&#xD;
      low-oxalate controlled diet.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It is known that glycolate, an intermediary molecule in normal metabolism, can be converted&#xD;
      into oxalate. The origin of urinary oxalate is of interest as calcium oxalate is a main&#xD;
      component of kidney stones. In the rare disease primary hyperoxaluria, excessive production&#xD;
      of oxalate by the body results in frequent kidney stones and can cause loss of kidney&#xD;
      function. Primary hyperoxaluria is caused by deficiencies in one of several enzymes involved&#xD;
      in the glycolate pathway.&#xD;
&#xD;
      This study will seek to determine how much oxalate is formed from glycolate in normal&#xD;
      subjects. After consuming a controlled diet, subjects will either ingest or have an&#xD;
      intravenous infusion of carbon 13 glycolate, a stable isotope of glycolate that can be&#xD;
      tracked and will also label downstream metabolic products. Blood and urine samples will be&#xD;
      assessed for their amounts of labeled glycolate and labeled oxalate to provide an accurate&#xD;
      measure of how much oxalate is made from normal glycolate breakdown in healthy human&#xD;
      subjects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 12, 2020</start_date>
  <completion_date type="Anticipated">December 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2025</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>Sequential Assignment</intervention_model>
    <intervention_model_description>Subject will undergo the gold-standard technique of steady-state intravenous infusion of 13-glycolate administration. Selected subjects will also undergo other modified modalities of 13-glycolate administration.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Urinary oxalate measured by ion chromatography coupled with mass spectrometry</measure>
    <time_frame>day 5 of dietary control</time_frame>
    <description>Measurement of carbon 13 labeled and unlabeled urinary oxalate following carbon 13 glycolate administration, after equilibration under a low-oxalate diet.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma glycolate measured by ion chromatography coupled with mass spectrometry</measure>
    <time_frame>day 5 of dietary control</time_frame>
    <description>Measurement of carbon 13 labeled and unlabeled plasma glycolate following carbon 13 glycolate administration, after equilibration under a low-oxalate diet.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Urinary creatinine</measure>
    <time_frame>day 5 of dietary control</time_frame>
    <description>Baseline assessment of 24hr urinary creatinine under controlled low-oxalate diet.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urinary glycolate measured by ion chromatography coupled with mass spectrometry</measure>
    <time_frame>day 5 of dietary control</time_frame>
    <description>Measurement of carbon 13 labeled and unlabeled urinary glycolate following carbon 13 glycolate administration, after equilibration under a low-oxalate diet.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Constant Infusion of 13C2-Glycolate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will consume a controlled diet for 5 days total. On Days 3 and 4, subjects will collect 24 hour urines. On Day 5, they will come to the Clinical Research Unit (CRU) in the fasted state for a visit lasting from 7:00 am to 5:30 pm. An intravenous (IV) catheter will be placed in a vein on the back of the hand at 7:30 am for the carbon 13 glycolate infusion which will occur at a constant rate for 10 hours, following a priming dose. From 7:30 am to 5:30 pm, urine collections will occur hourly, and from 8:30 am to 5:30 pm, IV blood collections will occur every half hour. Subjects will receive a meal at 5:30 pm, thus concluding the CRU visit. At home, subjects will collect timed urine until the next morning to be returned to the CRU.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Single Intravenous Dose of 13C2-Glycolate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will consume a controlled diet for 5 days total. On Days 3 and 4, subjects will collect 24 hour urines. On Day 5, they will come to the Clinical Research Unit (CRU) in the fasted state for a visit lasting from 7:00 am to 2:30 pm. An intravenous (IV) catheter will be placed in a vein on the back of the hand at 8:30 am for a single dose of carbon-13 glycolate to be administered. From 7:30 am to 2:30 pm, urine collections will occur hourly. At 8:30 am, IV blood samples will be taken every fifteen minutes until 9:30 am, every half hour from 9:30 am to 10:30 am, and then finally hourly from 10:30 am to 2:30 pm . Subjects will receive a meal at 2:30 pm, thus concluding the CRU visit. At home, subjects will collect timed urine until the next morning to be returned to the CRU.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Single Oral Dose of 13C2-Glycolate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will consume a controlled diet for 5 days total. On Days 3 and 4, subjects will collect 24 hour urines. On Day 5, they will come to the Clinical Research Unit (CRU) in the fasted state for a visit lasting from 7:00 am to 2:30 pm. At 8:30 am, subjects will ingest the carbon-13 glycolate, dissolved in to 50 ml (about 1/4 cup) of water. From 7:30 am to 2:30 pm, urine collections will occur hourly. At 8:30 am, intravenous (IV) blood samples will be taken every fifteen minutes until 9:30 am, every half hour from 9:30 am to 10:30 am, and then finally hourly from 10:30 am to 2:30 pm . Subjects will receive a meal at 2:30 pm, thus concluding the CRU visit. At home, subjects will collect timed urine until the next morning to be returned to the CRU.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Low oxalate controlled Diet</intervention_name>
    <description>Participants will consume a diet that is controlled in its contents of protein, carbohydrates, fat, calcium, oxalate, vitamin C and sodium. Participants will be asked not to take any dietary supplements, exercise strenuously, or consume food or drink that is not provided to them.</description>
    <arm_group_label>Constant Infusion of 13C2-Glycolate</arm_group_label>
    <arm_group_label>Single Intravenous Dose of 13C2-Glycolate</arm_group_label>
    <arm_group_label>Single Oral Dose of 13C2-Glycolate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Primed, continuous intravenous infusion of 13C2-Glycolate</intervention_name>
    <description>Participants will receive a continuous intravenous administration of carbon-13 glycolate, a naturally occurring form of glycolate, over the course of several hours until steady-state is achieved, using an IV catheter.</description>
    <arm_group_label>Constant Infusion of 13C2-Glycolate</arm_group_label>
    <other_name>Constant infusion of 13C2-Glycolate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Bolus intravenous infusion of 13C2-Glycolate</intervention_name>
    <description>Participants will receive a bolus intravenous administration of carbon-13 glycolate, a naturally occurring form of glycolate, using an IV catheter.</description>
    <arm_group_label>Single Intravenous Dose of 13C2-Glycolate</arm_group_label>
    <other_name>Single intravenous dose of 13C2-Glycolate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Oral bolus administration of 13C2-Glycolate</intervention_name>
    <description>Participants will orally ingest a single dose of carbon-13 glycolate, a naturally occurring form of glycolate.</description>
    <arm_group_label>Single Oral Dose of 13C2-Glycolate</arm_group_label>
    <other_name>Single oral dose of 13C2-Glycolate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Mentally competent adults, able to read and comprehend the consent form&#xD;
&#xD;
          -  18-75 years of age&#xD;
&#xD;
          -  Body Mass Index (BMI) between 19 and 40&#xD;
&#xD;
          -  In good health as judged from a medical history, reported medications, and a complete&#xD;
             blood metabolic profile&#xD;
&#xD;
          -  Acceptable 24 hour urine collections (performed twice for screening)&#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 urine excretion of ions&#xD;
&#xD;
          -  Abnormal urine chemistries or blood metabolic profiles&#xD;
&#xD;
          -  Poor 24 hour urine collections completed during screening, judged by 24 hour urine&#xD;
             creatinine excretion (indicative of not collecting all urine in the 24 hour period)&#xD;
&#xD;
          -  Pregnancy, intention to become pregnant in the near future, or lactation&#xD;
&#xD;
          -  Aged &lt;18 or &gt;75&#xD;
&#xD;
          -  BMI &lt;19 or &gt;40&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sonia Fargue, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Alabama at Birmingham</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sonia Fargue, M.D., Ph.D.</last_name>
    <phone>205-975-6932</phone>
    <email>kidneystone@uabmc.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sonia Fargue, M.D., Ph.D.</last_name>
      <phone>205-975-6932</phone>
      <email>kidneystone@uabmc.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>May 26, 2023</last_update_submitted>
  <last_update_submitted_qc>May 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 30, 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>Sonia Fargue</investigator_full_name>
    <investigator_title>Principle Investigator</investigator_title>
  </responsible_party>
  <keyword>oxalate metabolism</keyword>
  <keyword>kidney stones</keyword>
  <keyword>glycolate</keyword>
  <keyword>isotope tracer study</keyword>
  <keyword>urolithiasis</keyword>
  <keyword>oxalate</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glycolic acid</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04437225
org study id: IRB-160505004
nct id: NCT04437225
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study will determine the contribution of glycolate metabolism to urinary oxalate
      excretion in healthy subjects, using carbon 13 isotope glycolate tracer technique and a
      low-oxalate controlled diet.
It is known that glycolate, an intermediary molecule in normal metabolism, can be converted
      into oxalate. The origin of urinary oxalate is of interest as calcium oxalate is a main
      component of kidney stones. In the rare disease primary hyperoxaluria, excessive production
      of oxalate by the body results in frequent kidney stones and can cause loss of kidney
      function. Primary hyperoxaluria is caused by deficiencies in one of several enzymes involved
      in the glycolate pathway.

      This study will seek to determine how much oxalate is formed from glycolate in normal
      subjects. After consuming a controlled diet, subjects will either ingest or have an
      intravenous infusion of carbon 13 glycolate, a stable isotope of glycolate that can be
      tracked and will also label downstream metabolic products. Blood and urine samples will be
      assessed for their amounts of labeled glycolate and labeled oxalate to provide an accurate
      measure of how much oxalate is made from normal glycolate breakdown in healthy human
      subjects.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Subject will undergo the gold-standard technique of steady-state intravenous infusion of 13-glycolate administration. Selected subjects will also undergo other modified modalities of 13-glycolate administration.
primary purpose: Basic Science
masking: None (Open Label)
measure: Urinary oxalate measured by ion chromatography coupled with mass spectrometry
time frame: day 5 of dietary control
description: Measurement of carbon 13 labeled and unlabeled urinary oxalate following carbon 13 glycolate administration, after equilibration under a low-oxalate diet.
measure: Plasma glycolate measured by ion chromatography coupled with mass spectrometry
time frame: day 5 of dietary control
description: Measurement of carbon 13 labeled and unlabeled plasma glycolate following carbon 13 glycolate administration, after equilibration under a low-oxalate diet.
measure: Urinary creatinine
time frame: day 5 of dietary control
description: Baseline assessment of 24hr urinary creatinine under controlled low-oxalate diet.
measure: Urinary glycolate measured by ion chromatography coupled with mass spectrometry
time frame: day 5 of dietary control
description: Measurement of carbon 13 labeled and unlabeled urinary glycolate following carbon 13 glycolate administration, after equilibration under a low-oxalate diet.
arm group label: Constant Infusion of 13C2-Glycolate
arm group type: Experimental
description: Subjects will consume a controlled diet for 5 days total. On Days 3 and 4, subjects will collect 24 hour urines. On Day 5, they will come to the Clinical Research Unit (CRU) in the fasted state for a visit lasting from 7:00 am to 5:30 pm. An intravenous (IV) catheter will be placed in a vein on the back of the hand at 7:30 am for the carbon 13 glycolate infusion which will occur at a constant rate for 10 hours, following a priming dose. From 7:30 am to 5:30 pm, urine collections will occur hourly, and from 8:30 am to 5:30 pm, IV blood collections will occur every half hour. Subjects will receive a meal at 5:30 pm, thus concluding the CRU visit. At home, subjects will collect timed urine until the next morning to be returned to the CRU.
arm group label: Single Intravenous Dose of 13C2-Glycolate
arm group type: Experimental
description: Subjects will consume a controlled diet for 5 days total. On Days 3 and 4, subjects will collect 24 hour urines. On Day 5, they will come to the Clinical Research Unit (CRU) in the fasted state for a visit lasting from 7:00 am to 2:30 pm. An intravenous (IV) catheter will be placed in a vein on the back of the hand at 8:30 am for a single dose of carbon-13 glycolate to be administered. From 7:30 am to 2:30 pm, urine collections will occur hourly. At 8:30 am, IV blood samples will be taken every fifteen minutes until 9:30 am, every half hour from 9:30 am to 10:30 am, and then finally hourly from 10:30 am to 2:30 pm . Subjects will receive a meal at 2:30 pm, thus concluding the CRU visit. At home, subjects will collect timed urine until the next morning to be returned to the CRU.
arm group label: Single Oral Dose of 13C2-Glycolate
arm group type: Experimental
description: Subjects will consume a controlled diet for 5 days total. On Days 3 and 4, subjects will collect 24 hour urines. On Day 5, they will come to the Clinical Research Unit (CRU) in the fasted state for a visit lasting from 7:00 am to 2:30 pm. At 8:30 am, subjects will ingest the carbon-13 glycolate, dissolved in to 50 ml (about 1/4 cup) of water. From 7:30 am to 2:30 pm, urine collections will occur hourly. At 8:30 am, intravenous (IV) blood samples will be taken every fifteen minutes until 9:30 am, every half hour from 9:30 am to 10:30 am, and then finally hourly from 10:30 am to 2:30 pm . Subjects will receive a meal at 2:30 pm, thus concluding the CRU visit. At home, subjects will collect timed urine until the next morning to be returned to the CRU.
intervention type: Dietary Supplement
intervention name: Low oxalate controlled Diet
description: Participants will consume a diet that is controlled in its contents of protein, carbohydrates, fat, calcium, oxalate, vitamin C and sodium. Participants will be asked not to take any dietary supplements, exercise strenuously, or consume food or drink that is not provided to them.
arm group label: Constant Infusion of 13C2-Glycolate
arm group label: Single Intravenous Dose of 13C2-Glycolate
arm group label: Single Oral Dose of 13C2-Glycolate
intervention type: Other
intervention name: Primed, continuous intravenous infusion of 13C2-Glycolate
description: Participants will receive a continuous intravenous administration of carbon-13 glycolate, a naturally occurring form of glycolate, over the course of several hours until steady-state is achieved, using an IV catheter.
arm group label: Constant Infusion of 13C2-Glycolate
other name: Constant infusion of 13C2-Glycolate
intervention type: Other
intervention name: Bolus intravenous infusion of 13C2-Glycolate
description: Participants will receive a bolus intravenous administration of carbon-13 glycolate, a naturally occurring form of glycolate, using an IV catheter.
arm group label: Single Intravenous Dose of 13C2-Glycolate
other name: Single intravenous dose of 13C2-Glycolate
intervention type: Other
intervention name: Oral bolus administration of 13C2-Glycolate
description: Participants will orally ingest a single dose of carbon-13 glycolate, a naturally occurring form of glycolate.
arm group label: Single Oral Dose of 13C2-Glycolate
other name: Single oral dose of 13C2-Glycolate
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sonia Fargue, M.D., Ph.D.
role: Principal Investigator
affiliation: University of Alabama at Birmingham
last name: Sonia Fargue, M.D., Ph.D.
phone: 205-975-6932
email: kidneystone@uabmc.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Alabama at Birmingham
investigator full name: Sonia Fargue
investigator title: Principle Investigator
mesh term: Glycolic acid