A Placebo-Controlled Study of Clonidine for Fecal Incontinence.

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.

Study Overview

• Status: Completed
• Conditions: Fecal Incontinence
• Intervention / Treatment: Drug: Clonidine; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Clonidine; Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.; Other Names: Catapres; Kapvay; Nexiclon
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.	Drug: 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Center for Research Resources (NCRR)

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (ACTUAL): August 1, 2012
• Study Completion (ACTUAL): August 1, 2012

Study Registration Dates

• First Submitted: April 17, 2009
• First Submitted That Met QC Criteria: April 20, 2009
• First Posted (ESTIMATE): April 21, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): March 6, 2014
• Last Update Submitted That Met QC Criteria: January 20, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: incontinence; fecal incontinence; FI; stool leakage; Urge predominant fecal incontinence
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Fecal Incontinence; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympatholytics; Clonidine
• Other Study ID Numbers: 08-005892; UL1RR024150 (U.S. NIH Grant/Contract); R01DK078924 (U.S. NIH Grant/Contract)