<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/NCT02975986</url>
  </required_header>
  <id_info>
    <org_study_id>STU 092014-032</org_study_id>
    <secondary_id>R01DK081423-07</secondary_id>
    <nct_id>NCT02975986</nct_id>
  </id_info>
  <brief_title>Renal Uptake of Fatty Acids (FFA) in Patients With Idiopathic Uric Acid Nephrolithiasis (IUAN)</brief_title>
  <acronym>IUAN</acronym>
  <official_title>Renal Uptake of Fatty Acids (FFA) in Patients With Idiopathic Uric Acid Nephrolithiasis (IUAN)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Texas Southwestern Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Texas Southwestern Medical Center</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 investigators will test the hypothesis that renal uptake of free (i.e. non-esterified)&#xD;
      fatty acids (FFa) is increased in iuan. To accomplish this goal the investigators will&#xD;
      measure renal FFa uptake FFa uptake in vivo in patients with iuan and matched non-stone&#xD;
      forming subjects via single-photon emission computed tomography (SPeCT)/CT imaging.&#xD;
&#xD;
      The definitive proof of the hypothesis rests on whether increased renal FFa uptake is&#xD;
      demonstrable in humans with iuan.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a cross-sectional study of patients with iuan and matched non-stone formers to test&#xD;
      the hypothesis that renal FFa uptake is increased in iuan, using noninvasive 123i-labeled&#xD;
      [MiCRo-SYMBoL]-methyl-p-iodo-phenyl-pentadecanoic acid(123i-BMiPP) SPeCT/CT imaging, an&#xD;
      established FFa analog approved for human studies.&#xD;
&#xD;
      Participants will be placed on an instructed controlled metabolic diet (30% fat, 15% protein,&#xD;
      55% carbohydrate, 300 mg cholesterol per day, 400 mg calcium, 800mg phosphorus, 100 meq&#xD;
      sodium, with low acid ash content, and 3000 cc distilled water) for 5 days to exclude dietary&#xD;
      confounders (3 days as outpatient and the final 2 days as inpatient). On days 4 and 5, two&#xD;
      fasting blood samples will be collected for the measurement of CMP, insulin, FFa and two 24-h&#xD;
      urine samples will be collected under mineral oil to be analyzed for total volume, pH, Cr,&#xD;
      na, K, Ca, Mg, Cl, P, uric acid, nH4+, titratable acidity (Ta), sulfate, HCo3- and citrate.&#xD;
      The morning of day 6, patients will undergo dual 123i-BMiPP and 99mTc-MaG3 (99mTc&#xD;
      mercaptoacetyltriglycine mertiatide) SPeCT/CT imaging after 12 hrs of fasting. 99mTc-MaG3&#xD;
      (8-10mCi) will be injected intravenously for the flow phase of a standard renal scan which&#xD;
      includes dynamic imaging for 2 minutes. an additional 1 minute image will be acquired (the&#xD;
      2-3 minute image on a standard renal scan). acquisition will then stop. immediately afterward&#xD;
      123i-BMiPP (4-5mCi) will be injected intravenously for a 1hour uptake period. after the 1&#xD;
      hour uptake dual isotope (Tc-99m and i-123) SPeCT/CT images of the kidney will be acquired on&#xD;
      a clinical Siemens Symbia dual head SPeCT/CT system. The 99mTc-MaG3 flow image data will be&#xD;
      used to measure renal plasma flow,12 using the Ge Xeleris renal analysis software package&#xD;
      already installed on the clinical SPeCT/CT system. The 123i-BMiPP, a gamma emitter with a&#xD;
      half-life of 13.13 hours, is to measure renal 123i-BMiPP (FFa) uptake 13 123i-BMiPP uptake&#xD;
      will be corrected for effective renal plasma flow (mL/min) measured with 99mTc-MaG3, using&#xD;
      the Ge Xeleris renal analysis software package.&#xD;
&#xD;
      Expected findings: If the hypothesis is correct, the investigators expect increased FFa&#xD;
      uptake as measured by 123i-BMiPP SPeCT/CT corrected for renal effective plasma flow in the&#xD;
      kidney cortex of iuan patients vs. matched controls.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <start_date>January 2017</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">September 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Increased FFA uptake as measured by 123I-BMIPP SPECT/CT corrected for renal effective plasma flow in the kidney cortex of IUAN patients vs. matched controls</measure>
    <time_frame>6 days</time_frame>
    <description>Based on preliminary animal study, we anticipate a mean difference of approximately 26% between IUAN and control non-stone forming subjects, but with a higher CV of 20%. For 80% power (=0.05), will be able to detect at 1.5 standardized effect size (%change/CV) with n=10 per group. Comparisons between IUAN and non-stone former groups will be made with two-sample t-tests or Wilcoxon Rank Sum tests.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Uric Acid Nephrolithiasis</condition>
  <arm_group>
    <arm_group_label>Controlled metabolic diet</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All study patients will be placed on an instructed controlled metabolic diet. Intervention: Uptake of radioactive isotope by the kidney Radiotracer: 123I-BMIPP, 99mTc-MAG3</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>123I-BMIPP</intervention_name>
    <description>Uptake of radioactive isotope by the kidney</description>
    <arm_group_label>Controlled metabolic diet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>99mTc-MAG3</intervention_name>
    <description>Uptake of radioactive isotope by the kidney</description>
    <arm_group_label>Controlled metabolic diet</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  In the IUAN group (N=10), we will include adult subjects with documented IUAN, age &gt;&#xD;
             21 years, either sex, any ethnicity&#xD;
&#xD;
          -  In the Control group (N=10), we will include volunteers with no history of stone&#xD;
             disease matched for age (within 5 years), gender, ethnicity, BMI (within 10%) and&#xD;
             diabetes status&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindications to SPECT/CT, pregnancy, breastfeeding, chronic renal disease (eGFR &lt;&#xD;
             60 ml/min/1.73m2), proteinuria, genetic diseases of the kidney, inborn defects of&#xD;
             lipid metabolism, alcohol abuse, liver disease (patients with highly elevated total&#xD;
             bilirubin, elevated liver enzymes AST, ALT and alkaline phosphatase and those with an&#xD;
             established liver disease), anemia, and pharmacological treatment with insulin or&#xD;
             insulin-sensitizing drugs such as thiazolidinediones (TZD).&#xD;
&#xD;
          -  Patients on antidyslipidemic drugs, alkali therapy or allopurinol will be instructed&#xD;
             to discontinue these drugs 2 weeks prior to the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Khashayar Sakhaee, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UT Southwestern</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UT Southwestern Medical Center - Center for Mineral Metabolism</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390-8885</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>November 23, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>October 1, 2020</last_update_submitted>
  <last_update_submitted_qc>October 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Nephrolithiasis, Uric Acid</keyword>
  <keyword>Fatty Acid</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nephrolithiasis</mesh_term>
    <mesh_term>Kidney Calculi</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Technetium Tc 99m Mertiatide</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/NCT02975986
org study id: STU 092014-032
secondary id: R01DK081423-07
nct id: NCT02975986
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The investigators will test the hypothesis that renal uptake of free (i.e. non-esterified)
      fatty acids (FFa) is increased in iuan. To accomplish this goal the investigators will
      measure renal FFa uptake FFa uptake in vivo in patients with iuan and matched non-stone
      forming subjects via single-photon emission computed tomography (SPeCT)/CT imaging.

      The definitive proof of the hypothesis rests on whether increased renal FFa uptake is
      demonstrable in humans with iuan.
