<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/NCT03820635</url>
  </required_header>
  <id_info>
    <org_study_id>MVasCDN</org_study_id>
    <nct_id>NCT03820635</nct_id>
  </id_info>
  <brief_title>Markers of Vascular Calcification in Diabetic Nephropathy in Patients With Diabetic Nephropathy</brief_title>
  <official_title>Relation Between Plasma Concentration of Osteopontin Level and Vascular Calcification in Patients With Diabetic Nephropathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study will be conducted at Assiut University Hospital. Eligible subjects will be screened&#xD;
      for vascular calcification by Doppler ultrasound examination. A correation between the level&#xD;
      of serum Osteopontin (OPN) level and the extent of vascular calcification will be evaluated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Osteopontin (OPN) is one of integrin-binding N-linked glycoproteins, which is produced by&#xD;
      activated mononuclear cells and is linked to increasing evidence about the role of OPN in&#xD;
      vascular calcification[1].&#xD;
&#xD;
      Recent clinical studies have shown that vascular calcification is a pathological process&#xD;
      leading to mechanical rigidity and stiffness of vascular wall, endothelial dysfunction,&#xD;
      development and accelerating atherosclerosis even in the absence of established&#xD;
      cardiovascular (CV) disease . Ectopic calcification is explained by several mutually&#xD;
      counteracting molecular mechanisms, i.e. oxidative stress, microvascular inflammation, immune&#xD;
      cell-to-cell cooperation, accumulation of lipids and extracellular proteins, vascular&#xD;
      reparative systems, and metabolic disorders All these processes are under tight regulation of&#xD;
      vitamin D, parathyroid hormone-related peptides (fibroblast growth factor, transcription&#xD;
      factor Sox2, beta-catenin, etc) and matricellular proteins such as OPN. [2].&#xD;
&#xD;
      OPN was found to have relation with vascular calcification, atherosclerosis, and CV disease&#xD;
      associated with severe vascular remodelling including hypertension, chronic kidney disease,&#xD;
      diabetes mellitus . In this context, OPN is a promising biomarker of vascular remodelling&#xD;
      closely related to inflammation intensity, glucose level and pro-thrombotic state with&#xD;
      promising predictive value for CV events [3].&#xD;
&#xD;
      It is a matricellular protein that was first identified in 1995 by Heingard et al. as&#xD;
      sialoprotein derived from bovine bone matrix . During the last decade a number of studies&#xD;
      analysed the role of OPN in the pathogenesis of diabetic nephropathy. This proposed&#xD;
      association needs confirmation and detailed description by further research [4].&#xD;
&#xD;
      At first, OPN has been reported to be highly expressed in the tubular epithelium of the renal&#xD;
      cortex and in glomeruli in rat and mouse models of diabetic nephropathy [5]. This was&#xD;
      associated with extensive macrophage accumulation in the kidney interstitium indicating that&#xD;
      OPN upregulation and macrophage recruitment may play a role in the tubulo-interstitial injury&#xD;
      in diabetic nephropathy [6]. Consistently, OPN/mice are protected from diabetes-induced&#xD;
      albuminuria and renal damage, possibly by modulating podocyte signaling and motility [7]. In&#xD;
      humans, plasma OPN levels are independently associated with presence and severity of diabetic&#xD;
      nephropathy [8] Compelling evidence in the literature provides interesting clues about a link&#xD;
      between the rennin-angiotensin system (RAS) and OPN in diabetic kidney disease.&#xD;
      Diabetes-induced OPN expression and macrophage accumulation in the kidney interstitium of&#xD;
      diabetic rats are significantly ameliorated after treatment with the long acting ACE&#xD;
      inhibitor [9]. Showing that treatment with ramipril for nine month improves creatinine&#xD;
      clearance rate and decreases urinary protein excretion, systolic blood pressure, development&#xD;
      of glomerulosclerosis, tubulo-interstitial fibrosis and inflammatory cell infiltration in a&#xD;
      diabetics. Of note, all these effects of ACE inhibition were associated with markedly&#xD;
      suppressed OPN expression, suggesting that blockade of the RAS by ramipril may confer&#xD;
      renoprotection by decreasing OPN secretion in diabetic nephropathy [10]. Liver X receptors&#xD;
      (LXRs) have been identified as important lipid-dependent regulators of glucose metabolism and&#xD;
      immune functions in leukocytes [11]. Synthetic LXR ligands can inhibit cytokine-induced OPN&#xD;
