Mesenchymal Stromal Cells for Congenital Heart Disease

Not currently recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment using bone marrow-derived mesenchymal stromal cells, which can help repair tissue, for infants with certain types of congenital heart disease. The goal is to determine the safety and practicality of using these cells during heart surgery to improve outcomes. This trial targets infants under three months old who are scheduled for a two-ventricle heart repair without requiring aortic arch reconstruction. Families with infants in this situation might consider participating. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using bone marrow-derived cells, known as mesenchymal stromal cells (BM-MSCs), is generally safe for people. In studies with these cells, none of the 50 reported events were linked to the cells themselves. Researchers safely increased the dose to the planned maximum without issues. Additionally, over ten years of research in large animals supports the safety and feasibility of using these cells.

These findings suggest that the treatment is well-tolerated. However, since this trial is in an early stage, the complete safety profile in humans is still under investigation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for congenital heart disease, which often involve surgical repair and medication to manage symptoms, the investigational treatment using bone marrow-derived mesenchymal stromal cells (BM-MSC) offers a novel approach. Researchers are excited about BM-MSC because these cells have the potential to promote healing and reduce inflammation through their unique regenerative properties. Additionally, BM-MSCs are administered during pediatric cardiac surgery, which is a new delivery method that might enhance recovery and improve outcomes for infants with this condition. This innovative approach could pave the way for more advanced therapies in the future.

What evidence suggests that BM-MSC might be an effective treatment for congenital heart disease?

Research has shown that certain cells, called mesenchymal stromal cells (MSCs), might help with heart problems. In some people with heart failure, MSCs improved how well the heart pumps blood. In this trial, participants will receive bone marrow-derived mesenchymal stromal cells (BM-MSCs) during surgery for congenital heart disease (CHD). Early studies suggest that using MSCs during surgery could provide extra benefits, specifically aiding the heart's healing after surgery. While more research is needed, these early results are promising for using MSCs to treat CHD. ^{1 5 6 7 8}

Who Is on the Research Team?

Richard Jonas, MD

Principal Investigator

CNMC

Are You a Good Fit for This Trial?

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.

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

My birth weight was under 2.0 kg.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4762023/

The Emergence Of Stem Cell Therapy For Congenital ... Among these patients, LV ejection fraction improved 20–23% from baseline values in patients with dilated cardiomyopathy ranging from 4 months to 17 years of age ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11227704/

a meta-analysis of randomized controlled trials - PMC There is no clear evidence on the comparative effectiveness of bone-marrow mononuclear cell (BMMNC) vs. mesenchymal stromal cell (MSC) stem ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0142961219306738

Mesenchymal Stromal Cells from Patients with Cyanotic ... The current study is the first report, to our knowledge, that focuses on the therapeutic efficacy of MSCs from C-CHD donors in the tissue engineering field.

4. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-05352-y

Efficacy of mesenchymal stem cell transplantation on major ... Transplantation of MSCs for ischemic or dilated heart failure patients may reduce all-cause mortality and improve clinical condition.

5. ahajournals.org ahajournals.org/doi/10.1161/circulationaha.117.029607

Stem Cell Therapy for Congenital Heart Disease | Circulation It seems that stem cell delivery to the diseased heart as an adjunct to surgical palliation may provide some benefits over surgery alone.

6. stemcellres.biomedcentral.com stemcellres.biomedcentral.com/articles/10.1186/s13287-020-01764-x

Safety and efficacy of cell therapies in pediatric heart disease In this review, bone marrow-derived MSCs demonstrated similar effects on EF to cardiac stem cells (9.3%), yet these results should be ...

7. ahajournals.org ahajournals.org/doi/10.1161/circ.150.suppl_1.4142562?doi=10.1161/circ.150.suppl_1.4142562

Abstract 4142562: Mesenchymal Stromal Cell Delivery ... Among 50 total events, there were no adverse events related to BM-MSCs. The BM-MSC dose was successfully escalated to the planned MTD (40x10^6 ...

8. withpower.com withpower.com/trial/phase-1-heart-diseases-6-2020-3fb43

Mesenchymal Stromal Cells for Congenital Heart Disease 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 ...