Ranirestat for the Management of Diabetic Sensorimotor Polyneuropathy
Open Access
- 14 April 2009
- journal article
- research article
- Published by American Diabetes Association in Diabetes Care
- Vol. 32 (7), 1256-1260
- https://doi.org/10.2337/dc08-2110
Abstract
OBJECTIVE: Aldose reductase inhibitors (ARIs) are potential disease modifiers for diabetes complications. We aimed to determine whether ranirestat, an ARI, could slow or reverse the course of diabetic sensorimotor polyneuropathy (DSP). RESEARCH DESIGN AND METHODS: A total of 549 patients with DSP were randomly assigned to treatment with placebo or 10, 20, or 40 mg/day ranirestat for 52 weeks in this multicenter, double-blind study. Efficacy was evaluated by nerve conduction studies, the modified Toronto Clinical Neuropathy Score (mTCNS), and quantitative sensory tests (QSTs). RESULTS: At week 52, the summed sensory (bilateral sural plus proximal median sensory) nerve conduction velocity (NCV) did not show significant changes from baseline (2.0 m/s for placebo compared with 3.2–3.8 m/s for ranirestat). Significant improvement in the summed motor (peroneal, tibial, and median) NCV was observed with 20 and 40 mg/day ranirestat treatment at week 12 (P ≤ 0.05) and at weeks 24 and 36 and in peroneal motor NCV at weeks 36 and 52 (P ≤ 0.05) for the 20 mg/day ranirestat group. The mTCNS and QST results did not differ among the groups during the study. Ranirestat was well tolerated with no pertinent differences in drug-related adverse events or in effects on clinical laboratory parameters, vital signs, or electrocardiograms among the four groups. CONCLUSIONS: Treatment with ranirestat appears to have an effect on motor nerve function in mild to moderate DSP, but the results of this study failed to show a statistically significant difference in sensory nerve function relative to placebo.Keywords
This publication has 17 references indexed in Scilit:
- Reliability and validity of the modified Toronto Clinical Neuropathy Score in diabetic sensorimotor polyneuropathyDiabetic Medicine, 2009
- Oral Treatment With α-Lipoic Acid Improves Symptomatic Diabetic PolyneuropathyDiabetes Care, 2006
- Long-Term Effects of Ranirestat (AS-3201) on Peripheral Nerve Function in Patients With Diabetic Sensorimotor PolyneuropathyDiabetes Care, 2006
- Treatment of symptomatic diabetic peripheral neuropathy with the protein kinase C β-inhibitor ruboxistaurin mesylate during a 1-year, randomized, placebo-controlled, double-blind clinical trialClinical Therapeutics, 2005
- Aldose Reductase Inhibition by AS-3201 in Sural Nerve From Patients With Diabetic Sensorimotor PolyneuropathyDiabetes Care, 2004
- Can Motor Nerve Conduction Velocity Predict Foot Problems in Diabetic Subjects Over a 6-Year Outcome Period?Diabetes Care, 2002
- Effect of aldose reductase inhibition on nerve conduction and morphometry in diabetic neuropathyNeurology, 1999
- Clinical Trials of Diabetic Neuropathy: Past, Present, and FutureDiabetes, 1995
- The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population‐based cohortNeurology, 1993
- Analysis of polyols in uremic serum by liquid chromatography combined with atmospheric pressure chemical ionization mass spectrometryJournal of Chromatography B: Biomedical Sciences and Applications, 1993