Back to resultsA Placebo-Controlled Study of Clonidine for Fecal Incontinence.
Primary Purpose
Fecal Incontinence
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Clonidine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Fecal Incontinence focused on measuring fecal incontinence, stool leakage, incontinence, FI, Urge predominant fecal incontinence
Eligibility Criteria
Inclusion Criteria:
- Women aged 18-75 years with urge predominant FI, as defined by a validated questionnaire, for greater than or equal to 1 year duration will be eligible to participate
- Absence of organic disease (i.e., ulcerative colitis, cancer) as evidenced by colonoscopy, or barium enema and sigmoidoscopy within the last 3 years
Exclusion Criteria:
- History of clinically significant cardiovascular or pulmonary disease or EKG abnormalities within the last 6 months [i.e., atrial flutter or fibrillation, sinus tachycardia (> 110/minute) or bradycardia (< 45 beats/minute), or prolonged corrected QT (QTc) interval (> 460 msec)
- Current or past history of rectal cancer, scleroderma, inflammatory bowel disease, congenital anorectal abnormalities, greater than or equal to Grade 2 rectal prolapse, history of rectal resection or pelvic irradiation
- Neurological disorders - Spinal cord injuries, dementia (Mini-mental status score <20/25), multiple sclerosis, Parkinson's disease, peripheral neuropathy
- Conditions precluding safe use of clonidine, i.e., symptomatic hypotension, or systolic blood pressure of <100 mm Hg on initial screening visit
- Pregnant or nursing women
- Severe diarrhea during the run in phase defined as greater than 6 liquid stools daily (Bristol 6 or 7)
- Medications: Absolute - opioid analgesics, anticholinergic drugs [low doses of tricyclic antidepressants, e.g., nortriptyline (up to 50 mg/day) or amitriptyline (up to 25 mg/day) will be permitted provided they were begun 3 months prior to the screening period]
- Medications: Relative - other antihypertensive agents (i.e., if there is concern about synergistic effects and hypotension)
Sites / Locations
- Mayo Clinic
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Oral Clonidine
Oral Placebo
Arm Description
Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.
Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.
Outcomes
Primary Outcome Measures
Mean Fecal Incontinence and Constipation Assessment (FICA) Score
The FICA severity scale has 4 items (frequency, type, amount of leakage, and presence of urgency) and is used to rate the severity of fecal incontinence. The parameter was computed from values in the weekly diaries. The FICA score can range from 1 to 13. Symptom severity scores of 1-6, 7-10, and 11-13 are categorized as mild, moderate, and severe, respectively. Scores were averaged over the 4 week baseline period and the 4 week treatment periods.
Secondary Outcome Measures
Mean Number of Days With Fecal Incontinence
Values were averaged over 4 week baseline and 4 week treatment periods.
Mean Number of Fecal Incontinence Episodes
Values were averaged over 4 week baseline and 4 week treatment periods.
Mean Percentage of Bowel Movements Which Were Incontinent
Values were averaged over 4 week baseline and 4 week treatment periods.
Mean Severity of Fecal Incontinence
The Fecal Incontinence Severity Index was used to compute the severity of fecal incontinence (FI). 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 could range from 0 (no symptoms) to 61 (very frequent FI). Values were computed from pre- and post- treatment questionnaires.
Impact of Fecal Incontinence on Baseline Quality of Life
Scores were computed from a pre-treatment questionnaire, the Fecal Incontinence Quality of Life Scale. This scale is composed of a total of 29 items; these items form four scales: Lifestyle (10 items) Coping/Behavior (9 items), Depression/Self Perception (7 items), and Embarrassment (3 items).
Scales range from 1 to 4; with a 1 indicating a lower functional status of quality of life. Scales scores are the average (mean) response to all items in the scale (that is, add the responses to all questions in a scale together and then divide by the number of items in the scale, adjusting for missing values).
Impact of Fecal Incontinence on Post-Treatment Quality of Life
Scores were computed from a post-treatment questionnaire, the Fecal Incontinence Quality of Life Scale. This scale is composed of a total of 29 items; these items form four scales: Lifestyle (10 items) Coping/Behavior (9 items), Depression/Self Perception (7 items), and Embarrassment (3 items).
Scales range from 1 to 4; with a 1 indicating a lower functional status of quality of life. Scales scores are the average (mean) response to all items in the scale (that is, add the responses to all questions in a scale together and then divide by the number of items in the scale, adjusting for missing values).
Satisfaction With Treatment
This parameter was determined by a 100 mm visual analog scale, with possible scores ranging from 0 = "Not satisfied at all (no relief of symptoms)" to 100 = "Completely satisfied (symptoms resolved)." The parameter was computed from weekly diaries. Scores were averaged over the 4 week baseline period and the 4 week treatment periods.
Percentage of Bowel Movements Preceded by Rectal Urgency
Rectal urgency is defined as a sudden, irresistible need to have a bowel movement. Scores were averaged over the 4 week baseline period and the 4 week treatment periods.
