Factors that impact symptomatic diabetic peripheral neuropathy in placebo-administered patients from two 1-year clinical trials.
OBJECTIVE
The purpose of this study was to evaluate the change in neuropathy symptoms and disease progression in placebo-administered patients from two 1-year studies in which the impact of ruboxistaurin (RBX) in mild diabetic peripheral neuropathy (DPN) was tested.


METHODS
Data from 262 placebo-administered patients from two identical phase 3, randomized, double-blind trials were combined and analyzed.


RESULTS
After 1 year, change in the neuropathy impairment score of lower limbs [NIS(LL)] (-0.63 points; P = 0.005), vibration detection threshold (VDT) (-0.42 just noticeable difference units; P = 0.003), and Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire (-3.73 points; P < 0.001) improved, whereas some electrophysiology measures and heart rate deep breathing (HRDB) (-0.78 beats; P = 0.003) worsened 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 > or = 50% reduction in NTSS-6 score was less likely in patients who used antihypertensive or chronic symptom medication at baseline.


CONCLUSIONS
In placebo-administered patients with mild symptomatic DPN, there was a progressive improvement in symptoms over 12 months, whereas nerve conduction studies and HRDB declined, and clinically significant worsening of DPN would require > 1 year of observation.
Tesfaye
Solomon
S
Diabetes Research Unit, Royal Hallamshire Hospital, Q Floor, Room 26, Glossop Road, Sheffield S102JF, UK. solomon.tesfaye@sth.nhs.uk
Tandan
Rup
R
Bastyr
Edward J
EJ
Kles
Keri A
KA
Skljarevski
Vladimir
V
Price
Karen L
KL
D000700:Analgesics / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D015337:Multicenter Studies as Topic; D009431:Neural Conduction; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D016896:Treatment Outcome
D000700:Analgesics; D010919:Placebos