A Placebo-Controlled Study of Clonidine for Fecal Incontinence.
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 investigators are also trying to understand if genes predispose to fecal incontinence and whether the effects of a medication, atropine, on rectal functions can predict the response to clonidine. Atropine is also an FDA-approved drug for treating high blood pressure, but not for treating incontinence and rectal functions.
Drug: Normal saline
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Placebo-Controlled Study of Clonidine for Fecal Incontinence.|
- The primary objective end-points are rectal capacity, rectal sensory thresholds for the desire to defecate (expressed as pressure and volume), urgency, and severity of FI (FICA score). [ Time Frame: 4-week ] [ Designated as safety issue: Yes ]
- The secondary objective endpoints are number of episodes of FI per week, proportion of incontinent days per week, adequate relief of FI, rectal urgency (proportion of bowel movements preceded by urgency), impact of FI on quality of life. [ Time Frame: 4-week ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2008|
|Study Completion Date:||August 2012|
|Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
|Experimental: Oral Clonidine||
Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.
|Placebo Comparator: Oral Placebo||
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.
|Experimental: IV Atropine||
During the anorectal study at 4 weeks, subjects randomized to atropine will receive a bolus of 0.015 mg/kg intravenously followed by an infusion at the rate of 0.003 mg/kg/hr after 30 minutes to ensure stable plasma levels throughout the study.
|Placebo Comparator: IV Placebo||
Drug: Normal saline
During the anorectal study at 4 weeks, subjects randomized to placebo will receive a bolus of normal saline 0.015 mg/kg intravenously followed by an infusion at the rate of 0.003 mg/kg/hr after 30 minutes to ensure stable plasma levels throughout the study.
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. Intravenous atropine restored rectal capacity 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 IBS. Therefore, we now propose a placebo-controlled study of clonidine for FI. Our hypotheses, which pertain to women with urge GI, are that (i) clonidine will improve fecal continence, increase rectal capacity and reduce rectal sensation to a greater extent than placebo in women, (ii) atropine (i.v.) will increase rectal capacity and compliance and reduce rectal sensation, and (iii) the effects of atropine, will predict the effects of clonidine, on fecal continence and rectal sensorimotor functions. 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, (ii) evaluate the acute effects of atropine on anorectal sensorimotor functions, and (iii) assess if these acute effects of atropine can predict the subjective and objective response to oral clonidine. 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. During the pre-treatment anorectal study, the effects of atropine and saline on anorectal functions will be assessed. The primary outcome variables are the FI severity score, which provides an overall assessment of symptoms, while the primary objective outcome variables are rectal capacity and rectal sensory thresholds for desire to defecate and urgency.