<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/NCT03244449</url>
  </required_header>
  <id_info>
    <org_study_id>120465745008</org_study_id>
    <nct_id>NCT03244449</nct_id>
  </id_info>
  <brief_title>New IR Biomarkers (Myokines) in Colombian People</brief_title>
  <official_title>Identification and Validation of Myonectin, Myostatin and FGF-21 as Insulin Resistance Biomarkers in Colombian People</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Los Andes, Columbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Administrative Department of Science, Technology and Innovation, Colciencias</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Universidad Militar Nueva Granada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Los Andes, Columbia</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Around the world, the prevalence of type 2 diabetes mellitus (T2DM) has been increasing since&#xD;
      the last two decades, with approximately 347 million patients with diabetes by 2013 according&#xD;
      to the World Health Organization (WHO). This pronounced increase is due to an increase in the&#xD;
      prevalence of obesity, reduction in physical activity levels, accelerated urbanization and&#xD;
      aging of the population. In Colombia, T2DM ranks fifth in the main morbidity and mortality&#xD;
      causes, including only deaths caused directly and without adding the strong influence that&#xD;
      T2DM has on cardiovascular disease mortality.&#xD;
&#xD;
      Insufficient tissue response to normal insulin concentrations, called insulin resistance, is&#xD;
      one of the central pathophysiological mechanisms in the development of T2DM. However, there&#xD;
      is currently no simple, practical, safe and reproducible method that allows the diagnosis or&#xD;
      identification of insulin resistance, nor the follow-up to its evolution. At the moment, the&#xD;
      gold standard for assessing the degree of insulin sensitivity or resistance is the&#xD;
      &quot;hyperinsulinemic-euglycemic clamp&quot;, a laborious technique, of high cost and high technical&#xD;
      difficulty, requiring specialized personnel and hospitalization. Non-invasive methods based&#xD;
      on mathematical regressions, such as the Homeostatic Model Assessment (HOMA-IR), are&#xD;
      imperfect and widely variable, and have not been validated in the Latin American population,&#xD;
      less Still Colombian.&#xD;
&#xD;
      Therefore, the development of new, easily obtainable quantitative tools for the diagnosis of&#xD;
      insulin resistance is required. This requires not only the identification of new and better&#xD;
      biomarkers, but also the determination of their diagnostic performance and operational&#xD;
      characteristics.&#xD;
&#xD;
      This project will investigate 3 molecular targets (myokines), novel and easy to measure, with&#xD;
      high probability of being good biomarkers of insulin resistance. The research will include&#xD;
      validation of its association with insulin resistance measured by the reference method, as&#xD;
      well as its measurement in apparently healthy individuals. Finally, operator-receiver&#xD;
      characteristics of each test will be analyzed, in order to propose a cutoff point for the&#xD;
      diagnosis of insulin resistance.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objectives of the project are: 1) To identify, within a group of 3 potential new&#xD;
      biomarkers of insulin resistance, those that are significantly associated with the presence&#xD;
      of this phenomenon in our population, 2) Establish, analyze and apply reference values for&#xD;
      each one of these three biomarkers in Colombian population. 3) To evaluate the sensitivity,&#xD;
      specificity, statistical C (operational performance), predictive values and likelihood ratios&#xD;
      of each of the biomarkers studied for the diagnosis of insulin resistance versus a standard&#xD;
      gold technique and 4) Different biomarkers evaluated, in order to select the best one (s) for&#xD;
      clinical use, as well as to propose a cutoff point for detection of insulin resistance for&#xD;
      each of them.&#xD;
&#xD;
      Methodology: A cross-sectional, diagnostic test evaluation study will be conducted, including&#xD;
      apparently healthy Adults of both sexes, with ages between 35 and 65 years, coming from&#xD;
      Bogotá, without any significant comorbidity.&#xD;
&#xD;
      As initial evaluation will be carried out measurement of height, weight, percentage of body&#xD;
      fat, blood pressure, diet questionnaire, physical activity and sociocultural characteristics.&#xD;
      For patients with prediabetes and T2DM, the time elapsed since the diagnosis will be&#xD;
      obtained, as well as information about pharmacological or non-pharmacological treatment that&#xD;
      they are receiving.&#xD;
&#xD;
      For the serological evaluation, a sample of venous blood should be taken in the fasted state,&#xD;
      with the aim of measuring the following markers: Fibroblast Growth Factor 21 (FGF21) ,&#xD;
      Myonectin, and Myostatin. In addition to routine tests such as fasting glycemia, glycosylated&#xD;
      hemoglobin, fasting insulinemia, lipid profile (total cholesterol, HDL cholesterol,&#xD;
      triglycerides, LDL-C) and C-reactive protein. Additionally, all subjects will participate in&#xD;
      an oral glucose tolerance test (OGTT).&#xD;
&#xD;
      In addition to the gold standard of measurement of insulin resistance&#xD;
      (hyperinsulinemic-euglycemic clamp), six of the tools currently available for the search of&#xD;
      insulin resistance, all derived from calculations from the measurements of The HOMA beta-cell&#xD;
      function (HOMA beta-cell%), insulin sensitivity index (ISI), index 1 / fasting insulin,&#xD;
      corrected insulin response, insulin / glucose ratio and insulinemia Of fasting.&#xD;
&#xD;
      For each biomarker, an operator / receiver characteristics curve (ROC curve) will be&#xD;
      calculated, calculating diagnostic performance and cutoff points with the best combination of&#xD;
      sensitivity and specificity. A first approximation will be made to baseline values for these&#xD;
      tests, based on the distribution of the tests in healthy, and one or more insulin resistance&#xD;
      biomarkers with their recommended cutoff points will be proposed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 26, 2014</start_date>
  <completion_date type="Actual">December 16, 2016</completion_date>
  <primary_completion_date type="Actual">October 30, 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Ecologic or Community</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Incremental area under the insulin curve (iAUCins)</measure>
    <time_frame>Once in every participant (Cross-sectional). Participants assessed over 6-months</time_frame>
    <description>Area under the insulin curve in a 5-point oral glucose tolerance test, calculated with the trapezoid method, a reliable indicator of whole-body insulin resistance. Expressed in mg*(dL^-1)*(h^-1)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Whole-body glucose disposal</measure>
    <time_frame>Once in every participant (Cross-sectional). Participants assessed over 6-months</time_frame>
    <description>Glucose disposal when steady state is reached in a hyperinsulinemic-euglycemic clamp, the gold-standard measure of whole-body insulin sensitivity. Expressed in mg*(Kg^-1)*(min^-1)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>HOMA-IR (Homeostasis Model Assessment - Insulin Resistance)</measure>
    <time_frame>Once in every participant (Cross-sectional). Participants assessed over 6-months</time_frame>
    <description>Product of the fasting glycemia in mmol/L and fasting insulinemia in microunits/mL, a surrogate measure of insulin resistance, especially in the fasting state.</description>
  </secondary_outcome>
  <enrollment type="Actual">81</enrollment>
  <condition>Insulin Resistance</condition>
  <condition>Diabetes Mellitus, Type 2</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No apply</intervention_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Adults of both sexes, aged between 35 and 65 years, without any significant comorbidity&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age between 35-65 years&#xD;
&#xD;
          -  Diligence of informed consent&#xD;
&#xD;
          -  Absence of acute illness&#xD;
&#xD;
          -  Body mass index less or greater than 25 kg/m2, and presence or absence of a previous&#xD;
             diagnosis of diabetes according to the criteria previously stated.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current therapy with insulin&#xD;
&#xD;
          -  Type 1 diabetes&#xD;
&#xD;
          -  Oral or injectable anticoagulation&#xD;
&#xD;
          -  Previous diagnosis of insulinoma, insulinomatosis, glucagonoma, or other neoplastic&#xD;
             disorders of the endocrine pancreas.&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  BMI &lt;18.5 kg / m2&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carlos O Mendivil, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Los Andes</affiliation>
  </overall_official>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 4, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 9, 2017</study_first_posted>
  <last_update_submitted>August 8, 2017</last_update_submitted>
  <last_update_submitted_qc>August 8, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Los Andes, Columbia</investigator_affiliation>
    <investigator_full_name>Carlos O Mendivil</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>biomarker</keyword>
  <keyword>insulin resistance</keyword>
  <keyword>myokine</keyword>
  <keyword>clamp</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    <mesh_term>Insulin Resistance</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Undecided</ipd_description>
  </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/NCT03244449
org study id: 120465745008
nct id: NCT03244449
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Around the world, the prevalence of type 2 diabetes mellitus (T2DM) has been increasing since
      the last two decades, with approximately 347 million patients with diabetes by 2013 according
      to the World Health Organization (WHO). This pronounced increase is due to an increase in the
      prevalence of obesity, reduction in physical activity levels, accelerated urbanization and
      aging of the population. In Colombia, T2DM ranks fifth in the main morbidity and mortality
      causes, including only deaths caused directly and without adding the strong influence that
      T2DM has on cardiovascular disease mortality.

      Insufficient tissue response to normal insulin concentrations, called insulin resistance, is
      one of the central pathophysiological mechanisms in the development of T2DM. However, there
      is currently no simple, practical, safe and reproducible method that allows the diagnosis or
      identification of insulin resistance, nor the follow-up to its evolution. At the moment, the
      gold standard for assessing the degree of insulin sensitivity or resistance is the
      "hyperinsulinemic-euglycemic clamp", a laborious technique, of high cost and high technical
      difficulty, requiring specialized personnel and hospitalization. Non-invasive methods based
      on mathematical regressions, such as the Homeostatic Model Assessment (HOMA-IR), are
      imperfect and widely variable, and have not been validated in the Latin American population,
      less Still Colombian.

      Therefore, the development of new, easily obtainable quantitative tools for the diagnosis of
      insulin resistance is required. This requires not only the identification of new and better
      biomarkers, but also the determination of their diagnostic performance and operational
      characteristics.

      This project will investigate 3 molecular targets (myokines), novel and easy to measure, with
      high probability of being good biomarkers of insulin resistance. The research will include
      validation of its association with insulin resistance measured by the reference method, as
      well as its measurement in apparently healthy individuals. Finally, operator-receiver
      characteristics of each test will be analyzed, in order to propose a cutoff point for the
      diagnosis of insulin resistance.
The objectives of the project are: 1) To identify, within a group of 3 potential new
      biomarkers of insulin resistance, those that are significantly associated with the presence
      of this phenomenon in our population, 2) Establish, analyze and apply reference values for
      each one of these three biomarkers in Colombian population. 3) To evaluate the sensitivity,
      specificity, statistical C (operational performance), predictive values and likelihood ratios
      of each of the biomarkers studied for the diagnosis of insulin resistance versus a standard
      gold technique and 4) Different biomarkers evaluated, in order to select the best one (s) for
      clinical use, as well as to propose a cutoff point for detection of insulin resistance for
      each of them.

      Methodology: A cross-sectional, diagnostic test evaluation study will be conducted, including
      apparently healthy Adults of both sexes, with ages between 35 and 65 years, coming from
      Bogotá, without any significant comorbidity.

      As initial evaluation will be carried out measurement of height, weight, percentage of body
      fat, blood pressure, diet questionnaire, physical activity and sociocultural characteristics.
      For patients with prediabetes and T2DM, the time elapsed since the diagnosis will be
      obtained, as well as information about pharmacological or non-pharmacological treatment that
      they are receiving.

      For the serological evaluation, a sample of venous blood should be taken in the fasted state,
      with the aim of measuring the following markers: Fibroblast Growth Factor 21 (FGF21) ,
      Myonectin, and Myostatin. In addition to routine tests such as fasting glycemia, glycosylated
      hemoglobin, fasting insulinemia, lipid profile (total cholesterol, HDL cholesterol,
      triglycerides, LDL-C) and C-reactive protein. Additionally, all subjects will participate in
      an oral glucose tolerance test (OGTT).

      In addition to the gold standard of measurement of insulin resistance
      (hyperinsulinemic-euglycemic clamp), six of the tools currently available for the search of
      insulin resistance, all derived from calculations from the measurements of The HOMA beta-cell
      function (HOMA beta-cell%), insulin sensitivity index (ISI), index 1 / fasting insulin,
      corrected insulin response, insulin / glucose ratio and insulinemia Of fasting.

      For each biomarker, an operator / receiver characteristics curve (ROC curve) will be
      calculated, calculating diagnostic performance and cutoff points with the best combination of
      sensitivity and specificity. A first approximation will be made to baseline values for these
      tests, based on the distribution of the tests in healthy, and one or more insulin resistance
      biomarkers with their recommended cutoff points will be proposed.
observational model: Ecologic or Community
time perspective: Cross-Sectional
measure: Incremental area under the insulin curve (iAUCins)
time frame: Once in every participant (Cross-sectional). Participants assessed over 6-months
description: Area under the insulin curve in a 5-point oral glucose tolerance test, calculated with the trapezoid method, a reliable indicator of whole-body insulin resistance. Expressed in mg*(dL^-1)*(h^-1)
measure: Whole-body glucose disposal
time frame: Once in every participant (Cross-sectional). Participants assessed over 6-months
description: Glucose disposal when steady state is reached in a hyperinsulinemic-euglycemic clamp, the gold-standard measure of whole-body insulin sensitivity. Expressed in mg*(Kg^-1)*(min^-1)
measure: HOMA-IR (Homeostasis Model Assessment - Insulin Resistance)
time frame: Once in every participant (Cross-sectional). Participants assessed over 6-months
description: Product of the fasting glycemia in mmol/L and fasting insulinemia in microunits/mL, a surrogate measure of insulin resistance, especially in the fasting state.
intervention type: Other
intervention name: No apply
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 35 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Carlos O Mendivil, MD PhD
role: Principal Investigator
affiliation: University of Los Andes
responsible party type: Principal Investigator
investigator affiliation: University of Los Andes, Columbia
investigator full name: Carlos O Mendivil
investigator title: Associate Professor
mesh term: Diabetes Mellitus, Type 2
mesh term: Insulin Resistance
sharing ipd: Undecided
ipd description: Undecided