Mo1287 Efficacy of ONO-2952, a Novel and Selective Antagonist of Translocator Protein: Results of a Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Phase II Study (RESTORE-4)

Abstract

Background / Aims: Sleep disorders are often associated to functional gastro-intestinal disorders (FGIDs). The aim of this study is to evaluate prospectively if the presence of sleep disturbances is associated with specific FGID and to assess a possible association to psychological disorders. Methods: Six hundred and eleven consecutive FGID patients (71% female), aged 48.8±16.9 years (M±SD), (BMI 27.0±13.8 kg/m2) that have filled both psychological evaluation on anxiety and depression, and a Rome III questionnaire, were included in this study. The patients were classified according the importance of the sleep duration using a 7-points grading scale: Group 1 to 3 , hypersomnia, respectively severe, moderate and mild; Group 4: no sleep change, Group 5 to 7 insomnia, respectively mild, moderate, and severe. The backwards selection procedure was used for model selection during multivariate logistic regression. Results: 406 patients (66%) reported change of sleep pattern: decreased in 130 (21%), and increased in 276 (45%), while 205 (34%) reported no change. BMI did not differ between the different groups. Patients with increased sleep were the oldest Depression was lower in patients with no change in sleep pattern (P<0.001). Patients with mild change of sleep pattern (group 3 and 5) have depression score higher than patients with no change (P<0.001), and lower than other patients with moderate (Group 2 and 6) or severe (Group 1 and 7) change of sleep pattern (P<0.001). Patients with no sleep change (Group 4) have significant lower anxiety score than patients with moderate change of sleep pattern (Group 2, P<0.001; Group 6, P=0.002) or severe hypersomnia (P=0.001). Among patients that reported an increased sleep, severe hypersomnia is associated to age (P=0.001), high depression (P<0.001), low state anxiety (P=0.036), and increased constipation (P= 0.034;) or fecal incontinence (P=0.022). Moderate hypersomnia is associated to increased depression (P=0.044), state anxiety (P=0.024), constipation (P=0.021), bloating (P=0.026), and proctalgia fugax (P=0.010). Mild hypersomnia is associated to increased mixed IBS (P= 0.047) and fecal incontinence (P=0.032). In patients with no change in sleeping pattern (Group 4), IBS-diarrhea phenotype is a positive descriptor (P=0.018). For patients that report decreased sleep patterns, mild insomnia is associated to high trait anxiety (P=0.048) and low dyspepsia (P=0.011). Moderate insomnia is associated to high depression (P<0.001), low state anxiety (P=0.011), and to an increase of chest pain (P=0.008), IBS-diarrhea (P= 0.009), IBS-mixed (P=0.042) and diarrhea (P=0.021). Severe insomnia is associated to high depression (P=0.003), and an increased frequency of chest pain (P=0.026) and epigastric pain syndrome (P=0.012). Conclusion: This study leads us to consider sleep disorders as potential pathogenic factors in FGIDs.