Mesenchymal Stromal Cells for Congenital Heart Disease

Overseen By Nobuyuki Ishibashi, MD

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Catherine Bollard

Disqualifiers: Low birth weight, Phenotypic syndrome, Extracardiac anomalies, Previous cardiac surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: Immediate during surgery

17 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

What data supports the effectiveness of the treatment BM-MSC for congenital heart disease?

Research shows that mesenchymal stromal cells (MSCs) from patients with congenital heart disease can help repair heart tissue by promoting blood vessel growth and reducing inflammation. In animal studies, these cells improved heart function and survival, suggesting they could be a promising treatment for heart defects. ^{1 2 3 4 5}

Is it safe to use mesenchymal stromal cells (MSCs) in humans?

Research has shown that using mesenchymal stromal cells (MSCs) in humans, such as in heart conditions, is generally considered safe. For example, a study on patients with coronary artery disease found that injecting these cells into the heart was safe over a three-year follow-up period. ^{1 5 6 7 8}

How is the treatment with BM-MSCs different from other treatments for congenital heart disease?

The treatment using BM-MSCs (bone marrow-derived mesenchymal stromal cells) is unique because it involves using the patient's own cells to repair heart tissue, potentially improving heart function by promoting blood vessel growth and reducing inflammation. This approach is different from traditional treatments that may rely on synthetic materials or medications, as it uses the body's natural healing processes. ^{1 2 3 5 9}

What is the purpose of this trial?

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

Research Team

Richard Jonas, MD

Principal Investigator

CNMC

Eligibility Criteria

This trial is for infants ≤ 3 months old with congenital heart disease needing a two-ventricle repair but no aortic arch reconstruction. Parents must consent. Infants under 2 kg, with syndromes, severe extracardiac anomalies, prior heart surgery or hypoxic events, or at risk from study participation are excluded.

Inclusion Criteria

I am scheduled for a heart surgery to fix defects without needing to repair the aortic arch.

My child is 3 months old or younger.

My parent or guardian can legally agree to my participation.

Exclusion Criteria

Your test results show that you may have a higher chance of having problems if you join the study.

My birth weight was under 2.0 kg.

You have had a serious lack of oxygen in the past.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Allogeneic BM-MSC delivery through cardiopulmonary bypass during pediatric cardiac surgery with dose-escalation to determine safety and feasibility

Immediate during surgery

1 visit (in-person, during surgery)

Initial Follow-up

Participants are monitored for safety and adverse events following MSC administration

45 days

Long-term Follow-up

Monitoring of neurodevelopmental outcomes and other clinical measures until 18 months of age

18 months

Treatment Details

Interventions

• BM-MSC

Trial Overview The MedCaP trial tests the safety and feasibility of delivering allogeneic bone marrow-derived mesenchymal stromal cells (BM-MSC) to infants with CHD during cardiopulmonary bypass in their first six months.

Participant Groups

Group I: Bone marrow-derived mesenchymal stromal cell (BM-MSC) Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Catherine Bollard

Lead Sponsor

Trials

13

Recruited

290+

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Mesenchymal Stromal Cells from Patients with Cyanotic Congenital Heart Disease are Optimal Candidate for Cardiac Tissue Engineering. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Mesenchymal Stem/Stromal Cells from Discarded Neonatal Sternal Tissue: In Vitro Characterization and Angiogenic Properties. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Amniotic Fluid Mesenchymal Stromal Cells Derived from Fetuses with Isolated Cardiac Defects Exhibit Decreased Proliferation and Cardiomyogenic Potential. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Human Neonatal Thymus Mesenchymal Stem/Stromal Cells and Chronic Right Ventricle Pressure Overload. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Defining the optimal historical control group for a phase 1 trial of mesenchymal stromal cell delivery through cardiopulmonary bypass in neonates and infants. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Autotransplantation of mesenchymal stromal cells from bone-marrow to heart in patients with severe stable coronary artery disease and refractory angina--final 3-year follow-up. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Aging adversely impacts biological properties of human bone marrow-derived mesenchymal stem cells: implications for tissue engineering heart valve construction. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Bone marrow mesenchymal stem cells transfer in patients with ST-segment elevation myocardial infarction: single-blind, multicenter, randomized controlled trial. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. [2023]