Clinical trial NCT04776239: Allogeneic Mesenchymal Human Stem Cell Infusion Therapy for Endothelial DySfunctiOn in Diabetic Subjects With Symptomatic Ischemic Heart Disease. (ACESO-IHD)
Official title: Allogeneic Mesenchymal Human Stem Cell Infusion Therapy for Endothelial DySfunctiOn in Diabetic Subjects With Symptomatic Ischemic Heart Disease.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Diabetes Mellitus
Ischemic Heart Disease
Keywords: Endothelial dysfunction
Diabetes
Stem cells
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2021-03-01
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: EPC-CFU levels
timeFrame: 6 months post-infusion
measure: Flow Mediated Diameter Percentage (FMD%)
timeFrame: 6 months post-infusion
Secondary outcomes:
measure: Target lesion lumen loss
timeFrame: 6 months (post-infusion)
measure: Circulating angiogenic factors marker levels
timeFrame: 6 months post-infusion
measure: Circulating inflammatory markers
timeFrame: 6 months post-infusion
measure: Seattle Angina Questionnaire (SAQ) Angina Frequency
timeFrame: 6 months post-infusion
measure: EuroQol 5 Dimension (EQ-5D) Quality of life Questionnaire Overall Health Status Question
timeFrame: 6 months post-infusion
measure: Short Form (SF) 36 Questionnaire Quality of Life Questionnaire
timeFrame: 6 months post-infusion
measure: Number of Treatment-Emergent Serious Adverse Events (TE-SAE)
timeFrame: 1 month post infusion
measure: Number of Major Adverse Cardiac Events (MACE)
timeFrame: 12 months
measure: Number of Treatment Emergent Adverse Events
timeFrame: 12 months
measure: Number of participants with abnormal lab values
timeFrame: 12 months
measure: Number of participants with Target Vessel Failure
timeFrame: 12 months
measure: Post-Percutaneous Coronary Intervention (PCI) coronary artery endothelial function as assessed via CFR
timeFrame: 6 months (post-infusion)
measure: Post-PCI coronary artery endothelial function as assessed via FFR
timeFrame: 6 months (post infusion)
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
Study officials:
affiliation: University of Miami
name: Nikolaos Spilias, MD
role: PRINCIPAL_INVESTIGATOR
References: