Development and Use of a Tissue and Human Enteroid Biorepository to Study the Pathophysiology of NEC

NCT04549727 | Unknown

• 1 other identifier: BIENTERNIP
• Study Type: observational
• Target: 18
• Locations: 0 countries
• Sites: N/A

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. 1.Generate a tissue biorepository composed of: enteroids and other lamina propria cells
2. 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. 3.In vitro functional studies for the evaluation of critical factors in NEC pathophysiology
4. 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. 5.Correlative studies of the impact of perinatal variables on the intestinal barrier functionality at baseline and challenged with pathogens
6. 6.In vitro comparison of the intestinal barrier functionality in infants complicated by condition of prenatal hypoxia versus non hypoxic infants
7. 7.Validation the NEC enteroids as an in vitro model for the identification of treatments and prevention of NEC

Conditions

Enterocolitis, Necrotizing; Prematurity; Gastrointestinal Disease

Outcome Measures

Primary Outcomes (6)

• Comparative studies of gene expression

  assess the gene expression profile of tissue, epithelial enteroids and underlying lamina propria derived from NEC, non-NEC (further classified as hypoxic and non-hypoxic infants). NB: the unit of analysis will be the organoids derived from patients' tissues Investigators expect to be able to derive 1 cell line per patient, and the number of derived organoids will depend from the viability of individual cell lines.

  2 years

• functional studies barrier functionality

  evaluation of barrier functionality at the baseline and in enteroids-derived monolayers challenged with pathogens, dead bacteria (as postbiotics), LPS, pharmacological agents, enteral nutrients and to evaluate innate immune response and barrier functionality as previously investigated in fetal enteroids and the contribution of myofibroblast, immune and ENS to the immune response

  2 years

• functional studies on cellular death

  studies to identify the activation of processes leading to intestinal epithelium necroptosis and/or apoptosis in bacteria challenged and hypoxic conditions

  2 years

• Correlative studies of the impact of perinatal variables

  Assess how the perinatal features (expression of the neonatal phenotype, as IUGR, chorionamnionitis, perinatal hypoxia) on the intestinal barrier functionality at baseline and challenged with pathogens

  2 years

• compare the intestinal barrier functionality in pathological conditions

  comparison of the intestinal barrier functionality in infants complicated by condition of prenatal hypoxia versus non hypoxic infants

  2 years

• Validation of the enteroid NEC model

  Validate the NEC enteroids as an in vitro model for the identification of treatments and prevention of NEC.

  2 years

Study Arms (2)

infants with surgical NEC

Infants who undergo surgery for NEC disease

Other: Organoids creation

Infants with GI surgical diseases other than NEC

Infants who undergo surgery for other GI diseases than NEC

Other: Organoids creation

Interventions

Organoids creation OTHER

Organoids are created from discarded tissue

Infants with GI surgical diseases other than NEC; infants with surgical NEC

Eligibility Criteria

• Age: Up to 44 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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

You may qualify if:

• 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.

You may not qualify if:

• Infants presenting a devastating damage of the intestine

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead
• Massachusetts General Hospital: collaborator

MeSH Terms

Conditions

Enterocolitis, Necrotizing; Premature Birth; Gastrointestinal Diseases

Condition Hierarchy (Ancestors)

Enterocolitis; Gastroenteritis; Digestive System Diseases; Intestinal Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Paola Roggero, MD PHD

  University of Milan Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paola Roggero, MD PHD

CONTACT

+393472777054; paola.roggero@unimi.it

valentina bozzetti, md phd

CONTACT

+18573138200; vbozzetti@hotmail.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2020
• First Posted: September 16, 2020
• Study Start: November 1, 2020
• Primary Completion: February 17, 2022
• Study Completion: February 17, 2022
• Last Updated: September 17, 2020

Record last verified: 2020-09