ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Colesevelam in Fecal Incontinence

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02628626
Recruitment Status : Recruiting
First Posted : December 11, 2015
Last Update Posted : August 15, 2018
Sponsor:
Information provided by (Responsible Party):
Adil Bharucha, Mayo Clinic

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 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 : November 2015
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : October 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bowel Movement

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 Name: 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 Name: Catapres




Primary Outcome Measures :
  1. Percentage of patients who have a 50% reduction in the frequency of fecal incontinence (FI) episodes [ Time Frame: 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 :
  1. Change in the number of days with fecal incontinence [ Time Frame: 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.

  2. Change in the volume of fecal incontinence [ Time Frame: 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

  3. Change in composition of leaked stools [ Time Frame: 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.

  4. Change in number of episodes of passive and urge incontinence per week [ Time Frame: 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.

  5. Change in rectal urgency [ Time Frame: 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.

  6. Time for which a bowel movement can be deferred after occurrence of urgency [ Time Frame: 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.

  7. Change in stool consistency [ Time Frame: 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.

  8. Change in proportion of FI episodes that were diarrhea [ Time Frame: 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.

  9. Severity of bowel symptoms [ Time Frame: 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.

  10. Severity of FI [ Time Frame: 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

  11. Impact of FI on quality of life [ Time Frame: 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

  12. Impact on symptoms of anxiety and depression [ Time Frame: 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.

  13. Satisfaction with treatment measured by the visual analog scale [ Time Frame: 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.

  14. Proportion of days where patient used loperamide [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02628626


Locations
United States, Minnesota
Mayo Clinic in Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Kelly Feuerhak    507-255-6802    Feuerhak.Kelly@mayo.edu   
Principal Investigator: Adil E Bharucha, MBBS, MD         
Sub-Investigator: Subhankar Chakraborty, MBBS, PhD         
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Adil Bharucha, MBBS, MD Mayo Clinic

Responsible Party: Adil Bharucha, PI, Mayo Clinic
ClinicalTrials.gov Identifier: NCT02628626     History of Changes
Other Study ID Numbers: 15-005986
First Posted: December 11, 2015    Key Record Dates
Last Update Posted: August 15, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Adil Bharucha, Mayo Clinic:
Incontinence
Diarrhea
Bile acid
Microbiome

Additional relevant MeSH terms:
Malabsorption Syndromes
Fecal Incontinence
Rectal Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Metabolic Diseases
Clonidine
Colesevelam Hydrochloride
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Lipid Regulating Agents