Autologous Transplantation of BM-ECs With Platelet-Rich Plasma Extract for the Treatment of Critical Limb Ischemia

Study Overview
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Brief Summary
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The intent of this clinical study is to evaluate the safety of the injection composed of autologous bone marrow derived endothelial cells (BM-ECs) and platelet-rich plasma extract (PRPE) for the treatment of critical limb ischemia.

Conditions
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Leg Ulcer, Diabetic Foot, Gangrene, Peripheral Vascular Disease, Ischemia

Intervention / Treatment
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* Biological: BM-ECs and PRPE
* Biological: BM-ECs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Limb ischemia patients(e.g. arteriosclerosis obliterans,diabetic critical limb ischemia, thromboangitis obliterans) 18 Years to 80 Years (Adult, Senior); Have ability to understand and comply with the study requirements, and provide the written informed consent prior to any procedures ; Patient meets at least one of the following diagnostic criteria for the index limb: ABI<0.7mmHg TcpO2 <40 mm Hg Or, nonhealing ulcer due to local arterial compromise with no opportunity for revascularization; Have no improvement after conservative treatment and are not suitable for surgical bypass surgery because no outflow tract of diseased vessel can be found by imaging; Despite having good outflow artery, but the elderly and frail patients can also not tolerate revascularization or interventional surgery; Unlikelihood of major amputation of the leg during the next 12 months; Expected life span more than 2 years. Exclusion Criteria: Pregnant or lactating; Diabetics with poorly controlled blood glucose levels (defined as HbA1c>7% and/or proliferative retinopathy); Patients with decompensated cardiac, renal or liver disease; Patients with confirmed malignant tumor; Subjects are with serious heart, liver, kidney and lung failure or under poor general condition that are inability to undergo bone marrow harvesting and transplantation; Known or suspected disease of the immune system or osteomyelitis; Inability to sign informed consent form and to comply with the schedule of the study; There has reason to suspect that the patient is forced to join the study; Any other condition, in the opinion of the investigator, would render the patient unsuitable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BM-ECs and PRPE<br>Multipoint of intramuscular injections into ischemic limbs.Injections composed of bone marrow derived endothelial cells (BM-ECs) and platelet-rich plasma extract (PRPE). | Biological: BM-ECs and PRPE<br> <br> |
| Active Comparator: BM-ECs<br>Intramuscular injection of bone marrow derived endothelial cells only. | Biological: BM-ECs<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival without major amputation |  | 6 months after implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perfusion rate in treated tissue by measure of ankle-brachial index (ABI) |  | Within 6 months after implantation | 
| Perfusion rate in treated tissue by transcutaneous PO2 (TcPO2) |  | Within 6 months after implantation | 
| Perfusion rate in treated tissue by digital subtraction angiography (DSA) |  | Within 6 months after implantation | 
| wound size |  | Within 6 months after implantation | 
| wound stage |  | Within 6 months after implantation | 
| Pain intensity | Pain intensity using Visual Analogue Scale | Within 6 months after implantation | 
| Thermography |  | Within 6 months after implantation |