<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/NCT02245633</url>
  </required_header>
  <id_info>
    <org_study_id>0081-14-MMC</org_study_id>
    <nct_id>NCT02245633</nct_id>
  </id_info>
  <brief_title>Correlation Between Vitamin D Levels to ADAMTS13 , VWF and Micro RNA Expression in Diabetic Hemodialysis Patients</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Meir Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Meir Medical Center</source>
  <brief_summary>
    <textblock>
      The aim of this research is to study how vitamin D affects various aspects of the disease&#xD;
      process, such as inflammation, coagulation (ADAMTS13 and WVF) and miRNAs, in Diabetic kidney&#xD;
      disease hemodialysis patients.&#xD;
&#xD;
      Diabetes mellitus (DM) is one of the most common chronic diseases in nearly all countries.&#xD;
      Diabetic kidney disease (DKD) traditionally has been referred to as diabetic nephropathy and&#xD;
      is one of the microvascular complications of diabetes. Diabetic kidney disease (DKD) occurs&#xD;
      in 25%-40% of patients with diabetes .&#xD;
&#xD;
      Some studies have shown that the high risk of cardiovascular disease in diabetic patients&#xD;
      with nephropathy is associated with increased plasma levels of von Willebrand factor (VWF)&#xD;
      and decreased ADAMTS13 levels. VWF is a glycoprotein that plays an important role in platelet&#xD;
      thrombus formation, whereas ADAMTS13 is a proteolytic enzyme that is responsible for&#xD;
      degradation of large multimers of VWF released in the plasma by endothelial cells and&#xD;
      platelets. Patients with both chronic kidney disease and diabetes have been shown to have&#xD;
      higher plasma levels of VWF and decreased ADAMTS13 activity compared to healthy controls.&#xD;
&#xD;
      Increased plasma levels of VWF, which reflects damage to endothelial cells and a&#xD;
      hypercoagulability state, have been reported in atherosclerosis and diabetes. Thus, VWF and&#xD;
      ADAMTS13 seem to be important players in the interface between diabetic nephropathy,&#xD;
      hypercoagulability and atherosclerotic cardiovascular disease. Vitamin D deficiency is a risk&#xD;
      factor for DM and hypertension. The investigators previous studies showed that adding&#xD;
      calcitriol (activated vitamin D) to endothelial and vascular smooth muscle cells&#xD;
      significantly down-regulated the inflammatory response of gene and protein expression&#xD;
      involved in the nuclear factor kappa-light-chain-enhancer of activated B cells (NFĸB) signal&#xD;
      transduction pathway. Micro RNA (miRNA) are short noncoding RNAs, 22-25 nucleotides long. As&#xD;
      an endogenous production transcript, miRNAs can bind to the 3 untranslated regions (3 UTR) of&#xD;
      its target messenger RNA (mRNA) in an imperfect, complementary manner, leading to&#xD;
      post-transcriptional gene silencing. As a result, miRNAs can inhibit gene expression via mRNA&#xD;
      degradation, translation inhibition, or transcriptional inhibition.The critical role of&#xD;
      miRNAs has been established in several cellular and biologic processes, such as&#xD;
      proliferation, differentiation, and development, and in the regulation of genes related to&#xD;
      immune responses, cancer, and insulin secretion. MiRNA are involved in various biological&#xD;
      processes and become novel biomarkers, modulators and therapeutic targets for diseases such&#xD;
      as cancer, atherosclerosis, and DM.&#xD;
&#xD;
      Significance: The high prevalence of cardiovascular morbidity and mortality in patients with&#xD;
      DM on chronic hemodialysis remains a significant clinical problem and the finding of&#xD;
      potential new biomarkers should be further investigated. This study aims to establish a link&#xD;
      between ADAMTS13, VWF miRNA expression and vitamin D levels that can contribute to the&#xD;
      development of new treatments for hemodialysis patients with diabetes.&#xD;
&#xD;
      Methods: Each hemodialysis patient with diabetes in the investigators institute will be asked&#xD;
      to participate in the study. After explaining the research goals, patients that agree to&#xD;
