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

Prematurity Clinical Trial

Official title:

Development and Use of a Tissue and Human Enteroid Biorepository to Study the Pathophysiology of Neonatal Necrotizing Enterocolitis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04549727
• Other study ID #: BIENTERNIP
• Status: Not yet recruiting
• Start date: November 1, 2020
• Est. completion date: February 17, 2022

Study information

• Verified date: September 2020
• Source: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Contact: Paola Roggero, MD PHD
• Phone: +393472777054
• Email: paola.roggero[@]unimi.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 18
• Est. completion date: February 17, 2022
• Est. primary completion date: February 17, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 44 Weeks

Eligibility

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

Related Conditions & MeSH terms

• Digestive System Diseases
• Enterocolitis
• Enterocolitis, Necrotizing
• Gastrointestinal Disease
• Gastrointestinal Diseases
• Prematurity

Intervention

Other:
• Organoids creation
Organoids are created from discarded tissue

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico	Massachusetts General Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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