Identification of Host Factors of Norovirus Infections in Mini-Gut Model

NCT03342547 | Unknown

• 1 other identifier: MIC_CHAN_GRF_17_18_v1_20160930
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective in this study is to establish a list of host cellular proteins that mediate norovirus infection. Norovirus is one of the most common pathogens attributed to diarrheal diseases from unsafe food. It is also the primary cause of mortality among young children and adults in foodborne infections. Norovirus is not just a foodborne burden. In a recent meta-analysis, norovirus accounts for nearly one-fifth of all causes of (including person-to-person transmission) acute gastroenteritis in both sporadic and outbreak settings and affects all age groups. Undoubtedly, norovirus is of paramount public health concern in both developed and developing countries. Research efforts to better understand norovirus pathobiology will be necessary for targeted intervention. From Middle East respiratory syndrome coronavirus to Zika virus, efforts to identify host factors important for mediating virus infection has always been a research priority. Such information will shed light on potential therapeutic targets in antiviral intervention. Norovirus virus-host interaction studies have been hampered by the lack of a robust cell culture model in the past 20 years. In 2016, norovirus has finally been successfully cultivated in a stem cell-derived three-dimensional human gut-like structure called enteroid or mini-gut. In this study, intestinal stem cells will be isolated from duodenal biopsies collected from participants, followed by differentiation into mini-guts. Genome-wide genetic screening for host essential and restrictive factors will be performed on infected mini-guts by knockout CRISPR and gain-of-function CRISPR SAM, respectively. Shortlisted candidates will undergo preliminary functional validation in cell lines. These data will provide insights into potential therapeutic targets against norovirus infection.

Conditions

Gastrointestinal Infection

Keywords

Norovirus

Outcome Measures

Primary Outcomes (1)

• Establishment of human intestinal stem cell-derived enteroids

  Viability of enteroids as determined by microscopy

  An average of three months

Study Arms (1)

Intestinal stem cell-derived enteroids

EXPERIMENTAL

Duodenal biopsy samples and saliva will be collected from participants and then processed in laboratory to generate intestinal stem cell-derived enteroids.

Procedure: Duodenal biopsy; Procedure: Saliva

Interventions

Duodenal biopsy PROCEDURE

Two duodenal biopsy samples will be collected from each participant

Intestinal stem cell-derived enteroids

Saliva PROCEDURE

Saliva (1-2 mL) will be collected from each participant for secretor status testing

Intestinal stem cell-derived enteroids

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 18 years or above
• Prospective outpatients undergoing gastrointestinal endoscopy for symptoms of dyspepsia in the Endoscopy Unit of the Prince of Wales Hospital, Shatin, Hong Kong, China
• Able and willing to provide informed written consent

You may not qualify if:

• Use of anti-coagulants and/or aspirin that may have increased risk of bleeding
• History of bleeding diathesis
• Contraindications for biopsy sampling

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Endoscopy Centre, Prince of Wales Hospital

Hong Kong, China

RECRUITING

Study Officials

• Chi-Wai Chan, PhD

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chi-Wai Chan, PhD

CONTACT

+852 35051523; martin.chan@cuhk.edu.hk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: November 9, 2017
• First Posted: November 17, 2017
• Study Start: April 18, 2018
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: September 20, 2018

Record last verified: 2018-09

Locations

CN (1)