Allogeneic Mesenchymal Human Stem Cell Infusion Therapy for Endothelial DySfunctiOn in Diabetic Subjects With Symptomatic Ischemic Heart Disease. (ACESO-IHD) (ACESO-IHD)

Allogeneic Mesenchymal Human Stem Cell Infusion Therapy for Endothelial DySfunctiOn in Diabetic Subjects With Symptomatic Ischemic Heart Disease.

The purpose of this study is to test the hypothesis that allogeneic Mesenchymal Stem Cells (MSCs) promote systemic and coronary endothelial repair through rescue of bone marrow progenitors in type 2 diabetic patients with symptomatic IHD compared to placebo.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Ischemic Heart Disease
• Intervention / Treatment: Drug: 100 million Allogeneic Mesenchymal Human Stem Cells; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be ≥ 18 years of age (males and females).
2. Provide written informed consent.
3. Have a diagnosis of symptomatic ischemic heart disease (IHD) and an indication for standard-of-care coronary angiography.
4. Have Diabetes Mellitus (DM) type 2 documented by glycated hemoglobin (HbA1C) > 7%, or on medical therapy for diabetes.

Exclusion Criteria:

1. Be younger than 18 years of age.
2. Have history of prior myocardial Infarction and revascularization.
3. Have a baseline glomerular filtration rate (GFR) <30 ml/min 1.73m2 estimated using the Modification of Diet for Renal Disease (MDRD) formula.
4. Have poorly controlled blood glucose levels with hemoglobin A1C > 8.5% in the previous 3 months.
5. Have a history of proliferative retinopathy or severe neuropathy requiring medical treatment.
6. Have an indication for standard-of-care surgical (including valve surgery, placement of left-ventricular assist device) or percutaneous intervention for the treatment of valvular heart disease (including valvuloplasty).
7. Have known hypersensitivity or contraindication to aspirin; both heparin and bivalirudin; all available P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor); or any zotarolimus, cobalt, chromium, nickel, tungsten, acrylic, or fluoropolymers; or hypersensitivity to contrast media that cannot be adequately premedicated.
8. Have a hematologic abnormality as evidenced by hematocrit < 25%, white blood cell < 2,500/microliter (uL) or platelet values < 100,000/uL without another explanation (per investigator discretion).
9. Have liver dysfunction, as evidenced by enzymes (AST and ALT) greater than three times the upper limit of normal.
10. Have a bleeding diathesis or coagulopathy (INR > 1.3), cannot be withdrawn from anticoagulation therapy, or will refuse blood transfusions.
11. Be an organ transplant recipient or have a history of organ or cell transplant rejection.
12. Have a clinical history of malignancy within the past 5 years (i.e., subjects with prior malignancy must be disease free for 5 years), except curatively-treated basal cell or squamous cell carcinoma, or cervical carcinoma.
13. Have a condition that limits lifespan to < 1 year.
14. Have a history of drug or alcohol abuse within the past 24 months.
15. Be serum positive for HIV, hepatitis B surface antigen (sAg), or viremic hepatitis C.
16. Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial.
17. Be pregnant, nursing, or of childbearing potential and not on contraceptive medications. (May participate if on 2 forms of contraceptives).
18. Any other condition that in the judgment of the Investigator would be a contraindication to enrollment or follow-up.
19. Coronary lesions with restenosis or heavy calcification.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: Allogeneic Mesenchymal Stem Cells (MSCs) Group; Participants in this group will be receive a single administration of intravenous allogeneic human Mesenchymal Stem Cells (hMSCs) (100 million).	Drug: 100 million Allogeneic Mesenchymal Human Stem Cells; 1 single intravenous infusion; Other Names: allo-human Mesenchymal Stem Cells (hMSCs); stem cells
Placebo Comparator: Group B: Placebo Group; Participants in this group will receive a single dose of placebo (Cell-free PlasmaLyte-A medium supplemented with 1% HSA) infusion.	Other: Placebo; Placebo delivered via peripheral intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brachial Artery Flow Mediated Diameter Percentage (FMD%)	FMD% is measured via brachial artery ultrasound. The unit of measure is percent.	Baseline, Week 2, Month 1, Month 3, and Month 6
