Increased vascularity detected by digital subtraction angiography after VEGF gene transfer to human lower limb artery: a randomized, placebo-controlled, double-blinded phase II study

Mol Ther. 2002 Jul;6(1):127-33. doi: 10.1006/mthe.2002.0638.


Vascular endothelial growth factor (VEGF) gene therapy may be useful for the treatment of lower-limb ischemia. The objectives of this study were to evaluate safety and angiographic and hemodynamic responses of local catheter-mediated VEGF gene therapy in ischemic lower-limb arteries after percutaneous transluminal angioplasty (PTA). For this study, we recruited patients with chronic lower-limb ischemia and atherosclerotic infrainguinal occlusion or stenosis suitable for PTA. In the study, 18 patients received 2x10(10) plaque-forming units (pfu) VEGF-adenovirus (VEGF-Ad), 17 patients received VEGF-plasmid/liposome (VEGF-P/L; 2000 microg of VEGF plasmid, 2000 microl of DOTMA:DOPE), and 19 control patients received Ringer's lactate at the angioplasty site. Digital subtraction angiography (DSA) was used to evaluate vascularity before, immediately after, and 3 months after the PTA. Clinical follow-up data, basic laboratory tests, and ankle-brachial index (ABI) were evaluated. Primary endpoint was DSA analysis of vascularity, and secondary endpoints were restenosis rate, Rutherford class, and ABI after 3 months follow-up. No major gene transfer-related side effects or differences in laboratory tests were detected between the study groups. However, anti-adenovirus antibodies increased in 61% of the patients treated with VEGF-Ad. For the primary endpoint, follow-up DSA revealed increased vascularity in the VEGF-treated groups distally to the gene transfer site (VEGF-Ad P=0.03, VEGFP/L P=0.02) and in the VEGF-Ad group in the region of the clinically most severe ischemia (P=0.01). As for the secondary endpoints, mean Rutherford class and ABI showed statistically significant improvements in the VEGF-Ad and VEGF-P/L groups, but similar improvements were also seen in the control patients. We conclude that catheter-mediated VEGF gene therapy is safe and well tolerated. Angiography demonstrated that VEGF gene transfer increased vascularity after PTA in both VEGF-Ad- and VEGF-P/L-treated groups.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / metabolism
  • Aged
  • Aged, 80 and over
  • Angiography, Digital Subtraction
  • Angioplasty, Balloon
  • Arterial Occlusive Diseases / therapy
  • Endothelial Growth Factors / genetics*
  • Endothelial Growth Factors / metabolism
  • Female
  • Genetic Therapy*
  • Genetic Vectors / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Ischemia / therapy*
  • Leg / blood supply*
  • Liposomes / metabolism
  • Lymphokines / genetics*
  • Lymphokines / metabolism
  • Male
  • Middle Aged
  • Neovascularization, Physiologic / drug effects
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Liposomes
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors