Chronic Inflammation, Endothelial Dysfunction, Metabolic Syndrome
Conditions
Brief summary
This study is to compare the safety and efficacy of UCMSCs and BMMSCs administered intravenously in patients to evaluate cytokine suppression in patients with chronic inflammation. Cells administered via intravenous infusion (IV) and will be tested in 37 patients in two phases (Pilot and Randomized).
Interventions
Sponsors
The Marcus Foundation
Joshua M Hare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Pilot phase is open-label. Randomized phase is blinded.
Eligibility
Sex/Gender
ALL
Age
21 Years to 95 Years
Healthy volunteers
No
Inclusion criteria
* Provide written informed consent * Subjects age \> 21 and \< 95 years at the time of signing the Informed Consent Form. * Each subject must have endothelial dysfunction. Endothelial dysfunction Criteria: Impaired flow-mediated vasodilation (FMD \<7%) • At the time of enrollment, each subject must meet at least 3 out of the 5 criteria under the harmonized definition of the metabolic syndrome, consisting of the following: * Waist circumference - US defined: ≥ 102 cm (males) or ≥ 88 cm (females) * Elevated triglycerides - ≥ 150 mg/dL (1.7 mM) * Reduced HDL-C - Males: \<40 mg/dL (1.0 mM) Females: \<50 mg/dL (1.3 mM) * Elevated blood pressure - Systolic ≥ 130 mm Hg and/or Diastolic ≥ 85 mm Hg * Elevated fasting glucose - ≥ 100 mg/dL
Exclusion criteria
* Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods. Female subjects must undergo a blood or urine pregnancy test at screening and within 36 hours prior to infusion. * Inability to perform any of the assessments required for endpoint analysis. * Active listing (or expected future listing) for transplant of any organ. * Clinically important abnormal screening laboratory values, as determined by the P.I. * Serious comorbid illness or any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the subject or preclude successful completion of the study. * Have known allergies to penicillin or streptomycin. * Hypersensitivity to dimethyl sulfoxide (DMSO). * Be a solid organ transplant recipient. This does not include prior cell-based therapy (\>12 months prior enrollment) bone, skin, ligament, tendon or corneal grafting. Have a history of organ or cell transplant rejection. * Have a clinical history of malignancy within 3 years (i.e., subjects with prior malignancy must be disease free for 3 years), except curatively- treated basal cell carcinoma, squamous cell carcinoma, melanoma in situ or cervical carcinoma, if recurrence occurs. * Have a non-pulmonary condition that limits lifespan to \< 1 year. * 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 24 months. * Be serum positive for HIV, hepatitis B surface antigen or Viremic hepatitis C, and/or Syphilis. * Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial. * Patients with Ejection Fraction \<45% (heart failure patients). * Glomerular Filtration Rate \< or equal to 35 (chronic kidney disease stage 3 or higher). * Liver disease (elevated Liver Function Tests greater than 3x normal limit). * Advanced pulmonary disease (requiring home oxygen and/or less than 1 expected life span). * Proliferative diabetic retinopathy * Hemoglobin A1C greater than 7.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment-Emergent Serious Adverse Events (TE-SAEs) | one month post infusion | Number of treatment-emergent serious adverse events (SAE) (at one-month post infusion), defined as the composite of: death, non-fatal pulmonary embolism, stroke, hospitalization for worsening dyspnea and clinically significant laboratory test abnormalities, determined per the Investigator's judgment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stem Cell Factor (SCF) Levels | at Baseline, at Week 2, at Month 1, at Month 3, and at Month 6 | SCF levels from serum/plasma samples measured in units of mg/mL |
| Cytokine Levels | at Baseline, at Week 2, at Month 1, at Month 3, and at Month 6 | Cytokine levels including the following panel of inflammatory and angiogenic markers: Interleukin-1 (IL-1), Interleukin-6 (IL-6), Tumor Necrosis Factor alpha (TNFα), and Vascular Endothelial Growth Factor (VEGF), & Stromal Cell Derived Factor (SDF-1a) levels from serum/plasma samples all measured in pg/mL. |
| hsCRP Levels | at Baseline, at Week 2, at Month 1, at Month 3, and at Month 6 | values at baseline and follow up for the following inflammatory marker: Serum High sensitivity C-Reactive Protein (hsCRP) in mg/L. |
| Endothelial Progenitor Cell-Colony Forming Units (EPC-CFUs) | at Baseline, and at 3 months | Endothelial function will be reported as the change in Endothelial Progenitor Cell Colony Forming Unit (EPC-CFU) assessed via blood sample assay |
| Flow Mediated Diameter Percentage (FMD%) | at Baseline and at Month 3 | FMD% will be assessed using brachial artery ultrasound |
Countries
United States
Participant flow
Recruitment details
No subjects had been randomized to Group A or C at the time of trial termination.
Participants by arm
| Arm | Count |
|---|---|
| Pilot Phase: Group 1 (UCMSCs - 20 Million) Three (3) subjects will be treated with a single administration of 2 x 10\^7 (20 million) UCMSCs delivered via peripheral intravenous infusion.
UCMSCs: Allogeneic Umbilical Cord Tissue derived MSCs (UCMSCs) | 3 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) Three (3) subjects will be treated with a single IV administration of 2 x 10\^7 (20 million) BMMSCs delivered via peripheral intravenous infusion.
BMMSCs: Bone Marrow derived Mesenchymal Stem Cells (BMMSCs) | 3 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) Three (3) subjects will be treated with a single IV administration of 1 x 10\^8 (100 million) UCMSCs delivered via peripheral intravenous infusion.
UCMSCs: Allogeneic Umbilical Cord Tissue derived MSCs (UCMSCs) | 3 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) Three (3) subjects will be treated with a single IV administration of 1 x 10\^8 (100 million) BMMSCs delivered via peripheral intravenous infusion.
BMMSCs: Bone Marrow derived Mesenchymal Stem Cells (BMMSCs) | 3 |
| Group A (UCMSCs - 100 Million) Participants randomized to receive a single administration of 1 x 10\^8 (100 million) UCMSCs delivered via peripheral intravenous infusion.
UCMSCs: Allogeneic Umbilical Cord Tissue derived MSCs (UCMSCs) | 0 |
| Group B (BMMSCs - 100 Million) Participants randomized to receive a single administration of 1 x 10\^8 (100 million) BMMSC delivered via peripheral intravenous infusion.
BMMSCs: Bone Marrow derived Mesenchymal Stem Cells (BMMSCs) | 2 |
| Group C (Placebo) Participants randomized to receive a single administration of placebo via peripheral intravenous infusion.
Placebo: a single administration of placebo delivered via peripheral intravenous infusion. | 0 |
| Total | 14 |
Baseline characteristics
| Characteristic | Pilot Phase: Group 1 (UCMSCs - 20 Million) | Pilot Phase: Group 2 (BMMSCs - 20 Million) | Pilot Phase: Group 3 (UCMSCs - 100 Million) | Pilot Phase: Group 4 (BMMSCs -100 Million) | Group B (BMMSCs - 100 Million) | Total | Group C (Placebo) | Group A (UCMSCs - 100 Million) |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 85.67 years STANDARD_DEVIATION 5.13 | 62.00 years STANDARD_DEVIATION 8.72 | 61.67 years STANDARD_DEVIATION 12.9 | 60.67 years STANDARD_DEVIATION 12.42 | 52 years STANDARD_DEVIATION 12.73 | 65.17 years STANDARD_DEVIATION 13.29 | — | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 5 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 9 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants | 11 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 11 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 0 | 0 / 2 | 0 / 0 |
| other Total, other adverse events | 3 / 3 | 2 / 3 | 2 / 3 | 3 / 3 | 0 / 0 | 1 / 2 | 0 / 0 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 0 | 0 / 2 | 0 / 0 |
Outcome results
Primary
Number of Treatment-Emergent Serious Adverse Events (TE-SAEs)
Number of treatment-emergent serious adverse events (SAE) (at one-month post infusion), defined as the composite of: death, non-fatal pulmonary embolism, stroke, hospitalization for worsening dyspnea and clinically significant laboratory test abnormalities, determined per the Investigator's judgment.
Time frame: one month post infusion
Population: No subjects had been randomized to Group A or C at the time of trial termination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | Number of Treatment-Emergent Serious Adverse Events (TE-SAEs) | 0 Events |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | Number of Treatment-Emergent Serious Adverse Events (TE-SAEs) | 0 Events |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | Number of Treatment-Emergent Serious Adverse Events (TE-SAEs) | 0 Events |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | Number of Treatment-Emergent Serious Adverse Events (TE-SAEs) | 0 Events |
| Group B (BMMSCs - 100 Million) | Number of Treatment-Emergent Serious Adverse Events (TE-SAEs) | 0 Events |
Secondary
Cytokine Levels
Cytokine levels including the following panel of inflammatory and angiogenic markers: Interleukin-1 (IL-1), Interleukin-6 (IL-6), Tumor Necrosis Factor alpha (TNFα), and Vascular Endothelial Growth Factor (VEGF), & Stromal Cell Derived Factor (SDF-1a) levels from serum/plasma samples all measured in pg/mL.
Time frame: at Baseline, at Week 2, at Month 1, at Month 3, and at Month 6
Population: Some participants did not complete all of the study visits per protocol due to COVID-19 pandemic restrictions. Therefore not all data is available for all time-points for all participants.~Blood samples were collected for IL-1 and SDF-1a analysis, however due to cost and logistical reasons the samples were not analyzed.~VEGF were to be analyzed internally using frozen plasma aliquots. No plasma samples were retained for internal testing at week 2, month 1, and month 6 in all participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | Cytokine Levels | TNFa Baseline | 1.7 pg/mL | Standard Deviation 0.4 |
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | Cytokine Levels | IL-6 Week 2 | 5.8 pg/mL | Standard Deviation 5.2 |
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | Cytokine Levels | TNFa Month 1 | 1.7 pg/mL | Standard Deviation 1.1 |
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | Cytokine Levels | TNFa Week 2 | 1.9 pg/mL | Standard Deviation 0.8 |
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | Cytokine Levels | VEGF Baseline | 13.5 pg/mL | Standard Deviation 4.8 |
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | Cytokine Levels | IL-6 Month 1 | 5.4 pg/mL | Standard Deviation 3.9 |
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | Cytokine Levels | IL-6 Baseline | 5.7 pg/mL | Standard Deviation 4.8 |
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | Cytokine Levels | TNFa Month 6 | 1.5 pg/mL | Standard Deviation 0.6 |
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | Cytokine Levels | IL-6 Month 3 | 8.4 pg/mL | Standard Deviation 4.5 |
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | Cytokine Levels | IL-6 Month 6 | 2.9 pg/mL | Standard Deviation 2.2 |
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | Cytokine Levels | VEGF Month 3 | 15.3 pg/mL | Standard Deviation 3 |
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | Cytokine Levels | TNFa Month 3 | 2.2 pg/mL | Standard Deviation 1.7 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | Cytokine Levels | IL-6 Month 1 | 2.8 pg/mL | Standard Deviation 1 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | Cytokine Levels | TNFa Baseline | 1.6 pg/mL | Standard Deviation 0.4 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | Cytokine Levels | VEGF Month 3 | 16.5 pg/mL | Standard Deviation 12.4 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | Cytokine Levels | TNFa Month 1 | 1.5 pg/mL | Standard Deviation 0.3 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | Cytokine Levels | TNFa Month 6 | 1.4 pg/mL | Standard Deviation 0.3 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | Cytokine Levels | TNFa Month 3 | 1.2 pg/mL | Standard Deviation 0.5 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | Cytokine Levels | TNFa Week 2 | 1.5 pg/mL | Standard Deviation 0.6 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | Cytokine Levels | IL-6 Week 2 | 3.4 pg/mL | Standard Deviation 1 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | Cytokine Levels | IL-6 Baseline | 2.7 pg/mL | Standard Deviation 1.8 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | Cytokine Levels | VEGF Baseline | 19.2 pg/mL | Standard Deviation 9 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | Cytokine Levels | IL-6 Month 6 | 3.2 pg/mL | Standard Deviation 1.3 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | Cytokine Levels | IL-6 Month 3 | 2.5 pg/mL | Standard Deviation 1.2 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | Cytokine Levels | TNFa Month 3 | 1.8 pg/mL | Standard Deviation 1 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | Cytokine Levels | IL-6 Baseline | 3.2 pg/mL | Standard Deviation 2.5 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | Cytokine Levels | IL-6 Week 2 | 5.4 pg/mL | Standard Deviation 6.7 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | Cytokine Levels | IL-6 Month 1 | 2.5 pg/mL | Standard Deviation 1 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | Cytokine Levels | IL-6 Month 3 | 1.9 pg/mL | Standard Deviation 0.6 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | Cytokine Levels | IL-6 Month 6 | 3.8 pg/mL | Standard Deviation 3 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | Cytokine Levels | TNFa Baseline | 1.6 pg/mL | Standard Deviation 0.8 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | Cytokine Levels | TNFa Week 2 | 1.5 pg/mL | Standard Deviation 0.6 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | Cytokine Levels | TNFa Month 1 | 2.0 pg/mL | Standard Deviation 0.9 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | Cytokine Levels | TNFa Month 6 | 1.4 pg/mL | Standard Deviation 0.3 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | Cytokine Levels | VEGF Baseline | 25.1 pg/mL | Standard Deviation 14 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | Cytokine Levels | VEGF Month 3 | 15.5 pg/mL | Standard Deviation 6.4 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | Cytokine Levels | TNFa Baseline | 2.1 pg/mL | Standard Deviation 0.5 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | Cytokine Levels | TNFa Month 1 | 2.2 pg/mL | Standard Deviation 0.8 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | Cytokine Levels | TNFa Month 3 | 1.8 pg/mL | Standard Deviation 0.5 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | Cytokine Levels | IL-6 Month 1 | 2.1 pg/mL | Standard Deviation 0.9 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | Cytokine Levels | IL-6 Baseline | 2.9 pg/mL | Standard Deviation 1.9 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | Cytokine Levels | TNFa Month 6 | 1.0 pg/mL | Standard Deviation 0.5 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | Cytokine Levels | IL-6 Week 2 | 3.7 pg/mL | Standard Deviation 2.3 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | Cytokine Levels | VEGF Month 3 | 9.5 pg/mL | Standard Deviation 1.8 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | Cytokine Levels | VEGF Baseline | 13.5 pg/mL | Standard Deviation 1.7 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | Cytokine Levels | TNFa Week 2 | 2.1 pg/mL | Standard Deviation 0.7 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | Cytokine Levels | IL-6 Month 6 | 2.2 pg/mL | Standard Deviation 0.4 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | Cytokine Levels | IL-6 Month 3 | 2.3 pg/mL | Standard Deviation 1 |
| Group B (BMMSCs - 100 Million) | Cytokine Levels | TNFa Month 1 | 0.7 pg/mL | — |
| Group B (BMMSCs - 100 Million) | Cytokine Levels | TNFa Week 2 | 0.9 pg/mL | Standard Deviation 0.3 |
| Group B (BMMSCs - 100 Million) | Cytokine Levels | TNFa Baseline | 1.1 pg/mL | Standard Deviation 0.2 |
| Group B (BMMSCs - 100 Million) | Cytokine Levels | TNFa Month 6 | 0.5 pg/mL | — |
| Group B (BMMSCs - 100 Million) | Cytokine Levels | IL-6 Week 2 | 1.4 pg/mL | Standard Deviation 0.4 |
| Group B (BMMSCs - 100 Million) | Cytokine Levels | TNFa Month 3 | 0.7 pg/mL | — |
| Group B (BMMSCs - 100 Million) | Cytokine Levels | IL-6 Month 1 | 1.3 pg/mL | — |
| Group B (BMMSCs - 100 Million) | Cytokine Levels | IL-6 Baseline | 1.2 pg/mL | Standard Deviation 0.6 |
Secondary
Endothelial Progenitor Cell-Colony Forming Units (EPC-CFUs)
Endothelial function will be reported as the change in Endothelial Progenitor Cell Colony Forming Unit (EPC-CFU) assessed via blood sample assay
Time frame: at Baseline, and at 3 months
Population: No subjects had been randomized to Group A or C at the time of trial termination. Some participants did not complete all of the study visits per protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | Endothelial Progenitor Cell-Colony Forming Units (EPC-CFUs) | Month 3 | 20.4 Colony Forming Units per Well | Standard Deviation 20.8 |
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | Endothelial Progenitor Cell-Colony Forming Units (EPC-CFUs) | Baseline | 15.0 Colony Forming Units per Well | Standard Deviation 14.5 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | Endothelial Progenitor Cell-Colony Forming Units (EPC-CFUs) | Baseline | 0.8 Colony Forming Units per Well | Standard Deviation 0.9 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | Endothelial Progenitor Cell-Colony Forming Units (EPC-CFUs) | Month 3 | 1.3 Colony Forming Units per Well | Standard Deviation 1.1 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | Endothelial Progenitor Cell-Colony Forming Units (EPC-CFUs) | Baseline | 2.3 Colony Forming Units per Well | Standard Deviation 3.1 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | Endothelial Progenitor Cell-Colony Forming Units (EPC-CFUs) | Month 3 | 13.2 Colony Forming Units per Well | Standard Deviation 13.6 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | Endothelial Progenitor Cell-Colony Forming Units (EPC-CFUs) | Baseline | 4.8 Colony Forming Units per Well | Standard Deviation 6.6 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | Endothelial Progenitor Cell-Colony Forming Units (EPC-CFUs) | Month 3 | 1.9 Colony Forming Units per Well | Standard Deviation 2 |
| Group B (BMMSCs - 100 Million) | Endothelial Progenitor Cell-Colony Forming Units (EPC-CFUs) | Baseline | 0.6 Colony Forming Units per Well | Standard Deviation 0.6 |
Secondary
Flow Mediated Diameter Percentage (FMD%)
FMD% will be assessed using brachial artery ultrasound
Time frame: at Baseline and at Month 3
Population: No subjects had been randomized to Group A or C at the time of trial termination. Some participants did not complete all of the study visits per protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | Flow Mediated Diameter Percentage (FMD%) | Baseline | 3.6 percentage of change in brachial artery | Standard Deviation 2 |
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | Flow Mediated Diameter Percentage (FMD%) | Month 3 | 3.5 percentage of change in brachial artery | Standard Deviation 1.9 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | Flow Mediated Diameter Percentage (FMD%) | Month 3 | 5.4 percentage of change in brachial artery | Standard Deviation 3.7 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | Flow Mediated Diameter Percentage (FMD%) | Baseline | 4.1 percentage of change in brachial artery | Standard Deviation 1.1 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | Flow Mediated Diameter Percentage (FMD%) | Month 3 | 5.4 percentage of change in brachial artery | Standard Deviation 0.5 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | Flow Mediated Diameter Percentage (FMD%) | Baseline | 3.6 percentage of change in brachial artery | Standard Deviation 0.8 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | Flow Mediated Diameter Percentage (FMD%) | Month 3 | 4.0 percentage of change in brachial artery | Standard Deviation 0.8 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | Flow Mediated Diameter Percentage (FMD%) | Baseline | 3.1 percentage of change in brachial artery | Standard Deviation 1.4 |
| Group B (BMMSCs - 100 Million) | Flow Mediated Diameter Percentage (FMD%) | Baseline | 5.0 percentage of change in brachial artery | Standard Deviation 0.8 |
Secondary
hsCRP Levels
values at baseline and follow up for the following inflammatory marker: Serum High sensitivity C-Reactive Protein (hsCRP) in mg/L.
Time frame: at Baseline, at Week 2, at Month 1, at Month 3, and at Month 6
Population: No subjects had been randomized to Group A or C at the time of trial termination. Some participants did not complete all of the study visits per protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | hsCRP Levels | Month 1 | 10.7 mg/L | Standard Deviation 16 |
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | hsCRP Levels | Month 6 | 1.6 mg/L | Standard Deviation 1.1 |
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | hsCRP Levels | Month 3 | 5.0 mg/L | Standard Deviation 3.4 |
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | hsCRP Levels | Baseline | 2.0 mg/L | Standard Deviation 1.6 |
| Pilot Phase: Group 1 (UCMSCs - 20 Million) | hsCRP Levels | Week 2 | 9.2 mg/L | Standard Deviation 14.4 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | hsCRP Levels | Month 1 | 4.6 mg/L | Standard Deviation 4 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | hsCRP Levels | Week 2 | 5.7 mg/L | Standard Deviation 6 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | hsCRP Levels | Baseline | 13.0 mg/L | Standard Deviation 19.2 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | hsCRP Levels | Month 6 | 5.4 mg/L | Standard Deviation 7 |
| Pilot Phase: Group 2 (BMMSCs - 20 Million) | hsCRP Levels | Month 3 | 4.7 mg/L | Standard Deviation 5.1 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | hsCRP Levels | Month 3 | 2.7 mg/L | Standard Deviation 2.9 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | hsCRP Levels | Baseline | 1.4 mg/L | Standard Deviation 0.4 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | hsCRP Levels | Week 2 | 1.7 mg/L | Standard Deviation 1.4 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | hsCRP Levels | Month 1 | 2.1 mg/L | Standard Deviation 1.4 |
| Pilot Phase: Group 3 (UCMSCs - 100 Million) | hsCRP Levels | Month 6 | 2.6 mg/L | Standard Deviation 1.2 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | hsCRP Levels | Month 6 | 2.1 mg/L | — |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | hsCRP Levels | Month 3 | 3.4 mg/L | Standard Deviation 1.3 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | hsCRP Levels | Month 1 | 2.9 mg/L | Standard Deviation 1.2 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | hsCRP Levels | Week 2 | 4.3 mg/L | Standard Deviation 3.3 |
| Pilot Phase: Group 4 (BMMSCs -100 Million) | hsCRP Levels | Baseline | 3.2 mg/L | Standard Deviation 1.9 |
| Group B (BMMSCs - 100 Million) | hsCRP Levels | Week 2 | 0.6 mg/L | Standard Deviation 0.3 |
| Group B (BMMSCs - 100 Million) | hsCRP Levels | Month 1 | 0.6 mg/L | — |
| Group B (BMMSCs - 100 Million) | hsCRP Levels | Month 3 | 0.9 mg/L | — |
| Group B (BMMSCs - 100 Million) | hsCRP Levels | Month 6 | 0.6 mg/L | — |
| Group B (BMMSCs - 100 Million) | hsCRP Levels | Baseline | 0.5 mg/L | Standard Deviation 0.3 |
Secondary
Stem Cell Factor (SCF) Levels
SCF levels from serum/plasma samples measured in units of mg/mL
Time frame: at Baseline, at Week 2, at Month 1, at Month 3, and at Month 6
Population: Blood samples were collected for SCF analysis, however due to cost and logistical reasons the samples were not analyzed and hence no data were generated.