      participate will sign an informed consent. The investigators estimate that the study will&#xD;
      include 70 patients. Each patient will be assessed by a physician and 4 vials of blood will&#xD;
      be taken while the patient is connected to the dialysis machine. The blood will be sent to&#xD;
      the laboratory to check: 1) chemistry; 2) 1-25 vitamin D and 25- vitamin D levels; 3)&#xD;
      ADAMTS13 activity and VWF; and 4) miRNA extraction. The patients will be grouped according to&#xD;
      vitamin D levels (deficient /sufficient), and ADAMTS13, VWF and miRNA expression will be&#xD;
      compared between the groups.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">September 2015</completion_date>
  <primary_completion_date type="Anticipated">February 2015</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <target_duration>5 Years</target_duration>
  <primary_outcome>
    <measure>ADAMTS13 levels in diabetic hemodialysis patients</measure>
    <time_frame>1 day</time_frame>
    <description>blood will be collected from diabetic hemodialysis patients that will arrived to the hospital for receive dialysis for analysis ADAMTS13 levels</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>VWF levels in diabetic hemodialysis patients</measure>
    <time_frame>1 day</time_frame>
    <description>blood will be collected from diabetic hemodialysis patients that will arrived to the hospital for receive dialysis for analysis VWF levels</description>
  </secondary_outcome>
  <other_outcome>
    <measure>miRNA expression in plasma from diabetic hemodialysis patients</measure>
    <time_frame>1 day</time_frame>
    <description>blood will be collected from diabetic hemodialysis patients that will arrived to the hospital for receive dialysis for extract miRNA</description>
  </other_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">70</enrollment>
  <condition>Hemodialysis Patients</condition>
  <condition>Diabetes</condition>
  <arm_group>
    <arm_group_label>vitamin D levels deficient</arm_group_label>
    <description>Diabetic hemodialysis patients with vitamin D levels deficient</description>
  </arm_group>
  <arm_group>
    <arm_group_label>vitamin D levels sufficient</arm_group_label>
    <description>Diabetic hemodialysis patients with vitamin D levels sufficient</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      miRNA will be extract from patient'w plasma&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Hemodialysis patients with diabetes at Meir Medical Center&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical diagnosis of chronic kidney disease - hemodialysis patient with diabetes&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hemodialysis patient - non diabetic&#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_contact>
    <last_name>Sydney bensitrit, MD</last_name>
    <phone>+972-9-7472517</phone>
    <email>sydneybe@clalit.org.il</email>
  </overall_contact>
  <location>
    <facility>
      <name>Nephrology dept. Meir Medical Center</name>
      <address>
        <city>Kfar Saba</city>
        <zip>44281</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sydney Bensitrit, MD</last_name>
      <email>sydneybe@clalit.org.il</email>
    </contact>
    <investigator>
      <last_name>Sydney Bensitrit, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 9, 2014</study_first_submitted>
  <study_first_submitted_qc>September 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 19, 2014</study_first_posted>
  <last_update_submitted>September 18, 2014</last_update_submitted>
  <last_update_submitted_qc>September 18, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 19, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Meir Medical Center</investigator_affiliation>
    <investigator_full_name>Sydney Ben Shitrit</investigator_full_name>
    <investigator_title>Dr.</investigator_title>
  </responsible_party>
  <!-- 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/NCT02245633
org study id: 0081-14-MMC
nct id: NCT02245633
lead sponsor: 
The aim of this research is to study how vitamin D affects various aspects of the disease
      process, such as inflammation, coagulation (ADAMTS13 and WVF) and miRNAs, in Diabetic kidney
      disease hemodialysis patients.

      Diabetes mellitus (DM) is one of the most common chronic diseases in nearly all countries.
      Diabetic kidney disease (DKD) traditionally has been referred to as diabetic nephropathy and
      is one of the microvascular complications of diabetes. Diabetic kidney disease (DKD) occurs
      in 25%-40% of patients with diabetes .

      Some studies have shown that the high risk of cardiovascular disease in diabetic patients
      with nephropathy is associated with increased plasma levels of von Willebrand factor (VWF)
      and decreased ADAMTS13 levels. VWF is a glycoprotein that plays an important role in platelet
      thrombus formation, whereas ADAMTS13 is a proteolytic enzyme that is responsible for
      degradation of large multimers of VWF released in the plasma by endothelial cells and
      platelets. Patients with both chronic kidney disease and diabetes have been shown to have
      higher plasma levels of VWF and decreased ADAMTS13 activity compared to healthy controls.

      Increased plasma levels of VWF, which reflects damage to endothelial cells and a
      hypercoagulability state, have been reported in atherosclerosis and diabetes. Thus, VWF and
      ADAMTS13 seem to be important players in the interface between diabetic nephropathy,
      hypercoagulability and atherosclerotic cardiovascular disease. Vitamin D deficiency is a risk
      factor for DM and hypertension. The investigators previous studies showed that adding
      calcitriol (activated vitamin D) to endothelial and vascular smooth muscle cells
      significantly down-regulated the inflammatory response of gene and protein expression
      involved in the nuclear factor kappa-light-chain-enhancer of activated B cells (NFĸB) signal
      transduction pathway. Micro RNA (miRNA) are short noncoding RNAs, 22-25 nucleotides long. As
      an endogenous production transcript, miRNAs can bind to the 3 untranslated regions (3 UTR) of
      its target messenger RNA (mRNA) in an imperfect, complementary manner, leading to
      post-transcriptional gene silencing. As a result, miRNAs can inhibit gene expression via mRNA
      degradation, translation inhibition, or transcriptional inhibition.The critical role of
      miRNAs has been established in several cellular and biologic processes, such as
      proliferation, differentiation, and development, and in the regulation of genes related to
      immune responses, cancer, and insulin secretion. MiRNA are involved in various biological
      processes and become novel biomarkers, modulators and therapeutic targets for diseases such
      as cancer, atherosclerosis, and DM.

      Significance: The high prevalence of cardiovascular morbidity and mortality in patients with
      DM on chronic hemodialysis remains a significant clinical problem and the finding of
      potential new biomarkers should be further investigated. This study aims to establish a link
      between ADAMTS13, VWF miRNA expression and vitamin D levels that can contribute to the
      development of new treatments for hemodialysis patients with diabetes.

      Methods: Each hemodialysis patient with diabetes in the investigators institute will be asked
      to participate in the study. After explaining the research goals, patients that agree to
      participate will sign an informed consent. The investigators estimate that the study will
      include 70 patients. Each patient will be assessed by a physician and 4 vials of blood will
      be taken while the patient is connected to the dialysis machine. The blood will be sent to
      the laboratory to check: 1) chemistry; 2) 1-25 vitamin D and 25- vitamin D levels; 3)
      ADAMTS13 activity and VWF; and 4) miRNA extraction. The patients will be grouped according to
      vitamin D levels (deficient /sufficient), and ADAMTS13, VWF and miRNA expression will be
      compared between the groups.
observational model: Cohort
time perspective: Cross-Sectional
measure: ADAMTS13 levels in diabetic hemodialysis patients
time frame: 1 day
description: blood will be collected from diabetic hemodialysis patients that will arrived to the hospital for receive dialysis for analysis ADAMTS13 levels
measure: VWF levels in diabetic hemodialysis patients
time frame: 1 day
description: blood will be collected from diabetic hemodialysis patients that will arrived to the hospital for receive dialysis for analysis VWF levels
measure: miRNA expression in plasma from diabetic hemodialysis patients
time frame: 1 day
description: blood will be collected from diabetic hemodialysis patients that will arrived to the hospital for receive dialysis for extract miRNA
arm group label: vitamin D levels deficient
description: Diabetic hemodialysis patients with vitamin D levels deficient
arm group label: vitamin D levels sufficient
description: Diabetic hemodialysis patients with vitamin D levels sufficient
miRNA will be extract from patient'w plasma
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sydney bensitrit, MD
phone: +972-9-7472517
email: sydneybe@clalit.org.il
facility: 
status: Recruiting
contact: 
investigator: 
country: Israel
responsible party type: Principal Investigator
investigator affiliation: Meir Medical Center
investigator full name: Sydney Ben Shitrit
investigator title: Dr.