Evaluation of Fecal Microbiome Changes After Antegrade Continence Enema Placement and Initiation of Bowel Flush Regimen

This study will evaluate changes in the fecal microbiome in constipated pediatric patients before and after antegrade continence enema placement and initiation of antegrade enema flushes. Subjects will have their microbiome sequenced prior to placement by obtaining a fecal sample. Pre-antegrade continence enema placement results will be compared to fecal samples obtained at 0, 4, 8 months after placement of the antegrade continence enema and initiation of miralax or golytely flushes to look for changes in bacterial diversity.

Study Overview

• Status: Recruiting
• Conditions: Constipation
• Intervention / Treatment: Drug: PEG 3350; Drug: Glycerin; Drug: PEG-3350 with electrolytes

Detailed Description

This is a prospective, longitudinal study of children 2 -18 years of age who undergo a clinical Malone Antegrade Continence Enema (MACE) appendicostomy or cecostomy for treatment of chronic functional constipation as defined by the Rome IV criteria. Only patients with intact motility on colonic manometry (CMS) will be included. The antegrade enema flush medication regimen will be randomized in 1:1 ratio of PEG 3350 and PEG3350 with electrolytes. The study statistician will create a blocked randomization schedule which will be uploaded into REDCap. Glycerin and stimulant laxatives will be titrated as needed by a pediatric gastroenterologist in conjunction with the pediatric general surgery team. Neither patient nor providers will be blinded to laxative randomization as objective data in the form of microbiome composition is being evaluated.

Patients will have a pre-MACE placement stool sample obtained at time of colonic motility studies and repeat stool samples collected at 1 month, 4 months and 8 months post-MACE placement and initiation of antegrade enemas. Post-MACE samples will be submitted at standard follow-up appointments. All stool samples will be self-collected by patients. Samples will be collected with the OMNIgene GUT kit which provides stabilization of DNA at room temperature for up to 60 days. Once the sample is collected by the research team, sample tubes will be stored at -80 Celsius until all samples are collected and sent for sequencing. Pre-MACE stool samples will be collected while abstaining from osmotic laxative therapy for one week. If patients do not spontaneously pass stool during the week of osmotic laxative abstention, stool will be collected from the first bowel movement after pre-CMS bowel flush with PEG 3350 with or without electrolytes has been initiated. Data regarding if stool collection occurred before or after receiving PEG 3350 with or without electrolytes for CMS bowel flush will be recorded. Patients will perform daily flushes after MACE placement and post-MACE stool samples will be collected within the first 10 minutes of flush initiation.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Erik Andrewski, MD; Phone Number: 317-944-3774; Email: edandrew@iupui.edu
• Study Contact Backup: Name: Ann Klipsch, RN; Phone Number: 317-944-3774; Email: aeye@iu.edu

Study Locations

• United States
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Recruiting
      • IU North Hospital
      • Contact: Ann Klipsch, RN; Phone Number: 317-944-3774; Email: aeye@iu.edu
      • Contact: Erik Andrewski, MD; Phone Number: 317-944-3774; Email: edandrew@iu.edu
    • Indianapolis, Indiana, United States, 46224
      • Recruiting
      • Riley Hospital for Children
      • Contact: Erik Andrewski, MD; Phone Number: 317-944-3774; Email: edandrew@iupui.edu
      • Contact: Ann Klipsch, RN; Phone Number: 317-944-3774; Email: aeye@iu.edu
      • Principal Investigator: Kate Hawa, DO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Recalcitrant chronic functional constipation necessitating a MACE appendicostomy or cecostomy for treatment at Riley Hospital for Children
• Intact colonic motility as evidenced by CMS studies

