Constipation, Fecal Incontinence, Multiple Sclerosis
Conditions
Brief summary
The investigators seek to test whether incorporating the scheduled dosing of a bisacodyl 10 mg rectal suppository every other day improves bowel-related symptoms in patients with multiple sclerosis. Patients will be randomized to receive either a placebo suppository or bisacodyl suppository dosed every other day for 4 weeks.
Detailed description
The majority of patients with multiple sclerosis (MS) suffer from some form of anorectal dysfunction, and these difficulties with bowel function are often ranked as negatively impactful on quality of life as impaired mobility. Despite the significant clinical burden of these symptoms, there remains a paucity of published literature supporting specific therapeutic options to manage anorectal dysfunction in this clinical population. Most bowel regimens rely on either oral laxatives (i.e. PEG-3350) or anti-diarrheal agents (i.e. loperamide). In their study, the investigators propose to establish the efficacy of a bowel regimen that combines both oral agents (as needed; standard care) with scheduled, every other day dosing of a placebo or stimulant laxative rectal suppository -- bisacodyl 10 mg. Bisacodyl is a stimulant laxative medication that is available over-the-counter. It works by activating nerves in the rectum to elicit rectal contractions which ultimately leading to defecation.
Interventions
DRUGBisacodyl
Rectal suppository
OTHERPlacebo
Rectal suppository
Sponsors
Consortium of Multiple Sclerosis Centers
David Levinthal
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* MS patients with mild to moderately severe disease (Multiple Sclerosis Impact Scale \[MSIS-29\] physical domain scores \<61 or equivalent Extended Disability Severity Score \[EDSS\] \< 6.5) of any age, gender, disease subtype, duration of illness, current use of MS disease modifying therapy, or comorbid medical condition AND who also have anorectal dysfunction (chronic constipation and/or fecal incontinence) are eligible.
Exclusion criteria
* MS patients with severe disease (MSIS-29 physical domain scores greater than 61 or equivalently severe EDSS greater than 6.5), patients with surgically altered anorectal anatomy (i.e. proctectomy/partial colectomy, ostomy creation), active enteric infection (i.e., Clostidium Difficile), or inflammatory bowel disease (i.e. ulcerative proctitis, ulcerative colitis) will also be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With 30% Improvement From Baseline in Bowel Symptoms at 4 Weeks | Baseline, 4 weeks | All subjects were asked the following question at study entry ('baseline') and the end of 4 weeks of intervention: Using a scale of 1 to 10 (1 being no problem and 10 being maximally impactful symptoms), how would you rate the severity of your bowel symptoms over the past 2 weeks? The range of reported values was 2-9. We took a response to be a 30% decrease (i.e. improvement) in the subjective symptom score between the baseline and 4 week assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fecal Incontinence Severity Index (FISI) Score at 4 Weeks | Baseline, 4 Weeks | The Fecal Incontinence Severity Index (FISI) is measures of fecal incontinence severity. The FISI score ranges from 0 to 61, with higher scores interpreted as worse fecal incontinence severity. |
| Change From Baseline in Fecal Incontinence Quality of Life (FIQL) Score at 4 Weeks | Baseline, 4 weeks | The Fecal Incontinence Quality of Life (FIQL) Scale measures of the impact of fecal incontinence on aspects of quality of life. There are 4 subscales: Lifestyle, Coping/Behavior, Depression/Self-Perception, and Embarrassment, each of which is calculated as an average score ranging from 1 to 5, with higher scores indicating a greater functional status of quality of life. |
| Change From Baseline in PAC-QOL Scores at 4 Weeks | Baseline, 4 weeks | The Patient Assessment of Constipation Quality of Life (PAC-QOL) Questionnaire is a validated measure of the quality of life impact of constipation. The questionnaire is reported a total score, reported as the average item scores and ranging from 0 to 4, where higher scores represent poorer QOL. |
| Change From Baseline in Mean PAC-SYM Subscale Scores at 4 Weeks | Baseline, 4 weeks | The Patient Assessment of Constipation Symptom Questionnaire (PAC-SYM) is a validated measure of constipation severity. The questionnaire has a total score and three subscales: Abdominal Symptoms, Rectal Symptoms, and Stool Form. The mean total score and each of the scale subscores are reported in a range of 0-4, with higher scores meaning worse outcomes. A difference (number) of 0.75 in the mean PAC-SYM total and each of the subscale scores is regarded as a clinically significant change. |
| Change From Baseline In Percent of Subjects With Normal Average Stool Form at 4 Weeks | Baseline, 4 weeks | The Bristol Stool Scale (BSS) is a validated measure of stool form, ranging from 1-7. Normal stool form is regarded as average scores of 3 to 4. Subjects were asked to assess the BSS in their 'bowel diaries' during a preparatory phase of up to 4 weeks prior to study entry and for 4 weeks after intervention, but these 'bowel diaries' were not required for entry into the trial. |
| Change From Baseline In Average Number of Daily Bowel Movements at 4 Weeks | Baseline, 4 weeks | Subjects were asked to record each bowel movement in their 'bowel diaries' during a preparatory phase of up to 4 weeks prior to study entry and for 4 weeks after intervention. We used this information to calculate the average difference in number of bowel movements / day before and after exposure to placebo or Bisacodyl. However, these 'bowel diaries' were not required for entry into the trial. Thus, comparative data for bowel movement frequency was available for 3 of the 6 subjects randomized to placebo, and 2 of the 4 subjects randomized to receive Bisacodyl. |
| Change From Baseline In Average Number of Fecal Incontinence Episodes at 4 Weeks | Baseline, 4 weeks | Subjects were asked to record each episode of fecal incontinence in their 'bowel diaries' during a preparatory phase of up to 4 weeks prior to study entry and for 4 weeks after intervention. We used this information to calculate the mean difference in the average number of fecal incontinence episodes / day. |
| Change From Baseline in SF-36 Scores at 4 Weeks | Baseline, 4 weeks | The RAND Health Survey (v.1) is a 36 item questionnaire that measures health in multiple domains. The measure is reported as scores on eight subscales: Physical functioning, Role limitations due to physical health, Role limitations due to emotional problems, Energy/fatigue, Emotional well-being, Social functioning, Pain, and General health. Scores on each subscale range from 0 and 100, with higher scores indicative of better health function in the domain. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Every other day placement of a placebo rectal suppository for 4 weeks
Placebo: Rectal suppository | 6 |
| Bisacodyl Every other day placement of a bisacodyl 10 mg rectal suppository for 4 weeks
Bisacodyl: Rectal suppository | 5 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Bisacodyl | Total | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 3 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 8 Participants | 3 Participants |
| Age, Continuous | 58 years STANDARD_DEVIATION 5.2 | 60.6 years STANDARD_DEVIATION 6 | 62.3 years STANDARD_DEVIATION 6.3 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 5 participants | 11 participants | 6 participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 5 |
| other Total, other adverse events | 0 / 6 | 1 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 5 |
Outcome results
Primary
Number of Participants With 30% Improvement From Baseline in Bowel Symptoms at 4 Weeks
All subjects were asked the following question at study entry ('baseline') and the end of 4 weeks of intervention: Using a scale of 1 to 10 (1 being no problem and 10 being maximally impactful symptoms), how would you rate the severity of your bowel symptoms over the past 2 weeks? The range of reported values was 2-9. We took a response to be a 30% decrease (i.e. improvement) in the subjective symptom score between the baseline and 4 week assessment.
Time frame: Baseline, 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With 30% Improvement From Baseline in Bowel Symptoms at 4 Weeks | 2 Participants |
| Bisacodyl | Number of Participants With 30% Improvement From Baseline in Bowel Symptoms at 4 Weeks | 0 Participants |
Secondary
Change From Baseline In Average Number of Daily Bowel Movements at 4 Weeks
Subjects were asked to record each bowel movement in their 'bowel diaries' during a preparatory phase of up to 4 weeks prior to study entry and for 4 weeks after intervention. We used this information to calculate the average difference in number of bowel movements / day before and after exposure to placebo or Bisacodyl. However, these 'bowel diaries' were not required for entry into the trial. Thus, comparative data for bowel movement frequency was available for 3 of the 6 subjects randomized to placebo, and 2 of the 4 subjects randomized to receive Bisacodyl.
Time frame: Baseline, 4 weeks
Population: These 'bowel diaries' were not required for entry into the trial. Thus, comparative data for bowel movement frequency was available for 3 of the 6 subjects randomized to placebo, and 2 of the 4 subjects randomized to receive Bisacodyl.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline In Average Number of Daily Bowel Movements at 4 Weeks | 0.02 bowel movements per day | Standard Deviation 0.7 |
| Bisacodyl | Change From Baseline In Average Number of Daily Bowel Movements at 4 Weeks | -0.21 bowel movements per day | Standard Deviation 0.33 |
Secondary
Change From Baseline In Average Number of Fecal Incontinence Episodes at 4 Weeks
Subjects were asked to record each episode of fecal incontinence in their 'bowel diaries' during a preparatory phase of up to 4 weeks prior to study entry and for 4 weeks after intervention. We used this information to calculate the mean difference in the average number of fecal incontinence episodes / day.
Time frame: Baseline, 4 weeks
Population: These 'bowel diaries' were not required for entry into the trial. Thus, comparative data for bowel movement frequency was available for 3 of the 6 subjects randomized to placebo, and 2 of the 4 subjects randomized to receive Bisacodyl.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline In Average Number of Fecal Incontinence Episodes at 4 Weeks | 0.05 incontinence episodes per day | Standard Deviation 0.16 |
| Bisacodyl | Change From Baseline In Average Number of Fecal Incontinence Episodes at 4 Weeks | -0.04 incontinence episodes per day | Standard Deviation 0.32 |
Secondary
Change From Baseline in Fecal Incontinence Quality of Life (FIQL) Score at 4 Weeks
The Fecal Incontinence Quality of Life (FIQL) Scale measures of the impact of fecal incontinence on aspects of quality of life. There are 4 subscales: Lifestyle, Coping/Behavior, Depression/Self-Perception, and Embarrassment, each of which is calculated as an average score ranging from 1 to 5, with higher scores indicating a greater functional status of quality of life.
Time frame: Baseline, 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Fecal Incontinence Quality of Life (FIQL) Score at 4 Weeks | Lifestyle | -0.32 units on a scale | Standard Deviation 0.41 |
| Placebo | Change From Baseline in Fecal Incontinence Quality of Life (FIQL) Score at 4 Weeks | Coping / Behavior | -0.22 units on a scale | Standard Deviation 0.65 |
| Placebo | Change From Baseline in Fecal Incontinence Quality of Life (FIQL) Score at 4 Weeks | Depression/ Self-Perception | -0.17 units on a scale | Standard Deviation 0.36 |
| Placebo | Change From Baseline in Fecal Incontinence Quality of Life (FIQL) Score at 4 Weeks | Embarrassment | -0.44 units on a scale | Standard Deviation 0.62 |
| Bisacodyl | Change From Baseline in Fecal Incontinence Quality of Life (FIQL) Score at 4 Weeks | Embarrassment | 0.17 units on a scale | Standard Deviation 0.69 |
| Bisacodyl | Change From Baseline in Fecal Incontinence Quality of Life (FIQL) Score at 4 Weeks | Lifestyle | -0.1 units on a scale | Standard Deviation 0.03 |
| Bisacodyl | Change From Baseline in Fecal Incontinence Quality of Life (FIQL) Score at 4 Weeks | Depression/ Self-Perception | 0.07 units on a scale | Standard Deviation 0.21 |
| Bisacodyl | Change From Baseline in Fecal Incontinence Quality of Life (FIQL) Score at 4 Weeks | Coping / Behavior | -0.06 units on a scale | Standard Deviation 0.17 |
Secondary
Change From Baseline in Fecal Incontinence Severity Index (FISI) Score at 4 Weeks
The Fecal Incontinence Severity Index (FISI) is measures of fecal incontinence severity. The FISI score ranges from 0 to 61, with higher scores interpreted as worse fecal incontinence severity.
Time frame: Baseline, 4 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fecal Incontinence Severity Index (FISI) Score at 4 Weeks | -1.83 units on a scale | Standard Deviation 7.9 |
| Bisacodyl | Change From Baseline in Fecal Incontinence Severity Index (FISI) Score at 4 Weeks | 4.25 units on a scale | Standard Deviation 19.4 |
Secondary
Change From Baseline in Mean PAC-SYM Subscale Scores at 4 Weeks
The Patient Assessment of Constipation Symptom Questionnaire (PAC-SYM) is a validated measure of constipation severity. The questionnaire has a total score and three subscales: Abdominal Symptoms, Rectal Symptoms, and Stool Form. The mean total score and each of the scale subscores are reported in a range of 0-4, with higher scores meaning worse outcomes. A difference (number) of 0.75 in the mean PAC-SYM total and each of the subscale scores is regarded as a clinically significant change.
Time frame: Baseline, 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean PAC-SYM Subscale Scores at 4 Weeks | Change in PAC-SYM Total Score | -0.24 units on a scale | Standard Deviation 0.36 |
| Placebo | Change From Baseline in Mean PAC-SYM Subscale Scores at 4 Weeks | Change in Abdominal Symptoms | 0 units on a scale | Standard Deviation 0.16 |
| Placebo | Change From Baseline in Mean PAC-SYM Subscale Scores at 4 Weeks | Change in Rectal Subscale | 0 units on a scale | Standard Deviation 0.76 |
| Placebo | Change From Baseline in Mean PAC-SYM Subscale Scores at 4 Weeks | Stool Subscale | 0 units on a scale | Standard Deviation 1.3 |
| Bisacodyl | Change From Baseline in Mean PAC-SYM Subscale Scores at 4 Weeks | Stool Subscale | -0.05 units on a scale | Standard Deviation 0.19 |
| Bisacodyl | Change From Baseline in Mean PAC-SYM Subscale Scores at 4 Weeks | Change in PAC-SYM Total Score | 0.06 units on a scale | Standard Deviation 0.49 |
| Bisacodyl | Change From Baseline in Mean PAC-SYM Subscale Scores at 4 Weeks | Change in Rectal Subscale | -0.42 units on a scale | Standard Deviation 0.63 |
| Bisacodyl | Change From Baseline in Mean PAC-SYM Subscale Scores at 4 Weeks | Change in Abdominal Symptoms | 0.13 units on a scale | Standard Deviation 0.48 |
Secondary
Change From Baseline in PAC-QOL Scores at 4 Weeks
The Patient Assessment of Constipation Quality of Life (PAC-QOL) Questionnaire is a validated measure of the quality of life impact of constipation. The questionnaire is reported a total score, reported as the average item scores and ranging from 0 to 4, where higher scores represent poorer QOL.
