A Placebo-Controlled Trial of Pregabalin for Irritable Bowel Syndrome 2016 ACG Governors Award for Excellence in Clinical Research

Abstract

Introduction: There are limited treatments for Irritable bowel syndrome (IBS) pain. Pregabalin is a calcium channel α2δ ligand with analgesic activity used for fibromyalgia and has been shown to modify visceral hypersensitivity in IBS patients. Clinical data for Pregabalin in IBS are lacking.Aim: To collect preliminary data on Pregabalin's effect on GI symptoms in IBS patients. Methods: A randomized, double-blind, placebo-controlled, two-arm, parallel group clinical trial design was performed. Subjects 18-70 meeting Rome III criteria for IBS and reporting a pain score greater than 50 (on a scale of 0-100) were randomized to receive Pregabalin (PRG) 225 v. placebo (PLA) twice daily for 12 weeks. Symptom questionnaires were administered weekly including the visual analog Bowel Symptom Scale (BSS). The primary endpoint was the average pain BSS scores over the last 4 weeks of the treatment period. A priori secondary endpoints were also evaluated. An ITT analysis of covariance (ANCOVA) was used to assess effects of treatment on quantitative endpoints, adjusting for age and gender. Adequate relief and change in pain score were assessed using a chi-square test. Missing quantitative values were replaced with the overall mean or assumed to be a “No” response for the discrete endpoints. Results: 85 patients were recruited and eligible. Sample characteristics include: mean age 39.4 (sd=14.6); 73 (86%) female;18 (21%) IBS-C, 29 (35%) IBS-M, 37 (44%) IBS-D. For the primary endpoint, the PRG arm had lower average Pain-BSS scores weeks 9-12 (26.1 PRG v. 42 PLA, p=0.008). In addition, the average Overall-BSS severity score weeks 9-12 were lower in the PRG arm (28.5 v. 42.2, p=0.009). Differences were observed for the average Diarrhea-BSS and Bloating-BSS scores weeks 9-12 (p=0.049 and p=0.044, respectively). No differences between groups were seen for the Constipation-BSS scores. Similar findings were seen for comparison of end-of-treatment week 12 scores. Adequate relief at week 12 was not different between the two arms (46% v. 36%, p=0.35). 63% PRG v. 45% PLA arm had a change in pain scores ≥3 at week 12 from baseline (p=0.10). IBS-QoL scores did not differ post-treatment between the two arms. Conclusion: This pilot study suggests that Pregabalin may show beneficial effects on IBS symptoms including overall symptoms and abdominal pain, and potentially bloating and diarrhea. Additional studies are warranted to determine whether these findings are replicated.