Topical RM191A gel for chronic peripheral neuropathic pain: randomized, double-blind, placebo-controlled, crossover pilot study

Introduction Current pharmacotherapy options for neuropathic pain (NPP) are limited. RM191A is a novel copper-amino acid complex that mimics superoxide dismutase and has anecdotal evidence for fast-onset analgesia. The aim of this pilot randomized clinical trial (RCT) was to evaluate the safety and efficacy of a topical gel containing RM191A compared with placebo in adults with moderate-to-severe chronic peripheral NPP. Materials and methods This single-site study was conducted at an Australian pain clinic. Eligible patients were randomized to receive either active or placebo gel, applied four times daily to the painful site for 3 days, followed by a 4-day washout and crossover to the other gel. Co-primary outcomes were changes in the Numerical Pain Rating Scale (NPRS) scores for average pain from baseline to Days 1 and 3. Secondary outcomes included safety/tolerability and neuropathic pain characteristics. Results Twenty-seven participants (14 males, 13 females, mean age 67 ± 15 years) were screened, with 25 proceeding to randomization and 24 completing both treatment periods. No first-order ( p = 0.816) or second-order carryover effects ( p = 0.322) were detected. The Day 1 coprimary outcome was not significant ( p = 0.323), but there was a trend toward one-sided statistical significance for the Day 3 coprimary outcome ( p = 0.073). The mean reduction in NPRS Average Pain by Day 3 was significant for the active gel (–0.9 ± 1.6, p = 0.012) but not the placebo (–0.2 ± 1.7, p = 0.485). Post hoc analysis revealed the superiority of the active gel in participants with Douleur Neuropathique 4 (DN4) scores ≥4 ( n = 15, p = 0.047). The number needed to treat (NNT) for 50% pain reduction by Day 3 was 8 (95% CI: greater than 3.9). The active gel was more effective against burning pain, paroxysmal pain, and paraesthesia/dysesthesia than other types of NPP. There were no serious adverse events, while four (16%) participants reported mild skin irritation. Discussion This small pilot RCT found that 3 days of RM191A gel modestly reduced chronic peripheral neuropathic pain. The NNT of 8 compares favorably with topical lidocaine (14.5) and is similar to duloxetine (7.4) and gabapentinoids (8.9). Larger, longer studies in well-defined neuropathic pain populations are warranted. Clinical Trial Registration ANZCTRN 12617000206325. https://www.anzctr.org.au/