ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02915796
Recruitment Status : Recruiting
First Posted : September 27, 2016
Last Update Posted : September 28, 2016
Sponsor:
Information provided by (Responsible Party):
Maoquan Li, 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.

Condition or disease Intervention/treatment Phase
Peripheral Arterial Disease Biological: G-CSF + CD133(+) cells Biological: G-CSF Procedure: percutaneous transluminal angioplasty (PTA) Biological: Placebo infusion Phase 1

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  (Clinical Trial)
Estimated Enrollment : 345 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : September 2016
Estimated Primary Completion Date : April 2017
Estimated Study Completion Date : April 2018

Resource links provided by the National Library of Medicine


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
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.

Procedure: percutaneous transluminal angioplasty (PTA)
Subjects in this group only underwent below the knee percutaneous transluminal angioplasty .

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.




Primary Outcome Measures :
  1. 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).

  2. 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).

  3. Severe adverse effects (SAEs) [ Time Frame: 12 months ]
    Number of SAEs per subject across actual treatment cohorts (Safety Endpoint).


Secondary Outcome Measures :
  1. 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.

  2. Rutherford classification [ Time Frame: 6 and 12 months ]
    improvement in Rutherford scale of at least one category after the procedure.

  3. Transcutaneous oxygen pressures (TcPO2) [ Time Frame: 6 and 12 months ]
    .Changes in TcPO2 was assessed at each follow up interval and compared to baseline.

  4. Amputation-free survival (AFS) [ Time Frame: 6 and 12 months ]
    Time to below the knee amputation of the ipsilateral leg.

  5. 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. Six Minute Walk test [ Time Frame: 6 and 12 months ]
    Walking distance, time to onset of leg cramping/pain were recorded.

  7. Ulcer healing rate [ Time Frame: 6 and 12 months ]
    Ulcer status was assessed at each follow up interval and compared to baseline.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02915796


Contacts
Contact: Mao Q Li, Ph.D 02166313506 cjr.limaoquan@vip.163.com

Locations
China
Shanghai Tenth People's Hospital, Tong ji University Recruiting
Shanghai, China
Contact: Mao Q Li, Ph.D    02166313506    cjr.limaoquan@vip.163.com   
Sponsors and Collaborators
Shanghai 10th People's Hospital

Publications:

Responsible Party: Maoquan Li, Prof. Dr. Li, Shanghai 10th People's Hospital
ClinicalTrials.gov Identifier: NCT02915796     History of Changes
Other Study ID Numbers: 2016-xjs-08
First Posted: September 27, 2016    Key Record Dates
Last Update Posted: September 28, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Maoquan Li, Shanghai 10th People's Hospital:
Endothelial progenitor cell
Percutaneous transluminal angioplasty

Additional relevant MeSH terms:
Peripheral Arterial Disease
Peripheral Vascular Diseases
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Lenograstim
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs