Does Welchol (Colesevelam Hydrochloride) Improve Colonic Transit in D-IBS?
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.
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 (Odunsi et al) suggests 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 12-14days. A baseline colon transit, 24hour urine for colon permeability, and blood for serum 7alpha-hydroxy-4-cholesten-3-one (7alpha-HCO) will be measured and venous blood DNA will be collected and stored. The measurement of serum 7alpha-hydroxy-4-cholesten-3-one (7alpha-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.
Anticipated Results:
Colesevelam HCL will retard colon transit in participants with D-IBS. Effect of bile acid malabsorption at baseline (as measured by 7alpha-HCO) will be included as a covariate in the analysis of covariance. These data will provide preliminary data for future, adequately powered clinical trials of the effect of Colesevelam in patients with BAM associated with D-IBS.
Study Design
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Conditions
Irritable Bowel Syndrome
Intervention
colesevelam
Location
Mayo Clinic
Rochester
Minnesota
United States
55905
Status
Completed
Source
Mayo Clinic
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00911612
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Colonic Diseases, Functional
Chronic or recurrent colonic disorders without an identifiable structural or biochemical explanation. The widely recognized IRRITABLE BOWEL SYNDROME falls into this category.
Irritable Bowel Syndrome
A disorder with chronic or recurrent colonic symptoms without a clearcut etiology. This condition is characterized by chronic or recurrent ABDOMINAL PAIN, bloating, MUCUS in FECES, and an erratic disturbance of DEFECATION.
Short Bowel Syndrome
A malabsorption syndrome resulting from extensive operative resection of the SMALL INTESTINE, the absorptive region of the GASTROINTESTINAL TRACT.
Echogenic Bowel
A PRENATAL ULTRASONOGRAPHY finding of excessively dense fetal bowel due to MECONIUM buildup.
Postgastrectomy Syndromes
Sequelae of gastrectomy from the second week after operation on. Include recurrent or anastomotic ulcer, postprandial syndromes (DUMPING SYNDROME and late postprandial hypoglycemia), disordered bowel action, and nutritional deficiencies.
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