Back to resultsA Study of Colesevelam in Fecal Incontinence
Primary Purpose
Fecal Incontinence, Bile Acid Malabsorption
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Colesevelam
Clonidine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Fecal Incontinence focused on measuring Incontinence, Diarrhea, Bile acid, Microbiome
Eligibility Criteria
A. Phase 1
Inclusion Criteria:
i) Females aged 18-80 years with urge predominant or combined (i.e. urge plus passive) FI, as defined by a validated questionnaire, for at least 1 year duration will be eligible to participate.
Exclusion Criteria:
(i) History of clinically serious cardiovascular or pulmonary disease or EKG showing 2nd degree atrioventricular block or higher.
(ii) Current or past history of rectal cancer, scleroderma, inflammatory bowel disease, small bowel obstruction, congenital anorectal abnormalities, Grade 2 rectal prolapse, history of rectal resection or pelvic irradiation (iii) Neurological disorders - Spinal cord injuries, dementia (Mini-Mental status score <21), multiple sclerosis, Parkinson's disease, peripheral neuropathy (iv) Conditions precluding safe use of clonidine, i.e., symptomatic hypotension, or systolic blood pressure of <100 mm Hg on initial visit in Phase 1 of study (v) Currently pregnant or nursing women (vi) Prior history of intolerance to clonidine or colesevelam (vii) Medications Absolute - opioid analgesics. Relative - other antihypertensive agents (i.e. if there is concern about synergistic effects and hypotension). Patients using drugs with anticholinergic effects will be excluded if they are used at high doses (e.g. nortriptyline greater than 50 mg/day or amitriptyline greater than 25 mg/day). Patients who use lower doses will be eligible to participate provided the dose will be stable during the study
B. Phase 2
Inclusion Criteria:
i) Females aged 18-80 years with urge predominant or combined (i.e. urge plus passive) FI for at least 1 year, as defined by questionnaire
Exclusion criteria:
(i) Positive urine pregnancy screen
C. Phase 3
Inclusion criteria:
(i) Completion of at least 5 out of 7 days of the diary in the preceding week and 10 out of 14 in the preceding 2 weeks (ii) At least 1 episode of FI per week averaged over 2 weeks (iii) Average Bristol stool score of 3 or higher (iv) Average stool frequency of ≥1/day
Exclusion criteria (if at least one is satisfied):
(i) Missing data in bowel diaries, i.e. if patient did not record bowel symptoms data for more than 2 days in 1 week or 4 days over 2 weeks (ii) Greater than 6 liquid [Bristol 6 or 7]) stools daily (iii) Average of less than 1 bowel movement daily (iv) Average Bristol stool score <3 as assessed from analysis of bowel diaries
D. Phase 4
Inclusion criteria:
(i) All patients who complete at least 1 week of treatment with study drugs or placebo
Exclusion criteria:
(i) Patients who completed less than 1 week of treatment with study drugs or placebo
Sites / Locations
- Mayo Clinic Rochester
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
Placebo
Colesevelam and Clonidine
Arm Description
Participants in this arm will receive placebo for 4 weeks.
Participants in this arm will receive a combination of colesevelam (1.875 gm twice daily) and clonidine (0.1 mg oral twice daily) for 4 weeks.
Outcomes
Primary Outcome Measures
Number of Participants to Report a 50% or Greater Reduction in Weekly Fecal Incontinence (FI) Episodes
The number of participants that report a 50% or greater reduction in weekly incontinent episodes as measured by self-reported bowel diaries.
Secondary Outcome Measures
Daily Stool Frequency
The number of bowel movements daily measured by self-reported bowel diaries.
Stool Consistency
Stool consistency as measured by self-reported bowel diaries. Expressed in terms of the Bristol Stool Form Scale, where: 1= separate hard lumps; 2= lumpy sausage-shape; 3= cracked sausage; 4= smooth and soft sausage; 5=soft blobs; 6=mushy, fluffy pieces; 7= watery, no solid pieces.
Number of Semi-Formed Stools Per Week
The number of stools per week measured by self-reported bowel diaries where the Bristol stool score was 5, 6, or 7. (5=soft blobs; 6=mushy, fluffy pieces; 7= watery, no solid pieces)
Delay of Bowel Movement
The time in minutes a bowel movement can be delayed after sense of urgency to defecate as measured by self-reported bowel diaries.
