Clinical trial NCT06348563: AGED Diagnostics Liver Disease Assessment
Official title: AGED Diagnostics Epigenetic Modifications of Liver Disease Assessment
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: NASH With Fibrosis
NAFLD
Healthy
Lead sponsor: Active Genomes Expressed Diagnostics, Corp
Sponsor class: INDUSTRY
Collaborators: name: Arizona Clinical Trials
name: Walter Reed National Military Medical Center
First posted: 2024-04-04
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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

Primary outcomes:
measure: Test Method Verification, Whole genome bisulfite sequencing assessment for liver tissue and plasma
timeFrame: 6-9 months
Secondary outcomes:
measure: Biomarker Validation, Targeted Epigenetic Sequencing Assessment
timeFrame: 6-9 months
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: AGED Diagnostics
state: Maryland
Study officials:
References: