<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/NCT02209636</url>
  </required_header>
  <id_info>
    <org_study_id>CLNB-006-13F</org_study_id>
    <secondary_id>CX001030</secondary_id>
    <nct_id>NCT02209636</nct_id>
  </id_info>
  <brief_title>Phosphate Lowering in CKD Trial</brief_title>
  <official_title>Phosphate Lowering to Treat Vascular Dysfunction in Chronic Kidney Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>VA Office of Research and Development</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>
      The proposed research is a randomized-controlled trial to determine the effectiveness of&#xD;
      reducing serum phosphorus using a phosphate binder, lanthanum carbonate, for improving the&#xD;
      function of arteries in adults with moderate to severe chronic kidney disease (CKD). [COMIRB&#xD;
      13-0328] Additionally, it will determine phosphorus balance among adults with CKD and whether&#xD;
      there is a difference in phosphorus balance after three months of treatment with lanthanum&#xD;
      carbonate. [COMIRB 15-0384]&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic kidney disease (CKD) is a major health concern both in the general and Veteran&#xD;
      populations. Indeed, the prevalence of CKD in a large Veteran population is 20%.&#xD;
      Cardiovascular disease (CVD) is significantly increased in CKD and is an important cause of&#xD;
      morbidity and mortality. As much as 80% of all CVD is associated with vascular dysfunction,&#xD;
      particularly impaired endothelium-dependent dilation (EDD), measured by brachial artery&#xD;
      flow-mediate dilation (FMD), and stiffening of the large elastic arteries, measured by aortic&#xD;
      pulse-wave velocity (aPWV). Not surprisingly, patients with CKD demonstrate these&#xD;
      dysfunctional vascular phenotypes. Even in early stages of CKD, there is an increase in&#xD;
      oxidative stress resulting in structural and functional vascular changes, which, in turn,&#xD;
      contributes to vascular dysfunction (impaired EDD and large elastic artery stiffening). In&#xD;
      CKD, phosphorus remains within the normal range (2.5-4.5 mg/dL) until late in the disease.&#xD;
      However, elevated serum phosphorus, even within the normal range, is associated with impaired&#xD;
      EDD and with indirect measures of arterial stiffness. Whether lowering serum phosphorus in&#xD;
      patients with CKD will improve EDD and arterial stiffness is unknown. This study is a&#xD;
      randomized-controlled trial of lanthanum carbonate, a non-calcium based phosphate binder, to&#xD;
      treat vascular dysfunction. The efficacy of phosphate binding with lanthanum carbonate for&#xD;
      treating vascular endothelial dysfunction and large elastic artery stiffness in patients with&#xD;
      stage IIIb and IV CKD (estimated glomerular filtration rate 15-45 mL/min/1.73m2) with&#xD;
      baseline serum phosphorus of 2.8-5.5 mg/dL will be assessed. The study will also determine if&#xD;
      lowering serum phosphorus with lanthanum carbonate also reduces circulating and endothelial&#xD;
      cell markers of oxidative stress. This study could shift clinical practice guidelines by&#xD;
      establishing a novel therapy for reducing CVD risk in CKD patients not requiring chronic&#xD;
      hemodialysis. [COMIRB 13-0328]&#xD;
&#xD;
      Little is known about phosphorus balance in CKD. It is assumed that CKD patients remain in&#xD;
      neutral phosphorus balance despite decreases in kidney function. Serum phosphorus remains in&#xD;
      the normal range until late in CKD thus making it difficult to recognize perturbations in&#xD;
      phosphorus balance. Indeed, among CKD patients treated with the non-calcium containing&#xD;
      phosphate binder, sevelamer, serum phosphorus did not change after six weeks of treatment but&#xD;
      urinary phosphate excretion, parathyroid hormone, and fibroblast growth factor-23 changed&#xD;
      significantly, suggesting a shift in phosphorus homeostasis. However, two other studies found&#xD;
      that patients with CKD III-IV treated with calcium-containing phosphate binders remained in&#xD;
      neutral phosphorus balance. There are no studies evaluating the effects of non-calcium based&#xD;
      phosphate binders on phosphorus balance among patients with CKD nor other studies examining&#xD;
      the effect of changing phosphorus balance on vascular function.&#xD;
&#xD;
      An extension of the above-described 12-week prospective randomized, placebo-controlled&#xD;
      double-blind trial (COMIRB 13-0328) will be conducted in a subset of subjects. A total of 24&#xD;
      subjects from COMIRB 13-0328 will be recruited to participate in the Phosphorus Balance&#xD;
      sub-investigation (12 subjects treated with lanthanum carbonate and 12 subjects treated with&#xD;
      placebo). [15-0384] They will consume a diet with a fixed phosphorus content (1000 +/- 50 mg)&#xD;
      for seven days. They will then be admitted to the inpatient Center for Translational Clinical&#xD;
      Research at the University of Colorado Denver for 48 hours to accurately collect urine and&#xD;
      stool samples. The goal of the Phosphorus Balance sub-investigation (COMIRB 15-0384) is to&#xD;
      determine whether lowering serum phosphorus, accomplished during the parent phosphorus&#xD;
      lowering randomized-controlled trial (COMIRB 13-0328), affects phosphorus balance compared to&#xD;
      those subjects treated with placebo. A key secondary goal is to determine if differences in&#xD;
      phosphorus balance affect vascular function as measured by FMD. [15-0384]&#xD;
&#xD;
      To ensure adequate enrollment in the Phosphorus Balance Study (COMIRB 15-0384), an amendment&#xD;
      was approved to recruit patients with stage IIIb and IV CKD with normal or modestly elevated&#xD;
      serum phosphorus (2.8-5.5 mg/dL) who are not currently participating in the parent Phosphorus&#xD;
      Lowering RCT (COMIRB 13-0328). Similar to the Phosphorus Lowering RCT, these patients will&#xD;
      follow a low phosphorus diet and will be randomized to lanthanum carbonate or placebo for 12&#xD;
      weeks (run-in period) prior to beginning the current Phosphorus Balance protocol.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 15, 2014</start_date>
  <completion_date type="Actual">December 20, 2019</completion_date>
  <primary_completion_date type="Actual">June 28, 2019</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Brachial Artery Flow-mediated Dilation</measure>
    <time_frame>baseline and 12 weeks</time_frame>
    <description>Measurement of how well the brachial artery dilates in response to shear stress. It is a measure of endothelial function. It is reported as &quot;percent change&quot;, which represents the change in dilation of the artery before and after occlusion.&#xD;
Brachial artery flow-mediated dilation will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change brachial artery flow mediated dilation from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Aortic Pulse-wave Velocity</measure>
    <time_frame>baseline and 12 weeks</time_frame>
    <description>The speed that blood travels from the carotid artery to the femoral artery, expressed as cm/s (centimeters/second). It is a measure of arterial stiffness.&#xD;
Aortic pulse-wave velocity will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change aortic pulse wave velocity from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phosphorus Balance Sub-study (COMIRB 15-0384)</measure>
    <time_frame>9 days from the start of the sub-study, approximately 13 weeks and 2 days from the start of the Main/Parent Study</time_frame>
    <description>Balance is defined as oral intake minus urine output minus stool output.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Oxidative Stress-associated Suppression of EDD</measure>
    <time_frame>baseline and 12 weeks</time_frame>
    <description>The influence of oxidative stress on FMD will be determined by infusing a supraphysiologic dose of ascorbic acid or isovolemic saline. The difference in FMD, expressed as percentage change in FMD, which represents the change in dilation of the artery before and after occlusion, during ascorbic acid vs. saline infusion will be taken as a measure of the modulation of EDD/stiffness by oxidative stress.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vascular Endothelial Cell Protein Expression</measure>
    <time_frame>baseline and 12 weeks</time_frame>
    <description>Measures of different protein markers on endothelial cells. Will help understand the underlying pathophysiology of vascular dysfunction in chronic kidney disease. Vascular endothelial cell protein expression will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change vascular endothelial cell protein expression from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups. The expression of endothelial cells collected from patients will be compared to the expression in HUVEC (human umbilical vein endothelial cell) controls and this ratio will be reported as the outcomes measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interleukin-6 to Measure Systemic Inflammation</measure>
    <time_frame>baseline and 12 weeks</time_frame>
    <description>This is a blood test. Interleukin-6 and C-reactive protein will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change in interleukin-6 and C-reactive protein from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxidized Low-density Lipoprotein (Ox-LDL) to Measure Systemic Oxidized Stress</measure>
    <time_frame>baseline and 12 weeks</time_frame>
    <description>This is a blood test art. Oxidized low-density lipoprotein (ox-LDL) will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change in ox-LDL from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-reactive Protein to Measure Systemic Inflammation</measure>
    <time_frame>baseline and 12 weeks</time_frame>
    <description>This is a blood test. C-reactive protein will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change in C-reactive protein from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">66</enrollment>
  <condition>Chronic Kidney Disease</condition>
  <condition>Cardiovascular Disease</condition>
  <arm_group>
    <arm_group_label>Lanthanum carbonate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eligible subjects who are randomly assigned to the experimental arm will receive lanthanum carbonate (1500-4500 mg/day in divided doses) titrated to serum phosphorus levels.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Eligible subjects who are randomly assigned to the placebo arm will receive placebo tablets (identical to the active lanthanum carbonate tablets) to be taken 3 times daily and titrated to serum phosphorus levels.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lanthanum carbonate</intervention_name>
    <description>Non-calcium containing phosphorus binder</description>
    <arm_group_label>Lanthanum carbonate</arm_group_label>
    <other_name>Fosrenol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Table identical to lanthanum carbonate but with no active ingredient</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ascorbic Acid</intervention_name>
    <description>Intravenous administration during measurement of flow mediated dilation.</description>
    <arm_group_label>Lanthanum carbonate</arm_group_label>
    <arm_group_label>placebo</arm_group_label>
    <other_name>Vitamin C</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nitroglycerin</intervention_name>
    <description>Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.</description>
    <arm_group_label>Lanthanum carbonate</arm_group_label>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Flow-mediated dilation measurement</intervention_name>
    <description>Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.</description>
    <arm_group_label>Lanthanum carbonate</arm_group_label>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Aortic pulse-wave velocity</intervention_name>
    <description>Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.</description>
    <arm_group_label>Lanthanum carbonate</arm_group_label>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Endothelial cell collection</intervention_name>
    <description>Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
    <arm_group_label>Lanthanum carbonate</arm_group_label>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 40-79, women must be post-menopausal&#xD;
&#xD;
          -  CKD stage IIIb or IV (estimated glomerular filtration rate by MDRD 15-45&#xD;
             mL/min/1.73m2), stable for 3 months&#xD;
&#xD;
          -  Serum phosphorus 2.8-5.5 mg/dL, stable for 3 months&#xD;
&#xD;
          -  Not using phosphate binders&#xD;
&#xD;
          -  Albumin &gt; 3.0 g/dL&#xD;
&#xD;
          -  Free from alcohol dependence or abuse&#xD;
&#xD;
          -  Ability to provide informed consent&#xD;
&#xD;
          -  BMI &lt; 40 kg/m2&#xD;
&#xD;
          -  Not taking medications that interact with agents administered during experimental&#xD;
             sessions (e.g., sildenafil interacts with nitroglycerin)&#xD;
&#xD;
          -  For COMIRB 15-0384, completion of the prospective, randomized, placebo-controlled&#xD;
             double-blind trial, Phosphorus Lowering to Treat Vascular Dysfunction in Chronic&#xD;
             Kidney Disease (COMIRB 13-0328) or completion of 12-week run-in phase&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Life expectancy &lt;1 year&#xD;
&#xD;
          -  Uncontrolled hypertension&#xD;
&#xD;
          -  History of severe liver disease&#xD;
&#xD;
          -  History of congestive heart failure (EF &lt; 35%)&#xD;
&#xD;
          -  History of hospitalizations within the last 3 months&#xD;
