<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/NCT01703234</url>
  </required_header>
  <id_info>
    <org_study_id>GATARAMFGF232012</org_study_id>
    <nct_id>NCT01703234</nct_id>
  </id_info>
  <brief_title>FGF-23 and Endothelial Dysfunction in Diabetic Proteinuric Patients</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gulhane School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gulhane School of Medicine</source>
  <brief_summary>
    <textblock>
      There is no data about the effects of Renin angiotensin system blockage (RAS) on FGF23 and&#xD;
      ADMA levels in diabetic patients with proteinuria. The aim of this study was to find out&#xD;
      whether the beneficial effects of RAS blockage in diabetic proteinuria has any relation with&#xD;
      the alteration of ADMA and FGF-23 levels. We searched for the effects of ACE inhibitor&#xD;
      ramipril on the clinical and laboratory parameters of diabetic patients with proteinuria.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In recent years, diabetic nephropathy, which may lead to dialysis treatment, is the most&#xD;
      prevalent underlying disease of people in developed countries. A wide range of studies have&#xD;
      been carried out, from various points of view, to understand the progress of renal&#xD;
      dysfunction in diabetic nephropathy. The endogenous nitric oxide synthase (NOS) inhibitor&#xD;
      asymmetric dimethylarginine (ADMA) is elevated in patients with chronic kidney disease (CKD)&#xD;
      and may have a role in the cardiovascular mortality and morbidity of these patients. In&#xD;
      diabetic nephropathy, high ADMA levels were related to progression of diabetic nephropathy.&#xD;
&#xD;
      Fibroblast growth factor 23 (FGF-23) is a primary regulator of renal phosphate excretion.&#xD;
      FGF23 is inversely associated with the GFR, a relationship underlying a fundamental mechanism&#xD;
      for maintaining serum phosphate constancy during CKD progression. Such an adaptation may have&#xD;
      deleterious trade-offs because, independently of serum phosphate, high FGF23 signals a high&#xD;
      risk of death in ESRD patients. Some studies showed that there is a relationship between&#xD;
      FGF-23 levels and proteinuria in CKD patients.&#xD;
&#xD;
      There is no data about the effects of Renin angiotensin system blockage (RAS) on FGF23 and&#xD;
      ADMA levels in diabetic patients with proteinuria. The aim of this study was to find out&#xD;
      whether the beneficial effects of RAS blockage in diabetic proteinuria has any relation with&#xD;
      the alteration of ADMA and FGF-23 levels. We searched for the effects of ACE inhibitor&#xD;
      ramipril on the clinical and laboratory parameters of diabetic patients with proteinuria.&#xD;
&#xD;
      The study 'Effect of Renin Angiotensin System Blockade on the Fas Antigen (CD95) and&#xD;
      Asymmetric Dimethylarginine (ADMA) Levels in Type-2 Diabetic Patients With Proteinuria' has&#xD;
      been previously registered to ClinicalTrials.gov (Identifier:NCT00893425). The serum samples&#xD;
      of the above study will be used in order to measure the FGF23 levels in this study. Therefore&#xD;
      the eligibility criteria and the study design is similar to the previous study&#xD;
      (Identifier:NCT00893425).&#xD;
&#xD;
      The patients who were non-obese (BMI&lt;30kg/m2), non dyslipidemic (total cholesterol &lt;200mg/dl,&#xD;
      Triglyceride&lt;150mg/dl), and free of cardiovascular events (negative medical history, negative&#xD;
      ECG findings) were investigated for enrollment. CKD stage 1 patients older than 18 years of&#xD;
      age and willing to participate to the study were screened. From the 231 patients with&#xD;
      established type 2 diabetes mellitus, 126 had proteinuria and/or hypertension (24 h protein&#xD;
      excretion 1-2 g/day, systolic blood pressures ≥140mmHg and/or diastolic blood pressures ≥ 90&#xD;
      mmHg, respectively). All cases were first referrals and at the time of the study all were off&#xD;
      treatment. Patients with history of coronary artery disease, smokers and those taking statins&#xD;
      or renin-angiotensin blockers were excluded because of the effect of these factors on&#xD;
      endothelial dysfunction. Of 126 screened patients 78 met the study criteria and were included&#xD;
      in this study. The duration of proteinuria and diabetic nephropathy after initial diagnosis&#xD;
      was not known.&#xD;
&#xD;
      The exclusion criteria were as follows: A)Nephrotic syndrome, B)coronary heart disease&#xD;
      (patients with ischemic ST-T alterations and voltage criteria for LVH on electrocardiogram,&#xD;
      and with history of revascularization or myocardial infarction), C) elevated liver enzymes&#xD;
      (AST or ALT levels ≥ 40U/L) and D) renal failure (serum creatinine levels &gt; 1.3 mg/dl). In&#xD;
      order to evaluate the effect of RAS blockade on FGF 23 concentrations, patients with&#xD;
      proteinuria were given an ACE inhibitor (ramipril 10 mg/day) for 12 weeks. The effect of RAS&#xD;
      blockade on insulin sensitivity and proteinuria was also investigated.&#xD;
&#xD;
      After the intervention period, blood samples were obtained for assay of FGF-23&#xD;
      concentrations, HbA1c , and insulin resistance scores (HOMA-IR).&#xD;
&#xD;
      Urine samples were also collected over a 24-hour period to determine the degree of&#xD;
      proteinuria.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2008</start_date>
  <completion_date type="Actual">April 2009</completion_date>
  <primary_completion_date type="Actual">March 2009</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Flow Mediated Dilatation</measure>
  </primary_outcome>
  <secondary_outcome>
    <measure>FGF-23</measure>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">78</enrollment>
  <condition>Proteinuria</condition>
  <condition>Diabetic Nephropathy</condition>
  <condition>Chronic Kidney Disease</condition>
  <arm_group>
    <arm_group_label>Ramipril</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ramipril</intervention_name>
    <description>ramipril 10 mg/day during 3 months</description>
    <arm_group_label>Ramipril</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  CKD stage 1 patients&#xD;
&#xD;
          -  Older than 18 years of age&#xD;
&#xD;
          -  Type 2 Diabetic patients&#xD;
&#xD;
          -  Proteinuria&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of coronary artery disease&#xD;
&#xD;
          -  Smokers&#xD;
&#xD;
          -  Taking statins or renin-angiotensin blockers&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Gulhane School of Medicine</name>
      <address>
        <city>Ankara</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <verification_date>October 2012</verification_date>
  <study_first_submitted>October 4, 2012</study_first_submitted>
  <study_first_submitted_qc>October 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2012</study_first_posted>
  <last_update_submitted>October 6, 2012</last_update_submitted>
  <last_update_submitted_qc>October 6, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 10, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Gulhane School of Medicine</investigator_affiliation>
    <investigator_full_name>Mahmut Ilker Yilmaz</investigator_full_name>
    <investigator_title>Assoc.Prof.</investigator_title>
  </responsible_party>
  <keyword>FGF-23 , ramipril, 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>Diabetic Nephropathies</mesh_term>
    <mesh_term>Proteinuria</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ramipril</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/NCT01703234
org study id: GATARAMFGF232012
nct id: NCT01703234
lead sponsor: 
There is no data about the effects of Renin angiotensin system blockage (RAS) on FGF23 and
      ADMA levels in diabetic patients with proteinuria. The aim of this study was to find out
      whether the beneficial effects of RAS blockage in diabetic proteinuria has any relation with
      the alteration of ADMA and FGF-23 levels. We searched for the effects of ACE inhibitor
      ramipril on the clinical and laboratory parameters of diabetic patients with proteinuria.
In recent years, diabetic nephropathy, which may lead to dialysis treatment, is the most
      prevalent underlying disease of people in developed countries. A wide range of studies have
      been carried out, from various points of view, to understand the progress of renal
      dysfunction in diabetic nephropathy. The endogenous nitric oxide synthase (NOS) inhibitor
      asymmetric dimethylarginine (ADMA) is elevated in patients with chronic kidney disease (CKD)
      and may have a role in the cardiovascular mortality and morbidity of these patients. In
      diabetic nephropathy, high ADMA levels were related to progression of diabetic nephropathy.

