xml: <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/NCT06003348</url>
    </required_header>
    <id_info>
      <org_study_id>2023-0339</org_study_id>
      <nct_id>NCT06003348</nct_id>
    </id_info>
    <brief_title>Hydroxycitrate: A Novel Therapy for Calcium Phosphate Urinary Stones</brief_title>
    <official_title>Hydroxycitrate: A Novel Therapy for Calcium Phosphate Urinary Stones</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Texas Southwestern Medical Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Texas Southwestern Medical Center</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study tests whether hydroxycitrate, a molecule closely related to citrate, can reduce&#xD;
        calcium phosphate stone recurrence.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        In this double-blind, placebo-controlled, randomized, crossover study, each participant will&#xD;
        undergo 4 phases of study, with the order randomized by a blocked randomization scheme. The 4&#xD;
        phases will be Placebo, Super CitriMax (hydroxycitrate) OHCit low dose, OHCit standard dose,&#xD;
        or Potassium Citrate. Randomization will be stratified based on sex, concomitant thiazide&#xD;
        use, and concomitant alkali use.&#xD;
  &#xD;
        Each phase will be 1 week in duration, during which subjects will take assigned study&#xD;
        medications. A minimum 1-week washout period will be imposed between phases. During the first&#xD;
        2 days of each phase, subjects will be instructed to adhere to a prescribed diet. On the last&#xD;
        5 days of each phase, subjects will be kept on a constant metabolic diet. Use of metabolic&#xD;
        diet is essential to eliminate confounders that could occur from changes in dietary intake&#xD;
        across phases. During the final two study days (days 6-7), two 24-hr urines will be collected&#xD;
        for urine biochemistry and crystallization studies. Fasting blood will be obtained at the end&#xD;
        of the last urine collection.&#xD;
  &#xD;
        Study Medications: Subjects will receive three tablets twice daily during each phase. These&#xD;
        will consist of either placebo, Potassium Citrate (KCit), or Super CitriMax (OHCit). Study&#xD;
        tablets will be prepared by a compounding pharmacy, with placebo tablets similar in&#xD;
        appearance and size to the active medication tablets.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">August 31, 2028</completion_date>
    <primary_completion_date type="Anticipated">May 31, 2028</primary_completion_date>
    <phase>Phase 4</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Crossover Assignment</intervention_model>
      <intervention_model_description>In this double-blind, placebo-controlled, randomized, crossover study, each participant will undergo 4 phases of study, with the order randomized by a blocked randomization scheme. The 4 phases will be Placebo, Super CitriMax (OHCit) low dose, Super CitriMax (OHCit) standard dose, or Potassium Citrate. Randomization will be stratified based on sex, concomitant thiazide use, and concomitant alkali use.</intervention_model_description>
      <primary_purpose>Prevention</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Formation product (FP) for Calcium Phosphate</measure>
      <time_frame>After 1 week of treatment</time_frame>
      <description>FP is obtained by adding increasing amounts of Calcium Chloride (CaCl2) to a series of urine aliquots maintained at constant pH for 2 hours, and is identified by the point at which calcium phosphate (CaP) precipitates as detected by an absorbance microplate reader.&#xD;
  Calculated supersaturation using [Calcium] and [Phosphate] at that point represents FP.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Crystal growth of Calcium Phosphate</measure>
      <time_frame>After 1 week of treatment</time_frame>
      <description>We will assess crystal growth (CG) of CaP after seeding urine with a small amount of brushite (0.25 mg/ml urine) and incubating at 37°C for 3 hours (representing steady state) under constant stirring. A decrement in [Calcium]×[Phosphate] after seeding signifies crystal growth, while a [Calcium]×[Phosphate] increment represents crystal dissolution.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Calcium Phosphate supersaturation</measure>
      <time_frame>After 1 week of treatment</time_frame>
      <description>Supersaturation of calcium phosphate will be assessed by Joint Expert Speciation System (JESS).</description>
    </secondary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">25</enrollment>
    <condition>Calcium Phosphate Kidney Stones</condition>
    <arm_group>
