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

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ClinicalTrials.gov Identifier: NCT02886884
Recruitment Status : Recruiting
First Posted : September 1, 2016
Last Update Posted : September 25, 2018
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Ivonne Schulman, University of Miami

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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus Drug: 20 million Allogeneic Mesenchymal Human Stem Cells Drug: 100 million Allogeneic Mesenchymal Human Stem Cells Phase 1 Phase 2

Detailed Description:

Sixteen (16) diabetic subject with endothelial dysfunction will be scheduled to undergo a peripheral intravenous infusion after meeting all inclusion/exclusion criteria at baseline.

Eight (8) subjects will be treated with 20 million (2 x 10^7) allogeneic hMSC's and eight (8) subjects will be treated with 100 million (100 x 10^6) allogeneic hMSC's

Follow up: Subjects will be followed at 3, 7, 14, 28 days, and 3 month post-infusion to complete all safety and efficacy assessments and at 6 and 12 months post-infusion to complete safety assessments.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 20, 2017
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : September 2024

Arm Intervention/treatment
Experimental: 20 million allogeneic hMSCs
Eight (8) subjects will be delivered via 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:
  • allo-hMSCs
  • stem cells

Experimental: 100 million hMSCs
Eight (8) subjects will be delivered via 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:
  • allo-hMSCs
  • stem cells




Primary Outcome Measures :
  1. Assess treatment-emergent serious adverse events [ Time Frame: 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 :
  1. Assess Endothelial Progenitor cell - colony forming units [ Time Frame: Assess at Baseline, Day 3, 7, 14, Day 28 and Month 3 following IV allogeneic mesenchymal stem cells infusion ]
    Assess Endothelial Progenitor cell - colony forming units

  2. Assess circulating inflammatory markers (IL-1) [ Time Frame: Assess at Baseline, Day 3, 7, 14, Day 28 and Month 3 following IV allogeneic mesenchymal stem cells infusion ]
    Assess circulating inflammatory markers (IL-1)

  3. Assess circulating inflammatory markers (IL-6) [ Time Frame: Assess at Baseline, Day 3, 7, 14, Day 28 and Month 3 following IV allogeneic mesenchymal stem cells infusion ]
    Assess circulating inflammatory markers (IL-6)

  4. Assess circulating inflammatory markers (Tumor Necrosis Factor(TNF) alpha) [ Time Frame: Assess at Baseline, Day 3, 7, 14, Day 28 and Month 3 following IV allogeneic mesenchymal stem cells infusion ]
    Assess circulating inflammatory markers (Tumor Necrosis Factor(TNF) alpha)

  5. Assess circulating inflammatory markers (CRP) [ Time Frame: Assess at Baseline, Day 3, 7, 14, Day 28 and Month 3 following IV allogeneic mesenchymal stem cells infusion ]
    Assess circulating inflammatory markers (CRP)

  6. Assess circulating angiogenic factors [ Time Frame: Assess at Baseline, Day 3, 7, 14, Day 28 and Month 3 following IV allogeneic mesenchymal stem cells infusion ]
    Assess circulating angiogenic factors known to mobilize and recruit Endothelial Progenitor cell (EPCs) (VEGF, Stromal cell derived factor (SDF)-1 alpha, and SCF)

  7. Assess Stromal cell derived factor (SDF)-1 alpha [ Time Frame: Assess at Baseline, Day 3, 7, 14, Day 28 and Month 3 following IV allogeneic mesenchymal stem cells infusion ]
    Assess circulating angiogenic factors known to mobilize and recruit Endothelial Progenitor cell (EPCs) such as Stromal cell derived factor (SDF)-1 alpha

  8. Assess Vascular endothelial growth factor (VEGF) [ Time Frame: Assess at Baseline, Day 3, 7, 14, Day 28 and Month 3 following IV allogeneic mesenchymal stem cells infusion ]
    Assess circulating angiogenic factors known to mobilize and recruit Endothelial Progenitor cell (EPCs) such as Vascular endothelial growth factor (VEGF)

  9. Assess stem cell factor (SCF) [ Time Frame: Assess at Baseline, Day 3, 7, 14, Day 28 and Month 3 following IV allogeneic mesenchymal stem cells infusion ]
    Assess circulating angiogenic factors known to mobilize and recruit Endothelial Progenitor cell (EPCs) such as stem cell factor (SCF)

  10. Assess FMD% [ Time Frame: Assess at Baseline, Day 3, 7, 14, Day 28 and Month 3 following IV allogeneic mesenchymal stem cells infusion ]
    Assess FMD% change



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02886884


Contacts
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Contact: Ivonne Schulman, MD 305-243-3583 ISchulman@med.miami.edu
Contact: Study Coordinators 305-243-7444 ISCIStudyInfo@med.miami.edu

Locations
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United States, Florida
University of Miami Miller School of Medicine Recruiting
Miami, Florida, United States, 33136
Contact: Ivonne Schulman, RN, BSN    305-243-7444    ISchulman@med.miami.edu   
Sponsors and Collaborators
Ivonne Schulman
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Ivonne Schulman, MD ISCI / University of Miami Miller School of Medicine

Additional Information:
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Responsible Party: Ivonne Schulman, Sponsor - Investigator, University of Miami
ClinicalTrials.gov Identifier: NCT02886884     History of Changes
Other Study ID Numbers: 20160686
1R01HL134558-01 ( U.S. NIH Grant/Contract )
First Posted: September 1, 2016    Key Record Dates
Last Update Posted: September 25, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ivonne Schulman, University of Miami:
Diabetes
Endothelial dysfunction
Stem cells

Additional relevant MeSH terms:
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Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases