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

Phase 1

• Conditions: Peripheral Arterial Disease
• Interventions: Procedure: percutaneous transluminal angioplasty (PTA); Biological: G-CSF; Biological: G-CSF + CD133(+) cells; Biological: Placebo infusion

• Registration Number: NCT02915796
• Lead Sponsor: Shanghai 10th People's Hospital

Brief Summary

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.

Detailed 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.

Study Timeline

• Status Verified: 2016-09
• Study Start: 2016-09
• Study First Submitted: 2016-09-22
• Study First Submitted QC: 2016-09-26
• Study First Posted: 2016-09-27
• Last Update Submitted: 2016-09-27
• Last Update Posted: 2016-09-28
• Primary Completion: 2017-04
• Study Completion: 2018-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 345

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 -

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Only PTA	percutaneous transluminal angioplasty (PTA)	Only Percutaneous transluminal angioplasty along with placebo infusion of sodium chloride injection
PTA + G-CSF	G-CSF	Percutaneous transluminal angioplasty along with intramuscular injection of G-CSF
G-CSF + CD133(+) cells + PTA	G-CSF + CD133(+) cells	Intramuscular injection of G-CSF along with transarterial infusion of CD133 (+) cells combined with percutaneous transluminal angioplasty
G-CSF + CD133(+) cells + PTA	percutaneous transluminal angioplasty (PTA)	Intramuscular injection of G-CSF along with transarterial infusion of CD133 (+) cells combined with percutaneous transluminal angioplasty
PTA + G-CSF	percutaneous transluminal angioplasty (PTA)	Percutaneous transluminal angioplasty along with intramuscular injection of G-CSF
Only PTA	Placebo infusion	Only Percutaneous transluminal angioplasty along with placebo infusion of sodium chloride injection

Primary Outcome Measures

Name	Time	Method
Restenosis rate	12 months	Occurrence of \> 50% of restenosis in the treated vessel after 12 months as assessed by digital substraction angiography (DSA) (Efficacy endpoints).
Peak systolic velocity ratio	12 months	Peak systolic velocity ratio ≥ 2.4 by Doppler's ultrasonography for patients who did not undergo angiography after 12 months (Efficacy endpoints).
Severe adverse effects (SAEs)	12 months	Number of SAEs per subject across actual treatment cohorts (Safety Endpoint).

Secondary Outcome Measures

Name	Time	Method
ABI value	6 and 12 months	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.
Transcutaneous oxygen pressures (TcPO2)	6 and 12 months	.Changes in TcPO2 was assessed at each follow up interval and compared to baseline.
Amputation-free survival (AFS)	6 and 12 months	Time to below the knee amputation of the ipsilateral leg.
Rutherford classification	6 and 12 months	improvement in Rutherford scale of at least one category after the procedure.
Rest pain	6 and 12 months	Rest pain was measured using Wong-Baker FACES pain rating scale at baseline and each follow-up visit.
Six Minute Walk test	6 and 12 months	Walking distance, time to onset of leg cramping/pain were recorded.
Ulcer healing rate	6 and 12 months	Ulcer status was assessed at each follow up interval and compared to baseline.

Trial Locations

Locations (1)

Shanghai Tenth People's Hospital, Tong ji University; 🇨🇳 Shanghai, China