Does Welchol (Colesevelam Hydrochloride) Improve Colonic Transit in Diarrhea-predominant Irritable Bowel Syndrome (D-IBS)? (welchol)

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00911612
First received: May 29, 2009
Last updated: March 29, 2012
Last verified: March 2012

May 29, 2009
March 29, 2012
January 2009
May 2009   (final data collection date for primary outcome measure)
  • Colonic Transit, Geometric Center at 24 Hours [ Time Frame: After 12-14 days treatment ] [ Designated as safety issue: No ]
    The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit. A GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.
  • Ascending Colon Emptying T1/2 [ Time Frame: After 12-14 days' treatment ] [ Designated as safety issue: No ]
    The half time for the ascending colon emptying (T1/2) was measured by the scintigraphic method. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule that is swallowed by the subject. Anterior and posterior gamma images are taken hourly. From the hourly scans, a time-activity curve is plotted using linear interpolation between time points when content was measured. The time taken to empty 50% of the isotope from the ascending colon is read from this time-activity curve.
  • colonic transit, geometric center at 24 hours (GC 24) [ Time Frame: After 12-14 days treatment ] [ Designated as safety issue: No ]
  • Ascending Colon Emptying T1/2 [ Time Frame: After 12-14 days' treatment ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00911612 on ClinicalTrials.gov Archive Site
  • Colonic Permeability as Measured by Cumulative Urinary Excretion of Mannitol 8-24 Hours [ Time Frame: after 12-14 days' treatment ] [ Designated as safety issue: No ]
    Colonic permeability is measured through differential excretion of urine saccharides. The subject ingests a methacrylate-coated capsule that contains saccharides (mannitol 1g and lactulose 5 g powder). The capsule provides a means to protect the sugars from absorption, until the sugars are delivered to the colon by means of a standard delayed release capsule. The value reported is the mean for each arm of the total amount of mannitol excreted over the 8-24 hour time period.
  • Colonic Transit, Geometric Center at 48 Hours [ Time Frame: After 12-14 days' treatment ] [ Designated as safety issue: No ]
    The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit. A GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.
  • Stool Consistency [ Time Frame: After 12-14 days' treatment ] [ Designated as safety issue: No ]
    The subjects rated their stool consistency using the Bristol Stool Scale. The Bristol Stool Scale is a medical aid designed to classify the form of human feces into seven categories or types. Types 1 and 2 indicate constipation with 3 and 4 being the "ideal stools" especially the latter, as they are the easiest to defecate, and 5-7 tending towards diarrhea.
  • intestinal and colonic permeability in cumulative mannitol urine excretion at 0-2h and 2-24h collections [ Time Frame: after 12-14 days' treatment ] [ Designated as safety issue: No ]
  • Colonic GC 48 h [ Time Frame: After 12-14 days' treatment ] [ Designated as safety issue: No ]
  • Stool consistency [ Time Frame: After 12-14 days' treatment ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Does Welchol (Colesevelam Hydrochloride) Improve Colonic Transit in Diarrhea-predominant Irritable Bowel Syndrome (D-IBS)?
A Phase IIB Study to Evaluate the Effects of Welchol (Colesevelam Hydrochloride) on Colonic Transit, Intestinal Permeability and Bowel Function in Diarrhea-predominant Irritable Bowel Syndrome (D-IBS)

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Irritable Bowel Syndrome
  • Diarrhea
  • Drug: Colesevelam
    Welchol (Colesevelam HCL) 1.875 gram twice daily for 12-14 days
    Other Name: Welchol
  • Drug: Placebo
    Inert capsule matching the study drug, given twice daily
  • Experimental: Colesevelam
    Participants received colesevelam 1.875 g twice daily
    Intervention: Drug: Colesevelam
  • Placebo Comparator: Placebo
    Participants received an inert capsule matching the study drug twice daily, as prepared by the Mayo Clinic research pharmacy
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
May 2009
May 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with D-IBS
  • Aged 18-65 years
  • No abdominal surgery (except appendectomy or cholecystectomy as long as patients IBS-diarrhea symptoms preceded the cholecystectomy

Exclusion Criteria:

  • Participants with known chronic liver disease or Aspartate aminotransferase (AST) or Alanine transaminase (ALT) > 2.0 X upper limit of normal
  • Hypertriglyceridemia and pancreatitis by history
  • Diabetes or hypoglycemia
  • Significant coagulation disorder
  • History of bowel obstruction
  • Serum triglycerides >500 mg/dL
  • History of vitamin A, D, E, or K deficiencies
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00911612
08-007454, R01DK054681
No
Michael Camilleri, M.D., Mayo Clinic
Mayo Clinic
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Michael L. Camilleri, M.D. Mayo Clinic
Mayo Clinic
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP