Clinical trial NCT02008565: Controlling Anal Incontinence by Performing Anal Exercises With Biofeedback or Loperamide (CAPABLe)
Official title: Controlling Anal Incontinence by Performing Anal Exercises With Biofeedback or Loperamide (CAPABLe): a Randomized Placebo Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fecal Incontinence
Keywords: Fecal incontinence
Loperamide
anal exercises
biofeedback
Lead sponsor: NICHD Pelvic Floor Disorders Network
Sponsor class: NETWORK
Collaborators: name: The Cleveland Clinic
name: University of Alabama at Birmingham
name: University of California, San Diego
name: Duke University
name: National Institutes of Health (NIH)
name: University of New Mexico
name: Women and Infants Hospital of Rhode Island
name: RTI International
name: University of Pennsylvania
name: University of Pittsburgh
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2013-12-11
Enrollment: 300
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The study is a multi-center, randomized, placebo controlled trial with participants randomized into one of four groups:

1. placebo/usual care (educational pamphlet)
2. loperamide/usual care (educational pamphlet)
3. placebo/anal exercises with biofeedback
4. loperamide/anal exercises with biofeedback

The primary outcome, change from baseline in St. Marks (Vaizey) Score at 24 weeks, will be compared between treatment groups using linear regression.

Detailed description: The goals of this trial are to compare the use of loperamide to oral placebo and to compare the use of anal sphincter exercise training with biofeedback to usual care (educational pamphlet) in the treatment of women suffering from fecal incontinence (FI). We will test the following null hypotheses:

1. there is no difference in outcomes between women randomized to loperamide and women randomized to oral placebo for treatment of FI;
2. there is no difference in outcomes between women randomized to anal sphincter exercises with biofeedback and women randomized to usual care (educational pamphlet) for FI treatment;
3. there is no difference between women randomized to both treatments together and women randomized to either FI treatment alone; and
4. there is no correlation between anal manometry measurements and digital anal squeeze strength or measures of FI severity and bother.

A supplemental study, Stool Metabolome and Microbiome in Women with Fecal Incontinence in CAPABLe, will evaluate the stool metabolome and microbiome in women with fecal incontinence and unaffected age matched controls.

Eligibility criteria: Inclusion Criteria:

* Age ≥18 years
* Fecal incontinence defined as any uncontrolled loss of liquid or solid fecal material that occurs at least monthly over the last 3 months that is bothersome enough to desire treatment

Exclusion Criteria:

* Stool consistency over the last 3 months that includes items 1 or 7 based on the Bristol Stool form scale
* Current or past diagnosis of colorectal or anal malignancy
* Diagnosis of inflammatory bowel disease
* Current or history of rectovaginal fistula or cloacal defect
* Rectal prolapse (mucosal or full thickness)
* Prior removal or diversion of any portion of colon or rectum
* Prior pelvic floor or abdominal radiation
* Refusal or inability to provide written consent
* Inability to conduct telephone interviews conducted in English or Spanish
* Fecal impaction by exam
* Untreated pelvic organ prolapse beyond the hymen; Patients with prolapse beyond the hymen who are currently using a pessary are eligible
* Incontinence only to flatus
* Has taken any loperamide (Imodium®) or diphenoxylate plus atropine (Lomotil®) in the last 30 days
* Previously received and failed treatment of fecal incontinence using loperamide (Imodium®) or diphenoxylate plus atropine (Lomotil®) over the last 3 months
* Current supervised anal sphincter exercise/pelvic floor muscle training with biofeedback
* Previously received and failed treatment of fecal incontinence using supervised anal sphincter exercise/pelvic floor muscle training with biofeedback
* Previous allergy or intolerance to loperamide
* Pregnant, nursing, or planning to become pregnant before the end of the study follow-up period.
* Childbirth within the last 3 months
* Currently taking anti-retroviral drugs
* Neurological disorders known to affect continence, including spinal cord injury, advanced multiple sclerosis or Parkinson's disease and debilitating stroke
* Known diagnosis of hepatic impairment
* Chronic abdominal pain in the absence of diarrhea

Primary outcomes:
measure: Change From Baseline St. Mark's (Vaizey) Score
timeFrame: 12 and 24 weeks
Secondary outcomes:
measure: Change in Quality of Life on Colorectal-Anal Distress Inventory (CRADI)
timeFrame: 12 and 24 weeks
measure: Change in Colorectal-Anal Subscale of the Pelvic Floor Impact Questionnaire Short Form (CRAIQ) Score
timeFrame: 12 and 24 weeks
measure: Change From Baseline Accident-free Days at 12 and 24 Weeks
timeFrame: 12 and 24 weeks
measure: Change From Baseline Pad-change Leaks Per Day at 12 and 24 Weeks
timeFrame: 12 and 24 weeks
measure: Change From Baseline Pad-change Leaks Per Week at 12 and 24 Weeks
timeFrame: 12 and 24 weeks
measure: Change From Baseline Total Number of Leaks Per Day at 12 and 24 Weeks
timeFrame: 12 and 24 weeks
measure: Change in Fecal Incontinence Severity Index (FISI) Score
timeFrame: 12 and 24 weeks
measure: Participants With Improvement in Patient Global Impression of Improvement (PGI-I) Score
timeFrame: 12 and 24 Weeks
measure: Change From Baseline Resting Anal Canal Pressures (mm of Hg) at 2 cm, 1 cm, and 0 cm Insertion at 12 and 24 Weeks
timeFrame: 12 and 24 weeks
measure: Change From Baseline Volume of Air (mL) at First Sensation for Perception of Rectal Distention at 12 and 24 Weeks
timeFrame: 12 and 24 weeks
measure: Change From Baseline Volume of Air (mL) at Urge to Defecate at 12 and 24 Weeks
timeFrame: 12 and 24 weeks
measure: Change From Baseline Maximum Anal Pressures During Squeeze With the Catheter at the HPZ at 12 and 24 Weeks
timeFrame: 12 and 24 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: La Jolla
country: United States
facility: University of California at San Diego
state: California
city: San Diego
country: United States
facility: Kaiser San Diego
state: California
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Brown/Women and Infants Hospital of Rhode Island
state: Rhode Island
Study officials:
affiliation: The Cleveland Clinic
name: J E Jelovsek
role: STUDY_CHAIR
affiliation: The Cleveland Clinic
name: Matthew Barber
role: STUDY_CHAIR
References:
citation: Jelovsek JE, Markland AD, Whitehead WE, Barber MD, Newman DK, Rogers RG, Dyer K, Visco AG, Sutkin G, Zyczynski HM, Carper B, Meikle SF, Sung VW, Gantz MG; National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Controlling faecal incontinence in women by performing anal exercises with biofeedback or loperamide: a randomised clinical trial. Lancet Gastroenterol Hepatol. 2019 Sep;4(9):698-710. doi: 10.1016/S2468-1253(19)30193-1. Epub 2019 Jul 15.