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

NCT06145035 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 23.07121369707
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

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).

Conditions

Ischemic Heart Disease

Keywords

ischemic cardiopathy; UC-MSCs

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (18)

• Change in LV end-systolic volume index (ESVI)

  Baseline, 12 months

• Change in LV end-diastolic volume index (EDVI)

  Baseline, 12 months

• Change in LV end-diastolic wall thickness

  Baseline, 12 months

• Change in LV wall thickening

  Baseline, 12 months

• Change in LV sphericity index

  Baseline, 12 months

Other Outcomes (1)

• Serious adverse events

  2 hrs, 6 hrs, Months 2 & 6

Study Arms (3)

control group

PLACEBO COMPARATOR

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)

single-dose group

EXPERIMENTAL

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)

repeated-dose group

EXPERIMENTAL

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)

Interventions

umbilical cord-derived mesenchymal stromal cells (UC-MSCs) BIOLOGICAL

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.

control group; repeated-dose group; single-dose group

Eligibility Criteria

• Age: 21 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be ≥ 21 and ≤ 85 years of age.
• Have documented CAD (\> 70% lesion in at least 1 epicardial vessel) with evidence of myocardial injury, LV dysfunction, and clinical evidence of HF.
• Have a "detectable" area of myocardial injury defined as ≥ 5% LV involvement (infarct volume) and any subendocardial involvement by MRI.
• Have an EF ≤ 40% by MRI.
• 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.
• Have NYHA class I, II or III symptoms of HF (see Appendix A)
• 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

You may not qualify if:

• 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.
• Severe valvular (any valve) insufficiency and/or regurgitation within 12 months of consent
• History of ischemic or hemorrhagic stroke within 90 days of consent
• 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
• Pacemaker dependence with an ICD (Note: pacemaker dependent candidates without an ICD are not excluded)
• A cardiac resynchronization therapy (CRT) device implanted less than 3 months prior to consent.
• Other MRI contraindications (e.g. patient body habitus incompatible with MRI)
• An appropriate ICD firing or anti tachycardia pacing (ATP) for ventricular fibrillation or ventricular tachycardia within 30 days of consent
• 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

Sponsors & Collaborators

• Roberto Bolli: lead
• University of Miami: collaborator
• University of Texas: collaborator
• United States Department of Defense: collaborator

Study Sites (3)

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

RECRUITING

University of Louisville School of Medicine, Institute of Molecular Cardiology

Louisville, Kentucky, 40202, United States

RECRUITING

The Texas Heart Institute Houston Texas

Houston, Texas, 77030, United States

RECRUITING

Related Publications (2)

• 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.

  PMID: 41397478 DERIVED

• 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.

  PMID: 39163570 DERIVED

MeSH Terms

Conditions

Myocardial Ischemia

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Study Officials

• Roberto Bolli, MD

  University of Louisville School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Roberto Bolli, MD

CONTACT

502-608-5426; rbolli@louisville.edu

Michelle Unseld, RN

CONTACT

502-540-3423; michelle.unseld@louisville.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: As a double-blind study, bias control will be achieved by maintaining the blind on treatment group assignments. The master randomization lists containing the treatment assignments will be protected in secure, controlled access drives/folders and will not be released to any blinded study personnel prior to final database lock. A centralized Core laboratory will be used for MRI analyses to maintain the blind across the study team. The designated cell processing technicians will prepare the investigational product for infusion. The investigational agent infusions will be prepared in identical infusion bags and labeled with the identical investigational drug labels as to preserve the blind. The designated technicians in the ISCI Cell Processing Laboratory (CPL) or designee will be responsible for maintaining the investigational product records including randomized treatment assignments by subject identification.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Endowed Chair, M.D.

Model Details: randomized, double blind, placebo controlled,

Study Record Dates

• First Submitted: November 1, 2023
• First Posted: November 22, 2023
• Study Start: March 4, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)