Effects of Butyrate Enemas on Postoperative Intestinal Mobility Disorders in Hirschsprung's Disease

NCT03660176 | Unknown Phase 3 DMC

• 1 other identifier: 2018-02
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

Hirschsprung's disease (HD) is a rare disease defined as a congenital absence of enteric ganglia, resulting usually in neonatal bowel obstruction. The current treatment is the operative removal of the aganglionic bowel and anastomosis to the ganglionic zone considered as 'healthy'. However, postoperative course remains unpredictable. Functional intestinal disorders are present in up to 45% of patients and can occur in the immediate postoperative period or few weeks/years later. Until now, there are neither predictive factors of postoperative digestive complications nor established treatment for postoperative dysmotility in HD. Abnormalities in enteric nervous system (ENS) phenotype and functions in the 'healthy' ganglionic segment are increasingly suspected to be directly responsible for postoperative intestinal dysfunctions in HD. Therefore, approaches aimed at restoring the nitrergic phenotype could be of major therapeutical interest. Among targets regulating the nitrergic phenotype of ENS are the microbiota and/or derived metabolites. Indeed preclinical animal models deficient in bacterial sensing molecules have a loss of nitrergic neurons and reduced colonic transit. Conversely, microbiota transfer to newborn germ-free mice restored colonic transit time. Alternatively the investigators has shown that bacterial metabolites such as short-chain fatty acids, in particular butyrate, can increase nitrergic phenotype and enhance colonic motility in a gut immaturity animal model. Therefore the investigators hypothesize preoperative butyrate enema will reduce postoperative intestinal complications at short-term and medium/long-term.

Conditions

Hirschsprung's Disease

Outcome Measures

Primary Outcomes (1)

• The time to recovery of bowel function after the curative surgery. A 25% decrease of the time to recovery of bowel function in the experimental group as compared to the control group will be considered as clinically effective.

  The recovery of bowel function is defined as follows: * Tolerance of 2 feeds at full ration (as before surgery, breast-feeding or bottle-feeding), * And passing stools. The time to recovery of bowel function will be measured in hours from the end of the curative surgery.

  5 YEARS

Secondary Outcomes (2)

• The red carmin total transit time will be measured before the surgery

  5 YEARS

• The postoperative medium/long-term efficacy of butyrate enemas

  5 YEARS

Study Arms (2)

routine management

ACTIVE COMPARATOR

Children in the control group receive no additional treatment

Other: routine management

EXP GROUP

EXPERIMENTAL

children receiving butyrate enemas + routine management butyrate enemas every day before Curative surgery

Drug: butyrate enemas + routine management

Interventions

butyrate enemas + routine management DRUG

10ml/kg volume of butyrate enemas in addition to the colonic irrigations

EXP GROUP

routine management OTHER

the colonic irrigations

routine management

Eligibility Criteria

• Age: 7 Days - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Newborn with a diagnosis of Hirschsprung's disease the 2 first months of life,
• Born at or after 35 weeks of gestation (37 weeks of amenorrhea),
• With a short-segment Hirschsprung's disease limited to the rectum and/or sigmoid colon diagnosed on rectal biopsy with established pathological criteria (absence of ganglionic cells +/- hypertrophic extrinsic nerve fibres) (Kapur, Sem Ped Surg 2009),
• Managed successfully with colonic decompressions/irrigations before curative surgery (usually performed 2-3 times a day),
• Uncomplicated form (without enterocolitis and/or diverting colostomy),
• Curative surgery and follow-up in one of the included centres,
• With consent of the 2 parents or legal(s) representative(s),
• Absence of severe or lethal associated malformations,
• Affiliation with the French social security system.

You may not qualify if:

• \- Long segment Hirschsprung's disease prior to the junction between the left colon and the sigmoid colon,
• Hirschsprung's disease not managed successfully with colonic decompressions/irrigations and requiring a diverting colostomy before the curative surgery,
• Hirschsprung-associated enterocolitis occurring before the randomization,
• Severe or lethal associated malformation, including Down syndrome,
• Intestinal associated malformations (intestinal atresia, gastroschisis, omphalocele, intestinal malrotation and volvulus),
• Any pathological condition that can modify intestinal motility or intestinal transit time (cystic fibrosis, hypothyroidism),
• Refusal of parent(s) or legal representative(s).
• Patients under curatorship or tutorship

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Assistance Publique Des Hopitaux de Marseille

Marseille, PACA, 13354, France

Location

MeSH Terms

Conditions

Hirschsprung Disease

Condition Hierarchy (Ancestors)

Digestive System Abnormalities; Digestive System Diseases; Megacolon; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• EMILIE GARRIDO PRADALIE

  APHM

  STUDY DIRECTOR

Central Study Contacts

ANNE DARIEL, MD

CONTACT

+33 491964885; Anne.DARIEL@ap-hm.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2018
• First Posted: September 6, 2018
• Study Start: January 2, 2019
• Primary Completion: January 2, 2024
• Study Completion: July 2, 2024
• Last Updated: September 6, 2018

Record last verified: 2018-08

Locations

FR (1)