Cardiac Stem Cell Infusion in Patients With Ischemic CardiOmyopathy (SCIPIO)
Condition: Coronary Artery Disease; Congestive Heart Failure
MeSH terms: Heart Failure; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Cardiomyopathies
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to investigate the safety of intracoronary cardiac stem cells
      (CSCs) therapy in humans. Currently, there is no effective intervention to regenerate
      (regrow) dead heart muscle after a heart attack.

      The central hypothesis is that CSCs infused into nonviable myocardial segments will
      regenerate infarcted myocardium by differentiating into cardiomyocytes and other cell types.
      According to our hypothesis, CSC infusion regenerates myocardium with consequent improvement
      in contractile function of the heart and general clinical status.
    

Detailed description: 
      This will be a randomized, open-label study involving 20 patients and 20 controls. This study
      will be done as a collaborative project between Brigham Women's Hospital and The University
      of Louisville. This study is a phase I trial assessing the safety and feasibility of
      intracoronary autologous CSC [harvested from the right atrial appendage (RAA)]
      transplantation in patients with ischemic cardiomyopathy. The study will be conducted in two
      stages: Stage A, in which the investigators will obtain an initial assessment of safety and
      feasibility, and stage B, in which the investigators will adopt a block randomization
      strategy that will enable us to assess the feasibility of conducting a subsequent, randomized
      phase II trials. While the investigators also hope to have an estimate of efficacy, this
      focus will be the specific aim of future phase II trials. All patients who are undergoing
      on-pump CABG will be screened twice. The initial screening will be done to determine the
      preliminary eligibility (before-CABG screening) of patients for the study. If the patients
      satisfy the preliminary eligibility criteria stated below, the right atrial appendage, which
      is routinely resected during all on-pump bypass surgeries, will be collected and processed.
      Thereafter, the CSCs will be cultured and expanded from the RAA. The second screening will
      occur an average of 4 ± 1 months after CABG surgery, and will utilize a LVEF of < 40%
      assessed by cardiac MRI and/or the disk summation method [or Simpson's method] using
      echocardiography, for final enrollment.

        -  The preliminary eligibility criteria will utilize an EF < 40% measured by any of the
           following: cardiac imaging tests performed within 2 weeks prior to screening:
           echocardiography, gated SPECT and/or LV angiography.

        -  A maximum of 60 patients who satisfy the preliminary eligibility criteria will be
           enrolled in the preliminary phase of the study (i.e., will have RAA tissue
           harvested/cultured/expanded). Of these 60 patients, a maximum of 20 will be enrolled in
           the final phase of the study (i.e., will undergo CSC injections and subsequent
           follow-up).

        -  In this open-label study, a maximum of 20 patients will eventually receive intracoronary
           CSC transplantation. These patients will have nonviable myocardium/scar from prior MI
           and will undergo CABG for ICM.

        -  Enrollment of patients will be done in two stages: Stage A and stage B.

        -  In stage A, 9 consecutive patients will be enrolled in the treatment arm followed by 4
           consecutive patients in the control arm. Stage A will enable us to perform an initial
           assessment of whether the process of harvesting, processing, and administering cardiac
           stem cells is associated with common/frequent short-term adverse effects.

        -  In stage B, patients will be randomized to the treated and control arms using a 2:3
           ratio with a block size of 5 with a final variable block. As a result, the total number
           of both treated and control patients will be 20 each. More specifically, 11 treated and
           16 control patients will make up stage B. To ensure that randomization can be done at
           the time of final enrollment, right atrial tissue will be harvested and cardiac stem
           cells will be grown from all patients who meet the enrollment criteria at the time of
           initial enrollment. If a patient is then randomized to the control arm, his/her cells
           will be discarded.

        -  Patients who satisfy the preliminary eligibility criteria will be enrolled and
           revascularized within few days (< 2 weeks) of enrollment.

        -  Patients will receive venous and/or arterial grafts as needed during CABG surgery.
           Nonviable myocardial segments will also be revascularized in order to enable subsequent
           intracoronary delivery of CSCs into the scarred region.

        -  During on-pump CABG surgery, patients will undergo resection of part of the RAA at the
           cannulation site (this is done routinely during CABG surgery). Resected RAA tissue (< 1
           g) will be collected intra-operatively and handled as described in the preparation
           section.

        -  Cardiac catheterization (coronary angiography) for intracoronary injection of CSCs will
           be performed 4 ± 1 month after CABG surgery.

      Worldwide, more than 500 patients have received intracoronary infusions of stem cells
      (derived from the bone marrow and peripheral blood). None of these patients have had any
      adverse events as a result of these infusions.

      The overall objective of this project is to determine whether intracoronary delivery of CSCs
      can regenerate non-viable myocardial segments in patients with ICM. CSCs will be harvested
      from right atrial appendages (RAAs) of patients with ICM during surgical revascularization,
      cultured and expanded in vitro, and then transplanted back into the same patient.

      The specific aims are:

        1. To determine the feasibility of harvesting CSCs from RAAs of patients undergoing
           surgical revascularization, culturing and expanding them in vitro, and injecting them
           into patients via the intracoronary route

        2. To determine the safety of intracoronary infusion of CSCs

      In addition to these safety data, we hope to obtain initial evidence that CSC administration
      results in clinical improvement.
    

Intervention name(s): Treatment group
Intervention type(s): Biological
Intervention description(s): Intracoronary injection of cardiac stem cells
Other intervention name(s): Intracoronary Injection (cardiac stem cell therapy)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: coronary artery disease; Heart Attack; Heart failure; Cardiac Stem Cells; Coronary Artery Bypass