Phase II Clinical Trial of CD 34 + Cell Therapy to Explore Endpoint Selection and Timing in Patients With Critical Limb Ischemia

1,000 cases per million people in the developed countries.1 The prognosis of CLI patients is poor. The 1-year mortality and major amputation rate are reported to be 25% and 30%, respectively.1 Currently, revascularization of the ischemic limb with surgical bypass techniques or endovascular approaches is believed to be the best option for limb salvage.2,3 A total of 25– hronic critical limb ischemia (CLI) is defined as the endstage of lower limb ischemia due to atherosclerotic peripheral arterial disease (PAD) or vasculitis including thromboangiitis obliterans (Buerger’s disease). The clinical manifestations consist of rest pain and/or skin ulceration or gangrene. The annual incidence of CLI is estimated to be 500– C

[1]  H. Aihara,et al.  Comparison of clinical outcome after bypass surgery vs. endovascular therapy for infrainguinal artery disease in patients with critical limb ischemia. , 2013, Circulation journal : official journal of the Japanese Circulation Society.

[2]  W. Marston,et al.  A Randomized, Controlled Pilot Study of Autologous CD34+ Cell Therapy for Critical Limb Ischemia , 2012, Circulation. Cardiovascular interventions.

[3]  Y. Kurimoto,et al.  Long-term clinical outcome after intramuscular transplantation of granulocyte colony stimulating factor-mobilized CD34 positive cells in patients with critical limb ischemia. , 2012, Atherosclerosis.

[4]  H. Matsubara,et al.  Bone marrow mononuclear cells versus G-CSF-mobilized peripheral blood mononuclear cells for treatment of lower limb ASO: pooled analysis for long-term prognosis , 2011, Bone Marrow Transplantation.

[5]  M. Conte.  Understanding objective performance goals for critical limb ischemia trials. , 2010, Seminars in vascular surgery.

[6]  A. Avogaro,et al.  Autologous stem cell therapy for peripheral arterial disease meta-analysis and systematic review of the literature. , 2010, Atherosclerosis.

[7]  F. Moll,et al.  Stem cell therapy in PAD. , 2010, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[8]  T. Yamanaka,et al.  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 , 2009, Stem cells.

[9]  A Cremonesi,et al.  Clinical endpoints in peripheral endovascular revascularization trials: a case for standardized definitions. , 2008, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[10]  R. Morishita,et al.  Results of a Double-Blind, Placebo-Controlled Study to Assess the Safety of Intramuscular Injection of Hepatocyte Growth Factor Plasmid to Improve Limb Perfusion in Patients With Critical Limb Ischemia , 2008, Circulation.

[11]  T. Asahara,et al.  CD34-Positive Cells Exhibit Increased Potency and Safety for Therapeutic Neovascularization After Myocardial Infarction Compared With Total Mononuclear Cells , 2006, Circulation.

[12]  E. Dejana,et al.  Increase in Vascular Permeability and Vasodilation Are Critical for Proangiogenic Effects of Stem Cell Therapy , 2006, Circulation.

[13]  I. Komuro,et al.  Critical Roles of Muscle-Secreted Angiogenic Factors in Therapeutic Neovascularization , 2006, Circulation research.

[14]  H. Naritomi,et al.  Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. , 2004, The Journal of clinical investigation.

[15]  K. Shimada,et al.  Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial , 2002, The Lancet.

[16]  J. Isner,et al.  Therapeutic Potential of Ex Vivo Expanded Endothelial Progenitor Cells for Myocardial Ischemia , 2001, Circulation.

[17]  J. Isner,et al.  Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[18]  K. Jaeger,et al.  Transatlantic Conference on Clinical Trial Guidelines in Peripheral Arterial Disease: clinical trial methodology. Basel PAD Clinical Trial Methodology Group. , 1999, Circulation.

[19]  J E Ware,et al.  Psychometric and clinical tests of validity of the Japanese SF-36 Health Survey. , 1998, Journal of clinical epidemiology.

[20]  S. Fukuhara,et al.  Translation, adaptation, and validation of the SF-36 Health Survey for use in Japan. , 1998, Journal of clinical epidemiology.

[21]  Takayuki Asahara,et al.  Isolation of Putative Progenitor Endothelial Cells for Angiogenesis , 1997, Science.

[22]  N. Lowe,et al.  A critical review of visual analogue scales in the measurement of clinical phenomena. , 1990, Research in nursing & health.

[23]  Y. Jang,et al.  Comparison of clinical outcome of infrapopliteal angioplasty between Korean diabetic and non-diabetic patients with critical limb ischemia. , 2012, Circulation journal : official journal of the Japanese Circulation Society.

[24]  John V. White,et al.  Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). , 2007, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[25]  D. Wong,et al.  Pain in children: comparison of assessment scales. , 1988, The Oklahoma nurse.