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.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome With Diarrhea; Bile Acid Malabsorption; Chronic Diarrhea
• Intervention / Treatment: Drug: Colesevelam; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Colesevelam; Once randomized, subjects will have baseline testing period, treatment period, and treatment testing period the study drug. This consists of nine visits and will be over a period of five to nine weeks. Baseline testing period consists of: transit test, 4 day high fat diet with 48 hour stool collection, blood samples, rectosigmoid biopsies, one week stool diary, and medication pick up. Treatment period will have subject take the study drug 1875 mg of medication orally twice daily with lunch and supper for 4-5 weeks. The last period, is the treatment testing period. This consists of a full transit & urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused medication.	Drug: Colesevelam; Colesevelam (Welchol) is approved by the Food and Drug Administration (FDA) for the treatment of high blood cholesterol levels and to treat type 2 diabetes however, Colesevelam is not approved for the use proposed in this study and is considered investigational.
Placebo Comparator: Placebo; Once randomized, subjects will have a baseline testing period, treatment period and treatment testing period with the placebo. This consists of nine visits and will be over a period of five to nine weeks. The last period, is the treatment testing period. This consists of a full transit & urine permeability test, 4 day high fat diet with 48 hour stool collection, blood samples, one week stool diary collection, and the return of the unused placebo.	Other: Placebo; A placebo looks exactly like the study drug, but it contains no active ingredient. This is used to learn if the effects seen in research participants are truly from the study drug.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Fecal Bile Acid (BA) Excretion	Total fecal BA excretion was measured using High Performance Liquid Chromatography (HPLC)/tandem mass spectrometry (MS) where single stool samples obtained at baseline and end of treatment were prepared by assay by HPLC/MS by methanol extraction and results are presented as micromoles per gram (μmoles/g) of stool.	Treatment day 28
Stool Consistency	Stool consistency as reported by the participant via daily bowel diaries. Stool consistency was based on Bristol Stool Form Scale (BSFS) where 1 - hard lumps, 2 - lumpy sausage, 3 - cracked sausage, 4 - smooth sausage, 5 - soft lumps, 6 - mushy, and 7 - watery. Stool consistency was averaged for the 28 day treatment period.	Treatment days 1 through 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Stools Per Day	The total number of bowel movements as reported by the participant via daily bowel diaries. The number of bowel movements were averaged for the 28 day treatment period.	Treatment days 1 through 28

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Michael Camilleri, Mayo Clinic

Publications and helpful links

General Publications

• Vijayvargiya P, Camilleri M, Carlson P, Nair A, Nord SL, Ryks M, Rhoten D, Burton D, Busciglio I, Lueke A, Harmsen WS, Donato LJ. Effects of Colesevelam on Bowel Symptoms, Biomarkers, and Colonic Mucosal Gene Expression in Patients With Bile Acid Diarrhea in a Randomized Trial. Clin Gastroenterol Hepatol. 2020 Dec;18(13):2962-2970.e6. doi: 10.1016/j.cgh.2020.02.027. Epub 2020 Feb 21.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2017
• Primary Completion (Actual): May 31, 2019
• Study Completion (Actual): May 31, 2019

Study Registration Dates

• First Submitted: August 7, 2017
• First Submitted That Met QC Criteria: August 30, 2017
• First Posted (Actual): September 1, 2017

Study Record Updates

• Last Update Posted (Actual): April 27, 2020
• Last Update Submitted That Met QC Criteria: April 14, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Irritable Bowel Syndrome; Diarrhea; Malabsorption Syndromes; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Colesevelam Hydrochloride
• Other Study ID Numbers: 17-004639; UL1TR000135 (U.S. NIH Grant/Contract); R01DK115950 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No