Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03811821 |
| Other study ID # |
18-004651 |
| Secondary ID |
1U01DK115575-01 |
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 1, 2019 |
| Est. completion date |
December 31, 2025 |
Study information
| Verified date |
June 2024 |
| Source |
Mayo Clinic |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Patients with severe fecal incontinence (FI), defined as two or more episodes of staining,
solid or liquid FI per week, and who meet the inclusion criteria for Injection of Solesta
(INJ; an inert bulking agent), or Biofeedback (BIO) will be enrolled. The baseline rate of FI
will be assessed using a 2-week daily stool diary. All participants will initially be
enrolled into a 4-week trial of Enhanced Medical Management (EMM; education, pelvic floor
exercises, and use of non-prescription drugs to normalize stool consistency). Those who
demonstrate at least a 75% reduction in FI frequency will not be randomized to one of the two
treatment groups but will be followed-up for two years. Those not showing a 75% reduction in
FI frequency will be randomized to BIO or INJ and will be evaluated three months later with
respect to efficacy for reducing the frequency of fecal incontinence, safety of the
interventions, and cost of providing care. All participants who experience a 75% decrease in
FI after three months of treatment, compared to baseline, will be followed-up for a further
21 months, for a total of 24 months from the time of treatment initiation. To assess the
long-term response to treatment, those who improve less than 75% in FI episodes will be
offered an additional treatment with either the treatment to which they were not randomized
or sacral nerve stimulation (SNS). Anorectal manometry and Magnetic Evoked Potentials will be
used to subtype the physiological basis for FI. Quality of life and psychological factors
will be used to assess outcomes.
Description:
This is an unmasked, multisite, randomized, parallel group study comparing the effectiveness
of two treatments [BIO and INJ] for moderate to severe FI:
1. Baseline: Participants will keep a daily symptom diary for two weeks to (a) document
that they meet the minimum frequency required for inclusion in the study and (b) provide
a reference value for assessing treatment response at the end of EMM and at 3, 6, 12,
and 24 months follow-up points.
2. EMM: All participants meeting inclusion criteria will first be treated with EMM for 4
weeks. The key components of treatment are patient education about the basic
physiological mechanisms for defecation, diet and medication to normalize stool
consistency, and pelvic floor exercises taught by printed instructions. Additional goals
of the EMM protocol are (a) to ensure that participants randomized to BIO or INJ meet
the accepted criteria for these treatments by failing to respond to EMM, and (b) to
document the efficacy and the durability of systematically applied, optimized EMM.
Patients who are responders to EMM will be followed up 3 months later; those who remain
responders will be continued on EMM and followed for the remaining 24 months of the
study. However, those who are no longer responders to this conservative treatment after
3 months will be invited to be randomized to BIO or INJ and all outcome measures will be
assessed at 3 months from initiation of the treatment arm to which they are randomized.
They will be pooled with other patients randomly assigned to the same treatment for the
primary analyses and will be assessed at 6 months.
3. Randomly assigned treatment: Each participant who fails the EMM will be randomly
assigned to BIO or INJ and treated as follows:
- BIO will consist of 5-6 one-hour training sessions spaced at weekly intervals.
These will occur in the first 5-6 weeks of treatment. Treatment approaches will
include strength training in all participants, sensory training for participants
with hyposensitivity, and/or urge-resistance training for participants with
hypersensitivity to the sensations caused by rectal distention. Home exercises will
be assigned to participants to practice these skills, and these will be guided by a
brochure.
- INJ will include a preparation for treatment and a treatment visit. The preparation
will involve prophylactic antibiotics for the day of the procedure and minimal
restrictions on food intake. On the day of the procedure, a physician will inject 1
ml of dextranomer into each of 4 quadrants of the rectum proximal to the dentate
line. Ten seconds will be allowed to pass before the injection needle is withdrawn
to minimize drainage of the dextranomer. The participant will be scheduled to
return in 6 weeks for possible repeat injection of a second 4 ml of dextranomer. At
this second appointment, if FI has improved by 75% or more compared to baseline,
the participant will be continued without a second injection. However, if the rate
of FI is greater than 75% of baseline, the participant will be offered a second
injection of dextranomer.
4. Combination therapy: The primary assessment of efficacy is at 3 months following the
first treatment visit completed, and participants who have not achieved at least a 75%
reduction in FI frequency compared to baseline will be classified as treatment failures;
they will be invited to choose the treatment to which they were not randomized or SNS as
an adjunctive treatment for the remaining months of the study. One reason for this is to
increase the likelihood that participant will consent to be randomized despite possibly
having a priori preferences for one of the two treatments. Thus, the participants who
add a second treatment and continue to be monitored up to 24 months will constitute a
pragmatic clinical trial (i.e., the study design for these participants going forward
emulates the clinical situation in which patients who have an unsatisfactory response to
a treatment are offered a new treatment or an ancillary treatment).
5. Long-term follow-up: An intention-to-treat analysis of efficacy will be carried out at
6, 12 and 24 months. For these analyses, all participants randomized to treatment will
be included in the analysis. All treatments will continue to be active. The bulking
agents injected in the INJ treatment will remain in place. For BIO, participants will be
encouraged to continue to practice pelvic floor exercises and enhanced awareness of
rectal sensations following the initial training period. Participants who withdraw from
the study or who fail treatment at 3 months will be evaluated as treatment failures in
follow-up analyses of efficacy. Data will be collected from participants who add an
alternative treatment at 3 months, but these data will not be considered in this
analysis. Safety data will be collected at every visit. Participants who are responders
at 3 months will continue to monitor symptoms for an additional 21 months (2 years
total) whereas participants who are non-responders at 3 months will be retained as
treatment failures in the long-term analysis of the comparative effectiveness of the BIO
and INJ treatments. For longitudinal assessments of safety, cost, and secondary outcomes
such as quality of life and FI severity scales, statistical models will include data
from follow up time points through 24 months.
6. Adjust for Expectation of Benefit: In a trial comparing behavioral and medical therapy,
participants cannot be masked. The validated Credibility/Expectancy Questionnaire was
developed to assess the patient's expectation of benefit after initial exposure to
treatment and was used in previous studies to determine whether there is equipoise
between the active and control conditions in behavioral treatment trials.
7. Characterization of Enhanced Medical Treatment - Durability of improvement and
predictors of response: The primary purpose of treating all participants with an EMM
run-in is to be able to exclude participants who do not require more costly
interventions. However, the investigators will take advantage of the opportunity
provided by this run-in study to identify predictors of response to EMM and to assess
the durability of improvements. EMM will not be "usual care" but will follow a written
protocol that is intended to optimize EMM, which is why this is labelled enhanced
medical management. Participants who are treatment responders at the end of the EMM
run-in will be scheduled for 3-month follow-up, and those who are no longer treatment
responders at 3 months follow-up will be offered an opportunity to be randomized to one
of the 3 treatments at this point. However, those who remain responders to EMM at 3
months follow-up will continue to be followed for an additional 21 months. All
participants, regardless of their outcomes at the end of EMM, will be encouraged to
continue using the treatment approaches learned during the EMM phase.
Each participant will be studied for 24-27 months after completing the month of EMM and the
anticipated duration of the study is 4.5 years from first enrollment to completion of the
last participant. Approximately 285 adult participants, both male and female, will be
recruited for EMM to ensure that 194 participants who did not benefit from EMM will be
available for randomization to the two treatment arms (97 per treatment arm). The
participants may be referred by clinicians or may respond to posted advertisements about the
study.