      expression in macrophages [12]. Tachibana and colleges recently observed decreased urinary&#xD;
      albumin excretion and substantially attenuated macrophage infiltration, mesangial matrix&#xD;
      accumulation and interstitial fibrosis in streptozotocin-induced diabetics following&#xD;
      administration of the LXR agonist T0901317. Notably, this was paralleled by diminished OPN&#xD;
      expression in the kidney cortex indicating that inhibition of renal OPN by LXR activation may&#xD;
      provide a potential therapeutical approach for diabetic nephropathy [13].&#xD;
&#xD;
      Osteopontin (OPN) is a multifunctional protein expressed by several different cell types,&#xD;
      although the bone is known to be a major source [14].The exact excretion pathway of OPN from&#xD;
      the body is not known. OPN is involved in a number of physiological and pathological&#xD;
      conditions, including (1), urinary stones (2), wound healing (3), chronic inflammatory and&#xD;
      autoimmune diseases (4), obesity-related chronic inflammation, and insulin resistance.&#xD;
      However, OPN was originally found in bone and shown to regulate the formation and&#xD;
      calcification of bone tissue. [15].&#xD;
&#xD;
      Notably, OPN has also been linked to vascular remodelling and calcification, especially in&#xD;
      diabetic arteries, and has been shown to associate with diabetic retinopathy and nephropathy&#xD;
      in patients with type 2 diabetes (T2D), as well as cardiovascular disease (CVD) events in&#xD;
      diabetic subjects with history of long standing diabetes. [16]&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">March 1, 2019</start_date>
  <completion_date type="Anticipated">September 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>correlation coefficient between serum level of osteoponton and the rate of different aspects of vascular affection as discussed previously</measure>
    <time_frame>6 months</time_frame>
    <description>the correlation coefficient</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Diabetic Nephropathies</condition>
  <condition>Vascular Calcification</condition>
  <arm_group>
    <arm_group_label>Calcified</arm_group_label>
    <description>those with evidence of vascular calcification</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-calcified</arm_group_label>
    <description>those with no evidence of vascular calcification</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Osteopontin (OPN)</intervention_name>
    <description>the serum level of Osteopontin (OPN) will be measured in the subject's blood sample</description>
    <arm_group_label>Calcified</arm_group_label>
    <arm_group_label>Non-calcified</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        all patients diagnosed with diabetic nephropathies&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  adult patients diagnosed clinically as diabetic nephropathy within 5 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patients with any previous macrovascular complication: coronary heart disease,&#xD;
             cerebrovascular stroke, peripheral ischaemia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Assiut University</name>
      <address>
        <city>Asyūţ</city>
        <zip>71515</zip>
        <country>Egypt</country>
      </address>
    </facility>
    <contact>
      <last_name>Ahmed MA Ali, MSc</last_name>
      <phone>+201006918718</phone>
      <email>drahmedmosaed2016@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 26, 2019</study_first_submitted>
  <study_first_submitted_qc>January 26, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>January 26, 2019</last_update_submitted>
  <last_update_submitted_qc>January 26, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 29, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Ahmed Mahmoud ahmed ali</investigator_full_name>
    <investigator_title>Doctor</investigator_title>
  </responsible_party>
  <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>
    <mesh_term>Calcinosis</mesh_term>
    <mesh_term>Vascular Calcification</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03820635
org study id: MVasCDN
nct id: NCT03820635
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study will be conducted at Assiut University Hospital. Eligible subjects will be screened
      for vascular calcification by Doppler ultrasound examination. A correation between the level
      of serum Osteopontin (OPN) level and the extent of vascular calcification will be evaluated.
Osteopontin (OPN) is one of integrin-binding N-linked glycoproteins, which is produced by
      activated mononuclear cells and is linked to increasing evidence about the role of OPN in
      vascular calcification[1].

