Clinical Trial: Clostridium and Neonatal Necrotizing Enterocolitis Pathophysiology : Clinical and Molecular Approaches
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational
Official Title: Clostridium and Neonatal Necrotizing Enterocolitis Pathophysiology : Clinical and Molecular Approaches
Brief Summary: The clinical study involves a French network of 20 neonatology centres created as part of the EPIFLORE project. Investigators propose including all premature babies with confirmed necrotizing enterocolitis (NEC) diagnosis (Bell stage II or III) paired with a control group of healthy premature babies, over a 2-year period. The clinical data will be entered at inclusion until departure from the department, and the ASQ (Ages and Stages Questionnaires) will be collected after 24 months. Samples from NEC cases and from the control group will be submitted for microbiological testing by culture and pyrosequencing. This will enable the main aerobic micro-organisms in the dominant and subdominant intestinal microbiota to be isolated. This case-control study will be used to compile a collection of clinical and microbiological data, in order to confirm the role of bacteria in the pathophysiology of NEC, and to confirm the involvement of bacteria from the Clostridium genus in particular.
Detailed Summary:
Necrotizing enterocolitis (NEC) remains an important cause of morbidity and mortality among preterm neonates. Despite many investigations its pathogenesis remains unclear. The role of intestinal bacteria in NEC development is supported by epidemiologic evidence (outbreaks), the frequent isolation of infectious agents, and a decrease incidence of NEC resulting from preventive antibiotic treatment. Bacterial implication is thought to be due to colonic fermentation of nonhydrolyzed lactose, a consequence of the intestinal immaturity of preterm infants (intestinal lactase deficiency). To date, no specific bacteria or bacterial colonization pattern have been causally associated with the development of NEC. Clinical signs and some epidemiological studies are consistent with clostridia involvement in NEC. Indeed, Clostridium butyricum, Clostridium perfringens, and Clostridium paraputrificum have been isolated from the blood, feces, and peritoneal fluids of preterm neonates suffering from NEC. In addition, a correlation between the presence of C. butyricum and C. paraputrificum and pneumatosis intestinalis in tissue specimens from NEC neonates was reported. Furthermore, the role of these clostridia species in NEC pathogenesis has been demonstrated using NEC animal models (preterm piglet or gnotobiotic quails). Particularly, lactose fermentation end-products (butyrate or iso-butyrate) was linked to cecal NEC-like lesions onset in gnotobiotic quails animal model.
This project is lying within this context, and aims at confirming the clostridial involvement in the pathogenesis of NEC and search for bacterial pathogenicity biomarkers. For this purpose, investigators will use both clinical and experimental approaches.
The clinical study will take the opportunity of previous EPIFLORE project network (ANR 2012) to build during a one-year
Sponsor: Nantes University Hospital
Current Primary Outcome: The primary endpoint is the difference in prevalence of colonisation by bacteria from the Clostridium genus between the two study groups, CASE and CONTROL. [ Time Frame: Inclusion until departure from hospital, an average of three months ]
Original Primary Outcome: Same as current
Current Secondary Outcome: Phenotypic comparison of clostridia between the 2 CASE and CONTROL groups [ Time Frame: Inclusion until departure from hospital, an average of three months ]
Original Secondary Outcome: Same as current
Information By: Nantes University Hospital
Dates:
Date Received: February 16, 2015
Date Started: May 2015
Date Completion: January 2019
Last Updated: September 16, 2015
Last Verified: September 2015