This is a cross-sectional study of patients with iuan and matched non-stone formers to test
      the hypothesis that renal FFa uptake is increased in iuan, using noninvasive 123i-labeled
      [MiCRo-SYMBoL]-methyl-p-iodo-phenyl-pentadecanoic acid(123i-BMiPP) SPeCT/CT imaging, an
      established FFa analog approved for human studies.

      Participants will be placed on an instructed controlled metabolic diet (30% fat, 15% protein,
      55% carbohydrate, 300 mg cholesterol per day, 400 mg calcium, 800mg phosphorus, 100 meq
      sodium, with low acid ash content, and 3000 cc distilled water) for 5 days to exclude dietary
      confounders (3 days as outpatient and the final 2 days as inpatient). On days 4 and 5, two
      fasting blood samples will be collected for the measurement of CMP, insulin, FFa and two 24-h
      urine samples will be collected under mineral oil to be analyzed for total volume, pH, Cr,
      na, K, Ca, Mg, Cl, P, uric acid, nH4+, titratable acidity (Ta), sulfate, HCo3- and citrate.
      The morning of day 6, patients will undergo dual 123i-BMiPP and 99mTc-MaG3 (99mTc
      mercaptoacetyltriglycine mertiatide) SPeCT/CT imaging after 12 hrs of fasting. 99mTc-MaG3
      (8-10mCi) will be injected intravenously for the flow phase of a standard renal scan which
      includes dynamic imaging for 2 minutes. an additional 1 minute image will be acquired (the
      2-3 minute image on a standard renal scan). acquisition will then stop. immediately afterward
      123i-BMiPP (4-5mCi) will be injected intravenously for a 1hour uptake period. after the 1
      hour uptake dual isotope (Tc-99m and i-123) SPeCT/CT images of the kidney will be acquired on
      a clinical Siemens Symbia dual head SPeCT/CT system. The 99mTc-MaG3 flow image data will be
      used to measure renal plasma flow,12 using the Ge Xeleris renal analysis software package
      already installed on the clinical SPeCT/CT system. The 123i-BMiPP, a gamma emitter with a
      half-life of 13.13 hours, is to measure renal 123i-BMiPP (FFa) uptake 13 123i-BMiPP uptake
      will be corrected for effective renal plasma flow (mL/min) measured with 99mTc-MaG3, using
      the Ge Xeleris renal analysis software package.

      Expected findings: If the hypothesis is correct, the investigators expect increased FFa
      uptake as measured by 123i-BMiPP SPeCT/CT corrected for renal effective plasma flow in the
      kidney cortex of iuan patients vs. matched controls.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Increased FFA uptake as measured by 123I-BMIPP SPECT/CT corrected for renal effective plasma flow in the kidney cortex of IUAN patients vs. matched controls
time frame: 6 days
description: Based on preliminary animal study, we anticipate a mean difference of approximately 26% between IUAN and control non-stone forming subjects, but with a higher CV of 20%. For 80% power (=0.05), will be able to detect at 1.5 standardized effect size (%change/CV) with n=10 per group. Comparisons between IUAN and non-stone former groups will be made with two-sample t-tests or Wilcoxon Rank Sum tests.
arm group label: Controlled metabolic diet
arm group type: Other
description: All study patients will be placed on an instructed controlled metabolic diet. Intervention: Uptake of radioactive isotope by the kidney Radiotracer: 123I-BMIPP, 99mTc-MAG3
intervention type: Other
intervention name: 123I-BMIPP
description: Uptake of radioactive isotope by the kidney
arm group label: Controlled metabolic diet
intervention type: Other
intervention name: 99mTc-MAG3
description: Uptake of radioactive isotope by the kidney
arm group label: Controlled metabolic diet
criteria: 
gender: All
minimum age: 21 Years
maximum age: 99 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Khashayar Sakhaee, MD
role: Principal Investigator
affiliation: UT Southwestern
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Nephrolithiasis
mesh term: Kidney Calculi
mesh term: Technetium Tc 99m Mertiatide
sharing ipd: No