<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/NCT02256501</url>
  </required_header>
  <id_info>
    <org_study_id>Royan-Heart-004</org_study_id>
    <nct_id>NCT02256501</nct_id>
  </id_info>
  <brief_title>Intracoronary Transplantation of Bone Marrow Derived Mononuclear Cells in Pediatric Cardiomyopathy</brief_title>
  <official_title>Intracoronary Transplantation of Autologous Bone Marrow Derived Mononuclear Cells (MNC) in Idiopathic Dilated Cardiomyopathy in Pediatric Patients: Clinical Trial Phase I/II</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nasser Aghdami MD., PhD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Royan Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      According to the high morbidity and mortality of idiopathic Dilated CardioMyopathy (IDCM) in&#xD;
      pediatric, new modality of treatment is emerging. There are some case reports of&#xD;
      administration of stem cell therapy. The investigators design the first randomized clinical&#xD;
      trial in this setting. The investigators enroll 32 pediatric IDCM patients in two groups (16&#xD;
      pts. in each group including cell therapy and control). The investigators assess the safety&#xD;
      and efficacy of intracoronary transplantation of autologous bone marrow derived mononuclear&#xD;
      cells in this patients compared to control group.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Dilated cardiomyopathy as the most common form of cardiomyopathy is a rare but&#xD;
      life-threatening disorder in children. The primary cause of nearly 37 % of children with DCM&#xD;
      was unknown at diagnosis. Despite of the developing in the medical and surgical treatment&#xD;
      during the past several decades, standard treatments (including Digitalis, diuretics,&#xD;
      inhibitors of ACE, beta blockers, antiplatelet drugs and treatments Antiarrhythmic), may&#xD;
      stabilize the condition, but will not restore heart function to its previous condition.&#xD;
      Therapy remains complex and expensive. For some not all children the heart transplantation is&#xD;
      only option and mortality continues to be high, also. Stem cell and cell-based therapies&#xD;
      offer an innovative approach to reverse cardiac structure and function towards normal,&#xD;
      possibly reducing the need for aggressive therapies and cardiac transplantation. According to&#xD;
      the inclusion and exclusion criteria of trial, 32 patients with left ventricular ejection&#xD;
      fraction less than 45% who resistance to the standard medical therapy were randomly allocated&#xD;
      in 2 groups including BM-derived mononuclear (n=16) and control (n=16). Only the MNC group&#xD;
      underwent the bone marrow aspiration and intracoronary injection. The investigators followed&#xD;
      all of patients at 2 weeks, 1, 2, 4 and 6 months after transplantation for cell therapy group&#xD;
      or registration for placebo by physical examination, laboratory tests and imaging such as&#xD;
      echocardiography, CXR and CMR.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 2013</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</primary_completion_date>
  <phase>Phase 1/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>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Death</measure>
    <time_frame>3months</time_frame>
    <description>The rate of patients' death 3 months after cell transplantation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Arrest</measure>
    <time_frame>3 months</time_frame>
    <description>The rate of patients' arrests 3 months after cell transplantation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Dysrhythmia</measure>
    <time_frame>3 months</time_frame>
    <description>The rate of dysarthymia 3 months after cell transplantation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart transplantation</measure>
    <time_frame>3 months</time_frame>
    <description>The rate of demand for heart transplantation 3 months after cell transplantation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital admission for heart failure</measure>
    <time_frame>3 months</time_frame>
    <description>The rate of hospital administration 3 months after cell transplantation.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Cardiomyopathy</condition>
  <arm_group>
    <arm_group_label>Mono Nunlear Cell (MNC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The patients with idiopathic dilated cardiomyopathy who underwent intracoronary injection of autologous bone marrow-derived mononuclear cells .</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The patients with cardiomyopathy that are under observe during the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Mono Nuclear Cell (MNC) transplantation</intervention_name>
    <description>Intracoronary administration of autologous bone marrow derived mononuclear cells</description>
    <arm_group_label>Mono Nunlear Cell (MNC)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age between 1-16 year(s)&#xD;
&#xD;
          2. LVEF &lt;45% (echocardiography)&#xD;
&#xD;
          3. Duration of diagnosis more than 3 months&#xD;
&#xD;
          4. Resistance to Standard therapy more than 2 months&#xD;
&#xD;
          5. Informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Congenital Heart Disease&#xD;
&#xD;
          2. Active infection less than one month&#xD;
&#xD;
          3. Dysrhythmia&#xD;
&#xD;
          4. Cardiogenic shock&#xD;
&#xD;
          5. Renal failure&#xD;
&#xD;
          6. Immune Deficiency (Documentation)&#xD;
&#xD;
          7. Terminal illness or malignancy(Documentation)&#xD;
&#xD;
          8. TORCH (Documentation)&#xD;
&#xD;
          9. Metabolic disorder (Documentation)&#xD;
&#xD;
         10. Neuromuscular disorder (Documentation)&#xD;
&#xD;
         11. Autoimmune disease (Documentation)&#xD;
&#xD;
         12. Developmental delay&#xD;
&#xD;
         13. Cytotoxic drugs&#xD;
&#xD;
         14. Previous bone marrow transplant&#xD;
&#xD;
         15. Contraindications to CMR such as metallic implants&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>16 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hamid Gourabi, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Head of Royan Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nasser Aghdami, MD,PhD</last_name>
    <role>Study Director</role>
    <affiliation>Head of Department of Regenerative Medicine &amp; Cell therapy center of Royan Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mohammad Mahdavi, MD</last_name>
    <role>Study Director</role>
    <affiliation>Department of Pediatric Cardiology, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Koorosh Vahidshahi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Pediatric Cardiology, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Royan Institute</name>
      <address>
        <city>Tehran</city>
        <country>Iran, Islamic Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Iran, Islamic Republic of</country>
  </location_countries>
  <link>
    <url>http://Royaninstitute.org</url>
    <description>Related Info</description>
  </link>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>October 1, 2014</study_first_submitted>
  <study_first_submitted_qc>October 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2014</study_first_posted>
  <last_update_submitted>April 26, 2017</last_update_submitted>
  <last_update_submitted_qc>April 26, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 27, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Royan Institute</investigator_affiliation>
    <investigator_full_name>Nasser Aghdami MD., PhD</investigator_full_name>
    <investigator_title>Hear of department of Regenerative Medicine of Royan Institute 7 cell therapy center</investigator_title>
  </responsible_party>
  <keyword>Dilated cardiomyopathy pediatric heart failure cell therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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/NCT02256501
org study id: Royan-Heart-004
nct id: NCT02256501
lead sponsor: 
has dmc: Yes
According to the high morbidity and mortality of idiopathic Dilated CardioMyopathy (IDCM) in
      pediatric, new modality of treatment is emerging. There are some case reports of
      administration of stem cell therapy. The investigators design the first randomized clinical
      trial in this setting. The investigators enroll 32 pediatric IDCM patients in two groups (16
      pts. in each group including cell therapy and control). The investigators assess the safety
      and efficacy of intracoronary transplantation of autologous bone marrow derived mononuclear
      cells in this patients compared to control group.
Dilated cardiomyopathy as the most common form of cardiomyopathy is a rare but
      life-threatening disorder in children. The primary cause of nearly 37 % of children with DCM
      was unknown at diagnosis. Despite of the developing in the medical and surgical treatment
      during the past several decades, standard treatments (including Digitalis, diuretics,
      inhibitors of ACE, beta blockers, antiplatelet drugs and treatments Antiarrhythmic), may
      stabilize the condition, but will not restore heart function to its previous condition.
      Therapy remains complex and expensive. For some not all children the heart transplantation is
      only option and mortality continues to be high, also. Stem cell and cell-based therapies
      offer an innovative approach to reverse cardiac structure and function towards normal,
      possibly reducing the need for aggressive therapies and cardiac transplantation. According to
      the inclusion and exclusion criteria of trial, 32 patients with left ventricular ejection
      fraction less than 45% who resistance to the standard medical therapy were randomly allocated
      in 2 groups including BM-derived mononuclear (n=16) and control (n=16). Only the MNC group
      underwent the bone marrow aspiration and intracoronary injection. The investigators followed
      all of patients at 2 weeks, 1, 2, 4 and 6 months after transplantation for cell therapy group
      or registration for placebo by physical examination, laboratory tests and imaging such as
      echocardiography, CXR and CMR.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Investigator)
measure: Death
time frame: 3months
description: The rate of patients' death 3 months after cell transplantation
measure: Arrest
time frame: 3 months
description: The rate of patients' arrests 3 months after cell transplantation
measure: Dysrhythmia
time frame: 3 months
description: The rate of dysarthymia 3 months after cell transplantation
measure: Heart transplantation
time frame: 3 months
description: The rate of demand for heart transplantation 3 months after cell transplantation.
measure: Hospital admission for heart failure
time frame: 3 months
description: The rate of hospital administration 3 months after cell transplantation.
arm group label: Mono Nunlear Cell (MNC)
arm group type: Experimental
description: The patients with idiopathic dilated cardiomyopathy who underwent intracoronary injection of autologous bone marrow-derived mononuclear cells .
arm group label: Control
arm group type: No Intervention
description: The patients with cardiomyopathy that are under observe during the study.
intervention type: Biological
intervention name: Mono Nuclear Cell (MNC) transplantation
description: Intracoronary administration of autologous bone marrow derived mononuclear cells
arm group label: Mono Nunlear Cell (MNC)
criteria: 
gender: All
minimum age: 1 Year
maximum age: 16 Years
healthy volunteers: No
last name: Hamid Gourabi, PhD
role: Study Chair
affiliation: Head of Royan Institute
last name: Nasser Aghdami, MD,PhD
role: Study Director
affiliation: Head of Department of Regenerative Medicine & Cell therapy center of Royan Institute
last name: Mohammad Mahdavi, MD
role: Study Director
affiliation: Department of Pediatric Cardiology, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
last name: Koorosh Vahidshahi, MD
role: Principal Investigator
affiliation: Department of Pediatric Cardiology, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
facility: 
country: Iran, Islamic Republic of
url: http://Royaninstitute.org
description: Related Info
responsible party type: Sponsor-Investigator
investigator affiliation: Royan Institute
investigator full name: Nasser Aghdami MD., PhD
investigator title: Hear of department of Regenerative Medicine of Royan Institute 7 cell therapy center
mesh term: Cardiomyopathies