<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/NCT01660581</url>
  </required_header>
  <id_info>
    <org_study_id>Regent Vsel</org_study_id>
    <secondary_id>2011-005435-98</secondary_id>
    <nct_id>NCT01660581</nct_id>
  </id_info>
  <brief_title>Intracardiac CD133+ Cells in Patients With No-option Resistant Angina</brief_title>
  <acronym>RegentVsel</acronym>
  <official_title>A Randomized,Prospective,Double-blind Study to Evaluate Intracardiac Injections of Bone Marrow,Autologous CD133+Cells(Electromechanical Mapping Based)in Patients With Resistant Angina and no Effective Revascularization Option. RegentVsel</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Silesia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Silesia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to evaluate the efficacy of therapy with autological CD133+ cells&#xD;
      in patients with angina resistant to pharmacological treatment and without the possibility of&#xD;
      effective revascularization. Cells will be isolated from patients bone marrow and&#xD;
      administered directly into the muscle of left ventricle. The main objective is to assess the&#xD;
      treatments' influence on improvement of myocardial perfusion and function, and on decrease of&#xD;
      occurrence of symptomatic angina.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with a Stable angina pectoris (CCS II-IV) can potentially benefit from treatment&#xD;
      with autological CD133+ cell populations, which include cells with a higher expression of&#xD;
      cardiac and endothelial differentiation markers.&#xD;
&#xD;
      REGENT VSEL Trial will include Patients with Angina resistant to pharmacological treatment&#xD;
      and without the possibility of effective revascularization.&#xD;
&#xD;
      The main objective of the study is to assess the treatments influence on:&#xD;
&#xD;
        -  improvement of myocardial perfusion&#xD;
&#xD;
        -  global and segmental contractility (LVEF)&#xD;
&#xD;
        -  occurrence of symptomatic angina&#xD;
&#xD;
        -  quality of life&#xD;
&#xD;
      Regent Vsel is a prospective, randomized, double blind, placebo-controlled study with a&#xD;
      planned number of 60 Patients.&#xD;
&#xD;
      Randomization will be carried out according to a 1:1 mode. Every Patient will undergo a bone&#xD;
      marrow aspiration. CD133+ cells will be isolated from bone marrow aspirates. Patients&#xD;
      randomized to experimental group will receive isolated cells (direct left ventricular muscle&#xD;
      administration). Patients enrolled to control group will get only a placebo solution injected&#xD;
      into the muscle.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2012</start_date>
  <completion_date type="Actual">September 2016</completion_date>
  <primary_completion_date type="Actual">September 2016</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Myocardial perfusion change</measure>
    <time_frame>4 months after application of cell therapy</time_frame>
    <description>Myocardial perfusion change assessed by perfusion scintigraphy (99mTc SPECT)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Global and segmental contractility change and myocardial perfusion change</measure>
    <time_frame>MRI 4 months and echocardiography 4 and 12 months after application of cell therapy</time_frame>
    <description>Global and segmental contractility change and myocardial perfusion change assessed by magnetic resonance imaging with adenosine administration, and echocardiography with contrast</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exercise tolerance</measure>
    <time_frame>4 and 12 months after application of cell therapy</time_frame>
    <description>Exercise tolerance assessed in a treadmill test (TET, ESTD, TTLA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of symptomatic angina</measure>
