AGED Diagnostics Liver Disease Assessment

Early Phase 1

Not yet recruiting

• Conditions: NASH With Fibrosis; Healthy; NAFLD
• Interventions: Diagnostic Test: AGED Multiple Target Assay in Healthy Controls; Diagnostic Test: AGED Multiple Target Assay in NAFLD Participants; Diagnostic Test: AGED Multiple Target Assay in Fibrosis Participants

• Registration Number: NCT06348563
• Lead Sponsor: Active Genomes Expressed Diagnostics, Corp

Brief Summary

Continue development of previously established methods to further validate candidate biomarkers that can discriminate steatosis from NASH and separately stage fibrosis from blood. The first assessment is to conduct test method verification to expand sample size to several hundred samples through whole genome sequencing methods. The second assessment is focused on biomarker validation by comparing targeted sequencing from patient plasma. Several sub- assessments will be conducted to support overall biomarker development efforts.

Detailed Description

Aim 1: Test Method Verification, Whole genome bisulfite sequencing assessment for liver tissue and plasma Conduct whole genome bisulfite sequencing in patient liver tissue and patient plasma to identified candidate biomarkers that can discriminate between steatosis and NASH, and separately conduct a comparative analysis of patient liver tissue and patient plasma samples to assess NASH encompassing NASH with mild fibrosis, NASH with significant fibrosis and NASH with advanced fibrosis. The purpose of each is to identify a set of markers that have biological relevance on the liver and then identify epigenetic biomarkers in plasma derived from liver tissue. Note: both a subset of NASH specific biomarkers and fibrosis specific biomarkers have been previously reported for technical feasibility.

Aim 2: Biomarker Validation, Targeted Epigenetic Sequencing Assessment Select top NASH specific biomarkers and top fibrosis specific biomarkers and design, develop and test probes to assess overall performance of each candidate biomarker in plasma. Conduct comparative analysis between various targeted sequencing and PCR based modalities. Candidate biomarker performance will be evaluated based on sensitivity, specificity, AUROC and reproducibility, among several other assessments.

Study Timeline

• Status Verified: 2024-04
• Study First Submitted: 2024-04-01
• Study First Submitted QC: 2024-04-01
• Last Update Submitted: 2024-04-01
• Study First Posted: 2024-04-04
• Last Update Posted: 2024-04-04
• Study Start: 2024-05-15
• Primary Completion: 2025-05-15
• Study Completion: 2025-09-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

• Participant with liver biopsy over the past 1-2 years are permissible for study inclusion.
• Participant is considered to be a "Healthy Subject" relative to any form of liver disease OR
• Participant is suspected of having one of the following diagnoses: metabolic syndrome, NAFLD, fibrosis/cirrhosis, cardiovascular disease, chronic kidney disease.

Exclusion Criteria

• Participant is known to have HIV, Hepatitis B or Hepatitis C
• Participant has any other known form of chronic liver disease (aside from NAFLD/liver fibrosis)
• Participant has excess alcohol intake, excess alcohol is defined as participants that exceed an average 20g of alcohol daily for females (140g weekly intake) and average 30g of alcohol daily for males (210g weekly intake)
• Participant has had a bone marrow transplant at any time
• Participant is on anti-coagulation or anti-platelet therapy
• Participant is known to be pregnant
• Participant is unable to provide informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Health controls	AGED Multiple Target Assay in Healthy Controls	Diagnostic assessment
NAFLD	AGED Multiple Target Assay in NAFLD Participants	Diagnostic assessment. confirmation of diagnosis from liver biopsy is required. * NASH Diagnosis is on histological assessment from NASH CRN score: * NASH CRN score of ≤ 3 is classified as steatosis. * NASH CRN score of ≥ 5 is classified as NASH. * Participant samples can be subsequently diagnosed with CAP or MRI-PDFF to rule out NASH (or in rule in simple steatosis) but cannot be used to rule in NASH (as biopsy is required for confirmation). * All diagnostic criteria for participant at time of visit is requested.
Liver Fibrosis	AGED Multiple Target Assay in Fibrosis Participants	Diagnostic assessment, For fibrosis diagnosis and analysis, diagnostic tools can constitute zero or mild fibrosis (F0-F1), significant fibrosis (F2), and advanced fibrosis (F3-F4) in the presence or absence of NASH. * Participant samples can be diagnosed through non-invasive modalities such as but not limited to FIB4, ELF, PROC3, and/or imaging modalities such as but not limited to vibration controlled transient elastography (VCTE), magnetic resonance elastography (MRE), acoustic radiation force impulse (AFRI) or multiparameter imaging assessments. * All diagnostic criteria for participant at time of visit is requested.

Primary Outcome Measures

Name	Time	Method
Test Method Verification, Whole genome bisulfite sequencing assessment for liver tissue and plasma	6-9 months	Conduct whole genome bisulfite sequencing in patient liver tissue and patient plasma to identified candidate biomarkers that can discriminate between steatosis and NASH, and a separate assessment that can stage liver fibrosis.

Secondary Outcome Measures

Name	Time	Method
Biomarker Validation, Targeted Epigenetic Sequencing Assessment	6-9 months	Select top NASH specific biomarkers and top fibrosis specific biomarkers and design, develop and test probes to assess overall performance of each candidate biomarker in plasma through multiple targeted sequencing and PCR based modalities.

Trial Locations

Locations (1)

AGED Diagnostics; 🇺🇸 Bethesda, Maryland, United States