A Study of Colesevelam in Fecal Incontinence
Condition: Fecal Incontinence; Bile Acid Malabsorption
MeSH terms: Fecal Incontinence; Malabsorption Syndromes
Intervention: Colesevelam; Clonidine; Placebo
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.; 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.; Placebo will be identical in appearance to the active drug.
Intervention MeSH terms: Clonidine; Colesevelam Hydrochloride
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 88.0
Sex: Female
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Incontinence; Diarrhea; Bile acid; Microbiome

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.
    

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