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Fecal IncontinencePhase 4NCT02435069

A Within Subjects Comparison of Two Antegrade Flushing Regimens in Children

A Phase 4 study testing Dose Response - NS and USP Glycerin - First Intervention and Effectiveness - NS and USP Glycerin - Second Intervention in people with Fecal Incontinence and Neurogenic Bowel, run by Nemours Children's Clinic at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 3 to 12 years
Conditions the study is for
Fecal Incontinence, Neurogenic Bowel
What is being tested?
Dose Response - NS and USP Glycerin - First Intervention and Effectiveness - NS and USP Glycerin - Second Intervention
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited States
Study dates
9 Feb 2016to 30 Mar 2018
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 12 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.

Who cannot join

  • 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. -

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Nemours Children's Specialty Clinic

    Jacksonville, Florida, 32207

Other trials in United States

About this study

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.

Read the 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.

Being tested
Dose Response - NS and USP Glycerin - First Intervention, Effectiveness - NS and USP Glycerin - Second Intervention
Keywords
cecostomy, appendicostomy
Medical subject headings
Fecal Incontinence, Neurogenic Bowel

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dose Response - NS and USP Glycerin - First InterventionDrug

    Also called 0.9% sodium chloride solution, Glycerol, Glycerin

    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.

  • Effectiveness - NS and USP Glycerin - Second InterventionDrug

    Also called 0.9% sodium chloride solution, Glycerol, Glycerin

    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.

Study groups in NCT02435069
Study groupRoleWhat they receive
Pre-operative Baseline PhaseNo interventionBaseline 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.
Dose Response - NS and USP Glycerin - First InterventionExperimentalInitial 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.
Receives: Drug: Dose Response - NS and USP Glycerin - First Intervention
NS and USP Glycerin - Effectiveness - Second InterventionExperimentalTo 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.
Receives: Drug: Effectiveness - NS and USP Glycerin - Second Intervention

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Fecal Soiling - Number of Participants That Gained and Maintained Continence on Each Flushing Regimen

    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.

    Measured: 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.

  2. Fecal Soiling - Quantitative Count Detailing the Number of Episodes of Fecal Incontinence Per Day on NS and USP Glycerin

    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%).

    Measured: 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.

Secondary outcomes (6)
  1. NS and USP Glycerin Flush Solution Dosing Frequency Necessary to Achieve Continence

    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.

    Measured: 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

  2. Flush Volume

    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.

    Measured: Data for analysis was collected from the last flush of the NS and USP Glycerin dosing phase of the study

  3. Number of Participants With Any Electrolyte Abnormality

    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.

    Measured: 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

  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

    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.

    Measured: 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

  5. Cramping With Flush

    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.

    Measured: Data analysis was completed on data obtained during the last flush in both the NS and USP Glycerin dosing phase

  6. Number of Participants Experiencing Vagal Symptoms With Flush

    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.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 May 2015 (estimated)
  2. Study start9 Feb 2016
  3. Primary completion28 Mar 2017
  4. Study completion30 Mar 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02435069
Sponsor's protocol ID
ksj-1
Status last verified
Aug 2019
First submitted
27 Apr 2015
Last updated
28 Aug 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Aksnes G, Diseth TH, Helseth A, Edwin B, Stange M, Aafos G, Emblem R. Appendicostomy for antegrade enema: effects on somatic and psychosocial functioning in children with myelomeningocele. Pediatrics. 2002 Mar;109(3):484-9. doi: 10.1542/peds.109.3.484.

    PubMed 11875145
  • Andersson RE, Olaison G, Tysk C, Ekbom A. Appendectomy is followed by increased risk of Crohn's disease. Gastroenterology. 2003 Jan;124(1):40-6. doi: 10.1053/gast.2003.50021.

    PubMed 12512028
  • Aspirot A, Fernandez S, Di Lorenzo C, Skaggs B, Mousa H. Antegrade enemas for defecation disorders: do they improve the colonic motility? J Pediatr Surg. 2009 Aug;44(8):1575-80. doi: 10.1016/j.jpedsurg.2008.11.061.

