Stem Cell Therapy for Cardiomyopathy

(CATO Trial)

Recruiting at 2 trial locations

Overseen By Michelle Unseld, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Roberto Bolli

Must be taking: Beta blockers, Diuretics

Disqualifiers: Stroke, Pacemaker, Liver dysfunction, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 8 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using stem cells from umbilical cords to help people with ischemic cardiomyopathy, a condition where the heart struggles to pump blood due to blocked arteries. The study will determine if these stem cells, known as Umbilical Cord-derived Mesenchymal Stromal Cells (UC-MSCs), can be safely and effectively used to improve heart function. Participants will be divided into groups: one will receive multiple doses of stem cells, another will receive a single dose, and a third will receive a placebo. This trial may suit adults diagnosed with heart failure, who have a history of blocked arteries, and whose heart damage affects daily life. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in heart failure treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using cells from umbilical cords, known as UC-MSCs, is generally safe for people. Studies have found that administering these cells through an IV drip is well-tolerated by patients with stable heart failure, with no serious side effects reported. Another study found that UC-MSCs are safe and may improve heart health, such as enhancing heart function.

These cells treat heart conditions by reducing inflammation and supporting the growth of new blood vessels. While researchers continue to study this treatment, evidence so far suggests it is safe for people with certain heart conditions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cardiomyopathy?

Researchers are excited about using Umbilical Cord-derived Mesenchymal Stromal Cells (UC-MSCs) for treating cardiomyopathy because they offer a new, innovative approach compared to traditional options like medications, lifestyle changes, or surgery. Unlike most treatments that focus on managing symptoms, UC-MSCs have the potential to repair and regenerate heart tissue, addressing the root problem rather than just alleviating symptoms. These cells are administered intravenously, and they harness the natural regenerative power of stem cells, which might lead to improved heart function and outcomes for patients. Additionally, the use of stem cells is promising because they can potentially reduce inflammation and promote healing in ways that current standard therapies cannot.

What evidence suggests that umbilical cord-derived mesenchymal stromal cells might be an effective treatment for ischemic cardiomyopathy?

Research has shown that cells taken from umbilical cords, known as umbilical cord-derived mesenchymal stromal cells (UC-MSCs), may improve heart health in people with ischemic cardiomyopathy, a type of heart disease. In this trial, participants will receive either repeated doses or a single dose of UC-MSCs. Patients who received UC-MSCs in previous studies experienced noticeable improvements in heart function and symptoms. Studies indicate that these cells can potentially boost the heart's pumping ability, measured by left ventricular ejection fraction (LVEF). Both repeated and single doses of UC-MSCs have been linked to better outcomes for people with heart failure. These findings suggest that UC-MSCs could effectively enhance heart health and function. ^{2 6 7 8 9}

Who Is on the Research Team?

Roberto Bolli, MD

Principal Investigator

University of Louisville School of Medicine

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

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

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.

How Is the Trial Designed?

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, European Union, United States 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

Approved in European Union as UC-MSCs for:

• Graft Versus Host Disease
• Sepsis
• Inflammatory Bowel Disease
• Cerebral Palsy

Approved in United States as UC-MSCs for:

• Graft Versus Host Disease
• Sepsis
• Inflammatory Bowel Disease

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+

Published Research Related to This Trial

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]

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]

Intramuscular injection of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) significantly improved cardiac function in a rat model of dilated cardiomyopathy (DCM), as evidenced by increased left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) over a 4-week monitoring period.

hUCMSC treatment not only reduced harmful cardiac biomarkers like BNP and cTNI but also increased beneficial cytokines such as HGF, VEGF, and IGF-1, suggesting that the therapeutic effects may be linked to the regulation of these cytokines and the protection of heart cell structure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats. Mao, C., Hou, X., Wang, B., et al.[2022]

Transplanting human umbilical cord-derived mesenchymal stem cell (UC-MSC) sheets onto the heart significantly improved cardiac function in rat models of chronic ischemic heart failure compared to control groups, as shown by echocardiography after four weeks.

The UC-MSC sheets not only enhanced heart function but also reduced left ventricular remodeling and improved neovascularization, indicating their potential as an effective treatment strategy for heart disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human umbilical cord-derived stem cell sheets improve left ventricular function in rat models of ischemic heart failure. Wu, Y., Zhang, H., Wang, S., et al.[2022]

In a study involving 172 patients with active rheumatoid arthritis (RA), treatment with human umbilical cord mesenchymal stem cells (UC-MSCs) combined with disease-modifying anti-rheumatic drugs (DMARDs) showed significant clinical benefits, including reduced inflammation and improved disease activity scores, with effects lasting 3-6 months after treatment.

No serious adverse effects were reported from the UC-MSCs treatment, indicating a favorable safety profile, and the therapy was associated with an increase in regulatory T cells, which may contribute to its efficacy in managing RA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human umbilical cord mesenchymal stem cell therapy for patients with active rheumatoid arthritis: safety and efficacy. Wang, L., Wang, L., Cong, X., et al.[2022]

UC-MSCs (mesenchymal stromal/stem cells from human umbilical cord) demonstrate pro-angiogenic properties by promoting the proliferation and migration of endothelial cells, even without producing detectable levels of VEGF-A, indicating a VEGF-A-independent mechanism.

The study shows that UC-MSCs can differentiate into endothelial-like cells and form tubular structures, suggesting their potential for therapeutic angiogenesis in cell therapy applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of VEGF-A in angiogenesis promoted by umbilical cord-derived mesenchymal stromal/stem cells: in vitro study. Arutyunyan, I., Fatkhudinov, T., Kananykhina, E., 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11755126/

Umbilical cord-derived mesenchymal stromal cells Patients receiving UC-MSC treatment exhibited significant improvements in LVEF, cardiac function class, and Minnesota Living with Heart Failure ...

2. ahajournals.org ahajournals.org/doi/10.1161/circresaha.117.310712

Safety and Efficacy of the Intravenous Infusion of Umbilical ... Umbilical cord–derived mesenchymal stem cells (UC-MSCs) possess a superior migration capacity compared with marrow–derived mesenchymal stem cells (BM-MSCs).

3. sciencedirect.com sciencedirect.com/science/article/pii/S1465324924000896

Repeated intravenous doses of human umbilical cord ... The administration of repeated intravenous infusion of UC-MSCs in ELGANs at a high risk of developing BPD was feasible and safe in the short- and mid-term ...

4. cells4life.com cells4life.com/us/2024/08/umbilical-cord-stem-cells-trialed-for-heart-failure-treatment/

Umbilical Cord Stem Cells Trialed for Heart Failure ... A first-of-its-kind trial is investigating whether a therapy using umbilical cord stem cells could improve heart failure treatment outcomes.

5. stemcellres.biomedcentral.com stemcellres.biomedcentral.com/articles/10.1186/s13287-021-02222-y

Human umbilical cord-derived mesenchymal stem/stromal ... Umbilical cord-derived mesenchymal stem/stromal cells (UC-MSCs) emerge as a perspective for therapeutic use in immune and inflammatory diseases.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10686683/

The Safety and Efficacy of Human Umbilical Cord-Derived ... Our findings indicate that HUC-MSC transplantation can improve EF but has no meaningful effect on readmission or mortality rates.

7. wjgnet.com wjgnet.com/1949-8462/full/v17/i1/101153.htm

Umbilical cord-derived mesenchymal stromal cells Umbilical cord-derived MSCs (UC-MSCs) have demonstrated superior clinical potential compared to traditional bone marrow-derived MSCs.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38033439/

The Safety and Efficacy of Human Umbilical Cord-Derived ... The Safety and Efficacy of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Patients With Heart Failure and Myocardial Infarction: A Meta- ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1465324919304621

Umbilical cord–derived mesenchymal stromal cells in ... In the past decade, they have been adopted in cardiovascular disease and have shown promising results mainly due to their pro-angiogenic and anti-inflammatory ...