A Placebo-Controlled Study of Clonidine for Fecal Incontinence.

Condition(s) targeted: Fecal Incontinence

Intervention: Clonidine (Drug); Placebo (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Mayo Clinic

Official(s) and/or principal investigator(s):
Adil E Bharucha, M.D., Principal Investigator, Affiliation: Mayo Clinic

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Mean Fecal Incontinence and Constipation Assessment (FICA) Score

Secondary outcome:

Mean Number of Days With Fecal Incontinence

Mean Number of Fecal Incontinence Episodes

Mean Percentage of Bowel Movements Which Were Incontinent

Mean Severity of Fecal Incontinence

Impact of Fecal Incontinence on Baseline Quality of Life

Impact of Fecal Incontinence on Post-Treatment Quality of Life

Satisfaction With Treatment

Percentage of Bowel Movements Preceded by Rectal Urgency

Percentage of Bowel Movements With Semi-formed and Loose Stools in Subjects With and Without Diarrhea

Percentage of Bowel Movements With Semi-formed and Loose Stools Post-treatment Adjusted for Baseline

Percentage of Days With Fecal Incontinence (FI)

Percentage of Days With FI Post-treatment Adjusted for Baseline

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.

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Female.

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)

Mayo Clinic, Rochester, Minnesota 55905, United States

Starting date: October 2008
Last updated: January 20, 2014