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

Joshua M Hare

Status and phase: Completed; Phase 2; Phase 1

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: 100 million Allogeneic Mesenchymal Human Stem Cells; Drug: 20 million Allogeneic Mesenchymal Human Stem Cells

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02886884

1R01HL134558-01 (U.S. NIH Grant/Contract)

20160686

Details and patient eligibility

About

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

Enrollment: 16 patients

Sex: All

Ages: 21 to 90 years old

Volunteers: No Healthy Volunteers

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 1.3), cannot be withdrawn from anticoagulation therapy, or will refuse blood transfusions.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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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16 participants in 4 patient groups

Pilot Phase 20 million allogeneic hMSCs

Experimental group

Description:

Participants in this group will receive one peripheral intravenous infusion of 20 million allogeneic Mesenchymal Human Stem Cells (hMSCs)

Treatment:

Drug: 20 million Allogeneic Mesenchymal Human Stem Cells

Pilot Phase 100 million hMSCs

Experimental group

Description:

Participants in this group will receive one peripheral intravenous infusion of 100 million allogeneic Mesenchymal Human Stem Cells (hMSCs)

Treatment:

Drug: 100 million Allogeneic Mesenchymal Human Stem Cells

Randomized Phase 20 million allogeneic hMSCs

Experimental group

Description:

Participants in this group will receive one peripheral intravenous infusion of 20 million allogeneic Mesenchymal Human Stem Cells (hMSCs)

Treatment:

Drug: 20 million Allogeneic Mesenchymal Human Stem Cells

Randomized Phase 100 million allogeneic hMSCs

Experimental group

Description:

Participants in this group will receive one peripheral intravenous infusion of 100 million allogeneic Mesenchymal Human Stem Cells (hMSCs)

Treatment:

Drug: 100 million Allogeneic Mesenchymal Human Stem Cells