A Within Subjects Comparison of Two Antegrade Flushing Regimens in Children
Overview
- Phase
- Phase 4
- Intervention
- Dose Response - NS and USP Glycerin - First Intervention
- Conditions
- Fecal Incontinence
- Sponsor
- Nemours Children's Clinic
- Enrollment
- 5
- Locations
- 1
- Primary Endpoint
- Fecal Soiling - Number of Participants That Gained and Maintained Continence on Each Flushing Regimen
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
Kim Jarczyk
Retired. Non-associate Emeritus
Nemours Children's Clinic
Eligibility Criteria
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.
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. -
Arms & Interventions
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.
Intervention: Dose Response - NS and USP Glycerin - First Intervention
NS and USP Glycerin - Effectiveness - 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.
Intervention: Effectiveness - NS and USP Glycerin - Second Intervention
Outcomes
Primary Outcomes
Fecal Soiling - Number of Participants That Gained and Maintained Continence on Each Flushing Regimen
Time Frame: 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
Time Frame: 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 Outcomes
- 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 Volume(Data for analysis was collected from the last flush of the NS and USP Glycerin dosing phase of the study)
- 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)
- 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)
- Cramping With Flush(Data analysis was completed on data obtained during the last flush in both the NS and USP Glycerin 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.)