<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/NCT01720888</url>
  </required_header>
  <id_info>
    <org_study_id>ERGS/1/2011/SKK/UKM/02/72</org_study_id>
    <nct_id>NCT01720888</nct_id>
  </id_info>
  <brief_title>Intracoronary Autologous Mesenchymal Stem Cells Implantation in Patients With Ischemic Dilated Cardiomyopathy</brief_title>
  <official_title>A Controlled Open Label Phase II Study Assessing the Efficacy of Intracoronary Autologous Mesenchymal Stem Cells in Patients With Ischemic Dilated Cardiomyopathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National University of Malaysia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cytopeutics Sdn. Bhd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>National University of Malaysia</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Despite the recent advances in medical and surgical treatment, heart failure resulting from&#xD;
      ischemic cardiomyopathy (ICM) remains the leading cause of cardiovascular mortality. Ischemic&#xD;
      dilated cardiomyopathy(ICM) is defined as abnormally enlarged left ventricular (LV) cavity&#xD;
      with documented poor LV function as a result of severe coronary artery disease (CAD). LV&#xD;
      remodelling which is inevitable after an infarct has been postulated to contribute largely to&#xD;
      the poor outcome of patients with ICM, therefore prevention of LV remodelling is the goal for&#xD;
      the treatment in patients with severe CAD. Cell therapy represents a novel therapeutic&#xD;
      strategy for treating cardiac diseases including severe CAD and heart failure. A type of stem&#xD;
      cells known as mesenchymal stem cells(MSCs)can be isolated from bone marrow.This study aims&#xD;
      to test the differentiation potential and therapeutic capacity of MSC from severe CAD&#xD;
      patients after intracoronary implantation in an ischemic myocardial environment in Malaysian&#xD;
      population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Ischemic dilated cardiomyopathy(ICM) is defined as abnormally enlarged left ventricular (LV)&#xD;
      cavity with documented poor LV function as a result of severe coronary artery disease (CAD).&#xD;
      LV remodelling which is inevitable after an infarct has been postulated to contribute largely&#xD;
      to the poor outcome of patients with ICM, therefore prevention of LV remodelling is the goal&#xD;
      for the treatment in patients with severe CAD. Cell therapy represents a novel therapeutic&#xD;
      strategy for treating cardiac diseases including severe CAD and heart failure. A type of stem&#xD;
      cells known as mesenchymal stem cells(MSCs)can be isolated from bone marrow. Experimental and&#xD;
      clinical studies to date have shown that mesenchymal stem cells represent the most suitable&#xD;
      cell type for regeneration therapy after myocardial infarction (MI). After injection into&#xD;
      ischemic myocardium, bone marrow-derived MSC (BM-MSC) from various animal species can&#xD;
      differentiate into multiple cell lineages, including endothelial cells and cardiomyocytes,&#xD;
      thereby improving LV function.&#xD;
&#xD;
      In Malaysia we have previously demonstrated our capability in isolating and extracting MSC&#xD;
      from a small volume of bone marrow aspirates.The isolation, expansion and feasibility of&#xD;
      storage, transport and differentiation of human MSC for clinical application has been&#xD;
      performed locally. The researchers used autologous BM-MSC, ex vivo expanded, on three&#xD;
      patients with end-stage ischemic dilated cardiomyopathy who were on the heart transplant&#xD;
      waiting list and each patient was injected with MSCs directly into the myocardium during open&#xD;
      heart surgery. After twelve months, all patients remained alive and well with significant&#xD;
      improvement in cardiac function, quality of life and other parameters including reduction of&#xD;
      myocardial scar volume as seen from cardiac scans.&#xD;
&#xD;
      The same group of researchers further carried out a study on ten patients with severe dilated&#xD;
      cardiomyopathy and refractory cardiac function despite maximum medical therapy to receive&#xD;
      autologous BM-MSC implantation via intramyocardial or intracoronary route. All patients&#xD;
      remained alive at 1 year while recorded significant improvements in LV ejection fraction and&#xD;
      other LV parameters from baseline to 6 and 12 months. Reduction in scar was also noted in six&#xD;
      of the patients by 12 months.&#xD;
&#xD;
      Following these results, this study aims to test the differentiation potential and&#xD;
      therapeutic capacity of MSC from severe CAD patients after intracoronary implantation in an&#xD;
      ischemic myocardial environment in Malaysian population.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>July 2012</start_date>
  <completion_date type="Anticipated">December 2015</completion_date>
  <primary_completion_date type="Anticipated">December 2015</primary_completion_date>
  <phase>Phase 2</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in LV ejection fraction as measured by echocardiogram and cardiac MRI after implantation</measure>
    <time_frame>1 month, 3 months, 6 months, 9 months, 12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in functional status</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in other LV parameters as assessed by echocardiogram and cardiovascular magnetic resonance(CMR).</measure>
    <time_frame>1 months, 3 months, 6 months, 9 months, 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Resolution of scar tissue volume/area on cardiac MRI</measure>
    <time_frame>6 months, 12 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum N Terminal-pro B type natriuretic peptide(NT-proBNP)level</measure>
