Treating Anorectal Dysfunction in MS

• Sponsor: David Levinthal (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02609607
• Collaborator: Consortium of Multiple Sclerosis Centers (Other)
• Enrollment: 11
• Location: 1
• Arms: 2
• Duration (Months): 30
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Constipation; Fecal Incontinence; Multiple Sclerosis	Drug: Bisacodyl; Other: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Treating Anorectal Dysfunction Associated With Multiple Sclerosis
• Study Start Date: Jun 1, 2016
• Actual Primary Completion Date: Nov 1, 2018
• Actual Study Completion Date: Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Every other day placement of a placebo rectal suppository for 4 weeks	Other: Placebo; Rectal suppository
Experimental: Bisacodyl Every other day placement of a bisacodyl 10 mg rectal suppository for 4 weeks	Drug: Bisacodyl; Rectal suppository; Other Names: Dulcolax

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213

Sponsors and Collaborators

• David Levinthal
• Consortium of Multiple Sclerosis Centers

Investigators

• Principal Investigator: David J Levinthal, MD, PhD, University of Pittsburgh

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 26, 2018

More Information

Publications

None provided.

• Responsible Party: David Levinthal, Assistant Professor, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT02609607
• Other Study ID Numbers: PRO15100104
• First Posted: Nov 20, 2015
• Last Update Posted: Jan 22, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Fecal Incontinence; Multiple Sclerosis; Sclerosis; Constipation; Bisacodyl

Study Results

Participant Flow

Arm/Group Title	Placebo	Bisacodyl
Arm/Group Description	Every other day placement of a placebo rectal suppository for 4 weeks Placebo: Rectal suppository	Every other day placement of a bisacodyl 10 mg rectal suppository for 4 weeks Bisacodyl: Rectal suppository
Period Title: Overall Study
STARTED	6	5
COMPLETED	6	4
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Placebo	Bisacodyl	Total
Arm/Group Description	Every other day placement of a placebo rectal suppository for 4 weeks Placebo: Rectal suppository	Every other day placement of a bisacodyl 10 mg rectal suppository for 4 weeks Bisacodyl: Rectal suppository	Total of all reporting groups
Overall Participants	6	5	11
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 50%	5 100%	8 72.7%
>=65 years	3 50%	0 0%	3 27.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.3 (6.3)	58 (5.2)	60.6 (6.0)
Sex: Female, Male (Count of Participants)
Female	4 66.7%	3 60%	7 63.6%
Male	2 33.3%	2 40%	4 36.4%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	6 100%	5 100%	11 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With 30% Improvement From Baseline in Bowel Symptoms at 4 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Bisacodyl
Arm/Group Description	Every other day placement of a placebo rectal suppository for 4 weeks Placebo: Rectal suppository	Every other day placement of a bisacodyl 10 mg rectal suppository for 4 weeks Bisacodyl: Rectal suppository
Measure Participants	6	4
Count of Participants [Participants]	2 33.3%	0 0%

2. Secondary Outcome

Title	Change From Baseline in Mean PAC-SYM Subscale Scores at 4 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Bisacodyl
Arm/Group Description	Every other day placement of a placebo rectal suppository for 4 weeks Placebo: Rectal suppository	Every other day placement of a bisacodyl 10 mg rectal suppository for 4 weeks Bisacodyl: Rectal suppository
Measure Participants	6	4
Change in PAC-SYM Total Score	-0.24 (0.36)	0.06 (0.49)
Change in Abdominal Symptoms	0 (0.16)	0.13 (0.48)
Change in Rectal Subscale	0 (0.76)	-0.42 (0.63)
Stool Subscale	0 (1.30)	-0.05 (0.19)

3. Secondary Outcome

Title	Change From Baseline in Fecal Incontinence Severity Index (FISI) Score at 4 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Bisacodyl
Arm/Group Description	Every other day placement of a placebo rectal suppository for 4 weeks Placebo: Rectal suppository	Every other day placement of a bisacodyl 10 mg rectal suppository for 4 weeks Bisacodyl: Rectal suppository
Measure Participants	6	4
Mean (Standard Deviation) [units on a scale]	-1.83 (7.9)	4.25 (19.4)

4. Secondary Outcome

Title	Change From Baseline in Fecal Incontinence Quality of Life (FIQL) Score at 4 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Bisacodyl
Arm/Group Description	Every other day placement of a placebo rectal suppository for 4 weeks Placebo: Rectal suppository	Every other day placement of a bisacodyl 10 mg rectal suppository for 4 weeks Bisacodyl: Rectal suppository
Measure Participants	6	4
Lifestyle	-0.32 (0.41)	-0.1 (0.03)
Coping / Behavior	-0.22 (0.65)	-0.06 (0.17)
Depression/ Self-Perception	-0.17 (0.36)	0.07 (0.21)
Embarrassment	-0.44 (0.62)	0.17 (0.69)

5. Secondary Outcome

Title	Change From Baseline in PAC-QOL Scores at 4 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Bisacodyl
Arm/Group Description	Every other day placement of a placebo rectal suppository for 4 weeks Placebo: Rectal suppository	Every other day placement of a bisacodyl 10 mg rectal suppository for 4 weeks Bisacodyl: Rectal suppository
Measure Participants	6	4
Mean (Standard Deviation) [units on a scale]	-0.04 (0.23)	-0.33 (0.44)

6. Secondary Outcome

Title	Change From Baseline in SF-36 Scores at 4 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Bisacodyl
Arm/Group Description	Every other day placement of a placebo rectal suppository for 4 weeks Placebo: Rectal suppository	Every other day placement of a bisacodyl 10 mg rectal suppository for 4 weeks Bisacodyl: Rectal suppository
Measure Participants	6	4
Physical functioning	3.33 (7.45)	-1.25 (5.45)
Role limitations due to physical health	-16.67 (23.57)	-12.5 (21.65)
Role limitations due to emotional problems	-7.33 (37.8)	16.5 (16.5)
Energy/fatigue	-4.17 (3.44)	-6.25 (7.4)
Emotional well-being	-5.33 (7.89)	-1 (1.73)
Social functioning	-4.5 (17.22)	0 (8.49)
Pain	13.67 (19.94)	-1.75 (4.92)
General health	-4.17 (3.44)	-3.75 (9.60)

7. Secondary Outcome

Title	Change From Baseline In Percent of Subjects With Normal Average Stool Form at 4 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Bisacodyl
Arm/Group Description	Every other day placement of a placebo rectal suppository for 4 weeks Placebo: Rectal suppository	Every other day placement of a bisacodyl 10 mg rectal suppository for 4 weeks Bisacodyl: Rectal suppository
Measure Participants	3	1
Number [percentage of participants]	0 0%	0 0%

8. Secondary Outcome

Title	Change From Baseline In Average Number of Daily Bowel Movements at 4 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Bisacodyl
Arm/Group Description	Every other day placement of a placebo rectal suppository for 4 weeks Placebo: Rectal suppository	Every other day placement of a bisacodyl 10 mg rectal suppository for 4 weeks Bisacodyl: Rectal suppository
Measure Participants	3	2
Mean (Standard Deviation) [bowel movements per day]	0.02 (0.70)	-0.21 (0.33)

9. Secondary Outcome

Title	Change From Baseline In Average Number of Fecal Incontinence Episodes at 4 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Bisacodyl
Arm/Group Description	Every other day placement of a placebo rectal suppository for 4 weeks Placebo: Rectal suppository	Every other day placement of a bisacodyl 10 mg rectal suppository for 4 weeks Bisacodyl: Rectal suppository
Measure Participants	3	2
Mean (Standard Deviation) [incontinence episodes per day]	0.05 (0.16)	-0.04 (0.32)

Adverse Events

Time Frame	During trial duration (4 weeks)
Arm/Group Title	Placebo		Bisacodyl
Arm/Group Description	Every other day placement of a placebo rectal suppository for 4 weeks Placebo: Rectal suppository		Every other day placement of a bisacodyl 10 mg rectal suppository for 4 weeks Bisacodyl: Rectal suppository
All Cause Mortality
	Placebo		Bisacodyl
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/5 (0%)
Serious Adverse Events
	Placebo		Bisacodyl
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Bisacodyl
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		1/5 (20%)
Gastrointestinal disorders
Abdominal cramps	0/6 (0%)	0	1/5 (20%)	1

Limitations/Caveats

Early Termination due to Difficulty in Recruitment, leading to small numbers of subjects analyzed.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.