mesenchymal stromal cells for infants with congenital heart disease (medcap)

Conditions: Congenital Heart Disease (CHD)

Summary: the proposed study will be a prospective, open-label, single-center, safety and feasibility phase 1 trial of allogeneic bone marrow-derived mesenchymal stromal cell (bm-msc) delivery though cardiopulmonary bypass (cpb) using a homogeneous population of infants with congenital heart disease (chd) who will be undergoing a two-ventricle repair within the first six months of life

this study is a prospective, open-label, single-center, safety and feasibility phase 1 trial of allogeneic bone marrow-derived mesenchymal stromal cell (bm-msc) delivery though cardiopulmonary bypass (cpb) using a homogeneous population of infants with congenital heart disease (chd) who will be undergoing a two-ventricle repair within the first six months of life. the dose-escalation methods with a modified continual reassessment at the five dose levels (1x10\^6, 10x10\^6, 20x10\^6, 40x10\^6, 80x10\^6, cells/kg) will be performed to determine safety and feasibility of allogeneic bm-msc infusion during pediatric cardiac surgery and the maximum tolerated dose in infants with chd. in addition to the primary objective of assessing the safety and feasibility of bm-msc delivery through cpb, our secondary objectives are designed to develop biological signature measures and clinical outcome measures feasible for use in larger efficacy and effectiveness trials with a particular focus on neurodevelopmental outcome and early postoperative course after bm-msc treatment. we will determine actual magnitude of differences in neuroimaging and neurodevelopmental variables and postoperative inflammatory and pathophysiological variables after bm-msc delivery in infants with chd. enrollment, follow-up, and analysis are planned to occur over 36 months for the treatment and initial follow-up portions of the study. long-term follow-up until 18 months of age will be subsequently reported.

Eligibility criteria:
inclusion criteria: * neonatal and young infantile patients who are ≤ 3 months of age * scheduled to undergo reparative two-ventricle repair for congenital heart defects without aortic arch reconstruction, including the following: a. d-transposition of the great arteries (d-tga) group: i. d-tga with intact ventricular septum (d-tga, ivs) ii. d-tga with ventricular septal defect (d-tga, vsd) b. ventricular septal defect (vsd) group: i. vsd without aortic arch obstruction (aao) ii. complete common atrioventricular canal defect (cavc) c. tetralogy of fallot (tof) group: i. tetralogy of fallot (tof) ii. tetralogy of fallot with pulmonary atresia (tof,pa) iii. truncus arteriosus (ta) iv. double outlet right ventricle (dorv) * scheduled surgery at or before three months of age. * parent/guardian capable of providing informed consent. exclusion criteria: * birth weight less than 2.0 kg * recognizable phenotypic syndrome * associated extracardiac anomalies of greater than minor severity * previous cardiac surgery * associated cardiovascular anomalies requiring aortic arch reconstruction and/or additional open cardiac surgical procedures in infancy * prior severe hypoxic event * significant screening test values that place subjects at increased risk of complications from participation in the study