ELOBIXIBAT, A BILE ACID TRANSPORTER INHIBITOR, SIGNIFICANTLY IMPROVES STOOL AND/OR GAS DISTRIBUTION THROUGH TOTAL FECAL BILE ACIDS IN ELDERLY PATIENTS WITH CHRONIC CONSTIPATION: A RANDOMIZED, PARALLEL-GROUP, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

Background and aim: Bowel stools and/or gas (S/G) volume were reported to be important indicators of bowel function in patients with chronic constipation (CC). Previously, we reported the S/G distribution assessed by ultrasound was different between healthy subjects (HS) and patients with CC, as well as being an indirect indicator of the colonic transit time (CTT). An increase in the colonic concentrations of bile acids (BAs) following treatment with the ileal BA transporter inhibitor elobixibat increased the number of bowel movements and improved fecal consistency in patients with CC, but the changes in S/G distribution and relationship between the amount of change in fecal BAs and S/G distribution before and after medication are unknown. The aims of this study were to evaluate the effect of elobixibat on the S/G distribution in the colon and examine the relationship between changes in S/G distribution and the amount of change in fecal BAs.
Patients and methods: We prospectively compared the S/G distribution of 17 patients with CC aged ≥60 years with those of 9 HS in the same age range. We performed a prospective, randomized, parallel-group, double-blind, placebo-controlled clinical trial of 17 patients with CC who were administered elobixibat or placebo daily for 1 week. The S/G distribution was measured by previously validated ultrasound measurements before and after administration using the following parameters based on measurements of the transverse diameter of five segments including the ascending colon (AC), transverse colon (TC), descending colon (DC), sigmoid colon (SC), and rectum (R). The constipation index (CI) = (AC+TC+DC+SC+R)/5] and left-right ratio (L/R) = [(DC+SC)/(AC+TC)] were calculated. We also analyzed changes in the fecal concentration of BAs using fecal samples before and after medication.
Results: At baseline, the CI, an indirect indicator of CTT, of patients with CC was significantly higher than that of HS (Fig. 1a). A comparison of transverse diameters by colonic region indicated a significant difference between the two groups from AC to SC, but not in R (Fig. 1b). The total fecal BA concentrations, particularly secondary BAs, increased from baseline. Elobixibat significantly reduced the CI before and after medication (change from baseline, −8.3 ± 8.1 mm) whereas placebo showed no change (change from baseline, −1.1± 4.0 mm) (Fig. 2a). A significant negative correlation was found between the changes in CI and change in total fecal BAs [r= −0.564 (95% confidence interval: −0.828 to −0.094), P=0.0469] (Fig. 2b).
Conclusions: Elobixibat significantly improved S/G distribution in patients with CC. The effect was correlated with changes in total fecal BAs.