Fecal IncontinencePhase 3NCT02628626
A Study of Colesevelam in Fecal Incontinence
A Phase 3 study testing Colesevelam and Clonidine in people with Fecal Incontinence and Bile Acid Malabsorption, run by Mayo Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years, women only
- Conditions the study is for
- Fecal Incontinence, Bile Acid Malabsorption
- What is being tested?
- Colesevelam and Clonidine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2015to 14 Apr 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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
- 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
- All patients who complete at least 1 week of treatment with study drugs or placebo
Who cannot join
- History of clinically serious cardiovascular or pulmonary disease or EKG showing 2nd degree atrioventricular block or higher.
- 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
- Positive urine pregnancy screen
- Phase 3
- 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
- Phase 4
- Patients who completed less than 1 week of treatment with study drugs or placebo
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Placebo Controlled Study of Colesevelam in Fecal Incontinence
Compare the effects of a combination of colesevelam and clonidine to placebo on bowel symptoms in patients with urge or combined type of FI.
Read the 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.
- Conditions
- Fecal Incontinence, Bile Acid Malabsorption
- Being tested
- Colesevelam, Clonidine, Placebo
- Keywords
- Incontinence, Diarrhea, Bile acid, Microbiome
- Medical subject headings
- Fecal Incontinence, Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ColesevelamDrug
Also called Welchol
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
Also called Catapres
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.
PlaceboOther
Placebo will be identical in appearance to the active drug.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants in this arm will receive placebo for 4 weeks. Receives: Other: Placebo |
| Colesevelam and Clonidine | Active comparator | Participants 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. Receives: Drug: Colesevelam; Drug: Clonidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 weeks
Secondary outcomes (14)
Daily Stool Frequency
The number of bowel movements daily measured by self-reported bowel diaries.
Measured: 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.
Measured: 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)
Measured: 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.
Measured: 4 weeks
Total Fecal Incontinence Episodes
The total number of fecal incontinence episodes per week as measured by self-reported bowel diaries.
Measured: 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.
Measured: 4 weeks
Percent of Incontinent Bowel Movements Pre-treatment
The percentage of bowel movements that were incontinent prior to treatment initiation, per self-reported bowel diaries.
Measured: baseline
Percent of Incontinent Bowel Movements During Treatment
The percentage of bowel movements that were incontinent during treatment, per self-reported bowel diaries.
Measured: 4 weeks
Percent of Incontinent Bowel Movements to be Semi-Formed Stools Pre-Treatment
The percentage of incontinent bowel movements where the Bristol stool score was 5, 6 or 7. (5=soft blobs; 6=mushy, fluffy pieces; 7= watery, no solid pieces), pre-treatment, per self-reported bowel diaries.
Measured: baseline
Percent of Incontinent Bowel Movements to be Semi-Formed Stools During Treatment
The percentage of incontinent bowel movements where the Bristol stool score was 5, 6 or 7. (5=soft blobs; 6=mushy, fluffy pieces; 7= watery, no solid pieces) during treatment, per self-reported bowel diaries.
Measured: 4 weeks
Severity of Bowel Symptoms
The Fecal Incontinence Symptom Severity (FISS) score is based on five questions; (1) the frequency of FI; (2) the type of FI (stool only, liquid or mucus only, both liquid/mucus and stool, or gas only); (3) the amount of stool leaked (small, moderate, or large); (4) the frequency of having to rush to the toilet; and (5) the frequency of having stool leak without warning. Questions 4 \& 5 are merged to determine if the participant has passive FI (FI without warning), urge FI, both, or neither. The responses to the questions are assigned physician-derived weights and added together for a total score of 4 to 13. The higher the score the more severe the FI symptoms.
Measured: 4 weeks
Severity of Fecal Incontinence
Measured by the Fecal Incontinence Severity Index (FISI). It is a validated 4-item scale used to assess the frequency (never, 1-3 times a month, once a week, 2 or more times per week but not daily, once a day, 2 or more times per day) of 4 different types of FI (gas, mucus, liquid stool, solid stool). Each of the four types of FI is awarded a number of points, depending on the frequency at which that type of incontinence is experienced. The points are totaled and the scores can range from 0 to 61, where the higher the score, the higher the perceived severity of the fecal incontinence.
