Clinical Trial Phase I / II, Multicentre, Open, Randomized Study of the Use of Mesenchymal Stem Cells From Adipose Tissue (CeTMAd) as Cell Regeneration Therapy in Critical Chronic Ischemic Syndrome of Lower Limb in Nondiabetic Patients.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 33
- 试验地点
- 4
- 主要终点
- Number of adverse events and serious adverse events
研究概览
简要总结
Clinical trial phase I / II, prospective, multicenter, open, randomized, parallel-groups controlled by two levels of dose to assess the safety and feasibility of the infusion of mesenchymal stem cells from adipose tissue administered intra-arterially in nondiabetic patients with chronic ischemia of lower limbs (CLI) and no possibility of revascularization.
详细描述
A prospective, multicenter, open, randomized, parallel-group controlled study for two levels of dose.
The study population will consist of 30 non-diabetic patients with critical chronic ischemia in at least one of the lower limbs (CLI) and without possibility of revascularization, from whom results can clinically be evaluable, of whom, 20 patients will be included in the experimental group (10 for each dose level) and 10 in the control group.
In each of the two dose levels to be used in the study, 15 patients will be included, who will be randomized to the experimental group or the control group according to a distribution 2:1 (2 patients in the experimental group and 1 in control group), thus at each dose level, we will have 10 patients in the experimental group (treated with mesenchymal cells of adipose tissue) and 5 patients in the control group (conventional treatment, including the use of prostaglandins per protocol).
Patients who are randomized to experimental treatment Group with CeTMAd may receive one of the following dose levels:
- 0.5x106 cells / kg of patient weight
- 1x106 cells / kg of patient weight
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
- None
入排标准
- 年龄范围
- 18 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients of both sexes aged ≥ 18 and ≤ 89 years.
- •Nondiabetic.
- •Infrapopliteal atherosclerotic vascular disease of severe grade with either severe claudication or Rutherford-Becker grade II-III-IV, of at least one lower limb. It is defined critical ischemia of the lower limb as persistent/recurrent pain requiring analgesia and / or non-healing present ulcers > 4 weeks, with no evidence of improvement with conventional therapies and / or walking test (stress test) between 1-6 minutes in two exercise tests separated by at least 2 weeks and / or ankle-brachial index at rest <0.
- •Inability of surgical or endovascular revascularization as recommended by the TransAtlantic InterSociety Consensus (TASC).
- •Failure in the revascularization surgery performed at least 30 days before, with persistence or entry in critical ischemia phase.
- •Life expectancy> 2 years.
- •Not expected major amputation in the limb to treat in the next 12 months after inclusion.
- •Normal biochemical parameters defined by:
- •Leukocytes ≥ 3000
- •Neutrophils ≥ 1500
- •Platelets ≥ 100,000
- •Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) ≤ 2.5 standard range institution
- •Creatinine ≤ 2.5 mg / dl.
- •Patients give their written informed consent to participate in the study.
- •Women of childbearing potential must have negative results on a pregnancy test done at the time of inclusion in the study and agree to use a medically approved method of contraception for the duration of the study.
排除标准
- •History of malignancy or hematologic disease (myeloproliferative disease, myelodysplastic syndrome or leukemia) in the last two years.
- •Patients with uncontrolled hypertension (defined as blood pressure> 180/110 on more than one occasion).
- •Severe heart failure (New York Heart Association class IV) or ejection fraction of the left ventricle less than 30%.
- •Patients with malignant ventricular arrhythmias or unstable angina at the time of infusion.
- •Diagnosis of deep vein thrombosis in the previous 3 months.
- •Active infection or wet gangrene at day of infusion of Mesenchymal Stem Cells from Adipose Tissue.
- •Concomitant therapy including hyperbaric oxygen. It is allowed the use of antiplatelet agents.
- •Body mass index>40 kg/m
- •Patients with a diagnosis of alcoholism at the time of inclusion.
- •Untreated proliferative retinopathy.
- •Concomitant disease that reduces life expectancy to less than a year.
- •Predicted impossibility to obtain a biopsy providing 10 g of adipose tissue.
- •human immunodeficiency virus, hepatitis B virus or hepatitis C virus.
- •Difficulty in monitoring.
- •Stroke or myocardial infarction within the last 3 months.
- •Anemia (hemoglobin <7.9 mg / dl).
- •Leukopenia.
- •Thrombocytopenia (<100,000 platelets / ul).
- •Pregnant women or women of childbearing age who do not have adequate contraception.
- •Patients who participated in a clinical trial within the last 3 months prior to inclusion in this clinical trial.
研究组 & 干预措施
Control
Conventional treatment
High dose
- Infusion of mesenchymal stem cells from adipose tissue: 1x106 cells / kg of patient weight.
干预措施: Mesenchymal stem cells from adipose tissue (Other)
Low dose
- Infusion of mesenchymal stem cells from adipose tissue: 0.5x106 cells / kg of patient weight.
干预措施: Mesenchymal stem cells from adipose tissue (Other)
结局指标
主要结局
Number of adverse events and serious adverse events
时间窗: 12 months.
Number of adverse events and serious adverse events: 24h administration of CeTMAd, 1 month, 3 months, 6 months, 9 months and 12 months.
次要结局
- Evolution of chronic critical ischemia(1 month, 3 months, 6 months, 9 months and 12 months)