A Within Subjects Comparison of Two Antegrade Flushing Regimens in Children

Phase 4

Completed

• Conditions: Fecal Incontinence; Neurogenic Bowel
• Interventions: Drug: Dose Response - NS and USP Glycerin - First Intervention; Drug: Effectiveness - NS and USP Glycerin - Second Intervention

• Registration Number: NCT02435069
• Lead Sponsor: Nemours Children's Clinic

Brief Summary

There is a surgical procedure to help children with intractable fecal incontinence gain continence for stool through construction of a tube that connects the abdominal wall to the colon near or through the appendix. This tube allows easy administration of enema solution into the first part of the colon. Putting enema solution through that tube into the colon is called an antegrade continence enema (ACE) and has been shown to work well in helping some but not all children prevent stool accidents. The purpose of this study is to compare a large volume ACE flush using a salt water solution called normal saline with a small volume ACE flush using liquid glycerin. The aims of this study are to: 1) find the most effective dose and flush frequency of each solution needed to prevent stool accidents; 2) compare which solution given at the best dose has the least side effects and 3) to determine if administration of either of the ACE flushing solutions causes electrolyte abnormalities or affects colon health.

Detailed Description

Fecal incontinence past the time of toilet training is devastating to affected children. Antegrade continence enema (ACE) therapy administered through a catheterizable stoma surgically placed in the cecum has helped children with intractable fecal incontinence attain continence for stool. There are a number of retrospective studies demonstrating the variable effectiveness rates of ACE therapy. This variability may be due to what is used to flush. There are no prospective trials evaluating the effectiveness of different flushing regimens. The catheterizable stoma used for the antegrade administration of enema solution is frequently made by bringing the appendix out through the abdominal wall or by placing a skin-level device (button) in to the cecum. ACE therapy administration through the appendix or into the cecum has the potential to cause colonic dysfunction. The effects of ACE administration on colonic mucosal health has not been investigated. This pilot study will compare a high volume normal saline (NS) flush and a low volume United States Pharmacopeia (USP) glycerin flush. The primary aims of the study are to compare which solution, given at an optimal dose and frequency, is associated with fewer side effects, while promoting the higher degree of fecal continence, and to determine if antegrade enema solution administration through an appendicostomy/cecostomy causes electrolyte abnormalities or affects gut health.

Study Timeline

• Study First Submitted: 2015-04-27
• Study First Submitted QC: 2015-04-30
• Study First Posted: 2015-05-06
• Study Start: 2016-02-09
• Primary Completion: 2017-03-28
• Study Completion: 2018-03-30
• Results First Submitted: 2019-07-11
• Status Verified: 2019-08
• Results First Submitted QC: 2019-08-08
• Results First Posted: 2019-08-22
• Last Update Submitted: 2019-08-23
• Last Update Posted: 2019-08-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

• This study will involve twelve children ages 3 to 12 years recruited from subspecialty clinics at Nemours Children's Subspecialty Care and the Pediatric Spinal Defects Clinic in Jacksonville, Florida.
• Children will be selected by purposive sampling and will include those who are scheduled to have an ACE stoma and will require regular antegrade enema administration to maintain continence.

Read More

Exclusion Criteria

• Excluded will be children with preexisting electrolyte imbalance, chronic high rectal tone, quadriplegia, renal or cardiac disease, or those who require prophylactic antibiotics, cannot communicate, or have significant cognitive delay that would interfere with their ability to fully participate in the study.
• Parents must have English language competency and be willing and able to participate in administration or oversight of the flushing regimen and data collection for a minimum of 20 consecutive weeks. -

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Dose Response - NS and USP Glycerin - First Intervention	Dose Response - NS and USP Glycerin - First Intervention	Initial flush used NS or USP Glycerin randomized to treatment sequence. The starting volume and administration frequency for NS was 10mL/kg and glycerin 20 mL administered every other day. The NS dose was titrated in 10 mL increments to achieve continence so as not to exceed 500 mL daily for a child under five years of age and 1000 mL daily for a child over 5 years of age. USP Glycerin was titrated in 5 mL increments so as not to exceed 50 mL daily. For side effects greater than Wong Bailey Faces Pain Rating Scale (WBFPRS) level 4, NS was decreased by 2.5 mL/kg to the lowest dose of 5 mL/kg daily. USP Glycerin was decreased in 5 mL increments to the lowest dose of 5 mL daily. If the maximum dose did not result in continence, if the dose necessary to minimize side effects resulted in fecal soiling, or if there were side effects greater than WBFPRS level 4 at the lowest dose of administration, the child was be trialed on the alternate therapy and then dropped from the study.
NS and USP Glycerin - Effectiveness - Second Intervention	Effectiveness - NS and USP Glycerin - Second Intervention	To prevent statistical bias from subject loss due to treatment failure, each child was randomized to a second treatment sequence once they achieved continence on optimal dosing with minimal side effects.This arm evaluated the long term effectiveness of NS and glycerin at optimal dose and administration frequency for 4 weeks and served as comparison between flush solutions. The study concluded with the child being placed back on 2 weeks of the initial flush in the randomized sequence.

Primary Outcome Measures

Name	Time	Method
Fecal Soiling - Number of Participants That Gained and Maintained Continence on Each Flushing Regimen	Data collection started following consent and procedural training and was collected daily from day 1 for the duration of the study, an average of 135 days.	Fecal soiling was defined as non-toilet elimination, which was tracked and documented by the parent/child as direct event recording and tallied as the number of pairs of underwear/protective undergarments soiled with stool per day. The purpose of this outcome measure was to document the number of individuals who gained continence on NS and USP glycerin. Descriptive statistics was limited to percentage of total participants who achieved continence on each flushing regimen. Data was calculated on the last data point in the final phase for both the NS and USP glycerin flush.
Fecal Soiling - Quantitative Count Detailing the Number of Episodes of Fecal Incontinence Per Day on NS and USP Glycerin	Data collection began following consent and procedural training and was collected daily from day 1 for the duration of the study, an average of 135 days.	Fecal soiling was defined as non-toilet elimination, which was tracked and documented by the parent/child as direct event recording and tallied as the number of pairs of underwear/protective undergarments soiled with stool per day. Descriptive statistics included mean and standard deviation. Inferential statistical analysis was accomplished using a two-tailed, two-sample pooled variance t test with a significance level set at 0.05, calculated on the data from the last day of the completed NS and USP Glycerin phases of the study. Power analysis conducted using data from this study with α = 0.5, power of .80, correlation between two means of .598, and effect size of 1.554 estimated a sample size of 11 would be needed to minimize the risk of a Type II error to (20%).

Secondary Outcome Measures

Name	Time	Method
NS and USP Glycerin Flush Solution Dosing Frequency Necessary to Achieve Continence	Frequency of administration data was collected as the total number of flushes recieved over the last three days of each dosing phase for both NS and USP Glycerin and recorded as either daily (1), every other day (2), or every third day	Flush administration frequency necessary to achieve continence was recorded as a single measure per subject per flush solution obtained as the number of flushes in the last three days of each dosing phase and recorded as either daily (1), every other day (2), or every third day (3). The larger the value, the less frequent the flush, the better the clinical outcome. Dosing frequency was measured using direct observational recording completed by the parent or child. Descriptive analysis included mean, and standard deviation. Inferential statistical analysis was accomplished using a two-tailed, two-sample pooled variance t test with a significance level set at 0.05. Descriptive and inferential statistics were calculated on the data from the last day of the completed NS and USP Glycerin phases of the study.
Flush Volume	Data for analysis was collected from the last flush of the NS and USP Glycerin dosing phase of the study	Flush volume was measured in mL/flush using a graduated cylinder and recorded by the parent or child with each flush and later calculated in mL/kg. Data derived from the last flush of the completed dosing phase of both NS and USP Glycerin were used to calculate flush volume. Descriptive analysis included mean, median, range, and standard deviation. Reported data excludes subjects who failed to gain and maintain continence on either flushing regimen.
Number of Participants With Any Electrolyte Abnormality	Collection dates included a baseline sample (week 1) and at the completion of the dosing trail for both NS and USP glycerin for a total of 3 samples	Evaluated impact of NS and USP Glycerin antegrade flush on serum electrolytes using a blood test called a Basic Metabolic Panel. Data analysis limited to percentage of subjects demonstrating any electrolyte abnormality on NS or USP glycerin.
Change in Stool Calprotectin Levels Assessed Through Comparing Levels Obtained Following Completion of NS and USP Glycerin Dosing Phases With the Baseline Value For Each Subject	Collection dates included a baseline sample (week 1) and at the completion of the dosing trail for both NS and USP glycerin for a total of 3 samples	Stool calprotectin was used to evaluate the impact of NS and USP Glycerin antegrade flush on colonic health. Calprotectin levels were obtained at baseline and following completion of the NS and USP Glycerin dosing phase of the study. Descriptive data analysis included mean and standard deviation for each flush regimen. Inferential statistical analysis was accomplished using a two-tailed, two-sample pooled variance t test with a significance level set at 0.05. Both descriptive and inferential data analysis was calculated on the difference in calprotectin levels between samples obtained at baseline and samples obtained following the completion of the NS and USP Glycerin flush (value at completion of dosing phase - baseline value). The assumption was the length of each dosing phase was sufficient to achieve a credible active washout period and therefore levels obtained at the end of a phase reflected flushing regimen effects colonic health regardless of flush order.
Cramping With Flush	Data analysis was completed on data obtained during the last flush in both the NS and USP Glycerin dosing phase	Cramping with flush was measured using the Wong Baker Faces Pain Rating Scale (WBFPRS). The WBFPRS has undergone extensive testing and has well established psychometrics in the pediatric population. The scale ranges from 0 (very happy without pain) to 10 (the worse pain imaginable). Each pain level is associated with a facial expression. The child is asked to choose the face that best describes his/her level of discomfort (ordinal data). The parent was instructed to call if the child had flushing regimen-associated discomfort greater than a 4 on the WBFPRS. Documentation of pain severity was completed by the parent and child on a data-collection form at the time of occurrence. Descriptive statistics including mean and standard deviation. Inferential statistical analysis was accomplished using a two-tailed, two-sample pooled variance t test with a significance level set at 0.05. Descriptive and inferential statistics were calculated on the last data point in the dosing phase.
Number of Participants Experiencing Vagal Symptoms With Flush	Data collection started with the first flush administered following discharge from the hospital and was collected with every subsequent flush through completion of the study, an average of 115 days.	Vagal symptoms including nausea, vomiting, sweating, dizziness, and pallor were noted by the parent. The parent was instructed to call if the child had any vagal symptoms. Documentation of any vagal symptoms was completed by the parent and child on a data-collection form at the time of occurrence. Data was analyzed as a percentage of subjects experiencing vagal symptoms during flush with NS and USP glycerin.

Trial Locations

Locations (1)

Nemours Children's Specialty Clinic; 🇺🇸 Jacksonville, Florida, United States