Total Fecal Incontinence Episodes
The total number of fecal incontinence episodes per week as measured by self-reported bowel diaries.
Volume of Fecal Incontinence
The volume of fecal incontinence measured as the number of incontinent episodes per week as categorized by small (staining only), moderate (requiring change of underwear) or large (requiring change of all clothes) in self-reported bowel diaries.
Percent of Incontinent Bowel Movements Pre-treatment
The percentage of bowel movements that were incontinent prior to treatment initiation, per self-reported bowel diaries.
Percent of Incontinent Bowel Movements During Treatment
The percentage of bowel movements that were incontinent during treatment, per self-reported bowel diaries.
Percent of Incontinent Bowel Movements to be Semi-Formed Stools Pre-Treatment
The percentage of incontinent bowel movements where the Bristol stool score was 5, 6 or 7. (5=soft blobs; 6=mushy, fluffy pieces; 7= watery, no solid pieces), pre-treatment, per self-reported bowel diaries.
Percent of Incontinent Bowel Movements to be Semi-Formed Stools During Treatment
The percentage of incontinent bowel movements where the Bristol stool score was 5, 6 or 7. (5=soft blobs; 6=mushy, fluffy pieces; 7= watery, no solid pieces) during treatment, per self-reported bowel diaries.
Severity of Bowel Symptoms
The Fecal Incontinence Symptom Severity (FISS) score is based on five questions; (1) the frequency of FI; (2) the type of FI (stool only, liquid or mucus only, both liquid/mucus and stool, or gas only); (3) the amount of stool leaked (small, moderate, or large); (4) the frequency of having to rush to the toilet; and (5) the frequency of having stool leak without warning. Questions 4 & 5 are merged to determine if the participant has passive FI (FI without warning), urge FI, both, or neither. The responses to the questions are assigned physician-derived weights and added together for a total score of 4 to 13. The higher the score the more severe the FI symptoms.
Severity of Fecal Incontinence
Measured by the Fecal Incontinence Severity Index (FISI). It is a validated 4-item scale used to assess the frequency (never, 1-3 times a month, once a week, 2 or more times per week but not daily, once a day, 2 or more times per day) of 4 different types of FI (gas, mucus, liquid stool, solid stool). Each of the four types of FI is awarded a number of points, depending on the frequency at which that type of incontinence is experienced. The points are totaled and the scores can range from 0 to 61, where the higher the score, the higher the perceived severity of the fecal incontinence.
Fecal Incontinence Quality of Life (FI-QoL)
The Fecal Incontinence Quality of Life questionnaire measures specific quality of life issues expected to affect patients with fecal incontinence. The questions are grouped into four categories: lifestyle (10 questions), coping (9 questions), depression (7 questions), and embarrassment (3 questions). Each category is scored from 1 to 4. The scale scores are calculated by adding the numerical values of all responses in that specific scale and then dividing by its number of items. Higher scores indicate a better quality of life.
Loperamide Tablets Per Week
The number of tablets of loperamide used, per self-reported bowel diaries.
Full Information
NCT ID
NCT02628626
First Posted
December 1, 2015
Last Updated
May 26, 2023
Sponsor
Mayo Clinic
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Research Resources (NCRR)
1. Study Identification
Unique Protocol Identification Number
NCT02628626
Brief Title
A Study of Colesevelam in Fecal Incontinence
Official Title
A Placebo Controlled Study of Colesevelam in Fecal Incontinence
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
November 2015 (undefined)
Primary Completion Date
April 14, 2022 (Actual)
Study Completion Date
April 14, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Research Resources (NCRR)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Compare the effects of a combination of colesevelam and clonidine to placebo on bowel symptoms in patients with urge or combined type of FI.
Detailed Description
Fecal incontinence (FI) is a common symptom that can significantly impair quality of life. There is very limited, mostly uncontrolled, evidence to support the approaches currently used to manage FI. The alpha-2 adrenergic agonist clonidine decreased the frequency of loose stools in FI patients with diarrhea. Among patients with diarrhea, clonidine decreased the proportion of days with FI; however results were not statistically significant. Uncontrolled studies suggest that the bile acid binding resin colesevelam also increased stool consistency in patients with functional diarrhea. In this study, the investigators propose to compare the effects of a combination of colesevelam and clonidine to placebo on bowel symptoms in patients with urge or combined type of FI.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fecal Incontinence, Bile Acid Malabsorption
Keywords
Incontinence, Diarrhea, Bile acid, Microbiome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
88 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants in this arm will receive placebo for 4 weeks.
