Single or Repeated Intravenous Administration of umbiliCAl Cord Mesenchymal sTrOmal Cells in Ischemic Cardiomyopathy (CATO)

University of Louisville - 18642 / CATO Study, Single or Repeated Intravenous Administration of umbiliCAl Cord Mesenchymal sTrOmal Cells in Ischemic Cardiomyopathy

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, stem cells), administered intravenously (IV) as a single dose or repeated doses, in patients with ischemic cardiomyopathy (ICM).

Study Overview

• Status: Recruiting
• Conditions: Ischemic Heart Disease
• Intervention / Treatment: Biological: umbilical cord-derived mesenchymal stromal cells (UC-MSCs)

Detailed Description

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, stem cells), administered intravenously (IV) as a single dose or repeated doses, in patients with ischemic cardiomyopathy (ICM) (see summary in Figure 1).

A total of 60 participants will be assigned in a random fashion to three groups on a 1:1:1 basis: control, single dose, and repeated doses. All patients will receive four study product infusions (SPIs) 2 months apart. SPIs (performed in a double blind fashion) will consist of either UC MSCs (stem cells) or placebo (based on randomization), infused by the IV route. Patients in the control group will receive four doses of placebo. Patients in the single dose group will receive one dose of UC MSCs (stem cells) followed by three doses of placebo. Patients in the repeated dose group will receive four doses of UC MSCs (stem cells). A dose of UC MSCs will consist of 100 million cells suspended in 60 mL, infused at a rate of 2 mL/min. A dose of placebo will consist of an equivalent volume of Plasma Lyte A supplemented with 1% human serum albumin (HSA). After each SPI, patients will be monitored for a minimum of 2 hours and then examined at 1 week and 2 months. After the fourth SPI, patients will be followed for 6 months to complete all safety and efficacy assessments.

The UC MSCs will be derived from UC tissue obtained from a healthy pregnant woman at the time of caesarean delivery. The cells will be manufactured at the Interdisciplinary Stem Cell Institute at the University of Miami, Miller School of Medicine and then shipped to the Site for administration.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Roberto Bolli, MD; Phone Number: 502-608-5426; Email: rbolli@louisville.edu
• Study Contact Backup: Name: Michelle Unseld, RN; Phone Number: 502-540-3423; Email: michelle.unseld@louisville.edu

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami Miller School of Medicine
      • Contact: Joshua Hare, MD; Phone Number: 305-243-1152; Email: JHare@med.miami.edu
      • Contact: Ana Garzon; Phone Number: 305-243-1152; Email: amg9460@med.miami.edu
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • University of Louisville School of Medicine, Institute of Molecular Cardiology
      • Principal Investigator: Roberto Bolli, MD
      • Contact: Roberto Bolli, MD; Phone Number: 502-608-5426; Email: rbolli@louisville.edu
      • Contact: Michelle Unseld, RN; Phone Number: 502-540-3423; Email: michelle.unseld@louisville.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The Texas Heart Institute Houston Texas
      • Contact: Emerson Perin, MD; Phone Number: 832-355-9173; Email: eperin@texasheart.org
      • Contact: Nicole Piece; Phone Number: 832-355-9173; Email: npiece@texasheart.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be ≥ 21 and ≤ 85 years of age.
2. Have documented CAD (> 70% lesion in at least 1 epicardial vessel) with evidence of myocardial injury, LV dysfunction, and clinical evidence of HF.
3. Have a "detectable" area of myocardial injury defined as ≥ 5% LV involvement (infarct volume) and any subendocardial involvement by MRI.
4. Have an EF ≤ 40% by MRI.
5. Be receiving guideline driven medical therapy for HF (beta blockers, diuretics, ACE inhibitors or ARBs, or ARNIs, aldosterone antagonists, hydralazine isosorbide, sodium-glucose transporter 2 inhibitors) ) at stable, maximally tolerated doses for ≥ 1 month prior to consent. "Stable" is defined as stable dose with no changes for 30 days after last dose adjustment. For beta blockade "stable" is defined as no greater than a 50% reduction in dose or no more than a 100% increase in dose.
6. Have NYHA class I, II or III symptoms of HF (see Appendix A)
7. If a female of childbearing potential, be willing to use one form of birth control for the duration of the study and undergo a serum pregnancy test at baseline and within 36 hours prior to infusion

Exclusion Criteria:

1. Indication for standard of care surgery (including valve surgery, placement of left ventricular assist device, or imminent heart transplantation), coronary artery bypass grafting (CABG) procedure, and/or percutaneous coronary intervention (PCI) for the treatment of ischemic and/or valvular heart disease. Subjects who require or undergo PCI should undergo these procedures a minimum of 3 months in advance of randomization. Subjects who require or undergo CABG should undergo these procedures a minimum of 3 months in advance of randomization. In addition, subjects who develop a need for revascularization following enrollment should undergo revascularization without delay. Indication for imminent heart transplantation is defined as a high likelihood of transplant prior to collection of the 12 month study endpoint. Candidates cannot be UNOS 1A or 1B, and they must have documented a low probability of being transplanted.
2. Severe valvular (any valve) insufficiency and/or regurgitation within 12 months of consent
3. History of ischemic or hemorrhagic stroke within 90 days of consent

