<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/NCT02258698</url>
  </required_header>
  <id_info>
    <org_study_id>56/13</org_study_id>
    <nct_id>NCT02258698</nct_id>
  </id_info>
  <brief_title>Insulin Sensitivity, Irisin and Adipokines as Outcome Parameters in Patients Undergoing Cardiac Surgery</brief_title>
  <official_title>Insulin Sensitivity, Irisin and Adipokines as Outcome Parameters in Patients Undergoing Cardiac Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Basel, Switzerland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>McGill University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Basel, Switzerland</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      BACKGROUND: Surgical injury and inflammation provoke a stereotypical stress response. Insulin&#xD;
      resistance plays an intriguing role in these metabolic alterations and depends on the&#xD;
      intensity of injury. Metabolic derangements resulting from peripheral insulin resistance are&#xD;
      unambiguously related to adverse outcomes and higher perioperative complication rates.&#xD;
      Therefore, insulin resistance offers to act as a marker for stress and is potentially&#xD;
      relevant in predicting clinical outcome. Plasma-glycosylated hemoglobin A (HbA1c) is an&#xD;
      established indicator for blood glucose control and has a prognostic value regarding outcomes&#xD;
      after major surgical interventions.&#xD;
&#xD;
      Adipose tissue holds a key function in endocrine metabolism by releasing multiple substances,&#xD;
      so-called adipose-derived secreted factors or adipokines. Recent studies have linked several&#xD;
      adipokines to overall insulin sensitivity in metabolic syndrome-related conditions as well as&#xD;
      in critical illness. Irisin, a recently identified myokine acts on white adipose tissue and&#xD;
      plays a role in the prevention of insulin resistance.&#xD;
&#xD;
      AIMS OF THE STUDY: The aim of this study is to assess the level and the effects of&#xD;
      perioperative insulin resistance on clinical outcome in cardiac surgery patients. Based on&#xD;
      previous studies suggesting glucose homeostasis and insulin resistance are associated with&#xD;
      severity of illness and outcome in critically ill patients,it is proposed that patients with&#xD;
      marked insulin resistance suffer from worse clinical outcome. This study protocol evaluates&#xD;
      the ability of homeostasis model assessment (HOMA), quantitative insulin sensitivity check&#xD;
      index (QUICKI), HbA1c, the adipokines Angiopoietin-like protein 2 (ANGPTL2), C-X-C motif&#xD;
      chemokine 5 (CXCL5), and visfatin, and the myokine irisin to indicate perioperative insulin&#xD;
      resistance and explores for correlation with adverse clinical outcomes after 30 days.&#xD;
&#xD;
      MATERIAL &amp; METHODS: 325 patients admitted to the surgical intensive care unit after elective&#xD;
      on-pump cardiac surgery will be consecutively enrolled. Baseline characteristics and routine&#xD;
      blood samples will be assessed the day before surgery. Study blood samples will be drawn&#xD;
      preoperatively in the induction bay of anesthesia to measure the insulin resistance indices&#xD;
      HOMA and QUICKI, HbA1c, ANGPTL2, CXCL5, visfatin, and irisin. Blood glucose, irisin,&#xD;
      adipokines, and routine biochemical tests will be assessed upon admission to the intensive&#xD;
      care unit and on postoperative days 1 and 3. Adverse outcomes will be assessed 30 days after&#xD;
      surgery. Sample size is set to ensure at least 80% power at a significance level of 0.05.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      see Information below&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2013</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">May 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Number of adverse outcomes in relation to Insulin resistance measured as HOMA (homeostasis model assessment)</measure>
    <time_frame>30 days after surgery</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of adverse outcomes in relation to Insulin resistance measured as QUICKI</measure>
    <time_frame>30 days after surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of adverse outcomes in relation to Insulin resistance measured as HbA1c</measure>
    <time_frame>30 days after surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of adverse outcomes in relation to Insulin resistance measured as ANGPTL2</measure>
    <time_frame>30 days after surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of adverse outcomes in relation to Insulin resistance measured as CXCL5</measure>
    <time_frame>30 days after surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of adverse outcomes in relation to Insulin resistance measured as NAMPT</measure>
    <time_frame>30 days after surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of adverse outcomes in relation to Insulin resistance measured as irisin</measure>
    <time_frame>30 days after surgery</time_frame>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">348</enrollment>
  <condition>Insulin Resistance</condition>
  <condition>Diabetes Mellitus Type 2</condition>
  <condition>Other Functional Disturbances Following Cardiac Surgery</condition>
  <arm_group>
    <arm_group_label>Elective on-pump cardiac surgery</arm_group_label>
    <description>Observation of perioperative Insulin resistance in patients undergoing elective on-pump cardiac surgery (CABG and/or valve repair)</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Cardiac surgery</intervention_name>
    <description>Blood samples for assessing Insulin resistance by HOMA, QUICKI, HbA1c, ANGPTL2, CXCL5, visfatin and irisin are drawn during induction of anesthesia, upon arrival on the intensive care unit and on postoperative day 1 and 3. Thirty days after surgery adverse outcomes covering all-cause morbidity and mortality will be assessed.</description>
    <arm_group_label>Elective on-pump cardiac surgery</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood samples (Serum)&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        A total of 325 patients admitted to the surgical intensive care unit after elective on-pump&#xD;
        cardiac surgery (Table 1) will be consecutively enrolled. This study population has been&#xD;
        chosen not only because of the clinically relevant stress response to cardiac surgery but&#xD;
        also because of the opportunity to differentiate between the different impacts of the&#xD;
        cardiovascular system and the metabolic state on insulin resistance.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged &gt;18 years&#xD;
&#xD;
          -  Admission to the surgical intensive care unit after elective cardiac surgery&#xD;
             (aortocoronary bypass and/or valve repair)&#xD;
&#xD;
          -  Being capable of understanding and signing the consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Blood glucose values requiring continuous insulin infusion preoperatively&#xD;
&#xD;
          -  Ongoing selenium therapy&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Interventional valve repair&#xD;
&#xD;
          -  Intraoperative hypothermic cardiac arrest&#xD;
&#xD;
          -  Off-pump cardiac surgery&#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_official>
    <last_name>Andrea Kopp Lugli, MD, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Basel, Switzerland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Andrea Kopp Lugli</name>
      <address>
        <city>Basel</city>
        <state>BS</state>
        <zip>4031</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>September 29, 2014</study_first_submitted>
  <study_first_submitted_qc>October 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 7, 2014</study_first_posted>
  <last_update_submitted>January 31, 2017</last_update_submitted>
  <last_update_submitted_qc>January 31, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 1, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin Resistance</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_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/NCT02258698
org study id: 56/13
nct id: NCT02258698
lead sponsor: 
collaborator: 
has dmc: Yes
BACKGROUND: Surgical injury and inflammation provoke a stereotypical stress response. Insulin
      resistance plays an intriguing role in these metabolic alterations and depends on the
      intensity of injury. Metabolic derangements resulting from peripheral insulin resistance are
      unambiguously related to adverse outcomes and higher perioperative complication rates.
      Therefore, insulin resistance offers to act as a marker for stress and is potentially
      relevant in predicting clinical outcome. Plasma-glycosylated hemoglobin A (HbA1c) is an
      established indicator for blood glucose control and has a prognostic value regarding outcomes
      after major surgical interventions.

      Adipose tissue holds a key function in endocrine metabolism by releasing multiple substances,
      so-called adipose-derived secreted factors or adipokines. Recent studies have linked several
      adipokines to overall insulin sensitivity in metabolic syndrome-related conditions as well as
      in critical illness. Irisin, a recently identified myokine acts on white adipose tissue and
      plays a role in the prevention of insulin resistance.

      AIMS OF THE STUDY: The aim of this study is to assess the level and the effects of
      perioperative insulin resistance on clinical outcome in cardiac surgery patients. Based on
      previous studies suggesting glucose homeostasis and insulin resistance are associated with
      severity of illness and outcome in critically ill patients,it is proposed that patients with
      marked insulin resistance suffer from worse clinical outcome. This study protocol evaluates
      the ability of homeostasis model assessment (HOMA), quantitative insulin sensitivity check
      index (QUICKI), HbA1c, the adipokines Angiopoietin-like protein 2 (ANGPTL2), C-X-C motif
      chemokine 5 (CXCL5), and visfatin, and the myokine irisin to indicate perioperative insulin
      resistance and explores for correlation with adverse clinical outcomes after 30 days.

      MATERIAL & METHODS: 325 patients admitted to the surgical intensive care unit after elective
      on-pump cardiac surgery will be consecutively enrolled. Baseline characteristics and routine
      blood samples will be assessed the day before surgery. Study blood samples will be drawn
      preoperatively in the induction bay of anesthesia to measure the insulin resistance indices
      HOMA and QUICKI, HbA1c, ANGPTL2, CXCL5, visfatin, and irisin. Blood glucose, irisin,
      adipokines, and routine biochemical tests will be assessed upon admission to the intensive
      care unit and on postoperative days 1 and 3. Adverse outcomes will be assessed 30 days after
      surgery. Sample size is set to ensure at least 80% power at a significance level of 0.05.
see Information below
observational model: Cohort
time perspective: Prospective
measure: Number of adverse outcomes in relation to Insulin resistance measured as HOMA (homeostasis model assessment)
time frame: 30 days after surgery
measure: Number of adverse outcomes in relation to Insulin resistance measured as QUICKI
time frame: 30 days after surgery
measure: Number of adverse outcomes in relation to Insulin resistance measured as HbA1c
time frame: 30 days after surgery
measure: Number of adverse outcomes in relation to Insulin resistance measured as ANGPTL2
time frame: 30 days after surgery
measure: Number of adverse outcomes in relation to Insulin resistance measured as CXCL5
time frame: 30 days after surgery
measure: Number of adverse outcomes in relation to Insulin resistance measured as NAMPT
time frame: 30 days after surgery
measure: Number of adverse outcomes in relation to Insulin resistance measured as irisin
time frame: 30 days after surgery
arm group label: Elective on-pump cardiac surgery
description: Observation of perioperative Insulin resistance in patients undergoing elective on-pump cardiac surgery (CABG and/or valve repair)
intervention type: Procedure
intervention name: Cardiac surgery
description: Blood samples for assessing Insulin resistance by HOMA, QUICKI, HbA1c, ANGPTL2, CXCL5, visfatin and irisin are drawn during induction of anesthesia, upon arrival on the intensive care unit and on postoperative day 1 and 3. Thirty days after surgery adverse outcomes covering all-cause morbidity and mortality will be assessed.
arm group label: Elective on-pump cardiac surgery
blood samples (Serum)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andrea Kopp Lugli, MD, MSc
role: Principal Investigator
affiliation: University Hospital, Basel, Switzerland
facility: 
country: Switzerland
responsible party type: Sponsor
mesh term: Insulin Resistance
mesh term: Diabetes Mellitus, Type 2