<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/NCT03797092</url>
  </required_header>
  <id_info>
    <org_study_id>SCIENCE II - Pilot</org_study_id>
    <nct_id>NCT03797092</nct_id>
  </id_info>
  <brief_title>Stem Cell Therapy in Non-IschEmic Non-treatable Dilated CardiomyopathiEs II: a Pilot Study</brief_title>
  <official_title>Stem Cell Therapy in Non-IschEmic Non-treatable Dilated CardiomyopathiEs II: a Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>JKastrup</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University Medical Centre Ljubljana</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Rigshospitalet, Denmark</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall aim of the project is to test the feasibility and safety of allogeneic&#xD;
      adipose-derived stromal cells (CSCC_ASC) investigational medicinal product, to improve&#xD;
      myocardial function in patients with non-ischemic dilated cardiomyopathies (NIDCM) and heart&#xD;
      failure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study design&#xD;
&#xD;
      The primary objective of the study is to investigate safety and regenerative capacity of&#xD;
      direct intra-myocardial injection of 100 million allogeneic CSCC_ASCs in NIDCM patients with&#xD;
      reduced left ventricular EF (≤ 40%) and heart failure.&#xD;
&#xD;
      It is a proof of concept study enrolling a total of 30 NIDCM patients with heart failure who&#xD;
      will be randomly allocated in a 2:1 ratio to either CSCC_ASC cell therapy (Stem Cell Group)&#xD;
      or no cell therapy (Control Group). The treatment period is estimated to be 6 months&#xD;
      (efficacy end-point) with a 12-month follow-up period for safety end-points.&#xD;
&#xD;
      Patient treatment and follow-up&#xD;
&#xD;
        -  The cell IMP will be delivered by a courier service to from REGIONH to UKCL using&#xD;
           validated portable dry liquid nitrogen shipping containers. It will then be stored in&#xD;
           nitrogen vapour containers until treatment.&#xD;
&#xD;
        -  The preparation of the IMP will be performed as described in the treatment manual. The&#xD;
           IMP will be thawed and prepared for injection immediately before treatment.&#xD;
&#xD;
        -  A 3-D map of the left ventricle will be created using the NOGA XP® system (Biological&#xD;
           Delivery System, Cordis, Johnson &amp; Johnson, USA). The delivery of the IMP (100 million&#xD;
           ASCs) into the myocardium will be performed by 10-15 injections of 0.2 cc, as described&#xD;
           in the treatment manual.&#xD;
&#xD;
        -  The post cell therapy surveillance will include clinical and laboratory safety follow-up&#xD;
           with monitoring of cardiac enzymes, hemodynamic and rhythm stability. The clinical&#xD;
           follow-up will be obtained at pre-defined time points. The presence of allogeneic HLA&#xD;
           anti-bodies will be monitored three and six months after treatment. End-points will be&#xD;
           monitored continuously and reported as occurring throughout the 12 months follow-up&#xD;
           period.&#xD;
&#xD;
      Primary and secondary endpoints&#xD;
&#xD;
      The primary endpoint is change in left ventricle end-systolic volume (LVESV) at 6 months&#xD;
      follow-up measured by Echocardiography.&#xD;
&#xD;
      The secondary endpoints are safety evaluated by development of allogeneic antibodies and&#xD;
      laboratory safety measurements 1, 3 and 6 months after treatment and changes in left&#xD;
      ventricular ejection fraction (LVEF), end-diastolic volume and myocardial mass at 6 months&#xD;
      follow-up.&#xD;
&#xD;
      Additional secondary endpoints are changes in NYHA, Kansas City Cardiomyopathy Questionnaire,&#xD;
      EQ-5D3L Questionnaire, 6 min walking test, additional echocardiographic measures (Global&#xD;
      strain %) and NT-pro-BNP.&#xD;
&#xD;
      Safety of allogeneic CSCC_ASCs with respect to incidence and severity of serious adverse&#xD;
      events and suspected unrelated serious adverse events will be evaluated at 12 months&#xD;
      follow-up.&#xD;
&#xD;
      Outcome measures for safety Safety endpoints will be collected, reported to the authorities&#xD;
      and monitored according to legislation during the entire study period.&#xD;
&#xD;
