A randomized clinical trial of efficacy and safety of the topical clonidine and capsaicin in the treatment of painful diabetic neuropathy

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SCIENCE
A randomized clinical trial of efficacy and safety of the topical clonidine and capsaicin in the treatment of painful diabetic neuropathy
Key Take-Away: 
  • Clonidine and capsaicin drugs significantly relieved pain at 12 weeks (< 0.001 for both) but no significant difference in the efficacy between the two treatments was observed (=0.931).
  • Capsaicin treatment group reported more adverse effects than clonidine treatment group.

Diabetic peripheral neuropathy (DPN) is one of the most commonly encountered neuropathic pain syndromes in clinical practice; which is often inadequately controlled. Several medications, mostly antidepressants, and antiepileptic, have been used with varying degrees of success in the treatment of painful diabetic neuropathy (PDN)

ABSTRACT: 
Background: 

Diabetic peripheral neuropathy (DPN) is one of the most commonly encountered neuropathic pain syndromes in clinical practice; which is often inadequately controlled.

Diabetic peripheral neuropathy (DPN) is one of the most commonly encountered neuropathic pain syndromes in clinical practice; which is often inadequately controlled. Several medications, mostly antidepressants, and antiepileptic, have been used with varying degrees of success in the treatment of painful diabetic neuropathy (PDN). Incomplete efficiency of analgesics, systemic side effects, and cognitive impairment of these drugs due to central effects restrict their therapeutic success. Use of topical medications because of less systemic side effects is more acceptable. Topical capsaicin formulations those act by depletion of substance P and possibly other neurotransmitters from sensory nerve endings are widely used to manage neuropathic pain. Also, topical form of clonidine that is a α2-adrenergic receptor agonist and was originally approved as an oral treatment for hypertension is used recently for pain relief.

  • Rationale behind research
  1. Incomplete efficiency of analgesics, systemic side effects, and cognitive impairment of these drugs due to central effects restrict their therapeutic success.
  2. Use of topical medications because of less systemic side effects is more acceptable.
  • Objective

To compare the effect of clonidine gel and capsaicin cream in relieving pain associated with DPN.

Methods: 

 

Study outcomes

  • Primary outcome: Reduction in the median pain score from baseline, as assessed by the VAS (0-10 points) at each of the 4-weekly follow-up visits
  • Secondary outcome: Pain severity, vital signs, examination and questioning regarding the adverse effects were performed at each of the 4 weekly follow up visits

Note: The investigator was accessible by telephone to all patients throughout the study.

Time points:

  • Efficacy: Baseline and at each of the 4-weekly follow-up visits upto 3 months
  • Side effects : Baseline and at each of the 4-weekly follow-up visits upto 3 months
Results: 

 

Baseline: Treatment groups were well balanced with no significant baseline differences

  • Primary outcomes:
  • At week 12, ≥50% reduction from baseline on VAS assessment of clonidine group and capsaicin group , respectively (P = 0.051)
  • Both drugs significantly relieved pain at 12 weeks (P < 0.001 for both) but no significant difference in the efficacy between the two treatments was observed (P =0.931)
  • Secondary outcomes :
  • Systolic and diastolic blood pressures had no significant changes during the treatment in the clonidine group (P = 0.547, 0.247) respectively.
  • Dermatologic complications were more common in capsaicin group 40 (58%) patients than 4 (5.7%) patients in clonidine group (P = 0.001)
  • Skin dryness and itching were the most common in the clonidine group (4.2% and 1.4% respectively).
  • The most common side effects of capsaicin were itching, blister formation and erythema respectively (45.5%, 13.6% and 9.1%).

 

Conclusion: 

The result indicates that clonidine was well tolerated and safe during this 12 week study. There were more discontinuations due to adverse events in the capsaicin treatment group than in the clonidine treatment group. This study compared the efficacy of clonidine gel with capsaicin cream, a FDA approved drug, but prolonged therapy and evaluation for a longer duration than the 12 weeks can better evaluate the benefits of this drug. 

Despite the efficacy of some oral medications in neuropathic pain, side effects are experienced by most of the patients. The recent study Campbell et al. compared the efficacy of topical clonidine with placebo and found that 0.1% topical clonidine gel significantly reduced the level of foot pain in comparison with placebo (P = 0.01). Also, no severe adverse events were reported in treatment with clonidine.

J. Res Med Sci. 2015 Apr; 20(4):359-363
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