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

Mesenchymal Stromal Cells Delivery Through Cardiopulmonary Bypass in Pediatric Cardiac Surgery

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

Study Overview

• Status: Active, not recruiting
• Conditions: Congenital Heart Disease (CHD)
• Intervention / Treatment: Biological: BM-MSC

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 Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Nobuyuki Ishibashi, MD; Phone Number: 202-476-2388; Email: NIshibas@childrensnational.org

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 months (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bone marrow-derived mesenchymal stromal cell (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.	Biological: BM-MSC; Allogeneic bone marrow-derived mesenchymal stromal cell (BM-MSC) delivery through 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Catherine Bollard
• Investigators: Principal Investigator: Richard Jonas, MD, CNMC

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2020
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: January 15, 2020
• First Submitted That Met QC Criteria: January 17, 2020
• First Posted (Actual): January 22, 2020

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Heart Defects, Congenital
• Other Study ID Numbers: Pro00011914

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No