      Recent clinical studies have shown that vascular calcification is a pathological process
      leading to mechanical rigidity and stiffness of vascular wall, endothelial dysfunction,
      development and accelerating atherosclerosis even in the absence of established
      cardiovascular (CV) disease . Ectopic calcification is explained by several mutually
      counteracting molecular mechanisms, i.e. oxidative stress, microvascular inflammation, immune
      cell-to-cell cooperation, accumulation of lipids and extracellular proteins, vascular
      reparative systems, and metabolic disorders All these processes are under tight regulation of
      vitamin D, parathyroid hormone-related peptides (fibroblast growth factor, transcription
      factor Sox2, beta-catenin, etc) and matricellular proteins such as OPN. [2].

      OPN was found to have relation with vascular calcification, atherosclerosis, and CV disease
      associated with severe vascular remodelling including hypertension, chronic kidney disease,
      diabetes mellitus . In this context, OPN is a promising biomarker of vascular remodelling
      closely related to inflammation intensity, glucose level and pro-thrombotic state with
      promising predictive value for CV events [3].

      It is a matricellular protein that was first identified in 1995 by Heingard et al. as
      sialoprotein derived from bovine bone matrix . During the last decade a number of studies
      analysed the role of OPN in the pathogenesis of diabetic nephropathy. This proposed
      association needs confirmation and detailed description by further research [4].

      At first, OPN has been reported to be highly expressed in the tubular epithelium of the renal
      cortex and in glomeruli in rat and mouse models of diabetic nephropathy [5]. This was
      associated with extensive macrophage accumulation in the kidney interstitium indicating that
      OPN upregulation and macrophage recruitment may play a role in the tubulo-interstitial injury
      in diabetic nephropathy [6]. Consistently, OPN/mice are protected from diabetes-induced
      albuminuria and renal damage, possibly by modulating podocyte signaling and motility [7]. In
      humans, plasma OPN levels are independently associated with presence and severity of diabetic
      nephropathy [8] Compelling evidence in the literature provides interesting clues about a link
      between the rennin-angiotensin system (RAS) and OPN in diabetic kidney disease.
      Diabetes-induced OPN expression and macrophage accumulation in the kidney interstitium of
      diabetic rats are significantly ameliorated after treatment with the long acting ACE
      inhibitor [9]. Showing that treatment with ramipril for nine month improves creatinine
      clearance rate and decreases urinary protein excretion, systolic blood pressure, development
      of glomerulosclerosis, tubulo-interstitial fibrosis and inflammatory cell infiltration in a
      diabetics. Of note, all these effects of ACE inhibition were associated with markedly
      suppressed OPN expression, suggesting that blockade of the RAS by ramipril may confer
      renoprotection by decreasing OPN secretion in diabetic nephropathy [10]. Liver X receptors
      (LXRs) have been identified as important lipid-dependent regulators of glucose metabolism and
      immune functions in leukocytes [11]. Synthetic LXR ligands can inhibit cytokine-induced OPN
      expression in macrophages [12]. Tachibana and colleges recently observed decreased urinary
      albumin excretion and substantially attenuated macrophage infiltration, mesangial matrix
      accumulation and interstitial fibrosis in streptozotocin-induced diabetics following
      administration of the LXR agonist T0901317. Notably, this was paralleled by diminished OPN
      expression in the kidney cortex indicating that inhibition of renal OPN by LXR activation may
      provide a potential therapeutical approach for diabetic nephropathy [13].

      Osteopontin (OPN) is a multifunctional protein expressed by several different cell types,
      although the bone is known to be a major source [14].The exact excretion pathway of OPN from
      the body is not known. OPN is involved in a number of physiological and pathological
      conditions, including (1), urinary stones (2), wound healing (3), chronic inflammatory and
      autoimmune diseases (4), obesity-related chronic inflammation, and insulin resistance.
      However, OPN was originally found in bone and shown to regulate the formation and
      calcification of bone tissue. [15].

      Notably, OPN has also been linked to vascular remodelling and calcification, especially in
      diabetic arteries, and has been shown to associate with diabetic retinopathy and nephropathy
      in patients with type 2 diabetes (T2D), as well as cardiovascular disease (CVD) events in
      diabetic subjects with history of long standing diabetes. [16]
observational model: Case-Control
time perspective: Cross-Sectional
measure: correlation coefficient between serum level of osteoponton and the rate of different aspects of vascular affection as discussed previously
time frame: 6 months
description: the correlation coefficient
arm group label: Calcified
description: those with evidence of vascular calcification
arm group label: Non-calcified
description: those with no evidence of vascular calcification
intervention type: Diagnostic Test
intervention name: Osteopontin (OPN)
description: the serum level of Osteopontin (OPN) will be measured in the subject's blood sample
arm group label: Calcified
arm group label: Non-calcified
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
contact: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Ahmed Mahmoud ahmed ali
investigator title: Doctor
mesh term: Kidney Diseases
mesh term: Diabetic Nephropathies
mesh term: Calcinosis
mesh term: Vascular Calcification
sharing ipd: No