Clinical trial NCT05821309: Evaluation of Fecal Microbiome Changes After Antegrade Continence Enema Placement and Initiation of Bowel Flush Regimen
Official title: Evaluation of Fecal Microbiome Changes After Antegrade Continence Enema Placement and Initiation of Bowel Flush Regimen
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Constipation
Keywords: Fecal microbiome
Malone Antegrade Continence Enema (MACE)
Miralax
PEG 3350
Antegrade Continence Enema
Chronic Constipation
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2023-04-20
Enrollment: 65
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Change in Fecal Microbiome at 1 month
timeFrame: At baseline and 1 month post-MACE
measure: Change in Fecal Microbiome at 4 months
timeFrame: At baseline and 4 months post-MACE
measure: Change in Fecal Microbiome at 8 months
timeFrame: At baseline and 8 months post-MACE
Secondary outcomes:
measure: Effect of Bowel Regimen Solution on Fecal Bacterial Diversity
timeFrame: Through study completion, approximately 8 months
measure: Effect of Glycerin on Fecal Microbiome Diversity
timeFrame: Through study completion, approximately 8 months
measure: Effect of Redundant Sigmoid Colon on Microbiome Diversity
timeFrame: Through study completion, approximately 8 months
Other outcomes:
Locations:
city: Carmel
country: United States
facility: IU North Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
Study officials:
affiliation: Riley Hospital for Children
name: Kate Hawa, DO
role: PRINCIPAL_INVESTIGATOR
References: