CAPABLe Trial.

At 24 wks, loperamide and biofeedback did not provide a clinically important or statistically significant improvement in FI severity vs placebo or education, and combination therapy produced only small additional benefits while increasing constipation.

Question

In pts with bothersome FI and normal stool consistency, does loperamide +/- anal sphincter exercises with anorectal manometry-assisted biofeedback, compared with placebo +/- educational pamphlet, improve FI severity at 24 weeks?

DESIGN

• Population: N=300, mean ~64yo, with at least monthly FI for ≥3 months, Bristol stool types 2-6 (no severe diarrhea or constipation), negative colon cancer screening.

• Intervention:

  • PO Loperamide 2 mg/day with dose titration up to 8 mg/day based on symptom control and side effects, plus the NIDDK FI education pamphlet.

  • Anal sphincter exercises with anorectal manometry-assisted biofeedback: 6 structured sessions over 12 wks (strength + sensory/urge training) plus home exercises and the NIDDK FI education pamphlet

• Comparison:

  • Oral placebo with education pamphlet.

  • Education pamphlet alone (no biofeedback).

  • 4 arms - placebo+education, placebo+biofeedback, loperamide+education, loperamide+biofeedback.

Outcomes

At 24 wks, loperamide and biofeedback did not provide a clinically important or statistically significant improvement in FI severity vs placebo or education, and combination therapy produced only small additional benefits while increasing constipation.

• Primary outcome: Change in FI severity (St Mark’s/Vaizey score, baseline ~14):

  • Loperamide vs placebo: mean change −6.2 vs −4.7 points; model-estimated difference −1.5 (p = 0.12)

  • Biofeedback vs education: mean change −5.8 vs −5.1; difference −0.7 (p = 0.47)

  • Combination (loperamide+biofeedback) vs placebo+biofeedback: difference −1.9 (p = 0.09)

  • Combination (loperamide+biofeedback) vs loperamide+education: difference −1.1 (p = 0.33)

• Secondary efficacy and safety (selected):

  • Patient global improvement (PGI-I “a little/much/very much better” at 24 w):

    • loperamide 87% vs placebo 80% (adj OR 1.2, 95% CI 1.0-1.5, p = 0.10)

    • *biofeedback 88.7% vs education 78.0% (adj OR 1.3, 95% CI 1.0-1.6, p = 0.046)

  • Constipation: much more frequent with loperamide.

    • *38% (loperamide+education) and 51% (loperamide+biofeedback) vs 12% (placebo+education) and 23% (placebo+biofeedback) (p < 0.001 across all).

    • Any AE

      • *84% loperamide+biofeedback vs 74%, 70%, 62% in other arms (p = 0.04)

      • serious AEs similar between groups (6-11%, p = 0.62).

quiz

1. What is the primary mechanism by which loperamide reduces fecal incontinence episodes in patients with normal stool consistency?
A) Inhibition of chloride secretion in the colon via CFTR blockade
B) Stimulation of μ-opioid receptors in the gut to slow transit and increase internal anal sphincter tone
C) Direct activation of pelvic floor striated muscle fibers
D) Increased colonic absorption of bile acids

2. During biofeedback therapy for fecal incontinence, which physiologic function is most directly targeted to improve continence?
A) Increasing colonic transit speed
B) Enhancing relaxation of the internal anal sphincter
C) Strengthening external anal sphincter contraction and improving rectal sensory discrimination
D) Reducing rectal compliance