Mesenchymal Stromal Cells for Infants With Congenital Heart Disease (MedCaP)

Phase 1

Active, not recruiting

• Conditions: Congenital Heart Disease (CHD)
• Interventions: Biological: BM-MSC

• Registration Number: NCT04236479
• Lead Sponsor: Catherine Bollard

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.

Study Timeline

• Study First Submitted: 2020-01-15
• Study First Submitted QC: 2020-01-17
• Study First Posted: 2020-01-22
• Study Start: 2020-07-29
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-19
• Last Update Posted: 2023-09-21
• Primary Completion: 2024-09
• Study Completion: 2025-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 17

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bone marrow-derived mesenchymal stromal cell (BM-MSC)	BM-MSC	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.

Primary Outcome Measures

Name	Time	Method
Number of subjects who experience serious adverse events, adverse events, and/or early treatment discontinuations.	45 days following the MSC administration	Dose Limiting Toxicity is attributable to the MSC administration.

Secondary Outcome Measures

Name	Time	Method
Actual magnitude of differences in neuroimaging and neurodevelopmental variables will be measured after MSC delivery.	18 months	Secondary objective will be measured by using the Pediatric Cardiac Critical Care Consortium (PC4) registry system.

Trial Locations

Locations (1)

Children's National Health System; 🇺🇸 Washington, District of Columbia, United States