Clinical trial NCT02008565
Conditions: Fecal Incontinence
Keywords: Fecal incontinence Loperamide anal exercises biofeedback
Sponsor: NICHD Pelvic Floor Disorders Network
Start date: 2014-02-01; Completion date: 2016-05-01
Enrollment: 300 participants; Allocation: RANDOMIZED; Intervention model: FACTORIAL

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.

Arms: arm 1: Placebo and biofeedback intervention. Placebo doses range from 2mg every other day to 8mg per day. Capsules are taken by mouth once a day for 24 weeks.

Anal exercises with biofeedback intervention is a total of six sessions with trained personnel occurring every 2 weeks over a 12-week period. Sessions are held at the following study visits: baseline, 2, 4, 6, 9, and 12 week visits. arm 2: Loperamide and biofeedback intervention. Loperamide doses range from 2mg every other day to 8mg per day. Capsules are taken by mouth once a day for 24 weeks.

Anal exercises with biofeedback intervention is a total of six sessions with trained personnel occurring every 2 weeks over a 12-week period. Sessions are held at the following study visits: baseline, 2, 4, 6, 9, and 12 week visits. arm 3: Placebo and education (usual care). Placebo doses range from 2mg every other day to 8mg per day. Capsules are taken by mouth once a day for 24 weeks.

Participants receive education and a NIDDK Bowel Control Educational pamphlet. arm 4: Loperamide and education (usual care). Loperamide doses range from 2mg every other day to 8mg per day. Capsules are taken by mouth once a day for 24 weeks.

Participants receive education and a NIDDK Bowel Control Educational pamphlet.
Interventions: intervention 1: Loperamide intervention 2: Placebo intervention 3: Anal exercises with biofeedback intervention 4: Usual Care
Intervention descriptions: intervention 1: Participants randomized to the loperamide group will begin with 2mg of loperamide/day. The participant will be administered the Patient Global Symptom Control rating scale (PGSC) to determine dose escalation. Participants who report inadequate control of stool leakage on the PGSC will be instructed to increase the daily dose of loperamide by 2 mg up to a maximum of 8 mg per day (1-4 capsules). Bothersome adverse events and resulting dose reduction will be based exclusively on the result of the Patient Global Tolerability Scale (PGTS). The daily dose will be decreased by 2mg to a minimum of 2mg every other day. If a PGSC score indicates inadequate control of stool leakage combined with a PGTS score indicating bothersome side effects, the participant will discontinue the study medication. intervention 2: Participants randomized to the placebo arm will begin the a dose of one capsule per day and will be dose increased or dose decreased using the same algorithm described for the loperamide arm. intervention 3: Participants will receive a formal anal exercises training program that can be easily applied in an office setting with minimal participant burden. Participants will attend six anal exercises with biofeedback sessions with trained personnel over a 12-week period for the 24-week study. Sessions will include introduction, standard patient education, and exercises using anal manometry-assisted biofeedback introducing concepts such as shaping, generalization and termination. The protocol uses strength and sensory training including urge resistance training. During the final twelve weeks, participants will perform anal exercises on their own. The sessions with interventionists will occur every other week for 12 weeks (total 6 supervised sessions). intervention 4: Usual care consists of patients receiving an educational pamphlet on fecal incontinence created by the National Institute of Diabetes and Digestive and Kidney Diseases.

Protocol documents: