Autologous CD133(+) Cells as an Adjuvant to Below the Knee Percutaneous Transluminal Angioplasty

Shanghai 10th People's Hospital345 enrolled

Overview

The main aim of the present study was to evaluate the therapeutic potential and safety of transarterial infusion of granulocyte colony stimulating factor (G-CSF) mobilized cluster of differentiation (CD) 133(+) cells when combined with percutaneous transluminal angioplasty (PTA) in treatment of below the knee (BTK) peripheral arterial disease (PAD) in diabetic patients.

CD133+ cell, a bone marrow derived subpopulation of adult hematopoietic progenitor cells, confers high proliferative, vasculogenic and regenerative capacity in vitro and in vivo. thereby suggesting that CD133+ cells may induce vasculogenesis, improve limb perfusion, prevent tissue loss and restore ambulatory function in patients with critical limb ischemia. Although several small, randomized trials have been conducted so far demonstrating safety of autologous cells of bone marrow origin for the treatment, the reported benefits were found to be variable. A meta-analysis of autologous bone marrow derived cell therapy for critical limb ischemia trials suggested that application of autologous stem cell transplantation in curing limb ischemic patients does not have obviously effectiveness in the improvement of ankle brachial pressure (ABI) of the limb ischemic patients. But it can dramatically reduce the rate of amputation. Therefore, in the present study, the investigators aim to evaluate the therapeutic potential and safety of transarterial infusion of g-csf-mobilized CD 133(+) cells when combined with PTA in treatment of below the knee PAD in diabetic patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

345

Conditions

Peripheral Arterial Disease

Interventions

G-CSF + CD133(+) cellsBIOLOGICAL

Patients in the G-CSF + CD133(+) cells + PTA group, received 150 unit of recombinant human G-CSF intramuscular injection to mobilize CD 133 cells from bone marrow to peripheral blood. After 72-120 hrs, 100 ml suspension of peripheral arterial blood were collected and send to Good Products Manufacturing (GPM) certified laboratory (Shanghai Chen Chuan Biological Material Co. Ltd.) within 24 hrs of obtaining sample to isolate CD 133(+) endothelial progenitor cells (EPC) using magnetic cell separator. Subjects in this group, after vascular PTA treatment, received transarterial infusion of 50 ml suspension of isolated autologous CD 133(+) cells over 30 min via catheter opened into popliteal artery. The infusion of CD 133 cells was repeated after 24 hours.

G-CSFBIOLOGICAL

Subjects in this group, after vascular PTA treatment, received 150 unit of recombinant human G-CSF intramuscular injection to mobilize EPCs from bone marrow to peripheral blood. But the C133 (+) cells were not isolated from the peripheral blood to infuse transarterially as in G-CSF + CD133(+) + PTA.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age range: 18-75 years , Gender: Both 2. Patients with below the knee limb ischemia with diabetes. 3. Rutherford class 2-6. 4. Target lesions with a diameter reduction of at least 50% and have an occlusion of longer than 4 cm on angiography. 5. Have no previous history of any stem cell therapy \[infusion of CD133 endothelial progenitor cell (EPC)\]. Written informed consent signed by the patients or representatives. - Exclusion Criteria: 1. Previous bypass surgery or stent placement at the ipsilateral lower limb 2. History of intolerance to antiplatelet therapy, heparin, or contrast media. 3. Presence of any of the following conditions: 1. severe liver disease (such as ascites, esophageal varices, liver transplantation); 2. hemodynamic instability; 3. Severely impaired renal function (serum creatinine level \> 2.5 mg/dL). 4. Receiving immunosuppressive therapy; 5. History of decompensated heart failure (New York Heart Association class III or IV and level) or myocardial infarction, or heart bypass surgery; 6. Bleeding diathesis; 7. Active systemic bacterial infection; 8. Acute thrombophlebitis or deep vein thrombosis of the target limb; 4) Pregnant or lactating women, or women of child bearing age unable or unwilling to use effective contraception during the study period; 5) Expected survival time of less than 24 months -

Locations (1)

Shanghai Tenth People's Hospital, Tong ji University

Shanghai, China

RECRUITING

Outcomes

Primary Outcomes

Restenosis rate

Occurrence of \> 50% of restenosis in the treated vessel after 12 months as assessed by digital substraction angiography (DSA) (Efficacy endpoints).

Time frame: 12 months

Peak systolic velocity ratio

Peak systolic velocity ratio ≥ 2.4 by Doppler's ultrasonography for patients who did not undergo angiography after 12 months (Efficacy endpoints).

Time frame: 12 months

Severe adverse effects (SAEs)

Number of SAEs per subject across actual treatment cohorts (Safety Endpoint).

Time frame: 12 months

Secondary Outcomes

ABI value

Improvement in ABI value by ≥ 0.1 after the procedure and lack of deterioration \> 0.15 in relation to the maximal value recorded before the procedure.

Time frame: 6 and 12 months

Rutherford classification

improvement in Rutherford scale of at least one category after the procedure.

Time frame: 6 and 12 months

Transcutaneous oxygen pressures (TcPO2)

.Changes in TcPO2 was assessed at each follow up interval and compared to baseline.

Time frame: 6 and 12 months

Amputation-free survival (AFS)

Time to below the knee amputation of the ipsilateral leg.

Time frame: 6 and 12 months

Rest pain

Rest pain was measured using Wong-Baker FACES pain rating scale at baseline and each follow-up visit.

Central Contacts

Mao Q Li, Ph.D

CONTACT

02166313506 cjr.limaoquan@vip.163.com

Data from ClinicalTrials.gov

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