4. Presence of a pacemaker and/or implantable cardiac device (ICD) generator with any of the following limitations/conditions:

   • manufactured before the year 2000
   • leads implanted < 6 weeks prior to consent
   • non transvenous epicardial or abandoned leads
   • subcutaneous ICDs (if not MRI compatible)
   • leadless pacemakers
   • any other condition that, in the judgment of device trained staff, would deem an MRI contraindicated
5. Pacemaker dependence with an ICD (Note: pacemaker dependent candidates without an ICD are not excluded)
6. A cardiac resynchronization therapy (CRT) device implanted less than 3 months prior to consent.
7. Other MRI contraindications (e.g. patient body habitus incompatible with MRI)
8. An appropriate ICD firing or anti tachycardia pacing (ATP) for ventricular fibrillation or ventricular tachycardia within 30 days of consent
9. Ventricular tachycardia ≥ 20 consecutive beats without an ICD within 3 months of consent, or symptomatic Mobitz II or higher degree atrioventricular block without a functioning pacemaker within 3 months of consent
10. Evidence of active myocarditis
11. Baseline glomerular filtration rate (eGFR) < 35 ml/min/1.73m2
12. Blood glucose levels (HbA1c) >10%
13. Hematologic abnormality evidenced by hematocrit < 25%, white blood cell < 2,500/ul or platelet count < 100,000/ul
14. Liver dysfunction evidenced by enzymes (AST and ALT) ˃ 3 times the ULN.
15. HIV and/or active HBV or HCV
16. Known history of anaphylactic reaction to penicillin or streptomycin
17. Received gene or cell based therapy from any source within the previous 12 months.
18. History of malignancy within 2 years (i.e., subjects with prior malignancy must be disease free for 2 years), excluding basal cell carcinoma and cervical carcinoma in situ which have been definitively treated.
19. Condition that limits lifespan to < 1 year
20. History of drug abuse (illegal "street" drugs except marijuana, or prescription medications not being used appropriately for a pre-existing medical condition) or alcohol abuse (≥ 5 drinks/day for ˃ 3 months), or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 12 months.
21. Participation in an investigational therapeutic or device trial within 30 days of consent
22. Cognitive or language barriers that prohibit obtaining informed consent or any study elements
23. Pregnancy or lactation or plans to become pregnant in the next 12 months.
24. Any other condition that, in the judgment of the Investigator or Sponsor, would impair enrollment, study product administration, or follow up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: control group; 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.	Biological: umbilical cord-derived mesenchymal stromal cells (UC-MSCs); The study product will consist of 100 million UC-MSCs suspended in a final volume of 60 ml given at a rate of 3.3 million cells/min. The product will be infused into vein via intravenous line placed in the arm.
Experimental: single-dose group; 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.	Biological: umbilical cord-derived mesenchymal stromal cells (UC-MSCs); The study product will consist of 100 million UC-MSCs suspended in a final volume of 60 ml given at a rate of 3.3 million cells/min. The product will be infused into vein via intravenous line placed in the arm.
Experimental: repeated-dose group; 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).	Biological: umbilical cord-derived mesenchymal stromal cells (UC-MSCs); The study product will consist of 100 million UC-MSCs suspended in a final volume of 60 ml given at a rate of 3.3 million cells/min. The product will be infused into vein via intravenous line placed in the arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in LVEF (D LVEF) between baseline (M0) and 12 months after the first study product infusion (SPI) (M12)	Change in left ventricular ejection fraction as assessed via cardiac MRI. Units: %	Baseline, 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in LV end-systolic volume index (ESVI)	Change in left ventricular end systolic index (LVESVI) as assessed via cardiac MRI. Units: ml/m2	Baseline, 12 months
Change in LV end-diastolic volume index (EDVI)	Change in left ventricular end diastolic index (LVEDVI) as assessed via cardiac MRI. Units: ml/m2	Baseline, 12 months
Change in LV end-diastolic wall thickness	Change in LV end-diastolic wall thickness as assessed via cardiac MRI. Units: mm	Baseline, 12 months
Change in LV wall thickening	Change in LV wall thickening as assessed via cardiac MRI. Units: mm	Baseline, 12 months
Change in LV sphericity index	Change in LV sphericity index as assessed via cardiac MRI. Units: Index score Sphericity index is the ratio of the long and short axis measurements of the left ventricle.	Baseline, 12 months
Change in global and regional strain (tagged MRI): global and 16-segment values for peak circumferential strain, global and segmental longitudinal strain	Change in global and regional strain as assessed via cardiac MRI. Units: %	Baseline, 12 months
Change in scar mass (in grams)	Change in scar mass (in grams) as assessed via delayed gadolinium enhancement MRI. Units: grams	Baseline, 12 months
Change in scar mass (as %LV)	Change in scar mass (as %LV) as assessed via delayed gadolinium enhancement MRI. Units: %	Baseline, 12 months
Change in VO2 max (treadmill test)	Change in maximal oxygen consumption (peak VO2) as assessed via treadmill. Units: mL/kg/min	Baseline, month 8, month 12
Change in exercise tolerance (six-minute walk test)	Change in exercise tolerance as assessed as the distance covered via the six-minute walk test. Units: meters	Baseline, month 8, month 12
Change in New York Heart Association class	NYHA Classifications of heart failure are as follows: Class I (no limitations); Class II (mild symptoms); Class III (marked limitations); Class IV (Severe limitations). Units: score on a scale	Baseline, month 2,4,6,8, & 12
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score	KCCQ is a 12-item questionnaire in which scores are scaled from 0 to 100 and summarized in ranges to represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent. Units: score on a scale	Baseline, month 6, month 12
Change in Endothelial Progenitor Cell [EPC]-colony forming unit [EPC-CFU] assay	Change in endothelial function will be reported as the change in Endothelial Progenitor Cell Colony Forming Unit (EPC-CFU) assessed via blood sample assay. Units: CFUs/well	Baseline, month 2, 8, & 12
Change in branchial artery flow-mediated dilation [FMD] [diameter percent change]).	Change in branchial artery flow-mediated dilation will be reported as the percent change in flow mediated diameter assessed via flow mediated dilation (FMD). Units: %	Baseline, month 2, 8, & 12
Major adverse cardiac events (MACE)	Number of participants with adjudicated events including death, hospitalization for worsening HF, and exacerbation of HF requiring visit to the Emergency Department and/or IV therapy but not requiring hospitalization. Units: number of participants who have an incidence of MACE in each group	Month 12
Cumulative days alive and out of hospital for HF	Days alive and out of hospital during the study evaluation period. Units: days	Month 12
Biomarkers: Change in NT-proBNP	Change in NT-proBNP as assessed via blood draw. Units: pg/ml	Day 0, Month 2, 4, 6, 8, & 12
Biomarkers: hs-CRP	Blood level of hs-CRP as assessed via blood draw. Units: mg/ml	Day 0, Week 1, Month 2, 4, 6, 8, & 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious adverse events	Number of patients experiencing significant adjudicated clinical events including myocardial infarction (MI), stroke, pulmonary embolism, implantable cardioverter-defibrillator (ICD) firing for ventricular fibrillation/tachycardia, ventricular tachycardia (sustained and non-sustained), or hospitalization related to intravenous infusion of UC-MSCs. Units: number of participants who have an incidence of SAE in each group	2 hrs, 6 hrs, Months 2 & 6

