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

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ClinicalTrials.gov Identifier: NCT00911612
Recruitment Status : Completed
First Posted : June 2, 2009
Results First Posted : March 15, 2012
Last Update Posted : April 4, 2012
Sponsor:
Collaborator:
Information provided by:

Study Description
Brief 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.


Condition or disease Intervention/treatment Phase
Irritable Bowel Syndrome Diarrhea Drug: Colesevelam Drug: Placebo Phase 2

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.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)
Study Start Date : January 2009
Primary Completion Date : May 2009
Study Completion Date : May 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diarrhea
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Colesevelam
Participants received colesevelam 1.875 g twice daily
Drug: Colesevelam
Welchol (Colesevelam HCL) 1.875 gram twice daily for 12-14 days
Other Name: Welchol
Placebo Comparator: Placebo
Participants received an inert capsule matching the study drug twice daily, as prepared by the Mayo Clinic research pharmacy
Drug: Placebo
Inert capsule matching the study drug, given twice daily


Outcome Measures

Primary Outcome Measures :
  1. Colonic Transit, Geometric Center at 24 Hours [ Time Frame: After 12-14 days treatment ]
    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.

  2. Ascending Colon Emptying T1/2 [ Time Frame: After 12-14 days' treatment ]
    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.


Secondary Outcome Measures :
  1. Colonic Permeability as Measured by Cumulative Urinary Excretion of Mannitol 8-24 Hours [ Time Frame: after 12-14 days' treatment ]
    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.

  2. Colonic Transit, Geometric Center at 48 Hours [ Time Frame: After 12-14 days' treatment ]
    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.

  3. Stool Consistency [ Time Frame: After 12-14 days' treatment ]
    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.


Eligibility Criteria

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00911612


Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Michael L. Camilleri, M.D. Mayo Clinic
More Information

Additional Information:
Publications:
Responsible Party: Michael Camilleri, M.D., Mayo Clinic
ClinicalTrials.gov Identifier: NCT00911612     History of Changes
Other Study ID Numbers: 08-007454
R01DK054681 ( U.S. NIH Grant/Contract )
First Posted: June 2, 2009    Key Record Dates
Results First Posted: March 15, 2012
Last Update Posted: April 4, 2012
Last Verified: March 2012

Keywords provided by Mayo Clinic:
bile acid
malabsorption
permeability
diarrhea
IBS
stool

Additional relevant MeSH terms:
Syndrome
Diarrhea
Irritable Bowel Syndrome
Disease
Pathologic Processes
Signs and Symptoms, Digestive
Signs and Symptoms
Colonic Diseases, Functional
Colonic Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Colesevelam Hydrochloride
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents