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

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

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

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: 100 million Allogeneic Mesenchymal Human Stem Cells; Drug: 20 million Allogeneic Mesenchymal Human Stem Cells

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Pilot Phase 20 million allogeneic hMSCs; Participants in this group will receive one peripheral intravenous infusion of 20 million allogeneic Mesenchymal Human Stem Cells (hMSCs)	Drug: 20 million Allogeneic Mesenchymal Human Stem Cells; 1 single intravenous infusion; Other Names: stem cells; allo-hMSCs
EXPERIMENTAL: Pilot Phase 100 million hMSCs; Participants in this group will receive one peripheral intravenous infusion of 100 million allogeneic Mesenchymal Human Stem Cells (hMSCs)	Drug: 100 million Allogeneic Mesenchymal Human Stem Cells; 1 single intravenous infusion; Other Names: stem cells; allo-hMSCs
EXPERIMENTAL: Randomized Phase 20 million allogeneic hMSCs; Participants in this group will receive one peripheral intravenous infusion of 20 million allogeneic Mesenchymal Human Stem Cells (hMSCs)	Drug: 20 million Allogeneic Mesenchymal Human Stem Cells; 1 single intravenous infusion; Other Names: stem cells; allo-hMSCs
EXPERIMENTAL: Randomized Phase 100 million allogeneic hMSCs; Participants in this group will receive one peripheral intravenous infusion of 100 million allogeneic Mesenchymal Human Stem Cells (hMSCs)	Drug: 100 million Allogeneic Mesenchymal Human Stem Cells; 1 single intravenous infusion; Other Names: stem cells; allo-hMSCs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treatment Emergent Serious Adverse Events (TE-SAEs)	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.	Up to one month (post infusion)

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Joshua M Hare
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

Helpful Links

• Interdisciplinary stem cell institute at the University of Miami website

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 20, 2017
• Primary Completion (ACTUAL): August 26, 2019
• Study Completion (ACTUAL): September 3, 2020

Study Registration Dates

• First Submitted: August 29, 2016
• First Submitted That Met QC Criteria: August 31, 2016
• First Posted (ESTIMATE): September 1, 2016

Study Record Updates

• Last Update Posted (ACTUAL): May 11, 2022
• Last Update Submitted That Met QC Criteria: April 18, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Diabetes; Endothelial dysfunction; Stem cells
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 20160686; 1R01HL134558-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No