Allogeneic Mesenchymal Stromal Cells for Angiogenesis and Neovascularization in No-option Ischemic Limbs; A Double-blind, Randomized, Placebo-controlled Trial
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Therapy Success
研究概览
简要总结
The primary objective of this trial is to investigate whether intramuscular administration of allogeneic mesenchymal stromal cells (MSC) is safe and potentially effective, assessed as a composite outcome of mortality, limb status, clinical status (Rutherford classification) and pain score (visual analogue scale), in patients with no-option severe limb ischemia (SLI).
The investigators will conduct a double-blind, placebo-controlled randomized clinical trial to investigate the effect of allogeneic bone marrow(BM)-derived MSC in patients with SLI, who are not eligible for conventional surgical or endovascular therapies. The investigators intend to include 60 patients, who will be randomized to undergo 30 intramuscular injections with either BM-MSC (30 injection sites with 5*10^6 MSCs each) or placebo in the lower leg of the ischemic extremity. Primary outcome i.e. therapy success, a composite outcome considering mortality, limb status, clinical status (Rutherford classification) and changes in pain score, will be assessed at six months.
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)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 years
- •Severe Peripheral Artery Disease (PAD; Fontaine class III and / or IV):
- •Fontaine III (Rutherford 4): persistent, recurring rest pain requiring analgesia
- •Fontaine IV (Rutherford 5): non-healing ulcers present for > 4 weeks without evidence of improvement in response to conventional therapies
- •Ankle brachial index < 0.6 or unreliable (non-compressible or not in proportion to the Fontaine classification)
- •Not eligible for surgical or endovascular revascularization
- •Written informed consent.
排除标准
- •History of neoplasm or malignancy in the past 10 years
- •Serious known concomitant disease with life expectancy of less than one year
- •Rutherford 6 in which amputation on the short term (within 1-2 weeks) is inevitable
- •Pregnancy or unwillingness to use adequate contraception during study
- •Uncontrolled acute or chronic infection with systemic symptoms
- •Follow-up impossible.
研究组 & 干预措施
Allogeneic Mesenchymal Stromal Cell
Intramuscular Allogeneic Bone marrow-derived Mesenchymal Stromal Cell Injection
干预措施: Allogeneic Mesenchymal Stromal Cell (Drug)
Placebo
Intramuscular placebo injection
干预措施: Placebo (Other)
结局指标
主要结局
Therapy Success
时间窗: 6 months
Composite outcome measure considering mortality, limb status, clinical classification and changes in pain score. To be a "success" a subject must: A, be alive; B, be without a major amputation on the index limb; C, have not worsened in Rutherford classification or visual analog pain scale; and D, have improved in either Rutherford classification or visual analog pain scale. Subjects not meeting all of the criteria are classified as failures.
次要结局
- Major amputation(2, 6, 12, 24, and 60 months)
- Minor amputation(2, 6, 12, 24, and 60 months)
- Therapy Success(2, 6, 12, 24, and 60 months)
- Mortality(2, 6, 12, 24, and 60 months)
- Ulcer healing(2 and 6 months)
- Changes in pain(2, 6, 12, 24, and 60 months)
- Pain-free walking distance(2 and 6 months)
- Ankle-brachial index (ABI)(2 and 6 months)
- Toe-brachial index (TBI)(2 and 6 months)
- Quality of life based on EuroQol 5D (EQ5D) questionnaire scores(2, 6, 12, 24, and 60 months)
- Quality of life based on Short Form 36 (SF36) questionnaire scores(2, 6, 12, 24, and 60 months)
- Clinical status according to Fontaine classification(2, 6, 12, 24, and 60 months)
- Clinical status according to Rutherford classification(2, 6, 12, 24, and 60 months)
研究者
Martin Teraa, MD, PhD
Surgical Resident & Postdoc Physician
UMC Utrecht