Objective: We report the results of a pilot, enrichment-design, placebo-controlled crossover trial of pregabalin for the treatment of prediabetic small-fiber neuropathic pain.
Methods: Individuals with impaired fasting glucose or impaired glucose tolerance and neuropathic pain were evaluated according to UTAH Early Neuropathy Scale (UENS), Quantitative Sensory Testing, and intraepidermal nerve fiber density (IENFD). Symptoms were graded according to the Numeric Rating Scale (NRS). Individuals who responded to the administration of placebo were not eligible. Pregabalin was initiated at a dose of 75 mg qid and tapered up to 300 mg bid. Only individuals with a reduction of pain scores ≥30% were eligible to continue with the double-blind phase, which consisted of a randomized crossover period of 1 month of pregabalin and 1 month of placebo, with 7 days of washout between periods.
Results: Forty-five participants were enrolled in the study. There was 36% reduction in the NRS from baseline after 1 month of single-blind pregabalin (NRS=5.1±2.6). Twenty-six participants were eligible for the double-blind phase. There was further reduction of pain in the double-blind pregabalin and the placebo groups, but the pregabalin group had a statistically significant reduction of pain (NRS=3.2±2.2 vs. 4.0±2; P<0.05). Participants who did not respond showed a lower IENFD than those who responded, suggesting more severe nerve damage.
Conclusions: This pilot study showed improvement of prediabetic neuropathic pain. Participants with higher pain scores at baseline had higher UENS scores and a lower IENFD. Limitations of the study include the small number of participants and the carry-over effect.