Clinical trials of sorbinil on nerve function

Three clinical trials to evaluate the efficacy of the aldose reductase inhibitor sorbinil in improving or preventing diabetic neural function have either been completed or are currently in progress. In the first study from Seattle and Chicago, motor and sensory nerve conduction velocities (NCV) were evaluated in 39 insulin- and noninsulin-dependent, glycemic-stable diabetic patients in a randomized, double-blind, crossover trial. During the 9 weeks of treatment with 250 mg/d of sorbinil, there was a faster nerve conduction velocity of all 3 nerves tested when compared with the placebo period: peroneal motor NCV (+0.70 +/- 0.24 m/s; means +/- SEM; P less than 0.008), median motor NCV (+0.66 +/- 0.27 m/s; P less than 0.005), and median sensory NCV (+1.16 +/- 0.50 m/s; P less than 0.035). Conduction velocity for all 3 nerves declined significantly within 3 weeks following cessation of the drug. These effects of sorbinil were unrelated to glycemic control, which was constant during the study. Although the effects of sorbinil in improving nerve conduction velocity were small, the findings suggest that the polyol-pathway activity contributes to slowed nerve conduction velocity in diabetics. The second study is a seven-center, double-blind, randomized, 12-month trial of 210 to 280 diabetic patients with clinical signs, symptoms, and objective measurements of neuropathy. The trial has a common-core protocol with end-point evaluations of scored neural signs, symptoms, and neural measurements. Two unique neural tests were designed and validated for use in this trial: thermal and tactile perception thresholds of the fingers and toes.(ABSTRACT TRUNCATED AT 250 WORDS)