      <arm_group_label>Potassium Citrate (Urocit®-K)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Potassium Citrate KCit 10 mEq 2 tabs, twice daily and Placebo 1 tab, twice daily Total Daily Dose: Citrate 40 mEq/d</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Super CitriMax; OHCit-standard dose</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Super CitriMax 7 mEq 3 tabs, twice daily Total Daily Dose: OHCit 42 mEq/d</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Super CitriMax; OHCit-low dose</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Super CitriMax 7 mEq 2 tabs, twice daily And Placebo 1 tab, twice daily Total Daily Dose: OHCit 28 mEq/d</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Placebo 3 tablets twice daily Total Daily Dose: None</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>OHCit- standard dose</intervention_name>
      <description>Hydroxycitrate Over-the-counter supplement, not FDA approved or regulated.</description>
      <arm_group_label>Super CitriMax; OHCit-standard dose</arm_group_label>
      <other_name>Super Citrimax</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Potassium Citrate</intervention_name>
      <description>10 mEq Extended-release tablets for oral use</description>
      <arm_group_label>Potassium Citrate (Urocit®-K)</arm_group_label>
      <other_name>Urocit®-K</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Placebo</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>OHCit- low dose</intervention_name>
      <description>Hydroxycitrate Over-the-counter supplement, not FDA approved or regulated.</description>
      <arm_group_label>Super CitriMax; OHCit-low dose</arm_group_label>
      <other_name>Super Citrimax</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          - Calcium Phosphate stone formers&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History of recurrent urinary tract infections&#xD;
  &#xD;
            -  Chronic diarrhea&#xD;
  &#xD;
            -  Estimated Glomerular Filtration Rate (eGFR) &lt; 45 ml/min/1.73 m2&#xD;
  &#xD;
            -  History of primary hyperparathyroidism&#xD;
  &#xD;
            -  Hypokalemia&#xD;
  &#xD;
            -  Hyperkalemia&#xD;
  &#xD;
            -  Pregnancy&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>21 Years</minimum_age>
      <maximum_age>99 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>NAIM M MAALOUF</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Texas Southwestern Medical Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>NAIM M MAALOUF, MD</last_name>
      <phone>214/648-2954</phone>
      <email>naim.maalouf@utsouthwestern.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Miranda King</last_name>
      <phone>2146482117</phone>
      <email>Miranda.King@utsouthwestern.edu</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 14, 2023</study_first_submitted>
    <study_first_submitted_qc>August 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 25, 2023</last_update_submitted>
    <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Texas Southwestern Medical Center</investigator_affiliation>
      <investigator_full_name>Naim Maalouf</investigator_full_name>
      <investigator_title>Professor, Internal Medicine</investigator_title>
    </responsible_party>
    <keyword>Urolithiasis</keyword>
    <keyword>Calcium phosphate</keyword>
    <keyword>Citrate</keyword>
    <keyword>Acid-base</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Kidney Calculi</mesh_term>
      <mesh_term>Urinary Calculi</mesh_term>
      <mesh_term>Urolithiasis</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Potassium Citrate</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06003348
  org study id: 2023-0339
  nct id: NCT06003348
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  This study tests whether hydroxycitrate, a molecule closely related to citrate, can reduce
        calcium phosphate stone recurrence.
  In this double-blind, placebo-controlled, randomized, crossover study, each participant will
        undergo 4 phases of study, with the order randomized by a blocked randomization scheme. The 4
        phases will be Placebo, Super CitriMax (hydroxycitrate) OHCit low dose, OHCit standard dose,
        or Potassium Citrate. Randomization will be stratified based on sex, concomitant thiazide
        use, and concomitant alkali use.
  
        Each phase will be 1 week in duration, during which subjects will take assigned study
        medications. A minimum 1-week washout period will be imposed between phases. During the first
        2 days of each phase, subjects will be instructed to adhere to a prescribed diet. On the last
        5 days of each phase, subjects will be kept on a constant metabolic diet. Use of metabolic
        diet is essential to eliminate confounders that could occur from changes in dietary intake
        across phases. During the final two study days (days 6-7), two 24-hr urines will be collected
        for urine biochemistry and crystallization studies. Fasting blood will be obtained at the end
        of the last urine collection.
  
        Study Medications: Subjects will receive three tablets twice daily during each phase. These
        will consist of either placebo, Potassium Citrate (KCit), or Super CitriMax (OHCit). Study
        tablets will be prepared by a compounding pharmacy, with placebo tablets similar in
        appearance and size to the active medication tablets.
  allocation: Randomized
  intervention model: Crossover Assignment
  intervention model description: In this double-blind, placebo-controlled, randomized, crossover study, each participant will undergo 4 phases of study, with the order randomized by a blocked randomization scheme. The 4 phases will be Placebo, Super CitriMax (OHCit) low dose, Super CitriMax (OHCit) standard dose, or Potassium Citrate. Randomization will be stratified based on sex, concomitant thiazide use, and concomitant alkali use.
  primary purpose: Prevention
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Formation product (FP) for Calcium Phosphate
  time frame: After 1 week of treatment
  description: FP is obtained by adding increasing amounts of Calcium Chloride (CaCl2) to a series of urine aliquots maintained at constant pH for 2 hours, and is identified by the point at which calcium phosphate (CaP) precipitates as detected by an absorbance microplate reader.
  Calculated supersaturation using [Calcium] and [Phosphate] at that point represents FP.
  measure: Crystal growth of Calcium Phosphate
  time frame: After 1 week of treatment
  description: We will assess crystal growth (CG) of CaP after seeding urine with a small amount of brushite (0.25 mg/ml urine) and incubating at 37°C for 3 hours (representing steady state) under constant stirring. A decrement in [Calcium]×[Phosphate] after seeding signifies crystal growth, while a [Calcium]×[Phosphate] increment represents crystal dissolution.
  measure: Calcium Phosphate supersaturation
  time frame: After 1 week of treatment
  description: Supersaturation of calcium phosphate will be assessed by Joint Expert Speciation System (JESS).
  arm group label: Potassium Citrate (Urocit®-K)
  arm group type: Active Comparator
  description: Potassium Citrate KCit 10 mEq 2 tabs, twice daily and Placebo 1 tab, twice daily Total Daily Dose: Citrate 40 mEq/d
  arm group label: Super CitriMax; OHCit-standard dose
  arm group type: Experimental
  description: Super CitriMax 7 mEq 3 tabs, twice daily Total Daily Dose: OHCit 42 mEq/d
  arm group label: Super CitriMax; OHCit-low dose
  arm group type: Experimental
  description: Super CitriMax 7 mEq 2 tabs, twice daily And Placebo 1 tab, twice daily Total Daily Dose: OHCit 28 mEq/d
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Placebo 3 tablets twice daily Total Daily Dose: None
  intervention type: Dietary Supplement
  intervention name: OHCit- standard dose
  description: Hydroxycitrate Over-the-counter supplement, not FDA approved or regulated.
  arm group label: Super CitriMax; OHCit-standard dose
  other name: Super Citrimax
  intervention type: Drug
  intervention name: Potassium Citrate
  description: 10 mEq Extended-release tablets for oral use
  arm group label: Potassium Citrate (Urocit®-K)
  other name: Urocit®-K
  intervention type: Drug
  intervention name: Placebo
  description: Placebo
  arm group label: Placebo
  intervention type: Dietary Supplement
  intervention name: OHCit- low dose
  description: Hydroxycitrate Over-the-counter supplement, not FDA approved or regulated.
  arm group label: Super CitriMax; OHCit-low dose
  other name: Super Citrimax
  criteria: 
  gender: All
  minimum age: 21 Years
  maximum age: 99 Years
  healthy volunteers: No
  last name: NAIM M MAALOUF
  role: Principal Investigator
  affiliation: University of Texas Southwestern Medical Center
  last name: NAIM M MAALOUF, MD
  phone: 214/648-2954
  email: naim.maalouf@utsouthwestern.edu
  last name: Miranda King
  phone: 2146482117
  email: Miranda.King@utsouthwestern.edu
  responsible party type: Principal Investigator
  investigator affiliation: University of Texas Southwestern Medical Center
  investigator full name: Naim Maalouf
  investigator title: Professor, Internal Medicine
  mesh term: Kidney Calculi
  mesh term: Urinary Calculi
  mesh term: Urolithiasis
  mesh term: Potassium Citrate