Clinical trial NCT03543566: Bladder Antimuscarinic Medication and Accidental Bowel Leakage
Official title: Antimuscarinic Medication for Urgency Urinary Incontinence in Women With Dual Incontinence (Darifenacin for Treatment of Women With Dual Incontinence)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Urinary Incontinence, Urge
Fecal Incontinence
Keywords: antimuscarinic medication
medical management
dual incontinence
darifenacin
quality of life
bowel diary
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: Allergan
First posted: 2018-06-01
Enrollment: 32
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients presenting to UAB urogynecology and continence clinics

Brief summary: This observational research study will examine whether a medication known as darifenacin (Enablex ®) used for urgency urinary incontinence (UUI) also helps to improve fecal incontinence symptoms. Darifenacin is FDA approved for UUI, but is not FDA approved for fecal incontinence or specifically for dual incontinence (treatment of urinary incontinence and fecal incontinence at the same time). If participants are eligible for this study, they will have had symptoms of bothersome urgency urinary incontinence and fecal incontinence, and have decided to try medication for urgency urinary incontinence. Darifenacin (Enablex ®) is an oral medication which relaxes the bladder muscle to help prevent urgency urinary leakage. It is commonly used to treat overactive bladder and urgency urinary leakage. There is some evidence that this medication may also help with fecal incontinence by slowing the gut and preventing loose stools. Investigators are planning to enroll approximately 30 patients who have both UUI and fecal incontinence and who choose medical treatment as a part of their standard care.

Detailed description: Urgency urinary incontinence (UUI) and fecal incontinence (FI) are two highly prevalent pelvic floor disorders which negatively impact quality of life (QOL). Among women with urgency urinary incontinence (UUI), 8-20% also suffer from FI.

Initial management of both UUI and FI consists of behavioral therapies with or without pharmacologic management. First line management of FI includes diet, fluid and fiber intake adjustments (Grade A), antidiarrheal medication (Grade B) and exercises to strengthen and enhance awareness of the anal sphincter (Grade C). If symptoms fail to improve with these measures by 8-12 weeks, further investigations should be considered before moving to more invasive management options such as bulking agents, sphincterplasty or sacral nerve stimulation.

In addition to fiber and antidiarrheals, medications with antimuscarinic effects such as hyoscyamine and tricyclic antidepressants are often used in the treatment of FI and IBS-D. Antimuscarinic medications function in this setting by blockade of colonic muscarinic acetylcholine receptors causing smooth muscle relaxation, decreased gut motility and prolonged colon transit time.

In patients with overactive bladder (OAB) with UUI, anti-muscarinic medications or a β3-adrenoreceptor agonist medication can be added to behavioral therapy as first line to optimize symptom control and QOL (Gormley 2015). In patients being treated for UUI, constipation is often viewed as an unwanted side effect of antimuscarinic medications, with varying constipation rates observed among the different medications. Non-selective antimuscarinic medications such as fesoterodine (Toviaz ®) and tolterodine (Detrol ®) may be less likely to cause constipation, whereas newer M2 or M3-selective agents such as darifenacin (Enablex ®), solifencin (Vesicare®) or trospium (Sanctura ®) may be more constipating. Darifenacin is notable for the highest constipation rates- up to 15% for the 7.5mg dose, and up to 21% for the 15mg dose.

While there is no current evidence for one specific antimuscarinic medication use in patients suffering with dual incontinence (specifically UUI and FI), many providers use the more constipating antimuscarinic medications as treatment in this setting. Patients with loose-stool-predominant FI may benefit from the constipating side effects by slowed colonic transit time, firmer bowel movements and thereby improved bowel-related QOL. Only one study has previously examined the effect of antimuscarinic medication for OAB on bowel-related QOL. In this descriptive study, 90 patients who were treated with antimuscarinic medication for OAB were followed to measure change in ePAQ (electronic Personal Assessment Questionnaire) score. Investigators reported significant improvement in bowel-related QOL three to six months after treatment. Authors did not specify pre-treatment diagnoses, symptoms or details of the antimuscarinic treatment.

While anecdotally antimuscarinic medications are an effective first line medication in patients with dual incontinence, more evidence is needed. The goal of our study therefore, is to observe the effect of standard of care antimuscarinic therapy for UUI on fecal incontinence symptoms in women with dual incontinence. Investigators will compare patient reported fecal incontinence symptoms before and after treatment in women with dual incontinence who elect to undergo standard of care medical management for UUI with the antimuscarinic medication darifenacin.

Hypothesis: In patients with dual incontinence, treatment of urgency urinary incontinence with darifenacin 7.5mg will improve FI symptom severity at 8 weeks Primary Aim: To characterize change in FI symptom severity (change in Vaizey score) after darifenacin treatment in patients with dual incontinence at 8 weeks

Secondary Aims:

Secondary Aim #1: To characterize post-treatment change in FI frequency using 7-day bowel diaries, change in quality of life (change in Fecal Incontinence Quality of Life (FIQOL) total and subscale scores), and characterize treatment improvement using the Patient Global Impression of Improvement (PGI-I) measure Secondary Aim #2: To describe compliance and adverse effects of antimuscarinic medication in patients with dual incontinence.

Secondary Aim #3: To describe effect of antimuscarinic medication on OAB symptom bother and quality of life in patients with dual incontinence, using the OAB questionnaire short form (OAB-q SF)

Eligibility criteria: Inclusion Criteria:

* Women ≥18yrs presenting to UAB urogynecology and continence clinics with co-occurring UUI and FI
* Willing to complete all study related items

Exclusion Criteria:

* Severe constipation, fecal impaction or overflow fecal incontinence
* Inflammatory bowel disease, colorectal CA, spinal cord injury, multiple sclerosis, stroke, myasthenia gravis
* Infectious diarrhea
* Bothersome SUI (defined as "moderately" or greater bother on UDI-3)
* Patients planning to undergo surgery during study period
* Patients who are pregnant or intending to become pregnant during the study period
* Patients with contraindications to antimuscarinic medications (ie. closed angle glaucoma)
* Patients on unstable or changing dosage of fiber or narcotics in the past 14 days
* Patients taking more than 2mg/day of loperamide (patients taking more than 2mg will be required a 2 week washout period)
* Patients currently taking medication for urgency urinary incontinence (these patients will also require a 2 week washout period)
* Patients initiating care with a pelvic floor physical therapist during the study period

Primary outcomes:
measure: change in FI symptom severity
timeFrame: 8 weeks
Secondary outcomes:
measure: post-treatment change in FI frequency
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Kirklin Clinic
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Lindsay M Kissane, MD
role: PRINCIPAL_INVESTIGATOR
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