<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/NCT01673204</url>
  </required_header>
  <id_info>
    <org_study_id>SNUH-TNFR</org_study_id>
    <nct_id>NCT01673204</nct_id>
  </id_info>
  <brief_title>Clinical Trial Technology Development for the Validation of Surrogate Prognostic Markers in Patients With Diabetic Nephropathy</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Seoul National University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Seoul National University Hospital</source>
  <brief_summary>
    <textblock>
      Worldwide, the most common cause of chronic kidney disease (CKD) and end stage renal disease&#xD;
      (ESRD) is diabetes. Unlike the past, in south korea, diabetes account for more than 40% of&#xD;
      ESRD. According to WHO reports in 1998, 100 million people had type 2 diabetes in 1997, and&#xD;
      there is expected to increase by 300 million people in 2025. In addition, the expected&#xD;
      survival time of patients with diabetes increase compared to previous. In the future, ESRD&#xD;
      due to type 2 diabetes is expected to have a significant impact on the health industry.&#xD;
      Therefore, prevention of progression to CKD and ESRD in diabetic patients is important to&#xD;
      aspect of national health and economic problems. How to stop the progression of diabetic&#xD;
      nephropathy is part of modern medicine to be solved.&#xD;
&#xD;
      Strict glycemic control, blood pressure regulation, and use of renin-angiotensin system (RAS)&#xD;
      blockers inhibit the development and progression of diabetic nephropathy. Microalbuminuria in&#xD;
      diabetic patients has been recognized as a predictor of progression of diabetic nephropathy.&#xD;
      Thus, the prevention of elevated urinary albumin excretion is an important therapeutic target&#xD;
      for the prevention of renal and cardiovascular events.&#xD;
&#xD;
      In patients with diabetes and hypertension, the drugs that block the RAS are used to treat&#xD;
      proteinuria, but still a large number of patients with proteinuria are uncontrolled. In&#xD;
      addition, ACE inhibitors or ARB agents actually have a limited effect on reducing the risk of&#xD;
      cardiovascular or renal outcome. Also, sulodexide or pentoxyphylline which is reducing&#xD;
      proteinuria have some weak evidence in terms of efficacy and safety. Therefore, the&#xD;
      introduction of new alternative drugs are required.&#xD;
&#xD;
      Already several study reported that calcitriol or paricalcitol in the renal injury model have&#xD;
      renopreventive effect. In addition, in diabetic renal injury mice model reported that vitamin&#xD;
      D receptor deficiency leads to glomerulosclerosis. Inhibition of the RAS with combination of&#xD;
      paricalcitol and RAS inhibitors effectively prevent renal injury in diabetic nephropathy.&#xD;
      Recently, Dick de Zeeuw et al reported that addition of paricalcitol to RAS inhibition safely&#xD;
      lower residual albuminuria in patients with diabetic nephropathy. Recent studies reported&#xD;
      that elevated concentrations of serum markers of the TNFα and Fas-pathways are strongly&#xD;
      associated with decreased renal function in diabetic patients. However, the role of these&#xD;
      markers in early progressive renal function decline are not clear. Therefore, the objective&#xD;
      of this study is to identify the renoprotective effect as an new treatment of activated&#xD;
      vitamin D (Calcitriol) indicating the TNF-α-related anti-inflammatory action and to seek the&#xD;
      role as an important biomarker that the changes of TNFR in diabetic nephropathy can predict&#xD;
      response to treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>October 2012</start_date>
  <primary_completion_date type="Anticipated">April 2014</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>Screening</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in renal function with proteinuria</measure>
    <time_frame>12 month after administration</time_frame>
    <description>Comparison of in GFR level from baseline Comparison of proteinuria amount checked by random urine protein/creatinine ratio</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>changes in sTNFR and TNF-related proteins</measure>
    <time_frame>12 months after administration</time_frame>
    <description>Comparison of serum TNFR1, TNFR2 levels from baseline</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">276</enrollment>
  <condition>Diabetic Nephropathy</condition>
  <arm_group>
    <arm_group_label>Calcitriol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Calcitriol</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Calcitriol</intervention_name>
    <description>dosage of 0.5mcg administered orally once daily for 12 month</description>
    <arm_group_label>Calcitriol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients age 19-80 years&#xD;
&#xD;
          -  Clinically proven diabetic nephropathy&#xD;
&#xD;
          -  MDRD eGFR &gt;= 30mL/min/1.73m2&#xD;
&#xD;
          -  Patients with residual urine protein/creatinine ratio &gt;= 200mg/g&#xD;
&#xD;
          -  Adequate blood pressure control as treated systolic blood pressure &lt;=140 or diastolic&#xD;
             &lt;=90 mmHg with RAS inhibitor for more than 3months&#xD;
&#xD;
          -  Serum intact PTH &lt;500 mg/dL&#xD;
&#xD;
          -  Serum calcium &lt;10.2 mg/dL&#xD;
&#xD;
          -  Patients who have not been treated vitamin D within the 3months prior to signing the&#xD;
             informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients age &lt;19 years or &gt; 80years&#xD;
&#xD;
          -  Patients with rapidly progressive glomerulonephritis&#xD;
&#xD;
          -  Patients requiring renal replacement therapy immediately&#xD;
&#xD;
          -  Hypercalcemia(Uncorrected serum calcium level &gt;10.2 mg/dL) within recent 3month&#xD;
&#xD;
          -  Malignant hypertension&#xD;
&#xD;
          -  Heart failure (New York Heart Association functional class II to IV or LVEF &lt;40%)&#xD;
&#xD;
          -  Severe chronic obstructive lung disease&#xD;
&#xD;
          -  Decompensated liver disease (ALT &gt;3X upper normal limit)&#xD;
&#xD;
          -  Known allergy or hypersensitivity to vitamin D&#xD;
&#xD;
          -  Current treatment with steroids and/or immunosuppressive agents&#xD;
&#xD;
          -  Active primary malignancy requiring treatment or survival limits less than 2years&#xD;
&#xD;
          -  History of noncompliance to medical regimen&#xD;
&#xD;
          -  Inability to give an informed consent or to cooperate with researchers&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yonsu Kim, M.D., Ph.D</last_name>
    <role>Study Chair</role>
    <affiliation>Seoul National University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sumi Lee</last_name>
    <phone>82-2-2072-1724</phone>
    <email>promise131@hanmail.net</email>
  </overall_contact>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>110-744</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yonsu Kim, M.D., Ph.D</last_name>
      <phone>82-2-2072-2264</phone>
      <email>yonsukim@snu.ac.kr</email>
    </contact>
    <contact_backup>
      <last_name>Dongki Kim, M.D., Ph.D</last_name>
      <phone>82-2-2072-2303</phone>
      <email>dkkim73@gmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Yonsu Kim, Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Dongki Kim, M.D., Ph.D</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sumi Lee, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Seoul National University Boramae Medical Center</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jungpyo Lee, M.D., Ph.D</last_name>
      <phone>82-2-870-2261</phone>
      <email>kjwa1@medimail.co.kr</email>
    </contact>
    <investigator>
      <last_name>Jungpyo Lee, M.D., Ph.D</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>February 2014</verification_date>
  <study_first_submitted>August 21, 2012</study_first_submitted>
  <study_first_submitted_qc>August 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2012</study_first_posted>
  <last_update_submitted>February 12, 2014</last_update_submitted>
  <last_update_submitted_qc>February 12, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 13, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Seoul National University Hospital</investigator_affiliation>
    <investigator_full_name>Yon Su Kim</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>surrogate marker,</keyword>
  <keyword>circulating soluble TNF receptor,</keyword>
  <keyword>diabetic nephropathy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Diabetic Nephropathies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Calcitriol</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01673204
org study id: SNUH-TNFR
nct id: NCT01673204
lead sponsor: 
Worldwide, the most common cause of chronic kidney disease (CKD) and end stage renal disease
      (ESRD) is diabetes. Unlike the past, in south korea, diabetes account for more than 40% of
      ESRD. According to WHO reports in 1998, 100 million people had type 2 diabetes in 1997, and
      there is expected to increase by 300 million people in 2025. In addition, the expected
      survival time of patients with diabetes increase compared to previous. In the future, ESRD
      due to type 2 diabetes is expected to have a significant impact on the health industry.
      Therefore, prevention of progression to CKD and ESRD in diabetic patients is important to
      aspect of national health and economic problems. How to stop the progression of diabetic
      nephropathy is part of modern medicine to be solved.

      Strict glycemic control, blood pressure regulation, and use of renin-angiotensin system (RAS)
      blockers inhibit the development and progression of diabetic nephropathy. Microalbuminuria in
      diabetic patients has been recognized as a predictor of progression of diabetic nephropathy.
      Thus, the prevention of elevated urinary albumin excretion is an important therapeutic target
      for the prevention of renal and cardiovascular events.

      In patients with diabetes and hypertension, the drugs that block the RAS are used to treat
      proteinuria, but still a large number of patients with proteinuria are uncontrolled. In
      addition, ACE inhibitors or ARB agents actually have a limited effect on reducing the risk of
      cardiovascular or renal outcome. Also, sulodexide or pentoxyphylline which is reducing
      proteinuria have some weak evidence in terms of efficacy and safety. Therefore, the
      introduction of new alternative drugs are required.

      Already several study reported that calcitriol or paricalcitol in the renal injury model have
      renopreventive effect. In addition, in diabetic renal injury mice model reported that vitamin
      D receptor deficiency leads to glomerulosclerosis. Inhibition of the RAS with combination of
      paricalcitol and RAS inhibitors effectively prevent renal injury in diabetic nephropathy.
      Recently, Dick de Zeeuw et al reported that addition of paricalcitol to RAS inhibition safely
      lower residual albuminuria in patients with diabetic nephropathy. Recent studies reported
      that elevated concentrations of serum markers of the TNFα and Fas-pathways are strongly
      associated with decreased renal function in diabetic patients. However, the role of these
      markers in early progressive renal function decline are not clear. Therefore, the objective
      of this study is to identify the renoprotective effect as an new treatment of activated
      vitamin D (Calcitriol) indicating the TNF-α-related anti-inflammatory action and to seek the
      role as an important biomarker that the changes of TNFR in diabetic nephropathy can predict
      response to treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Screening
masking: Double (Participant, Investigator)
measure: Changes in renal function with proteinuria
time frame: 12 month after administration
description: Comparison of in GFR level from baseline Comparison of proteinuria amount checked by random urine protein/creatinine ratio
measure: changes in sTNFR and TNF-related proteins
time frame: 12 months after administration
description: Comparison of serum TNFR1, TNFR2 levels from baseline
arm group label: Calcitriol
arm group type: Experimental
description: Calcitriol
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
intervention type: Drug
intervention name: Calcitriol
description: dosage of 0.5mcg administered orally once daily for 12 month
arm group label: Calcitriol
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 19 Years
maximum age: 80 Years
healthy volunteers: No
last name: Yonsu Kim, M.D., Ph.D
role: Study Chair
affiliation: Seoul National University Hospital
last name: Sumi Lee
phone: 82-2-2072-1724
email: promise131@hanmail.net
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Seoul National University Hospital
investigator full name: Yon Su Kim
investigator title: Professor
mesh term: Kidney Diseases
mesh term: Diabetic Nephropathies
mesh term: Calcitriol