Clinical trial NCT01536483: Effects of Recto-colic Enemas of Butyrate on the Digestive Disorders of Very Low Birth Weight Preterms <1250 Grams
Official title: Effects of Recto-colic Enemas of Butyrate on the Digestive Disorders of Very Low Birth Weight Preterms <1250 Grams. Clinical Trial Prospective, Monocentric, Randomized in Double-blinded.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Very Low Birth Weight Preterms
Keywords: Butyrate
Preterms
Very Low Birth Weight (<1250g)
Rectocolonic enemas
Digestive maturation
Parenteral nutrition weaning
ECUN
Whole gut transit time
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2012-02-22
Enrollment: 61
Sex: ALL
Minimum age (years): 5
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria:

* Any preterm infant with a birth weight less than or equal to 1250 grams admitted in the neonatal intensive care unit of Nantes Hospital
* Inborn or outborn
* No signs of gastrointestinal perforation or ECUN
* Absence of severe congenital disease
* Written informed consent of parental authority.

Exclusion Criteria:

* Newborn with birth weight greater than 1250 grams,
* Gestational age \> 30 AG
* Digestive pathology diagnosed prior PND5: perforation, necrotizing enterocolitis, malformations
* Severe congenital pathology inconsistent with clinical assessment.
* Parental Refusal

Primary outcomes:
measure: Efficacy of colonic butyrate enemas in digestive maturation of preterms
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
Secondary outcomes:
measure: Gastrointestinal complications frequency
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
measure: Nosocomial infections frequency
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
measure: Iatrogenic effect
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
measure: whole gut transit time (red carmine test)
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
measure: Growth
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
measure: Invasive ventilation support
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
measure: Bronchopulmonary dysplasia incidence
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
measure: Hospitalization duration
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 5 weeks
measure: Neuromotor development
timeFrame: 2 years
Other outcomes:
Locations:
city: Nantes
country: France
facility: Nantes
Study officials:
References: