Bile Acid Malabsorption, Chronic Diarrhea, Irritable Bowel Syndrome With Diarrhea
Conditions
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.
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.
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.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
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.
Intervention model description
This is the third specific aim of a program on IBS-D with increased fecal bile acid excretion.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Fecal Bile Acid (BA) Excretion | Treatment day 28 | 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. |
| Stool Consistency | Treatment days 1 through 28 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Stools Per Day | Treatment days 1 through 28 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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: transit test, 4 day high fat diet with 48 hour stool collection, blood samples, rectosigmoid biopsies, one week stool diary, medication pick up.
Treatment period: subject takes study drug 1875 mg orally twice daily with lunch and supper for 4-5 weeks.
Treatment testing period: 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.
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. | 15 |
| 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.
Treatment testing period: 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.
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. | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Colesevelam | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 44 years | 56 years | 50 years |
| Body Mass Index | 33.2 kg/m2 | 33.6 kg/m2 | 33.4 kg/m2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 13 Participants | 15 Participants | 28 Participants |
| Region of Enrollment United States | 15 participants | 15 participants | 30 participants |
| Sex: Female, Male Female | 11 Participants | 13 Participants | 24 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Colesevelam | Stool Consistency | 4.6 units on a scale |
| Placebo | Stool Consistency | 4.6 units on a scale |
p-value: 0.81Wilcoxon (Mann-Whitney)
Primary
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Colesevelam | Total Fecal Bile Acid (BA) Excretion | 10.7 μmoles/g |
| Placebo | Total Fecal Bile Acid (BA) Excretion | 3.6 μmoles/g |
p-value: 0.001Wilcoxon (Mann-Whitney)
Secondary
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Colesevelam | Number of Stools Per Day | 3.1 number of stools per day |
| Placebo | Number of Stools Per Day | 2.2 number of stools per day |
p-value: 0.91Wilcoxon (Mann-Whitney)