Diabetes Mellitus, Ischemic Heart Disease
Conditions
Keywords
Endothelial dysfunction, Diabetes, Stem cells
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.
Interventions
1 single intravenous infusion
OTHERPlacebo
Placebo delivered via peripheral intravenous infusion
Sponsors
Joshua M Hare
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brachial Artery Flow Mediated Diameter Percentage (FMD%) | Baseline, Week 2, Month 1, Month 3, and Month 6 | FMD% is measured via brachial artery ultrasound. The unit of measure is percent. |
| EPC-CFU Counts | Baseline, Week 2, Month 1, Month 3, and Month 6 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fractional Flow Reserve (FFR) | Baseline, Month 6 | Fractional Flow Reserve as assessed by during cardiac catheterization angiography. The values are presented as a ratio. |
| Coronary Flow Reserve (CFR) | Baseline, Month 6 | Coronary Flow Reserve as assessed by during cardiac catheterization angiography. The values are presented as a ratio. |
| Seattle Angina Questionnaire (SAQ) Angina Frequency (AF) | Baseline, Week 2, Month 1, Month 3, and Month 6 | 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. |
| Seattle Angina Questionnaire (SAQ) Quality of Life (QL) | Baseline, Week 2, Month 1, Month 3, and Month 6 | 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. |
| Number of Participants With Treatment-Emergent Serious Adverse Events (TE-SAE) | 1 month post infusion | 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. |
| Number of Participants With Major Adverse Cardiac Events (MACE) | 12 months | 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. |
| Number of Participants With Target Vessel Failure | 12 months | 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. |
| Number of Participants With Treatment Emergent Adverse Events | 12 months | 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. |
| Number of Participants With Abnormal Lab Values | 12 months | 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. |
| Circulating Angiogenic Marker - VEGF | Baseline, Month 1, Month 3, Month 6 | 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. |
| Circulating Cytokine Biomarker - TNFα | Baseline, Month 1, Month 3, Month 6 | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORNikolaos Spilias, MD
University of Miami
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 63.85 years STANDARD_DEVIATION 6.47 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 24 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 |
| other Total, other adverse events | 11 / 13 | 9 / 13 |
| serious Total, serious adverse events | 2 / 13 | 4 / 13 |
Outcome results
None listed