Effects of Recto-colic Enemas of Butyrate on the Digestive Disorders of Very Low Birth Weight Preterms <1000 Grams (NEOTRANS)
Clinical management of very low birth weight newborns (VLBW <1000g) 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
- the immaturity of GI functions (prolonged ileus, bacterial overgrowth and translocation),
- the complication of GI tract immaturity: intestinal perforation and enterocolitis necrotizing)
- 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 (<1000g).
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 1000 grams, by facilitating the development of colic motility and clinical nutrition tolerance.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Effects of Recto-colic Enemas of Butyrate on the Digestive Disorders of Very Low Birth Weight Preterms <1000 Grams. Clinical Trial Prospective, Monocentric, Randomized in Double-blinded.|
- Efficacy of colonic butyrate enemas in digestive maturation of preterms [ Designated as safety issue: No ]
The primary outcome of NEOTRANS study consists in the evaluation of the effects of colonic butyrate enemas upon the digestive maturation of preterms.
This endpoint is based on a clinical criteria that is the delay of weaning of the parenteral nutrition support. An increase of 25% (50 vs 75%) will be considered clinically significant.
Parenteral nutrition weaning is defined as the day where enteral caloric intake reach 80% of total calories.
- Gastrointestinal complications frequency [ Designated as safety issue: No ]
- Nosocomial infections frequency [ Designated as safety issue: No ]
- Iatrogenic effect [ Designated as safety issue: No ]
- whole gut transit time (red carmine test) [ Designated as safety issue: No ]
- Growth [ Designated as safety issue: No ]Comparaison between 2 arms of height, weight and head circumference
- Invasive ventilation support [ Designated as safety issue: No ]
- Bronchopulmonary dysplasia incidence [ Designated as safety issue: No ]
- Hospitalization duration [ Designated as safety issue: No ]
|Study Start Date:||February 2012|
|Estimated Study Completion Date:||May 2015|
|Estimated Primary Completion Date:||May 2015 (Final data collection date for primary outcome measure)|
Seven enemas of butyrate will be performed daily between PND5 and PND11.
Drug: Butyrate enemas
Seven enemas will be performed daily between PND5 and PND11
No Intervention: Therapeutic Abstention
The protocol will pretend enema: instillation in the diaper the product under consideration, to make the two indistinguishable processes (time, odor, wicking diaper ...)
Please refer to this study by its ClinicalTrials.gov identifier: NCT01536483
|Contact: Cyril FLAMANT, PhD||+33 2 40 08 76 email@example.com|
|Contact: Cyril FLAMANT, PhD +33 2 40 08 76 79 firstname.lastname@example.org|
|Principal Investigator: Cyril FLAMANT, PhD|