EPC-CFU Counts	Endothelial progenitor cells (EPC)-colony forming units (CFUs) will be assessed from blood samples. The unit of measure is the average number of colonies per well.	Baseline, Week 2, Month 1, Month 3, and Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fractional Flow Reserve (FFR)	Fractional Flow Reserve as assessed by during cardiac catheterization angiography. The values are presented as a ratio.	Baseline, Month 6
Coronary Flow Reserve (CFR)	Coronary Flow Reserve as assessed by during cardiac catheterization angiography. The values are presented as a ratio.	Baseline, Month 6
Seattle Angina Questionnaire (SAQ) Angina Frequency (AF)	SAQ is a 7 item questionnaire with a total score ranging from 0-100 with the higher scores indicating less physical limitations, less angina, symptom frequency and better quality of life. The unit of measure is score on a scale.	Baseline, Week 2, Month 1, Month 3, and Month 6
Seattle Angina Questionnaire (SAQ) Quality of Life (QL)	SAQ is a 7 item questionnaire with a total score ranging from 0-100 with the higher scores indicating less physical limitations, less angina, symptom frequency and better quality of life. The unit of measure is score on a scale.	Baseline, Week 2, Month 1, Month 3, and Month 6
Number of Participants With Treatment-Emergent Serious Adverse Events (TE-SAE)	TE-SAEs will be defined as the composite of: death, non-fatal myocardial infarction (MI), stroke, hospitalization for heart failure, sustained ventricular arrhythmias (characterized by ventricular arrhythmias lasting longer than 30 sec or with hemodynamic compromise) or atrial fibrillation at 1 month post-infusion. TE-SAEs will be assessed by treating physician. The unit of measurement is the number of participants who experienced an event.	1 month post infusion
Number of Participants With Major Adverse Cardiac Events (MACE)	Defined as the composite incidence of (1) death, (2) hospitalization for cardiovascular events or (3) non-fatal myocardial infarction MI at 1 year. MACE will be assessed by treating physician. The unit of measurement is the number of participants who experienced an event.	12 months
Number of Participants With Target Vessel Failure	Number of participants with target vessel failure will be reported. Target vessel failure is defined as any participant that encounters revascularization, death, or MI attributed to the target vessel post-PCI (percutaneous coronary intervention). The unit of measure is number of participants.	12 months
Number of Participants With Treatment Emergent Adverse Events	The number of participants who experienced a Treatment Emergent Adverse Event (AE), as assessed by study physician, will be reported. The unit of measurement is the number of participants who experienced an event.	12 months
Number of Participants With Abnormal Lab Values	Number of participants with clinically significant abnormal serum hematology and clinical chemistry values will be reported. Clinical significance will be assessed by treating physician. The unit of measure is number of participants.	12 months
Circulating Angiogenic Marker - VEGF	Vascular Endothelial Growth Factor (VEGF) levels from serum samples. Results are provided in units of pg/mL. Higher levels of VEGF are associated with better cardiovascular health.	Baseline, Month 1, Month 3, Month 6
Circulating Cytokine Biomarker - TNFα	Circulating Tumor necrosis factor alpha (TNFα) levels from serum samples. Results are provided in units of pg/mL. Lower values are associated with reduced inflammation.	Baseline, Month 1, Month 3, Month 6

Collaborators and Investigators

• Sponsor: Joshua M Hare
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Nikolaos Spilias, MD, University of Miami

Publications and helpful links

Helpful Links

• Description: Interdisciplinary Stem Cell Institute at the University of Miami Miller School website

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2021
• Primary Completion (Actual): March 30, 2025
• Study Completion (Actual): August 26, 2025

Study Registration Dates

• First Submitted: February 26, 2021
• First Submitted That Met QC Criteria: February 26, 2021
• First Posted (Actual): March 1, 2021

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 15, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Diabetes; Endothelial dysfunction; Stem cells
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Diabetes Mellitus; Myocardial Ischemia; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: 20200874; 1R01HL134558-01 (U.S. NIH Grant/Contract)

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
• product manufactured in and exported from the U.S.: No