A Placebo-Controlled Study of Clonidine for Fecal Incontinence.

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Adil Bharucha, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00884832
First received: April 17, 2009
Last updated: January 20, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Fecal Incontinence
Drug: Clonidine
Drug: Placebo
Phase 2

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Mean Fecal Incontinence and Constipation Assessment (FICA) Score [ Time Frame: 4 weeks baseline, 4 weeks treatment ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Mean Number of Days With Fecal Incontinence [ Time Frame: 4 weeks baseline, 4 weeks treatment ] [ Designated as safety issue: No ]
    Values were averaged over 4 week baseline and 4 week treatment periods.

  • Mean Number of Fecal Incontinence Episodes [ Time Frame: 4 weeks baseline, 4 weeks treatment ] [ Designated as safety issue: No ]
    Values were averaged over 4 week baseline and 4 week treatment periods.

  • Mean Percentage of Bowel Movements Which Were Incontinent [ Time Frame: 4 weeks baseline, 4 weeks treatment ] [ Designated as safety issue: No ]
    Values were averaged over 4 week baseline and 4 week treatment periods.

  • Mean Severity of Fecal Incontinence [ Time Frame: 4 weeks baseline, 4 weeks treatment ] [ Designated as safety issue: No ]
    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.

  • Impact of Fecal Incontinence on Baseline Quality of Life [ Time Frame: 4 weeks baseline ] [ Designated as safety issue: No ]

    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).


  • Impact of Fecal Incontinence on Post-Treatment Quality of Life [ Time Frame: after 4 weeks treatment ] [ Designated as safety issue: No ]

    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).


  • Satisfaction With Treatment [ Time Frame: 4 weeks baseline, 4 week treatment ] [ Designated as safety issue: No ]
    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.

  • Percentage of Bowel Movements Preceded by Rectal Urgency [ Time Frame: 4 weeks baseline, 4 weeks treatment ] [ Designated as safety issue: No ]
    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.

  • Percentage of Bowel Movements With Semi-formed and Loose Stools in Subjects With and Without Diarrhea [ Time Frame: 4 weeks baseline, 4 weeks treatment ] [ Designated as safety issue: No ]
    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.

  • Percentage of Bowel Movements With Semi-formed and Loose Stools Post-treatment Adjusted for Baseline [ Time Frame: 4 weeks treatment ] [ Designated as safety issue: No ]
    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.

  • Percentage of Days With Fecal Incontinence (FI) [ Time Frame: 4 weeks baseline, 4 weeks treatment ] [ Designated as safety issue: No ]
  • Percentage of Days With FI Post-treatment Adjusted for Baseline [ Time Frame: 4 weeks treatment ] [ Designated as safety issue: No ]
    The "adjustment for baseline" was an analysis of covariance (ANCOVA) where the covariate was the baseline version of the endpoint.


Enrollment: 44
Study Start Date: October 2008
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Kapvay
  • Nexiclon
  • Catapres
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.

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00884832

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Adil E Bharucha, M.D. Mayo Clinic
  More Information

No publications provided by Mayo Clinic

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Adil Bharucha, PI, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00884832     History of Changes
Other Study ID Numbers: 08-005892, R01DK078924, UL1RR024150
Study First Received: April 17, 2009
Results First Received: October 16, 2013
Last Updated: January 20, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
fecal incontinence
stool leakage
incontinence
FI
Urge predominant fecal incontinence

Additional relevant MeSH terms:
Fecal Incontinence
Rectal Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Clonidine
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 22, 2014