Original article—alimentary tractEffects of Chenodeoxycholate and a Bile Acid Sequestrant, Colesevelam, on Intestinal Transit and Bowel Function
Section snippets
Study Design, Randomization, Medication, and Measurements
We conducted 2 double-blind, placebo-controlled, parallel-group, randomized studies evaluating the effects of oral sodium CDC or placebo, once daily for 4 days, in healthy volunteers. In a second trial, oral colesevelam hydrochloride or placebo was administered for 12 to 14 days in patients with IBS-D. The study was approved by the Mayo Clinic Institutional Review Board and all participants signed informed consent. The trial in patients with IBS-D is listed in ClinicTrials.gov (//www.clinicaltrials.gov/ct2/show/NCT00911612?term=welchol%26rank=2
Participants, Study Conduct, and Completion
All medical records were screened for major exclusion criteria (ie, prior gastrointestinal surgery and concomitant medications). Patients' responses to the bowel disease questionnaire, Hospital Anxiety and Depression scores, and SCL-90 also excluded the presence of significant gastrointestinal symptoms in the healthy volunteers or anxiety, depression, poor quality of life, or psychopathology that could act as confounders in our assessment of the effects of the administered CDC or colesevelam.
Discussion
We used 2 approaches to assess the effect of bile acids on colonic transit and of binding bile acids in the treatment of bowel dysfunction in unselected patients with IBS-D in whom indirect serum markers of bile acid synthesis were measured.
Conclusions
In summary, our studies show that the acceleration of overall colonic transit at 24 and 48 hours induced by sodium CDC is significant and comparable with the effects observed with a variety of pharmacologic agents (eg, prucalopride, lubiprostone, linaclotide) using the same colonic transit measurement. In addition, a subgroup of patients with IBS-D has amelioration of transit in response to colesevelam, fasting serum 7αC4 may predict responsiveness to bile acid binding in patients with IBS-D,
Acknowledgments
The excellent secretarial support of Mrs Cindy Stanislav is gratefully acknowledged.
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Conflicts of interest These authors disclose the following: the Mayo Clinic has filed a provisional patent application (inventors: Michael Camilleri and Duane Burton) related to this technology (no. 61/143,727). The remaining authors disclose no conflicts.
Funding Dr Camilleri is supported by a National Institutes of Health grant (DK-54681).