Ranirestat for the management of diabetic sensorimotor polyneuropathy.
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).


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 <or= 0.05) and at weeks 24 and 36 and in peroneal motor NCV at weeks 36 and 52 (P <or= 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.
Bril
Vera
V
University Health Network, University of Toronto, Toronto, Ontario, Canada. vera.bril@utoronto.ca
Hirose
Toshiyuki
T
Tomioka
Sasagu
S
Buchanan
Robert
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008475:Median Nerve / Q000187:drug effects / Q000503:physiopathology; D008875:Middle Aged; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D010919:Placebos; D011719:Pyrazines / Q000627:therapeutic use*; D012684:Sensory Thresholds / Q000187:drug effects / Q000502:physiology; D013141:Spiro Compounds / Q000627:therapeutic use*; D013497:Sural Nerve / Q000187:drug effects / Q000503:physiopathology; D055815:Young Adult
D010919:Placebos; D011719:Pyrazines; D013141:Spiro Compounds; D000449:Aldehyde Reductase; C115070:ranirestat