Treating Anorectal Dysfunction in MS

Study Overview
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Brief Summary
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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
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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.

Official Title
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Treating Anorectal Dysfunction Associated With Multiple Sclerosis

Conditions
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Constipation, Fecal Incontinence, Multiple Sclerosis

Intervention / Treatment
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* Drug: Bisacodyl
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Every other day placement of a placebo rectal suppository for 4 weeks | Other: Placebo<br>* Rectal suppository<br>|
| Experimental: Bisacodyl<br>Every other day placement of a bisacodyl 10 mg rectal suppository for 4 weeks | Drug: Bisacodyl<br>* Rectal suppository<br>* Other names: Dulcolax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, 4 weeks | 
| 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. | Baseline, 4 Weeks | 
| 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. | Baseline, 4 weeks | 
| 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. | Baseline, 4 weeks | 
| 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. | Baseline, 4 weeks | 
| 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. | Baseline, 4 weeks | 
| 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. | Baseline, 4 weeks | 
| 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. | Baseline, 4 weeks |