- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02444624
Clostridium and Neonatal Necrotizing Enterocolitis Pathophysiology : Clinical and Molecular Approaches (CLOSNEC)
Study Overview
Status
Conditions
Detailed Description
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 period a large collection of proved NEC cases. During that period, preterm neonates diagnosed as NEC cases (Bell stage II or III) from 20 French neonatal units will be included and matched to a control group of non-NEC neonates. Anthropometric data, clinical data, drug and feeding intakes will be collected from birth to the neonatal unit discharge. Microbiota analysis of NEC and non-NEC preterm neonates will be performed using culture and 16S rRNA gene pyrosequencing. This case-control study aims at obtaining the largest French collection of clinical and microbiological documented NEC cases that will allow reaching significance in results about the characteristics of the microbiota of NEC neonates. Additionally, it will confirm the involvement of specific bacteria, i.e. clostridia, which will be proposed as a biological marker of high risk to develop NEC.
Experimental approach will consist in the construction of mutants of clinical isolates of C.butyricum, C. perfringens, and C. paraputrificum impaired in butyrate production using the Clostron directed mutagenesis knock out tool recently adapted to clostridia. investigators will inactivate the gene encoding the enzyme responsible for butyrate production. The pathogenicity of wild type and mutants strains will be performed in previous gnotobiotic quail animal model of NEC. This will allow us to verify the hypothesis of clostridia species biological involvement in NEC pathogenesis through fermentation end-product metabolite. This work will be completed by a phenotypic characterization and proteomics analysis of the clinical strains linked to NEC development in order to search for a bacterial pathogenicity biomarker. The absence of a consensus for the prevention of NEC is partly due to the lack of knowledge of its pathogenesis. This project will give important information in terms of clinical and mechanistic data. Looking for biological markers as investigators propose will be helpful for clinical practice and strategies of prevention implementation
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
-
Nantes, France, 44000
- Nantes UH
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Recruitment of CASES (NEC group) will prospectively occure according to the following schedule:
Following the diagnosis confirmed ECUN (stage II or III Bell) during the stay in neonatology:
- stool sample at the earliest
- In case of surgery, if resection: a collection of intestinal contents and biopsy of the intestinal mucosa during the act
- collection of clinical data from birth until hospital discharge or transfer of the child and then collecting the ASQ 24 months.
Inclusion of control patients should be made within 7 days of the onset of the corresponding NEC case. Informed parents will previously allow enrollment of their child to set faeces sampling and data capture from birth to the output of hospitalization or transfer of the child and then collecting the ASQ 24 months.
Description
Inclusion Criteria "necrotizing enterocolitis group":
- Newborn gestational age less than or equal to 31 + 6 weeks of amenorrhea
- ECUN of diagnosis (Stage II or III Bell) confirmed
- Parental non-opposition / legal representative
Inclusion Criteria "not necrotizing enterocolitis group":
- Newborn gestational age less than or equal to 31 + 6 weeks of amenorrhea
- Respect for matching the order of priority set for criteria
- 1 of 2 control patients will be free of any antibiotic
- Parental non-opposition / legal representative
Exclusion criteria for both groups ("not necrotizing enterocolitis group" and "necrotizing enterocolitis group"): none
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
---|
not necrotizing enterocolitis group
not necrotizing enterocolitis preterm neonates matched with necrotizing enterocolitis preterm neonates
|
necrotizing enterocolitis group
necrotizing enterocolitis preterm neonates of gestational age less than or equal to 31+6 weeks of amenorrhoea with confirmed NEC diagnosis (Bell stage II or III)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Results from analyses will not be used back for patients enrolled in this non interventional study
|
Inclusion until departure from hospital, an average of three months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phenotypic comparison of clostridia between the 2 CASE and CONTROL groups
Time Frame: Inclusion until departure from hospital, an average of three months
|
Results from analyses will not be used back for patients enrolled in this non interventional study
|
Inclusion until departure from hospital, an average of three months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jean-Christophe Roze, Pr, Nantes University Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- RC14_0295
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Necrotizing Enterocolitis
-
Gorm GreisenCompletedComplications | NEC - Necrotizing EnterocolitisDenmark
-
Mednax Center for Research, Education, Quality...Phoenix Children's Hospital; Banner University Medical CenterCompletedTotal Parenteral Nutrition | Necrotizing Enterocolitis of NewbornUnited States
-
Ain Shams UniversityCompleted
-
Children's Hospital of PhiladelphiaBracco Diagnostics, IncRecruitingNecrotizing Enterocolitis of Newborn | Bowel IschemicUnited States
-
Medical University of WarsawNot yet recruitingNecrotizing EnterocolitisPoland
-
The University of Hong KongRecruitingNecrotizing EnterocolitisHong Kong
-
Marmara UniversityUnknownNecrotizing EnterocolitisTurkey
-
Maastricht University Medical CenterUnknown
-
Odense University HospitalCompletedNecrotizing EnterocolitisDenmark
-
Boston Children's HospitalYale University; Elizabeth Glaser Pediatric AIDS Foundation; Glaser Pediatric...Unknown