Collaborators and Investigators

• Sponsor: Roberto Bolli
• Collaborators: University of Miami; United States Department of Defense; University of Texas
• Investigators: Principal Investigator: Roberto Bolli, MD, University of Louisville School of Medicine

Publications and helpful links

General Publications

• Bolli R, Tang XL, Hare JM, Mitrani RD, Perin EC, Lima JA, Hurwitz BE, Kalra D, Singh G, Saltzman RG, Caceres LV, Nettina A, Lee YS, Bacallao K, Grant E, Khan A. Design and rationale of CATO, a Phase IIA, randomized, double-blind, placebo-controlled study of single or repeated intravenous administration of umbilical cord-derived mesenchymal stromal cells in ischemic cardiomyopathy. Am Heart J. 2026 Apr;294:107328. doi: 10.1016/j.ahj.2025.107328. Epub 2025 Dec 13.
• Tang XL, Wysoczynski M, Gumpert AM, Solanki M, Li Y, Wu WJ, Zheng S, Ruble H, Li H, Stowers H, Zheng S, Ou Q, Tanveer N, Slezak J, Kalra DK, Bolli R. Intravenous infusions of mesenchymal stromal cells have cumulative beneficial effects in a porcine model of chronic ischaemic cardiomyopathy. Cardiovasc Res. 2024 Dec 4;120(15):1939-1952. doi: 10.1093/cvr/cvae173.

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: November 1, 2023
• First Submitted That Met QC Criteria: November 17, 2023
• First Posted (Actual): November 22, 2023

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: UC-MSCs; ischemic cardiopathy
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Myocardial Ischemia
• Other Study ID Numbers: 23.0712; 1369707 (Other Grant/Funding Number: United States Department of Defence)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No