&#xD;
          -  History of ileus or bowel obstruction&#xD;
&#xD;
          -  Active infection or antibiotic therapy&#xD;
&#xD;
          -  Expected kidney transplant in the next 6 months&#xD;
&#xD;
          -  Active vitamin D analogue use (i.e. calcitriol, paricalcitol, doxercalciferol)&#xD;
&#xD;
          -  Vasculitis requiring immunosuppressive therapy within the last year&#xD;
&#xD;
          -  Current tobacco abuse&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anna J Jovanovich, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rocky Mountain Regional VA Medical Center, Aurora, CO</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rocky Mountain Regional VA Medical Center, Aurora, CO</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>July 21, 2014</study_first_submitted>
  <study_first_submitted_qc>August 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 6, 2014</study_first_posted>
  <results_first_submitted>December 1, 2021</results_first_submitted>
  <results_first_submitted_qc>August 2, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">August 26, 2022</results_first_posted>
  <last_update_submitted>August 2, 2022</last_update_submitted>
  <last_update_submitted_qc>August 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>hyperphosphatemia</keyword>
  <keyword>vascular dysfunction</keyword>
  <keyword>chronic kidney disease</keyword>
  <keyword>cardiovascular disease</keyword>
  <keyword>endothelial dysfunction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
    <mesh_term>Cardiovascular Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ascorbic Acid</mesh_term>
    <mesh_term>Nitroglycerin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 7, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/36/NCT02209636/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>N = 66 completed screening and signed consent so were considered enrolled; however, N = 5 did not receive allocated intervention because N = 3 withdrew consent, N = 1 had uncontrolled hypertension after screening, and N =1 had phosphorus levels that were too low to receive study drug after screening.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Lanthanum Carbonate</title>
          <description>Eligible subjects who are randomly assigned to the experimental arm will receive lanthanum carbonate (1500-4500 mg/day in divided doses) titrated to serum phosphorus levels.&#xD;
Lanthanum carbonate: Non-calcium containing phosphorus binder&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Eligible subjects who are randomly assigned to the placebo arm will receive placebo tablets (identical to the active lanthanum carbonate tablets) to be taken 3 times daily and titrated to serum phosphorus levels.&#xD;
placebo: Table identical to lanthanum carbonate but with no active ingredient&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Main/Parent Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
                <participants group_id="P2" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Balance Sub-study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Lanthanum Carbonate</title>
          <description>Eligible subjects who are randomly assigned to the experimental arm will receive lanthanum carbonate (1500-4500 mg/day in divided doses) titrated to serum phosphorus levels.&#xD;
Lanthanum carbonate: Non-calcium containing phosphorus binder&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Eligible subjects who are randomly assigned to the placebo arm will receive placebo tablets (identical to the active lanthanum carbonate tablets) to be taken 3 times daily and titrated to serum phosphorus levels.&#xD;
placebo: Table identical to lanthanum carbonate but with no active ingredient&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="32"/>
            <count group_id="B2" value="29"/>
            <count group_id="B3" value="61"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66" spread="8"/>
                    <measurement group_id="B2" value="65" spread="8"/>
                    <measurement group_id="B3" value="66" spread="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="52"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Brachial Artery Flow-mediated Dilation</title>
        <description>Measurement of how well the brachial artery dilates in response to shear stress. It is a measure of endothelial function. It is reported as &quot;percent change&quot;, which represents the change in dilation of the artery before and after occlusion.&#xD;
Brachial artery flow-mediated dilation will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change brachial artery flow mediated dilation from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.</description>
        <time_frame>baseline and 12 weeks</time_frame>
        <population>Participants were analyzed if they had baseline and end-of-study FMD measurements and the measurements were of sufficient quality to be analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Lanthanum Carbonate</title>
            <description>Eligible subjects who are randomly assigned to the experimental arm will receive lanthanum carbonate (1500-4500 mg/day in divided doses) titrated to serum phosphorus levels.&#xD;
Lanthanum carbonate: Non-calcium containing phosphorus binder&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Eligible subjects who are randomly assigned to the placebo arm will receive placebo tablets (identical to the active lanthanum carbonate tablets) to be taken 3 times daily and titrated to serum phosphorus levels.&#xD;
placebo: Table identical to lanthanum carbonate but with no active ingredient&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
          </group>
        </group_list>
        <measure>
          <title>Brachial Artery Flow-mediated Dilation</title>
          <description>Measurement of how well the brachial artery dilates in response to shear stress. It is a measure of endothelial function. It is reported as &quot;percent change&quot;, which represents the change in dilation of the artery before and after occlusion.&#xD;
Brachial artery flow-mediated dilation will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change brachial artery flow mediated dilation from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.</description>
          <population>Participants were analyzed if they had baseline and end-of-study FMD measurements and the measurements were of sufficient quality to be analyzed.</population>
          <units>percent change FMD</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.13" spread="2.87"/>
                    <measurement group_id="O2" value="3.74" spread="2.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.73" spread="2.48"/>
                    <measurement group_id="O2" value="3.09" spread="2.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Aortic Pulse-wave Velocity</title>
        <description>The speed that blood travels from the carotid artery to the femoral artery, expressed as cm/s (centimeters/second). It is a measure of arterial stiffness.&#xD;
Aortic pulse-wave velocity will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change aortic pulse wave velocity from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.</description>
        <time_frame>baseline and 12 weeks</time_frame>
        <population>Participants were included if they had baseline and end of study aPWV measurements and aPWV measurements were of sufficient quality to be analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Lanthanum Carbonate</title>
            <description>Eligible subjects who are randomly assigned to the experimental arm will receive lanthanum carbonate (1500-4500 mg/day in divided doses) titrated to serum phosphorus levels.&#xD;
Lanthanum carbonate: Non-calcium containing phosphorus binder&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Eligible subjects who are randomly assigned to the placebo arm will receive placebo tablets (identical to the active lanthanum carbonate tablets) to be taken 3 times daily and titrated to serum phosphorus levels.&#xD;
placebo: Table identical to lanthanum carbonate but with no active ingredient&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
          </group>
        </group_list>
        <measure>
          <title>Aortic Pulse-wave Velocity</title>
          <description>The speed that blood travels from the carotid artery to the femoral artery, expressed as cm/s (centimeters/second). It is a measure of arterial stiffness.&#xD;
Aortic pulse-wave velocity will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change aortic pulse wave velocity from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.</description>
          <population>Participants were included if they had baseline and end of study aPWV measurements and aPWV measurements were of sufficient quality to be analyzed.</population>
          <units>change in aPWV, cm/s</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1214" spread="394"/>
                    <measurement group_id="O2" value="993" spread="289"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1216" spread="321"/>
                    <measurement group_id="O2" value="977" spread="254"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phosphorus Balance Sub-study (COMIRB 15-0384)</title>
        <description>Balance is defined as oral intake minus urine output minus stool output.</description>
        <time_frame>9 days from the start of the sub-study, approximately 13 weeks and 2 days from the start of the Main/Parent Study</time_frame>
        <population>Subjects who participated in the Phosphorus Balance sub-study and had sufficient stool volume for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Lanthanum Carbonate</title>
            <description>Eligible subjects who are randomly assigned to the experimental arm will receive lanthanum carbonate (1500-4500 mg/day in divided doses) titrated to serum phosphorus levels.&#xD;
Lanthanum carbonate: Non-calcium containing phosphorus binder&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Eligible subjects who are randomly assigned to the placebo arm will receive placebo tablets (identical to the active lanthanum carbonate tablets) to be taken 3 times daily and titrated to serum phosphorus levels.&#xD;
placebo: Table identical to lanthanum carbonate but with no active ingredient&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
          </group>
        </group_list>
        <measure>
          <title>Phosphorus Balance Sub-study (COMIRB 15-0384)</title>
          <description>Balance is defined as oral intake minus urine output minus stool output.</description>
          <population>Subjects who participated in the Phosphorus Balance sub-study and had sufficient stool volume for analysis.</population>
          <units>mg/d</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-131" spread="163"/>
                    <measurement group_id="O2" value="320" spread="141"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Oxidative Stress-associated Suppression of EDD</title>
        <description>The influence of oxidative stress on FMD will be determined by infusing a supraphysiologic dose of ascorbic acid or isovolemic saline. The difference in FMD, expressed as percentage change in FMD, which represents the change in dilation of the artery before and after occlusion, during ascorbic acid vs. saline infusion will be taken as a measure of the modulation of EDD/stiffness by oxidative stress.</description>
        <time_frame>baseline and 12 weeks</time_frame>
        <population>Participants were included if they had baseline and end of study FMD measurements, FMD measurements were of sufficient quality to be analyzed, and were able to receive ascorbic acid infusion.</population>
        <group_list>
          <group group_id="O1">
            <title>Lanthanum Carbonate</title>
            <description>Eligible subjects who are randomly assigned to the experimental arm will receive lanthanum carbonate (1500-4500 mg/day in divided doses) titrated to serum phosphorus levels.&#xD;
Lanthanum carbonate: Non-calcium containing phosphorus binder&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Eligible subjects who are randomly assigned to the placebo arm will receive placebo tablets (identical to the active lanthanum carbonate tablets) to be taken 3 times daily and titrated to serum phosphorus levels.&#xD;
placebo: Table identical to lanthanum carbonate but with no active ingredient&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
          </group>
        </group_list>
        <measure>
          <title>Oxidative Stress-associated Suppression of EDD</title>
          <description>The influence of oxidative stress on FMD will be determined by infusing a supraphysiologic dose of ascorbic acid or isovolemic saline. The difference in FMD, expressed as percentage change in FMD, which represents the change in dilation of the artery before and after occlusion, during ascorbic acid vs. saline infusion will be taken as a measure of the modulation of EDD/stiffness by oxidative stress.</description>
          <population>Participants were included if they had baseline and end of study FMD measurements, FMD measurements were of sufficient quality to be analyzed, and were able to receive ascorbic acid infusion.</population>
          <units>percent change in FMD</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>baseline FMD</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.91" spread="2.81"/>
                    <measurement group_id="O2" value="3.54" spread="2.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>baseline FMD after ascorbic acid</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.24" spread="3.48"/>
                    <measurement group_id="O2" value="3.44" spread="2.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 12 FMD</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.48" spread="2.54"/>
                    <measurement group_id="O2" value="2.95" spread="2.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 12 FMD w/ ascorbic acid</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.44" spread="3.19"/>
                    <measurement group_id="O2" value="3.69" spread="3.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Vascular Endothelial Cell Protein Expression</title>
        <description>Measures of different protein markers on endothelial cells. Will help understand the underlying pathophysiology of vascular dysfunction in chronic kidney disease. Vascular endothelial cell protein expression will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change vascular endothelial cell protein expression from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups. The expression of endothelial cells collected from patients will be compared to the expression in HUVEC (human umbilical vein endothelial cell) controls and this ratio will be reported as the outcomes measure.</description>
        <time_frame>baseline and 12 weeks</time_frame>
        <population>Participants with sufficient number of collected endothelial cells for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Lanthanum Carbonate</title>
            <description>Eligible subjects who are randomly assigned to the experimental arm will receive lanthanum carbonate (1500-4500 mg/day in divided doses) titrated to serum phosphorus levels.&#xD;
Lanthanum carbonate: Non-calcium containing phosphorus binder&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Eligible subjects who are randomly assigned to the placebo arm will receive placebo tablets (identical to the active lanthanum carbonate tablets) to be taken 3 times daily and titrated to serum phosphorus levels.&#xD;
placebo: Table identical to lanthanum carbonate but with no active ingredient&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
          </group>
        </group_list>
        <measure>
          <title>Vascular Endothelial Cell Protein Expression</title>
          <description>Measures of different protein markers on endothelial cells. Will help understand the underlying pathophysiology of vascular dysfunction in chronic kidney disease. Vascular endothelial cell protein expression will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change vascular endothelial cell protein expression from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups. The expression of endothelial cells collected from patients will be compared to the expression in HUVEC (human umbilical vein endothelial cell) controls and this ratio will be reported as the outcomes measure.</description>
          <population>Participants with sufficient number of collected endothelial cells for analysis.</population>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.54" spread="0.31"/>
                    <measurement group_id="O2" value="1.41" spread="0.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.44" spread="0.26"/>
                    <measurement group_id="O2" value="1.40" spread="0.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Interleukin-6 to Measure Systemic Inflammation</title>
        <description>This is a blood test. Interleukin-6 and C-reactive protein will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change in interleukin-6 and C-reactive protein from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.</description>
        <time_frame>baseline and 12 weeks</time_frame>
        <population>Participants were included if they had baseline and end of study blood collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Lanthanum Carbonate</title>
            <description>Eligible subjects who are randomly assigned to the experimental arm will receive lanthanum carbonate (1500-4500 mg/day in divided doses) titrated to serum phosphorus levels.&#xD;
Lanthanum carbonate: Non-calcium containing phosphorus binder&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Eligible subjects who are randomly assigned to the placebo arm will receive placebo tablets (identical to the active lanthanum carbonate tablets) to be taken 3 times daily and titrated to serum phosphorus levels.&#xD;
placebo: Table identical to lanthanum carbonate but with no active ingredient&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
          </group>
        </group_list>
        <measure>
          <title>Interleukin-6 to Measure Systemic Inflammation</title>
          <description>This is a blood test. Interleukin-6 and C-reactive protein will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change in interleukin-6 and C-reactive protein from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.</description>
          <population>Participants were included if they had baseline and end of study blood collected.</population>
          <units>pg/ml</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Interleukin-6, baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.58" lower_limit="1.06" upper_limit="2.36"/>
                    <measurement group_id="O2" value="1.28" lower_limit="0.93" upper_limit="2.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Interleukin-6, week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.61" lower_limit="1.12" upper_limit="2.56"/>
                    <measurement group_id="O2" value="1.34" lower_limit="0.88" upper_limit="2.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Oxidized Low-density Lipoprotein (Ox-LDL) to Measure Systemic Oxidized Stress</title>
        <description>This is a blood test art. Oxidized low-density lipoprotein (ox-LDL) will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change in ox-LDL from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.</description>
        <time_frame>baseline and 12 weeks</time_frame>
        <population>Participants were included if they had blood collected at baseline and end of study.</population>
        <group_list>
          <group group_id="O1">
            <title>Lanthanum Carbonate</title>
            <description>Eligible subjects who are randomly assigned to the experimental arm will receive lanthanum carbonate (1500-4500 mg/day in divided doses) titrated to serum phosphorus levels.&#xD;
Lanthanum carbonate: Non-calcium containing phosphorus binder&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Eligible subjects who are randomly assigned to the placebo arm will receive placebo tablets (identical to the active lanthanum carbonate tablets) to be taken 3 times daily and titrated to serum phosphorus levels.&#xD;
placebo: Table identical to lanthanum carbonate but with no active ingredient&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
          </group>
        </group_list>
        <measure>
          <title>Oxidized Low-density Lipoprotein (Ox-LDL) to Measure Systemic Oxidized Stress</title>
          <description>This is a blood test art. Oxidized low-density lipoprotein (ox-LDL) will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change in ox-LDL from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.</description>
          <population>Participants were included if they had blood collected at baseline and end of study.</population>
          <units>mU/ml</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61837" lower_limit="49168" upper_limit="81461"/>
                    <measurement group_id="O2" value="62927" lower_limit="49634" upper_limit="82774"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59725" lower_limit="48650" upper_limit="86949"/>
                    <measurement group_id="O2" value="68057" lower_limit="52199" upper_limit="78069"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>C-reactive Protein to Measure Systemic Inflammation</title>
        <description>This is a blood test. C-reactive protein will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change in C-reactive protein from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.</description>
        <time_frame>baseline and 12 weeks</time_frame>
        <population>Participants were included if they had baseline and end of study blood collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Lanthanum Carbonate</title>
            <description>Eligible subjects who are randomly assigned to the experimental arm will receive lanthanum carbonate (1500-4500 mg/day in divided doses) titrated to serum phosphorus levels.&#xD;
Lanthanum carbonate: Non-calcium containing phosphorus binder&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Eligible subjects who are randomly assigned to the placebo arm will receive placebo tablets (identical to the active lanthanum carbonate tablets) to be taken 3 times daily and titrated to serum phosphorus levels.&#xD;
placebo: Table identical to lanthanum carbonate but with no active ingredient&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
          </group>
        </group_list>
        <measure>
          <title>C-reactive Protein to Measure Systemic Inflammation</title>
          <description>This is a blood test. C-reactive protein will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change in C-reactive protein from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.</description>
          <population>Participants were included if they had baseline and end of study blood collected.</population>
          <units>mg/ml</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>C-reactive protein, baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.92" lower_limit="1.36" upper_limit="6.61"/>
                    <measurement group_id="O2" value="2.72" lower_limit="1.06" upper_limit="5.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C-reactive protein, week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.06" lower_limit="1.02" upper_limit="5.93"/>
                    <measurement group_id="O2" value="2.24" lower_limit="1.18" upper_limit="3.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 weeks (i.e., study duration for each participant in the Main/Parent Study); 9 days (i.e., study duration of Phosphorus Balance Sub-study)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Lanthanum Carbonate</title>
          <description>Eligible subjects who are randomly assigned to the experimental arm will receive lanthanum carbonate (1500-4500 mg/day in divided doses) titrated to serum phosphorus levels.&#xD;
Lanthanum carbonate: Non-calcium containing phosphorus binder&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Eligible subjects who are randomly assigned to the placebo arm will receive placebo tablets (identical to the active lanthanum carbonate tablets) to be taken 3 times daily and titrated to serum phosphorus levels.&#xD;
placebo: Table identical to lanthanum carbonate but with no active ingredient&#xD;
Ascorbic Acid: Intravenous administration during measurement of flow mediated dilation.&#xD;
Nitroglycerin: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.&#xD;
Flow-mediated dilation measurement: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.&#xD;
Aortic pulse-wave velocity: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.&#xD;
Endothelial cell collection: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.</description>
        </group>
        <group group_id="E3">
          <title>Lanthanum Carbonate- Phosphorus Balance Sub-study</title>
          <description>Continued randomized intervention from Parent/Main Study on and received a fixed phosphorus diet for 9 days after the completion of the Parent/Main Study.</description>
        </group>
        <group group_id="E4">
          <title>Placebo- Phosphorus Balance Sub-study</title>
          <description>Continued randomized intervention from Parent/Main Study on and received a fixed phosphorus diet for 9 days after the completion og the Parent/Main Study.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="32"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hospitalization</sub_title>
                <description>Hospitalization for hepatic encephalopathy</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hospitalization</sub_title>
                <description>Hospitalization for pneumonia.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hospitalization</sub_title>
                <description>Hospitalization for cerebral vascular accident (CVA) (i.e., stroke).</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="32"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Non-serious adverse events</sub_title>
                <description>Constipation, diarrhea, nausea, vomiting</description>
                <counts group_id="E1" events="19" subjects_affected="12" subjects_at_risk="32"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Anna Jovanovich, MD</name_or_title>
      <organization>Rocky Mountain VA Medical Center</organization>
      <phone>303-724-8677</phone>
      <email>anna.jovanovich@va.gov</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02209636
org study id: CLNB-006-13F
secondary id: CX001030
nct id: NCT02209636
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The proposed research is a randomized-controlled trial to determine the effectiveness of
      reducing serum phosphorus using a phosphate binder, lanthanum carbonate, for improving the
      function of arteries in adults with moderate to severe chronic kidney disease (CKD). [COMIRB
      13-0328] Additionally, it will determine phosphorus balance among adults with CKD and whether
      there is a difference in phosphorus balance after three months of treatment with lanthanum
      carbonate. [COMIRB 15-0384]
Chronic kidney disease (CKD) is a major health concern both in the general and Veteran
      populations. Indeed, the prevalence of CKD in a large Veteran population is 20%.
      Cardiovascular disease (CVD) is significantly increased in CKD and is an important cause of
      morbidity and mortality. As much as 80% of all CVD is associated with vascular dysfunction,
      particularly impaired endothelium-dependent dilation (EDD), measured by brachial artery
      flow-mediate dilation (FMD), and stiffening of the large elastic arteries, measured by aortic
      pulse-wave velocity (aPWV). Not surprisingly, patients with CKD demonstrate these
      dysfunctional vascular phenotypes. Even in early stages of CKD, there is an increase in
      oxidative stress resulting in structural and functional vascular changes, which, in turn,
      contributes to vascular dysfunction (impaired EDD and large elastic artery stiffening). In
      CKD, phosphorus remains within the normal range (2.5-4.5 mg/dL) until late in the disease.
      However, elevated serum phosphorus, even within the normal range, is associated with impaired
      EDD and with indirect measures of arterial stiffness. Whether lowering serum phosphorus in
      patients with CKD will improve EDD and arterial stiffness is unknown. This study is a
      randomized-controlled trial of lanthanum carbonate, a non-calcium based phosphate binder, to
      treat vascular dysfunction. The efficacy of phosphate binding with lanthanum carbonate for
      treating vascular endothelial dysfunction and large elastic artery stiffness in patients with
      stage IIIb and IV CKD (estimated glomerular filtration rate 15-45 mL/min/1.73m2) with
      baseline serum phosphorus of 2.8-5.5 mg/dL will be assessed. The study will also determine if
      lowering serum phosphorus with lanthanum carbonate also reduces circulating and endothelial
      cell markers of oxidative stress. This study could shift clinical practice guidelines by
      establishing a novel therapy for reducing CVD risk in CKD patients not requiring chronic
      hemodialysis. [COMIRB 13-0328]

      Little is known about phosphorus balance in CKD. It is assumed that CKD patients remain in
      neutral phosphorus balance despite decreases in kidney function. Serum phosphorus remains in
      the normal range until late in CKD thus making it difficult to recognize perturbations in
      phosphorus balance. Indeed, among CKD patients treated with the non-calcium containing
      phosphate binder, sevelamer, serum phosphorus did not change after six weeks of treatment but
      urinary phosphate excretion, parathyroid hormone, and fibroblast growth factor-23 changed
      significantly, suggesting a shift in phosphorus homeostasis. However, two other studies found
      that patients with CKD III-IV treated with calcium-containing phosphate binders remained in
      neutral phosphorus balance. There are no studies evaluating the effects of non-calcium based
      phosphate binders on phosphorus balance among patients with CKD nor other studies examining
      the effect of changing phosphorus balance on vascular function.

      An extension of the above-described 12-week prospective randomized, placebo-controlled
      double-blind trial (COMIRB 13-0328) will be conducted in a subset of subjects. A total of 24
      subjects from COMIRB 13-0328 will be recruited to participate in the Phosphorus Balance
      sub-investigation (12 subjects treated with lanthanum carbonate and 12 subjects treated with
      placebo). [15-0384] They will consume a diet with a fixed phosphorus content (1000 +/- 50 mg)
      for seven days. They will then be admitted to the inpatient Center for Translational Clinical
      Research at the University of Colorado Denver for 48 hours to accurately collect urine and
      stool samples. The goal of the Phosphorus Balance sub-investigation (COMIRB 15-0384) is to
      determine whether lowering serum phosphorus, accomplished during the parent phosphorus
      lowering randomized-controlled trial (COMIRB 13-0328), affects phosphorus balance compared to
      those subjects treated with placebo. A key secondary goal is to determine if differences in
      phosphorus balance affect vascular function as measured by FMD. [15-0384]

      To ensure adequate enrollment in the Phosphorus Balance Study (COMIRB 15-0384), an amendment
      was approved to recruit patients with stage IIIb and IV CKD with normal or modestly elevated
      serum phosphorus (2.8-5.5 mg/dL) who are not currently participating in the parent Phosphorus
      Lowering RCT (COMIRB 13-0328). Similar to the Phosphorus Lowering RCT, these patients will
      follow a low phosphorus diet and will be randomized to lanthanum carbonate or placebo for 12
      weeks (run-in period) prior to beginning the current Phosphorus Balance protocol.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Brachial Artery Flow-mediated Dilation
time frame: baseline and 12 weeks
description: Measurement of how well the brachial artery dilates in response to shear stress. It is a measure of endothelial function. It is reported as "percent change", which represents the change in dilation of the artery before and after occlusion.
Brachial artery flow-mediated dilation will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change brachial artery flow mediated dilation from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.
measure: Aortic Pulse-wave Velocity
time frame: baseline and 12 weeks
description: The speed that blood travels from the carotid artery to the femoral artery, expressed as cm/s (centimeters/second). It is a measure of arterial stiffness.
Aortic pulse-wave velocity will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change aortic pulse wave velocity from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.
measure: Phosphorus Balance Sub-study (COMIRB 15-0384)
time frame: 9 days from the start of the sub-study, approximately 13 weeks and 2 days from the start of the Main/Parent Study
description: Balance is defined as oral intake minus urine output minus stool output.
measure: Oxidative Stress-associated Suppression of EDD
time frame: baseline and 12 weeks
description: The influence of oxidative stress on FMD will be determined by infusing a supraphysiologic dose of ascorbic acid or isovolemic saline. The difference in FMD, expressed as percentage change in FMD, which represents the change in dilation of the artery before and after occlusion, during ascorbic acid vs. saline infusion will be taken as a measure of the modulation of EDD/stiffness by oxidative stress.
measure: Vascular Endothelial Cell Protein Expression
time frame: baseline and 12 weeks
description: Measures of different protein markers on endothelial cells. Will help understand the underlying pathophysiology of vascular dysfunction in chronic kidney disease. Vascular endothelial cell protein expression will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change vascular endothelial cell protein expression from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups. The expression of endothelial cells collected from patients will be compared to the expression in HUVEC (human umbilical vein endothelial cell) controls and this ratio will be reported as the outcomes measure.
measure: Interleukin-6 to Measure Systemic Inflammation
time frame: baseline and 12 weeks
description: This is a blood test. Interleukin-6 and C-reactive protein will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change in interleukin-6 and C-reactive protein from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.
measure: Oxidized Low-density Lipoprotein (Ox-LDL) to Measure Systemic Oxidized Stress
time frame: baseline and 12 weeks
description: This is a blood test art. Oxidized low-density lipoprotein (ox-LDL) will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change in ox-LDL from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.
measure: C-reactive Protein to Measure Systemic Inflammation
time frame: baseline and 12 weeks
description: This is a blood test. C-reactive protein will be measured at baseline and at 12 weeks (end-of-study) in the treatment and placebo groups to determine if there is a change in C-reactive protein from baseline to 12 weeks and if this change is significantly different between the treatment and placebo groups.
arm group label: Lanthanum carbonate
arm group type: Experimental
description: Eligible subjects who are randomly assigned to the experimental arm will receive lanthanum carbonate (1500-4500 mg/day in divided doses) titrated to serum phosphorus levels.
arm group label: placebo
arm group type: Placebo Comparator
description: Eligible subjects who are randomly assigned to the placebo arm will receive placebo tablets (identical to the active lanthanum carbonate tablets) to be taken 3 times daily and titrated to serum phosphorus levels.
intervention type: Drug
intervention name: Lanthanum carbonate
description: Non-calcium containing phosphorus binder
arm group label: Lanthanum carbonate
other name: Fosrenol
intervention type: Drug
intervention name: placebo
description: Table identical to lanthanum carbonate but with no active ingredient
arm group label: placebo
intervention type: Drug
intervention name: Ascorbic Acid
description: Intravenous administration during measurement of flow mediated dilation.
arm group label: Lanthanum carbonate
arm group label: placebo
other name: Vitamin C
intervention type: Drug
intervention name: Nitroglycerin
description: Drug that is administered under the tongue that relaxes blood vessels. To be administered during measurement of flow mediated dilation.
arm group label: Lanthanum carbonate
arm group label: placebo
intervention type: Procedure
intervention name: Flow-mediated dilation measurement
description: Measurement of the blood flow in the brachial artery, an artery in the upper arm, using ultrasound.
arm group label: Lanthanum carbonate
arm group label: placebo
intervention type: Procedure
intervention name: Aortic pulse-wave velocity
description: Measurement of the stiffness of the arteries using a transcutaneous tonometer, a small device placed over the skin over the carotid, brachial, radial and femoral arteries.
arm group label: Lanthanum carbonate
arm group label: placebo
intervention type: Procedure
intervention name: Endothelial cell collection
description: Collection of endothelial cells from vein in arm. A flexible wire is inserted through an IV into a forearm vein to collect endothelial cells for further study. This is performed at the baseline visit and and the final study visit.
arm group label: Lanthanum carbonate
arm group label: placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: 79 Years
healthy volunteers: No
last name: Anna J Jovanovich, MD
role: Principal Investigator
affiliation: Rocky Mountain Regional VA Medical Center, Aurora, CO
facility: 
country: United States
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Cardiovascular Diseases
mesh term: Ascorbic Acid
mesh term: Nitroglycerin
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 