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

Sponsor

Indiana University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05821309

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

1.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Constipation	Drug: PEG 3350 Drug: PEG-3350 with electrolytes Drug: Glycerin	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Masking Description:

Only objective data in the form of fecal microbiome diversity will be obtained via 16s rRNA sequencing. Neither the participant nor the investigators will be blinded.

Primary Purpose:

Basic Science

Official Title:

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

Anticipated Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PEG 3350 Patients will receive miralax (PEG 3350) 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 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 Go-Lytely (PEG 3350 with electrolytes) for their MACE flushes	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 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.

Arm

Intervention/Treatment

Experimental: PEG 3350

Patients will receive miralax (PEG 3350) 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

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 Go-Lytely (PEG 3350 with electrolytes) for their MACE flushes

Drug: PEG-3350 with electrolytes

Other Names:

GoLytely

Drug: Glycerin

Outcome Measures

Primary Outcome Measures

Change in Fecal Microbiome at 1 month [At baseline and 1 month post-MACE]
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
Change in Fecal Microbiome at 4 months [At baseline and 4 months post-MACE]
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
Change in Fecal Microbiome at 8 months [At baseline and 8 months post-MACE]
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

Secondary Outcome Measures

Effect of Bowel Regimen Solution on Fecal Bacterial Diversity [Through study completion, approximately 8 months]
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).
Effect of Glycerin on Fecal Microbiome Diversity [Through study completion, approximately 8 months]
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.
Effect of Redundant Sigmoid Colon on Microbiome Diversity [Through study completion, approximately 8 months]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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
Underlying severe GI disease unrelated to the patient's chronic constipation
Use within the past month of probiotic supplements, prebiotic supplements or antibiotics