Clinical trial NCT04236479: Mesenchymal Stromal Cells for Infants With Congenital Heart Disease (MedCaP)
Official title: Mesenchymal Stromal Cells Delivery Through Cardiopulmonary Bypass in Pediatric Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Congenital Heart Disease (CHD)
Lead sponsor: Children's National Research Institute
Sponsor class: OTHER
First posted: 2020-01-22
Enrollment: 17
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Detailed description: 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

Primary outcomes:
measure: Number of subjects who experience serious adverse events, adverse events, and/or early treatment discontinuations.
timeFrame: 45 days following the MSC administration
Secondary outcomes:
measure: Actual magnitude of differences in neuroimaging and neurodevelopmental variables will be measured after MSC delivery.
timeFrame: 18 months
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's National Health System
state: District of Columbia
Study officials:
affiliation: CNMC
name: Richard Jonas, MD
role: PRINCIPAL_INVESTIGATOR
References: