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

NCT ID: NCT05821309

Last Updated: 2025-07-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-08
• Study Completion Date: 2026-07-31

Brief Summary

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.

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.

Conditions

Constipation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

PEG 3350

Patients will receive PEG 3350 (miralax or generic equivalent) for their MACE flushes.

Group Type: EXPERIMENTAL

PEG 3350

Intervention Type: DRUG

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

Glycerin

Intervention Type: DRUG

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.

PEG 3350 with electrolytes

Patients will receive PEG 3350 with electrolytes (Go-Lytely or generic equivalent) for their MACE flushes.

Group Type: EXPERIMENTAL

PEG-3350 with electrolytes

Intervention Type: DRUG

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

Glycerin

Intervention Type: DRUG

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.

Interventions

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

Intervention Type: 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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

MiraLAX or generic equivalent; GoLytely or generic equivalent

Eligibility Criteria

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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Kathryn Hawa, DO

Principle Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kate Hawa, DO

Role: PRINCIPAL_INVESTIGATOR

Riley Hospital for Children

Locations

IU North Hospital

Carmel, Indiana, United States

Site Status: RECRUITING

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Erik Andrewski, MD

Role: CONTACT

edandrew@iupui.edu

317-944-3774

Ann Klipsch, RN

Role: CONTACT

aeye@iu.edu

317-944-3774

Facility Contacts

Erik Andrewski, MD

Role: primary

edandrew@iu.edu

317-944-3774

Ann Klipsch, RN

Role: backup

aeye@iu.edu

317-944-3774

Erik Andrewski, MD

Role: primary

edandrew@iupui.edu

317-944-3774

Ann Klipsch, RN

Role: backup

aeye@iu.edu

317-944-3774

Other Identifiers

17083

Identifier Type: -

Identifier Source: org_study_id