    <time_frame>1, 4, 6 and 12 months after application of cell therapy</time_frame>
    <description>CCS, nitrates usage</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>1, 4, 6 and 12 months after application of cell therapy</time_frame>
    <description>Quality of life assessed by standard questionnaires: SF37, Seattle Angina</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of ventricular arrhythmia</measure>
    <time_frame>1, 4, 6 and 12 months after application of cell therapy</time_frame>
    <description>24 hrs ECG monitoring</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of in-stent restenosis and progression of artherosclerotic lesions in remained coronary artery segments</measure>
    <time_frame>4 months after application of cell therapy</time_frame>
    <description>Assessed by Intravascular Ultrasound (IVUS) and Optical coherence tomography (OCT) examination</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Stable Angina</condition>
  <arm_group>
    <arm_group_label>CD133+</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>intramyocardial injection (electromechanical mapping based) of autological CD133+ cells, isolated from bone marrow</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>intramyocardial injection (electromechanical mapping based) of placebo - 0,9% NaCl plus 0,5% solution of patients' serum</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>intramyocardial injection (electromechanical mapping based)</intervention_name>
    <description>Patient will undergo 3D electric and mechanical intracardiac mapping; based on maps generated intramyocardial administration of autologous CD133+ cells or placebo will be performed.</description>
    <arm_group_label>CD133+</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Patients in the placebo group receive 0.9% NaCl solution with 0.5% solution of the patient's own serum.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Stable angina CCS II-IV despite maximum pharmacotherapy for at least 2 weeks since&#xD;
             last medications change&#xD;
&#xD;
          2. Presence of ≥ 1 myocardial segment with ischemia features in Tc-99m SPECT&#xD;
&#xD;
          3. Patients disqualified from revascularization procedures by Heart Team&#xD;
&#xD;
          4. Patient age &gt; 18 and &lt; 75 year old&#xD;
&#xD;
          5. Patient must provide written informed consent for participation in study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Acute coronary syndrome in less than 6 months prior to enrollment&#xD;
&#xD;
          2. Heart failure NYHA III-IV&#xD;
&#xD;
          3. LVEF &lt;35%&#xD;
&#xD;
          4. Presence of intracardiac thrombus (echocardiography confirmed), massive calcification&#xD;
             of the aortic valve and left ventricular aneurysm&#xD;
&#xD;
          5. Previous cardioverter-defibrillator or cardiac stimulator implantation&#xD;
&#xD;
          6. Allergy to contrast agents&#xD;
&#xD;
          7. History of malignancy&#xD;
&#xD;
          8. HIV, HBV, HCV infection&#xD;
&#xD;
          9. Life expectancy less than 6 months&#xD;
&#xD;
         10. Bleeding diathesis&#xD;
&#xD;
         11. Renal insufficiency (GFR &lt; 30 mL/min/1.73m2)&#xD;
&#xD;
         12. Pregnancy, lactation, or ineffective contraception in women of childbearing potential&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wojciech Wojakowski, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Samodzielny Publiczny Szpital Kliniczny nr 7 Śląskiego Uniwersytetu Medycznego w Katowicach Górnośląskie Centrum Medyczne III Klinika Kardiologii</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Samodzielny Publiczny Szpital Kliniczny nr 7 Śląskiego Uniwersytetu Medycznego w Katowicach Górnośląskie Centrum Medyczne im. prof. Leszka Gieca</name>
      <address>
        <city>Katowice-Ochojec</city>
        <state>Silesian</state>
        <zip>40-635</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <reference>
