Introduction 

Elevated rectal sensory thresholds (RSTs) are associated with chronic constipation (CC), especially in elderly patients. Rectal hyposensitivity has been noted in 23-25% of CC patients, however, there are no approved medications for the treatment of RH. The ileal bile acid transport inhibitor, elobixibat, increases the colonic concentrations of bile acids and thus improved bowel movements, faecal consistency, and the quality of life (QOL) of CC patients. Bile acids have been shown to affect the RSTs of healthy people, but it is unknown whether elobixibat affected the RSTs of patients with CC.

Aim

To compare the effects of elobixibat with placebo on the defaecatory desire volume (DDV), RSTs and bowel movements of elderly patients with CC, and identify the clinical characteristics of patients with beneficial effects of elobixibat on rectal sensation. Further, to compare the RSTs of elderly patients with CC versus healthy without CC.

Patient Profile 

Method

Study Design

• Prospective, randomised, parallel-group, double-blind, placebo-controlled clinical trial 
• CC patients were randomly assigned to 10 mg placebo or elobixibat daily for 1 week 

Endpoints

• Primary outcome: Defaecatory desire volume (DDV)
• Secondary outcomes: first constant sensation volume (FCSV), maximum tolerable volume (MTV) thresholds, rectal compliance and faecal bile acid concentrations

Results 

Efficacy 

• Elobixibat significantly reduced the threshold for DDV (p=0.0433) in elderly CC patients, but placebo did not have an effect (p=0.9131), as per the full analysis set evaluation and the changes in the DDV thresholds in the two groups tended to be different
• Elobixibat significantly reduced the threshold for FCSV (p=0.0018) versus placebo
• It also tended to reduce the threshold for MTV (p=0.0767), whereas placebo had no effect (p=0.2209); there were no between-treatment differences (p=0.4819) 
• No significant difference seen in the rectal compliance before and after drug administration in either group and no between-treatment differences seen (p=0.2573)
• Elobixibat significantly improved the number of spontaneous bowel movements (change from baseline, 5.00, p=0.048), as did placebo (1.80, p=0.0141); between-treatment differences tended to be significant (2.46, p=0.0549)
• It also tended to increase the number of complete spontaneous bowel movements (1.00, p=0.0519), whereas placebo did not (0.80, p=0.1228), and there was no difference in the changes between the two groups (p=0.4395)
• Elobixibat significantly increased the total faecal bile acid concentration from baseline (by a mean of 7.904 μmol/g, p=0.0120) and secondary bile acids (by 5.594 μmol/g); effects were more marked versus placebo (p=0.0158); a significant increase in deoxycholic acid (DCA) was noted (5.563 μmol/g, p=0.0039) 
• A duration of CC >5 years (p=0.0200) and having a history of treatment for CC (p<0.0001) were associated with greater efficacy of elobixibat with respect to the RST for the desire to defaecate
• Participants >65 years (p=0.0664) and women (p=0.0615) also tended to show more marked effects of elobixibat
• The RST thresholds (DDV, FCSV, and MTV) tended to be higher, but not significant, in CC patients than in healthy individuals

Conclusion 

• This was the first study to show that the bile acid transport inhibitor elobixibat improved the RSTs of patients with CC aged ≥60 years
• The effect was more marked in those with a long history of CC and in those who have already been treated for CC

BMJ Open Gastroenterol. 2023; 10: e001257