Open AccessDouble‐blind, placebo‐controlled study of HGF gene therapy in diabetic neuropathy
Author(s) -
Kessler John A.,
Smith A. Gordon,
Cha BongSoo,
Choi Sung Hee,
Wymer James,
Shaibani Aziz,
AjroudDriss Senda,
Vinik Aaron
Publication year - 2015
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.186
Subject(s) - medicine , pregabalin , placebo , adverse effect , diabetic neuropathy , neuropathic pain , gabapentin , peripheral neuropathy , quality of life (healthcare) , anesthesia , randomized controlled trial , clinical trial , brief pain inventory , diabetes mellitus , chronic pain , physical therapy , alternative medicine , nursing , pathology , endocrinology
Objective To evaluate the safety and efficacy of a plasmid ( VM 202) containing two human hepatocyte growth factor isoforms given by intramuscular injections in patients with painful diabetic neuropathy. Methods In a double‐blind, placebo‐controlled study, patients were randomized to receive injections of 8 or 16 mg VM 202 per leg or placebo. Divided doses were administered on Day 0 and Day 14. The prospective primary outcome was change in the mean pain score measured by a 7 day pain diary. Secondary outcomes included a responder analysis, quality of life and pain measures, and intraepidermal nerve fiber density. Results There were no significant adverse events attributable to VM 202. Eighty‐four patients completed the study. Patients receiving 8 mg VM 202 per leg improved the most in all efficacy measures including a significant ( P = 0.03) reduction at 3 months in the mean pain score and continued but not statistically significant reductions in pain at 6 and 9 months. Of these patients, 48.4% experienced a ≥50% reduction in pain compared to 17.6% of placebo patients. There were also significant improvements in the brief pain inventory for patients with diabetic peripheral neuropathy and the questionnaire portion of the Michigan Neuropathy Screening Instrument. Patients not on pregabalin or gabapentin had the largest reductions in pain. Interpretation VM 202 was safe, well tolerated and effective indicating the feasibility of a nonviral gene therapy approach to painful diabetic neuropathy. Two days of treatment were sufficient to provide symptomatic relief with improvement in quality of life for 3 months. VM 202 may be particularly beneficial for patients not taking gabapentin or pregabalin.