A Study of Colesevelam in Fecal Incontinence

Sponsor

Mayo Clinic (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02628626

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Fecal Incontinence Bile Acid Malabsorption	Drug: Colesevelam Drug: Clonidine Other: Placebo	Phase 3

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. The investigators hypothesis is that combination treatment with clonidine and colesevelam is better than placebo in reducing stool frequency and rectal urgency in FI.

Study Design

Study Type:

Interventional

Actual Enrollment :

86 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Placebo Controlled Study of Colesevelam in Fecal Incontinence

Study Start Date :

Nov 1, 2015

Actual Primary Completion Date :

Jun 1, 2022

Anticipated Study Completion Date :

Sep 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Patients in this arm will receive placebo for 4 weeks.	Other: Placebo Placebo will be identical in appearance to the active drug.
Active Comparator: Colesevelam and Clonidine Patients 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.	Drug: Colesevelam Patients 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. Other Names: Welchol Drug: Clonidine Patients 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. Other Names: Catapres

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Patients in this arm will receive placebo for 4 weeks.

Other: Placebo

Placebo will be identical in appearance to the active drug.

Active Comparator: Colesevelam and Clonidine

Patients 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.

Drug: Colesevelam

Patients 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.

Other Names:

Welchol

Drug: Clonidine

Other Names:

Catapres

Outcome Measures

Primary Outcome Measures

Percentage of patients who have a 50% reduction in the frequency of fecal incontinence (FI) episodes [baseline, approximately 4 weeks after start of treatment with drug or placebo]
Patients will fill out daily bowel diaries and mail them in weekly. Frequency of incontinent episodes will be calculated by analysis of the bowel diaries. The investigators will compare number of episodes of fecal incontinence per week after 4 weeks of treatment with that at baseline.

Secondary Outcome Measures

Change in the number of days with fecal incontinence [baseline, approximately 4 weeks after start of treatment with drug or placebo]
Patients will fill out daily bowel diaries and mail them in weekly. Frequency of incontinent episodes will be calculated by analysis of the bowel diaries. The investigators will compare number of days per week with fecal incontinence after 4 weeks of treatment with that at baseline.
Change in the volume of fecal incontinence [baseline, approximately 4 weeks after start of treatment with drug or placebo]
This will be assessed using the Fecal incontinence and Constipation Assessment (FICA) Scale - This validated instrument, developed in our program, has 4-items (frequency, type, amount of leakage, and presence of urgency) used to rate the severity of fecal incontinence. It is the only instrument that incorporates the amount of leakage, which is an important yardstick for the severity of fecal incontinence
Change in composition of leaked stools [baseline, approximately 4 weeks after start of treatment with drug or placebo]
Patients will fill out daily bowel diaries and mail them in weekly. Composition of incontinent episodes will be calculated by analysis of the bowel diaries. Stool consistency will be expressed in terms of the Bristol stool form. The investigators will compare the average daily Bristol stool form after 4 weeks of treatment with that at baseline.
Change in number of episodes of passive and urge incontinence per week [baseline, approximately 4 weeks]
The number of episodes of passive and urge fecal incontinence per week will be calculated by analysis of the bowel diaries. The bowel diaries will be averaged first for each day and then for each week.
Change in rectal urgency [baseline, approximately 4 weeks after start of treatment with drug or placebo]
The number of episodes of rectal urgency will be calculated by analysis of daily bowel diaries. From that the percentage of daily bowel movements preceded by rectal urgency will be calculated. The mean percentage of bowel movements preceded by rectal urgency will then be calculated for each week.
Time for which a bowel movement can be deferred after occurrence of urgency [baseline, approximately 4 weeks]
The time for which a bowel movement can be deferred after occurrence of urgency (expressed in minutes) will be calculated by analysis of the bowel diaries. The bowel diaries will be averaged first for each day and then for each week. The average time for which a bowel movement can be deferred will be compared at the end of 4 weeks of treatment with that at baseline.
Change in stool consistency [baseline, approximately 4 weeks after start of treatment with drug or placebo]
The subjects will rate their stool consistency using the Bristol Stool Scale. The Bristol Stool Scale is a medical aid designed to classify the form of human feces into seven categories or types. Types 1 and 2 indicate constipation with 3 and 4 being the "ideal stools" especially the latter, as they are the easiest to defecate, and 5-7 tending towards diarrhea.
Change in proportion of FI episodes that were diarrhea [baseline, approximately 4 weeks after start of treatment with drug or placebo]
The proportion of FI episodes that were diarrhea will be calculated by analysis of the bowel diaries. The bowel diaries will be averaged first for each day and then for each week. Stool consistency will be determined using the Bristol stool scale.
Severity of bowel symptoms [baseline, approximately 4 weeks after start of treatment with drug or placebo]
This will be assessed by a Visual Analog Scale (VAS). The VAS does not have any pre-set marks between the extremes of 0 (no bowel symptoms) and 100 mm (extreme bowel symptoms). The investigator measures the mark made by the participant in mm and records this for the value of bowel symptoms. The higher the value the more severe the symptoms.
Severity of FI [baseline, approximately 4 weeks after start of treatment with drug or placebo]
This will be assessed by the Fecal Incontinence Severity Index (FISI). It is a validated 4-item scale used to assess the frequency of 4 different types of FI (gas, mucus, liquid stool, solid stool). The subject responses are weighted and summed for the 4 types of FI. Scores can range from 0 (no symptoms) to 61 (very frequent FI). Values will be computed from pre- and post- treatment questionnaires
Impact of FI on quality of life [baseline, approximately 4 weeks after start of treatment with drug or placebo]
This will be assessed by the Fecal Incontinence Quality of Life questionnaire which is a 30-item validated questionnaire that assesses the effects of fecal incontinence on quality of life. The difference in QOL will be compared by pre-treatment and post-treatment questionnaires
Impact on symptoms of anxiety and depression [baseline, approximately 4 weeks after start of treatment with drug or placebo]
This will be assessed by the Hospital Anxiety and Depression Scale (HADS). The HADS is a fourteen item scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression.
Satisfaction with treatment measured by the visual analog scale [approximately 4 weeks after start of treatment with drug or placebo]
In order to determine if patients are satisfied with the treatment received, we will use a previously validated visual analog score. Patients will be asked to subjectively indicate their level of satisfaction with continence function. This will be measured with a visual analogue sliding scale that ranges from 0 to 100 mm (0 means not satisfied while 100 means completely satisfied). The investigator measures the mark made by the participant in mm and records this for the value of bowel symptoms. The higher the value the more satisfied the patient is with continence.
Proportion of days where patient used loperamide [approximately 4 weeks after start of treatment with drug or placebo]
This will be caculated from daily bowel diaries. The number of doses of loperamide used/day will be averaged over each week and will be compared between post-treatment and pre-treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Phase 1

Inclusion Criteria:

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

Phase 2

Inclusion Criteria:

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

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