Single vs. double intracoronary injection of mesenchymal stromal cell after acute myocardial infarction: the study protocol from a randomized clinical trial: BOOSTER-TAHA7 trial

Abstract

Background Meta-analysis from previous studies have shown that treatment with mesenchymal stromal cell (MCSs) may increase the left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI) by 3.84%, and the effect is greater in those who are not aged and have developed a reduced LVEF. However, it seems that MSC transplantation does its effect through an indirect paracrine effect, and direct differentiation to the cardiomyocytes does not occur. Therefore, it can be hypothesized that this paracrine effect would be augmented if repeated doses of MSC are transplanted. This study is conducted to compare single vs. double injection of MSCs. Methods This is a single-blind, randomized, multicenter trial aiming to determine whether intracoronary infusion of double doses of umbilical cord-derived Wharton’s jelly MSCs (WJ-MSCs) improves LVEF more after AMI compared to single administration. Sixty patients 3 to 7 days after AMI will be enrolled. The patients should be under 65 years old and have a severe impairment in LV function (LVEF < 40%). They will be randomized to three arms receiving single or double doses of intracoronary infusion of WJ-MSCs or placebo. The primary endpoint of this study is assessment of improvement in LVEF at 6-month post intervention as compared to the baseline. Discussion This investigation will help to determine whether infusion of booster (second) dose of intracoronary WJ-MSCs in patients with AMI will contribute to increasing its effect on the improvement of myocardial function. Trial registration Iranian Registry of Clinical Trials (www.IRCT.ir) IRCT20201116049408N1. Registered on November 26 2020

Effect of once versus twice intracoronary injection of allogeneic-derived mesenchymal stromal cells after acute myocardial infarction: BOOSTER-TAHA7 randomized clinical trial

“…An independent Data and Safety and Monitoring Board (DSMB) monitored patient safety during the study. In-depth details regarding the study protocol are available in a previous publication [ 24 ] (Fig. 1 ).…”

“…Qualification was performed according to GMP grade qualification protocols, and viability was assessed with methylene blue before transplantation. More details are provided on the published protocol of study [ 24 ].…”

Effect of Once vs. Twice Intracoronary Injection of Allogeneic-Derived Mesenchymal Stromal Cells after Acute Myocardial Infarction: BOOSTER-TAHA7 Randomized Clinical Trial

“…This is while stem-cell-based therapies go one step further and attempt to reverse the damage through the provision of fresh, functional cells (22). While early studies on this topic were not very promising ( 9), later meta-analyses showed that this therapy might be effective in certain populations (23,25,26,27,28,29,30). Hence, in the present study, we selected patients below 65 with an echocardiographic LVEF <40%, yielding promising results.…”

“…This study had some limitations. Firstly, while we originally planned to conduct a sham procedure as a placebo treatment for the control group (25), this did not receive ethical clearance from our institute.…”

First-in-human pilot trial of combined intracoronary and intravenous mesenchymal stem cell therapy in acute myocardial infarction

“…As a pilot phase one study, it is not possible to draw a solid conclusion regarding the efficacy of UMSC01 transplantation. Nevertheless, another randomized clinical trial is ongoing, which compares single with double IC infusion of umbilical cord-derived Wharton’s jelly MSCs in patients with AMI ( 33 ). The result may provide better understanding of the effect of repeated transplantation of this cell type on myocardial function (LVEF).…”