Fecal Incontinence Treatment Study (FIT Study)

ABSTRACT
This is an initial application for a U01 in response to PAR-15-067. This program announcement grew out of an
NIDDK Workshop held in 2013 to identify pathways for promoting research on fecal incontinence (FI).
Conference attendees identified gaps in knowledge and the best approaches to progress, and all identified
Biofeedback (BIO), Sacral Neural Stimulation (SNS), and Injections of bulking agents (INJ) in the perianal
space as treatments supported by controlled trials, but with no clear indication of which is most effective,
safest, and least costly. Outcome measures have been variable, and inclusion criteria have also differed. The
recommendation was to compare all 3 using the same paradigm. Aims: (1) Compare all 3 treatments on the
basis of efficacy, safety, and cost, as well as secondary outcome measures. (2) Identify physiological, clinical,
and psychosocial predictors of who will respond to each treatment. (3) Allow patients who do not respond to
the randomly assigned treatment to select a second treatment at 3 months. (4) Compare treatment
combinations to see which appears best (uncontrolled). (5) Assess the effects of enhanced Medical
Management (MM) on efficacy, safety, and cost (uncontrolled). (6) Compare the cost-effectiveness of BIO,
SNS, and INJ for FI throughout the two years. Methods: Select 567 patients appropriate to all treatments
including >2 per week solid or liquid FI. A treatment responder is someone with >75% reduction in FI
frequency. Primary assessment is 3 months after the beginning of randomized treatment. If patients are
responders, they will continue to be studied for 24 months, but if they fail to respond they will be offered
alternative treatment and followed. Secondary outcomes include the rate of responding with a 50% decrease in
FI, continence, changes on the Bristol Stool Severity scale, FI Quality of Life, and validated severity scales (FI
Severity Scale, St. Mark’s FI Severity Scale). Psychological outcomes include the PROMIS Anxiety-7,
Depression-8, and Self-Efficacy scales. Costs effectiveness analysis will be based on Quality Adjusted Life
Years. Moderators will include (1) physiological assessments (anal ultrasound, anorectal motility, and magnetic
evoked potentials); (2) a priori beliefs in treatments (Credibility/Expectancy Questionnaire), quality of life
(general and FI specific), sex, and type of FI (passive, urge). The 4 clinical site principal investigators (PIs) are
Adil Bharucha (Mayo Clinic), Satish Rao (University of Augusta in Georgia), Ann Lowry (Colon and Rectal
Surgery in Minneapolis), and William Whitehead (Chapel Hill, NC) – all senior PIs. The PI of the data
coordinating center (DCC) is Marie Gantz, also an experienced PI. This is a collaborative agreement with
NIDDK, and Frank Hamilton will participate in program management. A successful outcome will guide
treatment algorithms and reimbursement policies.