Trial to Understand Efficacy of Colesevelam in Diarrhea Predominant IBS Patients With Bile Acid Malabsorption

NCT03270085 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 17-004639R01DK115950UL1TR000135
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Diarrhea; Irritable Bowel Syndrome With Diarrhea; Bile Acid Malabsorption

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Number of Stools Per Day

  Treatment days 1 through 28

Study Arms (2)

Colesevelam

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Colesevelam DRUG

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.

Colesevelam

Placebo OTHER

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• 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.

  PMID: 32088296 RESULT

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Interventions

Colesevelam Hydrochloride

Intervention Hierarchy (Ancestors)

Allylamine; Amines; Organic Chemicals; Allyl Compounds; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons

Results Point of Contact

• Title: Michael Camilleri, MD
• Organization: Mayo Clinic

camilleri.michael@mayo.edu

507-266-2305

Study Officials

• Michael Camilleri

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 30 subjects with irritable bowel syndrome and diarrhea and bile acid malabsorption will be randomized into 15 people per group in 4-week double-blind, parallel-group trial to Colesevelam or placebo.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Michael Camilleri, M.D. Professor of Medicine, Pharmacology and Physiology, Atherton and Winifred W. Bean Professor, College of Medicine Consultant, Division of Gastroenterology and Hepatology

Model Details: This is the third specific aim of a program on IBS-D with increased fecal bile acid excretion.

Study Record Dates

• First Submitted: August 7, 2017
• First Posted: September 1, 2017
• Study Start: December 7, 2017
• Primary Completion: May 31, 2019
• Study Completion: May 31, 2019
• Last Updated: April 27, 2020
• Results First Posted: April 27, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)