Infusion of Umbilical Cord Versus Bone Marrow Derived Mesenchymal Stem Cells to Evaluate Cytokine Suppression.

Phase 1

Terminated

Conditions: Metabolic Syndrome
Chronic Inflammation
Endothelial Dysfunction

Interventions: Biological: UCMSCs
Other: Placebo
Biological: BMMSCs

Registration Number: NCT03059355

Lead Sponsor: Joshua M Hare

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 14

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pilot Phase: Group 1 (UCMSCs - 20 million)	UCMSCs	Three (3) subjects will be treated with a single administration of 2 x 10\^7 (20 million) UCMSCs delivered via peripheral intravenous infusion.
Group C (Placebo)	Placebo	Participants randomized to receive a single administration of placebo via peripheral intravenous infusion.
Pilot Phase: Group 3 (UCMSCs - 100 million)	UCMSCs	Three (3) subjects will be treated with a single IV administration of 1 x 10\^8 (100 million) UCMSCs delivered via peripheral intravenous infusion.
Pilot Phase: Group 4 (BMMSCs -100 million)	BMMSCs	Three (3) subjects will be treated with a single IV administration of 1 x 10\^8 (100 million) BMMSCs delivered via peripheral intravenous infusion.
Pilot Phase: Group 2 (BMMSCs - 20 million)	BMMSCs	Three (3) subjects will be treated with a single IV administration of 2 x 10\^7 (20 million) BMMSCs delivered via peripheral intravenous infusion.
Group A (UCMSCs - 100 million)	UCMSCs	Participants randomized to receive a single administration of 1 x 10\^8 (100 million) UCMSCs delivered via peripheral intravenous infusion.
Group B (BMMSCs - 100 million)	BMMSCs	Participants randomized to receive a single administration of 1 x 10\^8 (100 million) BMMSC delivered via peripheral intravenous infusion.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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.
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.
Flow Mediated Diameter Percentage (FMD%)	at Baseline and at Month 3	FMD% will be assessed using brachial artery ultrasound