<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/NCT03043742</url>
  </required_header>
  <id_info>
    <org_study_id>15-1051</org_study_id>
    <nct_id>NCT03043742</nct_id>
  </id_info>
  <brief_title>Stem Cell Heart Injections During Laser Revascularization Surgery for Treatment of Chronic Ischemic Heart Disease</brief_title>
  <official_title>Prospective Controlled Trial of Intra-Myocardial Infusion of Bone Marrow Derived Autologous CD133+ Selected Cells During Trans-Myocardial Laser Revascularization (TMR) in Patients With Chronic Ischemic Heart Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Michael Sekela</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Kentucky</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Assess the safety and effectiveness of stem cell application with regard to improvement in&#xD;
      regional myocardial function in patients receiving Trans-Myocardial Laser Revascularization&#xD;
      (TMR) and stem cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Multiple case experiences and studies have been published reviewing clinical experiences with&#xD;
      Carbon Dioxide Trans-Myocardial Laser Revascularization (TMR) and autologous bone marrow&#xD;
      derived cell application. These experiences have demonstrated perfusion improvements,&#xD;
      ejection fraction improvements and improvements in angina or heart failure symptoms. The&#xD;
      investigators elected to examine the use of CD133 positive (CD133+) BM-derived stem cells&#xD;
      because of their pluripotent nature and the fact that during the CD133 selection process&#xD;
      inflammatory cells present in the bone marrow are being discarded. CD133+ is a recently&#xD;
      discovered marker for more primitive bone marrow derived multipotent stem and endothelial&#xD;
      progenitor cells and is of particular interest in studies directed to therapeutic&#xD;
      angiogenesis, as these cells have been shown to differentiate into endothelial and myogenic&#xD;
      cell lines. Multiple studies have utilized BM derived cells for myocardial regeneration.&#xD;
      Patients who received CD133+ cells showed improved perfusion at injection sites of stem cells&#xD;
      leading to a significant increase in volume of left ventricular ejection fraction, regional&#xD;
      wall motion in the infarct zone, and a reduction in end systolic left ventricular volume.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 12, 2016</start_date>
  <completion_date type="Actual">November 12, 2020</completion_date>
  <primary_completion_date type="Actual">November 12, 2020</primary_completion_date>
  <phase>Phase 1</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Occurrence of Treatment-emergent serious adverse events (SAE) and adverse events</measure>
    <time_frame>Assess from Procedure through 12 months</time_frame>
    <description>Major adverse cardiac event and adverse events defined in the common toxicity criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in left ventricular ejection fraction compared to baseline</measure>
    <time_frame>Assessed at baseline, 6 months, and 12 months</time_frame>
    <description>Measured as a percentage by Echocardiography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in myocardial regional function compared to baseline</measure>
    <time_frame>Assessed at baseline and 6 months</time_frame>
    <description>Measured by nuclear scanning.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in myocardial regional viability compared to baseline</measure>
    <time_frame>Assessed at baseline and 6 months</time_frame>
    <description>Measured by nuclear scanning.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in distance walked compared to baseline</measure>
    <time_frame>Assessed at baseline, 3 months, 6 months, and 12 months</time_frame>
    <description>Measured in feet during a 6 minute walk test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quality of life associated with heart failure compared to baseline</measure>
    <time_frame>Assessed at baseline, 3 months, 6 months, and 12 months</time_frame>
    <description>Measured using the Kansas City Cardiomyopathy Questionnaire.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in class of angina compared to baseline</measure>
    <time_frame>Assessed at baseline, 3 months, 6 months, and 12 months.</time_frame>
    <description>Measured using the Canadian Cardiovascular Society Grading Scale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in class of heart failure compared to baseline</measure>
    <time_frame>Assessed at baseline, 3 months, 6 months, and 12 months.</time_frame>
    <description>Measured using the New York Heart Association Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in regional left ventricular wall motion compared to baseline</measure>
    <time_frame>Assessed at baseline, 6 months, and 12 months</time_frame>
    <description>Measured using echocardiogram.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quality of life associated with angina compared to baseline</measure>
    <time_frame>Assessed at baseline, 3 months, 6 months, and 12 months</time_frame>
    <description>Measured using the Seattle Angina Questionnaire</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Chronic Ischemic Heart Disease</condition>
  <arm_group>
    <arm_group_label>Phase I Open Label</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>open label bone marrow derived autologous CD133+ selected stem cell application in patients receiving trans-myocardial laser revascularization to improve regional myocardial function as detailed below:&#xD;
Drug: CD133+ selected stem cells Dosage: Single injection of 0.1-0.2 ml around each laser channel Frequency: 10-20 channels Duration: Trans-Myocardial Revascularization</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bone Marrow Derived Autologous CD133+ Selected Cell Product</intervention_name>
    <description>Injection of bone marrow derived autologous CD133+ cell product into laser channels during Trans-Myocardial Revascularization</description>
    <arm_group_label>Phase I Open Label</arm_group_label>
    <other_name>Stem cell</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Presence of at least two vessel coronary artery disease not amenable to direct&#xD;
             revascularization&#xD;
&#xD;
          -  Area of interest defined as part of free left ventricular vall with reduced&#xD;
             contractility&#xD;
&#xD;
          -  Demonstration of reduced perfusion in the area of interest (&gt;30% of free wall)&#xD;
&#xD;
          -  Global ejection fraction 30-45% with symptoms class &gt;_ II on the NYHA scale&#xD;
&#xD;
          -  Significant refractory angina defined as symptoms class &gt;_ III that are refractory to&#xD;
             maximal medical and anti-angina therapy&#xD;
&#xD;
          -  Expected survival of at least two years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any condition that prevents successful stem cell collection or application, e.g.&#xD;
             systemic infection, puncture for stem cell collection impossible&#xD;
&#xD;
          -  Any condition that may adversely affect bone marrow such as malignancy or prior&#xD;
             irradiation to the pelvic bone&#xD;
&#xD;
          -  Mitral valve insufficiency &gt; moderate grade&#xD;
&#xD;
          -  History of ventricular arrhythmias not controlled by medication and/or AICD&#xD;
&#xD;
          -  Need for additional heart surgery (i.e. valve replacement)&#xD;
&#xD;
          -  Emergency or salvage operation defined as within 48 hours of diagnosis&#xD;
&#xD;
          -  Evidence of left ventricular thrombus&#xD;
&#xD;
          -  Previous heart surgery within the last 6 months&#xD;
&#xD;
          -  Increased Troponin T (&gt; 3X ULN) in patients with unstable angina at time of&#xD;
             intervention&#xD;
&#xD;
          -  History of symptomatic carotid disease within the last 3 months prior to study&#xD;
             intervention&#xD;
&#xD;
          -  Ejection fraction &lt; 30%&#xD;
&#xD;
          -  End stage renal disease&#xD;
&#xD;
          -  Untreatable cancer, current or within preceding 5 years&#xD;
&#xD;
          -  Severe COPD&#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>Michael Sekela, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Kentucky</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Kentucky Healthcare</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>June 17, 2016</study_first_submitted>
  <study_first_submitted_qc>February 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 6, 2017</study_first_posted>
  <last_update_submitted>December 9, 2020</last_update_submitted>
  <last_update_submitted_qc>December 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Kentucky</investigator_affiliation>
    <investigator_full_name>Michael Sekela</investigator_full_name>
    <investigator_title>Cardiothoracic Surgeon</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>to be determined per principal investigator and statistician</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/NCT03043742
org study id: 15-1051
nct id: NCT03043742
lead sponsor: 
has dmc: Yes
Assess the safety and effectiveness of stem cell application with regard to improvement in
      regional myocardial function in patients receiving Trans-Myocardial Laser Revascularization
      (TMR) and stem cells.
Multiple case experiences and studies have been published reviewing clinical experiences with
      Carbon Dioxide Trans-Myocardial Laser Revascularization (TMR) and autologous bone marrow
      derived cell application. These experiences have demonstrated perfusion improvements,
      ejection fraction improvements and improvements in angina or heart failure symptoms. The
      investigators elected to examine the use of CD133 positive (CD133+) BM-derived stem cells
      because of their pluripotent nature and the fact that during the CD133 selection process
      inflammatory cells present in the bone marrow are being discarded. CD133+ is a recently
      discovered marker for more primitive bone marrow derived multipotent stem and endothelial
      progenitor cells and is of particular interest in studies directed to therapeutic
      angiogenesis, as these cells have been shown to differentiate into endothelial and myogenic
      cell lines. Multiple studies have utilized BM derived cells for myocardial regeneration.
      Patients who received CD133+ cells showed improved perfusion at injection sites of stem cells
      leading to a significant increase in volume of left ventricular ejection fraction, regional
      wall motion in the infarct zone, and a reduction in end systolic left ventricular volume.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Occurrence of Treatment-emergent serious adverse events (SAE) and adverse events
time frame: Assess from Procedure through 12 months
description: Major adverse cardiac event and adverse events defined in the common toxicity criteria
measure: Change in left ventricular ejection fraction compared to baseline
time frame: Assessed at baseline, 6 months, and 12 months
description: Measured as a percentage by Echocardiography
measure: Change in myocardial regional function compared to baseline
time frame: Assessed at baseline and 6 months
description: Measured by nuclear scanning.
measure: Change in myocardial regional viability compared to baseline
time frame: Assessed at baseline and 6 months
description: Measured by nuclear scanning.
measure: Change in distance walked compared to baseline
time frame: Assessed at baseline, 3 months, 6 months, and 12 months
description: Measured in feet during a 6 minute walk test
measure: Change in quality of life associated with heart failure compared to baseline
time frame: Assessed at baseline, 3 months, 6 months, and 12 months
description: Measured using the Kansas City Cardiomyopathy Questionnaire.
measure: Change in class of angina compared to baseline
time frame: Assessed at baseline, 3 months, 6 months, and 12 months.
description: Measured using the Canadian Cardiovascular Society Grading Scale.
measure: Change in class of heart failure compared to baseline
time frame: Assessed at baseline, 3 months, 6 months, and 12 months.
description: Measured using the New York Heart Association Questionnaire
measure: Change in regional left ventricular wall motion compared to baseline
time frame: Assessed at baseline, 6 months, and 12 months
description: Measured using echocardiogram.
measure: Change in quality of life associated with angina compared to baseline
time frame: Assessed at baseline, 3 months, 6 months, and 12 months
description: Measured using the Seattle Angina Questionnaire
arm group label: Phase I Open Label
arm group type: Experimental
description: open label bone marrow derived autologous CD133+ selected stem cell application in patients receiving trans-myocardial laser revascularization to improve regional myocardial function as detailed below:
Drug: CD133+ selected stem cells Dosage: Single injection of 0.1-0.2 ml around each laser channel Frequency: 10-20 channels Duration: Trans-Myocardial Revascularization
intervention type: Drug
intervention name: Bone Marrow Derived Autologous CD133+ Selected Cell Product
description: Injection of bone marrow derived autologous CD133+ cell product into laser channels during Trans-Myocardial Revascularization
arm group label: Phase I Open Label
other name: Stem cell
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael Sekela, MD
role: Principal Investigator
affiliation: University of Kentucky
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Kentucky
investigator full name: Michael Sekela
investigator title: Cardiothoracic Surgeon
mesh term: Heart Diseases
mesh term: Myocardial Ischemia
mesh term: Coronary Artery Disease
mesh term: Ischemia
sharing ipd: No
ipd description: to be determined per principal investigator and statistician