Clinical trial NCT04549727: Development and Use of a Tissue and Human Enteroid Biorepository to Study the Pathophysiology of NEC
Official title: Development and Use of a Tissue and Human Enteroid Biorepository to Study the Pathophysiology of Neonatal Necrotizing Enterocolitis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Enterocolitis, Necrotizing
Prematurity
Gastrointestinal Disease
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
Collaborators: name: Massachusetts General Hospital
First posted: 2020-09-16
Enrollment: 18
Sex: ALL
Maximum age (years): 44
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Investigators will use surgically-resected intestinal samples from NEC patients and gestational age-matched non-NEC surgical controls with intestinal resection for other reasons than NEC to conduct various analysis. For comparative studies, Investigators aim to grow enteroids from intestinal tissues freshly collected from preterm and term babies with an age limit of 44 weeks of postmenstrual age (PMA).

Group 1: intestinal samples from small and/or large bowel in NEC preterm and term babies.

Group 2 (Control group): Age- and intestinal area-matched (small and/or large bowel) No NEC babies, which have surgical resection for other reason than NEC

Brief summary: Despite a greater understanding of NEC physiopathology, modest progress has been done in terms of intervention and prevention of the disease over the past three decades, being the mortality rate unchanged.

Investigators intend to leverage our knowledge and technical expertise developed with fetal enteroids to further investigate the processes leading to NEC by deriving and performing functional studies on human intestinal enteroids generated from intestinal resection for therapeutic reasons in NEC and non-NEC patients

1. Generate a tissue biorepository composed of: enteroids and other lamina propria cells
2. Comparative studies of the gene expression profile of tissue, epithelial enteroids and underlying lamina propria of NEC, non-NEC, hypoxic and non-hypoxic infants
3. In vitro functional studies for the evaluation of critical factors in NEC pathophysiology
4. In vitro functional studies to identify the activation of processes leading to intestinal epithelium necroptosis and/or apoptosis in bacteria challenged and hypoxic conditions
5. Correlative studies of the impact of perinatal variables on the intestinal barrier functionality at baseline and challenged with pathogens
6. In vitro comparison of the intestinal barrier functionality in infants complicated by condition of prenatal hypoxia versus non hypoxic infants
7. Validation the NEC enteroids as an in vitro model for the identification of treatments and prevention of NEC


Eligibility criteria: Inclusion Criteria:

* Infants, with a postconceptional age below 44 weeks of gestation, undergoing a clinically indicated intervention of partial intestinal resection while hospitalized at the NICU of the Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico.

Exclusion Criteria:

* Infants presenting a devastating damage of the intestine

Primary outcomes:
measure: Comparative studies of gene expression
timeFrame: 2 years
measure: functional studies barrier functionality
timeFrame: 2 years
measure: functional studies on cellular death
timeFrame: 2 years
measure: Correlative studies of the impact of perinatal variables
timeFrame: 2 years
measure: compare the intestinal barrier functionality in pathological conditions
timeFrame: 2 years
measure: Validation of the enteroid NEC model
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University of Milan Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
name: Paola Roggero, MD PHD
role: PRINCIPAL_INVESTIGATOR
References: