Adenoviral-mediated gene transfer of vascular endothelial growth factor in critical limb ischemia: Safety results from a phase I trial Academic Article uri icon


MeSH Major

  • Adenoviridae
  • Angiogenesis Inducing Agents
  • Angiogenic Proteins
  • Endothelial Growth Factors
  • Gene Transfer Techniques
  • Ischemia
  • Lower Extremity
  • Lymphokines
  • Peripheral Vascular Diseases
  • Vascular Endothelial Growth Factor A


  • Critical limb ischemia (CLI) is typified by rest pain and/or tissue necrosis secondary to advanced peripheral arterial disease (PAD) and is characterized by diminution in limb perfusion at rest. We tested the safety of an angiogenic strategy with CI-1023 (Ad(GV)VEGF121.10), a replication-deficient adenovirus encoding human vascular endothelial growth factor isoform 121 in patients with CLI as part of a phase I trial. Fifteen subjects >35 years of age with CLI and angiographic disease involving the infra-inguinal vessels underwent intramuscular injection of CI-1023 (4 x 10(8) to 4 x 10(10) particle units, n = 13) or placebo (n = 2). All of the patients tolerated the injection well and there were no serious complications related to the procedure. Transient edema was noted in one patient. A total of 79 adverse events were reported over the course of one year. One death (day 136) and one malignancy (day 332) occurred in the CI-1023 group. CI-1023 appears to be well tolerated and safe for single-dose administration in patients with critical limb ischemia due to PAD. Further studies are needed to determine the efficacy of this form of therapeutic angiogenesis.

publication date

  • July 11, 2003



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1191/1358863x03vm460oa

PubMed ID

  • 12866606

Additional Document Info

start page

  • 9

end page

  • 13


  • 8


  • 1