Back to results

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

Primary Purpose

Diarrhea Predominant Irritable Bowel Syndrome

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Colesevelam

About this trial

This is an interventional treatment trial for Diarrhea Predominant Irritable Bowel Syndrome

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Colesevelam

Arm Description

1875 mg of Colesevelam orally twice daily for 10 days

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change in Fasting Serum C4

Change in fasting serum C4 from baseline in response to treatment with colesevelam.

Change in Fecal Fat Excretion

Change in fecal fat excretion from baseline in response to treatment with colesevelam

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.

Change in Stool Frequency (Number of Stools Per Week)

Change in stool frequency from baseline in response to treatment with colesevelam.

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.

Full Information

NCT ID

NCT02111603

First Posted

April 9, 2014

Last Updated

April 8, 2016

Sponsor

Mayo Clinic

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

1. Study Identification

Unique Protocol Identification Number

NCT02111603

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2016

Overall Recruitment Status

Completed

Study Start Date

April 2014 (undefined)

Primary Completion Date

August 2014 (Actual)

Study Completion Date

September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Mayo Clinic

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diarrhea Predominant Irritable Bowel Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

13 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Colesevelam

Arm Type

Other

Arm Description

1875 mg of Colesevelam orally twice daily for 10 days

Intervention Type

Drug

Intervention Name(s)

Colesevelam

Other Intervention Name(s)

Welchol

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in Total 48 Hour Fecal Bile Acids (BA) From Baseline in Response to Treatment With Colesevelam

Description

Time Frame

baseline, 10 days

Secondary Outcome Measure Information:

Title

Change in Fasting Serum C4

Description

Change in fasting serum C4 from baseline in response to treatment with colesevelam.

Time Frame

baseline, 10 days

Title

Change in Fecal Fat Excretion

Description

Change in fecal fat excretion from baseline in response to treatment with colesevelam

Time Frame

baseline, 10 days

Title

Change in Stool Consistency

Description

Time Frame

baseline, 10 days

Title

Change in Stool Frequency (Number of Stools Per Week)

Description

Change in stool frequency from baseline in response to treatment with colesevelam.

Time Frame

baseline, 10 days

Title

Concordance Correlation Coefficients of the Relative Composition of Stool Total and the Main Individual Bile Acids (BA)

Description

Time Frame

baseline, 10 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Camilleri, MD

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic in Rochester

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Data already published in PMID: 25594801

Citations:

PubMed Identifier

25594801

Citation

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.

Results Reference

result

Learn more about this trial

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

We'll reach out to this number within 24 hrs