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

NCT03660176 · tracked via the Priya Life Science France tracker

Sponsor

Assistance Publique Hopitaux De Marseille

Phase

Phase 3

Started

2026-11

Last updated

2026-09-10

Condition(s) studied

Hirschsprung's Disease

Investigational drug(s) / intervention(s)

Sodium Butyrateroutine management

Sodium Butyrate: Daily recto-colonic enemas of sodium butyrate (1.1 g/L solution, 10 mL/kg) administered for 24 days (±4 days) before curative surgery.

routine management: Standard preoperative management for Hirschsprung's disease including colonic decompressions/irrigations before curative surgery.

Study summary

Hirschsprung's disease (HD) is a rare congenital disorder (1/5000) defined by the absence of ganglion cells in the submucosal and myenteric plexuses along a variable length of the digestive tract. This abnormality most often leads to distal bowel obstruction in newborns with delayed passage of meconium. Treatment is surgical and consists in the resection of the aganglionic and transitional segments. However, the postoperative outcomes remain unpredictable. Despite complete curative surgery, intestinal functional disorders persist in 40-50% of children, mainly obstructive symptoms, and 15-25% of children will also develop postoperative enterocolitis, which remains the leading cause of mortality in HD. There is currently no preventive treatment of these intestinal functional disorders and enterocolitis. Recent preclinical studies have identified butyrate, a short-chain fatty acid, as a regulator of intestinal homeostasis in newborns and adults, particularly involved in maintaining epithelial integrity, regulating the immune response, and regulating the phenotype of the digestive tract and its functions. Butyrate regulates intestinal epithelial barrier functions by strengthening intestinal permeability, and regulates the functions of the enteric nervous system and its phenotype. In newborn rats, butyrate enemas increase the proportion of nitrergic (and also cholinergic) neurons, leading to improved nitrergic neurotransmission and, ultimately, improved colonic transit time.

Our main hypothesis is that recto-colonic butyrate enemas administered preoperatively in newborns and infants with HD should reduce postoperative functional intestinal motility disorders and enterocolitis in the short, medium, and long terms.

The BUTYHIRSCH project is a phase III, multicenter, national (24 pediatric surgery departments), controlled, randomized, open-label, prospective clinical drug trial. Fifty-eight patients will be included over a period of two years.

The primary objective is to determine the short-term efficacy of preoperative butyrate enemas in reducing the time to postoperative bowel recovery. The secondary objectives are to determine the medium- and long-term efficacy of preoperative butyrate enemas on 1) the incidence of postoperative obstructive functional symptoms, 2) the stool consistency, 3) the total postoperative intestinal transit time, 4) the incidence and severity of postoperative enterocolitis, and 5) the intestinal inflammation.

Patients will be randomized into 2 groups: the experimental group (29 patients) receiving a sodium butyrate recto-colic enema for 24 days before curative surgery and the control group (29 patients). Postoperative clinical follow-up will be prospective over 3 years in order to collect data on complications such as intestinal motility disorders and enterocolitis. No invasive or radiation-based examinations will be performed postoperatively. Additional investigative procedures will include assessment of total postoperative intestinal transit time using carmine red transit and assessment of intestinal inflammation by measuring fecal calprotectin.

examinations will be performed postoperatively. Additional investigative procedures will include assessment of total postoperative intestinal transit time using carmine red transit and assessment of intestinal inflammation by measuring fecal calprotectin.

Eligibility

Sex

ALL

Min age

7 Days

Max age

17 Years

Healthy volunteers

The inclusion criteria are: * Newborn with a diagnosis of Hirschsprung's disease the 2 first months of life managed successfully with colonic decompressions/irrigations before curative surgery (usually performed 1-3 times a day) * 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, 2009) * Uncomplicated form (without enterocolitis as defined by the HAEC score 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 The non-inclusion criteria are: * 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 (as defined by the HAEC score) * 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) * Neonates under tutorship or guardianship Minors cannot be excluded because they are the population to be studied. The non-inclusion criteria are: * 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 (as defined by the HAEC score) * 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) * Neonates under tutorship or guardianship Minors cannot be excluded because they are the population to be studied. The non-inclusion criteria are: * 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 (as defined by the HAEC score) * 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) * Neonates under tutorship or guardianship Minors cannot be excluded because they are the population to be studied.

Primary outcome measure(s)

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. — Up to 30 days after surgery
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.

Trial sites (1)

Facility	City	Region	Status
Assistance Publique Des Hopitaux de Marseille	Marseille	PACA

More Assistance Publique Hopitaux De Marseille trials in France

Application of ihMT MRI in Multiple Sclerosis Recruiting

PREVenting-ENvIronment-Reprotoxic Exposures Before In Vitro Fertilization (PREVENIR-FIV) Starting soon

Safety and Efficacy of a STOPping Strategy Versus Classical Maintenance Dose of JAK Inhibitors in Deep Remission Patients With Ulcerative Colitis Starting soon

Assessment of Protein Intake Using 2 Types of Nutritional Collection in Chronic Kidney Disease. Recruiting

Clinical Evaluation of an IGRA Test for the Diagnosis of Active and Latent Tuberculosis Recruiting

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT03660176 on ClinicalTrials.gov ↗ ← All trials in France