<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/NCT02224144</url>
  </required_header>
  <id_info>
    <org_study_id>AAAM7850</org_study_id>
    <nct_id>NCT02224144</nct_id>
  </id_info>
  <brief_title>Bone Mass and Strength After Kidney Transplantation</brief_title>
  <official_title>A Comparative Trial of Calcitriol Versus Placebo for the Preservation of Bone Mass and Strength After Kidney Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Columbia University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Satellite Healthcare</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Columbia University</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>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to test whether active vitamin D (calcitriol) protects bones&#xD;
      from weakening and protects blood vessels from calcium deposits over the first year of kidney&#xD;
      transplantation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Kidney transplant recipients at highest fracture risk, as determined by epidemiologic studies&#xD;
      (Caucasians and older recipients). Rocaltrol (calcitriol) is a synthetic vitamin D analog&#xD;
      which is active in the regulation of the absorption of calcium from the gastrointestinal&#xD;
      tract and its utilization in the body.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 18, 2014</start_date>
  <completion_date type="Actual">October 12, 2016</completion_date>
  <primary_completion_date type="Actual">October 12, 2016</primary_completion_date>
  <phase>Phase 2</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>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent change in bone quality from pre to post-calcitriol treatment compared to placebo as assessed by both standard methodologies.</measure>
    <time_frame>Baseline, 12 months</time_frame>
    <description>Novel high resolution bone imaging can separately measure and quantify cortical and trabecular responses to bone active treatments. Finite element analysis (FEA) can be applied to HRpQCT datasets. to provide a computational estimate of bone mechanical competence that has been validated against true compressive tests of bone stiffness and strength.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Areal and Volumetric Bone Mass Density from baseline to 12 months after transplantation</measure>
    <time_frame>Baseline, 12 months</time_frame>
    <description>Apply imaging methods to shed light on whether preservation of areal bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) is accompanied by preservation of bone mechanical competence measured by a method that has been validated against true compressive tests of bone strength.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change in cortical and trabecular bone strength pre- and post-transplantation measured by high resolution imaging methods.</measure>
    <time_frame>Baseline, 12 months</time_frame>
    <description>Apply advanced imaging methods to determine the influence of calcitriol on cortical and trabecular microarchitecture and strength after kidney transplantation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent contribution of cortical porosity to mechanical competence pre- and post-intervention measured by Cortical Porosity Assessment techniques.</measure>
    <time_frame>Baseline, 12 months</time_frame>
    <description>Apply Cortical Porosity Assessment techniques to high resolution peripheral quantitative computed tomography (HRpQCT) scans to quantify the contribution of cortical porosity to mechanical competence in kidney transplant patients both pre- and post-calcitriol treatment compared to placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline to 12 months on vascular calcifications loads of the lower extremity</measure>
    <time_frame>Baseline, 12 months</time_frame>
    <description>Measured by a novel method applied to HRpQCT datasets.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with vascular calcifications of the lower extremity</measure>
    <time_frame>Baseline, 12 months</time_frame>
    <description>Quantification of calcifications of the anterior and posterior tibia arteries measured by a novel method applied to HRpQCT at baseline and 12 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in pre- and post- intervention parathyroid hormone (PTH) levels at baseline,1 month and 12 months after transplantation.</measure>
    <time_frame>Baseline, 1month, 12 months</time_frame>
    <description>Determine effects of calcitriol on post-transplantation PTH.&#xD;
.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in pre- and post- intervention levels of bone remodeling markers for bone remodeling assessment from baseline to 1 month and 12 months after transplantation.</measure>
    <time_frame>Baseline, 1 month, 12 months</time_frame>
    <description>Determine effects of calcitriol on post-transplantation bone remodeling markers.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">67</enrollment>
  <condition>End Stage Renal Disease</condition>
  <condition>Kidney Transplantation</condition>
  <condition>Bone Loss</condition>
  <condition>Fractures</condition>
  <condition>Vascular Calcifications</condition>
  <arm_group>
    <arm_group_label>Vitamin D3 plus Calcitriol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 pill of Vitamin D3 (cholecalciferol) 1000 IU daily for 12 months&#xD;
1 pill of Rocaltrol (calcitriol) 0.5 mcg daily for 12 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamin D3 plus Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>1 pill of Vitamin D3 (cholecalciferol) 1000 IU per day for 12 months&#xD;
1 pill of placebo (sugar pill) per day for 12 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin D3</intervention_name>
    <description>Vitamin D3 1000 IU per day for 12 months</description>
    <arm_group_label>Vitamin D3 plus Calcitriol</arm_group_label>
    <arm_group_label>Vitamin D3 plus Placebo</arm_group_label>
    <other_name>cholecalciferol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Calcitriol</intervention_name>
    <description>Calcitriol (Rocaltrol) 0.5 mcg per day for 12 months</description>
    <arm_group_label>Vitamin D3 plus Calcitriol</arm_group_label>
    <other_name>Rocaltrol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo (sugar pill) 1 pill per day for 12 months</description>
    <arm_group_label>Vitamin D3 plus Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age older than 18&#xD;
&#xD;
          -  Self-describes as White race&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Lower extremity amputations&#xD;
&#xD;
          -  Non-ambulatory&#xD;
&#xD;
          -  Paget´s disease of bone&#xD;
&#xD;
          -  Current hyperthyroidism, untreated hypothyroidism&#xD;
&#xD;
          -  Medical diseases (end stage liver, intestinal malabsorption)&#xD;
&#xD;
          -  Use within the prior year pod anti-seizure medications that induce the cytochrome P450&#xD;
             system, testosterone, estrogen, selective estrogen receptor modulators&#xD;
&#xD;
          -  Weight &gt;300 pounds&#xD;
&#xD;
          -  Dual organ transplant&#xD;
&#xD;
          -  Myocardial infarction or stroke&#xD;
&#xD;
          -  Tobacco use within the past year&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thomas Nickolas, MD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Columbia University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Columbia University Irving Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Iyer SP, Nikkel LE, Nishiyama KK, Dworakowski E, Cremers S, Zhang C, McMahon DJ, Boutroy S, Liu XS, Ratner LE, Cohen DJ, Guo XE, Shane E, Nickolas TL. Kidney transplantation with early corticosteroid withdrawal: paradoxical effects at the central and peripheral skeleton. J Am Soc Nephrol. 2014 Jun;25(6):1331-41. doi: 10.1681/ASN.2013080851. Epub 2014 Feb 7.</citation>
    <PMID>24511131</PMID>
  </reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>August 22, 2014</study_first_submitted>
  <study_first_submitted_qc>August 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 25, 2014</study_first_posted>
  <last_update_submitted>April 8, 2022</last_update_submitted>
  <last_update_submitted_qc>April 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Columbia University</investigator_affiliation>
    <investigator_full_name>Thomas Nickolas, MD MS</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Kidney Transplantation</keyword>
  <keyword>Calcitriol</keyword>
  <keyword>Bone Mineral Density</keyword>
  <keyword>Bone Mass and Strength</keyword>
  <keyword>Vascular Calcifications</keyword>
  <keyword>Hyperparathyroidism</keyword>
  <keyword>Parathyroid Hormone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Failure, Chronic</mesh_term>
    <mesh_term>Calcinosis</mesh_term>
    <mesh_term>Vascular Calcification</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
    <mesh_term>Cholecalciferol</mesh_term>
    <mesh_term>Calcitriol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02224144
org study id: AAAM7850
nct id: NCT02224144
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is to test whether active vitamin D (calcitriol) protects bones
      from weakening and protects blood vessels from calcium deposits over the first year of kidney
      transplantation.
Kidney transplant recipients at highest fracture risk, as determined by epidemiologic studies
      (Caucasians and older recipients). Rocaltrol (calcitriol) is a synthetic vitamin D analog
      which is active in the regulation of the absorption of calcium from the gastrointestinal
      tract and its utilization in the body.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percent change in bone quality from pre to post-calcitriol treatment compared to placebo as assessed by both standard methodologies.
time frame: Baseline, 12 months
description: Novel high resolution bone imaging can separately measure and quantify cortical and trabecular responses to bone active treatments. Finite element analysis (FEA) can be applied to HRpQCT datasets. to provide a computational estimate of bone mechanical competence that has been validated against true compressive tests of bone stiffness and strength.
measure: Change in Areal and Volumetric Bone Mass Density from baseline to 12 months after transplantation
time frame: Baseline, 12 months
description: Apply imaging methods to shed light on whether preservation of areal bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) is accompanied by preservation of bone mechanical competence measured by a method that has been validated against true compressive tests of bone strength.
measure: Percent change in cortical and trabecular bone strength pre- and post-transplantation measured by high resolution imaging methods.
time frame: Baseline, 12 months
description: Apply advanced imaging methods to determine the influence of calcitriol on cortical and trabecular microarchitecture and strength after kidney transplantation.
measure: Percent contribution of cortical porosity to mechanical competence pre- and post-intervention measured by Cortical Porosity Assessment techniques.
time frame: Baseline, 12 months
description: Apply Cortical Porosity Assessment techniques to high resolution peripheral quantitative computed tomography (HRpQCT) scans to quantify the contribution of cortical porosity to mechanical competence in kidney transplant patients both pre- and post-calcitriol treatment compared to placebo.
measure: Changes from baseline to 12 months on vascular calcifications loads of the lower extremity
time frame: Baseline, 12 months
description: Measured by a novel method applied to HRpQCT datasets.
measure: Number of patients with vascular calcifications of the lower extremity
time frame: Baseline, 12 months
description: Quantification of calcifications of the anterior and posterior tibia arteries measured by a novel method applied to HRpQCT at baseline and 12 months.
measure: Change in pre- and post- intervention parathyroid hormone (PTH) levels at baseline,1 month and 12 months after transplantation.
time frame: Baseline, 1month, 12 months
description: Determine effects of calcitriol on post-transplantation PTH.
.
measure: Change in pre- and post- intervention levels of bone remodeling markers for bone remodeling assessment from baseline to 1 month and 12 months after transplantation.
time frame: Baseline, 1 month, 12 months
description: Determine effects of calcitriol on post-transplantation bone remodeling markers.
arm group label: Vitamin D3 plus Calcitriol
arm group type: Experimental
description: 1 pill of Vitamin D3 (cholecalciferol) 1000 IU daily for 12 months
1 pill of Rocaltrol (calcitriol) 0.5 mcg daily for 12 months
arm group label: Vitamin D3 plus Placebo
arm group type: Placebo Comparator
description: 1 pill of Vitamin D3 (cholecalciferol) 1000 IU per day for 12 months
1 pill of placebo (sugar pill) per day for 12 months
intervention type: Drug
intervention name: Vitamin D3
description: Vitamin D3 1000 IU per day for 12 months
arm group label: Vitamin D3 plus Calcitriol
arm group label: Vitamin D3 plus Placebo
other name: cholecalciferol
intervention type: Drug
intervention name: Calcitriol
description: Calcitriol (Rocaltrol) 0.5 mcg per day for 12 months
arm group label: Vitamin D3 plus Calcitriol
other name: Rocaltrol
intervention type: Drug
intervention name: Placebo
description: Placebo (sugar pill) 1 pill per day for 12 months
arm group label: Vitamin D3 plus Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Thomas Nickolas, MD, MS
role: Principal Investigator
affiliation: Columbia University
facility: 
country: United States
citation: Iyer SP, Nikkel LE, Nishiyama KK, Dworakowski E, Cremers S, Zhang C, McMahon DJ, Boutroy S, Liu XS, Ratner LE, Cohen DJ, Guo XE, Shane E, Nickolas TL. Kidney transplantation with early corticosteroid withdrawal: paradoxical effects at the central and peripheral skeleton. J Am Soc Nephrol. 2014 Jun;25(6):1331-41. doi: 10.1681/ASN.2013080851. Epub 2014 Feb 7.
PMID: 24511131
responsible party type: Principal Investigator
investigator affiliation: Columbia University
investigator full name: Thomas Nickolas, MD MS
investigator title: Associate Professor of Medicine
mesh term: Kidney Failure, Chronic
mesh term: Calcinosis
mesh term: Vascular Calcification
mesh term: Vitamin D
mesh term: Cholecalciferol
mesh term: Calcitriol
sharing ipd: Undecided