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

Tongji University

Status and phase: Unknown; Phase 1

Conditions: Peripheral Arterial Disease

Treatments: Procedure: percutaneous transluminal angioplasty (PTA); Biological: Placebo infusion; Biological: G-CSF + CD133(+) cells; Biological: G-CSF

Study type: Interventional

Funder types: Other

Identifiers

NCT02915796

2016-xjs-08

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 345 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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 -

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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345 participants in 3 patient groups, including a placebo group

G-CSF + CD133(+) cells + PTA

Experimental group

Description:

Intramuscular injection of G-CSF along with transarterial infusion of CD133 (+) cells combined with percutaneous transluminal angioplasty

Treatment:

Biological: G-CSF + CD133(+) cells

Procedure: percutaneous transluminal angioplasty (PTA)

PTA + G-CSF

Active Comparator group

Description:

Percutaneous transluminal angioplasty along with intramuscular injection of G-CSF

Treatment:

Biological: G-CSF

Procedure: percutaneous transluminal angioplasty (PTA)

Only PTA

Placebo Comparator group

Description:

Only Percutaneous transluminal angioplasty along with placebo infusion of sodium chloride injection

Treatment:

Biological: Placebo infusion

Procedure: percutaneous transluminal angioplasty (PTA)