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

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Carlos E Alfonso, MD; Phone Number: (305) 2437589; Email: calfonso@med.miami.edu
• Study Contact Backup: Name: Russell G Saltzman, MSPH; Phone Number: 305-243-1152; Email: R.Saltzman@med.miami.edu

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami
      • Contact: Russell G Saltzman, MSPH; Phone Number: 305-243-1152; Email: R.Saltzman@med.miami.edu
      • Contact: Carlos E Alfonso, MD; Phone Number: 305-243-5554; Email: calfonso@med.miami.edu
      • Principal Investigator: Carlos E Alfonso, MD

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
Experimental: Group 2: 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
Post-Percutaneous Coronary Intervention (PCI) coronary artery endothelial function as assessed via CFR	Coronary Flow Reserve (CFR) as measured via cardiac catheterization angiography	6 months (post-infusion)
Post-PCI coronary artery endothelial function as assessed via FFR	Fractional Flow Reserve (FFR) as measured via cardiac catheterization angiography	6 months (post infusion)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target lesion lumen loss	Target lesion lumen loss as assessed by quantitative coronary angiography (QCA).	6 months (post-infusion)
Flow Mediated Diameter Percentage (FMD%)	FMD% is measured via brachial artery ultrasound	6 months post-infusion
EPC-CFUs levels	Endothelial progenitor cells (EPC)-colony forming units (CFUs) will be assessed from blood samples.	6 months post-infusion
Circulating angiogenic factors marker levels	Circulating angiogenic marker levels including Protein Kinase B, Stromal Cell Derived Factor 1 (SDF-1), Notch, Vascular Endothelial Growth Factor (VEGF) and Colony Forming Units (CFU) will be assessed from blood samples.	6 months post-infusion
Circulating inflammatory markers	Circulating inflammatory markers including Cluster of Differentiation (CD) 3 CD 25 or CD 3 CD 69 will be assessed from blood samples.	6 months post-infusion
Seattle Angina Questionnaire (SAQ) Angina Frequency	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.	6 months post-infusion
EuroQol(EQ)-5 Dimension (5D) Quality of Life Questionnaire	EQ-5D Quality of Life Questionnaire has a total score ranging from 0-10 with higher scores indicating better quality of life.	6 months post-infusion
EQ-5D Quality of life Questionnaire Overall Health Status Question	EQ-5D Quality of Life Questionnaire Overall Health Status question has a total score ranging from 0-100 with higher scores indicating better quality of life.	6 months post-infusion
Short Form (SF) 36 Questionnaire Quality of Life Questionnaire	SF 36 Quality of Life Questionnaire consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. Lower scores indicate the more disability, and higher scores indicate less disability.	6 months post-infusion
International Index of Erectile Function (IIEF) Questionnaire	IIEF is a 15 item questionnaire to be completed by males only, with scores ranging from 0-75. Higher scores indicate better male sexual function/quality of life.	6 months post-infusion
Sexual Quality of Life - Females (SQOL-F) Questionnaire	SQOL-F Questionnaire is an 18 item questionnaire in which female participants are asked to record responses on a 6-point Likert scale (completely agree to completely disagree). Total score can range from 18 to 108. Higher scores indicate better female sexual quality of life.	6 months post-infusion
Incidence of 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 or atrial fibrillation. TE-SAEs will be assessed by treating physician.	1 month post infusion
Incidence of Major Adverse Cardiac Events (MACE)	Defined as the composite incidence of (1) death, (2) hospitalization for cardiovascular events or (3) non-fatal MI. MACE will be assessed by treating physician.	12 months
Rates of Adverse Events	Rates of treatment emergent adverse event (AE) and serious adverse event (SAE) as assessed by treating physician will be reported.	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.	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	12 months

Collaborators and Investigators

• Sponsor: University of Miami
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Carlos E Alfonso, 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 (Estimated): July 16, 2024
• Study Completion (Estimated): July 16, 2024

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): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Diabetes; Endothelial dysfunction; Stem cells
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Ischemia
• 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