A Placebo-Controlled Study of Clonidine for Fecal Incontinence.

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Placebo-Controlled Study of Clonidine for Fecal Incontinence.

Conditions
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Fecal Incontinence

Intervention / Treatment
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* Drug: Clonidine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

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 |
| --- | --- |
| Experimental: Oral Clonidine<br>Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks. | Drug: Clonidine<br>* Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.<br>* Other names: Catapres;|
| Placebo Comparator: Oral Placebo<br>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. | Drug: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 4 weeks baseline, 4 weeks treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Number of Days With Fecal Incontinence | Values were averaged over 4 week baseline and 4 week treatment periods. | 4 weeks baseline, 4 weeks treatment | 
| Mean Number of Fecal Incontinence Episodes | Values were averaged over 4 week baseline and 4 week treatment periods. | 4 weeks baseline, 4 weeks treatment | 
| Mean Percentage of Bowel Movements Which Were Incontinent | Values were averaged over 4 week baseline and 4 week treatment periods. | 4 weeks baseline, 4 weeks treatment | 
| 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. | 4 weeks baseline, 4 weeks treatment | 
| 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). | 4 weeks baseline | 
| 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). | after 4 weeks treatment | 
| 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. | 4 weeks baseline, 4 week treatment | 
| 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. | 4 weeks baseline, 4 weeks treatment | 
| 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. | 4 weeks baseline, 4 weeks treatment | 
| 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. | 4 weeks treatment | 
| Percentage of Days With Fecal Incontinence (FI) |  | 4 weeks baseline, 4 weeks treatment | 
| 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. | 4 weeks treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FI, fecal incontinence, stool leakage, incontinence, Urge predominant fecal incontinence