Background: Detecting the efficacy of novel analgesic agents in neuropathic pain is challenging. There is a critical need for study designs with the desirable characteristics of assay sensitivity, low placebo response, reliable pain recordings, low cost, short duration of exposure to test drug and placebo, and relevant and recruitable population.
Methods: We designed a proof-of-concept, double-blind, randomized, placebo-controlled, crossover study in patients with post-traumatic peripheral neuropathic pain (PTNP) to evaluate whether such a study design had the potential to detect efficacious agents. Pregabalin, known to be efficacious in neuropathic pain, was used as the active analgesic. We also assessed physical activity throughout the study.
Results: Twenty-five adults (20-70 years of age) with PTNP for ≥3 months entered a screening week and were then randomized to one of the two following treatment sequences: (1) pregabalin followed by placebo or (2) placebo followed by pregabalin. These 2-week treatment periods were separated by a 2-week washout period. Patients on pregabalin treatment received escalating doses to a final dosage of 300 mg/day (days 5-15). In an attempt to minimize placebo response, patients received placebo treatment during the screening week and the 2-week washout period. Average daily pain scores (primary endpoint) were significantly reduced for pregabalin versus placebo, with a mean treatment difference of -0.81 (95% confidence interval: -1.45 to -0.17; P = 0.015).
Conclusion: The efficacy of pregabalin was similar to that identified in a large, parallel group trial in PTNP. Therefore, this efficient crossover study design has potential utility for future proof-of-concept studies in neuropathic pain.
Keywords: actigraphy; placebo response; post-traumatic peripheral neuropathic pain; pregabalin; randomized crossover trial.