Measured: 4 weeks
Fecal Incontinence Quality of Life (FI-QoL)
The Fecal Incontinence Quality of Life questionnaire measures specific quality of life issues expected to affect patients with fecal incontinence. The questions are grouped into four categories: lifestyle (10 questions), coping (9 questions), depression (7 questions), and embarrassment (3 questions). Each category is scored from 1 to 4. The scale scores are calculated by adding the numerical values of all responses in that specific scale and then dividing by its number of items. Higher scores indicate a better quality of life.
Measured: 4 weeks
Loperamide Tablets Per Week
The number of tablets of loperamide used, per self-reported bowel diaries.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2015 (estimated)
- Study startNov 2015
- Primary completion14 Apr 2022
- Study completion14 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Fecal IncontinenceStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Research Resources (NCRR)
- Responsible party
- Principal investigator, Adil Bharucha, MBBS, MD, Mayo Clinic
- Investigators
- Adil Bharucha, MBBS, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02628626
- Sponsor's protocol ID
- 15-005986
- Other IDs
- R01DK078924, UL1RR024150
- Status last verified
- May 2023
- First submitted
- 1 Dec 2015
- Last updated
- 22 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo Controlled Study of Colesevelam in Fecal Incontinence
- ClinicalTrials.gov ID
- NCT02628626
- Acronym / sponsor ID
- 15-005986
- Conditions
- Fecal Incontinence, Bile Acid Malabsorption
- Keywords
- Incontinence, Diarrhea, Bile acid, Microbiome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Research Resources (NCRR)
- Study start
- Nov 2015
- Primary completion
- 14 Apr 2022 (actual)
- Study completion
- 14 Apr 2022 (actual)
- First posted
- 11 Dec 2015 (estimated)
- Results
- Posted 22 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboParticipants in this arm will receive placebo for 4 weeks. |
| Colesevelam and Clonidine | Active comparator | Drug: Colesevelam, Drug: ClonidineParticipants 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
- 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
- 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
- All patients who complete at least 1 week of treatment with study drugs or placebo
Key exclusion criteria (8 listed)
- History of clinically serious cardiovascular or pulmonary disease or EKG showing 2nd degree atrioventricular block or higher.
- 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
- Positive urine pregnancy screen
- Phase 3
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ColesevelamAlso: WelcholParticipants 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. | Drug | Colesevelam and Clonidine |
| ClonidineAlso: CatapresParticipants 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. | Drug | Colesevelam and Clonidine |
| PlaceboPlacebo will be identical in appearance to the active drug. | Other | Placebo |
Primary outcome
Number of Participants to Report a 50% or Greater Reduction in Weekly Fecal Incontinence (FI) Episodes
Time frame: 4 weeks
The number of participants that report a 50% or greater reduction in weekly incontinent episodes as measured by self-reported bowel diaries.
14 secondary outcomes
Daily Stool Frequency
Time frame: 4 weeks
Stool Consistency
Time frame: 4 weeks
Number of Semi-Formed Stools Per Week
Time frame: 4 weeks
Delay of Bowel Movement
Time frame: 4 weeks
Total Fecal Incontinence Episodes
Time frame: 4 weeks
Volume of Fecal Incontinence
Time frame: 4 weeks
Percent of Incontinent Bowel Movements Pre-treatment
Time frame: baseline
Percent of Incontinent Bowel Movements During Treatment
Time frame: 4 weeks
Percent of Incontinent Bowel Movements to be Semi-Formed Stools Pre-Treatment
Time frame: baseline
Percent of Incontinent Bowel Movements to be Semi-Formed Stools During Treatment
Time frame: 4 weeks
Severity of Bowel Symptoms
Time frame: 4 weeks
Severity of Fecal Incontinence
Time frame: 4 weeks
Fecal Incontinence Quality of Life (FI-QoL)
Time frame: 4 weeks
Loperamide Tablets Per Week
Time frame: 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adil Bharucha, MBBS, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Colesevelam and Clonidine in people with Fecal Incontinence and Bile Acid Malabsorption, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants to Report a 50% or Greater Reduction in Weekly Fecal Incontinence (FI) Episodes (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2023.