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

Constipation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05821309
• Other study ID #: 17083
• Status: Recruiting
• Phase: Phase 4
• Start date: June 8, 2023
• Est. completion date: July 2024

Study information

• Verified date: November 2023
• Source: Indiana University
• Contact: Erik Andrewski, MD
• Phone: 317-944-3774
• Email: edandrew[@]iupui.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: July 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 2 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Constipation

Intervention

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
• 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
• 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.

Locations

Country	Name	City	State
United States	IU North Hospital	Carmel	Indiana
United States	Riley Hospital for Children	Indianapolis	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Indiana University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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