Brief Summary

The cascade of care for the non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH) requires crossing the barriers for their diagnosis and treatment. The multifactorial nature of NAFLD/NASH limits their diagnosis by a single factor solely. This project aimed at developing a powerful composite marker panel based on multi-omics technologies to detect NAFLD without or with fibrosis (potential for NASH) in high-risk populations (obesity, type 2 diabetes, hypertensive, dyslipidemia). This project is an exploratory study to unrevealing the intra-heterogeneity and inter-similarities of NAFLD without and with fibrosis versus those of healthy individuals. The molecular and clinical characteristics of 450 participants (225 adults aged 30-60 years and 225 children aged 12 -18 years) will be investigated; 150 NAFLD patients without, 150 NAFLD patients with fibrosis (potential NASH) compared to 150 healthy individuals. Detection of genetic polymorphism of SNP of 10 gene variants involved with NAFLD without and with fibrosis, gene discovery and molecular diagnosis of dyslipidemia using next-generation sequencing and whole-exome sequencing (genomics), the expression level for the top 5 of 168-panel genes of plasma miRNAs (epi-genomics), the glycosylation pattern of five glycoproteins (proteomics), salivary analysis of ten microbiomes and five microbial-related metabolites (metabolomics) will be investigated. Eventually, the development of precision therapies to target NAFLD without and with fibrosis and possibly reverse fibrosis could be achieved.

Trial Health

At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date

Enrollment

450

participants targeted

Target at P75+ for all trials

Timeline

Completed

Started Aug 2022

Geographic Reach

1 country

1 active site

Status

unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

1.7 years study duration

First Submitted

Initial submission to the registry

February 28, 2022

Completed

29 days until next milestone

First Posted

Study publicly available on registry

March 29, 2022

Completed

4 months until next milestone

Study Start

First participant enrolled

August 1, 2022

Completed

1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 30, 2023

Completed

4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 30, 2024

Completed

Last Updated

June 3, 2022

Status Verified

June 1, 2022

Enrollment Period

1.4 years

First QC Date

February 28, 2022

Last Update Submit

June 1, 2022

Conditions

Non-Alcoholic Fatty Liver Disease Non Alcoholic Steatohepatitis

Keywords

non-alcoholic fatty liver disease (NAFLD)non-alcoholic steatohepatitisepi-genomicsgenomicsmetabolomicsproteomics

Outcome Measures

Primary Outcomes (7)

Dyslipidemia-related variants related commonly to the Egyptian population
NGS panels of dyslipidemia main genes; (LDLR), (APOB), (PCSK9), and (LDLRAP) will be customized by Illumina to screen for mutations in 30 participants (as detected by OR in relation to controls).
12 months after the start of the recruitment
The most significant predisposing or protective genetic variants out of the studied risk and protective alleles associated with NAFLD without and with fibrosis in the Egyptian population.
The identification of people who carry a specific genetic variant predisposing them to NAFLD with fibrosis Through gene polymorphisms (as detected by OR in relation to controls)
12 months after the start of the recruitment
The expression level of altered plasma mRNAs detected among the Egyptian population
Expression profiling of plasma microRNAs expression profiling will be performed by locked nucleic acid PCR array for high plasma miRNAs. This will be applied to 2 subjects from each group (a total of 12 subjects).
12 months after the start of the recruitment
The glycosylation profile of the studied N- and O-glycoproteins among Egyptians
identifying the glycosylation pattern transferrin, apolipoprotein C III (Apoc III), haptoglobin, Mac2 binding protein, IgG (Santa Cruz, USA). The protein bands were visualized as a chemiluminescence reaction using ECL (Novex, Invitrogen, Thermo Scientific, US), and the images will be taken using a CDD camera.
12 months after the start of the recruitment
Differences in the compositions and types of the bacterial isolates among the Egyptian populations that are linked to NAFLD patients without and with fibrosis vs. controls
(out of 10 bacterial isolates) using -Rapid RT-PCR test for 16S rRNA gene amplicon library preparation and sequencing
12 months after the start of the recruitment
Concentration level of the high salivary detected microbiome-related metabolites
The salivary concentrations of the high salivary detected microbiome-related metabolites using Gas Chromatography-Mass Spectrometer (GC-MS) Analysis and their predictive value (Odds Ratio)
12 months after the start of the recruitment
Production of a novel non-invasive biomarker panel to be used for NAFLD without and with fibrosis prediction and diagnosis.
Using a logistic regression prediction model for the identification of significant multi-omics biomarkers will help in the development of a unique Egyptian scoring system.
24 months from the start of the study

Study Arms (3)

NAFLD group without fibrosis

Group diagnosed to have NAFLD without fibrosis according to the recommendation of EASL; AASLD (13) and ESPGHAN Hepatology Committee (14), (75 adults aged 30-60 years, 75 children aged 12-18 years) ,

Diagnostic Test: Genomics (DNA Extraction)Diagnostic Test: Epi-genomicsDiagnostic Test: Proteomics (Glycoproteomics)Diagnostic Test: Salivary MetabolomicsBehavioral: Individualized counselling for behavioural modification

NAFLD group with fibrosis (potential NASH)

Group diagnosed to have NAFLD with fibrosis according to the recommendation of EASL; AASLD (13) and ESPGHAN Hepatology Committee (14), (75 adults aged 30-60 years, 75 children aged 12-18 years),

Healthy group

Healthy control group age and sex-matched with the previous group (75 adults aged 30-60 years, 75 children aged 12-18 years),

Interventions

Genomics (DNA Extraction)DIAGNOSTIC_TEST

Blood samples for detection of: Genes for Dyslipidemia BY WES and NGS (4 GWA) (30 cases) Genes polymorphism for NAFLD/NASH BY TaqMan SNP Genotyping Assay on 10 GWAS