Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy.
A length-dependent neuropathy with pain in the feet is a common complication of diabetes (painful diabetic neuropathy). It was hypothesized that pain may arise from sensitized-hyperactive cutaneous nociceptors, and that this abnormal signaling may be reduced by topical administration of the α(2)-adrenergic agonist, clonidine, to the painful area. This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. Nociceptor function was measured by determining the painfulness of 0.1% topical capsaicin applied to the pretibial area of each subject for 30minutes during screening. Subjects were then randomized to receive 0.1% topical clonidine gel (n=89) or placebo gel (n=90) applied 3 times a day to their feet for 12weeks. The difference in foot pain at week 12 in relation to baseline, rated on a 0-10 numerical pain rating scale (NPRS), was compared between groups. Baseline NPRS was imputed for missing data for subjects who terminated the study early. The subjects treated with clonidine showed a trend toward decreased foot pain compared to the placebo-treated group (the primary endpoint; P=0.07). In subjects who felt any level of pain to capsaicin, clonidine was superior to placebo (P<0.05). 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 (P=0.01). Topical clonidine gel significantly reduces the level of foot pain in painful diabetic neuropathy subjects with functional (and possibly sensitized) nociceptors in the affected skin as revealed by testing with topical capsaicin. Screening for cutaneous nociceptor function may help distinguish candidates for topical therapy for neuropathic pain.
Johns Hopkins School of Medicine, Baltimore, MD 21224, USA Diabetes and Glandular Disease Clinic, San Antonio, TX 78229, USA BCS Consulting, Newtown Square, PA 19073, USA Arcion Therapeutics, Baltimore, MD 21224, USA University of California-San Francisco, San Francisco, CA 94143, USA California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA.
Claudia M
CM
Campbell
Mark S
MS
Kipnes
Bruce C
BC
Stouch
Kerrie L
KL
Brady
Margaret
M
Kelly
William K
WK
Schmidt
Karin L
KL
Petersen
Michael C
MC
Rowbotham
James N
JN
Campbell
D000279:Administration, Cutaneous; D000368:Aged; D000700:Analgesics / Q000627:therapeutic use*; D002211:Capsaicin; D003000:Clonidine / Q000627:therapeutic use*; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D059226:Nociceptive Pain / Q000188:drug therapy*; D009619:Nociceptors / Q000187:drug effects; D010147:Pain Measurement; D018689:Sensory System Agents; D016896:Treatment Outcome
D000700:Analgesics; D018689:Sensory System Agents; D003000:Clonidine; D002211:Capsaicin