A Study of Blood-Borne Autologous Angiogenic Cells Precursors Therapy in Patients With Critical Limb Ischemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Evaluate the safety of ACPs intramuscular injection
研究概览
简要总结
Study title: A Study of Blood-Borne Autologous Angiogenic Cell Precursors Therapy in Patients with Critical Limb Ischemia ( ACPs-CLI )
Principle Investigator: Assoc.Prof. Pramook Mutirangura,M.D. Head of Division of Vascular Surgery , Department of Surgery, Faculty of Medicine Siriraj Hospital , Mahidol University, BKK,Thailand
Study objective : To determine the safety and efficacy of intramuscular injection of blood-borne autologous ACPs in relieving symptoms of critical limb ischemia of patients treated with maximal medical therapy and don't have intravascular or operative revascularization option.
Study Design : A pilot study , a single center, a non-randomized, open-label trial.
Total expected no. of patients : 6 main selection criteria : A. Subjects will have one or more clinical indications diagnostic of CLI such as: distal extremity pain at rest that requires the subject to use analgesics for >2 weeks; or peripheral ischemic ulcer(s); or areas of gangrene ; or non-healing ischemic ulcers AND
B. Subjects will have one or more of the following hemodynamic indicators of severe peripheral arterial occlusive disease:
I. Ankle brachial index < 0.45 II. Toe brachial index < 0.35 III. TcPO2 / TcO2 of < 40 mmHg. C. The subject is a poor candidate for standard revascularization treatment for peripheral arterial disease, based on inadequate bypass conduit, or unfavorable anatomy D. Age 18 to 80 years
Investigational Product : At D-8 250 ml of blood drawn from the patients for production of autologous EPCs or ACPs (VescellTM). On D0 ,at least 1.5 million ACPs with viability >75 % suspended in 30 ml sterile cell culture medium will be injected 1.5 cm deep and 1.5 apart by a 23 -gauge needle into the gastrocnemius muscle of the leg chosen (ischemic leg) for treatment. For injection planning a grid of 10X10 cm will be prepared and in each point 1 ml of ACPs suspension will be injected.
The study consists of 4 periods: Screening ( D-14 to-9& D-8,Treatment(D0),Acute Safety follow-up (D1&D2),Chronic follow-up (D30 & D90)period ,total follow-up of each case is 3 months.
Evaluation criteria :
Safety : no.& duration of adverse event & serious adverse event Efficacy :Attenuate CLI patients symptoms (Rest pain,Pain-free walking distance,Ulcer size &Gangrene dimension and intensity)
详细描述
Six patients with Critical Limb Ischemia (CLI) or severe Peripheral Arterial Disease(PAD) will be enrolled, screened, treated with an injection of Blood-Borne Autologous Angiogenic Cell Precursors(ACPs) in to gastrocnemius of the ischemic leg by intramuscular under regional anesthesia. Following injection.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects will have one or more clinical indications diagnostic of CLI such as: distal extremity pain at rest that requires the subject to use analgesics for >2 weeks; or peripheral ischemic ulcer(s); or areas of gangrene ; or non-healing ischemic ulcers AND
- •Subjects will have one or more of the following hemodynamic indicators of severe peripheral arterial occlusive disease:
- •Ankle brachial index < 0.45
- •Toe brachial index < 0.35
- •TcPO2 / TcO2 of < 40 mmHg.
- •The subject is a poor candidate for standard revascularization treatment options for peripheral arterial disease, based on inadequate bypass conduit, or unfavorable anatomy
- •Age 18 to 80 years
- •Male or non-pregnant, non-lactating female
- •Informed consent obtained and consent form signed
排除标准
- •Patient having on angiography a meaningful supra popliteal occlusion that may relate to symptoms of CLI.
- •Subjects, who in the opinion of the investigator, have a vascular disease prognosis that indicates they would require a major amputation (at or above the ankle) within 4 weeks of start of treatment
- •Patient who received blood transfusions during the previous 4 weeks (to exclude the potential of non-autologous ACPs in the harvested blood).
- •Inability to communicate (that may interfere with the clinical evaluation of the patient)
- •Major operation during the preceding 3 months
- •Myocardial infarction or brain infarction or uncontrolled myocardial ischemia or persistent severe heart failure (EF< 25 %) during the preceding 3 months
- •Significant valvular disease or after valve replacement during the preceding 3 months
- •After heart transplantation
- •Severe cardiomyopathy (EF < 25 %)
- •Renal failure (creatinine > 2 mg/dl )
- •Hepatic failure
- •Anemia (lower than 11mg/dl.hemoglobin for female and lower than 12 mg/dl for male)
- •Abnormal coagulation tests [platelets, PT (INR), PTT]
- •Stroke within the preceding 3 years
- •Malignancy within the preceding 3 years
- •Concurrent chronic or acute infectious disease
- •Severe concurrent medical disease (e.g., septicemia, HIV-1,2/HBV/HCV infections, poorly controlled insulin-dependent diabetes mellitus ; HBA1c >8 % and proliferative retinopathy , systemic lupus erythematosus, multiple sclerosis, amyotrophic lateral sclerosis)
- •Chronic immunomodulating or cytotoxic drugs treatment
- •Patients who have rectal temp. above 38.40C for 2 consecutive days
- •Patient unlikely to be available for follow-up
结局指标
主要结局
Evaluate the safety of ACPs intramuscular injection
时间窗: 3 months
Efficacy
时间窗: 3 months
Safety
时间窗: 3 months
Attenuate CLI patients symptoms as
时间窗: 3 months
Rest pain
时间窗: 3 months
Pain-free walking distance
时间窗: 3 months
Ulcer size
时间窗: 3 months
Gangrene dimension and intensity
时间窗: 3 months
Obtain evidence for improvement of tissue perfusion due to ACPs injection
时间窗: 3 months
次要结局
- Reduction of CLI patients hospitalization time.(3 months)
- Decrease CLI patient amputation rate.(3 months)