Clinical Trial: A Within Subjects Comparison of Two Antegrade Flushing Regimens in Children

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Within Subjects Comparison of Two Antegrade Flushing Regimens in Children

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 or 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; 2) compare which solution given at the best dose takes the least amount of time to clear the colon of stool, has the least side effects, and is the most effective in preventing stool accidents; and 3) to determine if administration of either of the ACE flushing solution affects colon health and the bacteria in the colon.

Detailed Summary: 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 disrupt the gut microbial ecosystem, causing dysbiosis and immune dysfunction. The effects of ACE administration on colonic microbiome and mucosal immunity have not been investigated. This pilot study will compare a high volume normal saline (NS) flush and a low volume USP glycerin flush. The primary aims of the study are to compare which solution, given at an optimal dose and frequency, is delivered in the least amount of time, with fewer side effects, while promoting the higher degree of fecal continence and quality of life, and to determine if administration of antegrade enema solution through an appendicostomy/cecostomy affects gut microbiota.
Sponsor: Nemours Children's Clinic

Current Primary Outcome:

  • Fecal Soiling - Quantitative Count [ Time Frame: Data collection will start following consent and procedural training and will be collected daily from day 1 for the duration of the study, an expected average of 20 weeks ]
    Fecal soiling will be defined as non-toilet elimination, which will be 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 investigator will calculate episodes of fecal soiling per week
  • Fecal Soiling - Frequency and Volume Score [ Time Frame: Data collection will start following consent and procedural training and will be collected daily from day 1 for the duration of the study, an expected average of 20 weeks ]

    Document the severity of the accident and the estimated time of each accident. Documentation of timing and level of soiling will be tracked and documented by the parent/child as direct event recording. Scoring will be completed by the parent using the guidelines explicated it the following table.

    Table - Level of Soiling

    1. No soiling
    2. One smear per week
    3. Two smears per week
    4. >2 smears or one moderate volume accident per week that would be insufficient in volume to be visible through clothing if the child wears regular underwear

    5. any large volume accident that would be visible through clothing if the child wears regular underwear

      Original Primary Outcome: Same as current

      Current Secondary Outcome:

      • Basic Metabolic Panel [ Time Frame: Estimated collection dates include a baseline sample (week 1), following each dose response phase (weeks 6 and 10), and at the completion of the first two treatment effectiveness phases (weeks 14 and 18) for a total of 5 samples ]
        Serum Electrolytes
      • Stool for Calprotectin [ Time Frame: Estimated collection dates include a baseline sample (week 1), following each dose response phase (weeks 6 and 10), and at the completion of the first two treatment effectiveness phases (weeks 14 and 18) for a total of 5 samples ]
        Used as a measure of colonic mucosal health
      • Frequency and Severity of Abdominal Pain [ Time Frame: Data collection will start following consent and procedural training and will be collected daily from day 1 for the duration of the study, an expected average of 20 weeks ]
        Frequency and severity of abdominal pain will be recorded daily and measured using the Wong-Baker Faces Pain Rating Scale (WBFPRS) as the age-appropriate visual analog scale
      • Gut Microbiome Composition [ Time Frame: Estimated collection dates include a baseline sample (week 1), following each dose response phase (weeks 6 and 10), and at the completion of the first two treatment effectiveness phases (weeks 14 and 18) for a total of 5 samples ]
        Utilization of molecular techniques for identification of 16SrRNA gene sequence in stool samples to identify and quantify phylogenetic groups
      • Quality of Life [ Time Frame: Estimated timing of QOL completion includes at baseline (week 1) and at the completion of each flush effectiveness phase (weeks 14 and 18) for a total of 3 measures ]
        Child and parental perception of quality of life will be measured using the Fecal Incontinence and Constipation Quality of Life Measure in Children with Spinal Bifida (FICQOL).The FICQOL is a 51 item questionnaire with established validity and reliability in families of children with spina bifida who are incontinent for stool. This instrument measures aspects of daily living significantly impacted by fecal incontinence. Of the 51 items, four address subject and family demographics. The remaining 47 items are divided into seven groupings that include bowel program, diet, symptoms, travel and socialization, family relationships, caregiver support and emotional impact, and financial impact
      • Flush Administration Time [ Time Frame: Data collection will start with the first flush administered following discharge from the hospital (estimated to begin in week three) and will be collected with every subsequent flush through completion of the study, an expected average of 20 weeks ]
        Administration time in minutes per flush will be defined as the time at which the tubing connected to the bag or syringe holding the flush solution is unclamped and the cecostomy fluid starts to infuse into the patient to the time the infusion is completed (no more fluid left in the bag/syringe or tubing). Flush administration time will be measured using duration per occurrence direct observational recording completed by the parent or child.
      • Total Procedural Time [ Time Frame: Data collection will start with the first flush administered following discharge from the hospital (estimated to begin in week three) and will be collected with every subsequent flush through completion of the study, an expected average of 20 weeks ]
        The total procedural time is defined as the time the flush starts to infuse into the subject and ends following passage of stool when the child has sat on the commode for 5 minutes with no additional stool passage. Total procedural time will be measured using duration per occurrence direct observational recording completed by the parent or child.
      • Flush volume [ Time Frame: Data collection will start with the first flush administered following discharge from the hospital (estimated to begin in week three) and will be collected with every subsequent flush through completion of the study, an expected average of 20 weeks ]
        Volume will be measured and recorded by the parent or child using a graduated cylinder with each flush and calculated by the investigator in mL/kg using the weight obtained at the clinic visit preceding each effectiveness phase change.
      • Flush Side Effects [ Time Frame: Data collection will start with the first flush administered following discharge from the hospital (estimated to begin in week three) and will be collected with every subsequent flush through completion of the study, an expected average of 20 weeks ]
        Flush side effects will be measured using the Wong-Baker FACES Pain Rating Scale (WBFPRS). The WBFPRS has undergone extensive testing, is preferred by children, and has well established psychometrics in the pediatric population. The scale ranges from 0 (very happy without pain) to 5 (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. The WBFPRS will be used to evaluate the presence and severity of flush side effects, including a

        Original Secondary Outcome: Same as current

        Information By: Nemours Children's Clinic

        Dates:
        Date Received: April 27, 2015
        Date Started: November 2015
        Date Completion: August 2017
        Last Updated: April 27, 2016
        Last Verified: April 2016