Factors that Impact Symptomatic Diabetic Peripheral Neuropathy in Placebo-treated Patients from Two 1-year Clinical Trials

Abstract

Objective: To evaluate the change in neuropathy symptoms and disease progression in placebo-treated patients from two 1-year studies that tested the impact of ruboxistaurin (RBX) in mild diabetic peripheral neuropathy (DPN).

Research Design and Methods: Data from 262 placebo-treated patients from two identical phase 3, randomized, double-blind trials were combined and analyzed.

Results: After 1 year, change in Neuropathy Impairment Score of Lower Limbs (NIS[LL];-0.63 points; p = 0.005), vibration detection threshold (VDT, -0.42 JND Units; p = 0.003) and Neuropathy Total Symptom Score-6 (NTSS-6, -3.73 points; p < 0.001) improved while some electrophysiology measures and Heart Rate Deep Breathing (HRDB - 0.78 beats; p = 0.003) worsened when compared with baseline values. There was a small but significant worsening of A1C (0.28%; p < 0.001) and a greater percentage of patients were using analgesics at the end of the trials (33.6%; p = 0.003). At 1 year, the change in NTSS-6 directly correlated with changes in NIS(LL) and VDT, and inversely correlated with the peroneal nerve conduction velocity. On logistic regression analyses, a ≥ 50% reduction in NTSS-6 score was less likely in patients that used anti-hypertensive or chronic symptom medication at baseline.

Conclusions: In placebo-treated patients with mild symptomatic DPN: 1) there was a progressive improvement in symptoms over 12 months whilst nerve conduction studies and HRDB declined; 2) clinically significant worsening of DPN would require greater than 1 year of observation.