      Fibroblast growth factor 23 (FGF-23) is a primary regulator of renal phosphate excretion.
      FGF23 is inversely associated with the GFR, a relationship underlying a fundamental mechanism
      for maintaining serum phosphate constancy during CKD progression. Such an adaptation may have
      deleterious trade-offs because, independently of serum phosphate, high FGF23 signals a high
      risk of death in ESRD patients. Some studies showed that there is a relationship between
      FGF-23 levels and proteinuria in CKD patients.

      There is no data about the effects of Renin angiotensin system blockage (RAS) on FGF23 and
      ADMA levels in diabetic patients with proteinuria. The aim of this study was to find out
      whether the beneficial effects of RAS blockage in diabetic proteinuria has any relation with
      the alteration of ADMA and FGF-23 levels. We searched for the effects of ACE inhibitor
      ramipril on the clinical and laboratory parameters of diabetic patients with proteinuria.

      The study 'Effect of Renin Angiotensin System Blockade on the Fas Antigen (CD95) and
      Asymmetric Dimethylarginine (ADMA) Levels in Type-2 Diabetic Patients With Proteinuria' has
      been previously registered to ClinicalTrials.gov (Identifier:NCT00893425). The serum samples
      of the above study will be used in order to measure the FGF23 levels in this study. Therefore
      the eligibility criteria and the study design is similar to the previous study
      (Identifier:NCT00893425).

      The patients who were non-obese (BMI<30kg/m2), non dyslipidemic (total cholesterol <200mg/dl,
      Triglyceride<150mg/dl), and free of cardiovascular events (negative medical history, negative
      ECG findings) were investigated for enrollment. CKD stage 1 patients older than 18 years of
      age and willing to participate to the study were screened. From the 231 patients with
      established type 2 diabetes mellitus, 126 had proteinuria and/or hypertension (24 h protein
      excretion 1-2 g/day, systolic blood pressures ≥140mmHg and/or diastolic blood pressures ≥ 90
      mmHg, respectively). All cases were first referrals and at the time of the study all were off
      treatment. Patients with history of coronary artery disease, smokers and those taking statins
      or renin-angiotensin blockers were excluded because of the effect of these factors on
      endothelial dysfunction. Of 126 screened patients 78 met the study criteria and were included
      in this study. The duration of proteinuria and diabetic nephropathy after initial diagnosis
      was not known.

      The exclusion criteria were as follows: A)Nephrotic syndrome, B)coronary heart disease
      (patients with ischemic ST-T alterations and voltage criteria for LVH on electrocardiogram,
      and with history of revascularization or myocardial infarction), C) elevated liver enzymes
      (AST or ALT levels ≥ 40U/L) and D) renal failure (serum creatinine levels > 1.3 mg/dl). In
      order to evaluate the effect of RAS blockade on FGF 23 concentrations, patients with
      proteinuria were given an ACE inhibitor (ramipril 10 mg/day) for 12 weeks. The effect of RAS
      blockade on insulin sensitivity and proteinuria was also investigated.

      After the intervention period, blood samples were obtained for assay of FGF-23
      concentrations, HbA1c , and insulin resistance scores (HOMA-IR).

      Urine samples were also collected over a 24-hour period to determine the degree of
      proteinuria.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Flow Mediated Dilatation
measure: FGF-23
arm group label: Ramipril
arm group type: Experimental
intervention type: Drug
intervention name: Ramipril
description: ramipril 10 mg/day during 3 months
arm group label: Ramipril
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Turkey
responsible party type: Principal Investigator
investigator affiliation: Gulhane School of Medicine
investigator full name: Mahmut Ilker Yilmaz
investigator title: Assoc.Prof.
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Diabetic Nephropathies
mesh term: Proteinuria
mesh term: Ramipril