Clinical trial NCT02628626: A Study of Colesevelam in Fecal Incontinence
Official title: A Placebo Controlled Study of Colesevelam in Fecal Incontinence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fecal Incontinence
Bile Acid Malabsorption
Keywords: Incontinence
Diarrhea
Bile acid
Microbiome
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: National Center for Research Resources (NCRR)
First posted: 2015-12-11
Enrollment: 88
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants to Report a 50% or Greater Reduction in Weekly Fecal Incontinence (FI) Episodes
timeFrame: 4 weeks
Secondary outcomes:
measure: Daily Stool Frequency
timeFrame: 4 weeks
measure: Stool Consistency
timeFrame: 4 weeks
measure: Number of Semi-Formed Stools Per Week
timeFrame: 4 weeks
measure: Delay of Bowel Movement
timeFrame: 4 weeks
measure: Total Fecal Incontinence Episodes
timeFrame: 4 weeks
measure: Volume of Fecal Incontinence
timeFrame: 4 weeks
measure: Percent of Incontinent Bowel Movements Pre-treatment
timeFrame: baseline
measure: Percent of Incontinent Bowel Movements During Treatment
timeFrame: 4 weeks
measure: Percent of Incontinent Bowel Movements to be Semi-Formed Stools Pre-Treatment
timeFrame: baseline
measure: Percent of Incontinent Bowel Movements to be Semi-Formed Stools During Treatment
timeFrame: 4 weeks
measure: Severity of Bowel Symptoms
timeFrame: 4 weeks
measure: Severity of Fecal Incontinence
timeFrame: 4 weeks
measure: Fecal Incontinence Quality of Life (FI-QoL)
timeFrame: 4 weeks
measure: Loperamide Tablets Per Week
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Adil Bharucha, MBBS, MD
role: PRINCIPAL_INVESTIGATOR
References: