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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Number of Treatment Emergent Serious Adverse Events (TE-SAEs)
研究概览
简要总结
This is a 16 subject trial to demonstrate the safety of allogeneic hMSCs administered via infusion therapy for diabetic subjects with endothelial dysfunction.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Pilot phase is open label. Randomized phase is blinded.
入排标准
- 年龄范围
- 21 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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 1.3), cannot be withdrawn from anticoagulation therapy, or will refuse blood transfusions.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.
研究组 & 干预措施
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)
干预措施: 20 million Allogeneic Mesenchymal Human Stem Cells (Drug)
Pilot Phase 100 million hMSCs
Participants in this group will receive one peripheral intravenous infusion of 100 million allogeneic Mesenchymal Human Stem Cells (hMSCs)
干预措施: 100 million Allogeneic Mesenchymal Human Stem Cells (Drug)
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)
干预措施: 20 million Allogeneic Mesenchymal Human Stem Cells (Drug)
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)
干预措施: 100 million Allogeneic Mesenchymal Human Stem Cells (Drug)
结局指标
主要结局
Number of Treatment Emergent Serious Adverse Events (TE-SAEs)
时间窗: 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.
次要结局
- CRP Marker Levels(At Baseline, Day 3, Day 7, Day 14, Day 28, Day 90, Day 180, Day 365)
- EPC-CFU Levels(At Baseline, Day 3, Day 7, Day 14, Day 28, Day 90, Day 180, Day 365)
- Tumor Necrosis Factor (TNF) Alpha Levels(At Baseline, Day 3, Day 7, Day 14, Day 28, Day 90, Day 180, Day 365)
- Circulating Angiogenic Factor Levels(At Baseline, Day 3, Day 7, Day 14, Day 28, Day 90, Day 180, Day 365)
- Flow Mediated Diameter Percentage (FMD%)(At Baseline, Day 3, Day 7, Day 14, Day 28, Day 90, Day 180, Day 365)
- Circulating Inflammatory Marker Levels(At Baseline, Day 3, Day 7, Day 14, Day 28, Day 90, Day 180, Day 365)
研究者
Joshua M Hare
Sponsor - Investigator
University of Miami