Clinical trial NCT02111603: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diarrhea Predominant Irritable Bowel Syndrome
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2014-04-11
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in Total 48 Hour Fecal Bile Acids (BA) From Baseline in Response to Treatment With Colesevelam
timeFrame: baseline, 10 days
Secondary outcomes:
measure: Change in Fasting Serum C4
timeFrame: baseline, 10 days
measure: Change in Fecal Fat Excretion
timeFrame: baseline, 10 days
measure: Change in Stool Consistency
timeFrame: baseline, 10 days
measure: Change in Stool Frequency (Number of Stools Per Week)
timeFrame: baseline, 10 days
measure: Concordance Correlation Coefficients of the Relative Composition of Stool Total and the Main Individual Bile Acids (BA)
timeFrame: baseline, 10 days
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Michael Camilleri, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.