RCE With FMT in the Treatment of Childhood Constipation

Retrograde Colonic Enema With Fecal Microbiota Transplantation vs Retrograde Colonic Enema Only in the Treatment of Childhood Constipation

Constipation is the most common complaint in childhood gastrointestinal disease, affecting an estimated 20% of the global children.The treatment strategies consist of diet control, behavioral intervention and oral and sometimes rectal laxatives. Given higher success rate and fewer side effects, the laxative PEG3350 has been considered the first choice in childhood constipation.However, effectiveness of PEG 3350 laxative is not lasting, and the use of PEG increases the risk of fecal incontinence. Additional treatment interventions are still necessary.Enema can act directly on the rectum and distal colon to quickly relieve symptoms of fecal impaction which is considered one of main source of intractable constipation. Children with fecal impaction who received enema had fewer fecal incontinence and diarrhea than children who received PEG. There have been lots of evidence that enema is effective in fecal impaction in children with functional constipation.But there are still cases of recurrences noted after enema. Fecal bacteria transplantation (FMT) is a new treatment method emerging in recent years, which is widely used in the treatment of functional gastrointestinal diseases. FMT has been proved to play a very prominent role in correcting intestinal flora disorders. By transplanting exogenous flora into the intestinal tract of patients, FMT can inhibit bacterial reproduction, regulate intestinal environment and cascade the body immunity, so as to achieve the therapeutic effect of disease.

Retrograde colonic enema with FMT, an new method, provides the possibility for the treatment of childhood constipation. However, there is still a lack of evidence-based support for the treatment of childhood constipation by retrograde colonic enema with FMT. Therefore, we designed a randomized, controlled, double-blind clinical trial to confirm the efficacy and safety of retrograde colonic enema with FMT in the treatment of childhood constipation.

Study Overview

• Status: Completed
• Conditions: Constipation - Functional; Fecal Microbiota Transplantation
• Intervention / Treatment: Drug: Fecal supernatant; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Shengjing Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 14 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria:

• 4-14 years old;
• Roman IV criteria for childhood constipation;
• After a course of PEG and a course of Chinese medicine treatment was ineffective;
• Barium enema showing fecal impaction.

Exclusion criteria:

• Congenital and/or acquired intestinal diseases, such as congenital megacolon, intestinal stenosis, polyps, Crohn's disease, tuberculosis, inflammation, and tumors;
• Anorectal diseases, such as anal atresia, fistula, abscess, and tumor;
• Neurological diseases, such as brain and spinal cord diseases;
• genetic metabolic diseases;
• psychosocial and behavioral diseases;
• other systemic diseases;
• Refused to participate in.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Fecal supernatant; Fecal supernatant is used for treatment of childhood Constipation	Drug: Fecal supernatant; Fecal supernatant from a child registered in the specimen bank that matches the subject's age, gender, and weight .
Placebo Comparator: non-Fecal supernatant; Placebo is used for treatment of childhood Constipation	Drug: Placebo; a placebo designed to match the FMT+RCE group based on appearance including 0.9% physiological saline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Satisfaction with bowel function	Satisfaction with bowel function was collected from the parents and defined as whether they were satisfied with bowel function after the treatment (yes or no).	Baseline
Satisfaction with bowel function	Satisfaction with bowel function was collected from the parents and defined as whether they were satisfied with bowel function after the treatment (yes or no).	at the end of 4-weeks FMT treatment
Satisfaction with bowel function	Satisfaction with bowel function was collected from the parents and defined as whether they were satisfied with bowel function after the treatment (yes or no).	at the end of 12 weeks follow-up
improvement of spontaneous bowel movements(SBMs) per week	the frequency of defecation without drugs or other auxiliary methods	Baseline
improvement of spontaneous bowel movements(SBMs) per week	the frequency of defecation without drugs or other auxiliary methods	at the end of 4-weeks FMT treatment
improvement of spontaneous bowel movements(SBMs) per week	the frequency of defecation without drugs or other auxiliary methods	at the end of 12 weeks follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bowel movements	the frequency of bowel movements per week	Baseline
Bowel movements	the frequency of bowel movements per week	at the end of 4-weeks FMT treatment
Bowel movements	the frequency of bowel movements per week	at the end of 12 weeks follow-up
Painful or hard bowel movements	The feelings of children during defecation	Baseline
Painful or hard bowel movements	The feelings of children during defecation	at the end of 4-weeks FMT treatment
Painful or hard bowel movements	The feelings of children during defecation	at the end of 12 weeks follow-up
Large diameter or scybalous stools	appearance and wetness of stool	Baseline
Large diameter or scybalous stools	appearance and wetness of stool	at the end of 4-weeks FMT treatment
Large diameter or scybalous stools	appearance and wetness of stool	at the end of 12 weeks follow-up
Excessive volitional stool retention	The number of children who intentionally control or reduce the frequency of defecation	Baseline
Excessive volitional stool retention	The number of children who intentionally control or reduce the frequency of defecation	at the end of 4-weeks FMT treatment
Excessive volitional stool retention	The number of children who intentionally control or reduce the frequency of defecation	at the end of 12 weeks follow-up
Encopresis	the frequency of fecal incontinence	Baseline
Encopresis	the frequency of fecal incontinence	at the end of 4-weeks FMT treatment
Encopresis	the frequency of fecal incontinence	at the end of 12 weeks follow-up

Collaborators and Investigators

• Sponsor: Shengjing Hospital

Publications and helpful links

General Publications

• Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. 2011 Nov;53(10):994-1002. doi: 10.1093/cid/cir632.
• Wang S, Xu M, Wang W, Cao X, Piao M, Khan S, Yan F, Cao H, Wang B. Systematic Review: Adverse Events of Fecal Microbiota Transplantation. PLoS One. 2016 Aug 16;11(8):e0161174. doi: 10.1371/journal.pone.0161174. eCollection 2016.
• Vriesman MH, Koppen IJN, Camilleri M, Di Lorenzo C, Benninga MA. Management of functional constipation in children and adults. Nat Rev Gastroenterol Hepatol. 2020 Jan;17(1):21-39. doi: 10.1038/s41575-019-0222-y. Epub 2019 Nov 5.
• Dai M, Liu Y, Chen W, Buch H, Shan Y, Chang L, Bai Y, Shen C, Zhang X, Huo Y, Huang D, Yang Z, Hu Z, He X, Pan J, Hu L, Pan X, Wu X, Deng B, Li Z, Cui B, Zhang F. Rescue fecal microbiota transplantation for antibiotic-associated diarrhea in critically ill patients. Crit Care. 2019 Oct 21;23(1):324. doi: 10.1186/s13054-019-2604-5.
• Gurram B, Sue PK. Fecal microbiota transplantation in children: current concepts. Curr Opin Pediatr. 2019 Oct;31(5):623-629. doi: 10.1097/MOP.0000000000000787.
• Xu D, Chen VL, Steiner CA, Berinstein JA, Eswaran S, Waljee AK, Higgins PDR, Owyang C. Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis. Am J Gastroenterol. 2019 Jul;114(7):1043-1050. doi: 10.14309/ajg.0000000000000198.
• Tian H, Ding C, Gong J, Ge X, McFarland LV, Gu L, Wei Y, Chen Q, Zhu W, Li J, Li N. Treatment of Slow Transit Constipation With Fecal Microbiota Transplantation: A Pilot Study. J Clin Gastroenterol. 2016 Nov/Dec;50(10):865-870. doi: 10.1097/MCG.0000000000000472.
• Ohkusa T, Koido S, Nishikawa Y, Sato N. Gut Microbiota and Chronic Constipation: A Review and Update. Front Med (Lausanne). 2019 Feb 12;6:19. doi: 10.3389/fmed.2019.00019. eCollection 2019.
• Kassam Z, Dubois N, Ramakrishna B, Ling K, Qazi T, Smith M, Kelly CR, Fischer M, Allegretti JR, Budree S, Panchal P, Kelly CP, Osman M. Donor Screening for Fecal Microbiota Transplantation. N Engl J Med. 2019 Nov 21;381(21):2070-2072. doi: 10.1056/NEJMc1913670. Epub 2019 Oct 30. No abstract available.
• Clemente MG, Mandato C, Poeta M, Vajro P. Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions. World J Gastroenterol. 2016 Sep 28;22(36):8078-93. doi: 10.3748/wjg.v22.i36.8078.
• Woodworth MH, Carpentieri C, Sitchenko KL, Kraft CS. Challenges in fecal donor selection and screening for fecal microbiota transplantation: A review. Gut Microbes. 2017 May 4;8(3):225-237. doi: 10.1080/19490976.2017.1286006. Epub 2017 Jan 27.
• Vindigni SM, Surawicz CM. Fecal Microbiota Transplantation. Gastroenterol Clin North Am. 2017 Mar;46(1):171-185. doi: 10.1016/j.gtc.2016.09.012.
• Shen ZH, Zhu CX, Quan YS, Yang ZY, Wu S, Luo WW, Tan B, Wang XY. Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation. World J Gastroenterol. 2018 Jan 7;24(1):5-14. doi: 10.3748/wjg.v24.i1.5.

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2020
• Primary Completion (Actual): January 20, 2022
• Study Completion (Actual): May 13, 2022

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: August 30, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation
• Other Study ID Numbers: A333--1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No