Effects of Recto-colic Enemas of Butyrate on the Digestive Disorders of Very Low Birth Weight Preterms <1250 Grams

Summary

Clinical management of very low birth weight newborns (VLBW \<1250g) consists in several challenges to adapt immature physiological systems to extrauterine life. Advances in neonatal medicine for pulmonary and/or neurological and/or cardiovascular diseases have significantly improved outcomes of these children. However, the gastro-intestinal (GI) tract remains a major cause of morbidity due to

1. the immaturity of GI functions (prolonged ileus, bacterial overgrowth and translocation),
2. the complication of GI tract immaturity: intestinal perforation and enterocolitis necrotizing)
3. the need of a prolonged parenteral nutrition and its complications (central venous catheter infections, sepsis, electrolyte disturbances) but without generate a high proof level on this targeted population (\<1250g).

The GI functions are progressively acquired during development and are largely sensitive to the environment, especially the intestinal luminal content. Indeed, probiotics and prebiotics have shown beneficial effects upon GI functions of newborns. One of the metabolite of the gut flora potentially involved is the butyrate. Butyrate is a short chain fatty acid produced in the colon by the microbiota (carbo-hydrates degradation). The colonic amount of butyrate increases gradually after birth. The beneficial effects of butyrate are related to its properties upon the epithelial barrier (anti-inflammatory, antioxidant, barrier repair) and upon the enteric nervous system (network of neurons and glial cells) that regulate GI functions and in particular colonic motility.

To date, there is no clinical consensus to manage digestive disorders of VLBW. Several clinical studies have assessed the effects of prokinetic drugs, dietary supplements (probiotics, prebiotics) but without generate a high proof level on this targeted population. In this context, a recent study of our Research Unit (INSERM-CIC Mère-Enfant 004) has shown benefit effects of oral probiotics supplementation in children with birth weight greater than 1000g but not in extreme preterms with birth weight less than 1000g.

The main hypothesis to explain theses results lies in the intensive use of antibiotic and feeding interruption frequency in this targeted population which induce disturbances in the composition of the gut lumen (in particular the flora).

Colonic enemas assessed in various observational studies concerning VLBW seem to demonstrate a clinical efficiency upon the colonic transit, underlying by mechanical and osmotic mechanisms.

Here, the investigators propose to evaluate the clinical efficiency of butyrate enemas by a prospective randomized clinical trial blinded design.

The purpose of NEOTRANS study is to demonstrate that butyrate enemas may improve the nutritional management of extreme preterm less than 1250 grams, by facilitating the development of colic motility and clinical nutrition tolerance.

Conditions

• Very Low Birth Weight Preterms

Interventions

DRUG

Butyrate enemas

Seven enemas * Possibility to delay from 24 to 48 hours the procedure in case of clinical poor tolerance(maximum two enemas postponed and delayed at PND12 and PND13) * The study remains blinded for the investigation team through the intervention of a clinical research nurse * According to the procedure previously described by Nakaoka et al. (2009), a lubricated Foley catheter Ch 6 will be introduced into the rectum, the balloon will be inflated with 1 ml water for injections. Butyrate solution will be placed in a bag placed 50 cm above the child. Therefore, treatment administration will be performed at a controlled pressure of 50 cm H2O without any manual intervention * Installation time and retention is setted at 15 minutes * Treatment units will be directly placed in the incubator 30 min before the procedure to warm the enema to +36°C * Per-treatment clinical monitoring of the tolerance will be performed by a neonatologist

Sponsors & Collaborators

• Nantes University Hospital

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

5 Days

Max Age

5 Days

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-02-29

Primary Completion

2016-03-31

Completion

2016-03-31

Countries

• France

Study Locations