<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/NCT02993484</url>
  </required_header>
  <id_info>
    <org_study_id>Human A-strips Mitochondria</org_study_id>
    <nct_id>NCT02993484</nct_id>
  </id_info>
  <brief_title>The Role of Mitochondrial Respiration in the Cardioprotective Capacity of IPC in Diabetic and Non-diabetic Patients</brief_title>
  <official_title>The Role of Mitochondrial Respiration in the Cardioprotective Capacity of IPC in Diabetic and Non-diabetic Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Aarhus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Aarhus</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall aim of this study is to examine the role of mitochondrial respiration in human&#xD;
      diabetic tissue before and after ischemia. Furthermore we will examine the ability of&#xD;
      ischemic preconditioning (IPC) to preserve the mitochondrial function and hemodynamic&#xD;
      performance of both non-diabetic and diabetic fibers after ischemia. To increase our&#xD;
      understanding on the metabolic changes during ischemia in both non-diabetic and diabetic&#xD;
      tissue we will use Dimethyl Malonate and examine the impact of this blockade on post-ischemic&#xD;
      mitochondrial respiration.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      20 diabetic and 20 non-diabetic patients undergoing elective CABG surgery or other heart&#xD;
      surgery where extracorporal circulation is used will be included in the study. The patiens&#xD;
      will not be given any treatment prior to the operation. During the cardiac surgery a small&#xD;
      sample of the heart is routinely removed when the patient is connection to the heart-lung&#xD;
      machine. From this tissue sample it is possible to isolate muscle trabeculae which will be&#xD;
      used in an atrial strip model and randomized to one of four types of treatment.&#xD;
      Simultaneously with the isolation of the trabeculae, a fifth trabecular will be used to&#xD;
      assess mitochondrial respiration at baseline. Group 1 will serve as a sham control, group 2&#xD;
      will serve as ischemic control and receive an extended period of hypoxia, Group 3 will be&#xD;
      treated with ischemic preconditioning, where short periods of non lethal lack of oxygen will&#xD;
      be given directly to the tissue (after removal from the patient) prior to the extended period&#xD;
      of hypoxia, Group 4 will receive dimethyl malonate prior to the prolonged hypoxia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2016</start_date>
  <completion_date type="Actual">February 1, 2019</completion_date>
  <primary_completion_date type="Actual">February 1, 2019</primary_completion_date>
  <phase>N/A</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>Basic Science</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mitochondrial respiration of individual complexes</measure>
    <time_frame>Outcome will be assessed within a year when the inclusion of patients is complete</time_frame>
    <description>Mitochondrial respiration of individual complexes will serve as primary outcome and will be examined by oxygraph technique.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hemodynamic performance</measure>
    <time_frame>Outcome will be assessed within a year when the inclusion of patients is complete</time_frame>
    <description>Hemodynamic performance will be measured as contractile force of heart fibers before during and after ischemia.</description>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">39</enrollment>
  <condition>Reperfusion Injuries, Myocardial</condition>
  <arm_group>
    <arm_group_label>non-diabetic Sham control</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Heart tissue obtained from non-diabetic patients undergoing surgery will not receive drugs or ischemia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>non-diabetic Ischemia reperfusion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Heart tissue from non-diabetic patients undergoing surgery will not receive drugs but will receive ischemia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>non-diabetic Ischemic preconditioning</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Heart tissue from non-diabetic patients undergoing surgery will not receive drugs but will receive short periods of ischemia prior to index ischemia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>non-diabetic Dimethyl malonate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Heart tissue from non-diabetic patients undergoing surgery will receive a drug (Dimethyl Malonate) prior to index ischemia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diabetic Sham control</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Heart tissue obtained from diabetic patients undergoing surgery will not receive drugs or ischemia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diabetic Ischemia reperfusion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Heart tissue from diabetic patients undergoing surgery will not receive drugs but will receive ischemia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diabetic Ischemic preconditioning</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Heart tissue from diabetic patients undergoing surgery will not receive drugs but will receive short periods of ischemia prior to index ischemia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diabetic Dimethyl malonate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Heart tissue from diabetic patients undergoing surgery will receive a drug (Dimethyl Malonate) prior to index ischemia</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dimethyl Malonate</intervention_name>
    <description>Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.</description>
    <arm_group_label>Diabetic Dimethyl malonate</arm_group_label>
    <arm_group_label>non-diabetic Dimethyl malonate</arm_group_label>
    <other_name>Dimethyl Malonate; PubChem Substance ID 24848281</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Ischemic preconditioning</intervention_name>
    <description>Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.</description>
    <arm_group_label>Diabetic Ischemic preconditioning</arm_group_label>
    <arm_group_label>non-diabetic Ischemic preconditioning</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Ischemia reperfusion</intervention_name>
    <description>Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.</description>
    <arm_group_label>Diabetic Ischemia reperfusion</arm_group_label>
    <arm_group_label>non-diabetic Ischemia reperfusion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Sham</intervention_name>
    <description>Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.</description>
    <arm_group_label>Diabetic Sham control</arm_group_label>
    <arm_group_label>non-diabetic Sham control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients undergoing CABG or other surgery where extracorporal circulation will be&#xD;
             used.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  raise in ischemic markers within 4 weeks&#xD;
&#xD;
          -  ejection fraction &lt;30&#xD;
&#xD;
          -  Atrial fibrilation&#xD;
&#xD;
          -  Oral opioid treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>December 8, 2016</study_first_submitted>
  <study_first_submitted_qc>December 12, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 15, 2016</study_first_posted>
  <last_update_submitted>June 6, 2019</last_update_submitted>
  <last_update_submitted_qc>June 6, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 7, 2019</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>Reperfusion Injury</mesh_term>
    <mesh_term>Myocardial Reperfusion Injury</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/NCT02993484
org study id: Human A-strips Mitochondria
nct id: NCT02993484
lead sponsor: 
has dmc: No
The overall aim of this study is to examine the role of mitochondrial respiration in human
      diabetic tissue before and after ischemia. Furthermore we will examine the ability of
      ischemic preconditioning (IPC) to preserve the mitochondrial function and hemodynamic
      performance of both non-diabetic and diabetic fibers after ischemia. To increase our
      understanding on the metabolic changes during ischemia in both non-diabetic and diabetic
      tissue we will use Dimethyl Malonate and examine the impact of this blockade on post-ischemic
      mitochondrial respiration.
20 diabetic and 20 non-diabetic patients undergoing elective CABG surgery or other heart
      surgery where extracorporal circulation is used will be included in the study. The patiens
      will not be given any treatment prior to the operation. During the cardiac surgery a small
      sample of the heart is routinely removed when the patient is connection to the heart-lung
      machine. From this tissue sample it is possible to isolate muscle trabeculae which will be
      used in an atrial strip model and randomized to one of four types of treatment.
      Simultaneously with the isolation of the trabeculae, a fifth trabecular will be used to
      assess mitochondrial respiration at baseline. Group 1 will serve as a sham control, group 2
      will serve as ischemic control and receive an extended period of hypoxia, Group 3 will be
      treated with ischemic preconditioning, where short periods of non lethal lack of oxygen will
      be given directly to the tissue (after removal from the patient) prior to the extended period
      of hypoxia, Group 4 will receive dimethyl malonate prior to the prolonged hypoxia.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Single (Outcomes Assessor)
measure: Mitochondrial respiration of individual complexes
time frame: Outcome will be assessed within a year when the inclusion of patients is complete
description: Mitochondrial respiration of individual complexes will serve as primary outcome and will be examined by oxygraph technique.
measure: Hemodynamic performance
time frame: Outcome will be assessed within a year when the inclusion of patients is complete
description: Hemodynamic performance will be measured as contractile force of heart fibers before during and after ischemia.
arm group label: non-diabetic Sham control
arm group type: Experimental
description: Heart tissue obtained from non-diabetic patients undergoing surgery will not receive drugs or ischemia
arm group label: non-diabetic Ischemia reperfusion
arm group type: Experimental
description: Heart tissue from non-diabetic patients undergoing surgery will not receive drugs but will receive ischemia
arm group label: non-diabetic Ischemic preconditioning
arm group type: Experimental
description: Heart tissue from non-diabetic patients undergoing surgery will not receive drugs but will receive short periods of ischemia prior to index ischemia
arm group label: non-diabetic Dimethyl malonate
arm group type: Experimental
description: Heart tissue from non-diabetic patients undergoing surgery will receive a drug (Dimethyl Malonate) prior to index ischemia
arm group label: Diabetic Sham control
arm group type: Experimental
description: Heart tissue obtained from diabetic patients undergoing surgery will not receive drugs or ischemia
arm group label: Diabetic Ischemia reperfusion
arm group type: Experimental
description: Heart tissue from diabetic patients undergoing surgery will not receive drugs but will receive ischemia
arm group label: Diabetic Ischemic preconditioning
arm group type: Experimental
description: Heart tissue from diabetic patients undergoing surgery will not receive drugs but will receive short periods of ischemia prior to index ischemia
arm group label: Diabetic Dimethyl malonate
arm group type: Experimental
description: Heart tissue from diabetic patients undergoing surgery will receive a drug (Dimethyl Malonate) prior to index ischemia
intervention type: Drug
intervention name: Dimethyl Malonate
description: Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.
arm group label: Diabetic Dimethyl malonate
arm group label: non-diabetic Dimethyl malonate
other name: Dimethyl Malonate; PubChem Substance ID 24848281
intervention type: Biological
intervention name: Ischemic preconditioning
description: Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.
arm group label: Diabetic Ischemic preconditioning
arm group label: non-diabetic Ischemic preconditioning
intervention type: Other
intervention name: Ischemia reperfusion
description: Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.
arm group label: Diabetic Ischemia reperfusion
arm group label: non-diabetic Ischemia reperfusion
intervention type: Other
intervention name: Sham
description: Heart tissue will be obtained from patients undergoing heart surgery. The tissue will be used to test the properties of ischemia and different cardioprotective interventions.
arm group label: Diabetic Sham control
arm group label: non-diabetic Sham control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
responsible party type: Sponsor
mesh term: Reperfusion Injury
mesh term: Myocardial Reperfusion Injury
sharing ipd: No