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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.MT

Abstract

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.

Authors+Show Affiliations

Department of Surgery, University of Kuopio, Kuopio, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

12095313

Citation

Mäkinen, Kimmo, et al. "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." Molecular Therapy : the Journal of the American Society of Gene Therapy, vol. 6, no. 1, 2002, pp. 127-33.
Mäkinen K, Manninen H, Hedman M, et al. 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;6(1):127-33.
Mäkinen, K., Manninen, H., Hedman, M., Matsi, P., Mussalo, H., Alhava, E., & Ylä-Herttuala, S. (2002). 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. Molecular Therapy : the Journal of the American Society of Gene Therapy, 6(1), 127-33.
Mäkinen K, et al. 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;6(1):127-33. PubMed PMID: 12095313.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Mäkinen,Kimmo, AU - Manninen,Hannu, AU - Hedman,Marja, AU - Matsi,Pekka, AU - Mussalo,Hanna, AU - Alhava,Esko, AU - Ylä-Herttuala,Seppo, PY - 2002/7/4/pubmed PY - 2003/1/23/medline PY - 2002/7/4/entrez SP - 127 EP - 33 JF - Molecular therapy : the journal of the American Society of Gene Therapy JO - Mol. Ther. VL - 6 IS - 1 N2 - 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. SN - 1525-0016 UR - https://www.unboundmedicine.com/medline/citation/12095313/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1525-0016(02)90638-6 DB - PRIME DP - Unbound Medicine ER -