Clinical trial NCT02886884: Allogeneic Mesenchymal Human Stem Cells Infusion Therapy for Endothelial DySfunctiOn in Diabetic Subjects
Official title: A Phase I/II, Randomized, Double Blind, Pilot Trial to Evaluate the Safety and Efficacy of Allogeneic Mesenchymal Human Stem Cells Infusion Therapy for Endothelial DySfunctiOn in Diabetic Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Diabetes Mellitus, Type 2
Keywords: Diabetes
Endothelial dysfunction
Stem cells
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2016-09-01
Enrollment: 16
Sex: ALL
Minimum age (years): 21
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Treatment Emergent Serious Adverse Events (TE-SAEs)
timeFrame: Up to one month (post infusion)
Secondary outcomes:
measure: EPC-CFU Levels
timeFrame: At Baseline, Day 3, Day 7, Day 14, Day 28, Day 90, Day 180, Day 365
measure: CRP Marker Levels
timeFrame: At Baseline, Day 3, Day 7, Day 14, Day 28, Day 90, Day 180, Day 365
measure: Circulating Angiogenic Factor Levels
timeFrame: At Baseline, Day 3, Day 7, Day 14, Day 28, Day 90, Day 180, Day 365
measure: Flow Mediated Diameter Percentage (FMD%)
timeFrame: At Baseline, Day 3, Day 7, Day 14, Day 28, Day 90, Day 180, Day 365
measure: Circulating Inflammatory Marker Levels
timeFrame: At Baseline, Day 3, Day 7, Day 14, Day 28, Day 90, Day 180, Day 365
measure: Tumor Necrosis Factor (TNF) Alpha Levels
timeFrame: At Baseline, Day 3, Day 7, Day 14, Day 28, Day 90, Day 180, Day 365
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
Study officials:
affiliation: ISCI / University of Miami Miller School of Medicine
name: Joshua M Hare, MD
role: PRINCIPAL_INVESTIGATOR
References: