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

September 27, 2016 updated by: Maoquan Li, Shanghai 10th People's Hospital

Autologous CD133(+) Cells as an Adjuvant to Below the Knee Percutaneous Transluminal Angioplasty: A Randomized Controlled Clinical Trial in Diabetic Patients With Below the Knee Critical Limb Ischemia

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

345

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Shanghai, China
        • Recruiting
        • Shanghai Tenth People's Hospital, Tong ji University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: G-CSF + CD133(+) cells + PTA
Intramuscular injection of G-CSF along with transarterial infusion of CD133 (+) cells combined with percutaneous transluminal angioplasty
Biological: G-CSF + CD133(+) cells
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.
Procedure: percutaneous transluminal angioplasty (PTA)
Subjects in this group only underwent below the knee percutaneous transluminal angioplasty .
Active Comparator: PTA + G-CSF
Percutaneous transluminal angioplasty along with intramuscular injection of G-CSF
Procedure: percutaneous transluminal angioplasty (PTA)
Subjects in this group only underwent below the knee percutaneous transluminal angioplasty .
Biological: G-CSF
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.
Placebo Comparator: Only PTA
Only Percutaneous transluminal angioplasty along with placebo infusion of sodium chloride injection
Procedure: percutaneous transluminal angioplasty (PTA)
Subjects in this group only underwent below the knee percutaneous transluminal angioplasty .
Biological: Placebo infusion
Neither G-CSF was injected nor CD133(+) cells. Instead, subjects received placebo infusion (50 ml of 0.9% sodium chloride injection ) over 30 min.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai 10th People's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2016

Primary Completion (Anticipated)

April 1, 2017

Study Completion (Anticipated)

April 1, 2018

Study Registration Dates

First Submitted

September 22, 2016

First Submitted That Met QC Criteria

September 26, 2016

First Posted (Estimate)

September 27, 2016

Study Record Updates

Last Update Posted (Estimate)

September 28, 2016

Last Update Submitted That Met QC Criteria

September 27, 2016

Last Verified

September 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016-xjs-08

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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