Comparison of the Therapeutic Potential of Autologous Bone Marrow Mononuclear Cells Versus Allogenic Wharton Jelly-derived Mesenchymal Stem Cells in Diabetic Patients With Chronic Limb-threatening Ischemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Efficacy profile: Rutherford's classification
研究概览
简要总结
Patients in the severe stages of Chronic limb-threatening ischemia (CLTI) are prone to amputation and death, leading to poor quality of life and a great socioeconomic burden.
There is an urgent need to develop an effective therapeutic strategy to treat this disease. In this context, autologous bone marrow mononuclear cells (BM-MNC) and allogeneic mesenchymal stem cells derived from different sources have emerged as promising therapeutic approaches for this condition.
详细描述
Comparison of the therapeutic potential of BM-MNC vs. allogeneic Wharton jelly-derived mesenchymal stem cells (allo-WJ-MSCs) in diabetic patients with CLTI.
Twenty-four type 2 diabetic patients in the most severe stages of the CLTI (category 4 or 5 in Rutherford's classification and transcutaneous oxygen pressure (TcPO2) below 30 mm Hg were enrolled and randomized to receive 15 injections of (i) BM-MNC (7.197x106 ± 2.984 x106 cells/mL each with 2% of autologous serum) (n=7), (ii) allo-WJ-MSCs (1.333 x106 cells/mL each with 5% of human serum albumin serum) (n=7) or (iii) placebo solution (1 mL saline solution with 2% of autologous serum) (n=10), which were administered into the periadventitial arteries.
The follow-up visits were at months 1, 3, 6, and 12, to evaluate the following parameters:
(i) Rutherford classification (0 to 6) (ii) TcPO2 (mmHg) (iii) Wound closure (area cm2) (iv) pain (visual analogue scale (0-10) (v) pain-free walking distance (m) (vi) revascularization and limb-survival proportion during follow-up (vii) the quality of life (EQ-5D questionnaire).
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult male or female, 40 years of age or over (until 85 years old)
- •TcPO2 ≤ 30 mmHg.
- •Diagnosis of diabetes.
- •Patients with signs of critical ischemia such as (i) ulcer that does not heal, (ii) necrosis or loss of tissue, (iii) pain at rest, and (iv) intermittent claudication.
- •Basal Rutherford classification stage 3 to
- •Non-revascularizable patients due to comorbidities and/or anatomy.
- •Patients that despite revascularization (vascular surgery), have adequate distal beds to perfuse the limb.
- •Ankle/brachial index less than 0.
- •Stenosis or occlusion of the infrapatellar arteries.
排除标准
- •Participants that do not sign the informed consent.
- •Presence of osteomyelitis.
- •Hemodynamic instability (MAP<65 mmHg or vasopressor requirement).
- •Any acute systemic infectious disease process.
- •Severe sepsis.
- •Uncontrolled coagulopathy.
- •Condition of cancer.
- •Use of immunosuppressive or cytotoxic drugs
- •Alterations of the bone marrow that do not allow the adequate extraction of the components to be used as: acute leukemia, chronic leukemia, marrow aplasia, myelodysplastic syndrome, and myelophthisis.
- •Contraindication of sedation for bone marrow aspirate.
- •Patients who have suffered in a period < six months of myocardial infarction, disease cerebrovascular or coronary intervention.
- •Patients with liver failure indicated by serum transaminases (aspartate aminotransferase and alanine aminotransferase), with values twice the normal limit.
- •Any acute or chronic contagious disease including hepatitis B, hepatitis C, and HIV.
- •Any other comorbidity that the treating vascular surgeon considers as a contraindication to cell treatments.
结局指标
主要结局
Efficacy profile: Rutherford's classification
时间窗: 12 months
0 to 6
TcPO2
时间窗: 12 months
mmHg
Efficacy profile: Pain-free walking distance
时间窗: 12 months
meters
Safety profile: (adverse events (AEs) and serious AEs)
时间窗: 12 months
AEs: (i) local toxicity, including signs of local inflammation (swelling, warmth, impairment of function), worsening of ulcer, new ulcer, or hematomas after auto-BM-MNC or allo-WJ-MSCs administration. (ii) systemic toxicity as fever, allergies. (iii) maximum grade toxicity for tissue.
Safety profile
时间窗: 12 months
Serious AEs: hospitalization, malignancy, amputation, persistent or significant disability, or death.
Efficacy profile: Visual Analogue Scale pain
时间窗: 12 months
0 to10
Efficacy profile: Limb survival proportion
时间窗: 12 months
Percentage
Efficacy profile: Quality of life
时间窗: 12 months
EQ-5D questionnaire
Efficacy profile: Wound closure
时间窗: 12 months
cm2
Efficacy profile: Revascularization
时间窗: 12 months
Percentage
次要结局
未报告次要终点
研究者
Martha Ligia Arango Rodríguez
Director Technical and Scientific Centro de Terapias Avanzadas Fundación Ofalmológica de Santander (FOSCAL)
Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle