Studies Explore Safety and Efficacy of Stem Cell Therapies
Safety and efficacy of stem cell therapies were explored in two separate trials presented on Aug. 28 during ESC Congress 2016 in Rome.
In the CHART-1 Trial, cardiopoietic cell therapy did not significantly improve the primary outcome over a sham procedure among patients with congestive heart failure. However, a subgroup analysis of patients with severe heart enlargement at baseline (left ventricular end-diastolic volumes between 200 and 370 mL) suggests a positive effect of the stem cell treatment.
The trial randomized 271 patients with symptomatic ischemic heart failure from 39 hospital centers in Europe and Israel to either a sham procedure (n=151) or cardiopoietic cells (n=120). At 39 weeks there was no significant difference between groups for the primary efficacy endpoint – a composite of all-cause mortality, worsening heart failure events, Minnesota Living with Heart Failure Questionnaire total score, six-minute walk distance, left ventricular end-systolic volume and ejection fraction.
Although the findings were neutral in the overall patient population, an exploratory analysis identified a sub-group of patients who may benefit from cardiopoietic cell therapy, according to principal co-investigator Jozef Bartunek, MD, PhD. “Within a well-defined patient population, based on baseline heart failure severity, this therapy showed benefit,” he said. “Lessons learned from CHART-1 will now provide the foundation for the design of the ensuing CHART-2 trial which will target these patients.”
Meanwhile, a single dose of mesenchymal stem cells delivered intravenously to patients with chronic non-ischemic cardiomyopathy was not associated with significant cardiac structural or functional improvements, but did result in several clinically relevant benefits, according to results from a phase II-a randomized trial.
The single-blind, placebo-controlled, crossover, multicenter study randomized patients with non-ischemic cardiomyopathy and left ventricular ejection fraction (LVEF) ≤40 percent to receive intravenous itMSC therapy (n=10) or placebo (n=12) for 90 days and then cross over to the other treatment. Stem cells were donated by a health volunteer and grown under hypoxic conditions from the moment of extraction.
Results at 90-days post itMSC infusion indicated no major differences in primary safety endpoints of all-cause mortality, all-cause hospitalization and adverse events. Additionally, there was no difference in the secondary endpoints of cardiac remodeling (LVEF and ventricular volumes), assessed by cardiac magnetic resonance imaging, during that same period. However, treatment with itMSCs did show improved health status and functional capacity – which were also pre-specified secondary endpoints.
Specifically, compared to placebo, itMSC therapy resulted in statistically significant improvements in six-minute walk test (an estimated 36m more than placebo, p=0.02) as well as greater improvements in Kansas City Cardiomyopathy Questionnaire scores (clinical summary score +5.22, p=0.02, and functional status scores +5.65, p=0.06) at 90-days post-infusion.
Additionally, itMSCs infusion resulted in significant alterations in several inflammatory cells, “supporting the immunomodulatory and anti-inflammatory mechanisms of itMSCs,” according to lead investigator Javed Butler MD, FACC.
“To our knowledge, this trial represents the first experience with intravenously administered itMSCs in patients with any type of chronic cardiomyopathy,” Butler said. “Further studies should explore the efficacy of serial dosing to produce more sustained immunomodulatory effects and thereby perhaps facilitate improvement in left ventricular structure and function, and in clinical outcomes.”
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