<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/NCT02242149</url>
  </required_header>
  <id_info>
    <org_study_id>30194914.3.0000.5257</org_study_id>
    <nct_id>NCT02242149</nct_id>
  </id_info>
  <brief_title>Efficacy Study of Diacerein on Glycemic Control and Liver Fat in Type 2 Diabetes Subjects</brief_title>
  <acronym>DGCLFT2DM</acronym>
  <official_title>Efficacy Study of Diacerein on Glycemic Control and Liver Fat in Type 2 Diabetes Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidade Federal do Rio de Janeiro</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Rio de Janeiro State Research Supporting Foundation (FAPERJ)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universidade Federal do Rio de Janeiro</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is conducted to test the hypothesis that in uncontrolled type 2 diabetic adults&#xD;
      treatment with diacerein will improve glycemic control and will reduce liver fat within a 24&#xD;
      month period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Recently, knowledge about diacerhein, an anthraquinone drug with powerful&#xD;
      anti-inflammatory properties, revealed that this drug improves insulin sensitivity, mediated&#xD;
      by the reversal of chronic subclinical inflammation. Amongst the numerous pathogenetic&#xD;
      factors, oxidative stress and apoptosis of hepatocytes initiate many inflammatory processes&#xD;
      and are involved in the progression of Non alcoholic fatty liver disease.&#xD;
&#xD;
      Aims:The aim is to evaluate the effect of treatment with diacerein in improvement of glycemic&#xD;
      parameters (mean glycated hemoglobin, fasting blood sugar) and reduction of liver fat&#xD;
      fraction.&#xD;
&#xD;
      Methods:Two-hundred patients will be randomly allocated either to treatment with diacerein&#xD;
      plus their usual therapeutic regimen or to placebo for 24 months. Clinic, laboratory&#xD;
      evaluation (including glycated hemoglobin, fasting blood sugar, creatinine, ferritin,&#xD;
      aspartate aminotransferase (AST), alanine aminotransferase (ALT), g-glutamyl transpeptidase,&#xD;
      alkaline phosphatase, bilirubin, albumin, prothrombin time, platelet count, total&#xD;
      cholesterol, high-density and low-density lipoprotein cholesterol and triglycerides and&#xD;
      urinary albumin excretion rate no 24-hour urine collection) will be performed before and&#xD;
      every 3 months until the end of study. Pro-Inflammatory cytokines, adiponectin and&#xD;
      cytokeratin-18 were measured before, at 12 months and at the end of study. Liver fat fraction&#xD;
      measurement using controlled attenuation parameter (CAP) by transient elastography.&#xD;
      (Fibroscan) will be performed before and after the 12 and 24-month treatment, with the&#xD;
      observers blinded to the allocation group.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 14, 2014</start_date>
  <completion_date type="Actual">January 31, 2018</completion_date>
  <primary_completion_date type="Actual">January 31, 2017</primary_completion_date>
  <phase>Phase 3</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evidence of improvement in glycemic control and improvement in liver steatosis</measure>
    <time_frame>Within 12 and 24 months</time_frame>
    <description>Reduction of mean glycated hemoglobin (≥ 1%) and reduction of liver fat fraction as measured by transient elastography (≥ 20%)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Improvement of microalbuminuria</measure>
    <time_frame>Within 24 months</time_frame>
    <description>Reduction of albumin excretion rate on 24-hour urine collection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of adipocytokines and cytokeratin-18</measure>
    <time_frame>Within 24 months</time_frame>
    <description>Elevation of high molecular weight adiponectin and reduction of the apoptotic by-product cytokeratin (CK)-18</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">84</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <condition>Non-alcoholic Fatty Liver Disease</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>All subjects will be given placebo identically matched with regard to shape, color and taste. They will be given one tablet/day for 2 weeks and then two tablets/day for the duration of sudy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diacerein</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects will be given diacerein with a starting dose of 50 mg in one tablet once daily for 2 weeks. After 2 weeks, they will be given diacerein 50 mg in one tablet twice daily for the duration of sudy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Diacerein</intervention_name>
    <description>All subjects will be given diacerein with a starting dose of 50 mg in one tablet once daily for 2 weeks. After 2 weeks, they will be given diacerein 50 mg in one tablet twice daily for the duration of sudy.</description>
    <arm_group_label>Diacerein</arm_group_label>
    <other_name>Artrodar</other_name>
    <other_name>Artifit</other_name>
    <other_name>Acert</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Sugar pill manufactured to mimic Diacerein</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type 2 diabetes.&#xD;
&#xD;
          -  Presence of liver steatosis diagnosed by ultrasound or transient elastography&#xD;
             (Fibroscan®)&#xD;
&#xD;
          -  Age 30-75 years.&#xD;
&#xD;
          -  HbA1c 7.5- 9.5 for at least 8 weeks prior to screening.&#xD;
&#xD;
          -  Stable diabetes therapeutic regimen consisting of either diet, oral hypoglycemic&#xD;
             agents with or without insulin for 8 weeks prior to randomization.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Body mass index &gt; 40 kg/m2&#xD;
&#xD;
          -  Serum creatinine ≥180mmol/L or estimated glomerular filtration rate &lt; 30 ml/min.&#xD;
&#xD;
          -  Presence of any serious concomitant disease, such as a pulmonary disease or malignant&#xD;
             disorders.&#xD;
&#xD;
