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A Within Subjects Comparison of Two Antegrade Flushing Regimens in Children

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ClinicalTrials.gov Identifier: NCT02435069
Recruitment Status : Completed
First Posted : May 6, 2015
Results First Posted : August 22, 2019
Last Update Posted : August 28, 2019
Sponsor:
Collaborator:
University of Florida
Information provided by (Responsible Party):
Kim Jarczyk, 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.

Condition or disease Intervention/treatment Phase
Fecal Incontinence Neurogenic Bowel Drug: Dose Response - NS and USP Glycerin - First Intervention Drug: Effectiveness - NS and USP Glycerin - Second Intervention Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: A Within Subjects Comparison of Two Antegrade Flushing Regimens in Children
Actual Study Start Date : February 9, 2016
Actual Primary Completion Date : March 28, 2017
Actual Study Completion Date : March 30, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bowel Movement
Drug Information available for: Glycerin

Arm Intervention/treatment
No Intervention: Pre-operative Baseline Phase
Baseline data including frequency and severity of fecal soiling and frequency and severity of abdominal pain were collected for a minimum of 2 weeks prior to surgical construction of the ACE stoma. Baseline stool calprotectin and serum electrolytes were collected in the baseline phase prior to initiation of the preoperative bowel prep. Pre-operative data served as the control.
Experimental: 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.
Drug: Dose Response - NS and USP Glycerin - First Intervention
This trial used a repeated measures, single subjects alternating treatments A-B-C-B'-C'-B1' withdrawal design in which all subjects were tested under all conditions and each subject acted as his or her own control. The subjects were randomly assigned to either normal saline or USP glycerin to control for order effects. Baseline data A served as the control and was obtained pre-operatively. The B-C arm evaluated dose-response relationship and was used to identify the minimum dosing volume and frequency of ACE administration of NS and USP Glycerin necessary to promote fecal continence. When the optimal dose as identified, the child continued on that dose for 2 weeks to insure treatment stability and effectiveness.
Other Name: 0.9% sodium chloride solution, Glycerol, Glycerin

Experimental: 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.
Drug: 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 have achieved continence with minimal side effects on optimal dosing The second phase B'-C'-B1' of the study compared the two regimens at optimal dose and administration frequency. This phase was used to confirm the effectiveness of NS and USP Glycerin at optimal dosing on continence and assess side effects.
Other Name: 0.9% sodium chloride solution, Glycerol, Glycerin




Primary Outcome Measures :
  1. 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.

  2. 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 Outcome Measures :
  1. NS and USP Glycerin Flush Solution Dosing Frequency Necessary to Achieve Continence [ Time Frame: 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.

  2. Flush Volume [ Time Frame: 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.

  3. Number of Participants With Any Electrolyte Abnormality [ Time Frame: 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.

  4. 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 [ Time Frame: 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.

  5. Cramping With Flush [ Time Frame: 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.

  6. Number of Participants Experiencing Vagal Symptoms With Flush [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02435069


Locations
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United States, Florida
Nemours Children's Specialty Clinic
Jacksonville, Florida, United States, 32207
Sponsors and Collaborators
Nemours Children's Clinic
University of Florida
Investigators
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Principal Investigator: Kimberly S Jarczyk, PhD Nemours Children's Specialty Care
  Study Documents (Full-Text)

Documents provided by Kim Jarczyk, Nemours Children's Clinic:
Publications of Results:
Jarczyk, K.S. (2017). A within subjects comparison of two antegrade flushing regimens in children. University of Florida, Gainesville, FL. UFE0051658

Other Publications:
Chow, S., & Liu, J. (2014). Design and analysis of clinical trials: Concepts and methodologies (3rd ed.). Hoboken, NJ: John Wiley & Sons.
Gast, D.L. (2010). Single subjects research methodology in behavioral sciences. New York, NY: Routledge,Taylor & Francis Group
Janosky, J.E., Leininger, S.L., Hoerger, M.P., & Libkuman, T.M. (2009). Single subjects designs in biomedicine. New York, NY: Springer Science + Business Media.
Jones, B., & Kenward, M.G. (2003). Design and analysis of cross-over trials (2nd ed.). Boca Raton, FL: Chapman & Hall/CRC.
Kazdin, A.E. (2011). Single-case research designs: Methods for clinical and applied settings (2nd ed.). New York, NY: Oxford University Press.
National Institutes of Health. (1998). Policy on inclusion of children as research subjects in clinical research. Bethesda, MD: National Institutes of Health.
Piantadosi, S. (2005). Clinical trials: A methodologic perspective (2nd ed.). Hoboken, NJ: John Wiley & Sons.
Polit, D.F. (2010). Statistical and data analysis for nursing research (2nd ed.). New York, NY: Pearson.
Portney, L.G., & Watkins, M.P. (2009). Foundations of clinical research: Applications to practice (3rd ed.). Upper Saddle River, NJ: Pearson Prentice Hall.
Rempher, K.J., & Silkman, C. (2007). How to appraise quantitative research articles. American Nurse Today, 2, 26-28.
Senn, S. (2002). Cross-over trials in clinical research (2nd ed.). West Sussex, England: John Wiley & Sons.
Shuster, J.J. (2007). Design and analysis of experiments. In W.T. Ambrosius (Ed.). Topics in biostatistics (pp. 235-259). Totowa, NJ: Humana Press.

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Responsible Party: Kim Jarczyk, Retired. Non-associate Emeritus, Nemours Children's Clinic
ClinicalTrials.gov Identifier: NCT02435069    
Other Study ID Numbers: ksj-1
First Posted: May 6, 2015    Key Record Dates
Results First Posted: August 22, 2019
Last Update Posted: August 28, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kim Jarczyk, Nemours Children's Clinic:
cecostomy
appendicostomy
Additional relevant MeSH terms:
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Fecal Incontinence
Neurogenic Bowel
Flushing
Rectal Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Skin Manifestations
Colonic Diseases, Functional
Colonic Diseases
Pharmaceutical Solutions
Glycerol
Cryoprotective Agents
Protective Agents
Physiological Effects of Drugs