TIME, POSEIDON, ALCADIA, SCIPIO and Swiss Ami: Trials Offer New Insights Into Cell Therapies for Treating CVD

Two separate trials released on Nov. 5 as part of AHA 2012 and published simultaneously in the Journal of the American Medical Association offer continued insights into ways stem cells and bone marrow cells can be used to treat cardiovascular disease (CVD).

In the TIME trial, intracoronary autologous bone marrow mononuclear cell (BMC) treatment was found to have no overall effect on global and regional left ventricular (LV) function during the six months following myocardial infarction (MI). "To our knowledge, TIME is the first cardiovascular cell therapy trial that was specifically designed to determine whether the timing of BMC administration after primary PCI influences LV functional recovery," the study investigators said. "There was no overall effect of BMC treatment on this ongoing improvement at six months vs. placebo despite previous supportive clinical data. Additionally, the day of cell delivery did not demonstrate an effect on the recovery of LV function or on LV volumes or infarct size." However, study investigators did note that young patients randomized to BMCs had significant improvement with left ventricular ejection fraction (LVEF) at seven days following the procedure compared with placebo.

Meanwhile, results from the POSEIDON trial indicated that transendocardial injection of allogeneic and autologous mesenchymal stem cells (MSCs) without a placebo control were both associated with low rates of treatment-emergent serious adverse effects, including immunologic reactions, in patients with ischemic cardiomyopathy (ICM). The one-year incidence of serious adverse events was 33.3 percent (n=5) in the allogeneic group and 53.3 percent (n=8) in the autologous group (P=.46). The study also showed that allogeneic and autologous MSCs reduced mean early enhancement defect (EED) by -33.21 percent (95 percent CI, -43.61 percent to -22.81 percent; P<.001) and sphericity index, but did not increase ejection fraction (EF).

"Both MSCs favorably affect cardiac structure and function, patient functional capacity and quality of life," the study investigators said. Looking forward, "these data have implications for cell-based therapy including the possibility of allogeneic MSCs as an ‘off-the-shelf’ therapeutic," they said.

Three other studies were also presented on Nov. 6 at AHA 2012. 

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Results from the ALCADIA trial suggest that transplantation of autologous cardiac-derived stem cells (CSCs) with controlled release of basic fibroblast growth factor (bFGF) is both safe and effective in treating injured human hearts with reconstruction of the post-ischemic environment. Results from the study indicate that the five patients currently enrolled have improved from 3.8±0.4 to 1.4±0.17 (p<0.0001), associated with improved exercise tolerance as evaluated by peak oxygen consumption (VO2) (from 12.2±3.0 percent before hybrid therapy to 16.7±3.6 percent after six months, p=0.037). The loss of LV function in patients was restored to 12.1±4.9 percent of LVEF (MRI; from 22.6±4.5 percent to 34.7±7.9 percent, p=0.028), which was accompanied with improvements in global wall motion (MRI; from 17.0±3.4 percent to 6.6±3.8 percent, p=0.0023), and a tendency toward decreasing infarct size (MRI; from 21.8±4.9 percent to 17.8±4.8 percent, p=0.116).  Meanwhile, study investigators involved in the SCIPIO trial said their findings suggest that infusion of autologous CSCs in patients with ischemic heart failure is safe and that its beneficial effects are sustained and improve over time. 

In the Swiss Acute Myocardial Infraction (AMI) trial, patients with STEMI and LV dysfunction following reperfusion with percutaneous coronary intervention (PCI), intracoronary infusion of bone marrow derived mononuclear cells (BM-MNC) either five to seven days or three to four weeks after AMI, did not see improvement in LV-function at four months. With a baseline LVEF of 37.4 percent, results showed the absolute change in LVEF in four months was -0.4±8.8 percent (mean±SD; p=.74 versus baseline) in the control group, 1.8±8.4 percent (p=0.12 versus baseline) in the early group and 0.8±7.6 percent (p=0.45 versus baseline) in the late group. There was no significant difference seen for the between-group in relation to the secondary endpoints between the control and both therapy groups; however, the mean difference for the between-group was -2.1 percent; 95 percent CI, -5.27 to 0.99; p=0.18 (early vs. control) and -1.2 percent; 95 percent CI, -4.32 to 1.91; p=0.45 (late versus control).

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