Stem Cell Therapy for Cardiomyopathy

(CATO Trial)

Recruiting at 2 trial locations

Overseen by Roberto Bolli, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Roberto Bolli

Must be taking: Beta blockers, Diuretics

Disqualifiers: Stroke, Pacemaker, Liver dysfunction, others

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a Phase IIA, randomized, double blind, placebo controlled, multicenter study designed to assess the safety, feasibility, and efficacy of umbilical cord derived mesenchymal stromal cells (UC MSCs), administered intravenously (IV) as a single dose or repeated doses, in patients with ischemic cardiomyopathy (ICM).

Will I have to stop taking my current medications?

The trial requires participants to be on stable, maximally tolerated doses of heart failure medications for at least one month before joining. This means you should not stop taking your current medications, but they need to be stable without changes for 30 days.

What data supports the effectiveness of the treatment Umbilical Cord-derived Mesenchymal Stromal Cells (UC-MSCs) for cardiomyopathy?

Research shows that UC-MSCs can improve heart function and repair heart tissue in animal models of heart disease, suggesting they might help in treating cardiomyopathy. These cells have been shown to improve heart function in rat models of heart failure and have regenerative potential in heart conditions. ^{1 2 3 4 5}

Is stem cell therapy using umbilical cord-derived mesenchymal stromal cells (UC-MSCs) safe for humans?

Studies have shown that using umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in humans is generally safe, with no serious adverse effects reported in patients with heart failure or rheumatoid arthritis. ^{1 5 6 7 8}

How is the treatment with Umbilical Cord-derived Mesenchymal Stromal Cells (UC-MSCs) different from other treatments for cardiomyopathy?

This treatment is unique because it uses stem cells from umbilical cords, which are easily accessible and can be expanded in the lab. Unlike other treatments, UC-MSCs are administered intravenously and have shown potential to improve heart function by helping repair heart tissue in experimental models. ^{1 2 3 5 9}

Research Team

Roberto Bolli, MD

Principal Investigator

University of Louisville School of Medicine

Eligibility Criteria

Adults aged 21-85 with heart failure symptoms, documented coronary artery disease, and left ventricular dysfunction are eligible for this trial. They must be on stable heart medications for at least a month and women of childbearing age should use birth control. Exclusions include severe liver issues, certain allergies, recent cancer history, cognitive barriers to consent, or any condition that might interfere with the study.

Inclusion Criteria

I've been on stable heart failure medication for at least a month.

I am willing to use birth control and take a pregnancy test if I can have children.

I am between 21 and 85 years old.

Exclusion Criteria

I have been cancer-free for 5 years, except for treated skin or cervical cancer.

Your kidney function is too low, with a filtration rate less than 35 ml per minute.

I have not had a stroke in the last 3 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive four study product infusions (SPIs) 2 months apart, consisting of either UC MSCs or placebo, infused by the IV route.

8 months

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the fourth SPI, with assessments continuing for 6 months.

6 months

Multiple visits (in-person)

Treatment Details

Interventions

• Umbilical Cord-derived Mesenchymal Stromal Cells (UC-MSCs) (Stem Cell Therapy)

Trial Overview The trial is testing whether injecting umbilical cord-derived mesenchymal stromal cells into patients with ischemic cardiomyopathy can be safe and effective. Participants will receive either one dose or repeated doses intravenously in a randomized double-blind setup against a placebo.

Participant Groups

Group I: single-dose group Experimental Treatment 1 Intervention

One dose of UC-MSCs (100 x 106 cells) will be infused IV at a rate of 2 ml/min for a total of 60 ml over 30 minutes (3.3 million cells/ml/min). This will be followed by three IV infusions of placebo (same volume and rate) 2, 4, and 6 months later.

Group II: repeated-dose group Experimental Treatment 1 Intervention

Four doses of UC-MSCs (100 x 106 cells each) will be given 2 months apart. Each dose will be infused IV at a rate of 2 ml/min for a total of 60 ml over 30 minutes (3.3 million cells/ml/min).

Group III: control group Placebo Group 1 Intervention

Four doses of vehicle (Plasma-Lyte A supplemented with 1% HSA) will be given 2 months apart. Each dose will be infused IV at a rate of 2 ml/min for a total of 60 ml over 30 minutes.

Umbilical Cord-derived Mesenchymal Stromal Cells (UC-MSCs) is already approved in China for the following indications:

Approved in China as UC-MSCs for:

• Type 1 Diabetes
• Ischemic Cardiomyopathy
• Graft Versus Host Disease
• Sepsis
• Inflammatory Bowel Disease
• Cerebral Palsy

Who Is Running the Clinical Trial?

Roberto Bolli

Lead Sponsor

Trials

1

Recruited

60+

University of Miami

Collaborator

Trials

976

Recruited

423,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

University of Texas

Collaborator

Trials

193

Recruited

143,000+

Findings from Research

Transplanting human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) into the heart after a myocardial infarction in rats significantly improved heart function, as shown by a better left ventricular ejection fraction compared to the control group.

The hUC-MSCs not only engrafted into the heart tissue but also partially transformed into heart muscle cells (cardiomyocytes) and promoted new blood vessel formation, indicating their potential for enhancing heart regeneration after injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical cord mesenchymal stromal cells engraft and transdifferentiate into cardiomyocyte-like cells following acute myocardial ischemia⋆. Yigman, Z., Ozdemir, ED., Turan, NN., et al.[2021]

In a rat model of myocardial infarction, chorion-derived mesenchymal stem cells (C-MSCs) significantly improved heart function, as indicated by increased left ventricular ejection fraction (LVEF) and fractional shortening (FS) after 8 weeks compared to control and other stem cell types.

C-MSCs also enhanced capillary density and showed higher expression of cardiac markers (cTnT and α-SA), suggesting they have superior therapeutic potential for heart repair compared to bone marrow-derived (BM-MSCs) and umbilical cord-derived mesenchymal stem cells (UC-MSCs).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chorion-derived perinatal mesenchymal stem cells improve cardiac function and vascular regeneration: Preferential treatment for ischemic heart disease. Park, YS., Park, BW., Choi, H., et al.[2022]

A new enzymatic method for isolating mesenchymal stem cells (MSCs) from umbilical cord (UC) has been developed, allowing for efficient extraction and cryopreservation of a large number of cells from the entire length of the cord, with a yield of 0.65 million MSCs per cm.

The isolated MSCs maintained their characteristic markers and differentiation potential after thawing, indicating that this method preserves their therapeutic properties, making it suitable for umbilical cord banking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation of mesenchymal stem cells using the total length of umbilical cord for transplantation purposes. Tsagias, N., Koliakos, I., Karagiannis, V., et al.[2022]

The intravenous infusion of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in patients with chronic stable heart failure was found to be safe, with no adverse events related to the infusion and no development of alloantibodies.

Patients receiving UC-MSCs showed significant improvements in left ventricular ejection fraction and overall functional status compared to the placebo group, indicating that UC-MSCs can enhance heart function and quality of life in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: A Phase 1/2 Randomized Controlled Trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy]). Bartolucci, J., Verdugo, FJ., González, PL., et al.[2022]

A standardized manufacturing process for human umbilical cord-derived mesenchymal stem cells (UC-MSCs) was established, yielding 1.03-3.78 × 10^8 MSCs per batch while retaining their essential biological properties and safety.

Clinical testing showed no adverse events in two patients treated with UC-MSCs, indicating that banking and using these cells for clinical applications is both feasible and safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Banking human umbilical cord-derived mesenchymal stromal cells for clinical use. Gong, W., Han, Z., Zhao, H., et al.[2022]

References

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

Human umbilical cord-derived stem cell sheets improve left ventricular function in rat models of ischemic heart failure. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Umbilical cord mesenchymal stromal cells engraft and transdifferentiate into cardiomyocyte-like cells following acute myocardial ischemia⋆. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Chorion-derived perinatal mesenchymal stem cells improve cardiac function and vascular regeneration: Preferential treatment for ischemic heart disease. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Isolation of mesenchymal stem cells using the total length of umbilical cord for transplantation purposes. [2022]

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

Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: A Phase 1/2 Randomized Controlled Trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy]). [2022]

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

Banking human umbilical cord-derived mesenchymal stromal cells for clinical use. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Role of VEGF-A in angiogenesis promoted by umbilical cord-derived mesenchymal stromal/stem cells: in vitro study. [2022]

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

Human umbilical cord mesenchymal stem cell therapy for patients with active rheumatoid arthritis: safety and efficacy. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats. [2022]