<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/NCT01721902</url>
  </required_header>
  <id_info>
    <org_study_id>0801-133</org_study_id>
    <secondary_id>808756</secondary_id>
    <nct_id>NCT01721902</nct_id>
  </id_info>
  <brief_title>Stem Cell Implantation in Patients Undergoing CABG</brief_title>
  <official_title>Stem Cell Implantation in Patients Undergoing CABG</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Miltenyi Biotec, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Miltenyi Biotec, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to demonstrate the feasibility and safety of&#xD;
      intra-operative, intra-myocardial injection of autologous CD133 positive bone marrow cells at&#xD;
      the time of coronary artery bypass graft (CABG) surgery in patients with chronic ischemic&#xD;
      cardiomyopathy. Additionally, the feasibility of producing autologous CD133+ bone marrow stem&#xD;
      cells will be assessed.&#xD;
&#xD;
      The investigators hypothesize that collection of a sufficient number of CD133+ cells through&#xD;
      bone marrow aspiration prior to surgery, with subsequent processing and intra-myocardial&#xD;
      injection of high purity cells following completion of CABG, will be feasible without&#xD;
      significant adverse clinical consequences.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Coronary heart disease (CHD) is the leading cause of death in the U.S. in both men and women&#xD;
      and the aging of the population and rising prevalence of diabetes ensure that the number of&#xD;
      persons with CHD will continue to increase over the next several decades. Two major factors&#xD;
      contributing to adverse outcomes in patients undergoing coronary artery bypass grafting&#xD;
      (CABG) surgery are failure to achieve complete revascularization, and residual impairment in&#xD;
      left ventricular function.&#xD;
&#xD;
      In the present study, the investigators propose a Phase I randomized double-blind study&#xD;
      designed to assess the feasibility and safety of autologous CD133+ cells in patients referred&#xD;
      for CABG who have significant regions of viable but non-revascularizable myocardium and/or&#xD;
      significant LV systolic dysfunction not likely to improve with conventional coronary&#xD;
      revascularization.&#xD;
&#xD;
      Autologous CD133+ bone marrow progenitor cells will be harvested from study subjects at the&#xD;
      time of CABG, processed and then injected into patients' myocardium prior to completion of&#xD;
      CABG surgery. The test material consists of autologous CD133+ cells. Since intra-myocardial&#xD;
      injections per se could stimulate neovascularization, control group patients will receive a&#xD;
      placebo injection of carrier solution. Control subjects will thus have an identical procedure&#xD;
      to those randomized to autologous CD133+ cell injections.&#xD;
&#xD;
      The three goals of the study are as follows:&#xD;
&#xD;
        1. To demonstrate the feasibility and safety of intra-operative, intra-myocardial injection&#xD;
           of autologous CD133+ bone marrow cells in adults with chronic ischemic cardiomyopathy&#xD;
           associated with impair left ventricular function.&#xD;
&#xD;
        2. To assess the effect of autologous CD133+ cell injections on regional myocardial&#xD;
           perfusion and function by comparing paired magnet resonance scans obtained prior to CABG&#xD;
           and again 6 months post CABG.&#xD;
&#xD;
        3. To assess the effect of autologous CD133+ stem cell injections on symptom severity and&#xD;
           quality of life at 6 months after CABG surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The study was terminiated due the lack of recruitment.&#xD;
  </why_stopped>
  <start_date>January 2010</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">October 2013</primary_completion_date>
  <phase>Phase 1</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Freedom from a Major Adverse Cardiac Event (MACE)</measure>
    <time_frame>Six months</time_frame>
    <description>Defined as cardiac death, myocardial infarction (CK/CK-MB over 5 times the upper limit of normal), repeat coronary bypass grafting, or a repeat percutaneous intervention of bypassed coronary artery.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feedom from any major arrhythmias</measure>
    <time_frame>Six months</time_frame>
    <description>Defined as sustained ventricular tachycardia or survived sudden death.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Regional myocardial perfusion and function assessed by comparing paired magnetic resonance scans, ECHOs and SPECT scans obtained prior to CABG and again at 6 months post CABG.</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symptom severity and quality of life at 6 months after CABG surgery.</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">23</enrollment>
  <condition>Ischemic Cardiomyopathy</condition>
  <condition>Coronary Artery Disease</condition>
  <arm_group>
    <arm_group_label>Autologous CD133+ Bone Marrow Stem Cells</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intra-myocardial injection of autologous CD133+ cells in suspension.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Carrier Solution</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intra-myocardial inception of carrier solution.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Autologous CD133+ Bone Marrow Stem Cells</intervention_name>
    <description>Intra-myocardial injection of 2-3 x 10E6 CD133+ Bone Marrow Stem Cells</description>
    <arm_group_label>Autologous CD133+ Bone Marrow Stem Cells</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Carrier Solution</intervention_name>
    <description>Intra-myocardial injection of carrier solution</description>
    <arm_group_label>Carrier Solution</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 years of age or older&#xD;
&#xD;
          -  Patients with ischemic heart disease manifested by Canadian class II or greater angina&#xD;
             and/or New York Heart Association class II, III or IV exercise intolerance AND who&#xD;
             have undergone diagnostic coronary angiography demonstrating at least 70% diameter&#xD;
             narrowing of at least 2 major coronary arteries or branches or at least 50% diameter&#xD;
             narrowing of the left main coronary artery.&#xD;
&#xD;
          -  Left ventricular systolic dysfunction evaluated by echocardiography or LV angiography&#xD;
             (LV ejection fraction less than or equal to 49%).&#xD;
&#xD;
          -  No contraindications or exclusions (see below)&#xD;
&#xD;
          -  Willingness to participate and ability to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindications to magnetic resonance imaging .&#xD;
&#xD;
          -  Need for emergent revascularization.&#xD;
&#xD;
          -  Need for concomitant surgical procedure at the time of CABG (e.g. valve repair or&#xD;
             replacement, aneurysm resection, etc.).&#xD;
&#xD;
          -  Hemodynamically unstable patients.&#xD;
&#xD;
          -  Patients with confirmed transmural myocardial infarction within 4 weeks, and/or rising&#xD;
             cardiac biomarker proteins (i.e. troponin), and/or worsening ECG changes.&#xD;
&#xD;
          -  Prior CABG surgery.&#xD;
&#xD;
          -  Stroke within 1 month prior to planned CABG.&#xD;
&#xD;
          -  Diagnosed with human immunodeficiency virus (HIV) or any other immune disorder or&#xD;
             immunosuppressive medication (e.g. prednisone, cyclophosphamide, etanercept, etc.)&#xD;
&#xD;
          -  Organ dysfunction&#xD;
&#xD;
          -  Contra-indication for bone marrow aspiration (Thrombocytopenia &lt; 50.000 mm3, INR &gt;&#xD;
             2.0, use of antiplatelet agents other than aspirin).&#xD;
&#xD;
          -  Hemoglobin less than 8g/dL, white blood cell count less than 4,000/mm3, absolute&#xD;
             neutrophil count less than 1500/mm3&#xD;
&#xD;
          -  Active infection&#xD;
&#xD;
          -  Myelodysplastic syndrome (MDS)&#xD;
&#xD;
          -  Significant cognitive impairment&#xD;
&#xD;
          -  Any condition associated with a life expectancy of less than 6 months&#xD;
&#xD;
          -  Patients known allergic reaction or contraindication to any of the component of the&#xD;
             CD133+ enriched cells&#xD;
&#xD;
          -  Participation in other studies concomitant with this study&#xD;
&#xD;
          -  History of severe ventricular tachy-arrythmias&#xD;
&#xD;
          -  Inability or unwillingness to provide written informed consent&#xD;
&#xD;
          -  Positive serum pregnancy test&#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>Yi-Ping J Woo, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2013</verification_date>
  <study_first_submitted>October 1, 2012</study_first_submitted>
  <study_first_submitted_qc>November 2, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 6, 2012</study_first_posted>
  <last_update_submitted>December 3, 2013</last_update_submitted>
  <last_update_submitted_qc>December 3, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 4, 2013</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>Coronary Artery Disease</mesh_term>
    <mesh_term>Cardiomyopathies</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/NCT01721902
org study id: 0801-133
secondary id: 808756
nct id: NCT01721902
lead sponsor: 
has dmc: Yes
The primary objective of this study is to demonstrate the feasibility and safety of
      intra-operative, intra-myocardial injection of autologous CD133 positive bone marrow cells at
      the time of coronary artery bypass graft (CABG) surgery in patients with chronic ischemic
      cardiomyopathy. Additionally, the feasibility of producing autologous CD133+ bone marrow stem
      cells will be assessed.

      The investigators hypothesize that collection of a sufficient number of CD133+ cells through
      bone marrow aspiration prior to surgery, with subsequent processing and intra-myocardial
      injection of high purity cells following completion of CABG, will be feasible without
      significant adverse clinical consequences.
Coronary heart disease (CHD) is the leading cause of death in the U.S. in both men and women
      and the aging of the population and rising prevalence of diabetes ensure that the number of
      persons with CHD will continue to increase over the next several decades. Two major factors
      contributing to adverse outcomes in patients undergoing coronary artery bypass grafting
      (CABG) surgery are failure to achieve complete revascularization, and residual impairment in
      left ventricular function.

      In the present study, the investigators propose a Phase I randomized double-blind study
      designed to assess the feasibility and safety of autologous CD133+ cells in patients referred
      for CABG who have significant regions of viable but non-revascularizable myocardium and/or
      significant LV systolic dysfunction not likely to improve with conventional coronary
      revascularization.

      Autologous CD133+ bone marrow progenitor cells will be harvested from study subjects at the
      time of CABG, processed and then injected into patients' myocardium prior to completion of
      CABG surgery. The test material consists of autologous CD133+ cells. Since intra-myocardial
      injections per se could stimulate neovascularization, control group patients will receive a
      placebo injection of carrier solution. Control subjects will thus have an identical procedure
      to those randomized to autologous CD133+ cell injections.

      The three goals of the study are as follows:

        1. To demonstrate the feasibility and safety of intra-operative, intra-myocardial injection
           of autologous CD133+ bone marrow cells in adults with chronic ischemic cardiomyopathy
           associated with impair left ventricular function.

        2. To assess the effect of autologous CD133+ cell injections on regional myocardial
           perfusion and function by comparing paired magnet resonance scans obtained prior to CABG
           and again 6 months post CABG.

        3. To assess the effect of autologous CD133+ stem cell injections on symptom severity and
           quality of life at 6 months after CABG surgery.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Freedom from a Major Adverse Cardiac Event (MACE)
time frame: Six months
description: Defined as cardiac death, myocardial infarction (CK/CK-MB over 5 times the upper limit of normal), repeat coronary bypass grafting, or a repeat percutaneous intervention of bypassed coronary artery.
measure: Feedom from any major arrhythmias
time frame: Six months
description: Defined as sustained ventricular tachycardia or survived sudden death.
measure: Regional myocardial perfusion and function assessed by comparing paired magnetic resonance scans, ECHOs and SPECT scans obtained prior to CABG and again at 6 months post CABG.
time frame: 6 months
measure: Symptom severity and quality of life at 6 months after CABG surgery.
time frame: 6 months
arm group label: Autologous CD133+ Bone Marrow Stem Cells
arm group type: Active Comparator
description: Intra-myocardial injection of autologous CD133+ cells in suspension.
arm group label: Carrier Solution
arm group type: Placebo Comparator
description: Intra-myocardial inception of carrier solution.
intervention type: Device
intervention name: Autologous CD133+ Bone Marrow Stem Cells
description: Intra-myocardial injection of 2-3 x 10E6 CD133+ Bone Marrow Stem Cells
arm group label: Autologous CD133+ Bone Marrow Stem Cells
intervention type: Other
intervention name: Carrier Solution
description: Intra-myocardial injection of carrier solution
arm group label: Carrier Solution
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Yi-Ping J Woo, M.D.
role: Principal Investigator
affiliation: University of Pennsylvania
facility: 
country: United States
responsible party type: Sponsor
mesh term: Coronary Artery Disease
mesh term: Cardiomyopathies