Randomized Control Trial of Topical Clonidine for Treatment of Painful Diabetic Neuropath

SLR - July 2013 - James A. Averett

Reference:  Campbell CM, Kipnes MS, Stouch BC, Brady KL, Kelly M, Schmidt WK, Petersen KL, Rowbotham MC, Campbell JN. Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy Pain. 2012 Sep; 153(9): 1815-23.

Scientific Literature Review

Reviewed by: James A. Averett, DPM
Residency Program: Southern Arizona VA Health Care System

Podiatric Relevance:  Painful diabetic neuropathy is a very common and debilitating complication of diabetes mellitus. It is commonly encountered in the podiatric clinical practice and affects large portions of our diabetic patients. The information gathered from this article keys on an additional topical treatment for painful diabetic neuropathy in the use of topical clonidine, an α (2)-adrenergic agonist. It was hypothesized that neuropathic pain may arise from cutaneous nociceptors, and that this signaling may be decreased with application of topical clonidine. Topical application of clonidine used in the treatment of painful diabetic neuropathy may represent a viable option when it comes to treating our diabetic patients with painful diabetic neuropathy.
   

Methods: This study was a randomized, double blind, placebo-controlled, parallel-group, multi-center trial. Four hundred sixty-four patients were screened and 182 were randomized into two groups. Nociceptor function was measured by determining the painfulness of 0.1 percent topical capsaicin applied to the pretibial area of each subject for 30 minutes during inspection. Subjects were then randomized to receive 0.1 percent topical clonidine gel or placebo gel applied three times a day to their feet for 12 weeks. The difference in foot pain at week 12 in relation to baseline, rated on a 0-10 numerical pain rating scale (NPRS), was compared among groups. 

Results: The subjects treated with topical clonidine displayed decreased foot pain when compared to the placebo-treated group. In subjects who felt pain to capsaicin, clonidine was superior to placebo. In subjects with a capsaicin pain rating ≥2 (0-10, NPRS), the mean decrease in foot pain was 2.6 for active compared to 1.4 for placebo.
   

Conclusions: Topical clonidine gel reduces the level of foot pain in painful diabetic neuropathy subjects with functional, and possibly sensitized, nociceptors in the affected skin as discovered by testing with topical capsaicin. Screening for nociceptor function may help differentiate candidates for topical therapy for neuropathic pain. Topical clonidine should be considered in the treatment of painful diabetic neuropathy in the podiatric setting.