Percentage of Bowel Movements With Semi-formed and Loose Stools in Subjects With and Without Diarrhea
The percentage of bowel movements with semi-formed and loose stools was defined as those with a score of 5-7 on the Bristol stool form scale.
Percentage of Bowel Movements With Semi-formed and Loose Stools Post-treatment Adjusted for Baseline
The percentage of bowel movements with semi-formed and loose stools was defined as those with a score of 5-7 on the Bristol stool form scale. The "adjustment for baseline" was an analysis of covariance (ANCOVA) where the covariate was the baseline version of the endpoint.
Percentage of Days With Fecal Incontinence (FI)
Percentage of Days With FI Post-treatment Adjusted for Baseline
The "adjustment for baseline" was an analysis of covariance (ANCOVA) where the covariate was the baseline version of the endpoint.
Full Information
NCT ID
NCT00884832
First Posted
April 17, 2009
Last Updated
January 20, 2014
Sponsor
Mayo Clinic
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Research Resources (NCRR)
1. Study Identification
Unique Protocol Identification Number
NCT00884832
Brief Title
A Placebo-Controlled Study of Clonidine for Fecal Incontinence.
Official Title
A Placebo-Controlled Study of Clonidine for Fecal Incontinence.
Study Type
Interventional
2. Study Status
Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
October 2008 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
August 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Research Resources (NCRR)
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Fecal incontinence is the involuntary leakage of stool from the anus. Doctors at Mayo Clinic are doing a research study to assess the effects of a medication, clonidine, on fecal incontinence and rectal functions in women. Clonidine has been approved by the Food and Drug Administration (FDA) for treating high blood pressure, but not for treating incontinence and rectal functions. The hypothesis of this study is clonidine will improve fecal incontinence, increase rectal capacity and reduce rectal sensation to a greater extent than placebo in women.
Detailed Description
Available therapeutic options for idiopathic fecal incontinence (FI) are limited and unsatisfactory. In addition to weak anal sphincters, our data suggest that reduced rectal capacity may contribute to rectal hypersensitivity and the symptom of rectal urgency in FI. During a 4 week study, oral clonidine restored rectal capacity and improved fecal continence in women with urge-predominant FI. Clonidine improves fecal continence and stool consistency in diarrhea-predominant irritable bowel syndrome (IBS). Therefore, we now propose a placebo-controlled study of clonidine for FI. Our aims are to (i) compare the effects of clonidine and placebo, to be given for 4 weeks, on symptoms, anal pressures, rectal compliance and sensation in women with FI. Forty four women (18-75 y) with urge predominant "idiopathic" FI and ≥ 4 episodes of FI during a 4 week screening period will be recruited to this study. Thereafter, patients will be treated with clonidine or placebo for 4 weeks. Bowel symptoms will be recorded in a diary. Anal sphincter pressures, rectal compliance and sensation will be evaluated before and during treatment with clonidine.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fecal Incontinence
Keywords
fecal incontinence, stool leakage, incontinence, FI, Urge predominant fecal incontinence
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
44 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Oral Clonidine
Arm Type
Experimental
Arm Description
Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.
Arm Title
Oral Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Clonidine
Other Intervention Name(s)
Kapvay, Nexiclon, Catapres
Intervention Description
Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.
Primary Outcome Measure Information:
Title
Mean Fecal Incontinence and Constipation Assessment (FICA) Score
Description
The FICA severity scale has 4 items (frequency, type, amount of leakage, and presence of urgency) and is used to rate the severity of fecal incontinence. The parameter was computed from values in the weekly diaries. The FICA score can range from 1 to 13. Symptom severity scores of 1-6, 7-10, and 11-13 are categorized as mild, moderate, and severe, respectively. Scores were averaged over the 4 week baseline period and the 4 week treatment periods.
Time Frame
4 weeks baseline, 4 weeks treatment
Secondary Outcome Measure Information:
Title
Mean Number of Days With Fecal Incontinence
Description
Values were averaged over 4 week baseline and 4 week treatment periods.
Time Frame
4 weeks baseline, 4 weeks treatment
Title
Mean Number of Fecal Incontinence Episodes
Description
Values were averaged over 4 week baseline and 4 week treatment periods.
Time Frame
4 weeks baseline, 4 weeks treatment
Title
Mean Percentage of Bowel Movements Which Were Incontinent
Description
Values were averaged over 4 week baseline and 4 week treatment periods.
Time Frame
4 weeks baseline, 4 weeks treatment
Title
Mean Severity of Fecal Incontinence
Description
The Fecal Incontinence Severity Index was used to compute the severity of fecal incontinence (FI). 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 could range from 0 (no symptoms) to 61 (very frequent FI). Values were computed from pre- and post- treatment questionnaires.
Time Frame
4 weeks baseline, 4 weeks treatment
Title
Impact of Fecal Incontinence on Baseline Quality of Life
Description
Scores were computed from a pre-treatment questionnaire, the Fecal Incontinence Quality of Life Scale. This scale is composed of a total of 29 items; these items form four scales: Lifestyle (10 items) Coping/Behavior (9 items), Depression/Self Perception (7 items), and Embarrassment (3 items).
Scales range from 1 to 4; with a 1 indicating a lower functional status of quality of life. Scales scores are the average (mean) response to all items in the scale (that is, add the responses to all questions in a scale together and then divide by the number of items in the scale, adjusting for missing values).
Time Frame
4 weeks baseline
Title
Impact of Fecal Incontinence on Post-Treatment Quality of Life
Description
Scores were computed from a post-treatment questionnaire, the Fecal Incontinence Quality of Life Scale. This scale is composed of a total of 29 items; these items form four scales: Lifestyle (10 items) Coping/Behavior (9 items), Depression/Self Perception (7 items), and Embarrassment (3 items).
Scales range from 1 to 4; with a 1 indicating a lower functional status of quality of life. Scales scores are the average (mean) response to all items in the scale (that is, add the responses to all questions in a scale together and then divide by the number of items in the scale, adjusting for missing values).
Time Frame
after 4 weeks treatment
Title
Satisfaction With Treatment
Description
This parameter was determined by a 100 mm visual analog scale, with possible scores ranging from 0 = "Not satisfied at all (no relief of symptoms)" to 100 = "Completely satisfied (symptoms resolved)." The parameter was computed from weekly diaries. Scores were averaged over the 4 week baseline period and the 4 week treatment periods.
Time Frame
4 weeks baseline, 4 week treatment
Title
Percentage of Bowel Movements Preceded by Rectal Urgency
Description
Rectal urgency is defined as a sudden, irresistible need to have a bowel movement. Scores were averaged over the 4 week baseline period and the 4 week treatment periods.
Time Frame
4 weeks baseline, 4 weeks treatment
Title
Percentage of Bowel Movements With Semi-formed and Loose Stools in Subjects With and Without Diarrhea
Description
The percentage of bowel movements with semi-formed and loose stools was defined as those with a score of 5-7 on the Bristol stool form scale.
Time Frame
4 weeks baseline, 4 weeks treatment
Title
Percentage of Bowel Movements With Semi-formed and Loose Stools Post-treatment Adjusted for Baseline
Description
The percentage of bowel movements with semi-formed and loose stools was defined as those with a score of 5-7 on the Bristol stool form scale. The "adjustment for baseline" was an analysis of covariance (ANCOVA) where the covariate was the baseline version of the endpoint.
Time Frame
4 weeks treatment
Title
Percentage of Days With Fecal Incontinence (FI)
Time Frame
4 weeks baseline, 4 weeks treatment
Title
Percentage of Days With FI Post-treatment Adjusted for Baseline
Description
The "adjustment for baseline" was an analysis of covariance (ANCOVA) where the covariate was the baseline version of the endpoint.
Time Frame
4 weeks treatment
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Women aged 18-75 years with urge predominant FI, as defined by a validated questionnaire, for greater than or equal to 1 year duration will be eligible to participate
Absence of organic disease (i.e., ulcerative colitis, cancer) as evidenced by colonoscopy, or barium enema and sigmoidoscopy within the last 3 years
Exclusion Criteria:
History of clinically significant cardiovascular or pulmonary disease or EKG abnormalities within the last 6 months [i.e., atrial flutter or fibrillation, sinus tachycardia (> 110/minute) or bradycardia (< 45 beats/minute), or prolonged corrected QT (QTc) interval (> 460 msec)
Current or past history of rectal cancer, scleroderma, inflammatory bowel disease, congenital anorectal abnormalities, greater than or equal to Grade 2 rectal prolapse, history of rectal resection or pelvic irradiation
Neurological disorders - Spinal cord injuries, dementia (Mini-mental status score <20/25), multiple sclerosis, Parkinson's disease, peripheral neuropathy
Conditions precluding safe use of clonidine, i.e., symptomatic hypotension, or systolic blood pressure of <100 mm Hg on initial screening visit
Pregnant or nursing women
Severe diarrhea during the run in phase defined as greater than 6 liquid stools daily (Bristol 6 or 7)
Medications: Absolute - opioid analgesics, anticholinergic drugs [low doses of tricyclic antidepressants, e.g., nortriptyline (up to 50 mg/day) or amitriptyline (up to 25 mg/day) will be permitted provided they were begun 3 months prior to the screening period]
Medications: Relative - other antihypertensive agents (i.e., if there is concern about synergistic effects and hypotension)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adil E Bharucha, M.D.
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
23891925
Citation
Bharucha AE, Fletcher JG, Camilleri M, Edge J, Carlson P, Zinsmeister AR. Effects of clonidine in women with fecal incontinence. Clin Gastroenterol Hepatol. 2014 May;12(5):843-851.e2; quiz e44. doi: 10.1016/j.cgh.2013.06.035. Epub 2013 Jul 23.
Results Reference
derived
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A Placebo-Controlled Study of Clonidine for Fecal Incontinence.
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