Using umbilical cord cells to treat ischemic heart disease

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

This study is testing if giving umbilical cord cells to people with heart disease can help improve their heart function.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 21 Years to 85 Years
• Sex: All
• Sponsor: University of Louisville (Academic / other)
• Locations: 3 sites (Miami, Florida and 2 other locations)
• Trial ID: NCT06145035 on ClinicalTrials.gov

What this trial studies

This Phase IIA clinical trial evaluates the safety, feasibility, and efficacy of umbilical cord-derived mesenchymal stromal cells (UC MSCs) administered intravenously in patients with ischemic cardiomyopathy. Participants will be randomly assigned to receive either a single dose of UC MSCs, repeated doses, or a placebo, with a total of four infusions spaced two months apart. The study will monitor participants for safety and efficacy over a six-month follow-up period after the final infusion. The goal is to determine if UC MSCs can improve heart function in patients with significant heart disease.

Who should consider this trial

Good fit: Ideal candidates are adults aged 21 to 85 with documented coronary artery disease and heart failure symptoms.

Not a fit: Patients with stable heart function or those not meeting the specific inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve heart function and quality of life for patients with ischemic cardiomyopathy.

How similar studies have performed: Other studies using stem cell therapies for heart conditions have shown promise, but this specific approach with UC MSCs is relatively novel.

Eligibility criteria

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.

Where this trial is running

Miami, Florida and 2 other locations

• University of Miami Miller School of Medicine — Miami, Florida, United States (Recruiting)
• University of Louisville School of Medicine, Institute of Molecular Cardiology — Louisville, Kentucky, United States (Recruiting)
• The Texas Heart Institute Houston Texas — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Roberto Bolli, MD — University of Louisville School of Medicine
• Study coordinator: Roberto Bolli, MD

Conditions Ischemic Heart Disease; ischemic cardiopathy; UC-MSCs