Ability of Mayo Clinic High-performance Liquid Chromatography (HPLC) Method to Measure Fecal Bile Acids

Ability of Mayo Clinic HPLC Method to Measure Fecal Bile Acids to Demonstrate Response to Colesevelam in Patients With Diarrhea Predominant Irritable Bowel Syndrome

The investigators' hypothesis is that therapy with Colesevelam, reduces fecal bile acid excretion in patients with Irritable Bowel Syndrome (IBS)-diarrhea with prior evidence of increased fecal 48 hour total bile acid excretion. The investigators aim to study the ability of the HPLC assay for fecal bile acids to demonstrate responsiveness after treatment with Colesevelam.

Study Overview

• Status: Completed
• Conditions: Diarrhea Predominant Irritable Bowel Syndrome
• Intervention / Treatment: Drug: Colesevelam

Detailed Description

This study will evaluate whether Colesevelam, a bile acid sequestrant, is able to reduce fecal bile acids and improve bowel function in patients with IBS-diarrhea and Mayo's HPLC method can demonstrate a response to the Colesevelam.

The study design will be a single center, unblinded, single dose trial to study the ability to identify the effect of taking 1875 mg (3 tablets [625 mg/tablet]) of Colesevelam orally twice daily for ten days on fasting serum 7alphaC4 and total 48 hour fecal bile acid excretion. Stool and fasting serum samples will be collected predose and during final 48 hours' dosing for assessment. Participants will also fill out an 8-day stool diary assessing frequency, consistency, ease of passage of bowel movements before and during treatment with Colesevelam.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Patients with IBS-diarrhea with prior evidence of increased fecal 48 hour total bile acid and increased fasting serum 7alphaC4 who meet the following:

INCLUSION CRITERIA

• Bowel disease questionnaire (BDQ) - IBS symptoms: Positive by Rome lll criteria
• No restrictions on Hospital Anxiety/Depression Score (HADS).
• Gender: Men or women. Women of childbearing potential will have a negative pregnancy test before initiation of medication.

EXCLUSION CRITERIA

• Use of drugs or agents within the past 1 week or planned use in the subsequent 2 weeks during the study period (Birth control pill, estrogen replacement therapy, and thyroxine replacement are permissible exceptions):

  • Agents that alter GI transit including opioids, narcotics, anticholinergics, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRI) antidepressants.
  • Analgesic drugs including opiates, nonsteroidal anti-inflammatory drugs (NSAID), cyclooxygenase-2 (COX 2) inhibitors
  • Intake of medication that could interfere with the interpretation of the study.
• Female subjects who are pregnant or breast-feeding. Females must be either surgically sterilized, postmenopausal (>12 months since last menses), or, if of childbearing potential, using reliable methods of contraception as determined by the physician.
• Abdominal surgery (except Appendectomy)

• Patients with known chronic liver disease or history of elevated aspartate aminotransferase (AST)/ alanine transaminase (ALT) 2.0 X upper limit of normal.

  • Bile acid (BA) synthesis and possible false positive or negative fecal bile acid or serum 7alpha-hydroxy-4-cholesten-3-one (7alphaC4) result. If there is no AST or ALT values in the medical record, the study physicians will determine if the tests need to be run.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Colesevelam; 1875 mg of Colesevelam orally twice daily for 10 days	Drug: Colesevelam; Subjects will receive 1875 mg of Colesevelam orally twice daily for 10 days; Other Names: Welchol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total 48 Hour Fecal Bile Acids (BA) From Baseline in Response to Treatment With Colesevelam	Stool 48 hour collections (for BAs) were collected during baseline before treatment, and then during days 9-10 of the 10 days of colesevelam dosing for fecal BAs. Total fecal BA were measured using HPLC/tandem mass spectrometry.	baseline, 10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fasting Serum C4	Change in fasting serum C4 from baseline in response to treatment with colesevelam.	baseline, 10 days
Change in Fecal Fat Excretion	Change in fecal fat excretion from baseline in response to treatment with colesevelam	baseline, 10 days
Change in Stool Consistency	The subjects rated their stool consistency using the Bristol Stool Form Scale. The Bristol Stool Form Scale is a medical aid designed to classify the form of human feces into seven categories or types. Types 1 and 2 indicate constipation with 3 and 4 being the "ideal stools" especially the latter, as they are the easiest to defecate, and 5-7 tending towards diarrhea.	baseline, 10 days
Change in Stool Frequency (Number of Stools Per Week)	Change in stool frequency from baseline in response to treatment with colesevelam.	baseline, 10 days
Concordance Correlation Coefficients of the Relative Composition of Stool Total and the Main Individual Bile Acids (BA)	Stool 48 hour collections (for BAs) were collected during baseline before treatment, and then during days 9-10 of the 10 days of colesevelam dosing for fecal BAs. Relative composition of the main individual bile acids (cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA) and ursodeoxycholic acid (UDCA)) in 48 hour stool collection after colesevelam treatment were compared to baseline values. The concordance correlation coefficient (rc) measures agreement between two variables. The concordance correlation satisfies -1 ≤ rc ≤ +1. A value of rc = +1 corresponds to perfect agreement. A value of rc = -1 corresponds to perfect negative agreement, and a value of rc = 0 corresponds to no agreement.	baseline, 10 days

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

General Publications

• Camilleri M, Acosta A, Busciglio I, Boldingh A, Dyer RB, Zinsmeister AR, Lueke A, Gray A, Donato LJ. Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2015 Mar;41(5):438-48. doi: 10.1111/apt.13065. Epub 2015 Jan 16.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: April 9, 2014
• First Submitted That Met QC Criteria: April 10, 2014
• First Posted (Estimate): April 11, 2014

Study Record Updates

• Last Update Posted (Estimate): May 12, 2016
• Last Update Submitted That Met QC Criteria: April 8, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Diarrhea; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Colesevelam Hydrochloride
• Other Study ID Numbers: 14-000384; UL1TR000135 (U.S. NIH Grant/Contract); R01DK092179 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data already published in PMID: 25594801