Trial to Understand Efficacy of Colesevelam in Diarrhea Predominant IBS Patients With Bile Acid Malabsorption

Study Overview
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Brief Summary
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To compare with a randomized trial (n=15 per treatment group), effects of colesevelam and placebo treatment, on colonic transit, bowel functions, permeability and tight junction expression in rectosigmoid mucosa of IBS-D with Bile Acid Malabsorption.

Detailed Description
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Compare the effects of Colesevelam versus the placebo on diabetic subjects with chronic diarrhea. In this study, diabetic subjects will get either the Colesevelam or the placebo, not both. The plan is to have about 30 subjects complete this study at Mayo Clinic.

Official Title
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Randomized, Double Blinded, Placebo Controlled Trial to Understand Efficacy of Colesevelam in Diarrhea Predominant IBS Patients With Bile Acid Malabsorption

Conditions
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Chronic Diarrhea, Irritable Bowel Syndrome With Diarrhea, Bile Acid Malabsorption

Intervention / Treatment
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* Drug: Colesevelam
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females and males age 18 -75. An IBS diagnosis based on the Rome III criteria for at least 3 months, with onset at least 6 months previously, of recurrent abdominal pain or discomfort. Biomarkers serum alpha C4 ≥ 40 ng/mL or FGF19 ≤ 80 pg/mL or fecal bile acid >2000 micromoles/48h Exclusion Criteria: IBS patients with known clinically-relevant inflammation. IBS patient with known bleeding diathesis History of abdominal surgery Patients participating will not take any of the following disallowed medications for at least 7 days prior to and during the remainder of the study: Any treatment specifically taken for IBS-D, including loperamide, cholestyramine, alosetron Drugs with a known pharmacological activity at 5-HT4, 5-HT2b or 5-HT3 receptors All narcotics Anti-cholinergic agents Tramadol Oral anticoagulants Antimuscarinics Peppermint oil Systemic antibiotics, as well as antibiotics directed at colonic flora such as rifaximin and metronidazole Gastrointestinal preparations: Anti-nausea agents Osmotic laxative agents Prokinetic agents 5-HT3 antagonists

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is the third specific aim of a program on IBS-D with increased fecal bile acid excretion.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Colesevelam<br>Once randomized, subjects will have baseline testing period, treatment period, and treatment testing period the study drug. This consists of nine visits and will be over a period of five to nine weeks. Baseline testing period consists of: transit test, 4 day high fat diet with 48 hour stool collection, blood samples, rectosigmoid biopsies, one week stool diary, and medication pick up. Treatment period will have subject take the study drug 1875 mg of medication orally twice daily with lunch and supper for 4-5 weeks. The last period, is the treatment testing period. This consists of a full transit & urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused medication. | Drug: Colesevelam<br>* Colesevelam (Welchol) is approved by the Food and Drug Administration (FDA) for the treatment of high blood cholesterol levels and to treat type 2 diabetes however, Colesevelam is not approved for the use proposed in this study and is considered investigational.<br>|
| Placebo Comparator: Placebo<br>Once randomized, subjects will have a baseline testing period, treatment period and treatment testing period with the placebo. This consists of nine visits and will be over a period of five to nine weeks. The last period, is the treatment testing period. This consists of a full transit & urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused placebo. | Other: Placebo<br>* A placebo looks exactly like the study drug, but it contains no active ingredient. This is used to learn if the effects seen in research participants are truly from the study drug.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Fecal Bile Acid (BA) Excretion | Total fecal BA excretion was measured using High Performance Liquid Chromatography (HPLC)/tandem mass spectrometry (MS) where single stool samples obtained at baseline and end of treatment were prepared by assay by HPLC/MS by methanol extraction and results are presented as micromoles per gram (μmoles/g) of stool. | Treatment day 28 | 
| Stool Consistency | Stool consistency as reported by the participant via daily bowel diaries. Stool consistency was based on Bristol Stool Form Scale (BSFS) where 1 - hard lumps, 2 - lumpy sausage, 3 - cracked sausage, 4 - smooth sausage, 5 - soft lumps, 6 - mushy, and 7 - watery. Stool consistency was averaged for the 28 day treatment period. | Treatment days 1 through 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Stools Per Day | The total number of bowel movements as reported by the participant via daily bowel diaries. The number of bowel movements were averaged for the 28 day treatment period. | Treatment days 1 through 28 |