CArdiosphere-Derived aUtologous Stem CElls to Reverse ventricUlar dySfunction

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.

Timeline

Start

2009-05

Primary completion

2011-08

Completion

2012-02

Outcome

Missed primary endpoint

release “the ALLSTAR six-month data did not demonstrate evidence of scar size improvement with CAP-1002” capricor.com ↗

Publications

• Results 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.
• 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.
• 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.
• 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.

Drugs

Indications