Autologous Bone Marrow-derived Mononuclear Cells for Therapeutic Arteriogenesis in Patients With Limb Ischemia (ABC)
Autologous Bone Marrow-derived Mononuclear Cells for Therapeutic Arteriogenesis in Patients With Limb Ischemia A Double Blind, Placebo Controlled, Study in Diabetic and Non-diabetic Patients
研究概览
详细说明
Although the safety and beneficial effects of intramuscular transplantation of bone marrow derived mononuclear cells procedure appear well documented, a number of critical question regarding application of BM-MNC for peripheral vascular disease remain to be answered. First, although the original study has been partially performed as semi-blinded study (patients with double sided claudication were recruited and blindly treated with BM-MNC in one leg and peripheral blood injections in the other leg), this approach does exclude a placebo effect. Second, although patients with mild diabetes were included in the protocol, the results for diabetic patients were not analyzed separately. Diabetic disease is characterized by monocyte and endothelial progenitor cell dysfunction and it is still unclear whether this approach is also effective in diabetic patients. Third, although six-month results are reported long-term efficacy has not been established yet.
To address these issues, the investigators now propose confirm and extend the findings from open studies in a randomized double-blind study in patients with severe claudication or critical leg ischemia and pay special attention to the influence of diabetic disease on the outcome of the study and to the possible pro-atherogenic/ pro-inflammatory effects of BM-MNC injections.
研究类型
注册 (预期的)
阶段
- 阶段2
- 第三阶段
联系人和位置
学习地点
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Leiden、荷兰、2300RC
- 招聘中
- Leiden University Medical Center
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接触:
- Jan HN Lindeman, MD, PhD
- 电话号码:#31 (0)71 5263968
- 邮箱:Lindeman@lumc.nl
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- persistent (>3 months) disabling claudication (Fontaine's stages IIb or Rutherford's categories 3, viz. pain free walking distance less than 100 meter) despite optimal therapy or critical limb ischemia (Fontaine's stages III/IV or Rutherford's categories 4-6)
- ineligibility for angioplasty or bypass procedures
- male of female, >18 years old
- life expectancy > 1 year
- written informed consent
Exclusion Criteria:
- candidates for angioplasty or bypass procedures
- inability to undergo bone marrow harvesting
- any condition in the affected limb that is anticipated to require surgical intervention in the first weeks after BM-MNC treatment
- life threatening co-morbidity
- poorly controlled diabetes (HbA1C > 10%)
- active malignancy in the 5 years prior to treatment
- INR >1.5 at the time of bone-marrow harvest
- bleeding diathesis
- inability to undergo arterial catheterization
- inability to follow the protocol and to comply with the follow up requirements
- any other conditions that, in the opinion of the investigators, could interfere with the therapy or could pose a significant threat to the subject if the investigational therapy was to be initiated
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:四人间
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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有源比较器:1
non diabetic patients with Fontaine IIb-IV peripheral artery disease
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40 IM injections (calf muscle) of 1-8 10E9 mono nuclear cells
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安慰剂比较:2
non diabetic patients with Fontaine IIb-IV peripheral artery disease
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40 IM injections (calf muscle) of placebo suspension
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有源比较器:3
diabetic patients with Fontaine IIb-IV peripheral artery disease
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40 IM injections (calf muscle) of 1-8 10E9 mono nuclear cells
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安慰剂比较:4
diabetic patients with Fontaine IIb-IV peripheral artery disease
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40 IM injections (calf muscle) of placebo suspension
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研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
|---|---|
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Limb salvage/wound healing at t=6 months; Pain free walking distance
大体时间:6 months
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6 months
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次要结果测量
结果测量 |
大体时间 |
|---|---|
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quality of life (RAND-36), pain Scores (Brief Pain Inventory), tcO2 (wrist/ankle ratio) ABI Collateral artery scores (angiogram) at t=6 months, Limb salvage/wound healing at t= 3 and 12 months, Pain free walking distance at t=3 and 12 months,
大体时间:3, 6 and 12 months
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3, 6 and 12 months
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合作者和调查者
调查人员
- 首席研究员:Jan HN Lindeman, MD, PhD、Leiden University Medical Center
出版物和有用的链接
一般刊物
- Moazzami B, Mohammadpour Z, Zabala ZE, Farokhi E, Roohi A, Dolmatova E, Moazzami K. Local intramuscular transplantation of autologous bone marrow mononuclear cells for critical lower limb ischaemia. Cochrane Database Syst Rev. 2022 Jul 8;7(7):CD008347. doi: 10.1002/14651858.CD008347.pub4.
- Lindeman JHN, Zwaginga JJ, Kallenberg-Lantrua G, van Wissen RC, Schepers A, van Bockel HJ, Fibbe WE, Hamming JF. No Clinical Benefit of Intramuscular Delivery of Bone Marrow-derived Mononuclear Cells in Nonreconstructable Peripheral Arterial Disease: Results of a Phase-III Randomized-controlled Trial. Ann Surg. 2018 Nov;268(5):756-761. doi: 10.1097/SLA.0000000000002896.
研究记录日期
研究主要日期
学习开始
初级完成 (预期的)
研究完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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