    <time_frame>1 month, 6 months, 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Freedom from major adverse cardiac events as defined by myocardial infarction, hospitalization for angina, myocardial infarction or heart failure, or death (all cause of mortality).</measure>
    <time_frame>1 month, 3 months, 6 months, 9 months, 12 months</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>No peri-procedural complications</measure>
    <time_frame>1 month, 3 months, 6 months, 9 months, 12 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Significant improvement in overall left ventricular function</measure>
    <time_frame>12 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Resolution of scar tissue</measure>
    <time_frame>6 months, 12 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Reduction of major adverse cardiac events</measure>
    <time_frame>1 month, 3 months, 6 months, 9 months, 12 months</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Ischemic Dilated Cardiomyopathy</condition>
  <arm_group>
    <arm_group_label>Maximal medical therapy</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Maximal medical therapy which comprises of optimal pharmacological therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Maximal medical therapy and BM-MSCs</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Autologous Bone marrrow-derived mesenchymal stem cells implantation</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>BM-MSCs</intervention_name>
    <description>Intracoronary implantation of bone marrow-derived mesencymal stem cells</description>
    <arm_group_label>Maximal medical therapy and BM-MSCs</arm_group_label>
    <other_name>Bone marrow-derived mesenchymal stem cells implantation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  aged between 35 to 75 years&#xD;
&#xD;
          -  diagnosed to have ICM confirmed by previous coronary angiogram showing significant&#xD;
             coronary artery disease &gt;70% or history of previous myocardial infarction.&#xD;
&#xD;
          -  myocardial infarction event occured 6 months or longer from time of screening.&#xD;
&#xD;
          -  LV ejection fraction of ≤40% by echocardiogram or cardiac MRI.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Likelihood of heart failure from other causes such as idiopathic, infective or&#xD;
             metabolic cardiomyopathy,valvular heart disease and pericardial disease.&#xD;
&#xD;
          -  patients who had undergone a coronary artery bypass graft(CABG) procedure.&#xD;
&#xD;
          -  patients who do not have any visible/significant myocardial scar.&#xD;
&#xD;
          -  patients with any cardiovascular metallic implantation.&#xD;
&#xD;
          -  any contraindication to bone marrow aspiration&#xD;
&#xD;
          -  any contraindication to coronary contrast angiography and angioplasty.&#xD;
&#xD;
          -  any acute or chronic communicable diseases including Hepatitis B, Hepatitis C and HIV.&#xD;
&#xD;
          -  any past history of neoplasia and primary haematological disease.&#xD;
&#xD;
          -  any current, past or paroxysmal cardiac arrhythmias.&#xD;
&#xD;
          -  renal impairment indicated by creatinine clearance of less than 30 ml/min.&#xD;
&#xD;
          -  liver impairment indicated by serum alanine transferase level at 4 times greater than&#xD;
             normal value.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Oteh Maskon, MB Bch</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universiti Kebangsaan Malaysia Medical Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UKM Medical Centre</name>
      <address>
        <city>Cheras</city>
        <state>Kuala Lumpur</state>
        <zip>56000</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Malaysia</country>
  </location_countries>
  <verification_date>April 2015</verification_date>
  <study_first_submitted>November 1, 2012</study_first_submitted>
  <study_first_submitted_qc>November 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 2, 2012</study_first_posted>
  <last_update_submitted>April 15, 2015</last_update_submitted>
  <last_update_submitted_qc>April 15, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 16, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National University of Malaysia</investigator_affiliation>
    <investigator_full_name>Professor Dr Oteh Maskon</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Autologous</keyword>
  <keyword>Bone Marrow</keyword>
  <keyword>Mesenchymal Stem Cells</keyword>
  <keyword>Ischemic Dilated Cardiomyopathy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiomyopathies</mesh_term>
    <mesh_term>Cardiomyopathy, Dilated</mesh_term>
    <mesh_term>Ischemia</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/NCT01720888
org study id: ERGS/1/2011/SKK/UKM/02/72
nct id: NCT01720888
lead sponsor: 
collaborator: 
has dmc: Yes
Despite the recent advances in medical and surgical treatment, heart failure resulting from
      ischemic cardiomyopathy (ICM) remains the leading cause of cardiovascular mortality. Ischemic
      dilated cardiomyopathy(ICM) is defined as abnormally enlarged left ventricular (LV) cavity
      with documented poor LV function as a result of severe coronary artery disease (CAD). LV
      remodelling which is inevitable after an infarct has been postulated to contribute largely to
      the poor outcome of patients with ICM, therefore prevention of LV remodelling is the goal for
      the treatment in patients with severe CAD. Cell therapy represents a novel therapeutic
      strategy for treating cardiac diseases including severe CAD and heart failure. A type of stem
      cells known as mesenchymal stem cells(MSCs)can be isolated from bone marrow.This study aims
      to test the differentiation potential and therapeutic capacity of MSC from severe CAD
      patients after intracoronary implantation in an ischemic myocardial environment in Malaysian
      population.
Ischemic dilated cardiomyopathy(ICM) is defined as abnormally enlarged left ventricular (LV)
      cavity with documented poor LV function as a result of severe coronary artery disease (CAD).
      LV remodelling which is inevitable after an infarct has been postulated to contribute largely
      to the poor outcome of patients with ICM, therefore prevention of LV remodelling is the goal
      for the treatment in patients with severe CAD. Cell therapy represents a novel therapeutic
      strategy for treating cardiac diseases including severe CAD and heart failure. A type of stem
      cells known as mesenchymal stem cells(MSCs)can be isolated from bone marrow. Experimental and
      clinical studies to date have shown that mesenchymal stem cells represent the most suitable
      cell type for regeneration therapy after myocardial infarction (MI). After injection into
      ischemic myocardium, bone marrow-derived MSC (BM-MSC) from various animal species can
      differentiate into multiple cell lineages, including endothelial cells and cardiomyocytes,
      thereby improving LV function.

      In Malaysia we have previously demonstrated our capability in isolating and extracting MSC
      from a small volume of bone marrow aspirates.The isolation, expansion and feasibility of
      storage, transport and differentiation of human MSC for clinical application has been
      performed locally. The researchers used autologous BM-MSC, ex vivo expanded, on three
      patients with end-stage ischemic dilated cardiomyopathy who were on the heart transplant
      waiting list and each patient was injected with MSCs directly into the myocardium during open
      heart surgery. After twelve months, all patients remained alive and well with significant
      improvement in cardiac function, quality of life and other parameters including reduction of
      myocardial scar volume as seen from cardiac scans.

      The same group of researchers further carried out a study on ten patients with severe dilated
      cardiomyopathy and refractory cardiac function despite maximum medical therapy to receive
      autologous BM-MSC implantation via intramyocardial or intracoronary route. All patients
      remained alive at 1 year while recorded significant improvements in LV ejection fraction and
      other LV parameters from baseline to 6 and 12 months. Reduction in scar was also noted in six
      of the patients by 12 months.

      Following these results, this study aims to test the differentiation potential and
      therapeutic capacity of MSC from severe CAD patients after intracoronary implantation in an
      ischemic myocardial environment in Malaysian population.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in LV ejection fraction as measured by echocardiogram and cardiac MRI after implantation
time frame: 1 month, 3 months, 6 months, 9 months, 12 months
measure: Changes in functional status
time frame: 12 months
measure: Improvement in other LV parameters as assessed by echocardiogram and cardiovascular magnetic resonance(CMR).
time frame: 1 months, 3 months, 6 months, 9 months, 12 months
measure: Resolution of scar tissue volume/area on cardiac MRI
time frame: 6 months, 12 months.
measure: Change in serum N Terminal-pro B type natriuretic peptide(NT-proBNP)level
time frame: 1 month, 6 months, 12 months
measure: Freedom from major adverse cardiac events as defined by myocardial infarction, hospitalization for angina, myocardial infarction or heart failure, or death (all cause of mortality).
time frame: 1 month, 3 months, 6 months, 9 months, 12 months
measure: No peri-procedural complications
time frame: 1 month, 3 months, 6 months, 9 months, 12 months
measure: Significant improvement in overall left ventricular function
time frame: 12 months
measure: Resolution of scar tissue
time frame: 6 months, 12 months
measure: Reduction of major adverse cardiac events
time frame: 1 month, 3 months, 6 months, 9 months, 12 months
arm group label: Maximal medical therapy
arm group type: No Intervention
description: Maximal medical therapy which comprises of optimal pharmacological therapy
arm group label: Maximal medical therapy and BM-MSCs
arm group type: Experimental
description: Autologous Bone marrrow-derived mesenchymal stem cells implantation
intervention type: Other
intervention name: BM-MSCs
description: Intracoronary implantation of bone marrow-derived mesencymal stem cells
arm group label: Maximal medical therapy and BM-MSCs
other name: Bone marrow-derived mesenchymal stem cells implantation
criteria: 
gender: All
minimum age: 35 Years
maximum age: 75 Years
healthy volunteers: No
last name: Oteh Maskon, MB Bch
role: Principal Investigator
affiliation: Universiti Kebangsaan Malaysia Medical Centre
facility: 
country: Malaysia
responsible party type: Principal Investigator
investigator affiliation: National University of Malaysia
investigator full name: Professor Dr Oteh Maskon
investigator title: Professor
mesh term: Cardiomyopathies
mesh term: Cardiomyopathy, Dilated
mesh term: Ischemia