A Placebo-Controlled Study of Clonidine for Fecal Incontinence.
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Fecal Incontinence |
Drug: Clonidine Drug: Placebo Drug: Atropine Drug: Normal saline |
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. |
- 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 ]
| 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 |
Drug: 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 |
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.
|
| Experimental: IV Atropine |
Drug: 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.
|
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. 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.
Eligibility| Ages Eligible for Study: | 18 Years to 75 Years |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Women aged 18-75 years with urge predominant FI, as defined by a validated questionnaire, for 1 year duration will be eligible to participate 20
- 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 QTc interval (> 460 msec)
- Current or past history of rectal cancer, scleroderma, inflammatory bowel disease, congenital anorectal abnormalities, 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 (upto 50 mg/day) or amitriptyline (upto 25 mg/day) will be permitted provided they were begun 3 months prior to the screening period]
- Relative - other antihypertensive agents (i.e. if there is concern about synergistic effects and hypotension)
Contacts and Locations More Information
No publications provided
| Responsible Party: | Adil E. Bharucha, M.D., Mayo Clinic, Rochester |
| ClinicalTrials.gov Identifier: | NCT00884832 History of Changes |
| Other Study ID Numbers: | 08-005892 |
| Study First Received: | April 17, 2009 |
| Last Updated: | November 2, 2012 |
| 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 Atropine Clonidine Adjuvants, Anesthesia Central Nervous System Agents Therapeutic Uses Pharmacologic Actions Anti-Arrhythmia Agents Cardiovascular Agents Bronchodilator Agents Autonomic Agents |
Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Asthmatic Agents Respiratory System Agents Mydriatics Parasympatholytics Muscarinic Antagonists Cholinergic Antagonists Cholinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Antihypertensive Agents Sympatholytics Adrenergic alpha-2 Receptor Agonists Adrenergic alpha-Agonists |
ClinicalTrials.gov processed this record on May 19, 2013