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

doi:10.2337/dc07-0608

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

Solomon Tesfaye, MD, FRCP1,
Rup Tandan, MD, FRCP2,
Edward J. Bastyr III, MD3 4,
Keri A. Kles, PHD3,
Vladimir Skljarevski, MD3,
Karen L. Price, PHD3 and
for the Ruboxistaurin Study Group *

¹Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield, U.K
²University of Vermont, College of Medicine, Burlington, Vermont
³Lilly Research Laboratories, Indianapolis, Indiana
⁴Indiana University, Indianapolis, Indiana

Address correspondence and reprint requests to Professor Solomon Tesfaye, Royal Hallamshire Hospital, Q Floor, Room 26, Glossop Road, Sheffield S102JF, U.K. E-mail: solomon.tesfaye{at}sth.nhs.uk

Abstract

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.

Footnotes

Published ahead of print at http://care.diabetesjournals.org on 10 July 2007. DOI: 10.2337/dc07-0608. Clinical trial reg. no. NCT00044408 and NCT00044395, clinicaltrials.gov.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/dc07-0608.
R.T. has received research support and honoraria from Eli Lilly for serving on an advisory board.
*
↵* A complete list of the Ruboxistaurin Study Group members can be found in the appendix.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.
- Accepted June 28, 2007.
- Received March 27, 2007.
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