Does Welchol (Colesevelam Hydrochloride) Improve Colonic Transit in Diarrhea-predominant Irritable Bowel Syndrome (D-IBS)?
Condition: Irritable Bowel Syndrome; Diarrhea
MeSH terms: Irritable Bowel Syndrome; Syndrome; Diarrhea
Study type: Interventional
Phase: Phase 2

Summary: 
      Our hypothesis is that the medication approved for treatment of high blood cholesterol
      levels, Colesevelam HCl (WELCHOL), decreases colonic transit and permeability in patients
      with diarrhea due to irritable bowel syndrome.

      This effect is thought to result from the effect of the medication on bile acids, which can
      cause diarrhea.
    

Detailed description: 
      Background:

      Irritable bowel syndrome (IBS) affects about 15% of the U.S. population, about 5% having
      predominant diarrhea; current treatment is suboptimal as it may not be tolerated, lead to
      side effects or insufficient benefit. Bile acid malabsorption (BAM) is recognized as a cause
      of chronic diarrhea and has been investigated as a mechanism for the phenotype of diarrhea
      predominant IBS (D-IBS). Increased exposure of the colon to bile acids which may result from
      accelerated small bowel transit or abnormal function of the apical sodium bile acid
      transporter (ASBT) has been postulated to cause functional diarrhea or symptoms of D-IBS by a
      number of mechanisms, such as increase colonic secretion, and mucosal permeability. Recent
      preliminary data suggest that doses of chenodeoxycholate (CDC) that are approved for the
      dissolution of gall stones are associated with accelerated colonic emptying and looser stool
      consistency.

      Hypothesis:

      The bile acid binding agent, Colesevelam HCl, decreases colonic transit and permeability in
      patients with D-IBS.

      Specific Aim:

      To investigate the effect of Colesevelam, which binds bile acids in the small intestine and
      reduces the concentration of bile acids in the colon, on colonic transit, permeability and
      the bowel function of patients with D-IBS.

      Methods:

      Twenty-four D-IBS participants will be randomized to placebo or treatment with Welchol
      (Colesevelam HCL) 1.875 gram b.i.d. for 12-14 days. A baseline colon transit, 24 hour urine
      for colon permeability, and blood for serum 7 alpha-hydroxy-4-cholesten-3-one (7 alpha-HCO)
      will be measured and venous blood DNA will be collected and stored. The measurement of serum
      7 alpha-hydroxy-4-cholesten-3-one (7 alpha-HCO), which is a measurement of hepatic
      cholesterol synthesis, is closely related to the fecal loss of bile acids, and is a validated
      method for screening for BAM. Following treatment for 12 days, transit and permeability
      studies will be repeated. Bowel function symptoms will be recorded for the duration of the
      study.
    

Intervention name(s): Colesevelam; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Welchol (Colesevelam HCL) 1.875 gram twice daily for 12-14 days; Inert capsule matching the study drug, given twice daily
Other intervention name(s): Welchol
Intervention MeSH terms: Colesevelam Hydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: bile acid; malabsorption; permeability; diarrhea; IBS; stool