Allogeneic Mesenchymal Human Stem Cells Infusion Therapy for Endothelial DySfunctiOn in Diabetic Subjects

Phase 1

Completed

Conditions: Diabetes Mellitus, Type 2

Interventions: Drug: 20 million Allogeneic Mesenchymal Human Stem Cells
Drug: 100 million Allogeneic Mesenchymal Human Stem Cells

Registration Number: NCT02886884

Lead Sponsor: Joshua M Hare

Brief Summary: This is a 16 subject trial to demonstrate the safety of allogeneic hMSCs administered via infusion therapy for diabetic subjects with endothelial dysfunction.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 16

Inclusion Criteria

Be ≥ 21 and < 90 (inclusive) years of age.
Provide written informed consent.
Have endothelial dysfunction defined by impaired flow-mediated vasodilation (FMD <7%).
Have an ejection fraction > 45% by gated blood pool scan, two- dimensional echocardiogram, cardiac MRI, cardiac CT or left ventriculogram within the prior 3 months.
Have Diabetes mellitus type 2 documented by hemoglobin adult type 1 component (A1C) > 7% or on medical therapy for diabetes.
Females of childbearing potential must use two forms of birth control for the duration of the study. Female subjects must undergo a blood or urine pregnancy test at screening and within 36 hours prior to infusion.

Exclusion Criteria

In order to participate in this study, a subject Must Not:

Be younger than 21 years or older than 90 years of age.
Have a baseline glomerular filtration rate <35 ml/min 1.73m^2 estimated using the Modification of Diet in renal disease (MDRD) formula.
Have an ejection fraction <45% by gated blood pool scan, two-dimensional echocardiogram, cardiac MRI, cardiac CT or left ventriculogram within the past year, as documented by medical history.
Have poorly controlled blood glucose levels with hemoglobin A1C > 8.5%.
Have a history of proliferative retinopathy or severe neuropathy requiring medical treatment.
Have a hematologic abnormality as evidenced by hematocrit < 25%, white blood cell < 2,500/ul or platelet values < 100,000/ul without another explanation.
Have liver dysfunction, as evidenced by enzymes (AST and ALT) greater than three times the upper limit of normal.
Have a bleeding diathesis or coagulopathy (INR > 1.3), cannot be withdrawn from anticoagulation therapy, or will refuse blood transfusions.
Have Lymphadenectomy or Lymph node dissection in the right arm.
Be an organ transplant recipient or have a history of organ or cell transplant rejection.
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.
Have a condition that limits lifespan to < 1 year.
Have a history of drug or alcohol abuse within the past 24 months.
Be on chronic therapy with immunosuppressant medication, such as corticosteroids or Tumor Necrosis Factor - alpha (TNFα) antagonists.
Be serum positive for HIV, Syphilis - VDRL (Confirmation with FTA-ABS if needed (Syphilis)), hepatitis B surface antigen or viremic hepatitis C.
Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial.
Be pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods.
Any other condition that in the judgment of the Investigator would be a contraindication to enrollment or follow-up.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pilot Phase 20 million allogeneic hMSCs	20 million Allogeneic Mesenchymal Human Stem Cells	Participants in this group will receive one peripheral intravenous infusion of 20 million allogeneic Mesenchymal Human Stem Cells (hMSCs)
Pilot Phase 100 million hMSCs	100 million Allogeneic Mesenchymal Human Stem Cells	Participants in this group will receive one peripheral intravenous infusion of 100 million allogeneic Mesenchymal Human Stem Cells (hMSCs)
Randomized Phase 20 million allogeneic hMSCs	20 million Allogeneic Mesenchymal Human Stem Cells	Participants in this group will receive one peripheral intravenous infusion of 20 million allogeneic Mesenchymal Human Stem Cells (hMSCs)
Randomized Phase 100 million allogeneic hMSCs	100 million Allogeneic Mesenchymal Human Stem Cells	Participants in this group will receive one peripheral intravenous infusion of 100 million allogeneic Mesenchymal Human Stem Cells (hMSCs)

Primary Outcome Measures

Name	Time	Method
Number of Treatment Emergent Serious Adverse Events (TE-SAEs)	Up to one month (post infusion)	TE-SAEs as evaluated by the investigator which may include but not limited to: death, non-fatal pulmonary embolism, stroke, hospitalization for worsening dyspnea and clinically significant laboratory test abnormalities.

Secondary Outcome Measures

Name	Time	Method
CRP Marker Levels	At Baseline, Day 3, Day 7, Day 14, Day 28, Day 90, Day 180, Day 365	C-Reactive Protein (CRP) levels will be assessed from blood samples and reported in mg/L
EPC-CFU Levels	At Baseline, Day 3, Day 7, Day 14, Day 28, Day 90, Day 180, Day 365	Endothelial Progenitor Cell Colony Forming Units (EPC-CFU) will be assessed from blood samples
Tumor Necrosis Factor (TNF) Alpha Levels	At Baseline, Day 3, Day 7, Day 14, Day 28, Day 90, Day 180, Day 365	Measured from blood samples (pg/mL)
Circulating Angiogenic Factor Levels	At Baseline, Day 3, Day 7, Day 14, Day 28, Day 90, Day 180, Day 365	Circulating Angiogenic Factor levels including Vascular Endothelial Growth Factor (VEGF), Stem Cell Factor (SCF) and Stromal Cell-Derived Factor 1 (SDF-1) will be assessed from blood samples and reported in ng/mL
Flow Mediated Diameter Percentage (FMD%)	At Baseline, Day 3, Day 7, Day 14, Day 28, Day 90, Day 180, Day 365	FMD will be assessed using brachial artery ultrasound
Circulating Inflammatory Marker Levels	At Baseline, Day 3, Day 7, Day 14, Day 28, Day 90, Day 180, Day 365	Circulating inflammatory marker levels including Interleukin (IL) -1 and IL-6 will be assessed from blood samples and reported in pg/mL