      Adverse event (AE) is defined as any untoward medical occurrence in a subject who was treated&#xD;
      with an investigational product, and does not necessarily have a causal relationship with the&#xD;
      treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease,&#xD;
      whether or not related to the investigational product.&#xD;
&#xD;
      Serious adverse event (SAE) is defined as any untoward medical occurrence that:&#xD;
&#xD;
        1. results in death&#xD;
&#xD;
        2. is life-threatening&#xD;
&#xD;
        3. requires inpatient hospitalisation or prolongation of existing hospitalisation&#xD;
&#xD;
        4. results in persistent or significant disability/incapacity&#xD;
&#xD;
        5. is a congenital anomaly/birth defect&#xD;
&#xD;
        6. is medically important&#xD;
&#xD;
      Suspected unexpected serious adverse event reactions (SUSAR) is defined as a SAE occurring in&#xD;
      a subject in an interventional study that is assessed as both causally related to the suspect&#xD;
      product under clinical investigation and unexpected per the Investigator's Brochure (IB).&#xD;
&#xD;
      An independent Data Safety Monitoring Board (DSMB) will be established to evaluate the safety&#xD;
      of the treatment. The DSMB will report directly to the director of the Project Management&#xD;
      Board, which will take the necessary action upon the DSMB's recommendations.&#xD;
&#xD;
      Study medication The investigational cell product, CSCC_ASC, will be produced in an approved&#xD;
      GMP facility in Cardiology Stem Cell Centre at Rigshospitalet University Hospital,&#xD;
      Copenhagen, Denmark.&#xD;
&#xD;
      The production of the allogeneic CSCC_ASCs will follow the description in an approved&#xD;
      Investigational Medicinal Product Dossier. The cell product will come from healthy donors.&#xD;
&#xD;
      The production unit will label the investigational medicinal product (IMP) in accordance with&#xD;
      the legislation and keep the randomisation code until finalisation of the clinical trial. The&#xD;
      final cell products will be stored in nitrogen vapour containers until clinical use.&#xD;
&#xD;
      Allogeneic MSCs and ASCs have been administered to more than 600 patients with heart disease.&#xD;
      In the conducted clinical trials there has not been any serious adverse event due to the&#xD;
      treatment. A few patients have developed transient donor specific HLA-antibodies in serum&#xD;
      within the first months after treatment. However, none of the patients had any symptoms&#xD;
      related to the presence of antibodies. Transient fever was registered in a few patients, but&#xD;
      it could as well be due to the treatment procedure or the disease for treatment.&#xD;
&#xD;
      Based on the accumulated safety and efficacy evidence with clinical use of allogeneic MSCs&#xD;
      and ASCs in conducted clinical trials and the safety data from the CSCC_ASC phase I trial and&#xD;
      the two ongoing phase II trials then it is concluded that it is safe to conduct a pilot&#xD;
      CSCC_ASC trial in patients with NIDCM and HF.&#xD;
&#xD;
      Echocardiography&#xD;
&#xD;
      The echocardiography data will be recorded at pre-defined intervals according to American&#xD;
      Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI)&#xD;
      recommendations. For each patient at least five end-expiratory full cardiac cycles will be&#xD;
      recorded for each protocol specified view. All acquired images will be de-identified and&#xD;
      transferred to independent imaging core-lab (Stanford Cardiovascular Institute Clinical&#xD;
      Biomarker &amp; Phenotyping Core Lab). The recordings will be analyzed at the end of the study by&#xD;
      an independent echocardiographer who will be blinded to the patient's treatment status and&#xD;
      the timing of the recordings. All measurements will be performed according to ASE/EACVI&#xD;
      recommendations. All echocardiographic measurements will be averaged over 5 cardiac cycles.&#xD;
      Left ventricular end-systolic dimension (LVESD) and end-diastolic dimension (LVEDD) will be&#xD;
      measured in the parasternal long-axis view. Left ventricular end-systolic volume (LVESV),&#xD;
      left ventricular end-diastolic volume (LVEDV), and LVEF will be estimated using the Simpson's&#xD;
      biplane method. Peak longitudinal strains will be computed automatically to generate regional&#xD;
      data from each of the 17 segments and then averaged to calculate global longitudinal strain.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 1, 2019</start_date>
  <completion_date type="Anticipated">September 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2021</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>
    <intervention_model_description>Open randomized treatment group and control group clinical trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The patients will be randomized to either IMP or control in a 2:1 randomization.&#xD;
The outcome ECHO investigations will be analyzed blinded by an independent core lab.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Left ventricle end-systolic volume</measure>
    <time_frame>6 months after treatment</time_frame>
    <description>Measured using echocardiography</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Allogeneic antibodies</measure>
    <time_frame>Up to 12 months after treatment</time_frame>
    <description>Development of allogeneic antibodies and laboratory safety measurements 1, 3 and 6 months after treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Left ventricular ejection fraction</measure>
    <time_frame>6 months after treatment</time_frame>
    <description>Changes in LVEF</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Myocardial mass of left ventricle</measure>
    <time_frame>6 months after treatment</time_frame>
    <description>Change in echo measured global myocardial mass</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NYHA</measure>
    <time_frame>6 months after treatment</time_frame>
    <description>Symptoms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kansas City Cardiomyopathy Questionnaire</measure>
    <time_frame>6 months after treatment</time_frame>
    <description>Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EQ-5D3L Questionnaire</measure>
    <time_frame>6 months after treatment</time_frame>
    <description>Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6 min walking test</measure>
    <time_frame>6 months</time_frame>
    <description>Test</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Non-ischemic Dilated Cardiomyopathy</condition>
  <arm_group>
    <arm_group_label>Active</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Allogeneic adipose-derived stromal cells (CSCC_ASC)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Allogeneic adipose-derived stromal cells (CSCC_ASC)</intervention_name>
    <description>Active group</description>
    <arm_group_label>Active</arm_group_label>
    <other_name>Investigational medicinal product</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Control group</intervention_name>
    <description>No treatment</description>
    <arm_group_label>Active</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 30 to 80 years of age&#xD;
&#xD;
          2. Signed informed consent&#xD;
&#xD;
          3. Patients with non-ischemic dilated cardiomyopathy&#xD;
&#xD;
          4. NYHA ≥ II in spite of optimal heart failure treatment and have no other treatment&#xD;
             options&#xD;
&#xD;
          5. Heart failure medication unchanged two months prior to inclusion/signature of informed&#xD;
             consent. Changes in diuretics accepted&#xD;
&#xD;
          6. LVEF ≤ 405%&#xD;
&#xD;
          7. Plasma NT-pro-BNP &gt; 300 pg/ml (&gt; 35 pmol/L)&#xD;
&#xD;
          8. Patients cannot be included until three months after implantation of a cardiac&#xD;
             resynchronisation therapy device (CRTD) and until 1 month after an ICD unit&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Heart Failure NYHA I&#xD;
&#xD;
          2. Moderate to severe aortic stenosis (valve area &lt; 1.3 cm2) or valvular disease with&#xD;
             option for surgery or interventional therapy.&#xD;
&#xD;
          3. Heart failure caused by cardiac valve disease or untreated hypertension.&#xD;
&#xD;
          4. If the patient is expected to be candidate for MitraClip therapy of mitral&#xD;
             regurgitation in the 12 months follow-up period.&#xD;
&#xD;
          5. Cardiomyopathy with a reversible cause that has not been treated e.g. thyroid disease,&#xD;
             alcohol abuse, hypophosphataemia, hypocalcaemia, cocaine abuse, selenium toxicity &amp;&#xD;
             chronic uncontrolled tachycardia&#xD;
&#xD;
          6. Cardiomyopathy in association with a neuromuscular disorder e.g. Duchenne's&#xD;
             progressive muscular dystrophy&#xD;
&#xD;
          7. Previous cardiac surgery&#xD;
&#xD;
          8. Diminished functional capacity for other reasons such as: obstructive pulmonary&#xD;
             disease (COPD) with forced expiratory volume (FEV) &lt;1 L/min, moderate to severe&#xD;
             claudication or morbid obesity&#xD;
&#xD;
          9. Clinical significant anaemia (haemoglobin &lt; 6 mmol/L), leukopenia (leucocytes &lt; 2&#xD;
             109/L), leucocytosis (leucocytes &gt; 14 109/L) or thrombocytopenia (thrombocytes &lt; 50&#xD;
             109/L)&#xD;
&#xD;
         10. Reduced kidney function (eGFR &lt; 30 ml/min)&#xD;
&#xD;
         11. Left ventricular thrombus&#xD;
&#xD;
         12. Anticoagulation treatment that cannot be paused during cell injections.&#xD;
&#xD;
         13. Patients with reduced immune response&#xD;
&#xD;
         14. History with malignant disease within five years of inclusion or suspected malignity -&#xD;
             except treated skin cancer other than melanoma&#xD;
&#xD;
         15. Pregnant women&#xD;
&#xD;
         16. Woman of childbearing potential unless βHCG negative and they should be on&#xD;
             contraception during the trial&#xD;
&#xD;
         17. Other experimental treatment within four weeks of baseline tests&#xD;
&#xD;
         18. Participation in another intervention trial&#xD;
&#xD;
         19. Life expectancy less than one year&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bojan Vrtovec, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dep. of Cardiology, Uni. Medical Center Ljubljana, Slovenia</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jens Kastrup, MD, DMSc</last_name>
    <phone>004535452819</phone>
    <email>jens.akstrup@regionh.dk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Abbas A Qayyum, MD, PhD</last_name>
    <phone>004535451076</phone>
    <email>abbas.ali.qayyum@regionh.dk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The Heart Centre, Rigshospitalet University Hospital Copenhagen,</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Jens Kastrup, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/28880460</url>
    <description>PubMed abstract related to the used allogeneic stem cell product</description>
  </link>
  <results_reference>
    <citation>Kastrup J, Haack-Sorensen M, Juhl M, Harary Sondergaard R, Follin B, Drozd Lund L, Monsted Johansen E, Ali Qayyum A, Bruun Mathiasen A, Jorgensen E, Helqvist S, Jorgen Elberg J, Bruunsgaard H, Ekblond A. Cryopreserved Off-the-Shelf Allogeneic Adipose-Derived Stromal Cells for Therapy in Patients with Ischemic Heart Disease and Heart Failure-A Safety Study. Stem Cells Transl Med. 2017 Nov;6(11):1963-1971. doi: 10.1002/sctm.17-0040. Epub 2017 Sep 7.</citation>
    <PMID>28880460</PMID>
  </results_reference>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>June 28, 2018</study_first_submitted>
  <study_first_submitted_qc>January 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 8, 2019</study_first_posted>
  <last_update_submitted>January 15, 2021</last_update_submitted>
  <last_update_submitted_qc>January 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Rigshospitalet, Denmark</investigator_affiliation>
    <investigator_full_name>JKastrup</investigator_full_name>
    <investigator_title>Professor, Doctor</investigator_title>
  </responsible_party>
  <keyword>Stem cell therapy</keyword>
  <keyword>Heart failure</keyword>
  <keyword>Clinical trial</keyword>
  <keyword>Allogeneic</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>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>The entire study will be published and shared with other researchers</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/NCT03797092
org study id: SCIENCE II - Pilot
nct id: NCT03797092
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The overall aim of the project is to test the feasibility and safety of allogeneic
      adipose-derived stromal cells (CSCC_ASC) investigational medicinal product, to improve
      myocardial function in patients with non-ischemic dilated cardiomyopathies (NIDCM) and heart
      failure.
Study design

      The primary objective of the study is to investigate safety and regenerative capacity of
      direct intra-myocardial injection of 100 million allogeneic CSCC_ASCs in NIDCM patients with
      reduced left ventricular EF (≤ 40%) and heart failure.

      It is a proof of concept study enrolling a total of 30 NIDCM patients with heart failure who
      will be randomly allocated in a 2:1 ratio to either CSCC_ASC cell therapy (Stem Cell Group)
      or no cell therapy (Control Group). The treatment period is estimated to be 6 months
      (efficacy end-point) with a 12-month follow-up period for safety end-points.

      Patient treatment and follow-up

        -  The cell IMP will be delivered by a courier service to from REGIONH to UKCL using
           validated portable dry liquid nitrogen shipping containers. It will then be stored in
           nitrogen vapour containers until treatment.

        -  The preparation of the IMP will be performed as described in the treatment manual. The
           IMP will be thawed and prepared for injection immediately before treatment.

        -  A 3-D map of the left ventricle will be created using the NOGA XP® system (Biological
           Delivery System, Cordis, Johnson & Johnson, USA). The delivery of the IMP (100 million
           ASCs) into the myocardium will be performed by 10-15 injections of 0.2 cc, as described
           in the treatment manual.

        -  The post cell therapy surveillance will include clinical and laboratory safety follow-up
           with monitoring of cardiac enzymes, hemodynamic and rhythm stability. The clinical
           follow-up will be obtained at pre-defined time points. The presence of allogeneic HLA
           anti-bodies will be monitored three and six months after treatment. End-points will be
           monitored continuously and reported as occurring throughout the 12 months follow-up
           period.

      Primary and secondary endpoints

      The primary endpoint is change in left ventricle end-systolic volume (LVESV) at 6 months
      follow-up measured by Echocardiography.

      The secondary endpoints are safety evaluated by development of allogeneic antibodies and
      laboratory safety measurements 1, 3 and 6 months after treatment and changes in left
      ventricular ejection fraction (LVEF), end-diastolic volume and myocardial mass at 6 months
      follow-up.

      Additional secondary endpoints are changes in NYHA, Kansas City Cardiomyopathy Questionnaire,
      EQ-5D3L Questionnaire, 6 min walking test, additional echocardiographic measures (Global
      strain %) and NT-pro-BNP.

      Safety of allogeneic CSCC_ASCs with respect to incidence and severity of serious adverse
      events and suspected unrelated serious adverse events will be evaluated at 12 months
      follow-up.

      Outcome measures for safety Safety endpoints will be collected, reported to the authorities
      and monitored according to legislation during the entire study period.

      Adverse event (AE) is defined as any untoward medical occurrence in a subject who was treated
      with an investigational product, and does not necessarily have a causal relationship with the
      treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease,
      whether or not related to the investigational product.

      Serious adverse event (SAE) is defined as any untoward medical occurrence that:

        1. results in death

        2. is life-threatening

        3. requires inpatient hospitalisation or prolongation of existing hospitalisation

        4. results in persistent or significant disability/incapacity

        5. is a congenital anomaly/birth defect

        6. is medically important

      Suspected unexpected serious adverse event reactions (SUSAR) is defined as a SAE occurring in
      a subject in an interventional study that is assessed as both causally related to the suspect
      product under clinical investigation and unexpected per the Investigator's Brochure (IB).

      An independent Data Safety Monitoring Board (DSMB) will be established to evaluate the safety
      of the treatment. The DSMB will report directly to the director of the Project Management
      Board, which will take the necessary action upon the DSMB's recommendations.

      Study medication The investigational cell product, CSCC_ASC, will be produced in an approved
      GMP facility in Cardiology Stem Cell Centre at Rigshospitalet University Hospital,
      Copenhagen, Denmark.

      The production of the allogeneic CSCC_ASCs will follow the description in an approved
      Investigational Medicinal Product Dossier. The cell product will come from healthy donors.

      The production unit will label the investigational medicinal product (IMP) in accordance with
      the legislation and keep the randomisation code until finalisation of the clinical trial. The
      final cell products will be stored in nitrogen vapour containers until clinical use.

      Allogeneic MSCs and ASCs have been administered to more than 600 patients with heart disease.
      In the conducted clinical trials there has not been any serious adverse event due to the
      treatment. A few patients have developed transient donor specific HLA-antibodies in serum
      within the first months after treatment. However, none of the patients had any symptoms
      related to the presence of antibodies. Transient fever was registered in a few patients, but
      it could as well be due to the treatment procedure or the disease for treatment.

      Based on the accumulated safety and efficacy evidence with clinical use of allogeneic MSCs
      and ASCs in conducted clinical trials and the safety data from the CSCC_ASC phase I trial and
      the two ongoing phase II trials then it is concluded that it is safe to conduct a pilot
      CSCC_ASC trial in patients with NIDCM and HF.

      Echocardiography

      The echocardiography data will be recorded at pre-defined intervals according to American
      Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI)
      recommendations. For each patient at least five end-expiratory full cardiac cycles will be
      recorded for each protocol specified view. All acquired images will be de-identified and
      transferred to independent imaging core-lab (Stanford Cardiovascular Institute Clinical
      Biomarker & Phenotyping Core Lab). The recordings will be analyzed at the end of the study by
      an independent echocardiographer who will be blinded to the patient's treatment status and
      the timing of the recordings. All measurements will be performed according to ASE/EACVI
      recommendations. All echocardiographic measurements will be averaged over 5 cardiac cycles.
      Left ventricular end-systolic dimension (LVESD) and end-diastolic dimension (LVEDD) will be
      measured in the parasternal long-axis view. Left ventricular end-systolic volume (LVESV),
      left ventricular end-diastolic volume (LVEDV), and LVEF will be estimated using the Simpson's
      biplane method. Peak longitudinal strains will be computed automatically to generate regional
      data from each of the 17 segments and then averaged to calculate global longitudinal strain.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Open randomized treatment group and control group clinical trial
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: The patients will be randomized to either IMP or control in a 2:1 randomization.
The outcome ECHO investigations will be analyzed blinded by an independent core lab.
measure: Left ventricle end-systolic volume
time frame: 6 months after treatment
description: Measured using echocardiography
measure: Allogeneic antibodies
time frame: Up to 12 months after treatment
description: Development of allogeneic antibodies and laboratory safety measurements 1, 3 and 6 months after treatment
measure: Left ventricular ejection fraction
time frame: 6 months after treatment
description: Changes in LVEF
measure: Myocardial mass of left ventricle
time frame: 6 months after treatment
description: Change in echo measured global myocardial mass
measure: NYHA
time frame: 6 months after treatment
description: Symptoms
measure: Kansas City Cardiomyopathy Questionnaire
time frame: 6 months after treatment
description: Questionnaire
measure: EQ-5D3L Questionnaire
time frame: 6 months after treatment
description: Questionnaire
measure: 6 min walking test
time frame: 6 months
description: Test
arm group label: Active
arm group type: Active Comparator
description: Allogeneic adipose-derived stromal cells (CSCC_ASC)
arm group label: Control group
arm group type: No Intervention
description: No treatment
intervention type: Biological
intervention name: Allogeneic adipose-derived stromal cells (CSCC_ASC)
description: Active group
arm group label: Active
other name: Investigational medicinal product
intervention type: Other
intervention name: Control group
description: No treatment
arm group label: Active
criteria: 
gender: All
minimum age: 30 Years
maximum age: 80 Years
healthy volunteers: No
last name: Bojan Vrtovec, MD, PhD
role: Principal Investigator
affiliation: Dep. of Cardiology, Uni. Medical Center Ljubljana, Slovenia
last name: Jens Kastrup, MD, DMSc
phone: 004535452819
email: jens.akstrup@regionh.dk
last name: Abbas A Qayyum, MD, PhD
phone: 004535451076
email: abbas.ali.qayyum@regionh.dk
facility: 
status: Recruiting
investigator: 
country: Denmark
url: https://www.ncbi.nlm.nih.gov/pubmed/28880460
description: PubMed abstract related to the used allogeneic stem cell product
citation: Kastrup J, Haack-Sorensen M, Juhl M, Harary Sondergaard R, Follin B, Drozd Lund L, Monsted Johansen E, Ali Qayyum A, Bruun Mathiasen A, Jorgensen E, Helqvist S, Jorgen Elberg J, Bruunsgaard H, Ekblond A. Cryopreserved Off-the-Shelf Allogeneic Adipose-Derived Stromal Cells for Therapy in Patients with Ischemic Heart Disease and Heart Failure-A Safety Study. Stem Cells Transl Med. 2017 Nov;6(11):1963-1971. doi: 10.1002/sctm.17-0040. Epub 2017 Sep 7.
PMID: 28880460
responsible party type: Sponsor-Investigator
investigator affiliation: Rigshospitalet, Denmark
investigator full name: JKastrup
investigator title: Professor, Doctor
mesh term: Cardiomyopathies
mesh term: Cardiomyopathy, Dilated
sharing ipd: No
ipd description: The entire study will be published and shared with other researchers