CArdiosphere-Derived aUtologous Stem CElls to Reverse ventricUlar dySfunction (CADUCEUS)

This study has been completed.
Sponsor:
Collaborators:
Johns Hopkins University
The EMMES Corporation
Information provided by (Responsible Party):
Eduardo Marban, MD, PhD, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier:
NCT00893360
First received: May 5, 2009
Last updated: February 10, 2014
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
Recent Myocardial Infarction
Ventricular Dysfunction
Biological: Autologous stem cell infusion
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Randomized, Dose Escalation Study of the Safety and Efficacy of Intracoronary Delivery of Cardiosphere-Derived Stem Cells in Patients With Ischemic Left Ventricular Dysfunction and a Recent Myocardial Infarction

Resource links provided by NLM:


Further study details as provided by Cedars-Sinai Medical Center:

Primary Outcome Measures:
  • The primary objective is to demonstrate the safety of autologous cardiosphere-derived stem cells administered by intra-coronary infusion in patients with ischemic left ventricular dysfunction and a recent myocardial infarction. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The secondary objective is to demonstrate the efficacy of autologous cardiosphere-derived cells administered by intra-coronary infusion in patients with ischemic left ventricular dysfunction and a recent myocardial infarction. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 31
Study Start Date: May 2009
Study Completion Date: February 2012
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cardiac Stem Cell Treatment - Group 1
Autologous stem cell infusion of 12.5 MIL CDCs via intracoronary infusion.
Biological: Autologous stem cell infusion
Subjects will receive 12.5 million of autologous (grown from your own heart muscle specimen) cardiosphere-derived stem cells via intracoronary delivery.
Experimental: Cardiac Stem Cell Treatment -Group 2
Autologous stem cell infusion of 25 MIL CDCs via intracoronary infusion.
Biological: Autologous stem cell infusion
Subjects will receive 25 million of autologous (grown from your own heart muscle specimen) cardiosphere-derived stem cells via intracoronary delivery.
No Intervention: Observation (Control Group)
Observation of myocardial recovery after usual medical management.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Myocardial infarction due to coronary artery atherosclerotic disease. Myocardial infarction will be defined by a rise in serum troponin I to greater than the 99th percentile of the upper limits of normal with at least one of the following:

    • symptoms of ischemia
    • ECG changes indicative of new ischemia (new ST-T changes or new left bundle branch block)
    • development of pathological Q waves on the ECG
    • imaging evidence of new loss of viable myocardium, OR
    • new regional wall motion abnormality.
  • An area of regional dysfunction, i.e., hypokinetic, akinetic, or dyskinetic, as assessed by echocardiography, left ventriculography, or MRI.
  • History of successful angioplasty and stent placement, with resultant TIMI grade flow ≥ 2, in the artery supplying the infarcted, dysfunctional territory and through which the cells will be infused.
  • Left ventricular ejection fraction of ≥ .25 and ≤ .45 as determined by clinically-indicated assessment of cardiac function (echocardiogram, gated blood pool scan, x-ray contrast ventriculography, CT and/or MRI one day or more following successful reperfusion).
  • No further revascularization clinically indicated at the time the patient is assessed for participation in the clinical trial. This will be determined by a cardiologist who is not an investigator in the clinical trial. No further revascularization may be indicated by no arteries with significant stenosis, the location, and extent of any stenosis may not be suitable for angioplasty, the distal vessels may not be suitable for placement of bypass grafts, and/or the patient declines angioplasty or bypass surgery.
  • Ability to provide informed consent and follow-up with protocol procedures.
  • Age > 18 years.

Exclusion Criteria:

  • Non-cardiovascular disease with expected life expectancy of < 3 years.
  • Contraindications to MRI, including:

    • prior ICD placement
    • estimated glomerular filtration rate < 50 ml/min
    • known reaction to gadolinium
    • claustrophobia
    • pacemaker
    • ear implant, and cochlear implant.
  • History of possible presence of ferromagnetic material including programmable shunt, shrapnel, penile prosthesis, intra-uterine device, bullets, tattoos, artificial limb, blood vessel coil, and tissue expander may require special screening.
  • Septal infarction involving the right ventricular endocardium as demonstrated by screening MRI (because its presence might increase the potential risk of septal biopsy and decrease treatment benefit due to decreased viability of injured septal-based stem cells).
  • History of cardiac tumor, or cardiac tumor demonstrated on MRI.
  • Requirement for chronic immunosuppressive therapy.
  • Participation in an on-going protocol studying an experimental drug or device.
  • Diagnosis of right ventricular arrhythmogenic dysplasia.
  • Patients with occlusion of the infarct-related artery before administration of the study agent.
  • Current alcohol abuse.
  • Current drug abuse.
  • Pregnancy.
  • Child-bearing potential without use of effective contraception. Men intending to "father" children are also excluded.
  • Human Immunodeficiency virus infection.
  • Viral hepatitis.
  • Uncontrolled diabetes and/or hemoglobin A1C > 8.5%.
  • Abnormal liver function (SGPT > 3 times the upper reference range) and hematology (hematocrit < 25%, WBC < 3000, platelets < 100,000) studies without a reversible, identifiable cause.
  • Ventricular tachycardia or fibrillation not associated with an acute ischemic episode.
  • New York Heart Association Class 4 congestive heart failure.
  • Canadian Cardiovascular Society Angina Class 3 or 4.
  • Evidence of tumor on screening chest/abdominal/pelvic (body) CT scan.
  • Symptomatic ventricular tachyarrhythmia complicating the index myocardial infarction.
  • Individuals who are not fluent in English.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00893360

Locations
United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287-6568
Sponsors and Collaborators
Cedars-Sinai Medical Center
Johns Hopkins University
The EMMES Corporation
Investigators
Principal Investigator: Eduardo Marban, MD, PhD The Heart Institute, Cedars-Sinai Medical Center
  More Information

No publications provided by Cedars-Sinai Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Eduardo Marban, MD, PhD, Director, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT00893360     History of Changes
Other Study ID Numbers: IND 13930, U54HL081028
Study First Received: May 5, 2009
Last Updated: February 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Cedars-Sinai Medical Center:
Adult Stem cells
Cardiosphere derived stem cells
Myocardial infarction

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ventricular Dysfunction, Left
Ventricular Dysfunction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on April 17, 2014