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

NCT02915796 | Unknown Phase 1

• 1 other identifier: 2016-xjs-08
• Study Type: interventional
• Target: 345
• Locations: 1 country
• Sites: 1

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.

Conditions

Peripheral Arterial Disease

Keywords

Endothelial progenitor cell; Percutaneous transluminal angioplasty

Outcome Measures

Primary Outcomes (3)

• Restenosis rate

  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

  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)

  Number of SAEs per subject across actual treatment cohorts (Safety Endpoint).

  12 months

Secondary Outcomes (7)

• ABI value

  6 and 12 months

• Rutherford classification

  6 and 12 months

• Transcutaneous oxygen pressures (TcPO2)

  6 and 12 months

• Amputation-free survival (AFS)

  6 and 12 months

• Rest pain

  6 and 12 months

Study Arms (3)

G-CSF + CD133(+) cells + PTA

EXPERIMENTAL

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

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

PTA + G-CSF

ACTIVE COMPARATOR

Percutaneous transluminal angioplasty along with intramuscular injection of G-CSF

Biological: G-CSF; Procedure: percutaneous transluminal angioplasty (PTA)

Only PTA

PLACEBO COMPARATOR

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

Procedure: percutaneous transluminal angioplasty (PTA); Biological: Placebo infusion

Interventions

G-CSF + CD133(+) cells 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.

G-CSF + CD133(+) cells + PTA

G-CSF 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.

PTA + G-CSF

percutaneous transluminal angioplasty (PTA) PROCEDURE

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

G-CSF + CD133(+) cells + PTA; Only PTA; PTA + G-CSF

Placebo infusion 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.

Only PTA

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age range: 18-75 years , Gender: Both
• Patients with below the knee limb ischemia with diabetes.
• Rutherford class 2-6.
• Target lesions with a diameter reduction of at least 50% and have an occlusion of longer than 4 cm on angiography.
• 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. -

You may not qualify if:

• Previous bypass surgery or stent placement at the ipsilateral lower limb
• History of intolerance to antiplatelet therapy, heparin, or contrast media.
• Presence of any of the following conditions:
• severe liver disease (such as ascites, esophageal varices, liver transplantation);
• hemodynamic instability;
• Severely impaired renal function (serum creatinine level \> 2.5 mg/dL).
• Receiving immunosuppressive therapy;
• History of decompensated heart failure (New York Heart Association class III or IV and level) or myocardial infarction, or heart bypass surgery;
• Bleeding diathesis;
• Active systemic bacterial infection;
• 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 -

Sponsors & Collaborators

• Shanghai 10th People's Hospital: lead

Study Sites (1)

Shanghai Tenth People's Hospital, Tong ji University

Shanghai, China

RECRUITING

Related Publications (12)

• 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.

  PMID: 16730684 BACKGROUND

• 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.

  PMID: 10807776 BACKGROUND

• 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.

  PMID: 10648408 BACKGROUND

• 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.

  PMID: 16439688 BACKGROUND

• 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.

  PMID: 12241713 BACKGROUND

• 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.

  PMID: 12588106 BACKGROUND

• 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.

  PMID: 16482702 BACKGROUND

• 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.

  PMID: 17145986 BACKGROUND

• 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.

  PMID: 19711453 BACKGROUND

• 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.

  PMID: 21216483 BACKGROUND

• 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.

  PMID: 23192920 BACKGROUND

• 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.

  PMID: 26309525 BACKGROUND

MeSH Terms

Conditions

Peripheral Arterial Disease

Interventions

Granulocyte Colony-Stimulating Factor; AC133 Antigen; Cell Count; Angioplasty

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Membrane Glycoproteins; Membrane Proteins; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cell Physiological Phenomena; Catheterization; Therapeutics; Endovascular Procedures; Vascular Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures

Central Study Contacts

Mao Q Li, Ph.D

CONTACT

02166313506; cjr.limaoquan@vip.163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. Li

Study Record Dates

• First Submitted: September 22, 2016
• First Posted: September 27, 2016
• Study Start: September 1, 2016
• Primary Completion: April 1, 2017
• Study Completion: April 1, 2018
• Last Updated: September 28, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)