Vascular endothelial growth factor gene transfer for diabetic polyneuropathy: a randomized, double-blinded trial.

Objective: Randomized, blinded trial of intramuscular gene transfer using plasmid vascular endothelial growth factor (VEGF) to treat diabetic polyneuropathy.

Methods: Diabetic patients with polyneuropathy were randomized to receive a VEGF-to-placebo ratio of 3:1. Three sets of injections were given at eight standardized sites adjacent to the sciatic, peroneal, and tibial nerves of one leg.

Use of a constitutively active hypoxia-inducible factor-1alpha transgene as a therapeutic strategy in no-option critical limb ischemia patients: phase I dose-escalation experience.

Background: Critical limb ischemia, a manifestation of severe peripheral atherosclerosis and compromised lower-extremity blood flow, results in a high rate of limb loss. We hypothesized that adenoviral delivery of a constitutively active form of the transcription factor hypoxia-inducible factor-1alpha (ie, Ad2/HIF-1alpha/VP16 or HIF-1alpha) into the lower extremity of patients with critical limb ischemia would be safe and might result in a durable clinical response.

Methods And Results: This phase I dose-escalation program included 2 studies: a randomized, double-blind, placebo-controlled study and an open-label extension study.