A Study of Colesevelam in Fecal Incontinence

Mayo Clinic88 enrolled

Overview

Compare the effects of a combination of colesevelam and clonidine to placebo on bowel symptoms in patients with urge or combined type of FI.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Fecal Incontinence Bile Acid Malabsorption

Interventions

ColesevelamDRUG

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.

ClonidineDRUG

PlaceboOTHER

Placebo will be identical in appearance to the active drug.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (1)

Mayo Clinic Rochester

Rochester, Minnesota, United States

Outcomes

Primary Outcomes

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.

Time frame: 4 weeks

Secondary Outcomes

Daily Stool Frequency

The number of bowel movements daily measured by self-reported bowel diaries.

Time frame: 4 weeks

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.

Time frame: 4 weeks

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)

Time frame: 4 weeks

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.

Time frame: 4 weeks

Total Fecal Incontinence Episodes

The total number of fecal incontinence episodes per week as measured by self-reported bowel diaries.

Time frame: 4 weeks

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.

Data from ClinicalTrials.gov

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