CClinicalTrials.gg
CompletedNCT03270085Updated Apr 27, 2020Results posted

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

A Phase 2 interventional study of Colesevelam and Placebo in Chronic Diarrhea, Irritable Bowel Syndrome With Diarrhea and Bile Acid Malabsorption, sponsored by Mayo Clinic. Completed at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2020-04-27.

Sponsored by Mayo Clinic · Phase 2, Interventional, and Other

Phase
Phase 2
Study type
Interventional
Enrollment
30
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Chronic Diarrhea
  • Irritable Bowel Syndrome With Diarrhea
  • Bile Acid Malabsorption
03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Other
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
30 participants (actual)

Study arms

  • 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

  • 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

Interventions

  • DrugColesevelam

    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.

  • OtherPlacebo

    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.

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Treatment day 28

  2. 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.

    Time frame: Treatment days 1 through 28

Secondary outcomes

  1. 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.

    Time frame: Treatment days 1 through 28

06

Results

Posted Apr 27, 2020

Participant flow

Participant flow — Overall Study
MilestoneColesevelamPlacebo
Started1515
Completed1415
Not completed10
Withdrew: Withdrawal by subject10

Outcome measures

PrimaryTotal 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.

Time frame:
Treatment day 28
Reported as:
Median · μmoles/g
Total Fecal Bile Acid (BA) Excretion
μmoles/gColesevelamPlacebo
Total Fecal Bile Acid (BA) Excretion10.7 (8.2 to 17.4)3.6 (2.6 to 7.2)
Statistical analysis
  • Colesevelam vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.001
PrimaryStool 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.

Time frame:
Treatment days 1 through 28
Reported as:
Median · units on a scale
Stool Consistency
units on a scaleColesevelamPlacebo
Stool Consistency4.6 (3.9 to 5.2)4.6 (4.3 to 5.0)
Statistical analysis
  • Colesevelam vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.81
SecondaryNumber 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.

Time frame:
Treatment days 1 through 28
Reported as:
Median · number of stools per day
Number of Stools Per Day
number of stools per dayColesevelamPlacebo
Number of Stools Per Day3.1 (1.6 to 3.8)2.2 (1.6 to 2.9)
Statistical analysis
  • Colesevelam vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.91

Adverse events

Collected over Adverse events were collected for each subject from baseline to the end of the study, approximately 10 weeks, for a total study duration of approximately 18 months.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Colesevelam0/15 (0%)0/15 (0%)0/15 (0%)
Placebo0/15 (0%)0/15 (0%)0/15 (0%)

Baseline characteristics

Age, Continuous
Age, Continuous(years)ColesevelamPlaceboTotal
Median44 (34 to 52)56 (40 to 68)50 (34 to 67)
Sex: Female, Male
Sex: Female, Male(Participants)ColesevelamPlaceboTotal
Female111324
Male426
Race (NIH/OMB)
Race (NIH/OMB)(Participants)ColesevelamPlaceboTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American000
White131528
More than one race000
Unknown or Not Reported202
Region of Enrollment
Region of Enrollment(participants)ColesevelamPlaceboTotal
United States151530
Body Mass Index
Body Mass Index(kg/m2)ColesevelamPlaceboTotal
Median33.2 (28.0 to 37.6)33.6 (28.2 to 36.4)33.4 (28.0 to 36.7)
07

Study locations

1 site
  • Mayo Clinic in Rochester
    Rochester, Minnesota 55905, United States
08

References and documents

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. PubMed 32088296 ↗

Study documents

  • Protocol and statistical analysis plan · Oct 15, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03270085
Lead sponsor
Mayo Clinic
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Responsible party
Michael Camilleri, MD (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, Mayo Clinic) — Principal investigator
First posted
Sep 1, 2017
Start date
Dec 7, 2017
Primary completion
May 31, 2019
Completion
May 31, 2019
Results posted
Apr 27, 2020
Last update
Apr 27, 2020

Study contacts

Michael Camilleri
principal investigator · Mayo Clinic

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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