Time frame: Baseline, 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in PAC-QOL Scores at 4 Weeks | -0.04 units on a scale | Standard Deviation 0.23 |
| Bisacodyl | Change From Baseline in PAC-QOL Scores at 4 Weeks | -0.33 units on a scale | Standard Deviation 0.44 |
Secondary
Change From Baseline In Percent of Subjects With Normal Average Stool Form at 4 Weeks
The Bristol Stool Scale (BSS) is a validated measure of stool form, ranging from 1-7. Normal stool form is regarded as average scores of 3 to 4. Subjects were asked to assess the BSS in their 'bowel diaries' during a preparatory phase of up to 4 weeks prior to study entry and for 4 weeks after intervention, but these 'bowel diaries' were not required for entry into the trial.
Time frame: Baseline, 4 weeks
Population: Comparative data was available for only 3 of the 6 subjects randomized to placebo, and only 1 of the 4 subjects randomized to receive Bisacodyl.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Change From Baseline In Percent of Subjects With Normal Average Stool Form at 4 Weeks | 0 percentage of participants |
| Bisacodyl | Change From Baseline In Percent of Subjects With Normal Average Stool Form at 4 Weeks | 0 percentage of participants |
Secondary
Change From Baseline in SF-36 Scores at 4 Weeks
The RAND Health Survey (v.1) is a 36 item questionnaire that measures health in multiple domains. The measure is reported as scores on eight subscales: Physical functioning, Role limitations due to physical health, Role limitations due to emotional problems, Energy/fatigue, Emotional well-being, Social functioning, Pain, and General health. Scores on each subscale range from 0 and 100, with higher scores indicative of better health function in the domain.
Time frame: Baseline, 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in SF-36 Scores at 4 Weeks | Emotional well-being | -5.33 units on a scale | Standard Deviation 7.89 |
| Placebo | Change From Baseline in SF-36 Scores at 4 Weeks | Role limitations due to physical health | -16.67 units on a scale | Standard Deviation 23.57 |
| Placebo | Change From Baseline in SF-36 Scores at 4 Weeks | Physical functioning | 3.33 units on a scale | Standard Deviation 7.45 |
| Placebo | Change From Baseline in SF-36 Scores at 4 Weeks | Social functioning | -4.5 units on a scale | Standard Deviation 17.22 |
| Placebo | Change From Baseline in SF-36 Scores at 4 Weeks | Pain | 13.67 units on a scale | Standard Deviation 19.94 |
| Placebo | Change From Baseline in SF-36 Scores at 4 Weeks | Role limitations due to emotional problems | -7.33 units on a scale | Standard Deviation 37.8 |
| Placebo | Change From Baseline in SF-36 Scores at 4 Weeks | General health | -4.17 units on a scale | Standard Deviation 3.44 |
| Placebo | Change From Baseline in SF-36 Scores at 4 Weeks | Energy/fatigue | -4.17 units on a scale | Standard Deviation 3.44 |
| Bisacodyl | Change From Baseline in SF-36 Scores at 4 Weeks | General health | -3.75 units on a scale | Standard Deviation 9.6 |
| Bisacodyl | Change From Baseline in SF-36 Scores at 4 Weeks | Physical functioning | -1.25 units on a scale | Standard Deviation 5.45 |
| Bisacodyl | Change From Baseline in SF-36 Scores at 4 Weeks | Role limitations due to physical health | -12.5 units on a scale | Standard Deviation 21.65 |
| Bisacodyl | Change From Baseline in SF-36 Scores at 4 Weeks | Energy/fatigue | -6.25 units on a scale | Standard Deviation 7.4 |
| Bisacodyl | Change From Baseline in SF-36 Scores at 4 Weeks | Social functioning | 0 units on a scale | Standard Deviation 8.49 |
| Bisacodyl | Change From Baseline in SF-36 Scores at 4 Weeks | Emotional well-being | -1 units on a scale | Standard Deviation 1.73 |
| Bisacodyl | Change From Baseline in SF-36 Scores at 4 Weeks | Pain | -1.75 units on a scale | Standard Deviation 4.92 |
| Bisacodyl | Change From Baseline in SF-36 Scores at 4 Weeks | Role limitations due to emotional problems | 16.5 units on a scale | Standard Deviation 16.5 |