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

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

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.

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.

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