    <citation>Abdel-Latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA, Zuba-Surma EK, Al-Mallah M, Dawn B. Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med. 2007 May 28;167(10):989-97. doi: 10.1001/archinte.167.10.989.</citation>
    <PMID>17533201</PMID>
  </reference>
  <reference>
    <citation>Lipinski MJ, Biondi-Zoccai GG, Abbate A, Khianey R, Sheiban I, Bartunek J, Vanderheyden M, Kim HS, Kang HJ, Strauer BE, Vetrovec GW. Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction: a collaborative systematic review and meta-analysis of controlled clinical trials. J Am Coll Cardiol. 2007 Oct 30;50(18):1761-7. doi: 10.1016/j.jacc.2007.07.041. Epub 2007 Oct 15.</citation>
    <PMID>17964040</PMID>
  </reference>
  <reference>
    <citation>Wojakowski W, Tendera M, Zebzda A, Michalowska A, Majka M, Kucia M, Maslankiewicz K, Wyderka R, Krol M, Ochala A, Kozakiewicz K, Ratajczak MZ. Mobilization of CD34(+), CD117(+), CXCR4(+), c-met(+) stem cells is correlated with left ventricular ejection fraction and plasma NT-proBNP levels in patients with acute myocardial infarction. Eur Heart J. 2006 Feb;27(3):283-9. doi: 10.1093/eurheartj/ehi628. Epub 2005 Nov 2.</citation>
    <PMID>16267071</PMID>
  </reference>
  <reference>
    <citation>Wojakowski W, Tendera M, Michalowska A, Majka M, Kucia M, Maslankiewicz K, Wyderka R, Ochala A, Ratajczak MZ. Mobilization of CD34/CXCR4+, CD34/CD117+, c-met+ stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction. Circulation. 2004 Nov 16;110(20):3213-20. doi: 10.1161/01.CIR.0000147609.39780.02. Epub 2004 Nov 8.</citation>
    <PMID>15533859</PMID>
  </reference>
  <reference>
    <citation>van Ramshorst J, Bax JJ, Beeres SL, Dibbets-Schneider P, Roes SD, Stokkel MP, de Roos A, Fibbe WE, Zwaginga JJ, Boersma E, Schalij MJ, Atsma DE. Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial. JAMA. 2009 May 20;301(19):1997-2004. doi: 10.1001/jama.2009.685.</citation>
    <PMID>19454638</PMID>
  </reference>
  <reference>
    <citation>Dimmeler S, Burchfield J, Zeiher AM. Cell-based therapy of myocardial infarction. Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):208-16. doi: 10.1161/ATVBAHA.107.155317. Epub 2007 Oct 19.</citation>
    <PMID>17951319</PMID>
  </reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>August 6, 2012</study_first_submitted>
  <study_first_submitted_qc>August 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2012</study_first_posted>
  <last_update_submitted>September 27, 2017</last_update_submitted>
  <last_update_submitted_qc>September 27, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Silesia</investigator_affiliation>
    <investigator_full_name>Wojciech Wojakowski MD, PhD</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>CD133+</keyword>
  <keyword>stem cells</keyword>
  <keyword>Coronary Artery Disease</keyword>
  <keyword>Stable Angina Pectoris</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Angina Pectoris</mesh_term>
    <mesh_term>Angina, Stable</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/NCT01660581
org study id: Regent Vsel
secondary id: 2011-005435-98
nct id: NCT01660581
lead sponsor: 
has dmc: No
The purpose of the study is to evaluate the efficacy of therapy with autological CD133+ cells
      in patients with angina resistant to pharmacological treatment and without the possibility of
      effective revascularization. Cells will be isolated from patients bone marrow and
      administered directly into the muscle of left ventricle. The main objective is to assess the
      treatments' influence on improvement of myocardial perfusion and function, and on decrease of
      occurrence of symptomatic angina.
Patients with a Stable angina pectoris (CCS II-IV) can potentially benefit from treatment
      with autological CD133+ cell populations, which include cells with a higher expression of
      cardiac and endothelial differentiation markers.

      REGENT VSEL Trial will include Patients with Angina resistant to pharmacological treatment
      and without the possibility of effective revascularization.

      The main objective of the study is to assess the treatments influence on:

        -  improvement of myocardial perfusion

        -  global and segmental contractility (LVEF)

        -  occurrence of symptomatic angina

        -  quality of life

      Regent Vsel is a prospective, randomized, double blind, placebo-controlled study with a
      planned number of 60 Patients.

      Randomization will be carried out according to a 1:1 mode. Every Patient will undergo a bone
      marrow aspiration. CD133+ cells will be isolated from bone marrow aspirates. Patients
      randomized to experimental group will receive isolated cells (direct left ventricular muscle
      administration). Patients enrolled to control group will get only a placebo solution injected
      into the muscle.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Myocardial perfusion change
time frame: 4 months after application of cell therapy
description: Myocardial perfusion change assessed by perfusion scintigraphy (99mTc SPECT)
measure: Global and segmental contractility change and myocardial perfusion change
time frame: MRI 4 months and echocardiography 4 and 12 months after application of cell therapy
description: Global and segmental contractility change and myocardial perfusion change assessed by magnetic resonance imaging with adenosine administration, and echocardiography with contrast
measure: Exercise tolerance
time frame: 4 and 12 months after application of cell therapy
description: Exercise tolerance assessed in a treadmill test (TET, ESTD, TTLA)
measure: Occurrence of symptomatic angina
time frame: 1, 4, 6 and 12 months after application of cell therapy
description: CCS, nitrates usage
measure: Quality of life
time frame: 1, 4, 6 and 12 months after application of cell therapy
description: Quality of life assessed by standard questionnaires: SF37, Seattle Angina
measure: Occurrence of ventricular arrhythmia
time frame: 1, 4, 6 and 12 months after application of cell therapy
description: 24 hrs ECG monitoring
measure: Occurrence of in-stent restenosis and progression of artherosclerotic lesions in remained coronary artery segments
time frame: 4 months after application of cell therapy
description: Assessed by Intravascular Ultrasound (IVUS) and Optical coherence tomography (OCT) examination
arm group label: CD133+
arm group type: Experimental
description: intramyocardial injection (electromechanical mapping based) of autological CD133+ cells, isolated from bone marrow
arm group label: Placebo
arm group type: Placebo Comparator
description: intramyocardial injection (electromechanical mapping based) of placebo - 0,9% NaCl plus 0,5% solution of patients' serum
intervention type: Biological
intervention name: intramyocardial injection (electromechanical mapping based)
description: Patient will undergo 3D electric and mechanical intracardiac mapping; based on maps generated intramyocardial administration of autologous CD133+ cells or placebo will be performed.
arm group label: CD133+
intervention type: Biological
intervention name: Placebo
description: Patients in the placebo group receive 0.9% NaCl solution with 0.5% solution of the patient's own serum.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Wojciech Wojakowski, MD, PhD
role: Principal Investigator
affiliation: Samodzielny Publiczny Szpital Kliniczny nr 7 Śląskiego Uniwersytetu Medycznego w Katowicach Górnośląskie Centrum Medyczne III Klinika Kardiologii
facility: 
country: Poland
citation: Abdel-Latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA, Zuba-Surma EK, Al-Mallah M, Dawn B. Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med. 2007 May 28;167(10):989-97. doi: 10.1001/archinte.167.10.989.
PMID: 17533201
citation: Lipinski MJ, Biondi-Zoccai GG, Abbate A, Khianey R, Sheiban I, Bartunek J, Vanderheyden M, Kim HS, Kang HJ, Strauer BE, Vetrovec GW. Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction: a collaborative systematic review and meta-analysis of controlled clinical trials. J Am Coll Cardiol. 2007 Oct 30;50(18):1761-7. doi: 10.1016/j.jacc.2007.07.041. Epub 2007 Oct 15.
PMID: 17964040
citation: Wojakowski W, Tendera M, Zebzda A, Michalowska A, Majka M, Kucia M, Maslankiewicz K, Wyderka R, Krol M, Ochala A, Kozakiewicz K, Ratajczak MZ. Mobilization of CD34(+), CD117(+), CXCR4(+), c-met(+) stem cells is correlated with left ventricular ejection fraction and plasma NT-proBNP levels in patients with acute myocardial infarction. Eur Heart J. 2006 Feb;27(3):283-9. doi: 10.1093/eurheartj/ehi628. Epub 2005 Nov 2.
PMID: 16267071
citation: Wojakowski W, Tendera M, Michalowska A, Majka M, Kucia M, Maslankiewicz K, Wyderka R, Ochala A, Ratajczak MZ. Mobilization of CD34/CXCR4+, CD34/CD117+, c-met+ stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction. Circulation. 2004 Nov 16;110(20):3213-20. doi: 10.1161/01.CIR.0000147609.39780.02. Epub 2004 Nov 8.
PMID: 15533859
citation: van Ramshorst J, Bax JJ, Beeres SL, Dibbets-Schneider P, Roes SD, Stokkel MP, de Roos A, Fibbe WE, Zwaginga JJ, Boersma E, Schalij MJ, Atsma DE. Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial. JAMA. 2009 May 20;301(19):1997-2004. doi: 10.1001/jama.2009.685.
PMID: 19454638
citation: Dimmeler S, Burchfield J, Zeiher AM. Cell-based therapy of myocardial infarction. Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):208-16. doi: 10.1161/ATVBAHA.107.155317. Epub 2007 Oct 19.
PMID: 17951319
responsible party type: Principal Investigator
investigator affiliation: Medical University of Silesia
investigator full name: Wojciech Wojakowski MD, PhD
investigator title: MD, PhD
mesh term: Angina Pectoris
mesh term: Angina, Stable