    PubMed 19635308
  • Bani-Hani AH, Cain MP, King S, Rink RC. Tap water irrigation and additives to optimize success with the Malone antegrade continence enema: the Indiana University algorithm. J Urol. 2008 Oct;180(4 Suppl):1757-60; discussion 1760. doi: 10.1016/j.juro.2008.04.074. Epub 2008 Aug 21.

    PubMed 18721951
  • Balter M. Taking stock of the human microbiome and disease. Science. 2012 Jun 8;336(6086):1246-7. doi: 10.1126/science.336.6086.1246. Epub 2012 Jun 6. No abstract available.

    PubMed 22674333
  • Bazar KA, Lee PY, Joon Yun A. An "eye" in the gut: the appendix as a sentinel sensory organ of the immune intelligence network. Med Hypotheses. 2004;63(4):752-8. doi: 10.1016/j.mehy.2004.04.008.

    PubMed 15325028
  • Becmeur F, Demarche M, Lacreuse I, Molinaro F, Kauffmann I, Moog R, Donnars F, Rebeuh J. Cecostomy button for antegrade enemas: survey of 29 patients. J Pediatr Surg. 2008 Oct;43(10):1853-7. doi: 10.1016/j.jpedsurg.2008.03.043.

    PubMed 18926220
  • Biglan A, Ary D, Wagenaar AC. The value of interrupted time-series experiments for community intervention research. Prev Sci. 2000 Mar;1(1):31-49. doi: 10.1023/a:1010024016308.

    PubMed 11507793
  • Chertow GM, Brady HR. Hyponatraemia from tap-water enema. Lancet. 1994 Sep 10;344(8924):748. doi: 10.1016/s0140-6736(94)92236-5. No abstract available.

    PubMed 7915790
  • Chow, S., & Liu, J. (2014). Design and analysis of clinical trials: Concepts and methodologies (3rd ed.). Hoboken, NJ: John Wiley & Sons.

  • Chu DI, Balsara ZR, Routh JC, Ross SS, Wiener JS. Experience with glycerin for antegrade continence enema in patients with neurogenic bowel. J Urol. 2013 Feb;189(2):690-3. doi: 10.1016/j.juro.2012.08.209. Epub 2012 Oct 8.

    PubMed 22986031
  • Curry JI, Osborne A, Malone PS. The MACE procedure: experience in the United Kingdom. J Pediatr Surg. 1999 Feb;34(2):338-40. doi: 10.1016/s0022-3468(99)90204-x.

    PubMed 10052818
  • Dasso JF, Howell MD. Neonatal appendectomy impairs mucosal immunity in rabbits. Cell Immunol. 1997 Nov 25;182(1):29-37. doi: 10.1006/cimm.1997.1216.

    PubMed 9427807
  • Dey R, Ferguson C, Kenny SE, Shankar KR, Coldicutt P, Baillie CT, Lamont GL, Lloyd DA, Losty PD, Turnock RR. After the honeymoon--medium-term outcome of antegrade continence enema procedure. J Pediatr Surg. 2003 Jan;38(1):65-8; discussion 65-8. doi: 10.1053/jpsu.2003.50012.

    PubMed 12592621
  • Dolejs SC, Smith JK Jr, Sheplock J, Croffie JM, Rescorla FJ. Contemporary short- and long-term outcomes in patients with unremitting constipation and fecal incontinence treated with an antegrade continence enema. J Pediatr Surg. 2017 Jan;52(1):79-83. doi: 10.1016/j.jpedsurg.2016.10.022. Epub 2016 Oct 27.

    PubMed 27817835

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dose Response - NS and USP Glycerin - First Intervention and Effectiveness - NS and USP Glycerin - Second Intervention in people with Fecal Incontinence and Neurogenic Bowel, run by Nemours Children's Clinic at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02435069, which also lists 69 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2019.

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