CArdiosphere-Derived aUtologous Stem CElls to Reverse ventricUlar dySfunction
Condition: Recent Myocardial Infarction; Ventricular Dysfunction
MeSH terms: Myocardial Infarction; Ventricular Dysfunction; Infarction
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to determine whether giving cardiosphere-derived stem cells
      (CDCs) to patients with decreased heart function and/or a large amount of damaged muscle
      after a heart attack is safe. CDCs are cells grown from small biopsy samples taken from the
      heart. Giving a patient their own CDCs is an investigational procedure that has been approved
      by the Food and Drug Administration for this study. In addition to determining whether this
      treatment is safe, the study will also examine whether it can decrease the amount of heart
      muscle damage and/or improve heart function after a heart attack. The amount of heart muscle
      damage and the function of the heart directly affects prognosis (the predicted course of the
      disease), and the development of heart failure and other complications some patients
      experience after a heart attack.

      By way of background, scientists and physicians believed, until just a few years ago, that
      heart muscle damaged after a heart attack could not be replaced. Recently, however,
      scientists discovered that new heart muscle can form, or be regenerated, and that this
      process can be enhanced (or increased) by the administration of large numbers of certain
      cells isolated from the heart or bone marrow. These cells can be stem cells, or cells derived
      from stem cells, and they may achieve their benefit by forming new heart muscle cells,
      becoming heart muscle cells themselves, or releasing substances which increase the ability of
      already existing stem cells to form new heart muscle. All of the studies conducted so far
      have been experimental and no cell type is approved for routine clinical care of patients
      with heart disease. However, studies involving bone marrow stem cells do indicate some small
      improvement in heart function and one large study demonstrated a decrease in clinical events
      in the group which received bone marrow cells.

      Investigators of this study decided to study CDCs because they come from a person's own body,
      and therefore have no foreign immune antigens which may be rejected. Since the cells come
      from the person's heart, they are more likely to form heart tissue. In addition, animal
      studies indicate no safety problems and that these cells are capable of forming heart muscle
      and blood vessel cells after heart attacks. The investigators are now studying whether the
      same is true in humans.
    

Detailed description: 
      The type of study that is being proposed is called a prospective, randomized, dose escalation
      study. This means that some of the patients will receive a solution which contains the cells
      and some of the patients will receive conventional medical treatment. The ratio is 2:1, which
      means that twice as many patients will receive cells as will receive conventional medical
      treatment. The first 6 patients in each group will be randomized to receive the study drug at
      a dose of 12.5 million cells or conventional medical treatment. The remaining 18 patients
      will be randomized to receive study drug at a dose of 25 million cells or conventional
      medical treatment. The DSMB will evaluate unblinded AE data (including SAEs) when the first
      six patients have been enrolled and those receiving cells have been discharged. There are two
      study sites. Each site will enroll 15 participants. The total number of subjects will be 30,
      with an approximate 20% attrition rate.

      Subjects will be referred to participate in the study by physicians caring for them. The
      target number of participants is 24 patients who have an open artery to inject the stem cells
      and whose biopsy tissues have been grown to 12.5 million cells. If for some reason the cells
      cannot be expanded to 12.5 million or the subject's artery is not open enough to allow proper
      injection, the subject will be replaced in the study population of 24 patients but continue
      to be followed. This means that the subject will undergo all tests, procedures (except cell
      infusion) and follow-up visits that would have otherwise been required for participation in
      the study.

      When a subject is determined to be eligible for the study, the protocol will be reviewed with
      the subject and informed consent will be obtained by a physician participating in the study
      prior to any testing or treatment.

      This study is being conducted at the Cedars-Sinai Medial Center and The Johns Hopkins
      Hospital. The total length of a subject's participation in the study will be approximately 14
      months, from enrollment to 12 month follow-up visit.

      SCREENING PHASE - Participants will undergo a screening evaluation. A physical examination
      with medical history will be performed which includes medication review as well as alcohol or
      drug use. A blood specimen will be obtained, approximately three teaspoons, to assess for
      blood counts, chemistry, HIV, hepatitis and pregnancy test for females of childbearing age.
      An MRI scan will be performed to determine whether the portion of the heart from which the
      biopsy would be obtained was damaged from the heart attack. MRI will also detect if any
      cardiac tumors are present. An electrocardiogram will be performed to assess your heart's
      electrical activity. Additionally, a computed tomography (CT) scan of the chest, abdomen and
      pelvis will be performed to detect any existing cancer or tumors. If any of the tests are
      positive, the subject will not be able to participate in the study.

      RANDOMIZATION - After the screening visit is completed, subjects will be randomized to either
      cell infusion or conventional medical therapy. Randomization is 2:1, meaning that twice as
      many subjects will be randomized to receive cell infusion as conventional medical therapy.
      Conventional medical therapy after a heart attack can include beta blockers, aspirin,
      diuretics, cholesterol lowering agents, anticoagulants, ACE inhibitors or calcium channel
      blockers and enrollment in a cardiac rehabilitation program. Depending on the degree of heart
      damage and it's affects on the patient's heart rhythm, the patient may be eligible for
      pacemaker or implantable cardioverter-defibrillator. The specific medical management is
      determined by the patient's primary care physician or cardiologist.