          -  Current daily alcohol ingestion ≥20 g.&#xD;
&#xD;
          -  Hepatotoxic drugs.&#xD;
&#xD;
          -  Presence of other chronic liver disease other than nonalcoholic fatty liver disease,&#xD;
             including hepatitis B virus and hepatitis C virus infection, hemochromatosis, Wilson's&#xD;
             disease, alfa-1 antitrypsin deficiency, autoimmune hepatitis.&#xD;
&#xD;
          -  Women seeking pregnancy.&#xD;
&#xD;
          -  Current use or previous use within 6 months of vitamin E or pioglitazone&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gil F Salles, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universidade Federal do Rio de Janeiro</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Program of Arterial Hypertension, University Hospital Clementino Fraga Filho</name>
      <address>
        <city>Rio de Janeiro</city>
        <zip>21941913</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>September 14, 2014</study_first_submitted>
  <study_first_submitted_qc>September 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <last_update_submitted>May 2, 2018</last_update_submitted>
  <last_update_submitted_qc>May 2, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universidade Federal do Rio de Janeiro</investigator_affiliation>
    <investigator_full_name>Gil Fernando da Costa Mendes de Salles, PhD</investigator_full_name>
    <investigator_title>Full Professor, Faculty of Medicine</investigator_title>
  </responsible_party>
  <keyword>Fat liver</keyword>
  <keyword>Diabetes</keyword>
  <keyword>Diacerein</keyword>
  <keyword>Transient elastography</keyword>
  <keyword>Treatment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>Fatty Liver</mesh_term>
    <mesh_term>Non-alcoholic Fatty Liver Disease</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diacerein</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/NCT02242149
org study id: 30194914.3.0000.5257
nct id: NCT02242149
lead sponsor: 
collaborator: 
has dmc: No
This study is conducted to test the hypothesis that in uncontrolled type 2 diabetic adults
      treatment with diacerein will improve glycemic control and will reduce liver fat within a 24
      month period.
Background: Recently, knowledge about diacerhein, an anthraquinone drug with powerful
      anti-inflammatory properties, revealed that this drug improves insulin sensitivity, mediated
      by the reversal of chronic subclinical inflammation. Amongst the numerous pathogenetic
      factors, oxidative stress and apoptosis of hepatocytes initiate many inflammatory processes
      and are involved in the progression of Non alcoholic fatty liver disease.

      Aims:The aim is to evaluate the effect of treatment with diacerein in improvement of glycemic
      parameters (mean glycated hemoglobin, fasting blood sugar) and reduction of liver fat
      fraction.

      Methods:Two-hundred patients will be randomly allocated either to treatment with diacerein
      plus their usual therapeutic regimen or to placebo for 24 months. Clinic, laboratory
      evaluation (including glycated hemoglobin, fasting blood sugar, creatinine, ferritin,
      aspartate aminotransferase (AST), alanine aminotransferase (ALT), g-glutamyl transpeptidase,
      alkaline phosphatase, bilirubin, albumin, prothrombin time, platelet count, total
      cholesterol, high-density and low-density lipoprotein cholesterol and triglycerides and
      urinary albumin excretion rate no 24-hour urine collection) will be performed before and
      every 3 months until the end of study. Pro-Inflammatory cytokines, adiponectin and
      cytokeratin-18 were measured before, at 12 months and at the end of study. Liver fat fraction
      measurement using controlled attenuation parameter (CAP) by transient elastography.
      (Fibroscan) will be performed before and after the 12 and 24-month treatment, with the
      observers blinded to the allocation group.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Evidence of improvement in glycemic control and improvement in liver steatosis
time frame: Within 12 and 24 months
description: Reduction of mean glycated hemoglobin (≥ 1%) and reduction of liver fat fraction as measured by transient elastography (≥ 20%)
measure: Improvement of microalbuminuria
time frame: Within 24 months
description: Reduction of albumin excretion rate on 24-hour urine collection
measure: Changes of adipocytokines and cytokeratin-18
time frame: Within 24 months
description: Elevation of high molecular weight adiponectin and reduction of the apoptotic by-product cytokeratin (CK)-18
arm group label: Placebo
arm group type: Placebo Comparator
description: All subjects will be given placebo identically matched with regard to shape, color and taste. They will be given one tablet/day for 2 weeks and then two tablets/day for the duration of sudy.
arm group label: Diacerein
arm group type: Experimental
description: All subjects will be given diacerein with a starting dose of 50 mg in one tablet once daily for 2 weeks. After 2 weeks, they will be given diacerein 50 mg in one tablet twice daily for the duration of sudy.
intervention type: Drug
intervention name: Diacerein
description: All subjects will be given diacerein with a starting dose of 50 mg in one tablet once daily for 2 weeks. After 2 weeks, they will be given diacerein 50 mg in one tablet twice daily for the duration of sudy.
arm group label: Diacerein
other name: Artrodar
other name: Artifit
other name: Acert
intervention type: Drug
intervention name: Placebo
description: Sugar pill manufactured to mimic Diacerein
arm group label: Placebo
criteria: 
gender: All
minimum age: 30 Years
maximum age: 75 Years
healthy volunteers: No
last name: Gil F Salles, PhD
role: Principal Investigator
affiliation: Universidade Federal do Rio de Janeiro
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Universidade Federal do Rio de Janeiro
investigator full name: Gil Fernando da Costa Mendes de Salles, PhD
investigator title: Full Professor, Faculty of Medicine
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Diacerein