CArdiosphere-Derived aUtologous Stem CElls to Reverse ventricUlar dySfunction

NCT00893360 | Completed Phase 1 DMC

• 2 other identifiers: IND 13930U54HL081028
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Recent Myocardial Infarction; Ventricular Dysfunction

Keywords

Adult Stem cells; Cardiosphere derived stem cells; Myocardial infarction

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months

Secondary Outcomes (1)

• 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.

  12 months

Study Arms (3)

Cardiac Stem Cell Treatment - Group 1

EXPERIMENTAL

Autologous stem cell infusion of 12.5 MIL CDCs via intracoronary infusion.

Biological: Autologous stem cell infusion

Cardiac Stem Cell Treatment -Group 2

EXPERIMENTAL

Autologous stem cell infusion of 25 MIL CDCs via intracoronary infusion.

Biological: Autologous stem cell infusion

Observation (Control Group)

NO INTERVENTION

Observation of myocardial recovery after usual medical management.

Interventions

Autologous stem cell infusion BIOLOGICAL

Subjects will receive 12.5 million of autologous (grown from your own heart muscle specimen) cardiosphere-derived stem cells via intracoronary delivery.

Cardiac Stem Cell Treatment - Group 1

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Johns Hopkins University: collaborator
• The Emmes Company, LLC: collaborator

Study Sites (2)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287-6568, United States

Location

Related Publications (4)

• Makkar RR, Smith RR, Cheng K, Malliaras K, Thomson LE, Berman D, Czer LS, Marban L, Mendizabal A, Johnston PV, Russell SD, Schuleri KH, Lardo AC, Gerstenblith G, Marban E. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet. 2012 Mar 10;379(9819):895-904. doi: 10.1016/S0140-6736(12)60195-0. Epub 2012 Feb 14.

  PMID: 22336189 RESULT

• Malliaras K, Makkar RR, Smith RR, Cheng K, Wu E, Bonow RO, Marban L, Mendizabal A, Cingolani E, Johnston PV, Gerstenblith G, Schuleri KH, Lardo AC, Marban E. Intracoronary cardiosphere-derived cells after myocardial infarction: evidence of therapeutic regeneration in the final 1-year results of the CADUCEUS trial (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction). J Am Coll Cardiol. 2014 Jan 21;63(2):110-22. doi: 10.1016/j.jacc.2013.08.724. Epub 2013 Sep 11.

  PMID: 24036024 DERIVED

• Wang S, Li R, Fettermann A, Li Z, Qian Y, Liu Y, Wang X, Zhou A, Mo JQ, Yang L, Jiang P, Taschner A, Rossmanith W, Guan MX. Maternally inherited essential hypertension is associated with the novel 4263A>G mutation in the mitochondrial tRNAIle gene in a large Han Chinese family. Circ Res. 2011 Apr 1;108(7):862-70. doi: 10.1161/CIRCRESAHA.110.231811.

  PMID: 21454794 DERIVED

• D'Amario D, Fiorini C, Campbell PM, Goichberg P, Sanada F, Zheng H, Hosoda T, Rota M, Connell JM, Gallegos RP, Welt FG, Givertz MM, Mitchell RN, Leri A, Kajstura J, Pfeffer MA, Anversa P. Functionally competent cardiac stem cells can be isolated from endomyocardial biopsies of patients with advanced cardiomyopathies. Circ Res. 2011 Apr 1;108(7):857-61. doi: 10.1161/CIRCRESAHA.111.241380. Epub 2011 Feb 17.

  PMID: 21330601 DERIVED

MeSH Terms

Conditions

Ventricular Dysfunction; Myocardial Infarction

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Myocardial Ischemia; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Study Officials

• Eduardo Marban, MD, PhD

  The Heart Institute, Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: May 5, 2009
• First Posted: May 6, 2009
• Study Start: May 1, 2009
• Primary Completion: August 1, 2011
• Study Completion: February 1, 2012
• Last Updated: February 12, 2014

Record last verified: 2012-02

Locations

US (2)