      BASELINE VISIT- At this visit several tests will be performed to assess the heart's baseline
      function, i.e., the function before cells are infused. It will be conducted prior to the
      biopsy. These include completion of a questionnaire about how much activity the subject can
      perform; blood studies to measure blood count and the function of the liver and kidneys; an
      electrocardiogram which measures the electrical activity of the heart; an exercise test which
      will also measure blood pressure, heart rate, electrocardiogram, and the amount of oxygen and
      carbon dioxide in the exhaled air; a test which measures how much distance the subject can
      walk in six minutes; a test of lung function; a recording of the heart's rhythm over 48
      hours; and an MRI to provide information about the baseline function and recovery of the
      heart since the myocardial infarction.

      BIOPSY PHASE - For subjects randomized to receive stem cells, a biopsy of the heart will be
      performed in the catheterization laboratory. In this test, a small amount of tissue is
      removed from the internal lining of the heart. A long, flexible tube (catheter), called a
      bioptome, is inserted into a vein and threaded into the right side of the heart. Most often
      the catheter is threaded through the jugular vein of the neck under local anesthesia. The tip
      of the catheter is fitted with tiny jaws that allow the doctor to take very small snips of
      muscle for microscopic examination. The doctor will take 5-10 small pieces of heart tissue
      from the right side of the wall that separates the right side of the heart from the left side
      of the heart. This will be used to grow the cells over a four week period. Blood pressure and
      vital signs status will be monitored during and for several hours following the procedure. An
      electrocardiogram; blood (approximately 15 cc or 3 teaspoons) will be obtained to measure
      your blood count, kidney and liver function; and urine specimen for urinalysis will be
      collected. An echocardiogram will be performed before the patient leaves the hospital to
      determine whether the instrument obtaining the biopsy caused a hole in the wall from which
      the biopsy was obtained.

      INTRACORONARY INFUSION PHASE - During this phase, subjects randomized to receive cells will
      be brought to the cardiac catheterization laboratory to undergo a cardiac catheterization
      procedure similar to the angioplasty performed to treat the heart attack. However, rather
      than having an angioplasty, the cells will be injected into the coronary artery whose
      blockage was responsible for the heart attack. The cells will be infused through a balloon
      catheter inflated at the previously implanted stent. There will be no new stent implanted
      unless it is felt clinically necessary. Following the procedure, the subject will remain in
      the hospital for 24 hours at which time laboratory studies, including cardiac enzymes to rule
      out cardiac injury, or a heart attack, as well as ECG monitoring will be performed. The
      subject will be released from the hospital and asked to wear an ECG recording device for 48
      hours.

      FOLLOW UP VISITS - For all subjects enrolled in the study, there will be six follow-up
      visits. This is necessary to obtain and compare information from both sets of study
      participants. Additionally, it is necessary to obtain the information to determine the safety
      of the cell infusion and whether it has decreased the amount of the heart which is damaged,
      improved the blood flow and function of the heart and the portion of the heart which received
      the cells.

      A history and physical will be performed at all of the 6 visits, asking the subject about any
      side effects they may have had and what other medicines they are taking. Additionally, study
      staff will perform an electrocardiogram, obtain blood and urine studies measuring blood
      counts and kidney and liver function, and obtain a 48-hour recording of the subject's
      electrocardiogram. During the six and twelve month visits, a cardiac MRI scan will also be
      performed to measure the amount of the heart which is damaged and the blood flow and function
      of the heart and to assess the portion of the heart which received the cells. It will also
      determine whether any tumors have formed in the heart. At these visits, there will also be a
      test of lung function, a six-minute walk test, and questions about how much activity the
      subject can perform. Additionally, there will be an exercise test which will include
      measuring heart rate, blood pressure, electrocardiogram, and amount of oxygen and carbon
      dioxide in exhaled air. Patients who receive an implantable cardio-defibrillator during the
      study will have a cardiac CT instead of MRI.

      The patient will be followed in the study for a total of 12 months from the baseline visit
      and any unexpected effects of the study will be reported to the hospital's institutional
      review board, the study data safety monitoring board and the FDA, as appropriate, depending
      on the severity of the adverse event.
    

Intervention name(s): Autologous stem cell infusion; Autologous stem cell infusion
Intervention type(s): Biological; Biological
Intervention description(s): Subjects will receive 12.5 million of autologous (grown from your own heart muscle specimen) cardiosphere-derived stem cells via intracoronary delivery.; Subjects will receive 25 million of autologous (grown from your own heart muscle specimen) cardiosphere-derived stem cells via intracoronary delivery.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Adult Stem cells; Cardiosphere derived stem cells; Myocardial infarction