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

Diarrhea Predominant Irritable Bowel Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02111603
• Other study ID #: 14-000384
• Secondary ID: R01DK092179UL1TR
• Status: Completed
• Phase: Phase 4
• First received: April 9, 2014
• Last updated: January 26, 2016
• Start date: April 2014
• Est. completion date: September 2015

Study information

• Verified date: January 2016
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: September 2015
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diarrhea
• Diarrhea Predominant Irritable Bowel Syndrome
• Irritable Bowel Syndrome

Intervention

Drug:
• Colesevelam
Subjects will receive 1875 mg of Colesevelam orally twice daily for 10 days

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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):4 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change in Fasting Serum C4	Change in fasting serum C4 from baseline in response to treatment with colesevelam.	baseline, 10 days	No
Secondary	Change in Fecal Fat Excretion	Change in fecal fat excretion from baseline in response to treatment with colesevelam	baseline, 10 days	No
Secondary	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	No
Secondary	Change in Stool Frequency (Number of Stools Per Week)	Change in stool frequency from baseline in response to treatment with colesevelam.	baseline, 10 days	No
Secondary	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	No