Arm Title
Colesevelam and Clonidine
Arm Type
Active Comparator
Arm Description
Participants in this arm will receive a combination of colesevelam (1.875 gm twice daily) and clonidine (0.1 mg oral twice daily) for 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Colesevelam
Other Intervention Name(s)
Welchol
Intervention Description
Participants who satisfy symptom criteria in Phase 2 will be randomized in a 1:1 ratio to receive either a combination of colesevelam (1.875 gm twice daily) and clonidine (0.1 mg oral twice daily) or an identical placebo for 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Clonidine
Other Intervention Name(s)
Catapres
Intervention Description
Participants who satisfy symptom criteria in Phase 2 will be randomized in a 1:1 ratio to receive either a combination of colesevelam (1.875 gm twice daily) and clonidine (0.1 mg oral twice daily) or an identical placebo for 4 weeks.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo will be identical in appearance to the active drug.
Primary Outcome Measure Information:
Title
Number of Participants to Report a 50% or Greater Reduction in Weekly Fecal Incontinence (FI) Episodes
Description
The number of participants that report a 50% or greater reduction in weekly incontinent episodes as measured by self-reported bowel diaries.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Daily Stool Frequency
Description
The number of bowel movements daily measured by self-reported bowel diaries.
Time Frame
4 weeks
Title
Stool Consistency
Description
Stool consistency as measured by self-reported bowel diaries. Expressed in terms of the Bristol Stool Form Scale, where: 1= separate hard lumps; 2= lumpy sausage-shape; 3= cracked sausage; 4= smooth and soft sausage; 5=soft blobs; 6=mushy, fluffy pieces; 7= watery, no solid pieces.
Time Frame
4 weeks
Title
Number of Semi-Formed Stools Per Week
Description
The number of stools per week measured by self-reported bowel diaries where the Bristol stool score was 5, 6, or 7. (5=soft blobs; 6=mushy, fluffy pieces; 7= watery, no solid pieces)
Time Frame
4 weeks
Title
Delay of Bowel Movement
Description
The time in minutes a bowel movement can be delayed after sense of urgency to defecate as measured by self-reported bowel diaries.
Time Frame
4 weeks
Title
Total Fecal Incontinence Episodes
Description
The total number of fecal incontinence episodes per week as measured by self-reported bowel diaries.
Time Frame
4 weeks
Title
Volume of Fecal Incontinence
Description
The volume of fecal incontinence measured as the number of incontinent episodes per week as categorized by small (staining only), moderate (requiring change of underwear) or large (requiring change of all clothes) in self-reported bowel diaries.
Time Frame
4 weeks
Title
Percent of Incontinent Bowel Movements Pre-treatment
Description
The percentage of bowel movements that were incontinent prior to treatment initiation, per self-reported bowel diaries.
Time Frame
baseline
Title
Percent of Incontinent Bowel Movements During Treatment
Description
The percentage of bowel movements that were incontinent during treatment, per self-reported bowel diaries.
Time Frame
4 weeks
Title
Percent of Incontinent Bowel Movements to be Semi-Formed Stools Pre-Treatment
Description
The percentage of incontinent bowel movements where the Bristol stool score was 5, 6 or 7. (5=soft blobs; 6=mushy, fluffy pieces; 7= watery, no solid pieces), pre-treatment, per self-reported bowel diaries.
Time Frame
baseline
Title
Percent of Incontinent Bowel Movements to be Semi-Formed Stools During Treatment
Description
The percentage of incontinent bowel movements where the Bristol stool score was 5, 6 or 7. (5=soft blobs; 6=mushy, fluffy pieces; 7= watery, no solid pieces) during treatment, per self-reported bowel diaries.
Time Frame
4 weeks
Title
Severity of Bowel Symptoms
Description
The Fecal Incontinence Symptom Severity (FISS) score is based on five questions; (1) the frequency of FI; (2) the type of FI (stool only, liquid or mucus only, both liquid/mucus and stool, or gas only); (3) the amount of stool leaked (small, moderate, or large); (4) the frequency of having to rush to the toilet; and (5) the frequency of having stool leak without warning. Questions 4 & 5 are merged to determine if the participant has passive FI (FI without warning), urge FI, both, or neither. The responses to the questions are assigned physician-derived weights and added together for a total score of 4 to 13. The higher the score the more severe the FI symptoms.
Time Frame
4 weeks
Title
Severity of Fecal Incontinence
Description
Measured by the Fecal Incontinence Severity Index (FISI). It is a validated 4-item scale used to assess the frequency (never, 1-3 times a month, once a week, 2 or more times per week but not daily, once a day, 2 or more times per day) of 4 different types of FI (gas, mucus, liquid stool, solid stool). Each of the four types of FI is awarded a number of points, depending on the frequency at which that type of incontinence is experienced. The points are totaled and the scores can range from 0 to 61, where the higher the score, the higher the perceived severity of the fecal incontinence.
Time Frame
4 weeks
Title
Fecal Incontinence Quality of Life (FI-QoL)
Description
The Fecal Incontinence Quality of Life questionnaire measures specific quality of life issues expected to affect patients with fecal incontinence. The questions are grouped into four categories: lifestyle (10 questions), coping (9 questions), depression (7 questions), and embarrassment (3 questions). Each category is scored from 1 to 4. The scale scores are calculated by adding the numerical values of all responses in that specific scale and then dividing by its number of items. Higher scores indicate a better quality of life.
Time Frame
4 weeks
Title
Loperamide Tablets Per Week
Description
The number of tablets of loperamide used, per self-reported bowel diaries.
Time Frame
4 weeks
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
A. Phase 1
Inclusion Criteria:
i) Females aged 18-80 years with urge predominant or combined (i.e. urge plus passive) FI, as defined by a validated questionnaire, for at least 1 year duration will be eligible to participate.
Exclusion Criteria:
(i) History of clinically serious cardiovascular or pulmonary disease or EKG showing 2nd degree atrioventricular block or higher.
(ii) Current or past history of rectal cancer, scleroderma, inflammatory bowel disease, small bowel obstruction, congenital anorectal abnormalities, Grade 2 rectal prolapse, history of rectal resection or pelvic irradiation (iii) Neurological disorders - Spinal cord injuries, dementia (Mini-Mental status score <21), multiple sclerosis, Parkinson's disease, peripheral neuropathy (iv) Conditions precluding safe use of clonidine, i.e., symptomatic hypotension, or systolic blood pressure of <100 mm Hg on initial visit in Phase 1 of study (v) Currently pregnant or nursing women (vi) Prior history of intolerance to clonidine or colesevelam (vii) Medications Absolute - opioid analgesics. Relative - other antihypertensive agents (i.e. if there is concern about synergistic effects and hypotension). Patients using drugs with anticholinergic effects will be excluded if they are used at high doses (e.g. nortriptyline greater than 50 mg/day or amitriptyline greater than 25 mg/day). Patients who use lower doses will be eligible to participate provided the dose will be stable during the study
B. Phase 2
Inclusion Criteria:
i) Females aged 18-80 years with urge predominant or combined (i.e. urge plus passive) FI for at least 1 year, as defined by questionnaire
Exclusion criteria:
(i) Positive urine pregnancy screen
C. Phase 3
Inclusion criteria:
(i) Completion of at least 5 out of 7 days of the diary in the preceding week and 10 out of 14 in the preceding 2 weeks (ii) At least 1 episode of FI per week averaged over 2 weeks (iii) Average Bristol stool score of 3 or higher (iv) Average stool frequency of ≥1/day
Exclusion criteria (if at least one is satisfied):
(i) Missing data in bowel diaries, i.e. if patient did not record bowel symptoms data for more than 2 days in 1 week or 4 days over 2 weeks (ii) Greater than 6 liquid [Bristol 6 or 7]) stools daily (iii) Average of less than 1 bowel movement daily (iv) Average Bristol stool score <3 as assessed from analysis of bowel diaries
D. Phase 4
Inclusion criteria:
(i) All patients who complete at least 1 week of treatment with study drugs or placebo
Exclusion criteria:
(i) Patients who completed less than 1 week of treatment with study drugs or placebo
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adil Bharucha, MBBS, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials
Learn more about this trial
A Study of Colesevelam in Fecal Incontinence
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