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

Emile R. Mohler, Sanjay Rajagopaian, Jeffrey W. Olin, Jeffrey D. Trachtenberg, Henrik Rasmussen, Raphael Pak, Ronald Crystal

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

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 (AdGVVEGF121.10), 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 (4X 108 to 4 x 1010 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.

Original languageEnglish
Pages (from-to)9-13
Number of pages5
JournalVascular Medicine
Volume8
Issue number1
DOIs
Publication statusPublished - 11 Jul 2003
Externally publishedYes

Fingerprint

Vascular Endothelial Growth Factor A
Ischemia
Extremities
Safety
Genes
Peripheral Arterial Disease
Nociceptive Pain
Groin
Intramuscular Injections
Adenoviridae
Edema
Protein Isoforms
Necrosis
Perfusion
Placebos
Injections
Neoplasms
Therapeutics

Keywords

  • Angiogenesis
  • Endothelium

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Adenoviral-mediated gene transfer of vascular endothelial growth factor in critical limb ischemia : Safety results from a phase I trial. / Mohler, Emile R.; Rajagopaian, Sanjay; Olin, Jeffrey W.; Trachtenberg, Jeffrey D.; Rasmussen, Henrik; Pak, Raphael; Crystal, Ronald.

In: Vascular Medicine, Vol. 8, No. 1, 11.07.2003, p. 9-13.

Research output: Contribution to journalArticle

Mohler, Emile R. ; Rajagopaian, Sanjay ; Olin, Jeffrey W. ; Trachtenberg, Jeffrey D. ; Rasmussen, Henrik ; Pak, Raphael ; Crystal, Ronald. / Adenoviral-mediated gene transfer of vascular endothelial growth factor in critical limb ischemia : Safety results from a phase I trial. In: Vascular Medicine. 2003 ; Vol. 8, No. 1. pp. 9-13.
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