title: Vascular endothelial growth factor gene transfer for diabetic polyneuropathy: a randomized, double-blinded trial.
abstract: 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. Primary outcomes were change in symptom score at 6 months and a prespecified overall clinical and electrophysiological improvement score. Secondary outcomes were differences in symptoms, examination scores, visual analog pain scale, nerve conduction, and quantitative sensory testing.
  
  
  RESULTS
  Thirty-nine patients received plasmid VEGF and 11 received placebo. Mean symptom score improved in both legs at 6 months, favoring VEGF over placebo (-1.2 +/- 0.5 vs -0.9 +/- 0.5; p < 0.01 after adjustment for change in the untreated leg) and compared with the untreated leg (-0.7 +/- 0.5; p = 0.02). The region of sensory loss and visual analog pain scale improved in the treated group (-1.5 vs -0.5; p = 0.01). Twelve of 39 VEGF versus 2 of 11 placebo patients met criterion for overall improvement. Other measures including nerve conduction potentials did not improve. There were 84 adverse events in VEGF patients, and 22 were serious; there were 51 events in placebo patients, and 2 were serious.
  
  
  CONCLUSIONS
  Intramuscular plasmid VEGF gene transfer improved diabetic neuropathic symptoms, meeting primary end-point criteria for efficacy but not affecting most secondary measures. Treatment was associated with more serious adverse events that did not reach statistical significance. These results are not conclusive but may justify further clinical study.
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA. aropper@partners.org
authors.forename: Allan H
authors.initials: AH
authors.lastname: Ropper
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Gorson
authors.forename: Clifton L
authors.initials: CL
authors.lastname: Gooch
authors.forename: David H
authors.initials: DH
authors.lastname: Weinberg
authors.forename: Ann
authors.initials: A
authors.lastname: Pieczek
authors.forename: James H
authors.initials: JH
authors.lastname: Ware
authors.forename: Joshua
authors.initials: J
authors.lastname: Kershen
authors.forename: Adam
authors.initials: A
authors.lastname: Rogers
authors.forename: Drasko
authors.initials: D
authors.lastname: Simovic
authors.forename: Peter
authors.initials: P
authors.lastname: Schratzberger
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kirchmair
authors.forename: Douglas
authors.initials: D
authors.lastname: Losordo
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003929:Diabetic Neuropathies / Q000378:metabolism / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction / Q000235:genetics; D010147:Pain Measurement; D010525:Peripheral Nerves / Q000503:physiopathology; D012720:Severity of Illness Index; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000627:therapeutic use*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A