Exclusion Criteria

• Underlying anatomic or pathologic etiology for constipation
• History of prior gastrointestinal surgery (excluding placement of G or GJ tubes)
• Underlying severe GI disease unrelated to the patient's chronic constipation
• Use within the past month of consent of probiotic supplements, prebiotic supplements or antibiotics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PEG 3350; Patients will receive PEG 3350 (miralax or generic equivalent) for their MACE flushes.	Drug: PEG 3350; The purpose of this study is to determine if a sustained change in the fecal microbiome occurs after prolonged use of an antegrade continence enema bowel flush regimen. Patients' microbiomes will be evaluated via 16s rRNA sequencing. PEG 3350 will be compared to PEG 3350 with electrolytes; Other Names: MiraLAX or generic equivalent; Drug: Glycerin; Glycerin will be given to patients based on standard of care, at the discretion of the pediatric gastroenterology and pediatric surgery teams. Glycerin administration will not be randomized. For secondary analysis, the microbiomes of those who have and have not received glycerin will be compared.
Experimental: PEG 3350 with electrolytes; Patients will receive PEG 3350 with electrolytes (Go-Lytely or generic equivalent) for their MACE flushes.	Drug: Glycerin; Glycerin will be given to patients based on standard of care, at the discretion of the pediatric gastroenterology and pediatric surgery teams. Glycerin administration will not be randomized. For secondary analysis, the microbiomes of those who have and have not received glycerin will be compared.; Drug: PEG-3350 with electrolytes; The purpose of this study is to determine if a sustained change in the fecal microbiome occurs after prolonged use of an antegrade continence enema bowel flush regimen. Patients' microbiomes will be evaluated via 16s rRNA sequencing. PEG 3350 will be compared to PEG 3350 with electrolytes; Other Names: GoLytely or generic equivalent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fecal Microbiome at 1 month	The purpose of this study is to determine if a sustained change in the fecal microbiome occurs after prolonged use of an antegrade continence enema bowel flush regimen. Patients' microbiomes will be evaluated via 16s rRNA sequencing	At baseline and 1 month post-MACE
Change in Fecal Microbiome at 4 months	The purpose of this study is to determine if a sustained change in the fecal microbiome occurs after prolonged use of an antegrade continence enema bowel flush regimen. Patients' microbiomes will be evaluated via 16s rRNA sequencing	At baseline and 4 months post-MACE
Change in Fecal Microbiome at 8 months	The purpose of this study is to determine if a sustained change in the fecal microbiome occurs after prolonged use of an antegrade continence enema bowel flush regimen. Patients' microbiomes will be evaluated via 16s rRNA sequencing	At baseline and 8 months post-MACE

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Bowel Regimen Solution on Fecal Bacterial Diversity	Determine whether a difference in fecal bacterial diversity determined by 16s rRNA sequencing exists between differing MACE bowel regimens of 1. Bisacodyl and PEG 3350 in electrolyte solution (GoLytely) or 2. Bisacodyl and PEG 3350 without electrolytes (Miralax).	Through study completion, approximately 8 months
Effect of Glycerin on Fecal Microbiome Diversity	Determine whether patients receiving glycerin in addition to PEG 3350 with or without electrolytes display differences in their fecal microbiota as measured by 16s rRNA sequencing.	Through study completion, approximately 8 months
Effect of Redundant Sigmoid Colon on Microbiome Diversity	Evaluate for differences in the fecal microbiome determined by 16s rRNA sequencing between those patients who have a redundant sigmoid colon based on barium enema results and those who do not	Through study completion, approximately 8 months

Collaborators and Investigators

• Sponsor: Indiana University
• Investigators: Principal Investigator: Kate Hawa, DO, Riley Hospital for Children

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2023
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: April 7, 2023
• First Submitted That Met QC Criteria: April 7, 2023
• First Posted (Actual): April 20, 2023

Study Record Updates

• Last Update Posted (Estimated): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 10, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Chronic Constipation; Miralax; PEG 3350; Fecal microbiome; Malone Antegrade Continence Enema (MACE); Antegrade Continence Enema
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Physiological Effects of Drugs; Gastrointestinal Agents; Protective Agents; Laxatives; Cryoprotective Agents; Glycerol; Polyethylene glycol 3350
• Other Study ID Numbers: 17083

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No