Clinical trial NCT00884832: A Placebo-Controlled Study of Clonidine for Fecal Incontinence.
Official title: A Placebo-Controlled Study of Clonidine for Fecal Incontinence.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fecal Incontinence
Keywords: fecal incontinence
stool leakage
incontinence
FI
Urge predominant fecal incontinence
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: National Center for Research Resources (NCRR)
First posted: 2009-04-21
Enrollment: 44
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Mean Fecal Incontinence and Constipation Assessment (FICA) Score
timeFrame: 4 weeks baseline, 4 weeks treatment
Secondary outcomes:
measure: Mean Number of Days With Fecal Incontinence
timeFrame: 4 weeks baseline, 4 weeks treatment
measure: Mean Number of Fecal Incontinence Episodes
timeFrame: 4 weeks baseline, 4 weeks treatment
measure: Mean Percentage of Bowel Movements Which Were Incontinent
timeFrame: 4 weeks baseline, 4 weeks treatment
measure: Mean Severity of Fecal Incontinence
timeFrame: 4 weeks baseline, 4 weeks treatment
measure: Impact of Fecal Incontinence on Baseline Quality of Life
timeFrame: 4 weeks baseline
measure: Impact of Fecal Incontinence on Post-Treatment Quality of Life
timeFrame: after 4 weeks treatment
measure: Satisfaction With Treatment
timeFrame: 4 weeks baseline, 4 week treatment
measure: Percentage of Bowel Movements Preceded by Rectal Urgency
timeFrame: 4 weeks baseline, 4 weeks treatment
measure: Percentage of Bowel Movements With Semi-formed and Loose Stools in Subjects With and Without Diarrhea
timeFrame: 4 weeks baseline, 4 weeks treatment
measure: Percentage of Bowel Movements With Semi-formed and Loose Stools Post-treatment Adjusted for Baseline
timeFrame: 4 weeks treatment
measure: Percentage of Days With Fecal Incontinence (FI)
timeFrame: 4 weeks baseline, 4 weeks treatment
measure: Percentage of Days With FI Post-treatment Adjusted for Baseline
timeFrame: 4 weeks treatment
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Adil E Bharucha, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.