“Scipio” is best known as the name of the masterful Roman general, Scipio Africanus, who defeated Hannibal during the Second Punic War. Thanks to researchers at the University of Louisville and Brigham and Women’s Hospital, he may soon have to share his nominal glory with an ongoing clinical trial.
The phase 1 study, “Cardiac Stem Cell Infusion in Patients with Ischemic cardiOmyopathy” (SCIPIO), set out to do something perhaps even more impressive than beating the Carthaginians. SCIPIO was the first in-human trial to assess whether cardiac stem cells (CSCs) can restore heart function in patients suffering from post-myocardial-infarction heart failure. The CSCs were isolated and expanded from a 1 gram atrial tissue sample taken from each patient during their coronary artery bypass. Three to four months later, about one million CSCs were transplanted into each patient’s heart – the advantage of this design is the minimized risk of rejection due to the autologous source of the cells.
Over the following year, the patients’ left ventricular (LV) cardiac functions and their infarct sizes were assessed using echocardiography and MRI. The results of the study are nicely summarized in this commentary from The Lancet:
The results from SCIPIO raise new optimism because the study is based on rigorous quality standards and the reported benefits are of an unexpected magnitude. Patients were carefully characterised before their controlled allocation to cardiac cell therapy or control 4 months after initial coronary artery bypass surgery when there was a stable decrease in left ventricular function. Cardiac resident stem cells were thoroughly analysed for their phenotype and regenerative potential. Left ventricular function was assessed on the basis of objective and subjective measures by use of two different imaging modalities (three-dimensional echocardiography and MRI), New York Heart Association functional status, and a quality of life questionnaire. There was no change in left ventricular function and functional status in seven control patients. By contrast, 14 of 16 patients who received cardiac stem cells and could be studied by echocardiography had improved left ventricular function and the seven patients who were studied by use of MRI had reduced infarct size. The benefit was surprisingly large, with a 24% relative infarct size reduction and an 8·2% absolute improvement in ejection fraction after 4 months. The benefit not only persisted but was even greater in the eight patients studied after 12 months. Of note, no adverse effects were reported, confirming the excellent safety of cardiac cell treatment.
We corresponded with study author, Dr. John Loughran, about the current status of the SCIPIO trial as well as the applications of the technology:
Shiv Gaglani, Medgadget: The paper concludes, “The data from our study warrant further, larger, phase 2 studies.” What is the current status of the SCIPIO trial?
Dr. Loughran: We have enrolled 20 CSC-treated patients, all of whom have been treated with CSC infusion. The trial is currently closed to enrollment. All patients are followed at serial time points for 2 years. We are working diligently on the creation of an IND application to the FDA for a Phase 2 clinical trial. We hope for this next investigation to be underway within 2 years.
Medgadget: Please comment on the feasibility of, or alternatives to, using autologous CSCs for the broad application of this medical technology?
Dr. Loughran: We have shown, during the course of conducting this trial, that the process of isolation and expansion of this resident stem cell population is safe and feasible. The results of the trial also demonstrate the process of CSC infusion is safe and feasible. The ability to perform this intervention in a larger subset of heart failure patients will require us to include patients that are not solely dependent on surgery for tissue samples. As you may know, the vast majority of heart failure patients do not require surgery. Dr. Anversa’s laboratory demonstrated the ability to isolate and expand CSCs from biopsies taken ex vivo. This will broaden the scope of patients that can be included in CSC investigations.
The breadth of application of this technology concerning the spectrum of cardiovascular disease is currently limited to treatment of ischemic cardiomyopathy. We get many requests for the treatment of non-ischemic cardiomyopathies. Unfortunately, at this time we are not sanctioned to investigate the application of CSC therapy in the setting of other cardiovascular pathologies. There is always the possiblity that, in the future, investigations targeting other disease processes may be the focus of this exciting new treatment strategy.
It’s always encouraging to see basic science work transitioning to the bedside. We look forward to following this study as it progresses into phase 2 and, hopefully, beyond.
Commentary in The Lancet: SCIPIO brings new momentum to cardiac cell therapy
Clinical Trial Description: Cardiac Stem Cell Infusion in Patients With Ischemic CardiOmyopathy (SCIPIO)