Factors That Impact Symptomatic Diabetic Peripheral Neuropathy in Placebo-Administered Patients From Two 1-Year Clinical Trials

• Published in: Diabetes care Vol. 30; no. 10; pp. 2626 - 2632
• Main Authors: Tesfaye, Solomon, Tandan, Rup, Bastyr, Edward J. III, Kles, Keri A, Skljarevski, Vladimir, Price, Karen L
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.10.2007
• Subjects: analgesics; Analgesics - therapeutic use; Biological and medical sciences; breathing; Clinical trials; Clinical Trials as Topic; detection limit; Development and progression; Diabetes; Diabetes. Impaired glucose tolerance; Diabetic Neuropathies; Diabetic Neuropathies - drug therapy; Diabetic Neuropathies - physiopathology; Diabetic neuropathy; Diagnosis; disease course; Dosage and administration; drug therapy; electrophysiology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzyme inhibitors; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Evaluation; heart rate; Humans; Kinases; Medical sciences; Medical treatment; Metabolic diseases; Miscellaneous; Multicenter Studies as Topic; nerve tissue; Neural Conduction; normal values; patients; peripheral nervous system diseases; Peripheral Nervous System Diseases - drug therapy; Peripheral Nervous System Diseases - physiopathology; physiopathology; Placebo effect; Placebos; Public health. Hygiene; Public health. Hygiene-occupational medicine; questionnaires; Randomized Controlled Trials as Topic; regression analysis; Research Design; Studies; therapeutic use; Treatment Outcome; vibration; United Kingdom; Endocrinopathy; Human; Drug; Nervous system diseases; Nutrition; Diabetes mellitus; Patient; Metabolic diseases; Peripheral neuropathy; Placebo; Clinical trial; Peripheral nerve disease; Endocrinology
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc07-0608

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. RESEARCH DESIGN AND 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 >=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.