Neuromodulation for Accidental Bowel Leakage

Study Overview
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Brief Summary
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This study is a multi-center, randomized clinical trial of women with refractory accidental bowel leakage (ABL) symptoms who have failed to achieve satisfactory symptom control from 2 first-line treatments for ABL: supervised pelvic muscle training (PMT) and constipating medication. The purpose of this study is to compare percutaneous tibial nerve stimulation (PTNS) to a validated sham to determine if PTNS is effective for the treatment of fecal incontinence (FI) in women. The investigators will test the null hypothesis that change from baseline in St. Mark's (Vaizey) score after 12 weeks of stimulation is not significantly different in women with symptomatic ABL receiving PTNS treatments compared to women receiving sham PTNS treatments.

Detailed Description
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The overarching goal of this randomized clinical trial is to determine if PTNS is more effective than sham PTNS for the treatment of FI in women after 12 weeks of treatment and 1 year after initiating treatment. This is a two-part trial with a Run-In Phase prior to randomization. The trial has the following primary aim: To determine whether the change from baseline in St. Mark's (Vaizey) score in women with symptomatic ABL undergoing PTNS differs from sham after 12 weeks of stimulation. Additional secondary aims include: To compare changes from baseline in self-reported functional outcomes after 12 weekly stimulation sessions in both PTNS and sham groups in Part 1. To determine whether symptom relief amongst study responders can be sustained for one year with maintenance treatments in Part II. To determine the impact of completing a bowel diary and receiving education on FI on symptom severity. To determine the ability of the PFDN ABL phone app bowel diary to detect changes from baseline in fecal incontinence episodes recorded to after 12 weeks of stimulation sessions. To determine the association between St. Mark's score and both fat and fiber intake alone and in combination.

Official Title
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Neuromodulation for Accidental Bowel Leakage

Conditions
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Fecal Incontinence, Bowel Incontinence

Intervention / Treatment
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* Device: ES-130


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women ≥ 18 years of age FI symptoms ≥ 3 months Baseline St. Mark's score of ≥ 12 Attended ≥ 2 supervised PMT for ABL Intolerance, unwillingness, or inadequate response to constipating medications Current negative colon cancer screening based on the USPSTF's recommendation for colorectal cancer screening (2016) Exclusion Criteria: Previous PTNS treatment History of uncontrolled diarrhea in the past 3 months (usual or most common stool type over the preceding 3 months of 7 on the Bristol Stool Form Scale) History of severe constipation in the past 3 months (usual or most common stool type over the preceding 3 months of 1 on the Bristol Stool Form Scale) History of inflammatory bowel disease (includes Crohn's disease and ulcerative colitis, but does not include irritable bowel disease) Unrepaired rectovaginal fistula/chronic 4th degree laceration Full thickness rectal prolapse History of congenital anorectal malformation History of bowel resection surgery for any indication Minor anal procedures within 6 months for treatment of ABL (injection of bulking agent or radiofrequency energy) or ligation of hemorrhoids Prior pelvic or abdominal radiation Diagnosis of cancer of the descending colon or anus Diagnosis of cancer in the region where the PTNS or sham needles or surface electrodes would be placed Pacemaker, implantable defibrillator Current use of Interstim sacral nerve stimulator or TENS in the pelvic region, back, or legs Clinically significant neurological disorders known to affect anal continence Coagulopathy Severe peripheral edema preventing accurate placement of PTNS needles Chronic swollen, infected, inflamed skin or skin eruptions (e.g., phlebitis, thrombophlebitis, varicose veins) in the region where the PTNS or sham needles or surface electrodes would be placed Metal implant in foot/toes near TENS electrode location Marked sensory deficit (numbness) of feet or ankles in the region where the PTNS or sham needles or surface electrodes would be placed Childbirth within the last 3 months Pregnant or planning to become pregnant during the study duration 1 year; a urine pregnancy test will be performed and must be negative by the first intervention visit if the participant is of childbearing potential Unwilling to use acceptable form of contraceptive if the participant is of childbearing potential Participation in another intervention trial impacting bowel function Inability to provide informed consent, complete questionnaires independently, or to attend intervention sessions Unable or unwilling to complete the bowel diary in Run-In Phase (valid diary defined as data from ≥ 10 of 14 days with minimum of 3 consecutive days per week) Unwilling to download bowel diary app onto smartphone if the participant owns a smartphone Visual impairment prohibiting reading the paper diary, the smart phone screen Unable to speak, read, or write in English or Spanish at a basic level

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Percutaneous Tibial Nerve Stimulation (PTNS)<br>PTNS treatment entails insertion of a 36 gauge needle electrode at a 60 degree angle 3-4 cm deep towards the tibial nerve, approximately 5 cm or 3 finger breadths cephalad to the medial malleolus and posterior to the tibia. The PTNS grounding electrode, placed near the calcaneus and the needle electrode will be connected to the ES-130 device pulse generator. | Device: ES-130<br>* The ES-130 device will be used for the indication of Posterior Tibial Nerve Stimulation for the treatment of fecal incontinence using the FDA-approved protocol for treatment of urge urinary incontinence (UUI) in the PFDN NOTABLe study. There is no PTNS device cleared by the FDA for the indication of FI treatment; therefore, this is considered an investigational device.<br>|
| Sham Comparator: Validated Sham<br>Sham treatment will use the Streitberger acupuncture placebo needle in the same location as the needle electrode for PTNS. The sham uses an active gel surface electrode pad placed on the bottom of the foot just below the fifth (smallest) toe. This location is not part of the acupuncture nerve pathway connected to the bladder, pelvis or any major organs. Electrical current is delivered to this pad via a TENS unit resulting in sensory stimulation. | Device: ES-130<br>* The ES-130 device will be used for the indication of Posterior Tibial Nerve Stimulation for the treatment of fecal incontinence using the FDA-approved protocol for treatment of urge urinary incontinence (UUI) in the PFDN NOTABLe study. There is no PTNS device cleared by the FDA for the indication of FI treatment; therefore, this is considered an investigational device.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline St. Mark's (Vaizey) Score | The primary outcome measure is the change from baseline in St. Mark's (Vaizey) Score 12 weeks after treatment initiation to compare the outcomes of post-tibial nerve stimulation (PTNS) versus sham stimulation. The St. Mark's (Vaizey) score, published in 1999, is commonly used in clinical studies and reports and was based on the Jorge-Wexner score but added two further items for assessment: the use of constipating medication and the presence of fecal urgency. Minimum score is 0 = perfect continence; maximum score is 24 = totally incontinent. Change from baseline is calculated as Week [4, 8, or 12] Score minus the score at baseline. | 4, 8, and 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder to Treatment | Responder status is based on the primary chnage from St. Mark's Score. A responder is defined as any particpant with at least a 4 point reduction in score compared to their baseline score | 4, 8, and 12 Weeks | 
| Change From Baseline Number of Fecal Incontinence Events Per Week | Based on data collected from participant-completed diaries at baseline, 8, and 12 weeks, the outcome variable is computed as the difference in number of fecal incontinence episodes per week at 8 and 12 weeks and the number of fecal incontinence episodes at baseline. | 8 and 12 Weeks | 
| Change From Baseline Number of Urge Fecal Incontinence Events Per Week | Based on data collected from participant-completed diaries at baseline, 8, and 12 weeks, the outcome variable is computed as the difference in number of urge fecal incontinence episodes per week at 8 and 12 weeks and the number of urge fecal incontinence episodes at baseline. | 8 and 12 Weeks | 
| Change From Baseline Number of Bowel Movements Per Week | Based on data collected from participant-completed diaries at baseline, 8, and 12 weeks, the outcome variable is computed as the difference in number of bowel movements per week at 8 and 12 weeks and the number of bowel movements at baseline. | 8 and 12 Weeks | 
| Change From Baseline Number of Urge Bowel Movements Per Week | Based on data collected from participant-completed diaries at baseline, 8, and 12 weeks, the outcome variable is computed as the difference in number of urge bowel movements per week at 8 and 12 weeks and the number of urge bowel movements at baseline. | 8 and 12 Weeks | 
| Change From Baseline Number of Days Without Fecal Incontinence Episodes Per Week | Based on data collected from participant-completed diaries at baseline, 8, and 12 weeks, the outcome variable is computed as the difference in number of days without fecal incontinence episodes per week at 8 and 12 weeks and the number of days without fecal incontinence episodes at baseline. | 8 and 12 Weeks | 
| 50% Improvement in Fecal Incontinence Episodes Per Week | Based on data collected from participant-completed diaries at baseline, 8, and 12 weeks, the outcome is calculated as any participant with a 50% reduction in fecal incontinence episodes per week at 8 and 12 weeks compared to the fecal incontinence episodes at baseline | 8 and 12 Weeks | 
| 75% Improvement in Fecal Incontinence Episodes Per Week | Based on data collected from participant-completed diaries at baseline, 8, and 12 weeks, the outcome is calculated as any participant with a 75% reduction in fecal incontinence episodes per week at 8, and 12 weeks compared to the fecal incontinence episodes at baseline. | 8 and 12 Weeks | 
| Patient Global Impression-Improvement | The Patient Global Impression of Improvement (PGI-I) is a patient-reported measure of perceived improvement with treatment, as assessed on a scale of 1 (very much better) to 7 (very much worse). Included here are participants who had improvement as indicated by a rating of 1 (very much better) or 2 (much better) | 4, 8, and 12 Weeks |