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

NCT ID: NCT02915796

Last Updated: 2016-09-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

345 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-30

Study Completion Date

2018-04-30

Brief Summary

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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

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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.

Conditions

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Peripheral Arterial Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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G-CSF + CD133(+) cells + PTA

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

Group Type EXPERIMENTAL

G-CSF + CD133(+) cells

Intervention Type BIOLOGICAL

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.

percutaneous transluminal angioplasty (PTA)

Intervention Type PROCEDURE

Subjects in this group only underwent below the knee percutaneous transluminal angioplasty .

PTA + G-CSF

Percutaneous transluminal angioplasty along with intramuscular injection of G-CSF

Group Type ACTIVE_COMPARATOR

G-CSF

Intervention Type BIOLOGICAL

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.

percutaneous transluminal angioplasty (PTA)

Intervention Type PROCEDURE

Subjects in this group only underwent below the knee percutaneous transluminal angioplasty .

Only PTA

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

Group Type PLACEBO_COMPARATOR

percutaneous transluminal angioplasty (PTA)

Intervention Type PROCEDURE

Subjects in this group only underwent below the knee percutaneous transluminal angioplasty .

Placebo infusion

Intervention Type BIOLOGICAL

Neither G-CSF was injected nor CD133(+) cells. Instead, subjects received placebo infusion (50 ml of 0.9% sodium chloride injection ) over 30 min.

Interventions

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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.

Intervention Type 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.

Intervention Type BIOLOGICAL

percutaneous transluminal angioplasty (PTA)

Subjects in this group only underwent below the knee percutaneous transluminal angioplasty .

Intervention Type PROCEDURE

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.

Intervention Type BIOLOGICAL

Eligibility Criteria

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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 -
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shanghai 10th People's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Maoquan Li

Prof. Dr. Li

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Shanghai Tenth People's Hospital, Tong ji University

Shanghai, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Mao Q Li, Ph.D

Role: CONTACT

02166313506

Facility Contacts

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Mao Q Li, Ph.D

Role: primary

02166313506

References

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Ma N, Ladilov Y, Moebius JM, Ong L, Piechaczek C, David A, Kaminski A, Choi YH, Li W, Egger D, Stamm C, Steinhoff G. Intramyocardial delivery of human CD133+ cells in a SCID mouse cryoinjury model: Bone marrow vs. cord blood-derived cells. Cardiovasc Res. 2006 Jul 1;71(1):158-69. doi: 10.1016/j.cardiores.2006.03.020. Epub 2006 Apr 3.

Reference Type BACKGROUND
PMID: 16730684 (View on PubMed)

Gehling UM, Ergun S, Schumacher U, Wagener C, Pantel K, Otte M, Schuch G, Schafhausen P, Mende T, Kilic N, Kluge K, Schafer B, Hossfeld DK, Fiedler W. In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood. 2000 May 15;95(10):3106-12.

Reference Type BACKGROUND
PMID: 10807776 (View on PubMed)

Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, Oz MC, Hicklin DJ, Witte L, Moore MA, Rafii S. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood. 2000 Feb 1;95(3):952-8.

Reference Type BACKGROUND
PMID: 10648408 (View on PubMed)

Friedrich EB, Walenta K, Scharlau J, Nickenig G, Werner N. CD34-/CD133+/VEGFR-2+ endothelial progenitor cell subpopulation with potent vasoregenerative capacities. Circ Res. 2006 Feb 17;98(3):e20-5. doi: 10.1161/01.RES.0000205765.28940.93. Epub 2006 Jan 26.

Reference Type BACKGROUND
PMID: 16439688 (View on PubMed)

Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, Amano K, Kishimoto Y, Yoshimoto K, Akashi H, Shimada K, Iwasaka T, Imaizumi T; Therapeutic Angiogenesis using Cell Transplantation (TACT) Study Investigators. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet. 2002 Aug 10;360(9331):427-35. doi: 10.1016/S0140-6736(02)09670-8.

Reference Type BACKGROUND
PMID: 12241713 (View on PubMed)

Esato K, Hamano K, Li TS, Furutani A, Seyama A, Takenaka H, Zempo N. Neovascularization induced by autologous bone marrow cell implantation in peripheral arterial disease. Cell Transplant. 2002;11(8):747-52.

Reference Type BACKGROUND
PMID: 12588106 (View on PubMed)

Fadini GP, Avogaro A. Autologous transplantation of granulocyte colony-stimulating factor- mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Diabetes Care. 2006 Feb;29(2):478-9; author reply 479-80. doi: 10.2337/diacare.29.02.06.dc05-1770. No abstract available.

Reference Type BACKGROUND
PMID: 16482702 (View on PubMed)

Miyamoto K, Nishigami K, Nagaya N, Akutsu K, Chiku M, Kamei M, Soma T, Miyata S, Higashi M, Tanaka R, Nakatani T, Nonogi H, Takeshita S. Unblinded pilot study of autologous transplantation of bone marrow mononuclear cells in patients with thromboangiitis obliterans. Circulation. 2006 Dec 12;114(24):2679-84. doi: 10.1161/CIRCULATIONAHA.106.644203. Epub 2006 Dec 4.

Reference Type BACKGROUND
PMID: 17145986 (View on PubMed)

Kawamoto A, Katayama M, Handa N, Kinoshita M, Takano H, Horii M, Sadamoto K, Yokoyama A, Yamanaka T, Onodera R, Kuroda A, Baba R, Kaneko Y, Tsukie T, Kurimoto Y, Okada Y, Kihara Y, Morioka S, Fukushima M, Asahara T. Intramuscular transplantation of G-CSF-mobilized CD34(+) cells in patients with critical limb ischemia: a phase I/IIa, multicenter, single-blinded, dose-escalation clinical trial. Stem Cells. 2009 Nov;27(11):2857-64. doi: 10.1002/stem.207.

Reference Type BACKGROUND
PMID: 19711453 (View on PubMed)

Lu D, Chen B, Liang Z, Deng W, Jiang Y, Li S, Xu J, Wu Q, Zhang Z, Xie B, Chen S. Comparison of bone marrow mesenchymal stem cells with bone marrow-derived mononuclear cells for treatment of diabetic critical limb ischemia and foot ulcer: a double-blind, randomized, controlled trial. Diabetes Res Clin Pract. 2011 Apr;92(1):26-36. doi: 10.1016/j.diabres.2010.12.010. Epub 2011 Jan 8.

Reference Type BACKGROUND
PMID: 21216483 (View on PubMed)

Losordo DW, Kibbe MR, Mendelsohn F, Marston W, Driver VR, Sharafuddin M, Teodorescu V, Wiechmann BN, Thompson C, Kraiss L, Carman T, Dohad S, Huang P, Junge CE, Story K, Weistroffer T, Thorne TM, Millay M, Runyon JP, Schainfeld R; Autologous CD34+ Cell Therapy for Critical Limb Ischemia Investigators. A randomized, controlled pilot study of autologous CD34+ cell therapy for critical limb ischemia. Circ Cardiovasc Interv. 2012 Dec;5(6):821-30. doi: 10.1161/CIRCINTERVENTIONS.112.968321. Epub 2012 Nov 27.

Reference Type BACKGROUND
PMID: 23192920 (View on PubMed)

Sun X, Ying J, Wang Y, Li W, Wu Y, Yao B, Liu Y, Gao H, Zhang X. Meta-analysis on autologous stem cell transplantation in the treatment of limb ischemic. Int J Clin Exp Med. 2015 Jun 15;8(6):8740-8. eCollection 2015.

Reference Type BACKGROUND
PMID: 26309525 (View on PubMed)

Other Identifiers

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2016-xjs-08

Identifier Type: -

Identifier Source: org_study_id

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